The purpose of this study is to test the efficacy of bioactive natural product berberine in the treatment of patients with atrial fibrillation (AF). Data of 45 paroxysmal AF patients treated with berberine and 43 age, gender, New York Heart Association functional classification score, and concomitant cardiovascular disease matched patients treated with amiodarone were analyzed retrospectively to examine conversion rate, average conversion time, average heart rate, and echocardiographic parameters. There was no statistical difference between berberine and amiodarone on conversion rate or echocardiographic parameters. Berberine treatment showed a significantly longer average time to conversion and higher heart rate during sinus rhythm (SR) than amiodarone. Echocardiographic parameters showed that E/A ratio and left atrial diameter were significantly improved after 6- and 12-month berberine treatment, but only E/A ratio improved significantly at the same time points after amiodarone treatment. This is the first report to specifically compare efficacy of berberine and amiodarone in the treatment of patients with AF. We find that berberine and amiodarone are equally effective for conversion of AF and maintenance of normal SR.
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Σάββατο 16 Δεκεμβρίου 2017
Antimicrobial Natural Product Berberine Is Efficacious for the Treatment of Atrial Fibrillation
Angiotensin Converting Enzyme Inhibitory and Antioxidant Activities of Enzymatic Hydrolysates of Korean Native Cattle (Hanwoo) Myofibrillar Protein
The purpose of this study was to determine the angiotensin converting enzyme (ACE) inhibitory and antioxidant activities of myofibrillar protein hydrolysates (HMPHs) of different molecular weights (
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The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion: A Systematic Review and Meta-Analysis
Objective. To conduct systematic analyses to evaluate the efficacy of progesterone therapy for the prevention of miscarriages in pregnant women experiencing threatened abortion. Methods. In November 2016, we performed a systematic literature search and identified 51 articles in PubMed, Embase, and Cochrane databases. We identified nine randomized trials that included 913 pregnant women (including 322 treated with oral dydrogesterone, 213 treated with vaginal progesterone, and 378 control subjects) who met the selection criteria. Results. The incidence of miscarriage was significantly lower in the total progesterone group than in the control group (13.0% versus 21.7%; odds ratio, 0.53; 95% confidence interval (CI), 0.36 to 0.78; ; , 0%). Moreover, the incidence of miscarriage was significantly lower in the oral dydrogesterone group than in the control group (11.7% versus 22.6%; odds ratio, 0.43; 95% CI, 0.26 to 0.71; ; , 0%) and was lower in the vaginal progesterone group than in the control group, although this difference was nonsignificant (15.4% versus 20.3%; odds ratio, 0.72; 95% CI, 0.39 to 1.34; ; , 0%). However, the incidence of miscarriage was not different between the oral dydrogesterone and vaginal progesterone groups. Conclusion. Progesterone therapy, especially oral dydrogesterone, can effectively prevent miscarriage in pregnant women experiencing threatened abortion.
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Atypical Fractures: an issue of concern or a myth?
Publication date: Available online 16 December 2017
Source:Injury
Author(s): Mohammad Al-Ashqar, Michalis Panteli, Gautam Chakrabarty, Peter V. Giannoudis
Atypical Femoral Fractures (AFF) represent fractures located between the lesser trochanter and the supracondylar flare of a femur. An increasing pool of evidence supports their association with the prolonged use of bisphosphonates, even though a direct correlation is yet to be proved. The purpose of this review is to encapsulate the current evidence associating bisphosphonate use and the development of AFFs, the clinical features related to their presentation, as well as to report the armamentarium of strategies available in the prevention and treatment of AFFs. Based on these evidence, we propose a management algorithm for AFFs, that can serve as a guide for patients presenting with this condition.
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Distinct Features of Trampoline-related Orthopedic Injuries in Children Aged Under 6 Years
Publication date: Available online 16 December 2017
Source:Injury
Author(s): Eun Seok Choi, Jin Heon Hong, Jae Ang Sim
IntroductionConcern has been growing about trampoline-related injuries among young children. Several published policy statements have repeatedly recommended that children younger than 6 years should not use trampolines. However, few studies have investigated the injuries caused by trampoline-related accidents among young children. This study aimed to identify the distinct features of trampoline-related orthopedic injuries in children younger than 6 years.MethodsWe retrospectively reviewed the medical records of pediatric patients aged between 0 and 16 years who visited our regional emergency center due to trampoline-related orthopedic injuries between 2012 and 2015. Patients were divided into two groups: a preschool group (younger than 6 years) and a school group (older than 6 years). We compared the features of the injuries in the two groups.ResultsAmong 208 patients, 108 (52%) were male and 100 (48%) were female. The mean age was 5.4 years. The preschool group accounted for 66%. There were no seasonal variations. Fractures were sustained in 96 patients (46%). The anatomical locations of injuries differed significantly between the two age groups. Proximal tibia fractures were more frequent in the preschool group than the school group (34% and 6%, respectively). Distal tibia fractures were more prevalent in the school group than the preschool group (44% vs. 13%, respectively). Surgical treatment was needed more frequently in the school group (p = 0.035, hazard ratio 2.52, 95% confidence interval: 1.03–6.17). Most of the injuries (82%) occurred at trampoline parks.ConclusionsThe anatomical locations of trampoline-related orthopedic injuries differed significantly between age groups. Fractures were more common around the knee in younger children and the ankle in older children.
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Pain after ortho-plastic reconstruction of lower limb injuries: A snapshot study
Publication date: Available online 15 December 2017
Source:Injury
Author(s): Luke Harries, Ahmed Emam, Umraz Khan
IntroductionThe incidence of pain after flap reconstruction of complex lower limb injury is poorly reported in the literature, and yet represents a significant source of morbidity in these patients. In our centre (Southmead Hospital, Bristol, England) patients who have had flap reconstruction for complex lower limb injury are followed up at a joint ortho-plastics lower limb clinic run weekly. The aim of this study was to report the incidence of pain in such patients at follow-up in the specialist clinic. The impact of the experience of pain upon the quality of life, and the efficacy of analgesia was assessed these cases.Patients and MethodsThis was a cross sectional snapshot study of a cohort of complex lower limb patients attending our lower limb ortho-plastics outpatient clinic between the dates of: 17/5/16 and 28/6/16. Any patient attending clinic with previous flap reconstruction for lower limb injury was asked to complete the BPI (Brief Pain Index) questionnaire, and details regarding their injury and surgery were collected.ResultsThere was a 100% response rate, with 33 patients completing the questionnaire. 28 out of the 33 patients (85%) reported ongoing pain. There was no significant relationship between time post operatively and average pain scores (Spearman's Rank R = 0.077), nor was there significant difference by age or gender. Over 25% of the patients with pain were not taking analgesia, however those using simple analgesia (paracetamol, NSAIDS) derived on average over 70% pain relief.ConclusionsPain in a common complication following flap reconstruction for complex lower limb injury reported in 85% of our cohort. This pain does not seem to be correlated with time, gender or age, and responds well to simple analgesia in most cases. This emphasises the importance of asking about pain at follow up, and taking simple measures to improve pain outcomes.
