Medicine by Alexandros G.Sfakianakis: 04/16/18

The occurrence of nontuberculous mycobacterial (NTM) infection is rare, and the involvement of the musculoskeletal system is even less common. However, the incidence of soft tissue and skin NTM infection is increasing, particularly in patients who undergo injections and minor surgical procedures. Given the non-specific clinical manifestations of NTM infection, the lack of knowledge among physicians regarding this rare infection could lead to inaccurate and delayed diagnosis. Herein, we present a case of an isolated subcutaneous NTM infection caused by Mycobacterium abscessus in the upper back of an immunocompetent 68-year-old woman. The clinical presentation, magnetic resonance imaging findings (including diffusion-weighted imaging), and pathologic findings of subcutaneous NTM infection are described and compared with those of tuberculosis and tumor presentations to provide a more accurate clinical picture for a differential diagnosis.

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Avulsion fracture of an ossified pes anserinus tendon post-lateral patellar dislocation

Abstract

The pes anserinus is a common tendon comprising the tendinous insertions of the sartorius, gracilis, and semitendinosus muscles. It inserts at the anteromedial aspect of the tibia and plays a significant role in stabilization of the medial side of the knee joint. The current article presents a case with recurrent lateral patellar dislocations causing chronic stress along the medial knee stabilizers and consecutive enthesophyte formation at the insertion of the pes anserinus tendon that showed a transverse fracture upon a subsequent incident of traumatic lateral patellar dislocation. Avulsion injuries of the pes anserinus tendon are rarely encountered, and to our knowledge, association with recurrent lateral patellar dislocations has not been described before.

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2017 Award Winning Papers

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MRI in chronic groin pain: sequence diagnostic reliability compared to systematic surgical assessment

Abstract

Objective

To determine the diagnostic reliability of magnetic resonance imaging (MRI) sequences in chronic groin pain (CGP) compared to surgery and try to propose a suitable MRI protocol.

Materials and methods

Forty-three consecutive patients with resistant clinical CGP underwent a pre-surgical pelvis MRI. Eight MRI sequences were acquired: axial fast spin-echo T1-weighted (FSE T1), coronal FSE T1, axial-oblique (in symphysis plane) proton density weighted with fat saturation (PDFS), coronal PDFS, sagittal PDFS, axial FSE T1 with fat saturation and gadolinium enhancement (FSGE), coronal FSE T1 FSGE and axial FSE T1 with Valsalva maneuver (VM). These sequences were reviewed for pubic symphysis assessment, adductor longus (AL) tendon and abdominal wall (AW) injuries. The same surgeon operated on all of these patients (26 AL and 49 AW). Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative prospective value (NPV) and accuracy of each sequence and combinations for AL or AW injuries were calculated in comparison to surgical findings.

Results

One hundred ninety-two sequences were obtained. Coronal T1 FSGE and axial T1 VM proved to be the most reliable sequences (accuracy: 91.67% in AL and 83.33% in AW). The best sequence combination was coronal T1, axial PDFS, sagittal PDFS and axial T1 VM (accuracy: 77.78%; Se: 100.00%, Sp: 69.23%, PPV: 55.56%, NPV: 100.00%).

Conclusion

MRI has 77.78% accuracy, 100.00% sensitivity, 69.23% specificity, 55.56% PPV and 100.00% NPV in evaluating CGP, with coronal T1-axial PDFS-sagittal PDFS-axial T1 VM as the optimal protocol in terms of diagnostic performance within a reasonable scan time. Diagnostic performance of MRI was examined in the evaluation of CGP using surgery as reference standard.

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Response to: Periosteal mesenchymal chondrosarcoma of the tibia

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An intra-articular synovial lipoma of the hip, possibly causing osteoarthritis: a case report and review of the literature

Abstract

In this report, we present the case of an intra-articular synovial lipoma in a 58-year-old female with a coincident marked unilateral hip osteoarthritis. This patient suffered from right hip pain that developed gradually over 2 years. Physical examination noted decreased range of motion and evidence of impingement. MR and CT images showed an intra-articular fat-intense mass in the hip joint that was excised and confirmed as a synovial lipoma on histology. This case reveals that an intra-articular lipoma of the hip could be accompanied by pain or impingement and followed by hip osteoarthritis even in the absence of trauma.

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Browser’s notes

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MRI of the sacroiliac joints in spondyloarthritis: the added value of intra-articular signal changes for a ‘positive MRI’

Abstract

Objective

To determine if intra-articular signal changes at the sacroiliac joint space on MRI have added diagnostic value for spondyloarthritis, when compared to bone marrow edema (BME).

Materials and methods

A retrospective study was performed on the MRIs of sacroiliac joints of 363 patients, aged 16–45 years, clinically suspected of sacroiliitis. BME of the sacroiliac joints was correlated to intra-articular sacroiliac joint MR signal changes: high T1 signal, fluid signal, ankylosis and vacuum phenomenon (VP). These MRI findings were correlated with final clinical diagnosis. Sensitivity (SN), specificity (SP), likelihood ratios (LR), predictive values and post-test probabilities were calculated.

Results

BME had SN of 68.9%, SP of 74.0% and LR+ of 2.6 for diagnosis of spondyloarthritis. BME in absence of intra-articular signal changes had a lower SN and LR+ for spondyloarthritis (SN = 20.5%, LR+ 1.4). Concomitant BME and high T1 signal (SP = 97.2%, LR + = 10.5), BME and fluid signal (SP = 98.6%, LR + = 10.3) or BME and ankylosis (SP = 100%) had higher SP and LR+ for spondyloarthritis. Concomitant BME and VP had low LR+ for spondyloarthritis (SP = 91%, LR + =0.9). When BME was absent, intra-articular signal changes were less prevalent, but remained highly specific for spondyloarthritis.

Conclusion

Our results suggest that both periarticular and intra-articular MR signal of the sacroiliac joint should be examined to determine whether an MRI is 'positive' or 'not positive' for sacroiliitis associated with spondyloarthritis.

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Test yourself: weakness and wasting of forearm

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Hallux saltans due to stenosing tenosynovitis of flexor hallucis longus: dynamic sonography and arthroscopic findings

Abstract

Triggering of the toes is rare, with isolated cases reported in the literature involving predominantly the flexor hallucis longus (FHL) tendon, a condition known as "hallux saltans" (HS). We report the dynamic sonographic findings of a 42-year-old female with a 2-month history of ankle pain and triggering of right hallux, consistent with HS. Sonography demonstrated tenosynovitis and focal thickening of FHL at the level of hindfoot, with a fibrous band adjacent to the tendon. Dynamic ultrasound showed triggering and snapping of FHL tendon during hallux flexion and extension, respectively. We present comprehensive documentation of this rare entity, including sonographic still images and cine clips, as well as correlation with arthroscopic surgical findings.

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Atypical lipomatous tumor of the hand with transformation to dedifferentiated liposarcoma: a case report

Abstract

Atypical lipomatous tumor/well-differentiated liposarcoma is the most common sarcoma of soft tissue in adults. We describe the clinical, radiologic, and pathologic features of an atypical lipomatous tumor arising within the soft tissue of the left hand of a 68-year-old female that underwent transformation to dedifferentiated liposarcoma and eventually metastasized. At initial presentation, imaging demonstrated an extensively calcified fatty soft tissue mass with displacement of the digits. Following biopsy and staged debulking, the patient subsequently developed local recurrence, dedifferentiation, and widespread metastases to the lungs, pancreas, bone, and soft tissues. To our knowledge, this is the first case of a cytogenetically proven atypical lipomatous tumor of the hand that has undergone dedifferentiation with widespread metastases.

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Isolated avulsion fracture of the first metatarsal base at the peroneus longus tendon attachment: a case report

Abstract

Avulsion fractures of the first metatarsal (MT1) base at the peroneus longus (PL) tendon attachment are rare and may be undiagnosed during an emergency visit. If the injury is not treated properly, chronic pain or persistent impairment for inversion and plantar-flexion of the first ray may occur. This case report presents a 30-year-old woman who presented 10 weeks post trauma to a foot and ankle surgeon due to a swollen right midfoot with diffuse tenderness over the medial Lisfranc joint. Further evaluation showed an isolated avulsion fracture of the first metatarsal, which was undiagnosed during the emergent visit following the accident. In this case, the patient was successfully treated conservatively. The goal of this article is to raise awareness of this rare injury for radiologists and orthopedic surgeons.

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Metabolome analysis for pancreatic cancer risk in nested case‐control study: Japan Public Health Center‐based prospective Study

Cancer Science, EarlyView.

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Circulating exosomes contain protein biomarkers of metastatic non‐small‐cell lung cancer

Cancer Science, EarlyView.

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Spontaneous development of intratumoral heterogeneity in a transposon‐induced mouse model of glioma

Cancer Science, EarlyView.

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Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for uterine cervical cancer with lymph node metastasis

Cancer Science, EarlyView.

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Issue Information

Cancer Science, Volume 109, Issue 4, Page 879-881, April 2018.

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In this Issue

Cancer Science, Volume 109, Issue 4, Page 882-883, April 2018.

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Recurrent coronary disease in HIV‐infected patients: role of drug–drug interactions

British Journal of Clinical Pharmacology, EarlyView.

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Antibiotics and risk for birth defects

British Journal of Clinical Pharmacology, EarlyView.

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Invasive Listeriosis of Intracardiac Device

Introduction. Listeria monocytogenes is a food-borne pathogen which can cause invasive infection in immunocompromised adults. Listeria has been known to cause infections during pregnancy and in older adults. Listeria endocarditis is a rare condition. A case of listeria-related intracardiac device infection is reported below. Case Report. A 74-year-old male with a past medical history of coronary artery disease, congestive cardiac failure, permanent atrial fibrillation status after nodal ablation, and placement of a biventricular pacemaker presented to the hospital with complaints of generalized fatigue. He was found to have listeria bacteremia, and transthoracic echocardiogram (TTE) showed pacemaker lead vegetation. The patient was treated with 6 weeks of vancomycin followed by oral suppression with amoxicillin. Discussion. Listeria can affect native valves, prosthetic valves, or nonvalvular intracardiac devices. The mean age of prosthetic valve endocarditis has been reported to be 67 years with male-to-female ratio 1.7 : 1 and mitral-to-aortic valve ratio 1.3 : 1. There have been case reports of listeria prosthetic valve endocarditis; however, there is paucity of literature on listeria-related pacemaker lead infection. Treatment is mostly a combination of penicillin and aminoglycosides for 4–6 weeks. Surgical removal of the infected device is preferred. Invasive listeriosis is a rare but fatal entity which should be identified and treated promptly to ensure a good outcome.

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Microbleeds in ischemic vs hemorrhagic strokes on novel oral anticoagulants

Acta Neurologica Scandinavica, EarlyView.

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Serum magnesium and risk of incident heart failure in older men: The British Regional Heart Study

Abstract

To examine the association between serum magnesium and incident heart failure (HF) in older men and investigate potential pathways including cardiac function, inflammation and lung function. Prospective study of 3523 men aged 60–79 years with no prevalent HF or myocardial infarction followed up for a mean period of 15 years, during which 268 incident HF cases were ascertained. Serum magnesium was inversely associated with many CVD risk factors including prevalent atrial fibrillation, lung function (FEV₁) and markers of inflammation (IL-6), endothelial dysfunction (vWF) and cardiac dysfunction [NT-proBNP and cardiac troponin T (cTnT)]. Serum magnesium was inversely related to risk of incident HF after adjustment for conventional CVD risk factors and incident MI. The adjusted hazard ratios (HRs) for HF in the 5 quintiles of magnesium groups were 1.00, 0.72 (0.50, 1.05), 0.85 (0.59, 1.26), 0.76 (0.52, 1.11) and 0.56 (0.36, 0.86) respectively [p (trend) = 0.04]. Further adjustment for atrial fibrillation, IL-6, vWF and FEV₁ attenuated the association but risk remained significantly reduced in the top quintile (≥ 0.87 mmol/l) compared with the lowest quintile [HR 0.62 (0.40, 0.97)]. Adjustment for NT-proBNP and cTnT attenuated the association further [HR 0.70 (0.44, 1.10)]. The benefit of high serum magnesium on HF risk was most evident in men with ECG evidence of ischaemia [HR 0.29 (0.13, 0.68)]. The potential beneficial effect of high serum magnesium was partially explained by its favourable association with CVD risk factors. Further studies are needed to investigate whether serum magnesium supplementation in older adults may protect from the development of HF.

