Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders.

Background: Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy.

Safety and efficacy of factor XI (FXI) concentrate use in patients with FXI deficiency: a single-centre experience of 19 years.

Aim: Factor XI (FXI) concentrate is a pooled human plasma-derived factor concentrate used as replacement therapy for patients with FXI deficiency, which provides a predictable response and consistent haemostatic cover in emergency or elective situations. It has previously been implicated in adverse events such as thrombosis and inhibitor formation, with rare case reports of fatal incidents. We sought to establish the incidence of such complications in a retrospective case series between 1994 and 2012 at the Haemophilia Comprehensive Care Centre at Royal Free Hospital, London, UK.

Risk factors for reading disability in families with rolandic epilepsy.

Objective: The high prevalence and impact of neurodevelopmental comorbidities in childhood epilepsy are now well known, as are the increased risks and familial aggregation of reading disability (RD) and speech sound disorder (SSD) in rolandic epilepsy (RE). The risk factors for RD in the general population include male sex, SSD, and ADHD, but it is not known if these are the same in RE or whether there is a contributory role of seizure and treatment-related variables.

Methods: An observational study of 108 probands with RE (age range: 3.

Galectin-1 Prevents Infection and Damage Induced by Trypanosoma cruzi on Cardiac Cells.

Background: Chronic Chagas cardiomyopathy caused by Trypanosoma cruzi is the result of a pathologic process starting during the acute phase of parasite infection. Among different factors, the specific recognition of glycan structures by glycan-binding proteins from the parasite or from the mammalian host cells may play a critical role in the evolution of the infection.

Methodology And Principal Findings: Here we investigated the contribution of galectin-1 (Gal-1), an endogenous glycan-binding protein abundantly expressed in human and mouse heart, to the pathophysiology of T.

The effects of angiotensin II signaling blockade on platelet activity in subjects with hypertension.

Background: To investigate the effects of Angiotensin II receptor blockade (ARB) and angiotensin converting enzyme (ACE) inhibition on platelet reactivity in patients with mild to moderate hypertension. PFA-100 evaluates platelet function (expressed in seconds as closure time, CT) in anti-coagulated whole blood in vitro at high shear rates. The test cartridge is impregnated with either collagen and epinephrine (Col/Epi) or collagen and ADP (Col/ADP).

Risk of HIV-1 acquisition among women who use diff erent types of injectable progestin contraception in South Africa: a prospective cohort study.

Background: Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer different risks of HIV-1 acquisition.

Methods: We included data from South African women who used injectable contraception while participating in theVOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012.

The role of diabetes in acromegaly associated neoplasia.

Background: The risk and mortality due to cancer in patients with acromegaly have been previously investigated. Although GH/IGF-1 excess provides a probable pathophysiological explanation, the degree of IGF-1 excess and the role in acromegaly-associated neoplasms of diabetes, a common comorbidity in acromegaly with known association with cancer, remains unclear.

Methods: Acromegalic patients treated in three Canadian referral centers (Toronto, Montreal, Edmonton) were included.

Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders.

Background: Heritable bleeding and platelet disorders (BPD) are heterogeneous and frequently have an unknown genetic basis. The BRIDGE-BPD study aims to discover new causal genes for BPD by high throughput sequencing using cluster analyses based on improved and standardised deep, multi-system phenotyping of cases.

Methods: We report a new approach in which the clinical and laboratory characteristics of BPD cases are annotated with adapted Human Phenotype Ontology (HPO) terms.

Characteristics Associated with HIV Drug Resistance Among Women Screening for an HIV Prevention Trial in KwaZulu-Natal, South Africa.

While the expansion of antiretroviral therapy (ART) in sub-Saharan Africa has reduced morbidity and mortality from HIV/AIDS, it has increased concern about drug resistance. The Microbicide Trials Network 009 study assessed the prevalence of drug-resistance mutations among women at clinical sites in Durban, South Africa who tested seropositive for HIV-1 at screening for the VOICE trial. The objective of this paper was to identify characteristics and behaviors associated with drug resistance.

Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international, retrospective, 10-year survey.

Sparse data are available on presentation and management of acute coronary syndromes (ACS), including unstable angina and non-ST- and ST-elevation myocardial infarction, among persons with haemophilia (PWH). The aim of this study was to determine demographics, bleeding disorder characteristics, cardiovascular risk factors (CRFs), interventions, haemostatic protocol, revascularization outcomes and complications among PWH with ACS. Members of an international consortium comprising >2000 adult PWH retrospectively completed case report forms for episodes of ACS in a >10-year follow-up period (2003-2013).

