Improving oral absorption of a rapidly crystallizing parent drug using prodrug strategy: Comparison of phosphate versus glycine based prodrugs.

With an increasing number of Biopharmaceutical Classification System (BCS) II/IV pipeline compounds, solubilizing and supersaturating formulation strategies are becoming prevalent. Beyond formulation and solid form strategies, prodrugs are also employed to overcome solubility-limited absorption of poorly water-soluble compounds. Prodrugs can potentially yield supersaturated systems upon conversion to the parent drug intraluminally and thus enhance absorption.

Limb presentations of invasive Group A Streptococci infection in children.

Infections with invasive Group A streptococcus can have a wide range of presentations and be life threatening if not diagnosed and managed rapidly. Limb presentations in children can be especially challenging and we present our experience to help manage such cases. There can be multiple foci of infection with seeding to avascular structures.

Development of novel compact wind tunnel for testing efficacy of insecticide formulated products in mosquitoes.

Background: Ultra-low volume (ULV) space sprays aerosolize insecticide formulated products (FP) to contact flying mosquitoes, while barrier sprays expose mosquitoes to FP residue on vegetation and other surfaces. Centers for Disease Control and Prevention bottle bioassays used to assess insecticide resistance are based on residual active ingredient (AI) exposure and do not directly relate to FP efficacy. The current pilot study developed a novel compact wind tunnel for mosquito exposure to FP.

What if we never run out of oil? From certainty of "peak oil" to "peak demand".

The COVID-19 pandemic sent the oil industry into turmoil on a scale not seen since the 1970s. While the sector appears to be recovering, questions remain about the extent to which the pandemic has offered a glimpse into the possible future of the industry. This future is critical to the success of climate change mitigation, which requires significant cuts to the carbon dioxide emissions from using oil for energy.

Identification and validation of a novel pathogenic variant in GDF2 (BMP9) responsible for hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular dysplasia, characterized by arteriovenous malformations (AVMs), mucocutaneous telangiectasia and nosebleeds. HHT is caused by a heterozygous null allele in ACVRL1, ENG, or SMAD4, which encode proteins mediating bone morphogenetic protein (BMP) signaling. Several missense and stop-gain variants identified in GDF2 (encoding BMP9) have been reported to cause a vascular anomaly syndrome similar to HHT, however none of these patients met diagnostic criteria for HHT.

VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis.

Background: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit.

Methods: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial.

Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium.

Intrauterine progestin is a treatment option for women with atypical hyperplasia or low-risk endometrial cancer who wish to preserve their fertility, or whose poor surgical fitness precludes safe hysterectomy. We hypothesized that in such women with obesity, weight loss during progestin treatment may improve oncological outcomes. We conducted a prospective nonrandomized study of women with obesity and atypical hyperplasia or low-grade stage 1a endometrial cancer undergoing progestin treatment.

Preoperative versus Post-operative Radiotherapy for Extremity Soft tissue Sarcoma: a Systematic Review and Meta-analysis of Long-term Survival.

Background: The role of perioperative radiotherapy in the management of resectable extremity soft tissue sarcoma (ESTS) is widely recognised for local tumour control, wound complications (WC) and long-term function. However, debate continues regarding its implications on long-term survival. This study aimed to determine whether the timing of perioperative radiotherapy affects long-term survival outcomes in adults with ESTS.

Prosocial and Aggressive Behavior: A Longitudinal Study.

Developmental theorists have made strong claims about the fundamental prosocial or aggressive nature of the human infant. However, only rarely have prosocial behavior and aggression been studied together in the same sample. We charted the parallel development of both behaviors from infancy to childhood in a British community sample, using a two-construct, multimethod longitudinal design.

Multidimensional indicators of scholarly impact in the skin oncology literature: is there a correlation between bibliometric and altmetric profiles?

Bibliometric and altmetric analyses are used to identify landmark publications in their respective research field. We hypothesised that highly cited skin oncology articles correlate positively with the Oxford Evidence Based Medicine scoring level, altmetric score (AS) and rank within the top 100 manuscripts. Thomson Reuter's Web of Science citation indexing database was searched to identify all English-language skin oncology full-text articles in the last 75 years.

Association of elevated pre-operative HbA1c and post-operative complications in patients undergoing gynaecological oncology surgery.

HbA1c testing provides average blood glucose control, an elevated result may be associated with adverse post-operative outcomes. Our objective was to evaluate the association between elevated pre-operative HbA1c and post-operative complications in patients undergoing major gynaecological oncology surgery. HbA1c was measured pre-operatively in 364 patients.

Characterization of the Hydrodynamics in the USP Basket Apparatus Using Computational Fluid Dynamics.