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Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial–Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.

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Issue Cover (April 2018)

European Journal of Neuroscience, Volume 47, Issue 8, Page i-iii, April 2018.

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A unified hierarchical oscillatory network model of head direction cells, spatially periodic cells, and place cells

European Journal of Neuroscience, EarlyView.

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Synaptic organization of the dorsal lateral geniculate nucleus

European Journal of Neuroscience, EarlyView.

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Processing of interaural phase differences in components of harmonic and mistuned complexes in the inferior colliculus of the Mongolian gerbil

European Journal of Neuroscience, EarlyView.

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Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Clinical and Translational Science, EarlyView.

https://ift.tt/2J1rCQb

Moray micro forceps biopsy improves the diagnosis of specific pancreatic cysts

Cancer Cytopathology, EarlyView.

https://ift.tt/2qDeXfE

High Oct4 predicted worse prognosis of right-sided colon cancer patients

Future Oncology, Ahead of Print.

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Living on a farm, contact with farm animals and pets, and childhood acute lymphoblastic leukemia: pooled and meta‐analyses from the Childhood Leukemia International Consortium

Cancer Medicine, EarlyView.

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Risk factors for length of stay and charge per day differ between older and younger hospitalized patients with AML

Cancer Medicine, EarlyView.

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Functional Analysis of Hif1 Histone Chaperone in Saccharomyces cerevisiae

The Hif1 protein in the yeast Saccharomyces cerevisie is an evolutionarily conserved H3/H4-specific chaperone and a subunit of the nuclear Hat1 complex that catalyzes the acetylation of newly synthesized histone H4. Hif1, as well as its human homolog NASP, has been implicated in an array of chromatin-related processes including histone H3/H4 transport, chromatin assembly and DNA repair. In this study, we elucidate the functional aspects of Hif1. Initially we establish the wide distribution of Hif1 homologs with an evolutionarily conserved pattern of four tetratricopeptide repeats (TPR) motifs throughout the major fungal lineages and beyond. Subsequently, through targeted mutational analysis, we demonstrate that the acidic region that interrupts the TPR2 is essential for Hif1 physical interactions with the Hat1/Hat2-complex, Asf1, and with histones H3/H4. Furthermore, we provide evidence for the involvement of Hif1 in regulation of histone metabolism by showing that cells lacking HIF1 are both sensitive to histone H3 over expression, as well as synthetic lethal with a deletion of histone mRNA regulator LSM1. We also show that a basic patch present at the extreme C-terminus of Hif1 is essential for its proper nuclear localization. Finally, we describe a physical interaction with a transcriptional regulatory protein Spt2, possibly linking Hif1 and the Hat1 complex to transcription-associated chromatin reassembly. Taken together, our results provide novel mechanistic insights into Hif1 functions and establish it as an important protein in chromatin-associated processes.

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Accounting for Genotype-by-Environment Interactions and Residual Genetic Variation in Genomic Selection for Water-Soluble Carbohydrate Concentration in Wheat

Abiotic stress tolerance traits are often complex and recalcitrant targets for conventional breeding improvement in many crop species. This study evaluated the potential of genomic selection to predict water-soluble carbohydrate concentration (WSCC), an important drought tolerance trait, in wheat under field conditions. A panel of 358 varieties and breeding lines constrained for maturity was evaluated under rainfed and irrigated treatments across two locations and two years. Whole-genome marker profiles and factor analytic mixed models were used to generate genomic estimated breeding values (GEBVs) for specific environments and environment groups. Additive genetic variance was smaller than residual genetic variance for WSCC, such that genotypic values were dominated by residual genetic effects rather than additive breeding values. As a result, GEBVs were not accurate predictors of genotypic values of the extant lines, but GEBVs should be reliable selection criteria to choose parents for intermating to produce new populations. The accuracy of GEBVs for untested lines was sufficient to increase predicted genetic gain from genomic selection per unit time compared to phenotypic selection if the breeding cycle is reduced by half by the use of GEBVs in off-season generations. Further, genomic prediction accuracy depended on having phenotypic data from environments with strong correlations with target production environments to build prediction models. By combining high-density marker genotypes, stress-managed field evaluations, and mixed models that model simultaneously covariances among genotypes and covariances of complex trait performance between pairs of environments, we were able to train models with good accuracy to facilitate genetic gain from genomic selection.

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A 2‐year prospective study of single‐implant mandibular overdentures: Patient‐reported outcomes and prosthodontic events

Clinical Oral Implants Research, EarlyView.

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Systematic review of the influence of socioeconomic deprivation on mortality after colorectal surgery

British Journal of Surgery, EarlyView.

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Studying embryotoxicity of petroleum products for carp fish family

Abstract

To study the embryotoxicity of the oil fraction Karakuduk locality (Kazakhstan, oil deposit) for zebrafish Danio rerio (family Cyprinidae), in the conditions of the experiment. The method of breeding fishes of Danio rerio, receiving, and incubating zebrafish in vitro. Experiments have been carried out on the development of Danio rerio embryos in the oil-bearing fraction (Karakuduk locality) in various in vitro concentrations. The paper presents the results of experiments on exposure zebrafish embryos (Danio rerio) oil fractions in different concentrations and shows data on mortality of embryos and embryonic development violations. The originality of studying embryotoxicity of petroleum products for Cyprinidae fish family is that the object of our experiment is the most vulnerable age group in the population-fish larvae. Due to investigations, number of eggs could exactly determine the vitality of the fish population in general and can counter the number of the population through a certain period. Following the epidemic of mass mortality of caviar and larvae from oil pollution, the toxicant acts in the role of the immunosuppressive agent. Thus, it leads to the reduction of resistance to various infections with the reduction of the variability of even slight temperature and salinity fluctuations.

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Molecular characterization of qnrVC and their novel alleles in Vibrio spp. isolated from food products in China [PublishAheadOfPrint]

This study reported the prevalence of qnrVC genes in 74 ciprofloxacin-resistant Vibrio spp. isolates. Two novel functional qnrVC alleles, qnrVC8 and qnrVC9, sharing 98% and 99% nucleotide similarity with qnrVC6 and qnrVC7 respectively, were identified. Our findings suggested that carriage of qnrVC alleles, together with target mutations in gyrA and parC genes, may contribute to development of fluoroquinolone resistance in Vibrio species, posing serious threat to public health.

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Unexpected Replication Boost by Simeprevir for Simeprevir-resistant Variants in Genotype 1a Hepatitis C Virus [PublishAheadOfPrint]

Simeprevir is a novel NS3/4A protease inhibitor (PI) of hepatitis C virus (HCV). The baseline polymorphism NS3-Q80K is frequently observed in genotype (gt) 1a HCV and often associated with treatment failure in simeprevir-containing regimens. We aimed to elucidate mechanisms of treatment failure due to NS3-Q80K. We included a Q80R mutation in our study and generated a series of Huh-7.5 cells, each of which harbored either wild-type gt 1a H77S.3 or one of the variants, Q80K or Q80R. The cells were cultured with increasing concentrations of simeprevir, and NS3 domain sequences were determined. The mutations identified by sequence analyses were subsequently introduced into H77S.3. The sensitivity of each mutant to NS3/4A PIs simeprevir, asunaprevir, grazoprevir, and paritaprevir was analyzed. We introduced the mutations into gt 1b N.2 and compared the sensitivity to simeprevir with that in gt 1a H77S.3. While simeprevir treatment selected mutations at residue D168, such as D168A/V in the wild-type virus, an additional mutation at residue R155, R155K, was selected in Q80K/R variants at simeprevir concentrations lower than 2.5 μM. Sensitivity analyses showed that simeprevir concentrations of less than 1 μM significantly boosted the replication of Q80K/R+R155K variants. Interestingly, this boost was not observed with the other NS3/4A PIs, and not in Q80R+R155Q/G/T/W variants or gt 1b. The boosted replication of Q80K+R155K by simeprevir could be related to treatment failure in simeprevir-containing antiviral treatments in gt 1a HCV-infected patients with the NS3-Q80K polymorphism. This result provides a new insight into how resistance-associated variants can cause treatment failure.

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The Genetic Polymorphism UGT1A4*3 Is Associated with Low Posaconazole Plasma Concentrations in Hematological Malignancy Patients Receiving the Oral Suspension [PublishAheadOfPrint]

The metabolism of posaconazole is mediated mainly by uridine 5' -diphospho-glucuronosyltransferase (UGT) enzymes, especially the UGT1A4. The aim of this study was to investigate the effects of genetic polymorphisms on the posaconazole plasma concentration (PPC). This prospective study was conducted from September 2014 to August 2016. We enrolled patients with acute myeloid leukemia or myelodysplastic syndrome treated with posaconazole oral suspension (200 mg) three times daily for fungal prophylaxis. The multi-drug resistance gene 1 3435C>T and 2677G>T/A variations, and UGT1A4*3 were examined by direct sequencing of DNA from peripheral whole blood samples. We defined poor absorbers as those with PPCs <200 ng/mL and the optimal PPC as ≥700 ng/mL on day 8. The associations between genetic polymorphisms and the PPC were evaluated using multivariate logistic regression analysis including clinical variables. In the study period, 132 patients were enrolled. Six patients (4.5%) were defined as poor absorbers and 49 patients (37.1%) did not reach the optimal PPC on day 8. In multivariate analysis, the independent risk factors for a poor absorber were at least one UGT1A4*3 allele (adjusted odds ratio [lsqb]aOR[rsqb], 18.81; 95% confidence interval [lsqb]CI[rsqb], 1.09-324.44; p = 0.043) and poor oral food intake (aOR per -100 kcal, 1.44; 95% CI, 1.04-1.99; p = 0.029). There was no statistically significant association between the genetic polymorphisms and reaching the optimal PPC on day 8. The UGT1A4*3 polymorphism is an independent risk factor for being a poor absorber of posaconazole oral suspension in patients with hematologic malignancies.

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Characterising blood stage antimalarial drug minimum inhibitory concentrations in vivo using reinfection patterns [PublishAheadOfPrint]

The minimum inhibitory concentration (MIC) is an essential quantitative measure of the asexual blood stage effect of an antimalarial drug. In areas of high malaria transmission, and thus frequent individual infection, patients who are treated with slowly eliminated antimalarials become reinfected as drug concentrations decline. In the frequent relapse forms of P. vivax and in P. ovale malaria, recurrent infection occurs from relapses which begin to emerge from the liver approximately two weeks after the primary illness. An important determinant of the interval from starting treatment of a symptomatic infection to the patency of these recurrent infections is the in vivo concentration-response relationship and thus the in vivo MIC. Using mechanistic knowledge of parasite asexual replication and the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs, a generative statistical model was derived which relates the concentration-response relationship to time of reinfection patency. This model was used to estimate the in vivo MIC of chloroquine in the treatment of Plasmodium vivax malaria.

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Spread of clonally related Escherichia coli harboring an IncA/C1 plasmid encoding IMP-8 and its recruitment into an unrelated MCR-1-containing isolate [PublishAheadOfPrint]

Ten IMP-8-producing Escherichia coli isolates were recovered from the surveillance cultures of a neonatal intensive care unit, of which eight were clonally related. A 168.2-kb-bla_IMP-8 plasmid was fully sequenced, and it corresponded to the recently described IncA/C1-ST13. This plasmid was detected in all isolates, even in those no clonally related. One unrelated isolate was also resistant to colistin and positive for mcr-1. This marker was located in a 62.7-kb-IncI2 plasmid, which was also fully sequenced.

