Advanced high pressure hyperbaric techniques in tunnelling.

Work in compressed air and diving are both occupational activities that have been around since the mid-19th century, and those undertaking their work under elevated pressure. Meeting the demand to go to "higher pressure for longer" in tunneling has lagged in diving, but both activities have found it necessary to adopt mixed gas breathing and saturation exposure techniques. This paper explains how work in hyperbaric conditions at high pressure is undertaken in tunneling and is illustrated by the hyperbaric activity likely to be involved in constructing a large-diameter road tunnel below a body of water such as an estuary.

Plasma Cell Vulvitis: A Classification Into Two Clinical Phenotypes.

Objective: The etiology of plasma cell vulvitis (PCV) is debated. The authors aimed to test the hypothesis that PCV could be divided into 2 clinical phenotypes.

Methods: Patients with a clinico-pathological diagnosis of PCV and with available vulvar photos seen in a vulvar clinic were retrospectively studied.

Thermomechanical properties of 3D-printed sand moulds using inorganic binder.

Additive Manufacturing of 3D-printed sand cores using the binder jetting process is well-established in prototype manufacturing. Due to the rising focus on sustainability and the fact that printed cores are shifting to serial production, a transition from organic to inorganic binder systems is taking place. To ensure a stable casting process and reduce the scrap rate accurate simulation tools are required.

SARS-CoV-2 transmission modes: Why and how contamination occurs around shared meals and drinks?

In spite of prevention measures enacted all over the world to control the COVID-19 pandemic outbreak, including mask wearing, social distancing, hand hygiene, vaccination, and other precautions, the SARS-CoV-2 virus continues to spread globally at an unabated rate of about 1 million cases per day. The specificities of superspreading events as well as evidence of human-to-human, human-to-animal and animal-to-human transmission, indoors or outdoors, raise questions about a possibly neglected viral transmission route. In addition to inhaled aerosols, which are already recognized as key contributors to transmission, the oral route represents a strong candidate, in particular when meals and drinks are shared.

Are virtual consultations suitable for patients with vulval disease? A multicentre audit of outcomes in the COVID-19 pandemic.

Background: During the COVID-19 pandemic, virtual consultation (VC) was used to replace in-person consultations. This raises specific questions when dealing with vulval conditions.

Objectives: To assess the feasibility and the efficiency of VC with and without supplementary imaging, in patients with vulval conditions, and to evaluate the images provided as an aid to diagnosis.

Clinical Outcome and Treatment Sequences of Patients with Advanced Pancreatic Cancer Treated with Contemporary Chemotherapy Protocols.

Introduction: Systemic therapy is firmly established in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Clinical efficacy is still modest and options are limited. Combination therapy protocols such as FOLFIRINOX and gemcitabine/nab-paclitaxel (Gem/NP) define standard-of-care.

[Covid-19: is the oral transmission route during shared meals and drinks credible?].

Epidemiological and observational studies converge to suspect today a risk of contracting Covid-19 around shared meals and drinks. Contamination of table objects (plates, cutlery, glasses) or food and beverages put in the mouth is possible through droplets projected during speech or through direct contacts by dirty hands. This contamination could involve employees in the food chain, restaurant or bar staff and diners among themselves.

Shared Food, Meals and Drinks: 10 Arguments Suggesting an Oral Transmission Route of SARS-CoV-2.

Numerous observational, epidemiologic data have suggested that the risk of COVID19 is related to shared meals or drinks. The presence of ACE2 receptors in the gastrointestinal tract supports this hypothesis. Furthermore, several patients experience gastrointestinal symptoms without any respiratory disease.

Experimental Efficacy of the Face Shield and the Mask against Emitted and Potentially Received Particles.

There is currently not sufficient evidence to support the effectiveness of face shields for source control. In order to evaluate the comparative barrier performance effect of face masks and face shields, we used an aerosol generator and a particle counter to evaluate the performance of the various devices in comparable situations. We tested different configurations in an experimental setup with manikin heads wearing masks (surgical type I), face shields (22.

Nucleotide P2Y receptor agonists are in vitro and in vivo prodrugs of A/A adenosine receptor agonists: implications for roles of P2Y and A/A receptors in physiology and pathology.

Rapid phosphoester hydrolysis of endogenous purine and pyrimidine nucleotides has challenged the characterization of the role of P2 receptors in physiology and pathology. Nucleotide phosphoester stabilization has been pursued on a number of medicinal chemistry fronts. We investigated the in vitro and in vivo stability and pharmacokinetics of prototypical nucleotide P2Y receptor (P2YR) agonists and antagonists.

Combined systemic inflammation score (SIS) correlates with prognosis in patients with advanced pancreatic cancer receiving palliative chemotherapy.

