Medicine by Alexandros G.Sfakianakis: 09/22/18

Σάββατο 22 Σεπτεμβρίου 2018

A case report: autosomal recessive Myotonia congenita caused by a novel splice mutation (c.1401 + 1G > A) in CLCN1 gene of a Chinese Han patient

Autosomal recessive Myotonia congenita (Becker's disease) is caused by mutations in the CLCN1 gene. The condition is characterized by muscle stiffness during sustained muscle contraction and variable degree of mu...

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Sepsis and Pleural Empyema Caused by Streptococcus pyogenes after Influenza A Virus Infection

Streptococcus pyogenes (also referred to as group A streptococci, GAS) causes severe invasive diseases such as bacteremia, necrotizing fasciitis, pneumonia, osteomyelitis, septic arthritis, and toxic shock syndrome in children. However, there are only a few reports on pleural empyema caused by GAS in children. Here, we report the case of a 4-year-old boy who presented with pleural empyema due to GAS after influenza A virus infection. With intravenous antibiotic administration and continuous chest-tube drainage, followed by video-assisted thoracoscopic surgery, his condition improved. During the clinical course, cytokines induced in response to the influenza virus, especially IL-1β and IL-10, were elevated 1 week after influenza A infection, but these decreased as the symptoms improved. Reportedly, the IL-10 production increases during influenza virus-bacteria superinfection. These observations suggest that the immunological mechanisms induced by the influenza virus can play an important role in influencing the susceptibility to secondary bacterial infections, such as GAS, in children.

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Analysis of Treatment and Prognosis of 863 Patients with Spinal Tuberculosis in Guizhou Province

The objective of this study was to investigate the treatment and prognosis of patients with spinal tuberculosis in Guizhou province. A total of 863 patients with spinal tuberculosis admitted to our hospital from 2006 to 2017 were included in this study. All patients underwent standardized quadruple antituberculosis treatment. Eighty patients were lost to follow-up due to a change of their contact information or noncompliance. A total of 783 patients completed the follow-up. The average follow-up period was 20.33 ± 8.77 months (range: 6 to 38 months). Among these patients, 145 patients underwent conservative treatment, while 638 patients underwent surgical treatment. All patients in the surgery group were treated with lesion removal, bone graft fusion, and internal fixation. Preoperative and postoperative standard quadruple antituberculosis treatment was administered. The clinical efficacy was evaluated according to erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), visual analogue scale (VAS), Cobb angle correction, neurological functional recovery, and interbody fusion with bone graft and tuberculosis outcome. A total of 608 patients achieved clinical cure. The symptoms, physical signs, blood tests and imaging findings were improved in 143 patients. Twenty patients showed refractory clinical symptoms, and 12 patients had local tuberculosis recurrence. Conservative and surgical treatments are the mainstream treatments for spinal tuberculosis. According to the patients' individual conditions, individualized treatments should be used to achieve good efficacy. Standardized antituberculosis treatment should be applied over the course of spinal tuberculosis.

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The Antiosteoporosis Effects of Zhuanggu Guanjie Pill In Vitro and In Vivo

We investigated the beneficial effects and underlying mechanisms of Zhuanggu Guanjie (ZGGJ) pill in osteoporosis in vitro and in vivo. Bone marrow macrophages from 4–6-week-old mice were cultured in the presence of macrophage colony-stimulating factor (15 ng/mL) and receptor activator of nuclear factor-κB ligand (30 ng/mL). Osteoclast differentiation was determined by quantification of tartrate-resistant acid phosphatase activity. Gelatin zymography was used to detect the activity of matrix metalloproteinases in osteoclasts. Ovariectomized rats were administered orally with estradiol valerate or ZGGJ for 8 weeks. Blood was collected to measure serum indices. Tibiae were harvested to carry out bone microcomputed tomography scanning, histomorphological analysis, and bone strength determination. ZGGJ inhibited tartrate-resistant acid phosphatase activity, matrix metalloproteinase 9 expression, and bone resorption in vitro. At doses of 0.55, 1.1, and 2.2 g/kg, ZGGJ exerted significant osteoprotective effects including inhibition of bone turnover markers and improved tibia bone strength in ovariectomized rats. Microcomputed tomographic analysis showed that ZGGJ improved the trabecular architecture with increased connectivity density and trabecular thickness and decreased trabecular spacing. These results revealed that ZGGJ prevents bone loss induced by ovariectomy in rats and that inhibition of bone resorption is involved in the bone-protective effects of ZGGJ.

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IL-6: a cytokine at the crossroads of autoimmunity

Britta E Jones | Megan D Maerz | Jane H Buckner

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Emerging areas for therapeutic discovery in SLE

Naomi I Maria | Anne Davidson

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An Evaluation of Rapidly Progressive Dementia Culminating in a Diagnosis of Creutzfeldt–Jakob Disease

Rapidly progressive dementia is a curious and elusive clinical description of a pattern of cognitive deficits that progresses faster than typical dementia syndromes. The differential diagnosis and clinical workup for rapidly progressive dementia are quite extensive and involve searching for infectious, inflammatory, autoimmune, neoplastic, metabolic, and neurodegenerative causes. We present the case of a previously highly functional 76-year-old individual who presented with a 6-month history of rapidly progressive dementia. His most prominent symptoms were cognitive impairment, aphasia, visual hallucinations, and ataxia. Following an extensive battery of tests in hospital, the differential diagnosis remained probable CJD versus autoimmune encephalitis. He clinically deteriorated and progressed to akinetic mutism and myoclonus. He passed away 8 weeks after his initial presentation to hospital, and an autopsy confirmed a diagnosis of sporadic CJD. We use this illustrative case as a framework to discuss the clinical and diagnostic considerations in the workup for rapidly progressive dementia. We also discuss CJD and autoimmune encephalitis, the two main diagnostic possibilities in our patient, in more detail.

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Acute Brucellosis Presenting with Bleeding Tendency due to Isolated Severe Thrombocytopenia

Mild anemia and leukopenia are the most common hematologic findings in the course of acute brucellosis. Severe form of thrombocytopenia is less frequently reported. We describe a case of acute brucellosis in a 20-year-old man, who presented with fever, purpuric skin lesions, epistaxis, and hematuria. The absolute platelet count was 2 × 109/L. The patient was diagnosed as suffering from brucellosis on the basis of a strongly positive serologic reaction and was treated with antibiotics and a short course of corticosteroids, with a rapid rise in platelet count. Brucella infection can cause immune-mediated thrombocytopenia that is reversible after appropriate antimicrobial therapy and steroid treatment.