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HC2091 kills Mycobacterium tuberculosis by targeting the MmpL3 mycolic acid transporter [PublishAheadOfPrint]

Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), is a deadly disease that requires a long course of treatment. The emergence of drug resistant strains has driven efforts to discover new small molecules that can kill the bacterium. Here we report characterizations of the compound HC2091 that kills Mtb in a time- and dose-dependent manner in vitro, as well as inhibiting Mtb growth in macrophages. Whole genome sequencing of spontaneous resistant mutants to HC2091 identified single nucleotide variants in the mmpL3 mycolic acid transporter gene. HC2091 resistant mutants do not exhibit cross-resistance with the well-characterized MmpL3 inhibitor SQ109, suggesting a distinct mechanism of interaction with MmpL3. Additionally, HC2091 does not modulate bacterial membrane potential or kill non-replicating Mtb, thus acting differently from other known MmpL3 inhibitors. RNA-seq transcriptional profiling and lipid profiling of Mtb treated with HC2091 or SQ109 show that both compounds target a similar pathway. HC2091 has a dissimilar chemical structure from previously described MmpL3 inhibitors, supporting that HC2091 is a new class of MmpL3 inhibitor.

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Antimicrobial and antibiofilm efficacy of graphene oxide against chronic wound microorganisms [PublishAheadOfPrint]

Chronic wounds represent an increasing problem worldwide. Graphene oxide (GO) has been reported to exhibit strong antibacterial activity towards both Gram-positive and Gram-negative bacteria. The aim of this work was to investigate the in vitro antimicrobial and antibiofilm efficacy of GO against wound pathogens. Staphylococcus aureus PECHA 10, Pseudomonas aeruginosa PECHA 4 and Candida albicans X3 clinical isolates were incubated with 50 mg/L of GO for 2 and 24 h to evaluate the antimicrobial effect. Optical and Atomic force microscopy images were performed to visualize the GO effect on microbial cells. Moreover, the antibiofilm effect of GO was tested on biofilms both in formation and mature. When compared to the respective time controls, GO significantly reduced the S. aureus growth both at 2 and 24 h in a time dependent way, and displayed a bacteriostatic effect in respect to the GO t=0; an immediate (after 2 h) slowdown of bacterial growth was detected for P. aeruginosa whereas a tardive effect (after 24 h) was recorded for C. albicans. Atomic force microscopy images showed the complete wrapping of S. aureus and C. albicans with GO sheets that explains its antimicrobial activity. Moreover, significant inhibition of biofilm formation and a reduction of mature biofilm were recorded for each detected microorganism. The antibacterial and antibiofilm properties of GO against chronic wound microrganisms make it an interesting candidate to incorporate into wound bandages to treat and/or prevent microbial infections.

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Plasticity of aminoglycoside binding to antibiotic kinase APH(2")-Ia [PublishAheadOfPrint]

APH(2")-Ia aminoglycoside resistance enzyme forms the C-terminal domain of the bifunctional AAC(6')-Ie/APH(2")-Ia enzyme and confers high-level resistance to natural 4,6-disubstituted aminoglycosides. In addition, reports have suggested that the enzyme can phosphorylate 4,5-disubstituted compounds and aminoglycosides with substitutions at the N1-position. Previously determined structures of the enzyme with aminoglycosides bound have not indicated how these non-canonical substrates could bind and be modified by the enzyme. We carried out crystallographic studies to directly observe the interaction of these compounds with the aminoglycoside-binding site and probe the means by which these non-canonical substrates interact with the enzyme. We find that APH(2")-Ia maintains a preferred mode of binding aminoglycosides using the conserved neamine rings when possible, with flexibility that allows it to accommodate additional rings. However, if this binding mode is made impossible because of additional substitutions to the standard 4,5- or 4,6-disubstituted aminoglycoside architecture as in lividomycin A or the N1-substituted aminoglycosides, it is still possible for these aminoglycosides to bind to the antibiotic-binding site, using alternate binding modes, explaining the low rates of non-canonical phosphorylation activities seen in enzyme assays. Furthermore, structural studies of a clinically-observed arbekacin-resistant mutant of APH(2")-Ia reveals an altered aminoglycoside binding site that can stabilize an alternative binding mode for N1-substituted aminoglycosides. This mutation could alter and expand the aminoglycoside resistance spectrum of the wildtype enzyme in response to newly developed aminoglycosides.

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Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease [PublishAheadOfPrint]

Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated treatment outcomes of 77 patients with refractory NTM-LD caused by Mycobacterium abscessus complex (MABC) or M. avium complex (MAC) who initiated AMK inhalation therapy between February 2015 and June 2016. MABC was the most common etiology (n = 48, 62%), followed by MAC (n = 20, 26%) and mixed infections (n = 9, 12%). Macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and five (6%) patients, respectively. Twelve months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiologic improvement. Sputum negative culture conversion occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than with macrolide-resistant isolates (7/63, 11%, P = 0.003). Significant decreases in sputum semiquantitative culture positivity occurred after AMK inhalation therapy (P < 0.001). On multivariate analysis, sputum culture conversion was associated with mixed infections (P = 0.009), a forced expiratory volume in one second of greater than 60% (P = 0.008), and with the absence of macrolide resistance (P = 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity (n = 15) most common. AMK inhalation salvage therapy may improve treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of optimal dosage and intervals for AMK inhalation is needed.

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Refractory hypokalemia from syndrome of apparent mineralocorticoid excess on low-dose posaconazole [PublishAheadOfPrint]

A 67-year-old woman with acute myeloid leukemia experienced refractory hypokalemia while taking low-dose posaconazole....

https://ift.tt/2vkMAaP

Triclosan is an aminoglycoside adjuvant for the eradication of Pseudomonas aeruginosa biofilms [PublishAheadOfPrint]

One of the most important clinical obstacles in cystic fibrosis (CF) is antibiotic treatment failure due to biofilms produced by Pseudomonas aeruginosa. The ability of this pathogen to survive eradication by tobramycin and pathoadapt into a hyper-biofilm state leading to chronic infections is key to its success. Retrospective studies have demonstrated that preventing this pathoadaptation by improving eradication is essential to extend the lives of CF patients. To identify adjuvants that enhance tobramycin eradication of P. aeruginosa, we performed a high-throughput screen of 6,080 compounds from four drug repurposing libraries. We identified that the Food and Drug Administration (FDA) approved compound, triclosan, combined with tobramycin resulted in a 100-fold reduction of viable cells within biofilms at six hours, but neither compound alone had significant antimicrobial activity against biofilms. This synergistic treatment significantly accelerated killing of biofilms compared to tobramycin treatment alone, and the combination was effective against 6/7 CF clinical isolates compared to tobramycin treatment alone including a tobramycin resistant strain. Further, triclosan and tobramycin killed persister cells, causing a 100-fold reduction by 8-hrs and complete eradication by 24-hrs. Triclosan also enhances tobramycin killing of multiple Burkholderia cenocepacia and Staphylococcus aureus clinical isolates grown as biofilms. Additionally, triclosan synergized with other aminoglycosides such as gentamicin or streptomycin. Triclosan is a well-tolerated aminoglycoside adjuvant shown to be safe for human use that could improve treatment of biofilm-based infections.

https://ift.tt/2JN0p4V

Genetic diversity among S. aureus isolates showing oxacillin and/or cefoxitin resistance not linked to the presence of mec genes [PublishAheadOfPrint]

Methicillin-resistant Staphylococcus aureus isolates lacking mec-genes (n=32) collected from Belgian hospitals were characterized for their β-lactamase production and the presence of mutations in pbp-genes, the pbp4-promotor and genes (gdpP, yjbH) involved in PBP4-overproduction. Twelve isolates were β-lactamase hyperproducers (BHP), while 12 non-BHPs isolates may produce an incomplete GdpP protein. Most isolates showed nucleotide missense mutations at pbp genes. Few isolates showed also mutations at the pbp4-promoter.

https://ift.tt/2vq9zBw

Modeling and Simulation of Pretomanid Pharmacokinetics in Pulmonary Tuberculosis Patients [PublishAheadOfPrint]

Pretomanid is a nitroimidazole antibiotic in late phase clinical testing as a component of several novel antituberculosis (anti-TB) regimens. A population pharmacokinetic model for pretomanid was constructed using a Bayesian analysis of data from two phase 2 studies, PA-824-CL-007 and PA-824-CL-010, conducted with newly diagnosed adult (median age 27 years) pulmonary TB patients in Cape Town, South Africa. Combined, these studies included 63 males and 59 females administered once daily oral pretomanid doses of 50, 100, 150, 200, 600, 1000, or 1200 mg for 14 days. The observed pretomanid concentration-time profiles for all tested doses were described by a one-compartment model with first-order absorption and elimination, and a sigmoidal bioavailability dependent on dose, time, and predose fed state. Allometric scaling with body weight (normalized to 70 kg) was used for volume of distribution and clearance, with scaling exponents of 1 and 3/4, respectively. The posterior population geometric means for clearance and volume of distribution allometric constants were 4.8±0.2 L/h and 130±5 L, respectively, and 450±50 mg for the half-maximum effect dose for reduction of bioavailability. Interindividual variability, described by percent coefficient of variation, was 32±3% for clearance, 17±4% for volume of distribution, and 74±9% for half-maximum effect dose. This model provides a dose-exposure relationship for pretomanid in adult TB patients, with potential applications to dose selection in individuals and to further clinical testing of novel pretomanid-containing anti-TB regimens.

https://ift.tt/2EPhzLH

SOURCE OF THE FITNESS DEFECT IN RIFAMYCIN-RESISTANT M. TUBERCULOSIS RNA POLYMERASE AND THE MECHANISM OF COMPENSATION BY MUTATIONS IN THE {beta}'-SUBUNIT [PublishAheadOfPrint]

Mycobacterium tuberculosis (MTB) is a critical threat to human health due to the increased prevalence of rifampin resistance (RMP^R). Fitness defects have been observed in RMP^R mutants having amino acid substitutions in the β-subunit of RNA polymerase (RNAP). In clinical isolates, this fitness defect can be ameliorated by the presence of secondary mutations in the double-psi β-barrel (DPBB) domain of the β'-subunit of RNAP. To identify factors contributing to the fitness defects observed in vivo, several in vitro RNA transcription assays were utilized to probe initiation, elongation, termination, and 3' -RNA hydrolysis with the wild-type and RMP^R MTB RNAPs. We found that the less prevalent RMP^R mutants exhibit significantly poorer termination efficiencies relative to wild-type, an important factor for proper gene expression. We also found that several mechanistic aspects of transcription of the RMP^R mutant RNAPs are impacted relative to wild-type. For the clinically most prevalent, βS450L mutant, these defects are mitigated by the presence of secondary/compensatory mutations in the DPBB domain of the β'-subunit.

https://ift.tt/2JN0buB

Protein–lipid co‐oxidation in emulsions stabilized by microwave‐treated and conventional thermal‐treated faba bean proteins

Food Science &Nutrition, EarlyView.

https://ift.tt/2H5u8Zn

Investigation of antioxidant activities of Pleurotus ostreatus stored at different temperatures

Food Science &Nutrition, EarlyView.

https://ift.tt/2qBK36D

Gelatin versus its two major degradation products, prolyl‐hydroxyproline and glycine, as supportive therapy in experimental colitis in mice

Food Science &Nutrition, EarlyView.

https://ift.tt/2H6haut

Safety of ready‐to‐eat chicken in Burkina Faso: Microbiological quality, antibiotic resistance, and virulence genes in Escherichia coli isolated from chicken samples of Ouagadougou

Food Science &Nutrition, EarlyView.

https://ift.tt/2qEZzhQ

Melancholia and cancer: The bladder cancer narrative

Cancer, EarlyView.

https://ift.tt/2H2WSxO

Symptom and function profiles of men with localized prostate cancer

Cancer, EarlyView.

https://ift.tt/2HFzY0i

Managing work and cancer treatment: Experiences among survivors of hematological cancer

Cancer, EarlyView.

https://ift.tt/2H6BKqc

Racial disparities in postmastectomy breast reconstruction: National trends in utilization from 2005 to 2014

