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Background Partner notification services (PNS) are recommended by the Centers for Disease Control and Prevention as a public health intervention for addressing the spread of HIV and other sexually transmitted diseases (STDs). Barriers and facilitators to the partner notification process from a public health perspective have not been well described. Methods In 2015, a coalition of New England public health STD directors and investigators formed to address the increasing STD prevalence across the region (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) and to promote communication between state STD programs. To evaluate barriers and facilitators of PNS programs, a survey was administered to representatives from each state to describe PNS processes and approaches. Results Of the six PNS programs, Connecticut, Maine, Massachusetts, Vermont, and New Hampshire had combined HIV and STD PNS programs; Rhode Island’s programs were integrated but employed separate disease intervention specialists (DIS). All states performed PNS for HIV and syphilis. Maine, New Hampshire and Vermont performed services for all gonorrhea cases. Rhode Island, Connecticut, and Massachusetts performed limited partner notification for gonorrhea due to lack of resources. None of the six states routinely provided services for chlamydia, though Maine and Vermont did so for high-priority populations such as HIV co-infected or pregnant individuals. Across all programs, clients received risk reduction counseling and general STD education as a component of PNS, in addition to referrals for HIV/STD care at locations ranging from Planned Parenthood to community- or hospital-based clinics. Notable barriers to successful partner notification across all states included anonymous partners and index cases who did not feel comfortable sharing partners’ names with DIS. Other common barriers included insufficient staff, inability of DIS to identify and contact partners, and index cases declining to speak with DIS staff. Conclusions In New England, state health departments use different strategies to implement PNS programs and referral to STD care. Despite this, similar challenges exist across settings, including difficulty with anonymous partners and limited state resources.

Residents have bought out the green, red and maroon jerseys from Brownsville to McAllen, leaving the American counterparts to hang, forgotten, on store racks. Butchers at one supermarket here have spray-painted Mexican team memorabilia on store windows. And many residents are making plans to head across the border Monday night to join like-minded sports fans -- including relatives -- in bars or backyard barbecues. \"We along the border here live with one foot in Mexico and one foot in the U.S. and part of our heart in Mexico and part of our heart in the U.S.,\" said Dr. Tony Zavaleta, vice president of external affairs at the University of Texas at Brownsville and an authority on Mexican-American culture. \"The fact that both teams have made it to the second round is incredible.\" Dr. Zavaleta said that kind of ambivalence is common in an area where U.S. and Mexican cultures converge.

Four years ago Tuesday, Barbara and William Gooch Jr. salvaged what they could from the third floor of their Elmhurst home, which only a day before had been a distant five blocks from Salt Creek. The floods of 1987 caused $100 million in property damage and unmeasurable emotional damage, especially along the Des Plaines River and Salt Creek. On the other side is a rising tide of anti-tax sentiment that could dilute the Du Page County Board's ability to raise the money to pay for the projects, including $110 million for work on Salt Creek, $23 million for work on the East Branch of the Du Page River and $21 million for work on the West Branch of the Du Page.

Direct activation of the human phospholipase C-γ isozymes (PLC-γ1, -γ2) by tyrosine phosphorylation is fundamental to the control of diverse biological processes, including chemotaxis, platelet aggregation, and adaptive immunity. In turn, aberrant activation of PLC-γ1 and PLC-γ2 is implicated in inflammation, autoimmunity, and cancer. Although structures of isolated domains from PLC-γ isozymes are available, these structures are insufficient to define how release of basal autoinhibition is coupled to phosphorylation-dependent enzyme activation. Here, we describe the first high-resolution structure of a full-length PLC-γ isozyme and use it to underpin a detailed model of their membrane-dependent regulation. Notably, an interlinked set of regulatory domains integrates basal autoinhibition, tyrosine kinase engagement, and additional scaffolding functions with the phosphorylation-dependent, allosteric control of phospholipase activation. The model also explains why mutant forms of the PLC-γ isozymes found in several cancers have a wide spectrum of activities, and highlights how these activities are tuned during disease. Many enzymes are poised to receive signals from the surrounding environment and translate them into responses inside the cell. One such enzyme is phospholipase C-γ1 (PLC-γ1), which controls how cells grow, divide and migrate. When activating signals are absent, PLC-γ1 usually inhibits its own activity, a mechanism called autoinhibition. This prevents the enzyme from binding to its targets, which are fat molecules known as lipids. When activating signals are present, a phosphate group serves as a ‘chemical tag’ and is added onto PLC-γ1, allowing the enzyme to bind to lipids. Failure in the regulation of PLC-γ1 or other closely related enzymes may lead to conditions such as cancer, arthritis and Alzheimer’s disease. However, it remains unclear how autoinhibition suppresses the activity of the enzyme, and how it is stopped by the addition of the phosphate group. Here, Hajicek et al. determine in great detail the three-dimensional structure of the autoinhibited form of the enzyme using a method known as X-ray crystallography. This reveals that PLC-γ1 has two major lobes: one contains the active site that modifies lipids, and the other sits on top of the active site to prevent lipids from reaching it. The findings suggest that when the phosphate group attaches to PLC-γ1, it triggers a large shape change that shifts the second lobe away from the active site to allow lipids to bind. The three-dimensional structure also helps to understand how mutations identified in certain cancers may activate PLC-γ1. In particular, these mutations disrupt the interactions between elements that usually hold the two lobes together, causing the enzyme to activate more easily. The work by Hajicek et al. provides a framework to understand how cells control PLC-γ1. It is a first step toward designing new drugs that alter the activity of this enzyme, which may ultimately be useful to treat cancer and other diseases.

Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

Background Feed costs are a major expense in the production of beef cattle. Individual variation in the efficiency of feed utilization may be evident through feed efficiency-related phenotypes such as those related to major energetic sinks. Our objectives were to assess the relationships between feed efficiency with liver morphometry and metabolic blood profile in feedlot beef cattle. Methods Two populations (A = 112 and B = 45) of steers were tested for feed efficiency. Blood from the 12 most (efficient) and 12 least feed inefficient (inefficient) steers from population A was sampled hourly over the circadian period. Blood plasma samples were submitted for analysis on albumin, aspartate aminotransferase, γ-glutamyl transpeptidase urea, cholesterol, creatinine, alkaline phosphatase, creatine kinase, lipase, carbon dioxide, β-hydroxybutyrate, acetate and bile acids. Liver tissue was also harvested from 24 steers that were blood sampled from population A and the 10 steers with divergent feed efficiency in each tail of population B was sampled for microscopy at slaughter. Photomicroscopy images were taken using the portal triad and central vein as landmarks. Histological quantifications included cross-sectional hepatocyte perimeter and area, hepatocyte nuclear area and nuclei area as proportion of the hepatocyte area. The least square means comparison between efficient and inefficient steers for productive performance and liver morphometry and for blood analytes data were analyzed using general linear model and mixed model procedures of SAS, respectively. Results No differences were observed for liver weight; however, efficient steers had larger hepatocyte (i.e. hepatocyte area at the porta triad 323.31 vs. 286.37 µm 2 ) and nuclei dimensions at portal triad and central vein regions, compared with inefficient steers. The metabolic profile indicated efficient steers had lower albumin (36.18 vs. 37.65 g/l) and cholesterol (2.62 vs. 3.05 mmol/l) and higher creatinine (118.59 vs. 110.50 mmol/l) and carbon dioxide (24.36 vs. 23.65 mmol/l) than inefficient steers. Conclusions Improved feed efficiency is associated with increased metabolism by the liver (enlarged hepatocytes and no difference on organ size), muscle (higher creatinine) and whole body (higher carbon dioxide); additionally, efficient steers had reduced bloodstream pools of albumin and cholesterol. These metabolic discrepancies between feed efficient and inefficient cattle may be determinants of productive performance.

Evaluate system-wide antimicrobial stewardship program (ASP) update impact on intravenous (IV)-to-oral (PO) antimicrobial conversion in select community hospitals through pre- and postimplementation trend analysis. Retrospective study across seven hospitals: region one (four hospitals, 827 beds) with tele-ASP managed by infectious diseases (ID)-trained pharmacists and region two (three hospitals, 498 beds) without. Data were collected pre- (April 2022-September 2022) and postimplementation (April 2023-September 2023) on nine antimicrobials for the IV to PO days of therapy (DOTs). Antimicrobial administration route and (DOTs)/1,000 patient days were extracted from the electronical medical record (EMR). Primary outcome: reduction in IV DOTs/1,000 patient days. Secondary outcomes: decrease in IV usage via PO:total antimicrobial ratios and cost reduction. In region one, IV usage decreased from 461 to 209/1,000 patient days ( = < .001), while PO usage increased from 289 to 412/1,000 patient days ( = < .001). Total antimicrobial use decreased from 750 to 621/1,000 patient days ( = < .001). In region two, IV usage decreased from 300 to 243/1,000 patient days ( = .005), and PO usage rose from 154 to 198/1,000 patient days ( = .031). The PO:total antimicrobial ratios increased in both regions, from .42-.52 to .60-.70 in region one and from .36-.55 to .46-.55 in region two. IV cost savings amounted to $19,359.77 in region one and $4,038.51 in region two. The ASP intervention improved IV-to-PO conversion rates in both regions, highlighting the contribution of ID-trained pharmacists in enhancing ASP initiatives in region one and suggesting tele-ASP expansion may be beneficial in resource-constrained settings.

