Soluble Guanylyl Cyclase Activator BI 685509 Reduces Portal Hypertension and Portosystemic Shunting in a Rat Thioacetamide-Induced Cirrhosis Model.

Portal hypertension (PT) commonly occurs in cirrhosis. Nitric oxide (NO) imbalance contributes to PT via reduced soluble guanylyl cyclase (sGC) activation and cGMP production, resulting in vasoconstriction, endothelial cell dysfunction, and fibrosis. We assessed the effects of BI 685509, an NO-independent sGC activator, on fibrosis and extrahepatic complications in a thioacetamide (TAA)-induced cirrhosis and PT model.

Multimodal Pain Control Reduces Narcotic Use after Outpatient Abdominoplasty: Retrospective Analysis in an Ambulatory Surgery Practice.

Unlabelled: Despite dominating fewer headlines, the opioid epidemic continues to plague society. Surgeons have the responsibility to change their opioid prescribing habits while maintaining adequate patient comfort. This study examines the transition to a multimodal, perioperative protocol in an ambulatory surgery setting for abdominoplasty patients.

Using CT scans to determine the optimal sizes of hard armour plates to protect the torso for UK female Armed Forces personnel.

Introduction: Hard armour plates provide coverage to essential anatomical structures in the torso that, if injured, would likely be responsible for death before damage control surgery can be undertaken. Existing front and rear OSPREY plates in conjunction with Mark 2 plates used at the sides in current UK Armed Forces personal armour systems are provided in a single size, used by both female and male users.

Methods: CT scans of 45 female UK military personnel were analysed.

The Novel, Clinical-Stage Soluble Guanylate Cyclase Activator BI 685509 Protects from Disease Progression in Models of Renal Injury and Disease.

Activation of soluble guanylate cyclase (sGC) to restore cyclic guanosine monophosphate (cGMP) and improve functionality of nitric oxide (NO) pathways impaired by oxidative stress is a potential treatment of diabetic and chronic kidney disease. We report the pharmacology of BI 685509, a novel, orally active small molecule sGC activator with disease-modifying potential. BI 685509 and human sGC 1/1 heterodimer containing a reduced heme group produced concentration-dependent increases in cGMP that were elevated modestly by NO, whereas heme-free sGC and BI 685509 greatly enhanced cGMP with no effect of NO.

Effect of Novel Biotherapeutic Elevating Angiopoietin 1 on Progression of Diabetic Nephropathy in Diabetic/Obese Mice.

Diabetic nephropathy is a leading cause of end-stage renal disease, characterized by endothelial dysfunction and a compromised glomerular permeability barrier. Dysregulation of the angiopoietin 1 (ANGPT1)/angiopoietin 2 (ANGPT2) signaling axis is implicated in disease progression. We recently described the discovery of an IgG antibody, O010, with therapeutic potential to elevate circulating endogenous ANGPT1, a tyrosine kinase with Ig and epidermal growth factor (EGF) homology domains-2 (TIE2) agonist.

Temporal trends of mercury in Arctic biota: 10 more years of progress in Arctic monitoring.

Temporal trend analysis of (total) mercury (THg) concentrations in Arctic biota were assessed as part of the 2021 Arctic Monitoring and Assessment Programme (AMAP) Mercury Assessment. A mixed model including an evaluation of non-linear trends was applied to 110 time series of THg concentrations from Arctic and Subarctic biota. Temporal trends were calculated for full time series (6-46 years) and evaluated with a particular focus on recent trends over the last 20 years.

Visual memory failure presages conversion to MELAS phenotype.

Objective: To examine the correlation between verbal and visual memory function and correlation with brain metabolites (lactate and N-Acetylaspartate, NAA) in individuals with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).

Methods: Memory performance and brain metabolites (ventricular lactate, occipital lactate, and occipital NAA) were examined in 18 MELAS, 58 m.3243A > G carriers, and 20 familial controls.

Injury modelling for strategic planning in protecting the national infrastructure from terrorist explosive events.

