PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons.

An empirical model of carbon-ion relative biological effectiveness based on the linear correlation between radiosensitivity to photons and carbon ions.

To develop an empirical model to predict carbon ion (C-ion) relative biological effectiveness (RBE).We used published cell survival data comprising 360 cell line/energy combinations to characterize the linear energy transfer (LET) dependence of cell radiosensitivity parameters describing the dose required to achieve a given survival level, e.g.

ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.

Ataxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy.

Visceral Adiposity Index as a Measure of Cardiovascular Disease in Persons With Human Immunodeficiency Virus.

Background: Persons with well-treated human immunodeficiency virus (HIV) demonstrate a 2-fold higher risk of cardiovascular disease (CVD), which may be related to excess visceral adipose tissue (VAT). The visceral adiposity index (VAI) is a score to approximate VAT by combining biochemical measures with anthropometrics without quantification by imaging. We evaluated VAI in association with cardiometabolic factors among persons with HIV (PWH).

Post-traumatic stress disorder among individuals with traumatic spinal cord injury in Nepal: a cross-sectional study.

Study Design: Cross-sectional study OBJECTIVES: To identify the prevalence of posttraumatic stress disorder (PTSD) among the individuals with traumatic spinal cord injury (TSCI) and to examine the relationships between demographic and clinical characteristics, and PTSD.

Setting: Spinal Injury Rehabilitation Center (SIRC) and Dhulikhel Hospital, Kathmandu University Hospital (DH, KUH), Kavrepalanchowk, Nepal.

Methods: Individuals above 18 years of age with TSCI of at least one month from trauma and admitted to SIRC and DH, KUH from June 2019 to May 2021 were included.

Comparative Study of Common Bile Duct Diameter between Normal and Post Cholecystectomy Cases Using Trans-abdominal Ultrasonography.

Background Increase in common bile duct diameter can occur because of different causes. Post cholecystectomy status is one of the potential causes. Many studies done in the past show different results and are hence inconclusive.

Targeted Inhibition of DNA-PKcs, ATM, ATR, PARP, and Rad51 Modulate Response to X Rays and Protons.

Small molecule inhibitors are currently in preclinical and clinical development for the treatment of selected cancers, particularly those with existing genetic alterations in DNA repair and DNA damage response (DDR) pathways. Keen interest has also been expressed in combining such agents with other targeted antitumor strategies such as radiotherapy. Radiotherapy exerts its cytotoxic effects primarily through DNA damage-induced cell death; therefore, inhibiting DNA repair and the DDR should lead to additive and/or synergistic radiosensitizing effects.

An empirical model of proton RBE based on the linear correlation between x-ray and proton radiosensitivity.

Background: Proton relative biological effectiveness (RBE) is known to depend on physical factors of the proton beam, such as its linear energy transfer (LET), as well as on cell-line specific biological factors, such as their ability to repair DNA damage. However, in a clinical setting, proton RBE is still considered to have a fixed value of 1.1 despite the existence of several empirical models that can predict proton RBE based on how a cell's survival curve (linear-quadratic model [LQM]) parameters α and β vary with the LET of the proton beam.

Effect of boron compounds on the biological effectiveness of proton therapy.

Purpose: We assessed whether adding sodium borocaptate (BSH) or 4-borono-l-phenylalanine (BPA) to cells irradiated with proton beams influenced the biological effectiveness of those beams against prostate cancer cells to investigate if the alpha particles generated through proton-boron nuclear reactions would be sufficient to enhance the biological effectiveness of the proton beams.

Methods: We measured clonogenic survival in DU145 cells treated with 80.4-ppm BSH or 86.

Extremity Soft Tissue Sarcoma: A Multi-Institutional Validation of Prognostic Nomograms.

Background: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients.

Methods: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.

Genetic Code Expansion: Inception, Development, Commercialization.

Virtually all natural proteins are built from only 20 amino acids, and while this makes possible all the functions they perform, the ability to encode other amino acids selected for specific purposes promises to enable the discovery and production of proteins with novel functions, including therapeutic proteins with more optimal drug-like properties. The field of genetic code expansion (GCE) has for years enabled the production of such proteins for academic purposes and is now transitioning to commercialization for the production of more optimal protein therapeutics. Focusing on , we review the history and current state of the field.

Lipectomy for Symptomatic Relief of Lymphangioma Circumscriptum.

We present two cases of lymphangioma circumscriptum (LC) that demonstrated characteristics of half-and-half lacunae or hypopyon sign in dermoscopy. The first case was that of a 19-year-old female patient with localized lymphangioma since childhood, presenting with continuous oozing of blood and fluid from the lesion. The second patient presented with extensive disease with verrucous growths and clear vesicles over the right chest wall.

Collective interactions augment influenza A virus replication in a host-dependent manner.

Infection with a single influenza A virus (IAV) is only rarely sufficient to initiate productive infection. Instead, multiple viral genomes are often required in a given cell. Here, we show that the reliance of IAV on multiple infection can form an important species barrier.

Cross cultural adaptation and validation of burn specific health scale- brief in Nepali (BSHS-B-Np).

