Potential mechanisms of resistance to venetoclax and strategies to circumvent it.

Background: Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges.

Pre-existing diabetes is a risk factor for increased rates of cellular rejection after kidney transplantation: an observational cohort study.

Aim: To investigate whether people with diabetes have an elevated risk of kidney allograft rejection in a well characterized clinical cohort in the setting of contemporary immunosuppression.

Methods: We conducted a retrospective cohort study including all kidney allograft recipients at a single centre between 2007 and 2015, linking clinical, biochemical and histopathological data from electronic patient records.

Results: Data were analysed for 1140 kidney transplant recipients.

Do outcomes after kidney transplantation differ for black patients in England versus New York State? A comparative, population-cohort analysis.

Objectives: Inferior outcomes for black kidney transplant recipients in the USA may not be generalisable elsewhere. In this population cohort analysis, we compared outcomes for black kidney transplant patients in England versus New York State.

Design: Retrospective, comparative, population cohort study utilising administrative data registries.

Vulnerability of Small-Cell Lung Cancer to Apoptosis Induced by the Combination of BET Bromodomain Proteins and BCL2 Inhibitors.

Ten percent to 15% of all lung cancers are small-cell lung cancer (SCLC). SCLC usually grows and metastasizes before it is diagnosed and relapses rapidly upon treatment. Unfortunately, no new targeted agent has been approved in the past 30 years for patients with SCLC.

Bioactivity studies of Huh-7 cells derived human epidermal growth factor expressed in Pichia pastoris.

Previously, we have reported cloning of human epidermal growth factor gene from Huh-7 cells and its extracellular expression in Pichia pastoris. The presented work is a detailed report regarding molecular characterization of Huh-7 cells-derived hEGF expressed in Pichia pastoris with special reference to its glycosylation profiling and bioactivity studies. Densitometric scanning of SDS-PAGE separated extracellular proteins from hEGF recombinant Pichia pastoris strain indicated that about 84% of the extracellular proteins were glycosylated.

An insight into the evolutionary history of human MHC paralogon.

The vertebrate genome contains several closely spaced sets of paralogous genes from distinct gene families on typically two, three or four different chromosomes (paralogons). These four fold paralogy regions have been considered as historical remnants of whole genome duplication events (WGDs/2R hypothesis). To examine the 2R hypothesis, a robust phylogenetic analysis of 40 multigene families with triplicated or quadruplicated distribution on human MHC bearing chromosomes (1/6/9/19) was conducted.

β-arrestin signalling and bias in hormone-responsive GPCRs.

G protein-coupled receptors (GPCRs) play crucial roles in the ability of target organs to respond to hormonal cues. GPCRs' activation mechanisms have long been considered as a two-state process connecting the agonist-bound receptor to heterotrimeric G proteins. This view is now challenged as mounting evidence point to GPCRs being connected to large arrays of transduction mechanisms involving heterotrimeric G proteins as well as other players.

Cancer-related outcomes in kidney allograft recipients in England versus New York State: a comparative population-cohort analysis between 2003 and 2013.

It is unclear whether cancer-related epidemiology after kidney transplantation is translatable between countries. In this population-cohort study, we compared cancer incidence and all-cause mortality after extracting data for every kidney-alone transplant procedure performed in England and New York State (NYS) between 2003 and 2013. Data were analyzed for 18,493 and 11,602 adult recipients from England and NYS respectively, with median follow up 6.

Bone mineral density level by dual energy X-ray absorptiometry in rheumatoid arthritis.

Objective: To observe the level of bone mineral density by Dual Energy X-ray Absorptiometry in rheumatoid arthritis patients.

Methods: The observational study was conducted at Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, from January 2011 to December 2014. Bone mineral density was measured from the femoral neck, ward's triangle and lumbar spine, in patients 25-55 years of age, who were diagnosed with rheumatoid arthritis.

Structure prediction and network analysis of chitinases from the Cape sundew, Drosera capensis.

Background: Carnivorous plants possess diverse sets of enzymes with novel functionalities applicable to biotechnology, proteomics, and bioanalytical research. Chitinases constitute an important class of such enzymes, with future applications including human-safe antifungal agents and pesticides. Here, we compare chitinases from the genome of the carnivorous plant Drosera capensis to those from related carnivorous plants and model organisms.

In situ study of single-walled carbon nanotube growth in an environmental scanning electron microscope.

Monitoring individual single-walled carbon nanotubes (SWCNTs) during their growth is a highly sought-after goal in view of understanding the processes involved in the nucleation, elongation and termination which ultimately control the diameter and chiral selectivity. Here, we report on the first truly in situ observations of SWCNT growth in an environmental scanning electron microscope (ESEM). The CNT growth from lithographically patterned catalysts was investigated as a function of the catalyst type (Fe, Co or Ni), temperature, type of precursor (ethanol or acetylene), gas phase composition and pressure, and pretreatment conditions, and we report on the most appropriate conditions for SWCNT growth in ESEM conditions.