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The P300 component decreases in a bimodal oddball task in individuals with depression: An event-related potentials study

Event-related potentials (ERPs) are electroencephalogram (EEG) indexes that allow for non-invasive recordings of cerebral activity with a temporal resolution on the order of milliseconds (Boutros et al., 2011). Such recordings may also allow for further identification of the relationship between neural activity and stimulus processing, each of which may be abnormal in individuals with psychiatric disorders (Charney and Nestler, 2008). Many studies have attempted to identify distinct ERP properties of specific cognitive functions or processes, most frequently reporting on the P300 component (Hansenne,2006).

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Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals

Unexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy.

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EUS-guided versus percutaneous biliary access in patients with obstructive jaundice due to gastric cancer

Gastric cancer is sometimes complicated by obstructive jaundice. However, ERCP may be challenging in patients who have advanced gastric cancer, or recurrent gastric cancer after surgical resection that is complicated by obstructive jaundice. In such cases, percutaneous transhepatic biliary drainage (PTBD) is considered. Recently, EUS-guided biliary drainage (EUS-BD) has been developed. We conducted a retrospective study to compare the efficacy of EUS-BD and PTBD in patients with obstructive jaundice due to gastric cancer.

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SpyGlass rescue treatment of common bile duct impacted foreign bodies

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New findings on chronic pain syndrome in the mouth

The picture is becoming clearer regarding the chronic oral pain condition known as Burning Mouth Syndrome, or BMS, which mainly affects women who are middle-aged and older.

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Pathologic predictors of local recurrence in atypical meningiomas following gross total resection

Local recurrence following gross total resection of atypical meningiomas is difficult to prognosticate. Pathologic predictors could help risk stratify patients. This retrospective analysis assesses various pathologic variables, including the 2016 World Health Organization grade II criteria, through central review by a neuro-pathologist. Ki67 proliferative index and mitotic number strongly predict for local recurrence following gross total resection and 30.3% of patients locally recur by 3 years.

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Cost and Cost-Effectiveness of Image Guided Partial Breast Irradiation in Comparison to Hypofractionated Whole Breast Irradiation

Based on micro-costing analysis, accelerated partial breast irradiation (APBI) delivered with IMRT in 5 fractions was less costly to deliver than hypofractionated whole breast irradiation (HWBI) with or without boost and additionally had higher utility outcomes. When utilizing reimbursement, IMRT APBI was less costly than HWBI with or without boost, dominating the technique; however, when billed as SBRT it was not cost-effective.

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Local Relapse after Breast Conserving Therapy vs. Mastectomy for Extensive Pure Ductal Carcinoma In-Situ ≥4 cm

This study evaluates population-based outcomes for patients with extensive (≥4 centimeters) pure ductal carcinoma in-situ (DCIS). Local recurrence was 2% with mastectomy, 8% with breast conserving surgery (BCS) and radiotherapy and 16% with BCS alone. Mastectomy remains a standard local treatment for extensive DCIS, while BCS and radiotherapy may be reasonably considered in selected patients with a careful discussion of the benefits and side effects.

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Dosimetric benefits of mid-position compared with internal target volume strategy for esophageal cancer radiation therapy

Two strategies to account for respiration-induced target motion using 4D-CT in treatment planning of esophageal cancer patients (i.e., mid-position and internal target volume) were compared in 15 patients. Deformable image registration-based 4D-dose accumulation indicated adequate target coverage and a reduction of approximately 10% in the dose to the lungs, heart, and liver for the mid-position strategy. Our results suggest clinically relevant dosimetric benefits for the mid-position strategy and its feasibility of clinical implementation.

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EMCrit – How Do You Know You Are Actually Good at Airway Management by Laura Duggan

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Debrief Every Airway

EMCrit Project by Laura Duggan.

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Efficacy of glutamine in postinfection IBS

We read the randomised controlled trial (RCT) by Zhou et al.1 The authors recruited a highly selected group of patients with increased intestinal permeability and postinfection IBS with diarrhoea (IBS-D), defined by an unconfirmed enteric infection in the 12 months prior to symptom onset, and randomised them to 8 weeks of treatment with either glutamine or placebo. The population screened also had other curious features. For example, only four had rapid orocaecal transit on lactulose hydrogen breath testing, erroneously described as small intestinal bacterial overgrowth. This appears low, compared with other studies examining this issue in patients with IBS.

There are other minor issues with the trial conduct and analysis. First, compliance was checked by telephone calls, not a particularly robust method. Second, the efficacy analysis was per-protocol, rather than intention-to-treat, and minimal information on dropouts was provided, other than that they 'voluntarily withdrew'. Finally, the extremely low adverse event...

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Potential utility of the Genedrive point-of-care test for HCV RNA detection

In an article in Gut,1 Lemoine and Tillman reviewed our recent publication on the development and validation of a novel point-of-care (POC) HCV viral assay.2 They acknowledge that Genedrive is the only CE-In Vitro Diagnostic-qualified device for HCV detection, and that the limit of detection (LOD: 1406–3203 IU/mL) permits identification of the vast majority of HCV chronic cases.3 However, they emphasise some limitations of the study and Genedrive. One limitation highlighted is the need for plasma which is still required for 100% of HCV clinical tests. Nevertheless, recent studies demonstrated microfluidic plasma separation without centrifugation4 or with low-cost hand-powered paper centrifuges.5 It is feasible to foresee such devices overcoming the need for conventional centrifuges and facilitating Genedrive testing.

They also question whether 15 µL of plasma can be obtained by fingerprick. Published studies report 20–25 µL per drop of blood,6 so...

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Water immersion policies and guidelines: How are they informed?

Publication date: Available online 21 September 2018

Source: Women and Birth

Author(s): Megan Cooper, Helen McCutcheon, Jane Warland

Abstract

Background

Water immersion for labour and birth is consistently challenged as a practice lacking support from high quality evidence. Despite this, the option is available to Australian women. Practitioners are guided by policies and guidelines however, given the research paucity, questions surround the way in which water immersion policies and guidelines are informed.

Aims

The aims of the study were to determine how water immersion policies and/or guidelines are informed and to what extent the policy/guideline facilitates the option of water immersion for labour and birth with respect to women's choice and autonomy.

Methods

Phase two of a three phase mixed methods study used critical, post structural interpretive interactionism to examine the process of development and implementation of water immersion policies and guidelines from informant's experience. Semi-structured interviews were conducted with 12 Australian participants.

Findings

Participants highlighted that the lack of randomised controlled trials had resulted in other forms of evidence being drawn upon to inform water immersion policies and guidelines. This was influenced in part by individual interpretations of evidence with medical views taking precedence. This sometimes resulted in policy and guideline documents that were restrictive with this impacting on women's ability to access the option.

