Extrahepatic gallstones and abscess formation post-cholecystostomy: a rare complication in high-risk acute cholecystitis management.

This intriguing case report explores an interesting complication following percutaneous cholecystostomy for the management of acute cholecystitis in an elderly female with multiple comorbidities. Despite initial improvement, she later presented with recurrent symptoms, due to a collection of gallstones, that had migrated through the cholecystostomy tract, requiring exploration, stone retrieval and abscess drainage. While percutaneous cholecystostomy remains an effective treatment for managing acute cholecystitis in high-risk surgical candidates, this case highlights the rare yet critical risk of extrahepatic gallstones and abscess formation.

Species-tree topology impacts the inference of ancient whole-genome duplications across the angiosperm phylogeny.

Premise: The history of angiosperms is marked by repeated rounds of ancient whole-genome duplications (WGDs). Here we used state-of-the-art methods to provide an up-to-date view of the distribution of WGDs in the history of angiosperms that considers both uncertainty introduced by different WGD inference methods and different underlying species-tree hypotheses.

Methods: We used the distribution synonymous divergences (K) of paralogs and orthologs from transcriptomic and genomic data to infer and place WGDs across two hypothesized angiosperm phylogenies.

Global pannexin 1 deletion increases tumor-infiltrating lymphocytes in the BRAF/Pten mouse melanoma model.

Immunotherapies for malignant melanoma seek to boost the anti-tumoral response of CD8 T cells, but have a limited patient response rate, in part due to limited tumoral immune cell infiltration. Genetic or pharmacological inhibition of the pannexin 1 (PANX1) channel-forming protein is known to decrease melanoma cell tumorigenic properties in vitro and ex vivo. Here, we crossed Panx1 knockout (Panx1) mice with the inducible melanoma model Braf, Pten, Tyr::CreER (BPC).

Egg hatching success is influenced by the time of thermal stress in four hard tick species.

Ticks are blood-feeding arthropods responsible for the transmission of disease-causing pathogens to a wide range of vertebrate hosts, including livestock and humans. Tick-borne diseases have been implicated in significant economic losses to livestock production, and this threat will increase as these obligate parasites widen their geographical ranges. Similar to other ectotherms, thermal stress due to changing global temperatures has been shown to influence tick survival and distribution.

Reduced male fertility of an Antarctic mite following extreme heat stress could prompt localized population declines.

Climate change is leading to substantial global thermal changes, which are particularly pronounced in polar regions. Therefore, it is important to examine the impact of heat stress on the reproduction of polar terrestrial arthropods, specifically, how brief extreme events may alter survival. We observed that sublethal heat stress reduces male fecundity in an Antarctic mite, yielding females that produced fewer viable eggs.

Rapid stress hardening in the Antarctic midge improves male fertility by increasing courtship success and preventing decline of accessory gland proteins following cold exposure.

Rapid hardening is a process that quickly improves an animal's performance following exposure to potentially damaging stress. In this study of the Antarctic midge, Belgica antarctica (Diptera, Chironomidae), we examined how rapid hardening in response to dehydration (RDH) or cold (RCH) improves male pre- and post-copulatory function when the insects are subsequently subjected to a damaging cold exposure. Neither RDH nor RCH improved survival in response to lethal cold stress, but male activity and mating success following sublethal cold exposure were enhanced.

Cold hardening improves larval tick questing under low temperatures at the expense of longevity.

Questing in ticks is essential for locating a host, and this behavioral response can occur at regionally specific low temperatures for most tick species. Little is known about the dynamics between tick questing behavior and temperature in ticks, specifically how this may impact other aspects of tick biology. Here, we examine whether cold hardening increases questing in three larval tick species (Ixodes uriae, Dermacentor variabilis, and Amblyomma americanum) at low temperatures and whether cold hardening impacts longevity.

Patterns and Processes of Diploidization in Land Plants.

