Sulfonamides as Selective Na1.7 Inhibitors: Optimizing Potency, Pharmacokinetics, and Metabolic Properties to Obtain Atropisomeric Quinolinone (AM-0466) that Affords Robust in Vivo Activity.

Because of its strong genetic validation, Na1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as Na1.

Cervical cancer.

Essential facts In the UK in 2013 there were about 3,200 new cases of cervical cancer. It is the 12th most common cancer in UK women, resulting in 890 deaths in 2014. Deaths in England are more common in women living in the most deprived areas.

Comparison of self-collected meatal swabs with urine specimens for the diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in men.

Purpose: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are common bacterial causes of sexually transmitted infections. Self-taken meatal swabs are a possible alternative to urine samples in testing for infection; however, the data surrounding their use are limited.

Methodology: We carried out a prospective service review in a large sexual health clinic comparing urine samples and self-taken meatal swabs in men presenting for sexual transmissible infection screening for CT and GC with the BD Viper XTR system.

Benefits of the use of blood conservation in scoliosis surgery.

Aim: To investigate whether autologous blood transfusion (ABT) drains and intra-operative cell salvage reduced donor blood transfusion requirements during scoliosis surgery.

Methods: Retrospective data collection on transfusion requirements of patients undergoing scoliosis surgery is between January 2006 and March 2010. There were three distinct phases of transfusion practice over this time: Group A received "traditional treatment" with allogeneic red cell transfusion (ARCT) in response to an intra- or post-operative anaemia (Hb < 8 g/dL or a symptomatic anaemia); Group B received intra-operative cell salvage in addition to "traditional treatment".

Toxoplasma gondii autophagy-related protein ATG9 is crucial for the survival of parasites in their host.

Autophagy is a conserved, life-promoting, catabolic process involved in the recycling of nonessential cellular components in response to stress. The parasite Toxoplasma gondii is an early-diverging eukaryote in which part of the autophagy machinery is not exclusively involved in a catabolic process but instead has been repurposed for an original function in organelle inheritance during cell division. This function, depending essentially on protein TgATG8 and its membrane conjugation system, is crucial for parasite survival and prevented an in depth study of autophagy in the mutants generated so far in Toxoplasma.

Inhibition of plasmin generation in plasma by heparin, low molecular weight heparin, and a covalent antithrombin-heparin complex.

: The clinical limitations of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) led to the development of an antithrombin-heparin covalent complex (ATH), which displays superior anticoagulant abilities compared with UFH. A recent study investigating its interaction with fibrinolysis showed that ATH inhibited free and fibrin bound plasmin and decreased plasmin generation on fibrin clots. These studies were conducted using purified components and did not elucidate the interaction of ATH with plasmin in the presence of its natural inhibitors α2-antiplasmin (α2-AP) and α2-macroglobulin (α2-M).

Incidence and characteristics of needlestick injuries among medical trainees at a community teaching hospital: A cross-sectional study.

Objectives: This field study aimed to determine the incidence and distribution of needlestick injuries among medical trainees at a community teaching hospital in Toronto, Canada.

Methods: The study was performed during the 2013-2015 academic years at Toronto East General Hospital (TEGH), a University of Toronto-affiliated community-teaching hospital during the 2013-2015 academic years. Eight-hundred and forty trainees, including medical students, residents, and post-graduate fellows, were identified and invited via email to participate in an anonymous online fluidsurveys.

The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications.

Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene.

Skin cancer.

Essential facts Skin cancer can be split into 2 groups: malignant melanoma, which can be fatal; and non-melanoma, such as squamous cell carcinoma and basal cell carcinomas, which are rarely lethal. In 2013 there were 14,509 new cases of malignant melanoma in the UK and, in 2014, 2,459 people died from the disease. Non-melanoma skin cancers are more common; 72,100 new cases were diagnosed in the UK in 2013.

The complex behavioral phenotype of 15q13.3 microdeletion syndrome.

Background: Chromosome 15q13.3 represents a hotspot for genomic rearrangements due to repetitive sequences mediating nonallelic homologous recombination. Deletions of 15q13.

Realities of environmental toxicity and their ramifications for community engagement.

Research on community responses to environmental toxicity has richly described the struggles of citizens to identify unrecognized toxins, collect their own environmental health facts, and use them to lobby authorities for recognition and remediation. Much of this literature is based on an empiricist premise: it is concerned with exploring differences in how laypeople and experts perceive what is presumed to be a singular toxic reality that preexists these varying perspectives. Here, we seek to reexamine this topic by shifting the focus from facts to facticity-that is, by exploring the many types of knowledge that communities develop about toxicity and how these knowledges articulate with the ideas of scientific and governmental authorities about what kinds of information are valid bases for policymaking.

A unique PE_PGRS protein inhibiting host cell cytosolic defenses and sustaining full virulence of Mycobacterium marinum in multiple hosts.

Despite intense research, PE_PGRS proteins still represent an intriguing aspect of mycobacterial pathogenesis. These cell surface proteins influence virulence in several pathogenic species, but their diverse and exact functions remain unclear. Herein, we focussed on a PE_PGRS member from Mycobacterium marinum, MMAR_0242, characterized by an extended and unique C-terminal domain.

Our Commitment to You for End of Life Care.

Essential facts In July the government announced a new commitment to improve end of life care in England in response to What's Important to Me: A Review of Choice in End of Life Care (the Choice Review).

End of life care.

Essential facts In July, the government announced a new commitment to improve end of life care in England in response to What's Important to Me: A Review of Choice in End of Life Care.

The research relationship in narrative enquiry.

Background Many nurse researchers have embraced narrative methods because of the power of the stories they produce. Narrative enquiry relies on stories for data. Stories are the tools with which people build a sense of their experience of the world and the vehicle by which they share that sense with others.

Oral health for adults in care homes.

Essential facts It is estimated that more than 400,000 adults live in UK care homes, 80% of whom have dementia. More than half of older people in care homes have tooth decay compared with 40% of over 75s and 33% of over 85s who do not live in care homes. Care home residents are more likely to have fewer natural teeth, and those with teeth are less likely to have enough teeth to eat comfortably and socialise without embarrassment.

An evolutionarily conserved SSNA1/DIP13 homologue is a component of both basal and apical complexes of Toxoplasma gondii.

Microtubule-based cytoskeletal structures have fundamental roles in several essential eukaryotic processes, including transport of intracellular constituents as well as ciliary and flagellar mobility. Temporal and spatial organisation of microtubules is determined by microtubule organising centers and a number of appendages and accessory proteins. Members of the SSNA1/DIP13 family are coiled coil proteins that are known to localise to microtubular structures like centrosomes and flagella, but are otherwise poorly characterised.