Secondary Infertility due to Retained Fetal Bones Diagnosed via Saline Sonography.

Prolonged intrauterine retention of any fetal bones can lead to secondary infertility. The exact incidence remains unclear. This case report describes a 36-year woman with secondary infertility of eight years.

Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities.

Immune checkpoint therapies, such as ipilimumab, induce dramatic antitumor responses in a subset of patients with advanced malignancies, but they may also induce inflammatory responses and toxicities termed immune-related adverse events (irAEs). These irAEs are often low grade and manageable, but severe irAEs may lead to prolonged hospitalizations or fatalities. Early intervention is necessary to minimize morbidities that occur with severe irAEs.

Simple procedure applying lactose induction and one-step purification for high-yield production of rhCIFN.

Recombinant consensus interferon (CIFN) is a therapeutic protein with molecular weight of 19.5 kDa having broad spectrum antiviral activity. Recombinant human CIFN (rhCIFN) has previously been expressed in Escherichia coli using isopropyl-β-d-thiogalactopyranoside (IPTG), a non-metabolizable and expensive compound, as inducer.

Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy.

Background: On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma.

Methods: After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred.

Varied effects of untreated textile wastewater onto soil carbon mineralization and associated biochemical properties of a dryland agricultural soil.

Wastewater is an alternative, valuable and cost effective resource for irrigation in water-scarce arid and sami-arid regions of the world including Pakistan. Soils near urban centers are cultivated for vegetable and cash crops using untreated wastewater. Current study was performed with objectives of assessing impacts of untreated textile wastewater on some soil chemical, biological and enzymatic activities.

Sequence comparison, molecular modeling, and network analysis predict structural diversity in cysteine proteases from the Cape sundew, Drosera capensis.

Carnivorous plants represent a so far underexploited reservoir of novel proteases with potentially useful activities. Here we investigate 44 cysteine proteases from the Cape sundew, Drosera capensis, predicted from genomic DNA sequences. D.

Understanding communication pathways to foster community engagement for health improvement in North West Pakistan.

Background: This paper describes the community engagement process undertaken to ascertain the focus, development and implementation of an intervention to improve iodised salt consumption in rural communities in North West Pakistan. The Jirga is a traditional informal structure, which gathers men respected within their community and acts in a governing and decision-making capacity in the Pukhtoon culture. The Jirga system had a dual purpose for the study: to access men from the community to discuss the importance of iodised salt, and as an engagement process for the intervention.

Development of a flow cytometric method for quantification of BCL-2 family members in chronic lymphocytic leukemia and correlation with sensitivity to BCL-2 family inhibitors.

Background: We have developed a quantitative fluorescence cytometry (QFCM) method that can be used to measure BCL-2 family member proteins in cell lines and clinical samples. We described the validation of antibodies, methods development and application of the assay.

Method: We characterized and validated antibodies to BCL-2, BCL-X , and MCL-1 in cell lines to confirm specificity for flow cytometry.

Phase Imaging Using Focused Polycapillary Optics.

Conventional radiographic techniques depend on attenuation, which provides low contrast between soft tissues. However, X rays can accumulate large differential phase delays even in weakly absorbing materials. This can produce significantly higher contrast.

Staphylococcus aureus dry-surface biofilms are not killed by sodium hypochlorite: implications for infection control.

Background: Dry hospital environments are contaminated with pathogenic bacteria in biofilms, which suggests that current cleaning practices and disinfectants are failing.

Aim: To test the efficacy of sodium hypochlorite solution against Staphylococcus aureus dry-surface biofilms.

Methods: The Centers for Disease Control and Prevention Biofilm Reactor was adapted to create a dry-surface biofilm, containing 1.

Risk of post-transplantation diabetes mellitus is greater in South Asian versus Caucasian kidney allograft recipients.

South Asians have increased risk for type 2 diabetes mellitus compared with Caucasians in the general population, but data for the development of post-transplantation diabetes mellitus (PTDM) is scarce. In this retrospective analysis, data was extracted from electronic patient records at a single centre (2004-2014). Caucasians were more likely to be male, with higher age and BMI than South Asians.

Determination of liver and muscle aflatoxin B1 residues and select serum chemistry variables during chronic aflatoxicosis in broiler chickens.

Background: Aflatoxins are secondary metabolites of the fungus Aspergillus sp. The presence of aflatoxin in poultry feeds results in direct toxicity and economic losses, and human health hazards after consumption of contaminated liver and meat.

Objectives: The study was conducted to assess tissue residues of aflatoxin B1 (AFB1), and alterations in select clinical chemistry variables in serum during chronic aflatoxicosis in broiler chicks fed different dietary levels of AFB1.