Cancer, EarlyView.

https://ift.tt/2HFzFTc

Final results of a phase 2, open‐label study of indisulam, idarubicin, and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high‐risk myelodysplastic syndrome

Cancer, EarlyView.

https://ift.tt/2H63b3H

PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside

Cancer, EarlyView.

https://ift.tt/2H4EDIb

Advances in Controlling Differentiation of Adult Stem Cells for Peripheral Nerve Regeneration

Advanced Healthcare Materials, EarlyView.

https://ift.tt/2qD6Q1T

High TMB Predicts Immunotherapy Benefit in NSCLC [News in Brief]

Ipilimumab–nivolumab combo improves progression-free survival in subset of patients, study shows.

https://ift.tt/2H4bdd7

Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients

Clinical Anatomy, EarlyView.

https://ift.tt/2qBiaLG

Immunogenomic analyses of advanced serous ovarian cancer reveal immune score is a strong prognostic factor and an indicator of chemo-sensitivity

Purpose: Ovarian cancer is one of the first human cancers for which in situ immune response was reported to be important for the clinical outcome. To elucidate the mechanistic relationship between immune repertoire and cancer genotype in ovarian cancer, the development of a well-defined immune score for ovarian cancer is required. Experimental Design: From a collection of 2,203 patient samples of advanced ovarian cancer from public available resources, we evaluated the prognostic values for a compendium of immune marker genes and proposed an immune score. The relationships between immune score, tumor-infiltrating immune cells, cancer genotypes and their impact on patient outcome were characterized. Results: Loss of chemokine and IFN- pathway genes is frequent in ovarian cancer and is significantly associated with low immune score and poor outcome. Chemotherapy can increase the immune score of tumors by inducing the expression of IFN- inducible chemokines. High immune score is significantly associated with BRCA1/2 mutation status and the response to chemotherapy. Multivariate analysis revealed that immune score is a strong predictor of patient survival and the response to immunotherapy. Conclusions: Our results reveal the drivers of the immune repertoire of advanced ovarian cancer and demonstrate the importance of immune score as an independent prognostic signature and a potent indicator of intratumoral immune status.

https://ift.tt/2J0tgkZ

Accuracy, Safety, and Reliability of Novel Phase I Trial Designs

A number of novel model-based and model-assisted designs have been proposed to find the maximum tolerated dose (MTD) in phase I clinical trials, but their differences and relative pros and cons are not clear to many practitioners. We review three model-based designs, including the continual reassessment method (CRM), dose escalation with overdose control (EWOC), and Bayesian logistic regression model (BLRM), and three model-assisted designs, including the modified toxicity probability interval (mTPI), Bayesian optimal interval (BOIN), and keyboard designs. We conduct numerical studies to assess their accuracy, safety and reliability, and the practical implications of various empirical rules used in some designs, such as skipping a dose and imposing overdose control. Our results show that the CRM outperforms EWOC and BLRM with higher accuracy of identifying the MTD. For the CRM, skipping a dose is not recommended as it substantially increases the chance of overdosing patients, while providing limited gain for identifying the MTD. EWOC and BLRM appear excessively conservative. They are safe, but have relatively poor accuracy of finding the MTD. The BOIN and keyboard designs have similar operating characteristics, outperforming the mTPI, but the BOIN is more intuitive and transparent. The BOIN yields competitive performance comparable to the CRM, but is simpler to implement and free of the issue of irrational dose assignment caused by model misspecification, thereby providing an attractive approach for designing phase I trials.

https://ift.tt/2HxwSxM

Prospective clinical trial of ixazomib, dexamethasone and rituximab as primary therapy in Waldenström macroglobulinemia

Introduction: Proteasome inhibition is of proven efficacy in patients with Waldenström macroglobulinemia (WM). However, WM remains incurable with standard treatments. Novel agents, safe and effective, are needed. Methods: We designed a prospective phase II study evaluating the combination of ixazomib, dexamethasone and rituximab (IDR) as primary therapy in symptomatic patients with WM. Protocol therapy consisted of oral ixazomib, 4 mg, with intravenous or oral dexamethasone, 20 mg, on days 1, 8 and 15 every 4 weeks for induction cycles 1 and 2, and in combination with intravenous rituximab, 375 mg/m2, on day 1, every 4 weeks for cycles 3 to 6. Maintenance therapy followed 8 weeks later with IDR given every 8 weeks for 6 cycles. Results: Twenty-six patients were enrolled. All patients had the MYD88 L265P mutation, and 15 patients (58%) had a CXCR4 mutation. The median time to response was 8 weeks, which was longer (12 weeks) in WM patients with CXCR4 mutations (p=0.03). The overall response rate was 96% and the major response rate was 77%. With a median follow-up of 22 months, the median progression-free survival was not reached. Grade ≥2 adverse events reported in >1 patient included infusion-related reactions (19%), rash (8%) and insomnia (8%). Conclusion: IDR offers a highly effective and well tolerated, neuropathy-sparing regimen for primary therapy in patients with WM. This trial is registered at www.clinicaltrials.gov under ID NCT02400437.

https://ift.tt/2J3XSlY

Integrated genomic and immunophenotypic classification of pancreatic cancer reveals three distinct subtypes with prognostic/predictive significance

Purpose: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. Experimental Design: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins. Previous data on FOXP3 were integrated. Immune-cell counts and protein expression were correlated with tumor-derived driver mutations, clinicopathologic features (TNM 8. 2017), survival and epithelial-mesenchymal-transition (EMT)-like tumor budding. Results: Three PDAC-subtypes were identified: the "immune-escape" (54%), poor in T- and B-cells and enriched in FOXP3+Tregs, with high-grade budding, frequent CDKN2A- , SMAD4- and PIK3CA-mutations and poor outcome; the "immune-rich" (35%), rich in T- and B-cells and poorer in FOXP3+Tregs, with infrequent budding, lower CDKN2A- and PIK3CA-mutation rate and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11, ATM) and the best outcome; and the "immune-exhausted" (11%) with immunogenic microenvironment and two subpopulations: one with PD-L1-expression and high PIK3CA-mutation rate and a microsatellite-unstable subpopulation with high prevalence of JAK3-mutations. The combination of low budding, low stromal FOXP3-counts, presence of TLTs and absence of CDKN2A-mutations confers significant survival advantage in PDAC-patients. Conclusions:Immune host responses correlate with tumor characteristics leading to morphologically recognizable PDAC-subtypes with prognostic/predictive significance.

https://ift.tt/2HvdykM

Interferon-stimulated genes are involved in cross-resistance to radiotherapy in tamoxifen-resistant breast cancer

Purpose: Treatment resistance is a main cause of adverse disease outcome in breast cancer patients. Here we aimed to investigate common features in tamoxifen-resistant and radioresistant breast cancer, since tamoxifen-resistant breast cancer cells are cross-resistant to irradiation in vitro. Experimental Design: RNA sequencing of tamoxifen-resistant and radioresistant breast cancer cells was performed and validated by quantitative PCR. Pathways were further investigated in vitro and in breast cancer patient cohorts to establish their relation with treatment resistance. Results: Both tamoxifen-resistant and radioresistant breast cancer cells had increased expression levels of genes involved in type I IFN signaling compared to non-resistant cells. IFN-stimulated genes (ISGs) were induced in a dose-dependent and time-dependent manner after tamoxifen treatment and irradiation. Tamoxifen treatment also led to ssDNA presence in the cytoplasm, which is known to induce expression of ISGs, a phenomenon that has already been described for irradiation. Moreover, in a breast cancer patient cohort high expression levels of ISGs were found in the primary tumor in around half of the patients. This was associated with a tumor infiltrating lymphocyte expression signature, although the ISGs were also expressed by the tumor cells themselves. Importantly, the expression of ISGs correlated to outcome in breast cancer patients treated with adjuvant tamoxifen or radiotherapy, but not in systemically untreated patients or chemotherapy-treated patients. Conclusions: Our data indicate that expression of ISGs by tumor cells is involved in acquired, treatment-induced resistance to tamoxifen and radiotherapy, and might play a role in intrinsic resistance via interaction with tumor infiltrating lymphocytes.

https://ift.tt/2IZUPef

Issue Information

Chemical Biology &Drug Design, Volume 91, Issue 5, Page 971-973, May 2018.

https://ift.tt/2JQKpih

Cover Image

Chemical Biology &Drug Design, Volume 91, Issue 5, Page i-i, May 2018.

https://ift.tt/2vhUGkE

Synthesis and effect of a new Terbium gibberellic complex on the histopathological alteration induced by Gibberellic acid on liver and kidney of mice Mus musculus

Chemical Biology &Drug Design, EarlyView.

https://ift.tt/2JS4eGa

Extreme Toughening of Soft Materials with Liquid Metal

Advanced Materials, EarlyView.

https://ift.tt/2HqTWyd

Ionic Gel Modulation of RKKY Interactions in Synthetic Anti‐Ferromagnetic Nanostructures for Low Power Wearable Spintronic Devices

Advanced Materials, EarlyView.

https://ift.tt/2vq46uu

Real‐Time Observation of Order‐Disorder Transformation of Organic Cations Induced Phase Transition and Anomalous Photoluminescence in Hybrid Perovskites

Advanced Materials, EarlyView.

https://ift.tt/2qC4rW3

Women Less Likely to Fill Post-MI Statin Prescription

MONDAY, April 16, 2018 -- Women are less likely than men to fill a prescription for high-intensity statins after hospitalization for myocardial infarction (MI), according to a study published in the April 24 issue of the Journal of the American...

https://ift.tt/2ERlwQ6

Recommendations Developed on Gender Equity in Medicine

MONDAY, April 16, 2018 -- In a position paper published online April 17 in the Annals of Internal Medicine, recommendations are provided aimed at addressing gender equity in physician compensation and career advancement opportunities. Renee Butkus...

https://ift.tt/2JRXpV4

Similar Outcomes for Transplant With Overdose-Death Donors

MONDAY, April 16, 2018 -- Transplantation of organs from overdose-death donors (ODDs) is associated with similar five-year patient survival and graft survival as organs from trauma-death donors (TDDs) and medical-death donors (MDDs), according to a...

https://ift.tt/2vlanat

Adjuvant Pembrolizumab Beneficial in Metastatic NSCLC

MONDAY, April 16, 2018 -- For metastatic non-small-cell lung cancer (NSCLC), the addition of pembrolizumab to standard chemotherapy is beneficial; and nivolumab plus ipilimumab is associated with better survival than chemotherapy for NSCLC with high...

https://ift.tt/2JRCOAm

Most Doctors' Offices Don't Offer Flexibility for Uninsured

MONDAY, April 16, 2018 -- Most physician offices do not offer up-front payment flexibility or low-income discounts to uninsured people, according to a study published in the April issue of Health Affairs. Brendan Saloner, Ph.D., from Johns Hopkins...

https://ift.tt/2ET6BVs

Barakat syndrome revisited

American Journal of Medical Genetics Part A, EarlyView.

https://ift.tt/2JP7cuW

EphA2 receptor is a key player in the metastatic onset of Ewing sarcoma

International Journal of Cancer, EarlyView.

https://ift.tt/2qDXt1L

Diabetes and smoking as predictors of cancer in Indigenous adults from rural and remote communities of North Queensland – A 15‐year follow up study

International Journal of Cancer, EarlyView.

https://ift.tt/2H6c2GJ

Smoking, alcohol and cancer mortality in Eastern European men: Findings from the PrivMort retrospective cohort study

International Journal of Cancer, EarlyView.

https://ift.tt/2qDXlzj

A PRDX1‐p38α heterodimer amplifies MET‐driven invasion of IDH‐wildtype and IDH‐mutant gliomas

International Journal of Cancer, EarlyView.

https://ift.tt/2H5COyI

Differential effects of estrogen receptor beta isoforms on glioblastoma progression