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Anterolateral Distal Tibia Locking Plate Osteosynthesis and Their Ability to Capture OTAC3 Pilon Fragments
Publication date: Available online 16 December 2017
Source:Injury
Author(s): Arun Aneja, T.David Luo, Boshen Liu, Domingo Molina, Kerry Danelson, Jason J. Halvorson, Eben A. Carroll
BackgroundIntra-articular Pilon fractures remain therapeutically challenging due to osteochondral fracturing and comminution, marginal impaction, and insult to the soft tissue envelope. The purpose of this study was to compare the efficacy of anterolateral distal tibial locking plates in capturing main fracture fragments in tibial plafond fractures.MethodsFrom May 2011 to Dec 2015, 169 OTA C-type pilon fractures met inclusion and exclusion criteria with computed tomographic (CT) scans performed prior to definitive fixation. For each patient, the fracture lines were mapped, digitized, and graphically superimposed to create a compilation of fracture lines. Based on these average measurements, three distal tibia sawbones had three different anterolateral plates applied. Axial CT scan images were used to determine the efficacy of screw purchase in main fracture fragments in pilon fractures.ResultsThe Smith & Nephew PERI-LOC plate secured the largest number of fracture lines (90.1%) but missed the Volkmann fragment with greatest frequency at 3.6%. The Synthes 2.7/3.5 mm VA-LCP captured 87.3% of the fracture lines while missing the Volkmann fragment 3.2% of the time. The Synthes 3.5 mm LCP captured 86.5% of the fracture lines but was the best at securing the Volkmann fragment (1.2% missed). All three implants were deficient in capturing the medial malleolar fragment. The PERI-LOC and 2.7/3.5 mm VA-LCP did not differ with respect to percentage of fragments captured (p = 0.721) but both outperformed the 3.5 mm LCP (p = 0.021 and p = 0.05, respectively).ConclusionsThis study was consistent with prior literature in defining three main fracture fragments: anterior, medial, and posterior. All three plates were deficient in capturing the medial malleolar fragment. The Smith and Nephew PERI-LOC plate secured the most number of fracture lines, while the Synthes 3.5 mm LCP was least likely to miss the Volkmann fragment and most likely to miss the medial malleolar fragment. No plate was found to be superior to the other in capturing all fracture lines of the OTAC3 pilon fragments.Level of EvidenceThree.
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Analysis of mortality and fixation failure in geriatric fractures using quantitative computed tomography
Publication date: Available online 15 December 2017
Source:Injury
Author(s): Tyler S. Pidgeon, Joey P. Johnson, Matthew E. Deren, Andrew R. Evans, Roman A. Hayda
ObjectivesWhile osteoporosis has been shown to be a contributing factor in low energy fractures in the elderly, limited data exists regarding the correlation of bone mineral density (BMD) and T-Scores to mortality and failure of fracture fixation. This study seeks to determine the relationship between femoral neck BMD in elderly patients with typical geriatric fractures and mortality and fracture fixation failure using Quantitative Computed Tomography (QCT).Materials and methodsPatients over the age of 65 who sustained fractures of the proximal humerus, distal radius, pelvic ring, acetabulum, hip, proximal tibia, and ankle who also underwent a CT scan that included an uninjured femoral neck were retrospectively reviewed. QCT was used to assess bone mineral density and T scores. Mortality and fixation failure were recorded. Standard descriptive statistics, as well as logistic regression were used to correlate BMD and mortality, and BMD and fixation failure.ResultsOf the 173 patients initially screened, 150 met inclusion criteria. Patients who remained alive at the end of the study (LP) had significantly (P = .019) higher adjusted mean femoral neck BMD (0.502 g/cm2) than non-polytrauma patients who died (MNPT) (0.439 g/cm2) when controlling for age, time to mortality, follow up, CCI, and ASA.Patients who had fixation failure events (FE) had significantly (P = .002) lower adjusted mean femoral neck BMD (0.342 g/cm2) than patients without failure events (NE) (0.525 g/cm2) when controlling for age and time to radiographic follow-up.ConclusionsOur study illustrates that QCT is a reliable method for the determination of femoral neck BMD in elderly patients with geriatric fractures. Furthermore, lower BMD/T-Scores are associated with increased mortality and fixation failures in this patient population.
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Prognostic factors affecting overall survival and local control in meningioma patients treated with radiotherapy or combined radiotherapy and surgery
Abstract
Background
Meningiomas account for 15–20% of adult primary brain neoplasms. We reviewed 142 meningioma cases treated with radiotherapy (RT) alone or combined RT and surgery to assess prognostic factors affecting overall survival (OS) and local control (LC).
Methods
Medical records were reviewed for progesterone receptor (PR) status, World Health Organization (WHO) grade, and treatment given, and we evaluated how these factors affected OS and LC. We also assessed OS and LC in patients treated with adjuvant RT versus salvage RT.
Results
From 1997 to 2014, 142 patients with meningioma were treated with RT. The median follow-up time since the completion of RT was 4.43 years. When adjusted for age at diagnosis, there was no difference in OS for surgery + RT versus RT alone, p = 0.656. Local control at 5 years was 88.2% with adjuvant RT versus 74.9% with salvage RT, p = 0.326. Five-year OS and LC were higher for grade I (OS 92.4%, LC 80.8%) versus grade II or higher meningiomas (OS 88.0%, LC 53.7%), p < 0.05. Five-year LC was 82.9% in women and 64.2% in men, p = 0.011. Local control at 5 years was 76.1% in patients with strong PR expression versus 41.7% in patients with focal or no PR expression, p = 0.029.
Conclusions
We confirm that meningioma grade is prognostic for OS and LC. Gender and PR status were prognostic with respect to LC, with significantly better LC in women and patients with strong PR expression.
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Shape Optimization of Bone-Bonding Subperiosteal Devices with Finite Element Analysis
Subperiosteal bone-bonding devices have been proposed for less invasive treatments in orthodontics. The device is osseointegrated onto a bone surface without fixation screws and is expected to rapidly attain a bone-bonding strength that successfully meets clinical performance. Hence, the device's optimum shape for rapid and strong bone bonding was examined in this study by finite element analyses. First, a stress analysis was performed for a circular rod device with an orthodontic force parallel to the bone surface, and the estimate of the bone-bonding strength based on the bone fracture criterion was verified with the results of an animal experiment. In total, four cross-sectional rod geometries were investigated: circular (Cr), elliptical (El), semicircular (Sc), and rectangular (Rc). By changing the height of the newly formed bone to mimic the progression of new bone formation, the estimation of the bone-bonding strength was repeated for each geometry. The rod with the Rc cross section exhibited the best performance, followed by those with the Sc, El, and Cr cross sections, from the aspects of the rapid acquisition of strength and the strength itself. Thus, the rectangular cross section is the best for rod-like subperiosteal devices for rapid bone bonding.
