Ayaladempsey6131

Bacterial keratitis (BK) severity in murine models has traditionally been measured by subjective clinical grading or quantification of ocular bacterial burden. This investigation explores an objective and repeatable quantification of slit lamp photography (SLP) images to measure BK severity.

BALB/c strain mice underwent three parallel scratches of the right cornea with subsequent inoculation of 107Staphylococcus aureus cells. SLP imaging and clinical severity grading were performed at 48 hours post-infection. Stromal infiltrate (SI) area on SLP images were quantified. Bacterial burden was determined after enucleation and homogenization. Spearman rank correlations (rs) were used to estimate associations between SI area, clinical severity grades, and bacterial burden.

BALB/c strain mice (n = 14) were evaluated with an average SI area of 0.92 mm2 (standard deviation, SD = 0.65) and average bacterial burden of 3.16 × 105 colony forming units per milliliter (CFU/mL) (SD = 8.3 × 105). Clinical severity grade positively correlated with SI area (rs = 0.59, p = 0.0276) and bacterial burden (rs = 0.66, p = 0.0106). There was a trend towards positive association between SI area and bacterial burden (rs = 0.51, p = 0.0543).

SLP annotation of SI area is correlated with clinical severity and may provide an objective, quantitative, and repeatable assessment of BK disease severity.

SLP annotation of SI area is a novel quantitative method to evaluate bacterial keratitis severity longitudinally in mouse models which may be a powerful tool to better understand BK pathogenesis and response to treatments.

SLP annotation of SI area is a novel quantitative method to evaluate bacterial keratitis severity longitudinally in mouse models which may be a powerful tool to better understand BK pathogenesis and response to treatments.

Dry eye disease (DED) is a heterogeneous condition with poorly characterized subtypes. The DREAM study was a large multicenter randomized clinical trial that did not find omega-3 to be more effective than placebo in treating symptomatic DED. We performed secondary analysis of DREAM data to characterize DED subtypes and their omega-3 response.

A total of 535 patients with moderate-to-severe DED were randomized to omega-3 or placebo treatment for one year. We used latent profile analysis to identify subtypes based on baseline Ocular Surface Disease Index, tear break-up time (TBUT), anesthetized Schirmer's test, corneal and conjunctival staining, and meibomian gland dysfunction (MGD). We evaluated omega-3's effect for each subtype using generalized linear regression.

Five clinically meaningful DED subtypes were identified. They differed significantly in sex (P<0.001) and race (P=0.02). Subtype 1 had the most severe DED signs yet milder symptoms and was associated with more Sjögren's syndrome (21%, P<0.001). Subtype 2 had the mildest DED signs except MGD. Subtype 3 had the most severe symptoms, out of proportion to DED signs. Subtype 4 had relatively milder symptoms and MGD. Subtype 5 had severe MGD and TBUT and was associated with rosacea (29%, P=0.04). Omega-3 was not significantly more beneficial than placebo for any subtype.

Five clinically meaningful DED subtypes differed significantly in demographics, symptoms, signs, and systemic disease associations. Omega-3 was not significantly more effective than placebo for any subtype.

T3 translational research identifying subtypes in the DREAM study can improve DED clinical classification and targeted management.