The estrogen receptor beta (ERβ) functions as a tumor suppressor in glioblastoma cells (GBM). However, the in vivo significance of endogenous ERβ and the roles of its isoforms in GBM are incompletely understood. Using ERβ isoform-specific PCR screening, we found that GBM cells predominantly express ERβ1 and ERβ5, along with low levels of ERβ2 and ERβ4. We observed greater ERβ5 expression in higher grades of glioma than in lower grades. In CRISPR-based ERβ knockout (KO) cells and ERβ KO cells uniquely expressing ERβ1, ERβ1 significantly reduced proliferation. Compared to parental GBM cells, ERβ KO cells exhibited high migratory and invasive potentials, and re-expression of ERβ1 resulted in the reduction of this phenotype. Interestingly, ERβ5 expression increased foci formation and anchorage-independent growth of NIH3T3 cells and increased motile structure formation, including filopodia and ruffles in GBM cells. Only ERβ1-expressing tumors resulted in longer mouse survival. RNA-Seq analysis revealed unique pathways modulated by ERβ1 and ERβ5. Compared to ERβ KO cells, ERβ1 cells exhibited lower activation of mTOR signaling molecules, including p-mTOR, p-S6K, and p-S6; and ERβ5-expressing cells had enhanced mTOR downstream signaling. Unique proteins including several that function as regulators of mTOR, immunomodulatory, and apoptosis pathways bound to ERβ1 and ERβ5 isoforms. Our work confirms the tumor suppressive potential of ERβ1 and reveals the acquired oncogenic ability of ERβ5 in GBM cells. ERβ isoform status and their unique interactions with oncogenic pathways may have important implications in GBM progression.

https://ift.tt/2HFwWcq

Sustained adrenergic signaling promotes intratumoral innervation through BDNF induction

Mounting clinical and preclinical evidence supports a key role for sustained adrenergic signaling in the tumor microenvironment as a driver of tumor growth and progression. However, the mechanisms by which adrenergic neurotransmitters are delivered to the tumor microenvironment are not well understood. Here we present evidence for a feedforward loop whereby adrenergic signaling leads to increased tumoral innervation. In response to catecholamines, tumor cells produced brain-derived neurotrophic factor (BDNF) in an ADRB3/cAMP/Epac/JNK-dependent manner. Elevated BDNF levels in the tumor microenvironment increased innervation by signaling through host neurotrophic receptor tyrosine kinase 2 (TrkB) receptors. In cancer patients, high tumor nerve counts were significantly associated with increased BDNF and norepinephrine levels and decreased overall survival. Collectively, these data describe a novel pathway for tumor innervation with resultant biological and clinical implications.

https://ift.tt/2H7tINQ

Endoscopic management of bile duct stones in patients with surgically altered anatomy

Digestive Endoscopy, Volume 30, Issue S1, Page 67-74, April 2018.

https://ift.tt/2vmftmU

Endoscopic excavation technique for gastric gastrointestinal stromal tumor: A case report

Digestive Endoscopy, Volume 30, Issue S1, Page 33-34, April 2018.

https://ift.tt/2ERPROh

Potential of artificial intelligence‐assisted colonoscopy using an endocytoscope (with video)

Digestive Endoscopy, Volume 30, Issue S1, Page 52-53, April 2018.

https://ift.tt/2JQ0cxX

Issue Information

Digestive Endoscopy, Volume 30, Issue S1, Page ii-v, April 2018.

https://ift.tt/2JPhlb2

Endoscopic ultrasonography‐guided antegrade treatment for bile duct stone with multi‐step approach in a patient with surgically altered anatomy

Digestive Endoscopy, Volume 30, Issue S1, Page 77-78, April 2018.

https://ift.tt/2ERYCbd

Comparison between endoscopic and laparoscopic removal of gastric submucosal tumor

Digestive Endoscopy, Volume 30, Issue S1, Page 7-16, April 2018.

https://ift.tt/2JQyuRy

Treatment for difficult bile duct stones: Balloon enteroscopy assisted‐endoscopic retrograde cholangiopancreatography

Digestive Endoscopy, Volume 30, Issue S1, Page 76-77, April 2018.

https://ift.tt/2ES1qF3

Peroral endoscopic submucosal tumor resection

Digestive Endoscopy, Volume 30, Issue S1, Page 34-35, April 2018.

https://ift.tt/2vgcTyI

Endoscopic management of colorectal tumors less than 10 mm in size: Current status and future perspectives in Japan from a questionnaire survey

Digestive Endoscopy, Volume 30, Issue S1, Page 36-40, April 2018.

https://ift.tt/2JRE7iK

Case of multiple cholesterol common bile duct stones that were refractory to endoscopic mechanical lithotripsy

Digestive Endoscopy, Volume 30, Issue S1, Page 75-76, April 2018.

https://ift.tt/2ESmICD

Cover Image

Digestive Endoscopy, Volume 30, Issue S1, Page i-i, April 2018.

https://ift.tt/2JP3r8O

Laparoscopic endoscopic cooperative surgery for gastric cancer with severe fibrosis

Digestive Endoscopy, Volume 30, Issue S1, Page 32-33, April 2018.

https://ift.tt/2ESmyLx

Current status and future perspectives of endoscopic full‐thickness resection

Digestive Endoscopy, Volume 30, Issue S1, Page 25-31, April 2018.

https://ift.tt/2JSFg9K

Challenges associated with the pathological diagnosis of colorectal tumors less than 10 mm in size

Digestive Endoscopy, Volume 30, Issue S1, Page 41-44, April 2018.

https://ift.tt/2ERYAA7

Preface

Digestive Endoscopy, Volume 30, Issue S1, Page 1-1, April 2018.

https://ift.tt/2vjJX9g

Endoscopic full‐thickness resection for gastrointestinal submucosal tumors

Digestive Endoscopy, Volume 30, Issue S1, Page 17-24, April 2018.

https://ift.tt/2JSmS0A

Additional chromoendoscopy for colorectal lesions initially diagnosed with low confidence by magnifying narrow‐band imaging: Can it improve diagnostic accuracy?

Digestive Endoscopy, Volume 30, Issue S1, Page 45-50, April 2018.

https://ift.tt/2JTaHRg

Table of Content Volume 57, Number 6, June 2018

Genes, Chromosomes and Cancer, Volume 57, Issue 6, Page 279-280, June 2018.

https://ift.tt/2ERlZln

Premenstrual syndrome and alcohol consumption: a systematic review and meta-analysis

Objective

Premenstrual syndrome (PMS) is a very common disorder worldwide which carries an important economic burden. We conducted a systematic review and a meta-analysis to assess the role of alcohol in the occurrence of PMS.

Methods

We searched MEDLINE, EMBASE, the five regional bibliographic databases of the WHO, the Proceedings database and the Open Access Thesis and Dissertations (OATD) from inception to May 2017. We also reviewed the references of every article retrieved and established personal contact with researchers to trace further publications or reports. We did not include any language limitations. Studies were included if: (1) they presented original data from cohort, case-control or cross-sectional studies, (2) PMS was clearly defined as the outcome of interest, (3) one of the exposure factors was alcohol consumption, (4) they provided estimates of odds ratios, relative risks, or any other effect measure and their confidence intervals, or enough data to calculate them.

Results

We identified 39 studies of which 19 were eligible. Intake of alcohol was associated with a moderate increase in the risk of PMS (OR=1.45, 95% CI: 1.17 to 1.79). Heavy drinking yielded a larger increase in the risk than any drinking (OR=1.79, 95% CI: 1.39 to 2.32).

Discussion

Our results suggest that alcohol intake presents a moderate association with PMS risk. Future studies should avoid cross-sectional designs and focus on determining whether there is a threshold of alcohol intake under which the harmful effect on PMS is non-existent.

https://ift.tt/2J13qgP

Trends, geographical variation and factors associated with prescribing of gluten-free foods in English primary care: a cross-sectional study

Objectives

There is substantial disagreement about whether gluten-free foods should be prescribed on the National Health Service. We aim to describe time trends, variation and factors associated with prescribing gluten-free foods in England.

Setting

English primary care.

Participants

English general practices.

Primary and secondary outcome measures

We described long-term national trends in gluten-free prescribing, and practice and Clinical Commissioning Group (CCG) level monthly variation in the rate of gluten-free prescribing (per 1000 patients) over time. We used a mixed-effect Poisson regression model to determine factors associated with gluten-free prescribing rate.

Results

There were 1.3 million gluten-free prescriptions between July 2016 and June 2017, down from 1.8 million in 2012/2013, with a corresponding cost reduction from £25.4 million to £18.7 million. There was substantial variation in prescribing rates among practices (range 0 to 148 prescriptions per 1000 patients, IQR 7.3–31.8), driven in part by substantial variation at the CCG level, likely due to differences in prescribing policy. Practices in the most deprived quintile of deprivation score had a lower prescribing rate than those in the highest quintile (incidence rate ratio 0.89, 95% CI 0.87 to 0.91). This is potentially a reflection of the lower rate of diagnosed coeliac disease in more deprived populations.

Conclusion

Gluten-free prescribing is in a state of flux, with substantial clinically unwarranted variation between practices and CCGs.

https://ift.tt/2HFQgq7

Patient with mediastinitis caused by delayed mucosal damage after peroral endoscopic myotomy

Asian Journal of Endoscopic Surgery, EarlyView.

https://ift.tt/2H64gws

Splenic artery as a simple landmark indicating difficulty during laparoscopic distal pancreatectomy

Asian Journal of Endoscopic Surgery, EarlyView.

https://ift.tt/2qDzzDv

Seven additional families with spondylocarpotarsal synostosis syndrome with novel biallelic deleterious variants in FLNB

Clinical Genetics, EarlyView.

https://ift.tt/2ER9JRQ

Erratum

Clinical Genetics, Volume 93, Issue 5, Page 1117-1117, May 2018.

https://ift.tt/2ERqjRi

Correction to: PUGS: A novel scale to assess perceptions of uncertainties in genome sequencing

Clinical Genetics, Volume 93, Issue 5, Page 1119-1119, May 2018.

https://ift.tt/2HurQCq

Issue Information ‐ Editorial Board

Clinical Genetics, Volume 93, Issue 5, Page 941-941, May 2018.

https://ift.tt/2vn5r5b

Decorin modified umbilical cord mesenchymal stem cells (MSCs) attenuate radiation induced lung injuries via regulating inflammation, fibrotic factors and immune responses

Effective strategies are still lack for treating RILI. In experimental RILI model, we found MSCs.DCNcould home to injured lung tissues and produced decorin protein. Then, MSCs secreted cytokines to attenuate inflammation, regulated apoptosis and proliferation to promote tissue repair, and modulated pro-fibrotic factors to inhibit fibrosis. Secreted decorin protein inhibited pro-inflammatory and pro-fibrotic factors to enhance functions of MSCs. Therefore, MSCs.DCN might be a potential strategy for treating RILI.

https://ift.tt/2IZl44A

In vivo validation of Elekta’s Clarity Autoscan® for ultrasound-based intrafraction motion estimation of the prostate during radiotherapy

The manuscript describes an in vivo validation of the Elekta Clarity Autoscan® system for estimating intrafraction prostate motion during radiotherapy. Intrafraction motion was estimated using Autoscan. These 3D motion estimates were used to estimate intraprostatic fiducial marker positions in 2D portal images. Estimated positions were compared to the actual portal imaged marker positions. Clarity monitored intrafraction motion with an accuracy of 0.6 mm, which is comparable to other motion monitoring systems used in radiotherapy.

https://ift.tt/2HmqolB

The American College of Physicians Is Working Hard to Achieve Gender Equity, and Everyone Will Benefit

An American College of Physicians (ACP) position paper provides recommendations aimed at eliminating gender inequities in compensation and career advancement opportunities and providing a more inclusive environment to realize the full potential of all physicians. The editorialist discusses how gender stereotypes threaten the realization of ACP's goal and proposes strategies to combat their influence.

https://ift.tt/2qHFd7Z

Achieving Gender Equity in Physician Compensation and Career Advancement: A Position Paper of the American College of Physicians