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Integrative Analysis of miRNA and mRNA Expression Profiles in Calcium Oxalate Nephrolithiasis Rat Model
The microRNA (miRNA) expression profiles and their biological functions in calcium oxalate nephrolithiasis remain unclear. In this study, we investigate the miRNA and mRNA expression profiles of kidney tissues in calcium oxalate stone rats. 16 Sprague Dawley rats were divided into control group and stone-forming group. 24-hour urine samples and kidney tissues were collected for biochemical and histological determination after 4 weeks. MiRNA and mRNA microarray were applied to evaluate the miRNA and mRNA expression profiles. To validate the microarray results, the quantitative real-time PCR (qRT-PCR) was performed. A total of 38 miRNAs and 2728 mRNAs were significantly and differentially expressed in kidney tissues of stone-forming group versus control group. Gene Ontology (GO) analysis revealed that most of the target genes were enriched in terms of oxidation reduction, ion transport, inflammatory response, and response to wounding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of these targets highlights their critical role in cytokine-cytokine receptor interaction, gap junction, and chemokine signaling pathway. Furthermore, the reliability of the microarray-based results was confirmed by using qRT-PCR determination. The miRNA and mRNA expressions in calcium oxalate stone rat kidneys might provide a basis for further research on urolithiasis mechanism.
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Association between TSLP gene polymorphism and bronchial asthma in children in Beni Suef Governorate in Egypt
Abstract
Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2 (TH2) cells. Thymic stromal lymphopoietin (TSLP) gene can exacerbate the lung inflammatory process in asthma by enhancing TH2 differentiation through dendritic cell activation. Many studies showed that TSLP polymorphisms are related to bronchial asthma susceptibility in different populations. The objectives of this study are to study the polymorphism of the two SNPs Rs2289276 and Rs2289278 in TSLP gene and to analyze any possible relation to pediatric bronchial asthma liability in Egypt using case-control study. DNA was extracted from blood samples withdrawn from 40 asthmatic patients and 20 age- and sex-matched normal controls, then the genotypes of SNPs Rs2289276 and Rs2289278 in TSLP gene were identified with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and genotypes and allele frequencies were calculated and statistically analyzed. Genotypes of Rs2289276 site in the asthmatic patients were dissimilar from those of the controls (P = 0.045). The genotypes of Rs2289278 in asthmatic patients were significantly different between those of intermittent and severe asthma (P = 0.044). Bronchial asthma susceptibility and severity are related to TSLP variants. Thus, TSLP might be a new target molecule for asthma treatment.
http://ift.tt/2CJo8zF
Whole exome sequencing demonstrates recurrent somatic copy number alterations and sporadic mutations in specialized stromal tumors the prostate
In a previous array comparative genomic hybridization study, we detected common deletions of chromosomes 13 and 14 in prostatic stromal sarcoma and stromal tumor of uncertain malignant potential (STUMP). In this study, we performed whole exome sequencing (WES) and fluorescence in situ hybridization (FISH) to explore somatic mutations in 1 low-grade stromal sarcoma, 1 high-grade stromal sarcoma, and 12 STUMPs including 5 cases of degenerative atypia type, 1 myxoid type, 1 phyllodes type, and 5 cases of recently described round cell type.
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Identification of T-cell receptor expression in EBV-positive neoplastic cells in extranodal NK/T-cell lymphoma, nasal-type and comparison with T-cell receptor gene rearrangement by BIOMED-2 assay
The cellular lineage of extranodal NK/T-cell lymphoma, nasal-type (ENKTL) is determined by expression of T-cell receptor (TR) or TR gene rearrangement. In ENKTL, from TR immunohistochemistry it may often be difficult to decide whether TR-positive cells are tumor cells or not, especially when TR is expressed in a subset of tumor cells. To analyze TR expression pattern and TR rearrangement in T-lineage ENKTL, we performed double immunofluorescence staining for Epstein–Barr virus-encoded small RNAs (EBER) /T-cell receptor (TCR) βF1 and CD56/TCR βF1 in 12 cases of ENKTL that showed TCR βF1 expression in immunohistochemistry.
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The selected biomarker analysis in five types of uterine smooth muscle tumors
Uterine smooth muscle tumors (USMT) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study we reviewed 119 USMT with a diagnosis of LMS, STUMP (smooth muscle tumor of uncertain malignant potential), ALM/LM-BN (atypical leiomyomas/leiomyoma with bizarre nuclei) and CLM (cellular leiomyoma) as well as 46 ULM and 60 myometrial controls.
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Paip1 affects breast cancer cell growth and represents a novel prognostic biomarker
Polyadenylate-binding protein-interacting protein 1 (Paip1) regulates translational initiation. Increasing evidence suggests that Paip1 plays important roles in cancer development and progression. This study explored the role of Paip1 in breast cancer progression and evaluated its prognostic value. The cellular location of Paip1 protein was determined using immunofluorescence (IF). Then, Paip1 protein expression was evaluated by immunohistochemical (IHC) staining in 119 breast cancers and 40 normal breast tissues.
http://ift.tt/2kBQ00f
Association Between Low Plasma Level of Citrulline Before Allogeneic Hematopoietic Cell Transplantation and Severe Gastrointestinal Graft vs Host Disease
The gastrointestinal form of acute graft vs host disease increases morbidity and mortality following allogeneic hematopoietic cell transplantation. Plasma levels of citrulline, a non-proteinogenic amino acid, indicate functional enterocyte mass. We measured citrulline in patients before allogeneic hematopoietic cell transplantation and investigated its association with incidence and severity of gastrointestinal graft vs host disease.
http://ift.tt/2osj1k4
JGES guidelines for endoscopic sphincterotomy
Abstract
The Japan Gastroenterological Endoscopy Society (JGES) has recently compiled guidelines for endoscopic sphincterotomy (EST) using evidence-based methods. Content regarding actual clinical practice, including detailed endoscopic procedures, instruments, device types and usages, has already been published by the JGES postgraduate education committee in May 2015, and thus in these guidelines we avoided duplicating such content as much as possible. The guidelines do not address pancreatic sphincterotomy, endoscopic papillary balloon dilation (EPBD), and endoscopic papillary large balloon dilation (EPLBD). The guidelines for EPLBD are planned to be developed separately. The evidence level in this field is often low, and in many instances strong recommendation has to be determined on the basis of expert consensus. At this point in time, the guidelines are divided into 6 items including indications, techniques, specific cases, adverse events, outcomes, and postoperative follow up.