Conclusion

Perceived limitations of research and the subsequent translation of this perceived paucity of evidence into policies and guidelines, has impacted on women's ability to exercise choice and autonomy with respect to water immersion and indeed, on the professional autonomy of practitioners who wish to facilitate it.

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S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells

Abstract

Purpose

Triple negative breast cancer (TNBC) patients generally have an adverse clinical outcome because their tumors often recur and metastasize to distant sites in the first 3 years after surgery. Therefore, it has become pivotal to identify potential factors associated with metastasis. Here, we focused on the effects of S100P and Ezrin on the trans-endothelial migration (TEM) of TNBC cells, as they have both been suggested to play a role in this process in other malignancies.

Methods

The expression of S100P and Ezrin was examined by immunohistochemistry in 58 primary TNBC samples. The mRNA and protein levels of S100P and Ezrin were assessed in breast cancer-derived cell lines using qRT-PCR and Western blotting, respectively. Proliferation and migration assays were performed using TNBC-derived MFM-223 and SUM-185-PE cells transfected with S100P and Ezrin siRNAs. Two different timeframes were employed for TEM assays using TNBC-derived cells and human umbilical vein endothelial-derived cells, respectively. Correlations between the status of Ezrin^Thr-567 expression and various clinicopathological features were analyzed by immunohistochemistry.

Results

We found that S100P and Ezrin double negative TNBC cases were significantly associated with a better disease-free survival. We also found that single and double siRNA-mediated knockdown of S100P and Ezrin in TNBC-derived cells significantly inhibited their TEM and destabilized the intercellular junctions of endothelial cells. In addition, we found that Ezrin^Thr-567 immunoreactivity significantly correlated with vascular invasion in TNBC patients.

Conclusions

From our data we conclude that S100P, Ezrin and Ezrin^Thr-567 are involved in the trans-endothelial migration of TNBC cells and that they may serve as potential targets in TNBC patients.

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Differences in trauma mortality between ACS-verified and state-designated trauma centers in the US

Publication date: Available online 21 September 2018

Source: Injury

Author(s): Finn D. Schubert, Laura J. Gabbe, Marc A. Bjurlin, Audrey Renson

Abstract

Background

Traumatic injury is a leading cause of deaths worldwide, and designated trauma centers are crucial to preventing these. In the US, trauma centers can be designated as level I-IV by states and/or the American College of Surgeons (ACS), reflecting the resources available for care. We examined whether state- and ACS-verified facilities of the same level (I-IV) had differences in mortality, complications, and disposition, and whether differences varied by center level.

Materials and Methods

Using all admissions reported to the National Trauma Data Bank 2010-2015, we estimated risk ratios for the association between current ACS verification (vs. state designation) and patient mortality and complications, adjusting for trauma level and facility, injury, and demographic characteristics. We tested the interaction between trauma level and ACS verification, stratifying by trauma level in the presence of significant statistical interaction.

Results

Overall, patients admitted to ACS-verified vs state-designated facilities had similar adjusted mortality risk [RR 1.00; 95% CI 0.91 to 1.03] and lower risk of discharge to intermediate care facilities [RR 0.58; 95% CI 0.44 to 0.78]. However, Level III and IV facilities had lower adjusted mortality risk when ACS-verified, with much lower mortality risk in ACS-verified Level IV facilities [RR 0.25; 95% CI 0.12 to 0.54].

Discussion

Findings suggest that while outcomes are similar between ACS-verified and state-designated Level I and II centers, state-designated Level III and particularly Level IV centers show poorer outcomes relative to their ACS-verified counterparts. Further research could explore mechanisms for these differences, or inform potential changes to state designation processes for lower-level centers.

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The safety and efficacy of phaco-sleeve irrigation-assisted hydrodissection during femtosecond laser-assisted cataract surgery

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Reconsidering the minimally important difference: evidence of instability over time and across groups

Publication date: Available online 21 September 2018

Source: The Spine Journal

Author(s): Carolyn E. Schwartz, Jie Zhang, Bruce D. Rapkin, Joel A. Finkelstein

Abstract

Background Context

Underlying cognitive factors have been found to influence patients' symptom experience. Current evidence suggests that concomitant changes in appraisal must be taken into account to accurately interpret change as measured by standard spine patient-reported outcomes (PROs).

Purpose

To investigate changes in patients' minimally important differences (MID) over recovery from spinal surgery; whether and how cognitive appraisal processes are implicated in the change trajectories.

Study Design/Setting

Longitudinal cohort study with up to 12 months follow-up

Patient Sample

Surgical patients (n= 167) with a diagnosis of disc herniation or spinal stenosis

Outcome Measures

Standard spine patient-reported PROs were used (Rand-36, Oswestry Disability Index, Numerical Rating Scale for pain, PROMIS Pain Impact).

Methods

This study was funded by the Feldberg Chair in Spinal Research, Sunnybrook Health Sciences Centre and the authors have no conflicts of interest. MID used an anchor technique and was computed by global assessment of change (GAC) grouping. Participants were binned into groups based on their GAC response patterns at all time points: Consistently Better Post-Surgery, Consistently Worse Post-Surgery, and Bouncers, whose GAC ratings fluctuate (i.e., better-then-worse-then-better; or vice versa). Individuals' longitudinal quality of life (QOL) and appraisal-slope scores were computed. QOL-appraisal slopes' correlations were computed by GAC group. Fisher's Z transformation tested the hypothesis that GAC groups differed in the QOL-appraisal relationship over time.

Results

Moderate to large changes are recognized as clinically important in the early stages of recovery (i.e., 6 weeks post-surgery) and over time smaller and smaller changes become important. The three pattern groups emphasized and deemphasized different standards of comparison over time, with the Better group emphasizing personal goals and the Worse and Bouncers deemphasizing doctors' input. These group differences translated to differential relationships between PRO change and appraisal changes over time.

Conclusions

The MID reflects increasingly subtle change over time in PROs. Appraisal may influence how patients experience the same (MID) change over time, with better outcomes associated with emphasizing long-term goals. PRO change seems to be driven by different standards of comparison. Potential avenues for clinical intervention are discussed.