Women comprise more than one third of the active physician workforce, an estimated 46% of all physicians-in-training, and more than half of all medical students in the United States. Although progress has been made toward gender diversity in the physician workforce, disparities in compensation exist and inequities have contributed to a disproportionately low number of female physicians achieving academic advancement and serving in leadership positions. Women in medicine face other challenges, including a lack of mentors, discrimination, gender bias, cultural environment of the workplace, imposter syndrome, and the need for better work–life integration. In this position paper, the American College of Physicians summarizes the unique challenges female physicians face over the course of their careers and provides recommendations to improve gender equity and ensure that the full potential of female physicians is realized.

https://ift.tt/2H80bIc

If You Can't Beat It, Join It: Uncertainty and Trust in Medicine

The quest to eliminate uncertainty in clinical decision making has become central to biomedical research over the past 50 years, driving the emergence of evidence-based medicine, precision medicine, and most recently, biomedical artificial intelligence. This commentary discusses how, despite being a source of discomfort, the handling of uncertainty can also have an important positive effect on medical care.

https://ift.tt/2qCjwpD

Every Cloud Has a Silver Lining: Overdose-Death Donors in Organ Transplantation

In this issue, Durand and colleagues review the use of overdose-death donor (ODD) organ transplants involving 138 565 deceased donors and 337 934 solid organ transplant recipients from 2000 to 2017. The editorialist discusses the findings and the opportunities for expanding organ availability that the use of ODD organs provides.

https://ift.tt/2H7Bk75

The Need for Closed-Loop Systems for Management of Abnormal Test Results

The authors observe that their hospital performed approximately equal numbers of screening mammographies and Pap smears each year. Follow-up was appropriate for more than 99% of abnormal mammograms but only 91% of abnormal Pap smears. They examine the reasons for these differences and propose improvements for follow-up of abnormal results from other diagnostic tests.

https://ift.tt/2qCjoGF

Storing and Disposing of Opioid Analgesics: What Does Our Medicine Tell Us?

https://ift.tt/2H3VcrM

The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States A National Registry Study

Background:

The epidemic of drug overdose deaths in the United States has led to an increase in organ donors.

Objective:

To characterize donors who died of overdose and to analyze outcomes among transplant recipients.

Design:

Prospective observational cohort study.

Setting:

Scientific Registry of Transplant Recipients, 1 January 2000 to 1 September 2017.

Participants:

138 565 deceased donors; 337 934 transplant recipients at 297 transplant centers.

Measurements:

The primary exposure was donor mechanism of death (overdose-death donor [ODD], trauma-death donor [TDD], or medical-death donor [MDD]). Patient and graft survival and organ discard (organ recovered but not transplanted) were compared using propensity score–weighted standardized risk differences (sRDs).

Results:

A total of 7313 ODDs and 19 897 ODD transplants (10 347 kidneys, 5707 livers, 2471 hearts, and 1372 lungs) were identified. Overdose-death donors accounted for 1.1% of donors in 2000 and 13.4% in 2017. They were more likely to be white (85.1%), aged 21 to 40 years (66.3%), infected with hepatitis C virus (HCV) (18.3%), and increased–infectious risk donors (IRDs) (56.4%). Standardized 5-year patient survival was similar for ODD organ recipients compared with TDD organ recipients (sRDs ranged from 3.1% lower to 3.9% higher survival) and MDD organ recipients (sRDs ranged from 2.1% to 5.2% higher survival). Standardized 5-year graft survival was similar between ODD and TDD grafts (minimal difference for kidneys and lungs, marginally lower [sRD, −3.2%] for livers, and marginally higher [sRD, 1.9%] for hearts). Kidney discard was higher for ODDs than TDDs (sRD, 5.2%) or MDDs (sRD, 1.5%); standardization for HCV and IRD status attenuated this difference.

Limitation:

Inability to distinguish between opioid and nonopioid overdoses.

Conclusion:

In the United States, transplantation with ODD organs has increased dramatically, with noninferior outcomes in transplant recipients. Concerns about IRD behaviors and hepatitis C among donors lead to excess discard that should be minimized given the current organ shortage.

Primary Funding Source:

National Institutes of Health.

https://ift.tt/2H5geWS

Marijuana Use by Adolescents and Young Adults with Inflammatory Bowel Disease

To evaluate marijuana use by adolescents and young adults with inflammatory bowel disease (IBD).

https://ift.tt/2HrEpy4

Review: Adjunctive corticosteroids reduce mortality and clinical failure in adult inpatients with CAP

https://ift.tt/2qBi47B

Trends in Racial/Ethnic and Nativity Disparities in Cardiovascular Health Among Adults Without Prevalent Cardiovascular Disease in the United States, 1988 to 2014

Background:

Trends in cardiovascular disparities are poorly understood, even as diversity increases in the United States.

Objective:

To examine U.S. trends in racial/ethnic and nativity disparities in cardiovascular health.

Design:

Repeated cross-sectional study.

Setting:

NHANES (National Health and Nutrition Examination Survey), 1988 to 2014.

Participants:

Adults aged 25 years or older who did not report cardiovascular disease.

Measurements:

Racial/ethnic, nativity, and period differences in Life's Simple 7 (LS7) health factors and behaviors (blood pressure, cholesterol, hemoglobin A_1c, body mass index, physical activity, diet, and smoking) and optimal composite scores for cardiovascular health (LS7 score ≥10).

Results:

Rates of optimal cardiovascular health remain below 40% among whites, 25% among Mexican Americans, and 15% among African Americans. Disparities in optimal cardiovascular health between whites and African Americans persisted but decreased over time. In 1988 to 1994, the percentage of African Americans with optimal LS7 scores was 22.8 percentage points (95% CI, 19.3 to 26.4 percentage points) lower than that of whites in persons aged 25 to 44 years and 8.0 percentage points (CI, 6.4 to 9.7 percentage points) lower in those aged 65 years or older. By 2011 to 2014, differences decreased to 10.6 percentage points (CI, 7.4 to 13.9 percentage points) and 3.8 percentage points (CI, 2.5 to 5.0 percentage points), respectively. Disparities in optimal LS7 scores between whites and Mexican Americans were smaller but also decreased. These decreases were due to reductions in optimal cardiovascular health among whites over all age groups and periods: Between 1988 to 1994 and 2011 to 2014, the percentage of whites with optimal cardiovascular health decreased 15.3 percentage points (CI, 11.1 to 19.4 percentage points) for those aged 25 to 44 years and 4.6 percentage points (CI, 2.7 to 6.5 percentage points) for those aged 65 years or older.

Limitation:

Only whites, African Americans, and Mexican Americans were studied.

Conclusion:

Cardiovascular health has declined in the United States, racial/ethnic and nativity disparities persist, and decreased disparities seem to be due to worsening cardiovascular health among whites rather than gains among African Americans and Mexican Americans. Multifaceted interventions are needed to address declining population health and persistent health disparities.

Primary Funding Source:

National Institute of Neurological Disorders and Stroke and National Center for Advancing Translational Sciences of the National Institutes of Health.

https://ift.tt/2FT6o64

A Health App to Promote Colorectal Cancer Screening

https://ift.tt/2DmEbCk

Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients A Randomized Controlled Trial

Background:

Screening for colorectal cancer (CRC) reduces mortality, yet more than one third of age-eligible Americans are unscreened.

Objective:

To examine the effect of a digital health intervention, Mobile Patient Technology for Health–CRC (mPATH-CRC), on rates of CRC screening.

Design:

Randomized clinical trial. (ClinicalTrials.gov: NCT02088333)

Setting:

6 community-based primary care practices.

Participants:

450 patients (223 in the mPATH-CRC group and 227 in usual care) scheduled for a primary care visit and due for routine CRC screening.

Intervention:

An iPad application that displays a CRC screening decision aid, lets patients order their own screening tests, and sends automated follow-up electronic messages to support patients.

Measurements:

The primary outcome was chart-verified completion of CRC screening within 24 weeks. Secondary outcomes were ability to state a screening preference, intention to receive screening, screening discussions, and orders for screening tests. All outcome assessors were blinded to randomization.

Results:

Baseline characteristics were similar between groups; 37% of participants had limited health literacy, and 53% had annual incomes less than $20 000. Screening was completed by 30% of mPATH-CRC participants and 15% of those receiving usual care (logistic regression odds ratio, 2.5 [95% CI, 1.6 to 4.0]). Compared with usual care, more mPATH-CRC participants could state a screening preference, planned to be screened within 6 months, discussed screening with their provider, and had a screening test ordered. Half of mPATH-CRC participants (53%; 118 of 223) "self-ordered" a test via the program.

Limitation:

Participants were English speakers in a single health care system.

Conclusion:

A digital health intervention that allows patients to self-order tests can increase CRC screening. Future research should identify methods for implementing similar interventions in clinical care.

Primary Funding Source:

National Cancer Institute.

https://ift.tt/2FwJXYe

Annals for Educators - 17 April 2018

https://ift.tt/2qBiivt

like a winter freeze

https://ift.tt/2qBi9YX

Hemoglobin A 1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians

Description:

The American College of Physicians developed this guidance statement to guide clinicians in selecting targets for pharmacologic treatment of type 2 diabetes.

Methods:

The National Guideline Clearinghouse and the Guidelines International Network library were searched (May 2017) for national guidelines, published in English, that addressed hemoglobin A_1c (HbA_1c) targets for treating type 2 diabetes in nonpregnant outpatient adults. The authors identified guidelines from the National Institute for Health and Care Excellence and the Institute for Clinical Systems Improvement. In addition, 4 commonly used guidelines were reviewed, from the American Association of Clinical Endocrinologists and American College of Endocrinology, the American Diabetes Association, the Scottish Intercollegiate Guidelines Network, and the U.S. Department of Veterans Affairs and Department of Defense. The AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument was used to evaluate the guidelines.

Guidance Statement 1:

Clinicians should personalize goals for glycemic control in patients with type 2 diabetes on the basis of a discussion of benefits and harms of pharmacotherapy, patients' preferences, patients' general health and life expectancy, treatment burden, and costs of care.

Guidance Statement 2:

Clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes.

Guidance Statement 3:

Clinicians should consider deintensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%.

Guidance Statement 4:

Clinicians should treat patients with type 2 diabetes to minimize symptoms related to hyperglycemia and avoid targeting an HbA1c level in patients with a life expectancy less than 10 years due to advanced age (80 years or older), residence in a nursing home, or chronic conditions (such as dementia, cancer, end-stage kidney disease, or severe chronic obstructive pulmonary disease or congestive heart failure) because the harms outweigh the benefits in this population.

https://ift.tt/2oNePsU

Review: In community-dwelling older adults, calcium and vitamin D, alone or combined, do not reduce fractures

https://ift.tt/2H1qKhU

Annals Story Slam - Life Lessons

https://ift.tt/2H8Ty4k

Technology and Transparency: Empowering Patients and Clinicians to Improve Health Care Value

With patients and clinicians confronting daunting uncertainties in health care, arguments rage about quality, costs, and how to improve the lives of both those who seek and those who provide care. In light of rapidly evolving health information technologies, the authors anticipate that widespread societal movement toward greater transparency will spur important advances.

https://ift.tt/2H6PQYh

Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus–Infected Donors to Noninfected Recipients An Open-Label Nonrandomized Trial

Background:

Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource.

Objective:

To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non–HCV-infected recipients (that is, HCV D⁺/R⁻ transplantation).

Design:

Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649)

Setting:

Single center.

Participants:

10 HCV D⁺/R⁻ kidney transplant candidates older than 50 years with no available living donors.

Intervention:

Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR–EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR–EBR for 12 weeks of triple therapy.

Measurements:

The primary safety outcome was the incidence of adverse events related to GZR–EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis.

Results:

Among 10 HCV D⁺/R⁻ transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.

Limitation:

Nonrandomized study design and a small number of patients.

Conclusion:

Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D⁺/R^– kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.

Primary Funding Source:

Merck Sharp & Dohme.

https://ift.tt/2FoBkOx

Eliminating Alcohol-Impaired Driving Fatalities: What Can Be Done?