T3 translational research identifying subtypes in the DREAM study can improve DED clinical classification and targeted management.Sepsis, a dysregulated host immune response to infection, is one of the leading causes of neonatal mortality worldwide. Improved understanding of the perinatal immune system is critical to improve therapies to both term and preterm neonates at increased risk of sepsis. Our narrative outlines the known and unknown aspects of the human immune system through both the immune tolerant in utero period and the rapidly changing antigen-rich period after birth. We will highlight the key differences in innate and adaptive immunity noted through these developmental stages, and how the unique immune phenotype in early life contributes to the elevated risk of overwhelming infection and dysregulated immune responses to infection upon exposure to external antigens shortly after birth. Given an initial dependence on neonatal innate immune host responses, we will discuss the concept of innate immune memory, or "trained immunity", and describe several potential immune modulators which show promise in altering the dysregulated immune response in newborns and improving resilience to sepsis.This randomised controlled trial examined the effect of volume-equated programmes of Nordic hamstring exercise (NHE) training, executed at frequencies of 1- or 2-days per week, on explosive athletic tasks (30 m sprint, 15 m manoeuvrability and standing long jump [SLJ]) in male youth soccer players (mean age 10.3 ± 0.5 years). Players were divided into an experimental group (n = 31) which was further subdivided into 1-day (n = 16) and 2-days (n = 15) per week training conditions, and a control group (n = 14). There were significant group-by-time interactions for 30-m sprint (p less then 0.001, d = 0.6), SLJ (p = 0.001, d = 1.27) and 15 m manoeuvrability (p less then 0.001, d = 0.61). The experimental group demonstrated small to moderate effect sizes in 30-m sprint (d = 0.42, p = 0.077), SLJ (d = 0.97, p less then 0.001) and 15 m manoeuvrability (d = 0.61, p less then 0.001). The control group showed small significant performance decrements or no change in these variables. There were no significant differences between the 1-day and 2-day training groups. In two of the three tests (30 m sprint, SLJ) the 2-day group demonstrated larger effect sizes. The NHE enhances explosive athletic task performance in prepubertal youth soccer players and there may be only small advantages to spreading training over two days instead of one.An efficient regioselective functionalization of 2-aryl-heteroarenes and aryl aldehydes via an azaaryl BF2 complex has been developed. Mechanistically the reaction comprises fluoride to bromide ligand exchange on an aryl boron species and consecutive C-B bond cleavage to deliver a broad range of functionalized products. The reaction is high yielding, has a broad substrate scope where several different heteroarenes can be functionalized with chloro, bromo, iodo, hydroxyl, amine and BF2 in a highly regioselective fashion. The method can be applied for late-stage functionalization or for rapid skeleton remodeling with for instance cross-couplings.

Less than 10% of research on psychotic disorders has been conducted in settings in the Global South, which refers broadly to the regions of Latin America, Asia, Africa, and Oceania. There is a lack of basic epidemiological data on the distribution of and risks for psychoses that can inform the development of services in many parts of the world.

To compare demographic and clinical profiles of cohorts of cases and rates of untreated psychoses (proxy for incidence) across and within 3 economically and socially diverse settings in the Global South. Two hypotheses were tested (1) demographic and clinical profiles of cases with an untreated psychotic disorder vary across setting and (2) rates of untreated psychotic disorders vary across and within setting by clinical and demographic group.

The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II) comprises incidence, case-control, and cohort studies of untreated psychoses in catchment areas in 3 countries in the Global South h that suggests that core aspects of psychosis vary by historic, economic, and social context, with far-reaching implications for understanding and treatment of psychoses globally.

Pituitary adenoma is the second most common primary brain tumor. Perioperative hydrocortisone has been used for decades to avoid postoperative adrenal insufficiency. Recent studies suggest that withholding perioperative hydrocortisone may be safe for patients with an intact hypothalamus-pituitary-adrenal (HPA) axis.

To assess the safety of withholding hydrocortisone during the perioperative period of pituitary adenoma surgery for patients with an intact HPA axis.

A parallel-group, triple-masked, noninferiority randomized clinical trial was conducted at Peking Union Medical College Hospital from November 1, 2020, to January 31, 2022, among 436 patients aged 18 to 70 years with an intact HPA axis undergoing surgery for pituitary adenomas.

Hydrocortisone supplementation protocol (intravenous and subsequent oral hydrocortisone, using a taper program) or no-hydrocortisone protocol.

The primary outcome was the incidence of new-onset adrenal insufficiency (morning cortisol level, <5 μg/dL with adrenal in the hydrocortisone group (difference, 0.5%; 95% CI, -3.0% to 3.9%). Incidences of new-onset diabetes mellitus (1 of 218 [0.5%] vs 9 of 218 [4.1%]), hypernatremia (9 of 218 [4.1%] vs 21 of 218 [9.6%]), hypokalemia (23 of 218 [10.6%] vs 34 of 218 [15.6%]), and hypocalcemia (6 of 218 [2.8%] vs 19 of 218 [8.7%]) were lower in the no-hydrocortisone group than in the hydrocortisone group. CDK inhibitor Lower preoperative morning cortisol levels were associated with higher risks of the primary event (<9.3 µg/dL; odds ratio, 3.0; 95% CI, 1.5-5.9) and the secondary event (<8.8 µg/dL; odds ratio, 7.8; 95% CI, 2.6-23.4) events.

This study found that withholding hydrocortisone was safe and demonstrated noninferiority to the conventional hydrocortisone supplementation regimen regarding the incidence of new-onset adrenal insufficiency among patients with an intact HPA axis undergoing pituitary adenomectomy.

ClinicalTrials.gov Identifier NCT04621565.

ClinicalTrials.gov Identifier NCT04621565.

Herpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk.

To assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection.

This cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the earl, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.

In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.