Computational fluid dynamics (CFD) has been extensively used for the USP paddle apparatus II, but limited CFD studies have been conducted on the USP basket apparatus I. We expanded on past CFD basket studies to consider the presence of a tablet inside the basket, compared predictions to in vivo conditions, and confirmed observations around the complexity of nonuniform hydrodynamics. Tablets near the basket perimeter experienced near 5-fold increase in maximum velocity and surface shear stress compared to tablets placed at the center of the basket.

Impact of blood group on survival following critical illness: a single-centre retrospective observational study.

Background: Predicting patient outcomes following critical illness is challenging. Recent evidence has suggested that patients with blood group AB are more likely to survive following major cardiac surgery, and this is associated with a reduced number of blood transfusions. However, there are no current data to indicate whether a patient's blood group affects general intensive care outcomes.

Electron Communication of Bacillus subtilis in Harsh Environments.

Elucidating the effect of harsh environments on the activities of microorganisms is important in revealing how microbes withstand unfavorable conditions or evolve mechanisms to counteract those effects, many of which involve electron transfer phenomena. Here we show that the non-acidophilic and non-thermophilic Bacillus subtilis is able to maintain activity after being subjected to extreme temperatures (100°C for up to 8 h) and acidic environments (pH = 1.50 for over 2 years).

PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a Multi-Center, Randomized Double-Blind, Placebo-Controlled Phase III Trial.

Purpose: Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth . Presurgical window studies allow rapid assessment of antitumor activity.

A behavioural dose-response model for migrating humpback whales and seismic air gun noise.

The behavioural responses of migrating humpback whales to an air gun, a small clustered seismic array and a commercial array were used to develop a dose-response model, accounting for the presence of the vessel, array towpath relative to the migration and social and environmental parameters. Whale groups were more likely to show an avoidance response (increasing their distance from the source) when the received sound exposure level was over 130 dB re 1 μPa·s and they were within 4 km of the source. The 50% probability of response occurred where received levels were 150-155 dB re 1 μPa·s and they were within 2.

The Use of Keystone Flaps in Periarticular Wound Closure: A Case Series.

The Keystone perforator island flap (Keystone flap), is a Type A fasciocutaneous advancement flap, consisting of two V to Y advancement flaps. Skin cancer excision around joints presents a number of reconstructive challenges. Owing to the mobile nature of joints, the optimal periarticular reconstructive option should possess the ability to provide adequate tissue coverage and withstand regional changes in tensile pressures.

The behavioural response of migrating humpback whales to a full seismic airgun array.

Despite concerns on the effects of noise from seismic survey airguns on marine organisms, there remains uncertainty as to the biological significance of any response. This study quantifies and interprets the response of migrating humpback whales () to a 3130 in (51.3l) commercial airgun array.

Preventing Violence: A Public Health Participatory Approach to Homicide Reviews.

Death review teams are a common method for assessing preventable deaths, yet they rarely review adult homicides and do not typically include community members. Academic-community partnerships can enhance public health research by encouraging translation of research into practice and support a data-driven approach to improve community health and well-being. We describe the Pittsburgh Homicide Review Group, a community-partnered initiative to prevent future homicides through data review and community dialogue.

Mechanistic Physiologically Based Pharmacokinetic Modeling of the Dissolution and Food Effect of a Biopharmaceutics Classification System IV Compound-The Venetoclax Story.

Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system class IV compound. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion formulation of venetoclax in humans. A mechanistic PBPK model was developed incorporating measured amorphous solubility, dissolution, metabolism, and plasma protein binding.

Determining the behavioural dose-response relationship of marine mammals to air gun noise and source proximity.

The effect of various anthropogenic sources of noise (e.g. sonar, seismic surveys) on the behaviour of marine mammals is sometimes quantified as a dose-response relationship, where the probability of an animal behaviourally 'responding' (e.

Evaluation of an E-learning resource on approach to the first unprovoked seizure.

Aim: To develop and evaluate an online educational package instructing paediatricians and trainees in the diagnosis and management of a first unprovoked seizure in children.

Methods: The E-learning content was created following a comprehensive literature review that referenced current international guidelines. Rigorous consultation with local paediatric neurologists, paediatricians and epilepsy nurses was undertaken.

Core-Shell Co/CoO Integrated on 3D Nitrogen Doped Reduced Graphene Oxide Aerogel as an Enhanced Electrocatalyst for the Oxygen Reduction Reaction.

Here, we demonstrate that Cobalt/cobalt oxide core-shell nanoparticles integrated on nitrogen-doped (N-doped) three-dimensional reduced graphene oxide aerogel-based architecture (Co/CoO-NGA) were synthesized through a facile hydrothermal method followed by annealing treatment. The unique endurable porous structure could provide sufficient mass transfer channels and ample active sites on Co/CoO-NGA to facilitate the catalytic reaction. The synthesized Co/CoO-NGA was explored as an electrocatalyst for the oxygen reduction reaction, showing comparable oxygen reduction performance with excellent methanol resistance and better durability compared with Pt/C.