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Chlamydophila psittaci pneumonia associated to exposure to fulmar birds (Fulmaris glacialis) in the Faroe Islands

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Molecular investigation of Lawsonia intracellularis in diarrheic and healthy captive ostriches ( Struthio camelus ) in Iran

Abstract

Lawsonia intracellularis is the causative agent of proliferative enteropathy (PE) in pigs, a disease of economic importance worldwide. The present study aimed to investigate the occurrence of L. intracellularis in ostriches using a sensitive and specific nested polymerase chain reaction (nested PCR). A total number of 112 fecal samples (64 healthy, 48 diarrheic) were collected from 11 ostrich farms located in four provinces in Iran (Semnan, Tehran, Gilan, Yazd). The results showed the presence of L. intracellularis in three diarrheic and four apparently healthy birds. The frequency of positive results was the same in both groups (6.25% healthy vs. 6.25% diarrheic). Although the results of this study did not reveal any relationship between this organism and diarrhea (P > 0.05), the molecular detection of L. intracellularis on a farm where birds were suffering from the typical clinical symptoms of PE highlights the need for evaluation of PE in ratites.

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Coadministration of cytotoxic chemotherapeutic agents with irinotecan is a risk factor for irinotecan-induced cholinergic syndrome in Japanese patients with cancer

Abstract

Background

Cholinergic syndrome is an acute adverse event frequently observed in patients administered irinotecan, and can sometimes negatively affect their quality of life. In some manifestations of the syndrome such as bradycardia, careful monitoring of patients is advised. In this study, we retrospectively investigated the risk factors associated with irinotecan-induced cholinergic syndrome in Japanese patients with cancer.

Methods

Patients who received irinotecan-based chemotherapy between April 2014 and June 2018 were examined. Patient backgrounds and clinical data during the first cycle of an irinotecan-containing regimen, including cholinergic syndrome manifestation within 24 h after the start of treatment, were collected from medical records. Univariate and multivariate analyses were performed to assess the risk of irinotecan-induced cholinergic syndrome.

Results

Among 179 patients administered an irinotecan-containing regimen, 51 experienced cholinergic syndrome after the initiation of treatment. The most common symptom was sweating followed by diarrhea, abdominal pain, lacrimation, and nasal discharge. 42 patients developed symptoms of cholinergic syndrome during their first treatment with irinotecan. Multivariate analyses revealed that the incidences of cholinergic syndrome in patients administered 2 or 3 chemotherapeutic agents; i.e., irinotecan plus 1 or 2 other cytotoxic anticancer drug(s), were significantly higher than that in patients administered irinotecan alone [odds ratio (OR) 4.35, 95% confidence interval (CI) 1.5–12, p = 0.0053 and OR 4.50, 95% CI 1.5–14, p = 0.0093, respectively]. The addition of a molecularly targeted drug did not affect the incidence of cholinergic syndrome.

Conclusion

The incidence rate of irinotecan-induced cholinergic syndrome increased concomitantly with the addition of cytotoxic chemotherapeutic agents administered.

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8K ultra-high-definition microscopic camera for ophthalmic surgery

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Comparison of variations in cornea after one-handed and two-handed coaxial phacoemulsification

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Intestinal microorganisms involved in colorectal cancer complicated with dyslipidosis

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The intact postsynaptic protein neurogranin is reduced in brain tissue from patients with familial and sporadic Alzheimer’s disease

Abstract

Synaptic degeneration and neuronal loss are early events in Alzheimer's disease (AD), occurring long before symptom onset, thus making synaptic biomarkers relevant for enabling early diagnosis. The postsynaptic protein neurogranin (Ng) is a cerebrospinal fluid (CSF) biomarker for AD, also in the prodromal phase. Here we tested the hypothesis that during AD neurodegeneration, processing of full-length Ng into endogenous peptides in the brain is increased. We characterized Ng in post-mortem brain tissue and investigated the levels of endogenous Ng peptides in relation to full-length protein in brain tissue of patients with sporadic (sAD) and familial Alzheimer's disease (fAD), healthy controls and individuals who were cognitively unaffected but amyloid-positive (CU-AP) in two different brain regions. Brain tissue from parietal cortex [sAD (n = 10) and age-matched controls (n = 10)] and temporal cortex [sAD (n = 9), fAD (n = 10), CU-AP (n = 13) and controls (n = 9)] were included and all the samples were analyzed by three different methods. Using high-resolution mass spectrometry, 39 endogenous Ng peptides were identified while full-length Ng was found to be modified including disulfide bridges or glutathione. In sAD parietal cortex, the ratio of peptide-to-total full-length Ng was significantly increased for eight endogenous Ng peptides compared to controls. In the temporal cortex, several of the peptide-to-total full-length Ng ratios were increased in both sAD and fAD cases compared to controls and CU-AP. This finding was confirmed by western blot, which mainly detects full-length Ng, and enzyme-linked immunosorbent assay, most likely detecting a mix of peptides and full-length Ng. In addition, Ng was significantly associated with the degree of amyloid and tau pathology. These results suggest that processing of Ng into peptides is increased in AD brain tissue, which may reflect the ongoing synaptic degeneration, and which is also mirrored as increased levels of Ng peptides in CSF.

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Exposure–response analysis and simulation of lenvatinib safety and efficacy in patients with radioiodine-refractory differentiated thyroid cancer

Abstract

Purpose

Once-daily lenvatinib 24 mg is the approved dose for radioiodine-refractory differentiated thyroid cancer. In a phase 3 trial with lenvatinib, the starting dose of 24 mg was associated with a relatively high incidence of adverse events that required dose reductions. We used an exposure–response model to investigate the risk–benefit of different dosing regimens for lenvatinib.

Methods

A population pharmacokinetics/pharmacodynamics modeling analysis was used to simulate the potential benefit of lower starting doses to retain efficacy with improved safety. The seven lenvatinib regimens tested were: 24 mg; and 20 mg, 18 mg, and 14 mg, all with or without up-titration to 24 mg. Exposure–response models for efficacy and safety were created using a 24-week time course.

Results

The approved dose of lenvatinib at 24 mg, predicted the best efficacy. However, the lenvatinib dosing regimens of 14 mg with up-titration or 18 mg without up-titration potentially provides comparable efficacy (objective response rate at 24 weeks) and a better safety profile.

Conclusions

Treatment with lenvatinib at starting doses lower than the approved once-daily 24 mg dose could provide comparable antitumor efficacy and a similar or better safety profile. Based on the results from this modeling and simulation study, a comparator dose of lenvatinib 18 mg without up-titration was selected for evaluation in a clinical trial.

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Corrigendum to “Sorafenib Dose Recommendation in Acute Myeloid Leukemia Based on Exposure‐FLT3 Relationship”

Clinical and Translational Science, EarlyView.

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The Effect of Social Network Size on Hashtag Adoption on Twitter

Cognitive Science, EarlyView.