Terrorist events in the form of explosive devices have occurred and remain a threat currently to the population and the infrastructure of many nations worldwide. Injuries occur from a combination of a blast wave, energised fragments, blunt trauma and burns. The relative preponderance of each injury mechanism is dependent on the type of device, distance to targets, population density and the surrounding environment, such as an enclosed space, to name but a few.

Reversible cerebral vasoconstriction syndrome in children: an update.

Headaches are one of the most common neurologic complaints leading to emergency room visits in pediatric patients. Of the different type of headache presentations, thunderclap headaches require a particularly urgent work-up. In children, recurrent thunderclap headaches are more often associated with reversible cerebral vasoconstriction syndrome (RCVS) than other etiologies such as subarachnoid hemorrhage.

Comparing the medical coverage provided by four contemporary military combat helmets against penetrating traumatic brain injury.

Introduction: Modern military combat helmets vary in their shapes and features, but all are designed to protect the head from traumatic brain injury. Recent recommendations for protection against energised projectiles that are characteristic of secondary blast injury is to ensure coverage of both the brain and brainstem.

Method: Graphical representations of essential coverage of the head (cerebral hemispheres, cerebellum and brainstem) within an anthropometrically sized model were superimposed over two standard coverage helmets (VIRTUS helmet, Advanced Combat Helmet (ACH)) and two 'high-cut' helmets (a Dismounted Combat Helmet (DCH)) and Combat Vehicle Crewman (CVC) helmet), both of which are designed to be worn with communications devices.

Discovery of a Series of Pyrazinone RORγ Antagonists and Identification of the Clinical Candidate BI 730357.

The interleukin (IL)-23/T helper (Th)17 axis plays a critical role in autoimmune diseases, and there is an increasing number of biologic therapies that target IL-23 and IL-17. The transcription factor retinoic acid receptor-related orphan nuclear receptor γt (RORγt) is important for the activation and differentiation of Th17 cells and thus is an attractive pharmacologic target for the treatment of Th17-mediated diseases. A novel series of pyrazinone RORγ antagonists was discovered through hybridization of two distinct screening hits and scaffold hopping.

Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.

Mitochondrial disorders represent a large collection of rare syndromes that are difficult to manage both because we do not fully understand biochemical pathogenesis and because we currently lack facile markers of severity. The m.3243A>G variant is the most common heteroplasmic mitochondrial DNA mutation and underlies a spectrum of diseases, notably mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS).

Torso body armour coverage defined according to feasibility of haemorrhage control within the prehospital environment: a new paradigm for combat trauma protection.

Developments in military personal armour have aimed to achieve a balance between anatomical coverage, protection and mobility. When death is likely to occur within 60 min of injury to anatomical structures without damage control surgery, then these anatomical structures are defined as '' However, the medical terminology used to describe coverage is challenging to convey in a Systems Requirements Document (SRD) for acquisition of new armour and to ultimately translate to the correct sizing and fitting of personal armour. Many of those with Ministry of Defence responsible for the procurement of personal armour and thereby using SRDs will likely have limited medical knowledge; therefore, the potentially complex medical terminology used to describe the anatomical boundaries must be translated into easily recognisable and measurable external landmarks.

Theoretical and experimental study of temperature effect on electronic and optical properties of TiO: comparing rutile and anatase.

To gain fundamental understanding of the high-temperature optical gas-sensing and light-energy conversion materials, we comparatively investigate the temperature effects on the band gap and optical properties of rutile and anatase TiOexperimentally and theoretically. Given that the electronic structures of rutile and anatase are fundamentally different, i.e.

Defining the medical coverage of ballistic protection to the pelvis and thigh.

Introduction: Pelvis, lower limb and associated genital injury caused by explosive devices was responsible for mortality and considerable long-term morbidity for the UK Armed Forces during combat operations in Afghanistan, resulting in the issue of a pelvic protection system in 2010. The aim of this current research was to determine the medical coverage of the pelvis and thigh and to define the vertical dimensions of ballistic protective material for future pelvic protection (PP).