More than 10 000 alcohol-related driving fatalities occur each year. To identify ways of reinvigorating efforts to stem these tragic events, the National Highway Traffic Safety Administration asked the National Academies of Sciences, Engineering, and Medicine to form a committee to rigorously study the problem and make recommendations. This commentary highlights those recommendations.

https://ift.tt/2FMFi0E

The Short-Lived Epidemic of Botulism From Commercially Canned Foods in the United States, 1919 to 1925

In 1919, three deadly outbreaks of botulism caused by consumption of canned olives packed in California captured national headlines. In all of the outbreaks, which occurred in separate locales, unsuspecting people died after consuming tainted food during a banquet or family meal. The press's sensational portrayal of canned food as hazardous aroused alarm among consumers at a time when commercial canning was becoming more common. Intent on restoring the image of their product as safe and wholesome, canning industry leaders funded a "botulism commission" of scientific experts in 1919 to investigate how to systematically eliminate the threat of botulism that had imperiled their business. The commissioners identified the scientific reasons for the outbreaks, and on the basis of their findings, the California Department of Public Health issued explicit recommendations for sterilization procedures intended to ensure safety. However, the department did not mandate inspections for all canneries. When commercially packed fruits and vegetables continued to cause botulism, industry leaders voluntarily backed a cannery inspection act to legally require all California canners to possess appropriate equipment and follow scientifically validated sterilization procedures. After the California legislature approved the act in 1925, canneries were inspected, regulations were enforced, and no further outbreaks occurred.This botulism epidemic is an example of a disease outbreak that was controlled when business interests became aligned with public health goals. The press's portrayal of afflicted persons as innocent victims and worthy citizens galvanized businessmen to implement safeguards to protect consumers from botulism intoxication. To preserve their customer base and salvage their corporations, leaders of the canning industry acknowledged the public health threat of their unregulated procedures and acted on the recommendations of scientists.

https://ift.tt/2qC5K7m

In perfusion imaging–selected acute ischemic stroke, thrombectomy at 6 to 16 hours improved functional outcomes

https://ift.tt/2H3kEto

The Black–White Cardiovascular Health Disparity Is Narrowing, But Not for the Reason You Think

Disparities in cardiovascular health remain pervasive in the United States, with higher mortality in blacks than whites. Brown and colleagues' report showed a narrowing of the black–white gap in cardiovascular health. The editorialist notes that while this result seems encouraging, the report adds an unexpected but important wrinkle to the health disparities saga.

https://ift.tt/2DG0NxQ

In type 2 diabetes, weekly semaglutide reduced HbA 1c and increased weight loss more than weekly exenatide ER

https://ift.tt/2J13yNq

Advancing Patient Care Through Focused Innovation

NCI Director Dr. Ned Sharpless describes the four focus areas of opportunity he has identified that, with enhanced attention from NCI, he believes can accelerate progress in cancer research and care.

https://ift.tt/2EQZNaQ

Too Much of a Good Thing: How Novelty Biases and Vocabulary Influence Known and Novel Referent Selection in 18‐Month‐Old Children and Associative Learning Models

Cognitive Science, EarlyView.

https://ift.tt/2ERPbbF

Aerobic bacteria on cervical cytology

Diagnostic Cytopathology, EarlyView.

https://ift.tt/2H2Ux5W

Adenocarcinoma in situ admixed with small cell neuroendocrine carcinoma of the cervix: A case report with cytological features

Diagnostic Cytopathology, EarlyView.

https://ift.tt/2HDgauK

Issue Information

Diagnostic Cytopathology, Volume 46, Issue 5, Page 367-368, May 2018.

https://ift.tt/2H3Z9IX

Diagnosis of pseudo‐gout (calcium pyrophosphate deposition disease) clinched on cytology

Diagnostic Cytopathology, EarlyView.

https://ift.tt/2IZs9SD

Copy number gain in recurrent anaplastic lymphoma kinase (ALK) rearrangement‐lung adenocarcinoma in the pleural effusion

Diagnostic Cytopathology, EarlyView.

https://ift.tt/2HDL2eB

Cytological features of hepatoid adenocarcinoma of the gallbladder: A case report with immunocytochemical analyzes

Diagnostic Cytopathology, EarlyView.

https://ift.tt/2H6sUcj

Cyto‐morphologic spectrum of thyroid lesions in children

Diagnostic Cytopathology, EarlyView.

https://ift.tt/2HGcLvi

Evaluation of the effect of self‐cutting and nonself‐cutting thread designed implant with different thread depth on variable insertion torques: An histomorphometric analysis in rabbits

Clinical Implant Dentistry and Related Research, EarlyView.

https://ift.tt/2H3pCu9

Issue Information

Clinical Implant Dentistry and Related Research, Volume 20, Issue 2, Page 93-95, April 2018.

https://ift.tt/2qE9rsb

Cardiac responses to viewing facial emotion differentiate frontotemporal dementias

Annals of Clinical and Translational Neurology, EarlyView.

https://ift.tt/2EQxf1h

The impact of rituximab infusion protocol on the long‐term outcome in anti‐MuSK myasthenia gravis

Annals of Clinical and Translational Neurology, EarlyView.

https://ift.tt/2HnH10b

Issue Information

Annals of Clinical and Translational Neurology, Volume 5, Issue 4, Page 383-385, April 2018.

https://ift.tt/2ERfnmN

Cognitive and functional connectivity alterations in Friedreich's ataxia

Annals of Clinical and Translational Neurology, EarlyView.

https://ift.tt/2HnGGur

Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers

Annals of Clinical and Translational Neurology, EarlyView.

https://ift.tt/2HnFUh1

Subclinical vestibular dysfunction in migraineurs without vertigo: A Clinical study

Acta Neurologica Scandinavica, EarlyView.

https://ift.tt/2J2U443

Hyponatremia in neuromyelitis optica spectrum disorders: Literature review

Acta Neurologica Scandinavica, EarlyView.

https://ift.tt/2H3CYCx

Comments on marital status is a prognostic factor in amyotrophic lateral sclerosis

Acta Neurologica Scandinavica, Volume 137, Issue 5, Page 538-538, May 2018.

https://ift.tt/2HD7Ivw

Cover Image

Acta Neurologica Scandinavica, Volume 137, Issue 5, Page i-i, May 2018.

https://ift.tt/2IZjJL1

Issue Information

Acta Neurologica Scandinavica, Volume 137, Issue 5, Page 439-441, May 2018.

https://ift.tt/2HDDsAF

Response to the letter to the Editor: Comments on marital status is a prognostic factor in amyotrophic lateral sclerosis. Safiri S et al

Acta Neurologica Scandinavica, Volume 137, Issue 5, Page 539-539, May 2018.

https://ift.tt/2H3CHiZ

Intravenous lacosamide for treatment of absence status epilepticus in genetic generalized epilepsy: A case report and review of literature

Acta Neurologica Scandinavica, EarlyView.

https://ift.tt/2HFl1f1

Neurofilament light protein levels in cerebrospinal fluid predict long‐term disability of Guillain‐Barré syndrome: A pilot study

Acta Neurologica Scandinavica, EarlyView.

https://ift.tt/2J04i5i

An In Vitro Model to Study the Effect of 5-Aminolevulinic Acid-mediated Photodynamic Therapy on Staphylococcus aureus Biofilm

This manuscript describes a protocol to study the antimicrobial effect of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) on a Staphylococcus aureus biofilm. This protocol can be used to develop an in vitro model to study the treatment of bacterial biofilms with PDT in the future.

https://ift.tt/2qD2rM7

Electrochemical Detection of Deuterium Kinetic Isotope Effect on Extracellular Electron Transport in Shewanella oneidensis MR-1

Here we present a protocol of whole-cell electrochemical experiments to study the contribution of proton transport to the rate of extracellular electron transport via the outer-membrane cytochromes complex in Shewanella oneidensis MR-1.

https://ift.tt/2H4CFM9

A silent eligibility trace enables dopamine‐dependent synaptic plasticity for reinforcement learning in the mouse striatum

European Journal of Neuroscience, EarlyView.

https://ift.tt/2HszMUI

Dose‐dependent modulation of the visually evoked N1/N170 by perceptual surprise: a clear demonstration of prediction‐error signalling

European Journal of Neuroscience, EarlyView.

https://ift.tt/2ERw2qj

Treatment with the GSK3‐beta inhibitor Tideglusib improves hippocampal development and memory performance in juvenile, but not adult, Cdkl5 knockout mice

European Journal of Neuroscience, EarlyView.

https://ift.tt/2qHp3fF

Issue Information

Histopathology, Volume 72, Issue 6, Page 889-891, May 2018.

https://ift.tt/2EQnvEf

Malignant Spindle Cell Tumor Breast—a Diagnostic Dilemma

Abstract

Primary malignant spindle cell tumors are rare constituting 1.0% of breast malignancies. Spindle cell lesions occurring in soft tissues can occur in breast with overlapping morphologies. It can present as benign lesion and have inconclusive cytological findings, so easily missed if not properly dealt with. Stromal sarcoma should be diagnosed only after thorough sectioning and negative staining for p63, broad spectrum, and high molecular weight keratin. We present a case of right breast lump. Cytological features revealed fibro histiocytic lesion. There were no areas of necrosis, hemorrhage, or calcification. Histopathologically, it showed partially encapsulated tumor with cells arranged in sheets, composed of oval to epithelioid cells with spindling at places with moderate pleomorphism (mitotic activity 6–7/10 hpf). Differential diagnosis of primary stromal sarcoma, metaplastic sarcoma, and phyllodes was made. Immunohistochemistry revealed vimentin positivity with focal positivity of S-100. Desmin, cytokeratin and smooth muscle actin, p63, ER, PR, and Her2-neu were negative. A final diagnosis of primary breast sarcoma of neural origin was established with the help of histopathology and immunohistochemistry. To conclude, it is of utmost importance to identify primary stromal sarcomas as they are known to spread very rapidly and have a poor prognosis.

https://ift.tt/2qAhW7y

Abstract Journal Vascular Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 223-229, May 2018.

https://ift.tt/2vfxiE4

Abstract Journal Indigenous Health

ANZ Journal of Surgery, Volume 88, Issue S1, Page 101-102, May 2018.

https://ift.tt/2JM9yux

Abstract Journal Medico‐legal Program

ANZ Journal of Surgery, Volume 88, Issue S1, Page 103-105, May 2018.

https://ift.tt/2JPmmjT

Abstract Journal Military Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 106-107, May 2018.

https://ift.tt/2JRxhJN

Abstract Journal Trauma Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 210-215, May 2018.

https://ift.tt/2vrKOoz

Abstract Journal Women in Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 230-230, May 2018.

https://ift.tt/2JOz8iI

Abstract Journal Breast Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 9-17, May 2018.

https://ift.tt/2EQjnnJ

Abstract Journal Neurosurgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 108-112, May 2018.

https://ift.tt/2ERWMa7

Abstract Journal Craniomaxillofacial Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 41-47, May 2018.

https://ift.tt/2JOyVfq

Abstract Journal Transplantation Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 206-209, May 2018.

https://ift.tt/2EPLyDl

Abstract Journal Endocrine Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 48-53, May 2018.

https://ift.tt/2JOyRfG

Abstract Journal General Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 54-67, May 2018.

https://ift.tt/2JOyKRi

Abstract Journal Bariatric Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 3-8, May 2018.

https://ift.tt/2EOZcXe

Abstract Journal Hand Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 71-79, May 2018.

https://ift.tt/2JSctSm

Abstract Journal Burn Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 18-23, May 2018.

https://ift.tt/2ERWjon

Abstract Journal Head & Neck Surgery

ANZ Journal of Surgery, Volume 88, Issue S1, Page 80-89, May 2018.

https://ift.tt/2JOyCRO

Effective school-based cavity prevention program

School-based prevention programs can substantially reduce children's cavities -- but what type of treatment should be delivered in schools to best prevent tooth decay? A new study suggests that cavity prevention programs with a combination of prevention strategies may be more effective than one alone for reducing tooth decay.

https://ift.tt/2qBuXOs

EMT remains friends with mom and child she saved 20 years ago

By Molly Crane-Newman New York Daily News NEW YORK — EMT Vivian Lomacang was in the final minutes of her shift when her two-way radio crackled to life with what seemed like an unremarkable job. It was a mild March evening, and the emergency dispatcher reported "a heavy bleeder" inside an apartment at Monroe St. and Marcus Garvey Blvd. in Bedford-Stuyvesant, Brooklyn. Lomacang and her ...

https://ift.tt/2qAEm9G

Imaging appearance of well-differentiated liposarcomas with myxoid stroma

Abstract

Objective

Describe the imaging appearance of well-differentiated liposarcoma with myxoid stroma (WDLMS) and correlate with histopathology.