Tenofovir-based preexposure prophylaxis for HIV infection among African women.

Background: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.

Methods: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly.

Transcriptional diversity during lineage commitment of human blood progenitors.

Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation.

A kinetico-mechanistic study on the C-H bond activation of primary benzylamines; cooperative and solid-state cyclopalladation on dimeric complexes.

The cyclometallation reactions of dinuclear μ-acetato complexes of the type [Pd(AcO)(μ-AcO)L]2 (L = 4-RC6H4CH2NH2, R = H, Cl, F, CF3), a process found to occur readily even in the solid state, have been studied from a kinetico-mechanistic perspective. Data indicate that the dinuclear acetato bridged derivatives are excellent starting materials to activate carbon-hydrogen bonds in a facile way. In all cases the established concerted ambiphilic proton abstraction by a coordinated acetato ligand has been proved.

Coordination, microprotonation equilibria and conformational changes of myo-inositol hexakisphosphate with pertinence to its biological function.

Within all the eukaryotic cells there is an important group of biomolecules that has been potentially related to signalling functions: the myo-inositol phosphates (InsPs). In nature, the most abundant member of this family is the so called InsP6 (phytate, L(12-)), for which our group has strived in the past to elucidate its intricate chemical behaviour. In this work we expand on our earlier findings, shedding light on the inframolecular details of its protonation and complexation processes.

Regulatory volume increase and regulatory volume decrease responses in HL-1 atrial myocytes.

Background/aims: we have investigated whether cultured cardiomyocytes of the cell line HL-1 have the ability to perform regulatory volume responses both in hypotonic and hypertonic conditions. Furthermore, we characterized those regulatory responses and studied the effects of bumetanide and DIDS in volume regulation of HL-1 cells.

Methods: we used a light scattering system to measure the transient volume changes of HL-1 cells when subjected to osmotic challenge.

Cytokine production but lack of proliferation in peripheral blood mononuclear cells from chronic Chagas' disease cardiomyopathy patients in response to T. cruzi ribosomal P proteins.

Background: Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.

HPTN 035 phase II/IIb randomised safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 for the prevention of sexually transmitted infections in women.

Objectives: To estimate the effectiveness of candidate microbicides BufferGel and 0.5% PRO 2000 Gel (P) (PRO 2000) for prevention of non-ulcerative sexually transmitted infections (STIs).

Methods: Between 2005 and 2007, 3099 women were enrolled in HIV Prevention Trials Network (HPTN) protocol 035, a phase II/IIb evaluation of the safety and effectiveness of BufferGel and PRO 2000 for prevention of STIs, including Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV).

Acetic Acid, the active component of vinegar, is an effective tuberculocidal disinfectant.

Effective and economical mycobactericidal disinfectants are needed to kill both Mycobacterium tuberculosis and non-M. tuberculosis mycobacteria. We found that acetic acid (vinegar) efficiently kills M.

Heterochromatin position effects on circularized sex chromosomes cause filicidal embryonic lethality in Drosophila melanogaster.

Some circularized X-Y chromosomes in Drosophila melanogaster are mitotically unstable and induce early embryonic lethality, but the genetic basis is unknown. Our experiments suggest that a large region of X-linked satellite DNA causes anaphase bridges and lethality when placed into a new heterochromatic environment within certain circularized X-Y chromosomes. These results reveal that repetitive sequences can be incompatible with one another in cis.

Global Emerging HEmophilia Panel (GEHEP): A Multinational Collaboration for Advancing Hemophilia Research and Treatment.

GEHEP, established in 2009, is an independent, multi-institutional, international consortium of early career hematology specialists in the field of hemophilia and other inherited bleeding disorders. The main objective of the group, whose members practice at institutions in North America, Europe, and South Africa, is to advance hemophilia care by providing a forum for mentored collaborative research, developing programs for improving clinical care, and promoting academic career development of junior faculty. GEHEP members collect and document anonymized data on intra- and interinstitutional differences in patient populations, diagnosis, and treatment in the field of hemophilia and other bleeding disorders.

May-Hegglin anomaly and pregnancy: a systematic review.

May-Hegglin anomaly (MHA) is an autosomal dominant disorder, characterized by a variable degree of thrombocytopaenia, large platelets and inclusion bodies in white blood cells. Bleeding manifestations are generally mild, but severe bleeding episodes have been reported. This is a systematic review of literature for MHA during pregnancy.