Background: Burns are a global health problem affecting the survivors and disrupting many aspects of their lives. It is the second most common injury in rural Nepal accounting 5% of disabilities. Burn Specific Health Scale (BSHS) is a valid and most commonly used tool to measure Health Related Quality of Life (HRQoL) of the patient with Burns.

Association between body mass index and folate insufficiency indicative of neural tube defects risk among nonpregnant women of childbearing age in the United States, NHANES, 2007-2010.

Background: Maternal folate status and obesity are known risk factors for neural tube defects (NTD) in the offspring. We examined the association between body mass index (BMI) categories and blood folate concentrations, specifically, red blood cell (RBC) folate concentrations indicative of NTD risk among nonpregnant women of child-bearing age (20-44 years) in the United States.

Methods: We used data from 2007 to 2010 US National Health and Nutrition Examination Survey (NHANES).

Factors affecting symptom presentation in an early-phase clinical trials clinic patient population.

Increasing numbers of oncology therapies are being approved based on early-phase single-arm studies. Yet, little is known regarding the use of patient-reported outcomes in single-arm oncology trials testing novel therapies. We examined patient-reported symptom severity and symptom interference with activity- (WAW: work, general activity, walking) and mood-(REM: relations with others, enjoyment of life, mood) related functioning, and their association with factors known to influence symptom severity reporting, in early-phase clinical trials clinic patients.

Randomized clinical trial of accelerated enhanced recovery after minimally invasive colorectal cancer surgery (RecoverMI trial).

Background: Minimally invasive surgery (MIS) and enhanced recovery protocols (ERPs) have improved postoperative recovery and shortened length of hospital stay (LOS). Telemedicine technology has potential to improve outcomes and patient experience further. This study was designed to determine whether the combination of MIS, ERP and a structured telemedicine programme (TeleRecovery) could shorten total 30-day LOS by 50 per cent.

Gender, health and the 2030 agenda for sustainable development.

Gender refers to the social relationships between males and females in terms of their roles, behaviours, activities, attributes and opportunities, and which are based on different levels of power. Gender interacts with, but is distinct from, the binary categories of biological sex. In this paper we consider how gender interacts with the 2030 agenda for sustainable development, including sustainable development goal (SDG) 3 and its targets for health and well-being, and the impact on health equity.

Tools and approaches to operationalize the commitment to equity, gender and human rights: towards leaving no one behind in the Sustainable Development Goals.

The objective of this article is to present specific resources developed by the World Health Organization on equity, gender and human rights in order to support Member States in operationalizing their commitment to leave no one behind in the health Sustainable Development Goals (SDGs), and other health-related goals and targets. The resources cover: (i) health inequality monitoring; (ii) barrier analysis using mixed methods; (iii) human rights monitoring; (iv) leaving no one behind in national and subnational health sector planning; and (v) equity, gender and human rights in national health programme reviews. Examples of the application of the tools in a range of country contexts are provided for each resource.

A Canonical Biotin Synthesis Enzyme, 8-Amino-7-Oxononanoate Synthase (BioF), Utilizes Different Acyl Chain Donors in Bacillus subtilis and Escherichia coli.

BioF (8-amino-7-oxononanoate synthase) is a strictly conserved enzyme that catalyzes the first step in assembly of the fused heterocyclic rings of biotin. The BioF acyl chain donor has long been thought to be pimeloyl-CoA. Indeed, the and enzymes have been shown to condense pimeloyl-CoA with l-alanine in a pyridoxal 5'-phosphate-dependent reaction with concomitant CoA release and decarboxylation of l-alanine.

Patterns and determinants of pathways to reach comprehensive emergency obstetric and neonatal care (CEmONC) in South Sudan: qualitative diagrammatic pathway analysis.

Background: Maternity referral systems have been under-documented, under-researched, and under-theorised. Responsive emergency referral systems and appropriate transportation are cornerstones in the continuum of care and central to the complex health system. The pathways that women follow to reach Emergency Obstetric and Neonatal Care (EmONC) once a decision has been made to seek care have received relatively little attention.

Accelerated enhanced y following inimally nvasive colorectal cancer surgery (): a study protocol for a novel randomised controlled trial.

Introduction: Definitive treatment of localised colorectal cancer involves surgical resection of the primary tumour. Short-stay colectomies (eg, 23-hours) would have important implications for optimising the efficiency of inpatient care with reduced resource utilisation while improving the overall recovery experience with earlier return to normalcy. It could permit surgical treatment of colorectal cancer in a wider variety of settings, including hospital-based ambulatory surgery environments.

Transcriptional consequences of XPA disruption in human cell lines.

Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined.

The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes.

Reactions that activate carboxylates through acyl-adenylate intermediates are found throughout biology and include acyl- and aryl-CoA synthetases and tRNA synthetases. Here we describe the characterization of Aquifex aeolicus BioW, which represents a new protein fold within the superfamily of adenylating enzymes. Substrate-bound structures identified the enzyme active site and elucidated the mechanistic strategy for conjugating CoA to the seven-carbon α,ω-dicarboxylate pimelate, a biotin precursor.