Most land plants are now known to be ancient polyploids that have rediploidized. Diploidization involves many changes in genome organization that ultimately restore bivalent chromosome pairing and disomic inheritance, and resolve dosage and other issues caused by genome duplication. In this review, we discuss the nature of polyploidy and its impact on chromosome pairing behavior.

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study.

Objective: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection.

Design: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken.

Multi-level analysis of reproduction in an Antarctic midge identifies female and male accessory gland products that are altered by larval stress and impact progeny viability.

The Antarctic midge, Belgica antarctica, is a wingless, non-biting midge endemic to Antarctica. Larval development requires at least 2 years, but adults live only 2 weeks. The nonfeeding adults mate in swarms and females die shortly after oviposition.

Custody early warning scores; Do they predict patient deterioration in police custody?

Unlabelled: This paper analyses the results of a three month trial based in a police custody suite, where we assigned a value; using the recently developed Custody Early Warning Score, to detainees arriving into police custody, as part of their 'booking in' process. We then compared this to the more established National Early Warning Scoring system and then looked at the predictive accuracy of these two systems and how they correlated to one another, when applied to three different clinical groups of detainees in police custody. Police Custody Sergeants and Custody Detention Officers continue to experience difficulties in identifying those detainees with health care needs; be they subtle, emerging or more evident.

Comparative nonclinical assessments of the biosimilar PF-06410293 and originator adalimumab.

Adalimumab, a recombinant fully human monoclonal antibody targeting tumor necrosis factor (TNF), is approved in the United States and Europe to treat various inflammatory and autoimmune indications. Biosimilars are approved biologics highly similar, but not identical, to approved biotherapeutics. To support clinical development of PF-06410293, an adalimumab biosimilar, nonclinical studies evaluated the structural, functional, toxicologic, and toxicokinetic similarity to originator adalimumab sourced from the United States (adalimumab-US) and European Union (adalimumab-EU).

High-resolution nuclear magnetic resonance spectroscopy in microfluidic droplets.

A generic approach is presented that allows high-resolution NMR spectroscopy of water/oil droplet emulsions in microfluidic devices. Microfluidic NMR spectroscopy has recently made significant advances due to the design of micro-detector systems and their successful integration with microfluidic devices. Obtaining NMR spectra of droplet suspensions, however, is complicated by the inevitable differences in magnetic susceptibility between the chip material, the continuous phase, and the droplet phases.

Nonclinical assessments of the potential biosimilar PF-06439535 and bevacizumab.

Bevacizumab, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), is approved for treatment of metastatic colorectal cancer, nonsquamous non-small-cell lung cancer, metastatic kidney cancer, and glioblastoma. To support clinical development of the potential bevacizumab biosimilar PF-06439535, nonclinical studies evaluated structural, functional, toxicological, and toxicokinetic similarity to bevacizumab sourced from the European Union (bevacizumab-EU) and United States (bevacizumab-US). Peptide mapping demonstrated the amino acid sequence of PF-06439535 was identical to bevacizumab-EU and bevacizumab-US.

Successful management of an aorto-gastric fistula occurring 15 years after oesophagectomy with covered aortic stent graft placement followed by open surgery.

Aorto-gastric fistula (AGF) is an uncommon and life threatening complication of oesophagectomy. Usually occurring in the immediate weeks following the procedure at anastomosis lines, this case describes a rare development of an AGF 15 years after an oesophagectomy due to the presence of a benign ulcer. Initially successful endovascular stenting of the thoracic aorta was followed by re-bleed, further stenting but eventually open surgery was required.

Para-spinal abscess following gallstones spillage during laparoscopic cholecystectomy: an unusual presentation.

Gallbladder perforation with subsequent gallstone spillage can occur with higher frequency in laparoscopic cholecystectomy than in traditional open approach. Gallstone abscess formation from stone spillage post-cholecystectomy is extremely rare. We present a case of para-spinal abscess formation 5 years after spilled gallstones following laparoscopic cholecystectomy.