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Clinicopathologic and Immunohistochemical Study of Combined Small Cell Carcinoma and Urothelial Carcinoma Molecular Subtype
Abstract
Muscle invasive bladder cancer, an aggressive disease with heterogeneous molecular profiles, has recently been subclassified into three major molecular subtypes -basal, luminal and "p53-like" urothelial carcinomas (UCas), which bear prognostic and therapeutic implication. Similar to breast cancer, basal and luminal subtype UCas are designated by basal (CK5/14) and luminal (CK20) markers. The "p53-like" subtype presents with wild-type p53 gene with upregulated p53 pathways and is implicated in chemoresistance. Urinary bladder is one of the most common primary sites of extrapulmonary small cell carcinoma (SmCC). Bladder SmCC frequently coexists with UCa; however, the relation of SmCC with specific UCa molecular subtypes has not been studied. The aim of this study is to investigate the clinicopathology and immunophenotypes of the combined SmCC and UCa molecular subtypes. A total of 22 combined SmCC and UCa cases were studied for the clinicopathology and immunohistochemical (IHC) profiles by luminal and basal cell markers as well as Her2/Neu and p53. Our results demonstrated that all the urinary bladder SmCCs were associated with high grade UCas. They were more commonly seen in older male patients with a smoking history and had a poor prognosis. Based on the reported molecular subtyping, the UCas could be immunohistochemically subclassified into luminal, basal, dual and null types, which showed different clinicopathologic and IHC features. Compared to non-SmCC associated UCa, the subtypes of UCa in the combined SmCCs and UCas were characterized by: 1) Although overall luminal type was still relatively more common in men, basal marker-expressing subtypes were significantly increased in incidence and were more common in women. 2) Her2/Neu overexpression was more commonly observed in luminal than basal cell marker-expressing UCas. 3) IHC overexpression of p53 was common in all the subtypes, with UCas and SmCCs sharing the same p53 expression pattern. Although limited by relatively a small number of cases, the results of this study will enhance our understanding of the combined SmCC and UCa entity and potentially lead to a future therapeutic management.
http://ift.tt/2CqXLNE
Developing a healing environment for broken souls of patients with life-threatening illnesses and their caregivers
What a privilege it is to be able to touch those sacred spaces in the soul of each person that we encounter every day. Patients with life-threatening illnesses can struggle with physical, emotional, and existential and spiritual concerns and the suffering of caregivers. A key goal of our supportive and palliative care teams is to alleviate patient and caregiver suffering. When caring for patients with advanced and terminal illness the spirituality of each member of the palliative care team becomes a single collective spirituality or soul with common goals, values, and belonging, with a main goal of providing the best care for patients and caregivers in the alleviation of suffering.
http://ift.tt/2BkZt41
Modulation of the Tumor Microenvironment by Epstein-Barr virus Latent Membrane Protein-1 in Nasopharyngeal Carcinoma
Abstract
Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein-Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre-invasive NPC tumors and in approximately 50% of advanced NPC tumors. Moreover, a small population of LMP1-expressing cells in advanced NPC tumor tissue is proposed to orchestrate NPC tumor tissue maintenance and development through cancer stem cells and progenitor cells. Recent studies suggest that LMP1 activity shifts according to tumor development stage, but still has a pivotal role during all stages of NPC development.
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Ovarian cancer risk, ALDH2 polymorphism and alcohol drinking: Asian data from the Ovarian Cancer Association Consortium
Summary
The ALDH2 polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case-control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1,274 controls of Asian descent with information on recent alcohol consumption. The pooled odds ratios (OR) with 95% confidence intervals (CI) for OvCa risk associated with alcohol consumption, rs671 and their interaction were estimated using logistic regression models adjusted for potential confounders. No significant association was observed for daily alcohol intake with invasive OvCa (OR comparing any consumption to none =0.83; 95% CI=0.58-1.18) or with individual histotypes. A significant decreased risk was seen for carriers of one or both Lys alleles of rs671 for invasive mucinous OvCa (OR=0.44; 95% CI=0.20-0.97) and for invasive and borderline mucinous tumors combined (OR=0.48; 95% CI=0.26-0.89). No significant interaction was observed between alcohol consumption and rs671 genotypes. In conclusion, self-reported alcohol consumption at the quantities estimated was not associated with OvCa risk among Asians. Because the rs671 Lys allele causes ALDH2 inactivation leading to increased acetaldehyde exposure, the observed inverse genetic association with mucinous ovarian cancer is inferred to mean that alcohol intake may be a risk factor for this histotype. This association will require replication in a larger sample.
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MiR-155 promotes gastric cancer growth and invasion by negatively regulating Transforming Growth Factor Beta Receptor 2
Summary
Gastric cancer (GC) has a high morbidity and mortality among the common malignancies worldwide. It is essential to elucidate the molecular events of GC proliferation and invasion, which will provide new therapeutic targets for GC. The inactivation of TGFβR2 is correlates with cancer cells growth and metastasis, but the mechanisms underlying the down-regulation of TGFβR2 expression remain unknown. MicroRNAs (miRNAs) act as post-transcriptional regulators play a key role in the development of cancers. The bioinformatics analysis and luciferase reporter assay demonstrated that miR-155 directly bind the 3′-untranslated region (3′-UTR) of TGFβR2 mRNA. In this study, we found that the TGFβR2 protein levels, but not mRNA levels, were down-regulated in GC tissues, while the levels of miR-155 were significantly increased in GC tissues. We deduced miR-155 inversely correlated with TGFβR2 in GC cells. In vitro studies showed that over-expression of miR-155 in SGC7901 inhibited the expression of TGFβR2 and then promoted GC cell proliferation and migration, whereas miR-155 inhibitor showed opposite effects. In addition, the tumor suppressing function of TGFβR2 was verified by using siRNA (small interfering RNA) and TGFβR2 over-expressing plasmid respectively. The results illustrated the miR-155 promotes cell growth and migration by negatively regulating TGFβR2. Thus, miR-155-regulated TGFβR2 as a potential therapeutic target in GC.
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ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death
Abstract
ADAMs (a disintegrin and metalloproteinases) are involved in various biological events such as cell adhesion, migration and invasion, membrane protein shedding and proteolysis. However, there have been no systematic studies on the expression of ADAMs in human ovarian carcinomas. We therefore examined the mRNA expression of all the proteolytic ADAM species including ADAM8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30, 33 and ADAMDEC1 in human ovarian carcinomas, and found that prototype membrane-anchored ADAM9m, but not secreted isoform ADAM9s, is significantly over-expressed in the carcinomas than in the control non-neoplastic ovarian tissue. Among the histological sub-types of serous, endometrioid, mucinous and clear cell carcinomas, the ADAM9m expression was highest in the clear cell carcinomas. Immunohistochemistry demonstrated that all the clear cell carcinoma samples exhibit ADAM9m primarily on the carcinoma cell membrane. By immunoblotting, ADAM9m was detected mainly in an active form in the clear cell carcinoma tissues. When two clear cell carcinoma cell lines (RMG-I and TOV21G cells) with ADAM9m expression were treated with cisplatin, the viability was significantly reduced and apoptosis increased in ADAM9m knock-down cells compared with mock transfectants. In addition, treatment of the cells with neutralizing anti-ADAM9m antibody significantly decreased viability compared with non-immune IgG, whereas ADAM9m over-expression significantly increased viability compared with mock transfectants. Our data demonstrate, to the best of our knowledge, for the first time that ADAM9m is over-expressed in an activated form in human ovarian clear cell carcinomas, and suggest that ADAM9m plays a key role in the cisplatin-resistance.