Method: CT scans from 120 male UK Armed Forces personnel were analysed to identify the anthropometric landmarks and vertical boundaries of coverage for the pelvis and thigh.

Determining the optimum anatomical coverage of side plates for the VIRTUS body armour and load carriage system.

Introduction: Side plates are worn by UK Armed Forces as part of the VIRTUS body armour and load carriage systems to protect the thorax and abdomen from high-velocity threats. The VIRTUS project has provided the impetus to objectively demonstrate the anatomical coverage provided by side plates.

Method: CT scans of 120 male UK Armed Forces personnel were analysed to ascertain the vertical distance between the anterior axillary fold and iliac crest, and horizontal distance between anterior and posterior borders of the liver, delineating the boundaries of essential medical coverage from the side aspects.

Sizing of ballistic arm protection for the VIRTUS body armour and load carriage system.

Introduction: Severe haemorrhage from the arm that is unresponsive to direct pressure necessitates the application of a tourniquet. Detachable arm protection, referred to as brassards, are used by the UK Armed Forces to protect the upper arm from fragmentation threats. However, the coverage they originally provided was based on limited medical evidence.

These are not the trends you are looking for: poorly calibrated single-pass electrofishing data can bias estimates of trends in fish abundance.

There is increasing interest in the potential of single-pass and timed electrofishing to assess status and trends in fish populations. However, where capture probability varies over time, there is a risk that uncalibrated electrofishing data could fail to detect, or provide biased estimates of trends. This study analysed a long-term electrofishing dataset collected over 50 years in an intensively studied catchment where egg deposition and emigrant production declined by c.

Non-neutralizing antibodies increase endogenous circulating Ang1 levels.

Ang1 is a soluble ligand to receptor Tie2, and increasing the circulating Ang1 level may improve vascular stabilization under certain disease conditions. Here, we found that the circulating Ang1 level was significantly increased in cynomolgus monkeys treated with non-neutralizing anti-Ang1 antibodies. Improving the antibodies' pharmacokinetic properties by IgG Fc mutations further increased the circulating Ang1 level.

Effects of individual variation in length, condition and run-time on return rates of wild-reared Atlantic salmon Salmo salar smolts.

Groups of wild-reared Atlantic salmon Salmo salar smolts were captured during their seaward migration on a tributary of the River Conon, Scotland, U.K., from 1999 to 2014 and tagged with passive integrated transponders (PIT).

A spatio-temporal statistical model of maximum daily river temperatures to inform the management of Scotland's Atlantic salmon rivers under climate change.

The thermal suitability of riverine habitats for cold water adapted species may be reduced under climate change. Riparian tree planting is a practical climate change mitigation measure, but it is often unclear where to focus effort for maximum benefit. Recent developments in data collection, monitoring and statistical methods have facilitated the development of increasingly sophisticated river temperature models capable of predicting spatial variability at large scales appropriate to management.

A Multiplatform Approach for the Discovery of Novel Drug-Induced Kidney Injury Biomarkers.

Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrated the use of label-free liquid chromatography-mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety biomarker assessments for identification of new toxicity marker candidates and for improved mechanistic understanding. Two different anticancer drugs, doxorubicin (DOX) and cisplatin (cis-diamminedichloridoplatinum, CDDP), were chosen as the toxicants due to their different modes of nephrotoxicity.

Reversible Cerebral Vasoconstriction Syndrome in Pediatrics: A Case Series and Review.

Reversible cerebral vasoconstriction syndrome is a transient vasculopathy associated with severe headaches and stroke. In most cases of reversible cerebral vasoconstriction syndrome, there is a precipitating event or trigger, such as pregnancy, serotonin agonist treatment or illicit drug use. The authors present 2 pediatric cases of reversible cerebral vasoconstriction syndrome and review the previous 11 pediatric cases in the literature.