This study aimed to assess the effective tissue concentrations of the current standard of care for pain mitigation in calves during castration (injectable lidocaine) and to assess the ability of a lidocaine-loaded elastration band (LLB) to deliver effective concentrations into the scrotal tissue over time. This study comprised two different trials: (1) effective concentrations of injectable lidocaine in the scrotal tissue; and (2) the in vivo delivery of effective concentrations of lidocaine from LLBs placed on the calf scrotums. Sensation in the scrotal tissue was assessed by electrocutaneous stimulation. Injectable lidocaine allowed for short-term anesthesia for up to 60 min, highlighting the importance of finding additional strategies to mitigate long-term pain. An elastomeric ligation band impregnated with lidocaine could provide a suitable alternative, as it yielded tissue levels of lidocaine that approached EC50 and exceeded EC95 at 2 and 72 h following application, respectively, and remained above those levels for at least 28 days after application. Further studies are warranted to compare the use of LLBs to injectable local anesthetics.

The objectives of this study were to assess the pharmacokinetics and pharmacodynamics of the current standard-of-care for pain mitigation in lambs during castration and tail docking (injectable lidocaine) and assess the ability of Lidocaine-Loaded Bands (LLBs) to deliver therapeutic concentrations into the contacted tissues over time. The study was comprised of four different trials: (1) investigation of in vitro release of lidocaine from LLBs; (2) pharmacokinetics and pharmacodynamics of injectable lidocaine in scrotal and tail tissue; (3) pharmacokinetics and pharmacodynamics of in vivo delivery of lidocaine with LLBs placed on the tail and scrotum of lambs; and (4) a “proof-of-concept” study comparing the sensation of control- versus LLB-banded tail tissue over time. The use of injectable lidocaine provides effective short-term anesthesia for 120 to 180 min following the injection; however, additional strategies are needed to manage long-term pain. The use of an LLB could provide an alternative where tissue lidocaine concentrations meet or exceed the EC50 for at least 21–28 days and, based on electrostimulation data, provides local anesthesia for at least 3 days when compared to a control band. Further studies are needed to compare the use of an injectable local anesthetic to the LLBs.

The primary objective of this study was to demonstrate the non-inferiority between lidocaine-impregnated ligation bands (LLBs) and control bands (CBs) with respect to the efficacy of castration and tail docking. Secondary objectives were to compare castration and tail-docking success, evaluate local site reactions, and compare average daily gain (ADG) between the treatment groups. A total of 238 male lambs were enrolled and randomly assigned to receive LLBs or CBs on their tail and scrotum. Lambs were weighed, had a health assessment, and the band site was observed on −3, 7, 14, 21, 28, 35, and 42 days after the bands were applied. A linear regression model was built to assess average daily gain, whereas a repeated measures model was used to evaluate body weight differences at each of the measured timepoints. Furthermore, logistic regression models were used to evaluate associations with casting outcomes. Few differences were noted between treatment groups with respect to casting success for the scrotum and tail and ADG over the entire experimental period. Non-inferiority calculations demonstrated no differences in tail docking and scrotal casting success, with casting occurring for the majority of animals by d 21 and d 42 for castration and tail docking, respectively. However, lambs receiving LLBs gained more weight from d −3 to 7 (+0.03 kg/d; 95% CI: 0 to 0.07), which may be an indication of effective pain control during the first week following band application. Overall, the use of an LLB does not affect the time to successful casting of the tail and could improve short-term growth when compared to a control band. Further studies are needed to compare LLBs to multimodal methods of pain relief.