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Whole exome sequencing to identify genetic markers for trastuzumab-induced cardiotoxicity
Abstract
Although trastuzumab-induced cardiotoxicity is an important determinant to limit the use of this drug, the molecular mechanism of risk for this toxicity is not well understood. To identify genetic variants determining the risk of trastuzumab-induced cardiotoxicity, we performed whole exome sequencing of germline DNA samples from 9 patients with trastuzumab-induced cardiotoxicity, and conducted a case–control association study of 2,258 genetic variants between 9 cases (with trastuzumab-induced cardiotoxicity) and general Japanese population controls registered in Human Genetic Variation Database (HGVD). The top variant which revealed the lowest P value in the screening study was rs139503277 in PHD Finger Protein 3 (Pmin = 0.00012, odds ratio (OR) = 51.23). To further validate the result of screening study, we carried out a replication study of 10 variants showing Pmin < 0.001 in the screening study using 234 independent patients treated with trastuzumab, including 10 cases and 224 controls (without trastuzumab-induced cardiotoxicity). In the replication study, we observed that three variants had effect in the same direction as in the screening study (rs78272919 in exon 2 of Keratin 15, rs5762940 in exon 2 of zinc and ring finger 3 and rs139944387 in exon 44 of Eyes shut homologs (EYS)). A combined result of the screening and the replication studies suggested an association of a locus on chromosome 6q12 with trastuzumab-induced cardiotoxicity (rs139944387 in EYS, combined-Pmin = 0.00056, OR = 13.73). This finding provides new insights into personalized trastuzumab therapy for the patients with HER2 positive cancer.
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Reduced deep regional cerebral venous oxygen saturation in hemodialysis patients using quantitative susceptibility mapping
Abstract
Cerebral venous oxygen saturation (SvO2) is an important indicator of brain function. There was debate about lower cerebral oxygen metabolism in hemodialysis patients and there were no reports about the changes of deep regional cerebral SvO2 in hemodialysis patients. In this study, we aim to explore the deep regional cerebral SvO2 from straight sinus using quantitative susceptibility mapping (QSM) and the correlation with clinical risk factors and neuropsychiatric testing. 52 hemodialysis patients and 54 age-and gender-matched healthy controls were enrolled. QSM reconstructed from original phase data of 3.0 T susceptibility-weighted imaging was used to measure the susceptibility of straight sinus. The susceptibility was used to calculate the deep regional cerebral SvO2 and compare with healthy individuals. Correlation analysis was performed to investigate the correlation between deep regional cerebral SvO2, clinical risk factors and neuropsychiatric testing. The deep regional cerebral SvO2 of hemodialysis patients (72.5 ± 3.7%) was significantly lower than healthy controls (76.0 ± 2.1%) (P < 0.001). There was no significant difference in the measured volume of interests of straight sinus between hemodialysis patients (250.92 ± 46.65) and healthy controls (249.68 ± 49.68) (P = 0.859). There were no significant correlations between the measured susceptibility and volume of interests in hemodialysis patients (P = 0.204) and healthy controls (P = 0.562), respectively. Hematocrit (r = 0.480, P < 0.001, FDR corrected), hemoglobin (r = 0.440, P < 0.001, FDR corrected), red blood cell (r = 0.446, P = 0.003, FDR corrected), dialysis duration (r = 0.505, P = 0.002, FDR corrected) and parathyroid hormone (r = −0.451, P = 0.007, FDR corrected) were risk factors for decreased deep regional cerebral SvO2 in patients. The Mini-Mental State Examination (MMSE) scores of hemodialysis patients were significantly lower than healthy controls (P < 0.001). However, the deep regional cerebral SvO2 did not correlate with MMSE scores (P = 0.630). In summary, the decreased deep regional cerebral SvO2 occurred in hemodialysis patients and dialysis duration, parathyroid hormone, hematocrit, hemoglobin and red blood cell may be clinical risk factors.
http://ift.tt/2CLlIR6
Live Imaging Followed by Single Cell Tracking to Monitor Cell Biology and the Lineage Progression of Multiple Neural Populations
A robust protocol to monitor neural populations by time-lapse video-microscopy followed by software-based post-processing is described. This method represents a powerful tool to identify biological events in a selected population during live imaging experiments.
http://ift.tt/2kDPiPU
Mouse Model for Pancreas Transplantation Using a Modified Cuff Technique
Among abdominal solid organ transplantation, pancreatic grafts are prone to develop severe ischemia reperfusion injury-associated graft damage, leading eventually to early graft loss. This protocol describes a model of murine pancreas transplantation using a non-suture cuff technique, ideally suited for analyzing these early, deleterious damages.
http://ift.tt/2kAbGKi
Why does the need for medication become a barrier to breastfeeding? A narrative review
Publication date: Available online 16 December 2017
Source:Women and Birth
Author(s): Alyson K. McClatchey, Alison Shield, Lynn H. Cheong, Sally L. Ferguson, Gabrielle M. Cooper, Gregory J. Kyle
ProblemThe need for medication during lactation can contribute to the early cessation of breastfeeding.BackgroundBreastfeeding women may require medication for acute or chronic health conditions. For some women this need for medication can become a barrier to breastfeeding; this is despite the fact that the majority of medications are considered to be compatible with lactation.AimThis narrative review aims to investigate factors relating to medicines safety that could contribute to medication unnecessarily becoming a barrier to breastfeeding.MethodsA selective literature search using PubMed, Scopus and Google Scholar was conducted over a 6-month period using the search terms "breastfeeding", "lactation", "medication" and "information". Articles were assessed to identify whether they addressed the impact of medication use on the decision to breastfeed.FindingsFifty six articles were identified as having appropriate discussion about decision making for the safe use of medication during lactation. Themes identified included variable and conflicting safety advice for medicines; difficulty interpreting risks associated with medicine use; societal pressures faced by the breastfeeding woman; and the varied knowledge and training of health professionals involved in the care of breastfeeding women.ConclusionPoor quality of information about medicine safety during lactation can contribute to confusion in giving recommendations. This confusion can result in early cessation of breastfeeding or insufficient health care for the breastfeeding woman.
http://ift.tt/2oo48PZ
Herbal medicines use during pregnancy in Sierra Leone: An exploratory cross-sectional study
Publication date: Available online 16 December 2017
Source:Women and Birth
Author(s): Peter Bai James, Abdulai Jawo Bah, Michael Steven Tommy, Jon Wardle, Amie Steel
BackgroundThe influence of complementary therapies on maternal health has attracted the attention of policy makers, health professionals and researchers globally especially in developing countries. However, there is lack of evidence on whether Sierra Leonean women use herbal medicine during pregnancy which limit the chance of providing better maternity care.AimThis study was conducted to determine the prevalence and pattern of herbal medicines use among pregnant women attending an antenatal clinic at a tertiary maternal hospital in Sierra Leone.MethodsA cross-sectional study was conducted among pregnant women (n=134) who were at least 18 years of age and who have had at least one previous pregnancy, using face to face interview. Descriptive statistics, univariate and multivariate logistic regression analysis were used for data analysis.ResultsThe response rate was 82.7%. Nearly two-thirds of pregnant women reported using herbal medicine (62.7%). Herbal medicine users were more likely to be Muslim than Christian. Luffa acutangula (L.) Roxb was the most cited herbal medicine used and was mostly indicated for urinary tract infection and pedal oedema. Perceived effectiveness and safety over conventional medicine (70.2%) was key driver for use, and majority did not disclose their use of herbs to their maternal health professional (95.2%).ConclusionHerbal medicine use among pregnant women in this study was widespread. Maternal health providers should be aware of this relatively common practice and routinely discuss and educate pregnant women on the potential risks and benefits associated with the use of herbs.
http://ift.tt/2CID3tV
Triple-stapled quadrilateral anastomosis: a new technique for creation of an esophagogastric anastomosis
Abstract
Background
Esophagogastric anastomosis performed after esophagectomy is technically complex and often the source of postoperative complications. The best technique for this anastomosis remains a matter of debate. We describe a new all-stapled side-to-side anastomosis, which we refer to as triple-stapled quadrilateral anastomosis (TRIQ), that can be performed after minimally invasive surgery, and we report results of a retrospective evaluation of postoperative outcomes among the 60 patients in whom this anastomosis has been performed thus far.