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Cancers, Vol. 10, Pages 349: Epidemiology of Moderate Alcohol Consumption and Breast Cancer: Association or Causation?

Cancers, Vol. 10, Pages 349: Epidemiology of Moderate Alcohol Consumption and Breast Cancer: Association or Causation?

Cancers doi: 10.3390/cancers10100349

Authors: Samir Zakhari Jan B. Hoek

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate additional approaches to move beyond the associations that are reported in traditional epidemiological analyses and incorporate information on molecular pathologic signatures as a requirement to posit causal inferences. In particular, we point to the efforts of the transdisciplinary field of molecular pathological epidemiology (MPE) to evaluate possible causal relationships, if any, of alcohol consumption and breast cancer. A wider application of the principles of MPE to this field would constitute a giant step that could enhance our understanding of breast cancer and multiple modifiable risk factors, a step that would be particularly suited to the era of “personalized medicine”.

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Combination of IFITM1 knockdown and radiotherapy inhibits the growth of oral cancer

Cancer Science, EarlyView.

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Human Femoral Vein Diameter and Topography of Valves and Tributaries: A Post Mortem Analysis

Clinical Anatomy, EarlyView.

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Posterior interosseous nerve intraneural ganglion cyst from the scapholunate joint

Clinical Anatomy, EarlyView.

https://ift.tt/2xGaKue

Primary anterior abdominal wall leiomyoma in a pregnant woman

ANZ Journal of Surgery, EarlyView.

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Dramatic progression of a chest wall desmoid‐like fibromatosis

ANZ Journal of Surgery, EarlyView.

https://ift.tt/2I4vVLm

Cystic lesion in the left upper quadrant

ANZ Journal of Surgery, EarlyView.

https://ift.tt/2pu3NsJ

Pericardial empyema after cardiac surgery: a diagnostic challenge

ANZ Journal of Surgery, EarlyView.

https://ift.tt/2I7t5FB

Mycobacterium ulcerans disease management in Australian patients: the re‐emergence of surgery as an important treatment modality

ANZ Journal of Surgery, EarlyView.

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How to repair parastomal hernias involving the abdominal apron: to move or not to move

ANZ Journal of Surgery, EarlyView.

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Pharmacological and non‐surgical renal protective strategies for cardiac surgery patients undergoing cardiopulmonary bypass: a systematic review

ANZ Journal of Surgery, EarlyView.

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Chest pain that does not make the cut: a case study of a surgical patient with Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis syndrome

ANZ Journal of Surgery, EarlyView.

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Ovarian‐type epithelial tumour of borderline malignancy: a rare testicular tumour in Australia

ANZ Journal of Surgery, EarlyView.

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Minimizing Propionibacterium acnes contamination in shoulder arthroplasty: use of a wound protector

ANZ Journal of Surgery, EarlyView.

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Day case versus inpatient stay for excisional haemorrhoidectomy

ANZ Journal of Surgery, EarlyView.

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Intra‐abdominal desmoid tumour presenting as an acute abdomen

ANZ Journal of Surgery, EarlyView.

https://ift.tt/2pu3L45

Inguinal node metastases in testicular cancer following previous childhood orchidopexy

ANZ Journal of Surgery, EarlyView.

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Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival

Background Regulatory T cell (Treg)-based immunotherapies have been studied as potential cell-based modalities for promoting transplant survival. However, the efficacy of local delivery of Tregs in corneal transplantation has not been fully elucidated. Herein, we investigated the kinetics of migration of subconjunctivally injected Tregs and their role in promoting corneal allograft survival. Methods GFP+CD4+CD25+Foxp3+ Tregs were isolated from draining lymph nodes (DLNs) of GFP transgenic mice and were subconjunctivally injected to corneal allograft recipients. Next, Tregs, conventional T cells (Tconv) or a combination of both was locally injected to graft recipients, and graft survival was determined by evaluating opacity scores for 10 weeks. Transplanted mice without treatment served as controls. The frequencies of MHC-II+CD11b+ antigen presenting cells (APCs), IFNγ+CD4+ Th1 cells, and CD45+ cells in the DLNs and cornea were evaluated at week 2 posttransplantation using flow cytometry. Expression of IFNγ, IL-10 and TGF-β in the grafts were assessed using RT-PCR and ELISA. Results GFP+ Tregs were detected in the ipsilateral cornea and DLNs of recipients 6 hours after injection. Subconjunctival injection of Tregs significantly decreased the frequencies of mature APCs in the graft and DLNs, suppressed Th1 frequencies in DLNs, and inhibited CD45+ cell infiltration to the graft. Finally, locally delivered Tregs significantly reduced the expression of IFN-γ, enhanced the levels of IL-10 and TGF-β in the graft, and promoted long-term allograft survival. Conclusions Our study elucidates the kinetics of migration of locally delivered Tregs and shows their role in suppressing host immune response against the allograft. * These authors contributed equally to this study. Corresponding Author: Reza Dana, M.D., M.P.H., M.Sc., Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA, Tel: +1-617-912-7401; Fax: +617-912-0117. Email: Reza_Dana@meei.harvard.edu Authorship: Chunyi Shao: Research design, performance of the research, data analysis, writing the paper Yihe Chen: Research design, performance of the research, data analysis, writing the paper Takeshi Nakao: Performance of the research Afsaneh Amouzegar: Data analysis, writing the paper Jia Yin: Performance of the research Maryam Tahvildari: Performance of the research Zala Lužnik: Performance of the research Sunil K. Chauhan: Research design, data analysis, writing the paper Reza Dana: Research design, data analysis, writing the paper Disclosure: The authors have no financial conflicts of interest. Funding: This study was supported by the National Institutes of Health/National Eye Institute Grant R01 EY012963 to RD. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zmoVXB

Perspectives on the Optimal Genetically-Engineered pig in 2018 for Initial Clinical Trials of Kidney or Heart Xenotransplantation