Nanomedicines: From Bench to Bedside and Beyond.

Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration.

Monoclonal Antibody and Fusion Protein Biosimilars Across Therapeutic Areas: A Systematic Review of Published Evidence.

Background: Despite regulatory efforts to formalize guidance policies on biosimilars, there remains a need to educate healthcare stakeholders on the acknowledged definition of biosimilarity and the data that underpin it.

Objectives: The objectives of the study were to systematically collate published data for monoclonal antibodies and fusion protein biosimilars indicated for cancer, chronic inflammatory diseases, and other indications, and to explore differences in the type and weight (quantity and quality) of available evidence.

Methods: MEDLINE, Embase, and ISI Web of Science were searched to September 2015.

An optimised detector for in-situ high-resolution NMR in microfluidic devices.

Integration of high-resolution nuclear magnetic resonance (NMR) spectroscopy with microfluidic lab-on-a-chip devices is challenging due to limited sensitivity and line broadening caused by magnetic susceptibility inhomogeneities. We present a novel double-stripline NMR probe head that accommodates planar microfluidic devices, and obtains the NMR spectrum from a rectangular sample chamber on the chip with a volume of 2μl. Finite element analysis was used to jointly optimise the detector and sample volume geometry for sensitivity and RF homogeneity.

Pelvic Actinomyces israelii abscess: a differential diagnosis of a pelvic mass.

A 52-year-old woman was admitted to our district general hospital, with a rapidly growing, increasingly tender mass in the right iliac fossa, difficulty mobilising with a fixed flexion deformity of the right hip and 15 kg weight loss in 5 months. Her 8-month long surgical history for investigation of a pelvic mass stemmed from the removal of an intrauterine device. It included radiological and surgical investigations.

Key considerations in the preclinical development of biosimilars.

Biosimilar development requires several steps: selection of an appropriate reference biologic, understanding the key molecular attributes of that reference biologic and development of a manufacturing process to match these attributes of the reference biologic product. The European Medicines Agency (EMA) and the FDA guidance documents state that, in lieu of conducting extensive preclinical and clinical studies typically required for approval of novel biologics, biosimilars must undergo a rigorous similarity evaluation. The aim of this article is to increase understanding of the preclinical development and evaluation process for biosimilars, as required by the regulatory agencies, that precedes the clinical testing of biosimilars in humans.

Two-year carcinogenicity study in rats with a nonnucleoside reverse transcriptase inhibitor.

Administration of lersivirine, a nonnucleotide reverse transcriptase inhibitor, daily by oral gavage to Sprague-Dawley rats for up to 2 yr was associated with decreased survival, decreased body weights, and an increase in neoplasms and related proliferative lesions in the liver, thyroid, kidney, and urinary bladder. Thyroid follicular adenoma and carcinoma, the associated thyroid follicular hypertrophy/hyperplasia, hepatocellular adenoma/adenocarcinoma, altered cell foci, and hepatocellular hypertrophy were consistent with lersivirine-related induction of hepatic microsomal enzymes. Renal tubular adenoma and renal tubular hyperplasia were attributed to the lersivirine-related exacerbation of chronic progressive nephropathy (CPN), while urinary bladder hyperplasia and transitional cell carcinoma in the renal pelvis and urinary bladder were attributed to urinary calculi.

Comparative nonclinical assessments of the proposed biosimilar PF-05280014 and trastuzumab (Herceptin(®)).

Background And Objectives: Trastuzumab (Herceptin(®)) is a humanized monoclonal antibody (mAb) that binds to the HER2 protein. PF-05280014 is being developed as a potential biosimilar to trastuzumab products marketed in the United States (trastuzumab-US) and European Union (trastuzumab-EU). Nonclinical studies were designed to evaluate the similarity of PF-05280014 to trastuzumab-US and trastuzumab-EU using in vitro structural and functional analyses, and in vivo pharmacokinetic and immunogenicity assessments.