Methods
The anastomosis is created by apposition of the posterior walls of the esophagus and stomach. A linear stapler is applied to create a V-shaped posterior anastomotic wall. The anterior wall is closed in a gentle chevron-like shape with the use of 2 separate linear staplers, resulting in a wide quadrilateral anastomosis. The anastomosis is then wrapped with a greater omentum flap.
Results
The patient group comprised 48 men and 12 women with a mean age of 67.8 years. Neoadjuvant chemotherapy was performed in 43 of these patients. Neither the thoracoscopic or laparoscopic procedure was converted to open surgery in any patient. The median operation time was 474 min (range 680–320 min). The intraoperative blood loss volume was 104.4 mL (range 240–30 mL). There were no anastomosis-related complications above Clavien-Dindo grade II.
Conclusions
TRIQ can be performed easily and safely, and good short-term outcome can be expected.
http://ift.tt/2k5lWun
Angiogenic factors: role in esophageal cancer, a brief review
Abstract
Esophageal cancer has an aggressive behavior with rapid tumor mass growth and frequently poor prognosis; it is known as one of the most fatal types of cancer worldwide. The identification of potential molecular markers that can predict the response to treatment and the prognosis of this cancer has been subject of a vast investigation in the recent years. Among several molecules, various angiogenic factors that are linked to the tumor development, growth, and invasion, such as VEGF, HGF, angiopoietin-2, IL-6, and TGF-B1, were investigated. In this paper, the authors sought to review the role of these angiogenic factors in prognosis and hypothesize how they can be used as a treatment target.
http://ift.tt/2k1eoZI
Inhibition of autophagy enhances synergistic effects of Salidroside and anti-tumor agents against colorectal cancer
Various plant extracts have been suggested to be used as auxiliary agents in chemotherapy considering their anti-proliferative effect on cancer cells. However, recent reports reveal that plant extracts may fun...
http://ift.tt/2BmlRKx
Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study
The standardized maritime pine bark extract (Pycnogenol®) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for thi...
http://ift.tt/2Cog9qw
MOK, a pharmacopuncture medicine, regulates thyroid dysfunction in L-thyroxin-induced hyperthyroidism in rats through the regulation of oxidation and the TRPV1 ion channel
In this study, we evaluated the therapeutic effect of MOK, a pharmacopuncture medicine, on thyroid dysfunction in L-thyroxin (LT4)-induced hyperthyroidism rats.
http://ift.tt/2BkFUcd
The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice
The increasing use of complementary and alternative medicine (CAM) has kindled the need for scientific evaluation of the mechanism of action of CAMs. Although, licorice, a common ingredient in many Traditional...
http://ift.tt/2Cn7pRw
Distinguishing features of microglia- and monocyte-derived macrophages after stroke
Abstract
After stroke, macrophages in the ischemic brain may be derived from either resident microglia or infiltrating monocytes. Using bone marrow (BM)-chimerism and dual-reporter transgenic fate mapping, we here set out to delimit the responses of either cell type to mild brain ischemia in a mouse model of 30 min transient middle cerebral artery occlusion (MCAo). A discriminatory analysis of gene expression at 7 days post-event yielded 472 transcripts predominantly or exclusively expressed in blood-derived macrophages as well as 970 transcripts for microglia. The differentially regulated genes were further collated with oligodendrocyte, astrocyte, and neuron transcriptomes, resulting in a dataset of microglia- and monocyte-specific genes in the ischemic brain. Functional categories significantly enriched in monocytes included migration, proliferation, and calcium signaling, indicative of strong activation. Whole-cell patch-clamp analysis further confirmed this highly activated state by demonstrating delayed outward K+ currents selectively in invading cells. Although both cell types displayed a mixture of known phenotypes pointing to the significance of 'intermediate states' in vivo, blood-derived macrophages were generally more skewed toward an M2 neuroprotective phenotype. Finally, we found that decreased engraftment of blood-borne cells in the ischemic brain of chimeras reconstituted with BM from Selplg−/− mice resulted in increased lesions at 7 days and worse post-stroke sensorimotor performance. In aggregate, our study establishes crucial differences in activation state between resident microglia and invading macrophages after stroke and identifies unique genomic signatures for either cell type.
http://ift.tt/2zhzZVT
Preoxygenation and injectable anesthesia in dog: evaluation of maintenance and recovery periods of anesthesia and hemoglobin desaturation
Abstract
This study was conducted to evaluate the efficacy of preoxygenation during the injectable general anesthesia in dogs and estimate the maintenance and recovery times besides measuring the time of hemoglobin desaturation following preoxygenation. Ten young healthy mix-breed dogs were selected and divided into two equal groups. They premedicated with IM administration of acepromazine. The first group received pure oxygen via face mask for 5 min just before induction of anesthesia. The other group received room air similarly. The general anesthesia was induced with IV injection of ketamine-xylazine mixture. The SpO2 changes were recorded before and after preoxygenation in both groups. In addition, the duration of induction, maintenance, and recovery time of anesthesia, heart rate, rectal temperature, and respiratory rate were recorded before administration of acepromazine and were repeated each 5 min. There was no significant difference between groups in induction, anesthesia maintenance, and recovery periods. The opposite of the room air group, SpO2 increased significantly in the preoxygenated group after preoxygenation. According to the analyzed results, preoxygenation had no impact on respiratory rate and heart rate. So, it is concluded that preoxygenation does not affect maintenance and recovery periods of injectable anesthesia in dogs. But significant oxygen saturation of blood after IV injection of ketamine was found as an important result of preoxygenation.
http://ift.tt/2zgClEu
Advances in ovarian cancer therapy
Abstract
Epithelial ovarian cancer is typically diagnosed at an advanced stage. Current state-of-the-art surgery and chemotherapy result in the high incidence of complete remissions; however, the recurrence rate is also high. For most patients, the disease eventually becomes a continuum of symptom-free periods and recurrence episodes. Different targeted treatment approaches and biological drugs, currently under development, bring the promise of turning ovarian cancer into a manageable chronic disease. In this review, we discuss the current standard in the therapy for ovarian cancer, major recent studies on the new variants of conventional therapies, and new therapeutic approaches, recently approved and/or in clinical trials. The latter include anti-angiogenic therapies, polyADP-ribose polymerase (PARP) inhibitors, inhibitors of growth factor signaling, or folate receptor inhibitors, as well as several immunotherapeutic approaches. We also discuss cost-effectiveness of some novel therapies and the issue of better selection of patients for personalized treatment.
http://ift.tt/2k5NQGX
Changes in bone mineral density in women with breast cancer receiving aromatase inhibitor therapy
Abstract
Purpose
We assessed bone mineral density (BMD) change with aromatase inhibitor (AI) treatment in a contemporary cohort of women with breast cancer treated in Kaiser Permanente Northern California.