For a clinical trial today, what might realistically be the optimal pig among those currently available? Deletion of expression of the 3 pig carbohydrate antigens against which humans have natural (preformed) antibodies (triple-knockout [TKO] pigs) should form the basis of any clinical trial. However, because both complement and coagulation can be activated in the absence of antibody, the expression of human complement- and coagulation-regulatory proteins is likely to be important in protecting the graft further. Any genetic manipulation that might reduce inflammation of the graft, eg, expression of hemeoxygenase-1 (HO-1) or A20, may also be beneficial to the long-term survival of the graft. The transgene for human CD47 is likely to have a suppressive effect on monocyte/macrophage and T cell activity. Furthermore, deletion of xenoantigen expression, and expression of a human complement-regulatory protein, are both associated with a reduced T cell response. Although there are several other genetic manipulations that may reduce the T cell response further, it seems likely that exogenous immunosuppressive therapy, particularly if it includes costimulation blockade, will be sufficient. We would therefore suggest that, with our present knowledge and capabilities, the optimal pig might be a TKO pig that expressed 1 or more human complement-regulatory proteins, 1 or more human coagulation-regulatory proteins, a human antiinflammatory transgene, and CD47. Absent or minimal antibody binding is important, but we suggest that the additional insertion of protective human transgenes will be beneficial, and may be essential. Address for correspondence: David K.C. Cooper MD, PhD, FRCS, ZRB 701, 1720 2nd Avenue South, University of Alabama at Birmingham, Birmingham, AL 35294, USA, Tel: (USA) 205-996-7772. E-mail: dkcooper@uabmc.edu Authorship The initial draft of the manuscript was prepared by DKCC with subsequent contributions and approval by all authors. Disclosure The authors declare no conflicts of interest. Funding Work on xenotransplantation at UAB is supported in part by NIH grant #U19 AI090959/08. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The challenges associated with a calcineurin inhibitor free regimen after heart transplantation

No abstract available

https://ift.tt/2znb0QM

DONOR HYPOTHERMIA AND HEART TRANSPLANTATION

No abstract available

https://ift.tt/2ONukMI

Early Hypertension and Diabetes after Living Kidney Donation: A National Cohort Study

Background Living kidney donors have an increased risk of end-stage renal disease, with hypertension and diabetes as the predominant causes. In this study, we sought to better understand the timeline when these diseases occur, focusing on the early postdonation period. Methods We studied 41 260 living kidney donors in the US between 2008-2014 from the SRTR and modeled incidence rates and risk factors for hypertension and diabetes. Results At 6-months, 1-year, and 2-years postdonation, there were 74, 162, and 310 cases of hypertension per 10 000 donors. Donors who were older (per 10 years, aIRR 1.40, 95% CI 1.29-1.51), male (aIRR 1.31, 95% CI 1.14-1.50), had higher BMI (per 5 units, aIRR 1.29, 95% CI 1.17-1.43), and were related to their recipient (first degree relative, aIRR 1.28, 95% CI 1.08-1.52; spouse, aIRR 1.34, 95% CI 1.08-1.66) were more likely to develop hypertension, while donors who were Hispanic/Latino were less likely (aIRR 0.71, 95% CI 0.55-0.93). At 6-months, 1-year, and 2-years, there were 2, 6, and 15 cases of diabetes per 10 000 donors. Donors who were older (per 10 years, aIRR 1.42, 95% CI 1.11-1.82), had higher BMI (per 5 units, aIRR 1.52, 95% CI 1.04-2.21), and were Hispanic/Latino (aIRR 2.45, 95% CI 1.14-5.26) were more likely to develop diabetes. Conclusions In this national study, new-onset diabetes was rare, but 3% of donors developed hypertension within 2 years of nephrectomy. These findings reaffirm that disease pathways for kidney failure differ by donor phenotype and estimate the population most at-risk for later kidney failure. Received 9 May 2018. Revision received DD MMMM YYYY. Accepted 7 August 2018. Contact Information: Dorry Segev, M.D., Ph.D. Associate Vice Chair, Department of Surgery, Johns Hopkins Medical Institutions, 2000 E. Monument St. Baltimore, MD 21205, 410-502-6115 (tel) 410-614-2079 (fax), dorry@jhmi.edu AUTHORSHIP The individual contributions of each author are as follows: • CMH designed the study, analyzed and interpreted data, drafted and revised the article, and had final approval of this version; • SB designed the study, analyzed and interpreted data, revised the article, and had final approval of this version; • AT designed the study, analyzed and interpreted data, revised the article, and had final approval of this version; • MH designed the study, revised the article, and had final approval of this version; • CEH interpreted data, revised the article, and had final approval of this version; • SD interpreted data, revised the article, and had final approval of this version; • ADM designed the study, revised the article, and had final approval of this version; • JGW designed the study, drafted and revised the article, and had final approval of this version; • ABM designed the study, interpreted data, revised the article, and had final approval of this version; • KL designed the study, revised the article, and had final approval of this version; and • DS designed the study, interpreted data, revised the article, and had final approval of this version. DISCLOSURES The authors declare no conflicts of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format. FUNDING This work was supported by grant numbers F32DK109662 (Holscher), K01DK114388 (Henderson), F32DK105600 (DiBrito), K01DK101677 (Massie), K24DK101828 (Segev), and R01DK096008 (Segev) from the National Institute of Diabetes and Digestive and Kidney Diseases, grant number F32AG053025 (Haugen) from the National Institute on Aging, and by an American College of Surgeons Resident Research Scholarship (Holscher). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cardiotrophin 1 improves kidney preservation, graft function, and survival in transplanted rats

Background Cold ischemia-reperfusion injury is unavoidable during organ transplantation, and prolonged preservation is associated with poorer function recovery. Cardiotrophin-1 (CT-1) is an IL-6 family cytokine with cytoprotective properties. This preclinical study in rats tested whether CT-1 mitigates cold renal ischemia-reperfusion injury in the context of the transplantation of long-time preserved kidneys. Methods Kidneys were flushed with cold (4°C) University of Wisconsin solution (UW) containing 0.2 μg/mL CT-1 and stored for several periods of time at 4 °C in the same solution. In a second approach, kidneys were first cold-preserved for 6 hours and then were perfused with UW containing CT-1 (0, 16, 32, or 64 μg/mL) and further cold-preserved. Organ damage markers were measured in the kidneys at the end of the storage period. For renal transplantation, recipient consanguineous Fischer rats underwent bilateral nephrectomy and received a previously cold-preserved (24 hours) kidney as described above. Survival and creatinine clearance were monitored over 30 days. Results CT-1 in perfusion and preservation fluids reduced oxidative stress markers (SOA and iNOS), inflammation markers (NF-κB and TNF-α), and vascular damage (VCAM-1) and activated LIFR and STAT-3 survival signaling. Transplantation of kidneys cold-preserved with CT-1 increased rat survival and renal function (ie, lower plasma creatinine and higher creatinine clearance) and improved kidney damage markers after transplantation (ie, lower SOA, TNF-α, ICAM-1, and VCAM-1 and higher NF-κB). Conclusions CT-1 represents a novel therapeutic strategy to reduce ischemia-reperfusion and cold preservation injury, to rescue suboptimal kidneys and, consequently, to improve the clinical outcomes of renal transplantation. Received 13 January 2018. Revision received 30 April 2018. Accepted 24 May 2018. *These authors share first authorship. Correspondence: José M. Lopez-Novoa, Department of Physiology and Pharmacology, University of Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain. E-mail: jmlnovoa@usal.es. Fax number: +34 923294669 AUTHORSHIP PAGE 1. Authorship: BG-C, VB-G, JML-N, and FJL-H participated in the research design and writing of the paper. BG-C, VB-G, DL-M, and JRSG-R participated in the performance of the research. BG-C, VB-G, JML-N, and FJL-H participated in the data analysis. 2. Disclosure: The authors have no conflicts of interest to declare. 3. Funding: This study was supported by funds from Digna Biotech, Instituto de Salud Carlos III (grants DT15S/00166 and PI15/01055), and the European Commission (FEDER). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The selective RNA polymerase I inhibitor CX-5461 mitigates neointimal remodeling in a modified model of rat aortic transplantation

