High-throughput screen identifies non inflammatory small molecule inducers of trained immunity.

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines.

Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study.

Background: Multiple organ dysfunction syndrome (MODS) is a critical driver of sepsis morbidity and mortality in children. Early identification of those at risk of death and persistent organ dysfunctions is necessary to enrich patients for future trials of sepsis therapeutics. Here, we sought to integrate endothelial and PERSEVERE biomarkers to estimate the composite risk of death or organ dysfunctions on day 7 of septic shock.

Intraarterial Nimodipine Versus Induced Hypertension for Delayed Cerebral Ischemia: A Modified Treatment Protocol.

Background: Rescue treatment for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can include induced hypertension (iHTN) and, in refractory cases, endovascular approaches, of which selective, continuous intraarterial nimodipine (IAN) is one variant. The combination of iHTN and IAN can dramatically increase vasopressor demand. In case of unsustainable doses, iHTN is often prioritized over IAN.

Workplace Intervention for Heat Stress: Essential Elements of Design, Implementation, and Assessment.

Heat stress is associated with numerous health effects that potentially harm workers, especially in a warming world. This investigation occurred in a setting where laborers are confronted with occupational heat stress from physically demanding work in high environmental temperatures. Collaboration with a major Nicaraguan sugarcane producer offered the opportunity to study interventions to prevent occupational heat-stress-related kidney disease.

Brace treatment for patients with scoliosis: State of the art.

Background: Physiotherapy, brace applications or surgery are the treatment options utilised to manage patients with scoliosis. Many different brace applications are used, and the success rates of orthoses vary.

Objectives: Brace applications can have detrimental impacts on the patient leading to physical discomfort, psychological discomfort, and in some instance the use of braces may even be painful.

Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface.

During tumor progression, cancer cells come into contact with various non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq to characterize tumor-microenvironment interactions at the tumor boundary. Using a zebrafish model of melanoma, we identify a distinct "interface" cell state where the tumor contacts neighboring tissues.

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis.

Background: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown.

Methods: We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time).

Plasma protein patterns as comprehensive indicators of health.

Proteins are effector molecules that mediate the functions of genes and modulate comorbidities, behaviors and drug treatments. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested.

Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model.

Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rational development, testing, and targeting of new therapies.

ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals.

Background: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

Background: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.

Evaluation and management of traumatic diaphragmatic injuries: A Practice Management Guideline from the Eastern Association for the Surgery of Trauma.

Background: Traumatic diaphragm injuries (TDI) pose both diagnostic and therapeutic challenges in both the acute and chronic phases. There are no published practice management guidelines to date for TDI. We aim to formulate a practice management guideline for TDI using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

Objective: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)-related dyskinesia and genotype-phenotype relationship.

Methods: We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification.

Asthma.

Asthma is the most common inflammatory disease of the lungs. The prevalence of asthma is increasing in many parts of the world that have adopted aspects of the Western lifestyle, and the disease poses a substantial global health and economic burden. Asthma involves both the large-conducting and the small-conducting airways, and is characterized by a combination of inflammation and structural remodelling that might begin in utero.

Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma.

Background: The impact of adjuvant radiation in patients with atypical meningioma remains poorly defined. We sought to determine the impact of adjuvant radiation therapy in this population.

Methods: We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women's Cancer Center between 1997 and 2011.

The prevalence and causes of nocturia.

Purpose: Nocturia is a troubling condition with implications for daytime functioning. However, it often goes unreported. Many prevalence studies exist but differences in populations and definitions of nocturia render assimilation of the data difficult.

The prevalence and causes of nocturia.

Purpose: Nocturia is a troubling condition with implications for daytime functioning. However, it often goes unreported. Many prevalence studies exist but differences in populations and definitions of nocturia render assimilation of the data difficult.

Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.

Raltegravir is the first licensed compound in 2007 of the new integrase inhibitor drug class. At the dose of 400 mg twice daily, raltegravir showed a potent antiviral action in antiretroviral-naïve patients when associated with tenofovir and emtricitabine. Raltegravir was also found to be highly active in antiretroviral-experienced patients with virological failure and displaying multiresistant virus, as shown with the BENCHMRK and ANRS 139 TRIO trials.

Blue cone monochromatism.

Blue cone monochromatism (BCM) is a subtype of achromatopsia in which the blue cone mechanism predominates. Each of the four patients in this study had BCM proven by their having peak spectral sensitivities in the blue region of the visible spectrum (near 440 nm). Clinically, the diagnosis was suspected because of x-linked inheritance, the presence of acuities better than 20/200 in two patients and myopia ranging from -1.

Colour-blindness in Colombia.

The frequency of defective colour vision was studied in two neighbouring villages in the Andes Mountains of Colombia using AO H-R-R Pseudoisochromatic plates. The frequency of the red-green colour-blindness in males is almost the same in both villages (2.36-2.

[Serum lipase activity and endoscopic retrograde pancreatography in chronic pancreatitis and pancreatic neoplasm (author's transl)].

Serum lipase activity was measured in 360 patients with the clinical suspicion of chronic pancreatic disease, 60 of them also having the lipase evocation test (serum lipase activity before and after pancreatic stimulation with secretin and pancreozymin). Of 48 with chronic pancreatitis (40 confirmed at operation) the diagnosis was made by endoscopic retrograde pancretography in all but one. Serum lipase activity was abnormal in 38.