Methods
Percent and estimated annual percent changes in BMD at the total hip and lumbar spine were examined in 676 women receiving AI therapy who had two serial BMD reports available (at least 1 year apart) before and after AI initiation (N = 317) or during continued AI therapy (N = 359). BMD changes were examined at the total hip and lumbar spine and compared by age and clinical subgroups.
Results
Women experienced BMD declines after AI initiation or continued therapy, with median annual percent change − 1.2% (interquartile range, IQR − 2.4 to − 0.1%) at the hip and − 1.0% (IQR − 2.3 to 0.1%) at the spine after AI initiation, and − 1.1% (IQR − 2.4 to 0.1%) at the hip and − 0.9% (IQR − 2.4 to 0.5%) at the spine during continued therapy. Higher levels of bone loss were observed among younger (< 55 years) compared with older (≥ 75 years) women at the hip (− 1.6% vs. − 0.8%) and at the spine (− 1.5% vs. − 0.5%) after AI initiation, and at the hip (− 1.4% vs. − 1.2%) and at the spine (− 2.4% vs. − 0.001%) during continued therapy.
Conclusions
Small but consistent declines in total hip and lumbar spine BMD were present in breast cancer patients following AI therapy initiation or continued AI therapy. Although the overall rates of osteoporosis were low, greater estimated levels of annual bone loss were evident among women < 55 years.
http://ift.tt/2oimlya
Cardiac output changes after osmotic therapy in neurosurgical and neurocritical care patients: A systematic review of the clinical literature
Abstract
Aim
Osmotherapy constitutes a first-line intervention for intracranial hypertension management. However, hyperosmolar solutes exert various systematic effects, among which their impact on systemic hemodynamics is poorly clarified. This review aims to appraise the clinical evidence of the effect of mannitol and hypertonic saline (HTS) on cardiac performance in neurosurgical and neurocritical care patients.
Method
A database search was conducted to identify randomized clinical trials and observational studies reporting HTS or mannitol use in acute brain injury setting. The primary end-points were alterations of cardiac output (CO) and other hemodynamic variables, while the impact of osmotic agents on intracranial pressure, brain relaxation, plasma osmolality, electrolyte levels and urinary output constituted secondary outcomes.
Results
Eight studies, enrolling 182 patients, were included. HTS exerted a more profound CO augmentation than mannitol, but no distinct difference between groups occurred. Central venous pressure, stroke volume and stroke volume variation were favourably affected by both osmotic agents, whilst the reported changes in blood pressure were inconclusive. HTS-infusion yielded a larger intracranial pressure reduction than mannitol but had an equivalent effect on brain relaxation. Mannitol presented a more potent diuretic effect than HTS. Effect on serum osmolality was alike in both osmotic agents, but contrary to HTS-promoted hypernatremia, mannitol use induced transient hyponatremia.
Conclusions
Mannitol or HTS administration seems to induce an enhancement of cardiac performance; being more prominent after HTS infusion. This effect combined with mannitol-induced enhancement of diuresis and HTS-promoted increase of plasma sodium concentration could partially explain the effects of osmotherapy on cerebral hemodynamics.
http://ift.tt/2ACBr3p
Expression and clinical value of programmed cell death-ligand 1 (PD-L1) in diffuse large B cell lymphoma: a retrospective study
The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses...
http://ift.tt/2orC8uT
Impact of high-intensity interval training and moderate-intensity continuous training on resting and post-exercise cardiac troponin T concentration
Abstract
We evaluated the influence of 12 weeks high-intensity interval training (HIIT, repeated 4-min cycling at 90% V̇O2max interspersed with 3-min rest, 200–300 KJ/session, 3–4 days wk−1) and work-equivalent moderate-intensity continuous training (MICT, continuous cycling at 60% V̇O2max) on resting cardiac troponin T (cTnT) as well as exercise-induced cTnT appearance. Forty-eight sedentary obese young women were randomly assigned to HIIT, MICT, or a control group. V̇O2max and body composition were measured before and after training. At baseline, cTnT was assessed using a high-sensitivity assay at rest and immediately, 2 h and 4 h after 45-min cycling at 60% V̇O2max. After a 12-wk training period, cTnT was assessed before and after 45-min cycling at the same relative and absolute intensities as before training. Training led to higher V̇O2max and lower fat mass in both HIIT and MICT (all P < 0.05). Before training, cTnT was significantly elevated in all three groups (35 to 118%, all P < 0.05) with acute exercise. After training both resting and post-exercise cTnT levels (same relative intensity) were similar to pre-training values. In contrast, post-exercise cTnT (same absolute intensity, which represented a smaller exercise stimulus) was not elevated from rest in both HIIT and MICT groups. In conclusion, 12 weeks of either HIIT or MICT largely abolished the elevation of post-exercise cTnT concentration when exercise was performed at the same absolute intensity. There was, however, no impact of training on resting cTnT or post-exercise cTnT appearance for exercise performed at the same relative intensity.
This article is protected by copyright. All rights reserved
http://ift.tt/2BgENdx
Cancers, Vol. 9, Pages 172: PRIMA-1 and PRIMA-1Met (APR-246): From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies
Cancers, Vol. 9, Pages 172: PRIMA-1 and PRIMA-1Met (APR-246): From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies
Cancers doi: 10.3390/cancers9120172
Authors: Anne Perdrix Ahmad Najem Sven Saussez Ahmad Awada Fabrice Journe Ghanem Ghanem Mohammad Krayem
p53 protects cells from genetic assaults by triggering cell-cycle arrest and apoptosis. Inactivation of p53 pathway is found in the vast majority of human cancers often due to somatic missense mutations in TP53 or to an excessive degradation of the protein. Accordingly, reactivation of p53 appears as a quite promising pharmacological approach and, effectively, several attempts have been made in that sense. The most widely investigated compounds for this purpose are PRIMA-1 (p53 reactivation and induction of massive apoptosis )and PRIMA-1Met (APR-246), that are at an advanced stage of development, with several clinical trials in progress. Based on publications referenced in PubMed since 2002, here we review the reported effects of these compounds on cancer cells, with a specific focus on their ability of p53 reactivation, an overview of their unexpected anti-cancer effects, and a presentation of the investigated drug combinations.
http://ift.tt/2kA3VDS
Troubling disease syndrome in endangered live Patagonian huemul deer (Hippocamelus bisulcus) from the Protected Park Shoonem: unusually high prevalence of osteopathology
The last 1500 endangered Patagonian huemul deer (Hippocamelus bisulcus) exist in > 100 groups which are not recovering. Prevalence of osteopathology in dead huemul was 57+% (Argentina), whereas similar cases in C...
