By hook or by crook? Morphometry, competition and cooperation in rodent sperm

Background Sperm design varies enormously across species and sperm competition is thought to be a major factor influencing this variation. However, the functional significance of many sperm traits is still poorly understood. The sperm of most murid rodents are characterised by an apical hook of the sperm head that varies markedly in extent across species. In the European woodmouse Apodemus sylvaticus (Muridae), the highly reflected apical hook of sperm is used to form sperm groups, or “trains,” which exhibited increased swimming velocity and thrusting force compared to individual sperm. Methodology/Principal Findings Here we use a comparative study of murine rodent sperm and demonstrate that the apical hook and sperm cooperation are likely to be general adaptations to sperm competition in rodents. We found that species with relatively larger testes, and therefore more intense sperm competition, have a longer, more reflected apical sperm hook. In addition, we show that sperm groups also occur in rodents other than the European woodmouse. Conclusions Our results suggest that in rodents sperm cooperation is more widespread than assumed so far and highlight the importance of diploid versus haploid selection in the evolution of sperm design and function

Coronary angiography and angioplasty in diabetic patients

Screening, diagnosis and revascularization of coronary artery disease (CAD) in type 2 diabetes mellitus are major challenges for current clinical practice. Diagnostic (angiography) and therapeutic (angioplasty) cardiac catheterization are important resources for the clinical assessment and management of coronary atherosclerosis. Anatomic peculiarities of CAD in diabetics can be well characterized by angiography, associated or not by intravascular ultrasound. The worse outcome following coronary revascularization procedures, either angioplasty or surgery, in diabetic is one of the main fields of clinical research. In spite of controversies, about one quarter of angioplasty and one third of surgical revascularization procedures are performed in diabetics. Two ongoing, large, randomized, multicentric trials are investigating the best management of CAD in diabetics. The BARI 2D trial is randomizing asymptomatic or mildly symptomatic patients with CAD for either medical therapy or revascularization (angioplasty or surgery, according to the best clinical judgment). The FREEDOM trial is randomizing stable patients with multivessel CAD for either angioplasty with drug eluting stents or surgery, with or without extracorporeal circulation. While the evidences are not available, in order to decide on the best revascularization procedure for individual patients, medical practice has been balanced according to a number of variables. Conditions that favor angioplasty: short lesions, lesions in large vessels, absence of left anterior descending artery disease, previous coronary bypass surgery and high surgical risk due to co-morbidities. Conditions that favor surgery: long lesions, lesions in small vessels, presence of left anterior descending artery disease and need for associated valve surgery.O rastreamento, o diagnóstico e a revascularização da doença arterial coronária (DAC) no diabetes tipo 2 representam enormes desafios para a prática médica. Neste contexto, o cateterismo cardíaco diagnóstico (angiografia) e terapêutico (angioplastia) são recursos fundamentais na avaliação clínica e manejo da aterosclerose coronária. Avaliações das particularidades anatômicas da DAC no diabetes são detalhadamente caracterizadas pela angiografia coronária, associada ou não ao ultra-som intracoronário. Por outro lado, a resposta pior aos procedimentos de revascularização (angioplastia e cirurgia) da DAC nos diabéticos representa umas das áreas de maior investigação clínica contemporânea. A despeito das controvérsias, cerca de um quarto dos pacientes submetidos a angioplastia e um terço dos pacientes submetidos a cirurgia são diabéticos. Dois grandes estudos multicêntricos randomizados, em andamento, investigam o melhor manejo da DAC nos diabéticos. O BARI 2D está randomizando pacientes com DAC assintomáticos ou com sintomas leves para tratamento clínico ou revascularização (angioplastia ou cirurgia, conforme melhor julgamento clínico). O FREEDOM está randomizando pacientes diabéticos estáveis com DAC multiarterial, para angioplastia com stent farmacológico ou cirurgia, com ou sem uso de circulação extra-corpórea. Enquanto as evidências não estão disponíveis, a prática médica atual é balanceada por um conjunto de variáveis na decisão sobre a melhor alternativa de revascularização. Condições que favorecem a angioplastia: estenoses curtas, vasos grandes, ausência de estenose na artéria descendente anterior (ADA), cirurgia de revascularização prévia e risco cirúrgico elevado. Condições que favorecem a indicação de cirurgia: estenoses longas, vasos pequenos, presença de estenose da ADA e cirurgia valvar associada.UNIFESP-EPMSPDM Hospital São Paulo Serviço de Hemodinâmica e Cardiologia IntervencionistaFOR Hospital do Rim e HipertensãoUNIFESP, EPMSPDM Hospital São Paulo Serviço de Hemodinâmica e Cardiologia IntervencionistaSciEL

Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells

NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells are engineered to co-express NKG2D with a fusion protein that comprises Dap10 joined to a Dap12 endodomain. NKG2D/Dap10-12 T cells elicit compelling efficacy, eradicating or controlling NKG2DL-expressing tumors in several established xenograft models. Importantly, durable responses, long-term survival, and rejection of tumor re-challenge are reproducibly achieved. Efficacy is markedly superior to a clinical stage CAR analog, comprising an NKG2D-CD3ζ fusion. Structure-function analysis using an extended CAR panel demonstrates that potency is dependent on membrane proximity of signaling units, high NKG2D cell surface expression, adaptor structure, provision of exogenous Dap10, and inclusion of one rather than three immune tyrosine activation motifs per signaling unit. Potent therapeutic impact of NKG2D/Dap10-12 T cells is also underpinned by enhanced oxidative phosphorylation, reduced senescence, and transcriptomic re-programming for increased ribosomal biogenesis

Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

BACKGROUND: Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP). METHODS: We reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). RESULTS: The expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP. CONCLUSION: Our results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen

BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy

Poor data have been previously reported about the mutation rates in K-RAS, BRAF, and PIK3CA genes among patients with hepatocellular carcinoma (HCC). Here we further elucidated the role of these genes in pathogenesis of primary hepatic malignancies. Archival tumour tissue from 65 HCC patients originating from South Italy were screened for mutations in these candidate genes by direct sequencing. Overall, oncogenic mutations were detected in 15 (23%) patients for BRAF gene, 18 (28%) for PIK3CA gene, and 1 (2%) for K-RAS gene. Using statistical analysis, BRAF mutations were significantly correlated with the presence of either multiple HCC nodules (P=0.021) or higher proliferation rates (P=0.034). Although further extensive screenings are awaited in HCC patients among different populations, our findings clearly indicated that mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population

Use of complementary/alternative therapies by women with advanced-stage breast cancer

BACKGROUND: This study sought to describe the pattern of complementary/alternative medicine (CAM) use among a group of patients with advanced breast cancer, to examine the main reasons for their CAM use, to identify patient's information sources and their communication pattern with their physicians. METHODS: Face-to-face structured interviews of patients with advanced-stage breast cancer at a comprehensive oncology center. RESULTS: Seventy three percent of patients used CAM; relaxation/meditative techniques and herbal medicine were the most common. The most commonly cited primary reason for CAM use was to boost the immune system, the second, to treat cancer; however these reasons varied depending on specific CAM therapy. Friends or family members and mass media were common primary information source's about CAM. CONCLUSIONS: A high proportion of advanced-stage breast cancer patients used CAM. Discussion with doctors was high for ingested products. Mass media was a prominent source of patient information. Credible sources of CAM information for patients and physicians are needed

Sensitivity and specificity of blood-fluid levels for oral anticoagulant-associated intracerebral haemorrhage

Intracerebral haemorrhage (ICH) is a life-threatening emergency, the incidence of which has increased in part due to an increase in the use of oral anticoagulants. A blood-fluid level within the haematoma, as revealed by computed tomography (CT), has been suggested as a marker for oral anticoagulant-associated ICH (OAC-ICH), but the diagnostic specificity and prognostic value of this finding remains unclear. In 855 patients with CT-confirmed acute ICH scanned within 48 h of symptom onset, we investigated the sensitivity and specificity of the presence of a CT-defined blood-fluid level (rated blinded to anticoagulant status) for identifying concomitant anticoagulant use. We also investigated the association of the presence of a blood-fluid level with six-month case fatality. Eighteen patients (2.1%) had a blood-fluid level identified on CT; of those with a blood-fluid level, 15 (83.3%) were taking anticoagulants. The specificity of blood-fluid level for OAC-ICH was 99.4%; the sensitivity was 4.2%. We could not detect an association between the presence of a blood-fluid level and an increased risk of death at six months (OR = 1.21, 95% CI 0.28–3.88, p = 0.769). The presence of a blood-fluid level should alert clinicians to the possibility of OAC-ICH, but absence of a blood-fluid level is not useful in excluding OAC-ICH

Identifying youth-friendly service practices associated with adolescents’ use of reproductive healthcare services in post-conflict Burundi: a cross-sectional study

BACKGROUND: Very little is known about reproductive health service (RHS) availability and adolescents’ use of these services in post-conflict settings. Such information is crucial for targeted community interventions that aim to improve quality delivery of RHS and outcomes in post-conflict settings. The objectives of this study therefore was to examine the density of RHS availability; assess spatial patterns of RHC facilities; and identify youth-friendly practices associated with adolescents’ use of services in post-conflict Burundi. METHODS: A cross-sectional survey was conducted from a full census of all facilities (n = 892) and provider interviews in Burundi. Surveyed facilities included all public, private, religious and community association owned-centers and hospitals. At each facility efforts were made to interview the officer-in-charge and a group of his/her staff. We applied both geospatial and non-spatial analyses, to examine the density of RHS availability and density, and to explore the association between youth-friendly practices and adolescents’ use of RHS in post-conflict Burundi. RESULTS: High spatial patterning of distances of RHC facilities was observed, with facilities clustered predominantly in districts exhibiting persistent violence. But, use of services remained undeterred. We further found a stronger association between use of RHS and facility and programming characteristics. Community outreach, designated check-in/exam rooms, educational materials (posters, print, and pictures) in waiting rooms, privacy and confidentiality were significantly associated with adolescents’ use of RHS across all facility types. Cost was associated with use only at religious facilities and youth involvement at private facilities. No significant association was found between provider characteristics and use of RHS at any facility. CONCLUSIONS: Our findings indicate the need to improve youth-friendly service practices in the provision of RHS to adolescents in Burundi and suggest that current approaches to provider training may not be adequate for improving these vital practices. Our mixed methods approach and results are generalizable to other countries and post-conflict settings. In post-conflict settings, the methods can be used to identify service availability and spatial patterns of RHC facilities to plan for targeted service interventions, to increase demand and uptake of services by youth and young adults