Background Transplant vasculopathy is a major cause of chronic rejection of transplanted organs. In the present study, we examined the effects of CX-5461, a novel selective inhibitor of RNA polymerase I, on development of transplant vasculopathy using a modified model of rat aortic transplantation. Methods The thoracic aortas from Fischer rats were transplanted into the abdominal cavity of Lewis rats. CX-5461 was mixed in pluronic gel and administered via peri-vascular release. Results Treatment with CX-5461 mitigated the development of neointimal hyperplasia and vascular inflammation. This effect was likely to be attributable in part to inhibition of macrophage-dependent innate immunity reactions. Specifically, CX-5461 exhibited potent inhibitory effects on macrophage migration and lipopolysaccharide-induced activation. Treatment with CX-5461 also prevented macrophage differentiation and maturation from primary bone marrow cells. In macrophages, CX-5461 did not alter the total amount of p53 protein, but significantly increased p53 phosphorylation, which was involved in regulating cytokine-stimulated macrophage proliferation. Conclusions In conclusion, our results suggest that pharmacological inhibition of Pol I may be a novel strategy to treat transplantation-induced arterial remodeling. Received 11 January 2018. Revision received 27 June 2018. Accepted 29 June 2018. These authors contributed equally to the work, Chaochao Dai, MBBS, Mengyao Sun. Address correspondence to: Dr. Fan Jiang (fjiang@sdu.edu.cn) or Dr. Jianli Wang (wangmaq@sdu.edu.cn), School of Basic Medicine, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong Province 250012, China. Phone: +86 531 8838 2044; Fax +86 531 8295 9051 Conflict of interest declaration: none Author contributions: Chaochao Dai: performed experiments; did data acquisition and analysis; involved in drafting the manuscript Mengyao Sun: performed experiments; did data acquisition and analysis; involved in drafting the manuscript Fengjiao Wang: performed experiments and data acquisition/analysis Jiankang Zhu: performed experiments and data acquisition/analysis Yaping Wei: performed experiments and data acquisition/analysis Xiaotong Guo: performed experiments and data acquisition/analysis Siqin Ma: participated in data acquisition and analysis Bo Dong: participated in data acquisition and analysis Gejin Wang: participated in data acquisition and analysis Fan Jiang: conceived the study; provided intellectual inputs for data interpretations; revised the manuscript Jianli Wang: conceived the study; provided intellectual inputs for data interpretations Funding support This study was supported by grants from Natural Science Foundation of China (91539102 and 31471087 for F.J.; 81500496 for J.Z.), National 973 Basic Research Program (2010CB732605 for F.J.), Natural Science Foundation of Shandong Province (No. ZR2016HM24 for J.W.) and University Innovation Fund of Jinan City (201401251 for J.W.). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Second primary cancers in non‐Hodgkin lymphoma: Bidirectional analyses suggesting role for immune dysfunction

International Journal of Cancer, EarlyView.

https://ift.tt/2MTqr78

Cancer incidence in older adults in selected regions of sub‐Saharan Africa, 2008‐2012

International Journal of Cancer, Volume 0, Issue ja, -Not available-.

https://ift.tt/2xuQGvt

Cleft palate and hypopituitarism in a patient with Noonan‐like syndrome with loose anagen hair‐1

American Journal of Medical Genetics Part A, EarlyView.

https://ift.tt/2PWvnK7

Use of nutritional devices in Cornelia de Lange syndrome: Data from a large Italian cohort

American Journal of Medical Genetics Part A, EarlyView.

https://ift.tt/2O0N26k

Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features

American Journal of Medical Genetics Part A, EarlyView.

https://ift.tt/2PWvllt

Risk of Down syndrome birth: Consanguineous marriage is associated with maternal meiosis‐II nondisjunction at younger age and without any detectable recombination error

American Journal of Medical Genetics Part A, EarlyView.

https://ift.tt/2O4xgHt

Emergency Department Procedural Sedation Practice Limitations: A Statewide California ACEP Survey

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.

https://ift.tt/2MTYoV5

Development of a Novel Computerized Clinical Decision Support System to Improve Adolescent Sexual Health Care Provision

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.

https://ift.tt/2xu0BBQ

An Insight into the Phase Transformation of WS2 upon Fluorination

Advanced Materials, EarlyView.

https://ift.tt/2pvayu6

Dissipative Self‐Assembly of Anisotropic Nanoparticle Chains with Combined Electrodynamic and Electrostatic Interactions

Advanced Materials, EarlyView.

https://ift.tt/2I9JpWk

Biomineralization as a Paradigm of Directional Solidification: A Physical Model for Molluscan Shell Ultrastructural Morphogenesis

Advanced Materials, EarlyView.

https://ift.tt/2put3PC

Dynamic Electronic Doping for Correlated Oxides by a Triboelectric Nanogenerator

Advanced Materials, EarlyView.

https://ift.tt/2I3rfVX

Evaluating the Managing Medicines for People With Dementia Website Version 2

The Managing Medicines for People With Dementia version 2 website was developed in three languages, English, Italian, and Macedonian, to assist informal caregivers in the task of managing medications. Medication management is a complex task with potentially high stakes health outcomes, including hospitalization and death. A mixed-methods evaluation was carried out. A survey was available to site users and Web log data were collected over a 3-month period. Subsequently, the quality and suitability of the information and readability and usability of the Web site were evaluated. Focus groups and interviews were conducted with end users from all three language groups. Data collected from the evaluation surveys during the pilot test showed that users were generally satisfied with site usability (77%). The results of the readability testing indicate that future versions could be improved. Feedback from the focus groups and interviews was generally positive. The use of multiple methodologies provided comprehensive testing that is likely to have identified the majority of usability issues. Ways in which the site can be maintained with up-to-date information and be promoted to the target population, informal carers, need to be explored. The evaluation reported here was funded by a seed grant from the Global Challenges Program at the University of Wollongong. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Corresponding author: Pippa Burns, PhD, MPH(Dist), BSc(Hons), University of Wollongong, Northfields Ave, Wollongong, New South Wales 2522, Australia (pippa@uow.edu.au). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2pryPkQ