http://ift.tt/2zfS6vp
Microsatellite marker development from next-generation sequencing in the New England cottontail (Sylvilagus transitionalis) and cross-amplification in the eastern cottontail (S. floridanus)
The New England cottontail (Sylvilagus transitionalis) is a species of high conservation priority in the Northeastern United States, and was a candidate for federal listing under the Endangered Species Act until ...
http://ift.tt/2jb7znL
ABO and Rhesus blood group distribution and frequency among blood donors at Kilimanjaro Christian Medical Center, Moshi, Tanzania
This study aims to determine the distribution of blood groups and the demographic background of blood donors in a referral hospital in Northern Tanzania.
http://ift.tt/2zgsGh1
The complete chloroplast genome sequence of Asian Palmyra palm (Borassus flabellifer)
Borassus flabellifer or Asian Palmyra palm is widely distributed in South and Southeast Asia and is horticultural and economic importance for its fruit and palm sugar production. Howev...
http://ift.tt/2j7FKN6
A novel method for the detection of R-peaks in ECG based on K-Nearest Neighbors and Particle Swarm Optimization
Cardiovascular diseases are associated with high morbidity and mortality. However, it is still a challenge to diagnose them accurately and efficiently. Electrocardiogram (ECG), a bioelectrical signal of the he...
http://ift.tt/2j6qrUI
Possible interference between seasonal epidemics of influenza and other respiratory viruses in Hong Kong, 2014–2017
Unlike influenza viruses, little is known about the prevalence and seasonality of other respiratory viruses because laboratory surveillance for non-influenza respiratory viruses is not well developed or suppor...
http://ift.tt/2AUuI94
A two-month follow-up evaluation testing interventions to limit the emergence and spread of antimicrobial resistant bacteria among Maasai of northern Tanzania
In sub-Saharan Africa, efforts to control antimicrobial resistance (AMR) are aggravated by unregulated drug sales and use, and high connectivity between human, livestock, and wildlife populations. Our previous...
http://ift.tt/2ATYfQ5
Co-infection of sexually transmitted pathogens and Human Papillomavirus in cervical samples of women of Brazil
Some sexually transmitted infectious agents, such as Chlamydia trachomatis and Herpes simplex, cause local inflammation, and could contribute to Human Papillomavirus (HPV) and cervical lesion progression. Thus, t...
http://ift.tt/2yHCnli
Effect of early mobilization on postoperative pulmonary complications in patients undergoing video-assisted thoracoscopic surgery on the esophagus
Abstract
Background
Esophagectomy performed via thoracotomy is associated with a high rate of postoperative pulmonary complications. Video-assisted thoracoscopic surgery at the esophagus (VATS-E) can reduce the rate of postoperative pulmonary complications. VATS-E is being increasingly implemented owing to its benefits. This procedure makes early patient mobilization possible, because there is minimal thoracic wall invasion, and thus, less postoperative pain. This study aimed to identify the efficacy of early mobilization in patients undergoing VATS-E.
Methods
We retrospectively reviewed the patients who underwent VATS-E between November 2008 and October 2016. All the patients underwent preoperative physiotherapy and postoperative early mobilization for standard perioperative management. We examined the relation between early mobilization and the factors affecting postoperative pulmonary complications and the duration of physiotherapy with regard to the surgical outcome of VATS-E.
Results
A total of 118 patients who underwent VATS-E were assessed. The incidence of postoperative pulmonary atelectasis decreased with early mobilization, and earlier mobilization was associated with a better decrease (P < 0.001). Multiple logistic regression analysis identified the percentage of volume capacity [odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93–0.99] and initial walking (OR 1.82; 95% CI 1.40–2.48) as independent risk factors for postoperative pulmonary atelectasis. In addition, the presence or absence of atelectasis was found to reduce the necessary period of physiotherapy (P < 0.001).
Conclusion
Our results indicated that early mobilization reduces the incidence of postoperative pulmonary atelectasis, which may also contribute to early recovery in patients who undergo VATS-E.
http://ift.tt/2Bsz0nL
Human c-SRC kinase (CSK) overexpression makes T cells dummy
Abstract
Adoptive cell therapy with T-cell receptor (TCR)-engineered T cells represents a powerful method to redirect the immune system against tumours. However, although TCR recognition is restricted to a specific peptide–MHC (pMHC) complex, increasing numbers of reports have shown cross-reactivity and off-target effects with severe consequences for the patients. This demands further development of strategies to validate TCR safety prior to clinical use. We reasoned that the desired TCR signalling depends on correct pMHC recognition on the outside and a restricted clustering on the inside of the cell. Since the majority of the adverse events are due to TCR recognition of the wrong target, we tested if blocking the signalling would affect the binding. By over-expressing the c-SRC kinase (CSK), a negative regulator of LCK, in redirected T cells, we showed that peripheral blood T cells inhibited anti-CD3/anti-CD28-induced phosphorylation of ERK, whereas TCR proximal signalling was not affected. Similarly, overexpression of CSK together with a therapeutic TCR prevented pMHC-induced ERK phosphorylation. Downstream effector functions were also almost completely blocked, including pMHC-induced IL-2 release, degranulation and, most importantly, target cell killing. The lack of effector functions contrasted with the unaffected TCR expression, pMHC recognition, and membrane exchange activity (trogocytosis). Therefore, co-expression of CSK with a therapeutic TCR did not compromise target recognition and binding, but rendered T cells incapable of executing their effector functions. Consequently, we named these redirected T cells "dummy T cells" and propose to use them for safety validation of new TCRs prior to therapy.
http://ift.tt/2BgdWOL
Cancers, Vol. 9, Pages 171: Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis
Cancers, Vol. 9, Pages 171: Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis
Cancers doi: 10.3390/cancers9120171
Authors: Trung Vu Pran Datta
Epithelial to mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, for instance cell polarity and cell–cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer (CRC), EMT is associated with an invasive or metastatic phenotype. In this review, we discuss recent studies exploring novel regulation mechanisms of EMT in CRC, including the identification of new CRC EMT regulators. Upregulation of inducers can promote EMT, leading to increased invasiveness and metastasis in CRC. These inducers can downregulate E-cadherin and upregulate N-cadherin and vimentin (VIM) through modulating EMT-related signaling pathways, for instance WNT/β-catenin and TGF-β, and EMT transcription factors, such as zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2. In addition, several microRNAs (miRNAs), including members of the miR-34 and miR-200 families, are found to target mRNAs of EMT-transcription factors, for example ZEB1, ZEB2, or SNAIL. Downregulation of these miRNAs is associated with distant metastasis and advanced stage tumors. Furthermore, the role of EMT in circulating tumor cells (CTCs) is also discussed. Mesenchymal markers on the surface of EMT CTCs were found to be associated with metastasis and could serve as potential biomarkers for metastasis. Altogether, these studies indicate that EMT is orchestrated by a complicated network, involving regulators of different signaling pathways. Further studies are required to understand the mechanisms underlying EMT in CRC.
http://ift.tt/2yIehXm
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