Purpose: The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains dismal. New cytotoxic agents such as nab-paclitaxel and liposomal irinotecan (nal-Iri) have extended the armamentarium of therapeutic options in the last years. Nowadays, sequential therapeutic strategies with moderately toxic chemotherapeutic protocols can be administered to the patients.

Homeopathic Treatment of Insomnia and Symptom Clusters Related to Cerebral Chemotoxicity in Oncology.

Background:  During chemotherapy, the correlation between insomnia and fatigue, anxiety, pain, depressed mood, and cognitive disorders makes these subjective complaints a 'symptom cluster' with common biological mechanisms. The theory of cerebral inflammation following the production of pro-inflammatory cytokines (high level of interleukin 1-β [IL1-β], IL6 and tumour necrosis factor-alpha) is currently the most generally accepted. Understanding these mechanisms should allow us to propose a chemoprotective homeopathic treatment of the nervous system.

Specialist advice may improve patient selection for decompression therapy following diving accidents: a retrospective observational study.

Background: Even in a landlocked country like Switzerland recreational diving is becoming more and more popular. Smaller lakes in the Alps are located at an altitude of 2500 m above sea level. The incidence of diving accidents among all helicopter emergency service missions and the consecutive medical knowledge about decompression injuries is low.

Sterol metabolism controls T(H)17 differentiation by generating endogenous RORγ agonists.

Retinoic acid receptor-related orphan receptor γ (RORγt) controls the differentiation of naive CD4(+) T cells into the TH17 lineage, which are critical cells in the pathogenesis of autoimmune diseases. Here we report that during TH17 differentiation, cholesterol biosynthesis and uptake programs are induced, whereas their metabolism and efflux programs are suppressed. These changes result in the accumulation of the cholesterol precursor, desmosterol, which functions as a potent endogenous RORγ agonist.

Vulvar dermatosis.

Vulvar dermatoses are inflammatory conditions responsible for chronic or recurrent itching and soreness. The lesions are either circumscribed to the vulva or associated with extragenital localizations which may help to assess the diagnosis. They should be differentiated from infectious or neoplastic diseases which may have clinical similarities.

Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients.

Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles.

[Diving - fitness to dive: a challenge for the family doctor].

A certificate for divers should be based on expertise and risk assessment. The doctor needs knowledge of the divers history, diving technique, motivation and risk exposure.

Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1.

SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P (sphingosine 1-phosphate). S1P promotes cell growth, survival and migration, and is a key regulator of lymphocyte trafficking. Inhibition of S1P signalling has been proposed as a strategy for treatment of inflammatory diseases and cancer.

Telemedicine in the management of diving accidents: correlation of phone-assessed symptom severity with clinical findings.

Introduction: The object of this study was to evaluate to what extend the severity of decompression illness (DCI) assessed by a diving medicine specialist over the phone correlates with actual clinical findings.

Methods: The phone protocols of calls received by a diving medical hotline between January 2008 and December 2009 were analysed. Each case was followed up after completion of the treatment and categorized into one out of four severity groups according to the same standard protocol used for categorisation at the time of the initial hotline call.

In vivo crystallization of human IgG in the endoplasmic reticulum of engineered Chinese hamster ovary (CHO) cells.

Protein synthesis and secretion are essential to cellular life. Although secretory activities may vary in different cell types, what determines the maximum secretory capacity is inherently difficult to study. Increasing protein synthesis until reaching the limit of secretory capacity is one strategy to address this key issue.

Structure-based parallel medicinal chemistry approach to improve metabolic stability of benzopyran COX-2 inhibitors.

Combination of the structure-based design and solid-phase parallel synthesis provided an integrated approach to rapidly develop the structure-activity relationship of benzopyran COX-2 inhibitors. Binding free energies predicted by free energy perturbation theory yielded good agreement with experimental results. New potent and selective lead compounds with improved metabolic properties were identified.

Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy.

We have discovered a novel class of nonsteroidal pyrazoline antagonists of the mineralocorticoid receptor (MR) that show excellent potency and selectivity against other nuclear receptors. Early analogues were poorly soluble and had a propensity to inhibit the hERG channel. Remarkably, both of these challenges were overcome by incorporation of a single carboxylate moiety.

A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation.

Autotaxin is the enzyme responsible for the production of lysophosphatidic acid (LPA) from lysophosphatidyl choline (LPC), and it is up-regulated in many inflammatory conditions, including but not limited to cancer, arthritis, and multiple sclerosis. LPA signaling causes angiogenesis, mitosis, cell proliferation, and cytokine secretion. Inhibition of autotaxin may have anti-inflammatory properties in a variety of diseases; however, this hypothesis has not been tested pharmacologically because of the lack of potent inhibitors.