A novel de novo mutation p.Ala428Asp in KRT5 gene as a cause of localized epidermolysis bullosa simplex

Experimental Dermatology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2QRA35f

Effect of oral isotretinoin on the nucleo‐cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris

Experimental Dermatology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2xHV7Cz

Population‐Based Priors in Cardiac Model Personalisation for Consistent Parameter Estimation in Heterogeneous Databases

International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.

https://ift.tt/2xtZO3Q

Variably protease‐sensitive prionopathy presenting within ALS/FTD spectrum

Annals of Clinical and Translational Neurology, EarlyView.

https://ift.tt/2MVgrKk

Phenomenon of Endothelial Antibody Capture: Principles and Potential for Locoregional Targeting of Hepatic Tumors

Hepatology, EarlyView.

https://ift.tt/2OGgLOP

Reply Letter 17‐2110.R2

Hepatology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2znkjAw

RNF34 modulates the mitochondrial biogenesis and exercise capacity in muscle and lipid metabolism through ubiquitination of PGC-1 in Drosophila

Abstract

The transcriptional co-activator PGC-1α is a key regulator of mitochondrial function and muscle fiber specification in the skeletal muscle. The E3 ubiquitin ligase RNF34 ubiquitinates PGC-1α and negatively regulates mammalian brown fat cell metabolism. However, the functional importance of RNF34 in the skeletal muscle and its impact on energy metabolism remain unknown. The Drosophila PGC-1 homolog dPGC-1 and its mammalian counterparts have conserved functions in mitochondria and insulin signaling. Here, we showed that the Drosophila RNF34 (dRNF34) ubiquitinates the Drosophila PGC-1α (dPGC-1) and promotes its degradation in HEK293T cells by immunoprecipitation and western blot analysis. This allows us to use Drosophila as a powerful model system to study the physiological role of RNF34 in mitochondrial function and metabolism. In the in vivo studies, by separately expressing two independent UAS-dRNF34 RNAi transgenes driven by the muscle-specific 24B-Gal4 driver, we found that knockdown of dRNF34 specifically in muscle promotes mitochondrial biogenesis, improves negative geotaxis, extends climbing time to exhaustion in moderate aged flies and counteracts high-fat-diet-induced high triglyceride content. Furthermore, we showed that knockdown of dPGC-1 reversed the effects of the dRNF34 knockdown phenotypes described above. Our results reveal that dRNF34 plays an important role in regulating mitochondrial biogenesis in muscle and lipid metabolism through dPGC-1. Thus, inhibition of RNF34 activity provides a potential novel therapeutic strategy for the treatment of age-related muscle dysfunction.

https://ift.tt/2QQM3UD

Inhibitory effect of IFITM5 on cementoblast differentiation is associated with Wnt signaling

https://ift.tt/2xG6tqG

Decadal Experience of Renal Cell Carcinoma from a Tertiary Care Teaching Institute in North India

Abstract

To study the current trends of renal cell carcinoma (RCC) in terms of demographic characteristics, clinical presentation, staging, mode of management, histopathology, and survival characteristics from a high volume tertiary care teaching institute in North India. We retrospectively reviewed the records of all patients of RCC between January 2006 and December 2015 and variables like age, gender, symptoms, tumor size/location/number, stage, type of surgery, histopathology, and survival characteristics were studied. One hundred forty-four patients were included in the study. Most common age group of presentation was 50–59 years (29.8%), male to female ratio was 2.5, and majority of cases were smokers. Flank pain was the most common presenting complaint (38.2%), classical triad (pain, fever, hematuria) was present in 25%, and incidental diagnosis was made in 11.1% cases. Stage T2a was most common presentation with majority of tumors present in upper pole (27.1%). Renal vein involvement (T3a) was present in 10.4%, hilar lymph node involvement in 25%, and distant metastasis was observed in 20.1% cases. Radical nephrectomy was most common surgery performed (75%) and clear cell carcinoma was the most common histopathology (75.7%) followed by papillary (11.1%). Women reported more chromophobe type and low-grade cancers, although rest of clinico-pathological features did not show any gender difference. Mean follow-up of the study was 6–122 months with younger (< 29 years) patients reporting lower 5-year survival and higher stage disease. Renal cell carcinoma shows a different trend in our study population, compared to western data, with large size tumors and advanced stage presentation being more common.

https://ift.tt/2Dk3Wsw

Motor Control Training Compared to Transcutaneous Electrical Nerve Stimulation in Patients with Disc Herniation with Associated Radiculopathy: A Randomized Controlled Trial

Objective To compare the effectiveness of motor control training(MCT)and transcutaneous electrical nerve stimulation (TENS) in relieving pain, reducing functional disability, and improving transversus abdominis (TrA) activation in patients with lumbar disc herniation(LDH) with associated radiculopathy. Design Randomized controlled trial. Methods Forty patients diagnosed with LDH were randomly divided into two groups: motor control training group (MCTG; n=20) and TENS group(TG; n=20). Interventions The MCTG and TG attended 60-minsessions twice a week for 8 weeks, totaling to 16 sessions. Main outcome measures Pain, functional disability, and TrA activation capacity. Results Differences between both groups were observed after 8 weeks, favoring the MCTG. MCT was more effective than TENS in relieving pain (mean difference=3.3 points, 95% confidence interval [CI] 2.12–4.48), reducing functional disability (mean difference=8.4 points, 95% CI 5.44–11.36), improving the quality of pain (mean difference=17 points, 95% CI 7.93–26.07), sensory quality of pain (mean difference=10.3 points, 95% CI5.55–15.05), and TrA activation (mean difference=1.5 points, 95% CI0.90–2.10). Conclusions The results suggest that MCT is more effective than TENS with respect to relieving pain, reducing functional disability, and improving TrA activation in patients with LDH. Registration number NCT01640431 clinicaltrials.gov Corresponding Author: Bianca Callegari – Laboratory of Human Motricity Studies, Institute of Health Sciences, Federal University of Pará, Belém (PA), Brazil. Phone: (+55 91) 982210054 E-mail: callegaribi@uol.com.br FUNDING This study received public financial support from the: State of São Paulo Research Foundation (FAPESP), and there is not conflict of interest in the work. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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