Materials and methods

A keyword search of the institution medical records was performed from 1 January 2000 to 30 June 2017. The histopathology slides of cases identified in this fashion were then reviewed by a pathologist. Additional cases were prospectively collected from extramural referrals and tumor boards. Diagnostic imaging studies of pathologically proven cases of WDLMS were then reviewed in consensus and correlated with pathology.

Results

Ten cases of pathologically proven WDLMS were identified (7 men, 3 women, ages 26–81). Tumor location included the retroperitoneum (n = 5), thigh (n = 4), and the shin (n = 1). Nine patients had macroscopic fat on imaging. The nonlipomatous components had a variable appearance, including septal, nodular, and lacelike patterns. Two cases included two distinct areas that were predominantly myxoid or lipomatous ("bi-morphic"). One tumor had no macroscopic fat on imaging. On CT, the nonlipomatous nodular components were hypodense/had hypodense areas. On MRI, the nodular components had intermediate/bright T2W signal. Interval nonlipomatous nodular growth was identified in 3 cases.

Conclusion

WDLMS may present on imaging as a mass with variable morphology and amounts of nonlipomatous components. Histopathological diagnosis of WDLMS is challenging and imaging correlation may be helpful, as this tumor may have ≥50% fatty volume, may have a myxoid nodular component or bi-morphic appearance, or may be located in the retroperitoneum, features that are unusual for myxoid liposarcoma. WDLMS with a nodular component cannot be distinguished from dedifferentiated liposarcoma based on imaging alone.

https://ift.tt/2IZcXVD

CT-guided biopsy in suspected spondylodiscitis: microbiological yield, impact on antimicrobial treatment, and relationship with outcome

Abstract

Purpose

To investigate the clinical impact of CT-guided biopsy, as performed in routine clinical practice, in patients with suspected spondylodiscitis on MRI in terms of culture yield, impact on antimicrobial treatment, and outcome.

Methods

This study included 64 patients with MRI findings compatible with spondylodiscitis who underwent CT-guided biopsy.

Results

Initial CT-guided biopsies were culture-positive in 20/64 (31.3%, 95% confidence interval [CI] 21.2–43.3%). Repeat CT-guided biopsies (after initial negative biopsy) were culture-positive in an additional 5/15 (33.3%, 95% CI 15.2–58.3%). Serum leukocytes, C-reactive protein, pre-biopsy use of antibiotics, neurological symptoms, MRI findings, vertebral height loss, and hyperkyphosis were not significantly different between culture-positive and culture-negative cases (P = 0.214–1.000); 75% (15/20) of initial CT-guided biopsies that were culture-positive provided additional information to clinicians for guiding antibiotic treatment. Sixty-two of 64 patients (96.9%, 95% CI 89.3–99.1%) would have been adequately treated if a strategy was followed that would subject all patients without clinical findings suspicious for "atypical" microorganisms and negative blood cultures to empirical antibiotics (i.e., clindamycin for coverage of Gram-positive bacteria) without using biopsy results to determine the optimal antibiotic regimen. Outcome within 6 months (development of neurologic or orthopedic complications, surgery, and death) was not significantly different (P = 0.751) between culture-positive and culture-negative patients.

Conclusions

Although CT-guided biopsies are culture-positive in a minority of cases, the majority of positive cultures are useful to tailor antibiotic treatment. Empirical treatment with clindamycin may cover almost all micro-organisms in positive biopsy specimens, provided patients are not immunocompromised. Outcome appears similar between culture-positive and culture-negative patients.

https://ift.tt/2HDOllL

Contents: Eur. J. Lipid Sci. Technol. 4∕2018

European Journal of Lipid Science and Technology, Volume 120, Issue 4, April 2018.

https://ift.tt/2HHMdty

Identifying Transcription Factor Olig2 Genomic Binding Sites in Acutely Purified PDGFRα+ Cells by Low-cell Chromatin Immunoprecipitation Sequencing Analysis

Here we present a protocol which is designed to analyze the genome-wide binding of the oligodendrocyte transcription factor 2 (Olig2) in acutely purified brain oligodendrocyte precursor cells (OPCs) by performing low-cell chromatin immunoprecipitation (ChIP), library preparation, high-throughput sequencing and bioinformatic data analysis.

https://ift.tt/2HEAWdv

A Simple and Efficient Method for In Vivo Cardiac-specific Gene Manipulation by Intramyocardial Injection in Mice

Here we present a protocol for cardiac-specific gene manipulation in mice. Under anesthesia, the mouse hearts were externalized through the fourth intercostal space. Subsequently, adenoviruses encoding specific genes were injected with a syringe into the myocardium, followed by protein expression measurement via in vivo imaging and Western blot analysis.

https://ift.tt/2H3poPz

Illbutrin

dan.jpg?resize=150%2C150&ssl=1

by Dan Rusyniak Let me just get this out of the way, I hate bupropion (Wellbutrin™ ) with the "white-hot intensity of a thousand suns" (Hulu). There is nothing "Well" about this drug. It was first synthesized by Burroughs-Wellcome (no, you are not Wellcome) in 1966, and was first approved by the […]

EMCrit Project by Tox & Hound.

https://ift.tt/2qCtBnj

Issue Information

Cancer Cytopathology, Volume 126, Issue 4, Page 219-224, April 2018.

https://ift.tt/2IZ6EBp

Desperately seeking subjects

Cancer Cytopathology, Volume 126, Issue 4, Page 225-226, April 2018.

https://ift.tt/2HHKDI8

Molecular testing for indeterminate thyroid nodules: Performance of the Afirma gene expression classifier and ThyroSeq panel

Cancer Cytopathology, EarlyView.

https://ift.tt/2J2IOoj

Can mutation‐mediated effects occurring early in development cause long‐term seizure susceptibility in genetic generalized epilepsies?

Epilepsia, EarlyView.

https://ift.tt/2JRovvl

The effectiveness of a group self‐management education course for adults with poorly controlled epilepsy, SMILE (UK): A randomized controlled trial

Epilepsia, EarlyView.

https://ift.tt/2EScj9U

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders

Epilepsia, EarlyView.

https://ift.tt/2ERRDij

Automated video‐based detection of nocturnal convulsive seizures in a residential care setting

Epilepsia, EarlyView.

https://ift.tt/2JSmjDV

Nonconvulsive status epilepticus in rats leads to brain pathology

Epilepsia, EarlyView.

https://ift.tt/2vjQjp5

The primary prevention of epilepsy: A report of the Prevention Task Force of the International League Against Epilepsy

Epilepsia, EarlyView.

https://ift.tt/2JNwvh0

Automated detection of focal cortical dysplasia type II with surface‐based magnetic resonance imaging postprocessing and machine learning

Epilepsia, EarlyView.

https://ift.tt/2ESbM7U

Movement‐based seizure detection

Epilepsia, EarlyView.

https://ift.tt/2JRoBmH

Ictal connectivity in childhood absence epilepsy: Associations with outcome

Epilepsia, EarlyView.

https://ift.tt/2ESb6PU

Postictal suppression and seizure durations: A patient‐specific, long‐term iEEG analysis

Epilepsia, EarlyView.

https://ift.tt/2JRnSlt

“Anatomists have ever been engaged in contention”

Clinical Anatomy, Volume 31, Issue 4, Page 449-449, May 2018.

https://ift.tt/2H4oAyh

Issue Information

Clinical Anatomy, Volume 31, Issue 4, Page C1-C1, May 2018.

https://ift.tt/2qEmvOj

Hand fasciae innervation: The palmar aponeurosis

Clinical Anatomy, EarlyView.

https://ift.tt/2H36aOg

The fasciacytes: A new cell devoted to fascial gliding regulation

Clinical Anatomy, EarlyView.

https://ift.tt/2qCM7Ln

Internal and external morphology of mandibular molars: An original micro‐CT study and meta‐analysis with review of implications for endodontic therapy

Clinical Anatomy, EarlyView.

https://ift.tt/2H4Ify2

Clinical characteristics of peri‐implant mucositis and peri‐implantitis

Clinical Oral Implants Research, EarlyView.

https://ift.tt/2JPneFd

Randomized controlled clinical study assessing two membranes for guided bone regeneration of peri‐implant bone defects: 3‐year results

Clinical Oral Implants Research, EarlyView.

https://ift.tt/2JRQPOs

Neurochemical abnormalities in premanifest and early spinocerebellar ataxias

Annals of Neurology, EarlyView.

https://ift.tt/2H4OEVQ

Status epilepticus: Role for etiology in determining response to benzodiazepines

Annals of Neurology, EarlyView.

https://ift.tt/2J0DKku

Enhancing swallowing recovery after a stroke by harnessing its bihemispheric organization

Annals of Neurology, EarlyView.

https://ift.tt/2qBDWQB

Regional brain volumetry and brain function in severely brain‐injured patients

Annals of Neurology, EarlyView.

https://ift.tt/2HvkJd3

Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

Inhibitors of programmed death 1 (PD-1) and its ligand PD-L1 are effective therapies for metastatic non–small-cell lung cancer (NSCLC) lacking sensitizing EGFR or ALK mutations. Pembrolizumab (Keytruda, Merck), nivolumab (Opdivo, Bristol-Myers Squibb), and atezolizumab (Tecentriq, Genentech) are…

https://ift.tt/2qBB9a5

Neoadjuvant PD-1 Blockade in Resectable Lung Cancer

Antibodies that block the immune inhibitory pathway of programmed death 1 (PD-1) protein have provided a major treatment advance in patients with cancer. In some patients with advanced non–small-cell lung cancer (NSCLC), these drugs unleash antitumor immunity, resulting in tumor regression and…

https://ift.tt/2vhVqWJ

Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti‐inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors

Alimentary Pharmacology &Therapeutics, EarlyView.

https://ift.tt/2IY6omm

Editorial: patient‐reported outcomes in chronic HCV—a PROMISing approach to an ongoing problem. Authors' reply

Alimentary Pharmacology &Therapeutics, Volume 47, Issue 9, Page 1320-1321, May 2018.

https://ift.tt/2HBdeP3

Editorial: patient‐reported outcomes in chronic HCV—a PROMISing approach to an ongoing problem

Alimentary Pharmacology &Therapeutics, Volume 47, Issue 9, Page 1319-1320, May 2018.

https://ift.tt/2IY6haq

Editorial: optimal dose of carvedilol in portal hypertension…nearly there

Alimentary Pharmacology &Therapeutics, Volume 47, Issue 9, Page 1328-1329, May 2018.

https://ift.tt/2HCY6AX

Editorial: the prevalence of Helicobacter pylori infection worldwide—knowns and unknowns. Authors' reply

Alimentary Pharmacology &Therapeutics, Volume 47, Issue 9, Page 1331-1332, May 2018.

https://ift.tt/2H3dSrF

Editorial: the sphincter of Oddi strikes again—eluxadoline illuminates a controversial mechanism for the pathogenesis of acute pancreatitis

Alimentary Pharmacology &Therapeutics, Volume 47, Issue 9, Page 1324-1325, May 2018.

https://ift.tt/2HDqTFv

Issue Information

Alimentary Pharmacology &Therapeutics, Volume 47, Issue 9, Page 1235-1237, May 2018.

https://ift.tt/2J1W8cX

Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Δευτέρα 16 Απριλίου 2018

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