Intra-articular drug delivery has a number of advantages over systemic administration; however, for the past 20 years, intra-articular treatment options for the management of knee osteoarthritis (OA) ...have been limited to analgesics, glucocorticoids, hyaluronic acid (HA) and a small number of unproven alternative therapies. Although HA and glucocorticoids can provide clinically meaningful benefits to an appreciable number of patients, emerging evidence indicates that the apparent effectiveness of these treatments is largely a result of other factors, including the placebo effect. Biologic drugs that target inflammatory processes are used to manage rheumatoid arthritis, but have not translated well into use in OA. A lack of high-level evidence and methodological limitations hinder our understanding of so-called 'stem' cell therapies and, although the off-label administration of intra-articular cell therapies (such as platelet-rich plasma and bone marrow aspirate concentrate) is common, high-quality clinical data are needed before these treatments can be recommended. A number of promising intra-articular treatments are currently in clinical development in the United States, including small-molecule and biologic therapies, devices and gene therapies. Although the prospect of new, non-surgical treatments for OA is exciting, the benefits of new treatments must be carefully weighed against their costs and potential risks.
The employment of spectroscopically-resolved NMR techniques as analytical probes have previously been both prohibitively expensive and logistically challenging in view of the large sizes of ...high-field facilities. However, with recent advances in the miniaturisation of magnetic resonance technology, low-field, cryogen-free “benchtop” NMR instruments are seeing wider use. Indeed, these miniaturised spectrometers are utilised in areas ranging from food and agricultural analyses, through to human biofluid assays and disease monitoring. Therefore, it is both intrinsically timely and important to highlight current applications of this analytical strategy, and also provide an outlook for the future, where this approach may be applied to a wider range of analytical problems, both qualitatively and quantitatively.
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•Low field, compact or mobile, benchtop NMR spectroscopy has wide use in chemical and biochemical analysis.•Recent applications of the technology and methodology are reviewed.•Applications include materials science, forensics, continuous flow processes/reaction monitoring, quality control, food, and biomedical/metabolomics analysis.
This preliminary study tested the efficacy of an evidence-based correctional intervention (Thinking for a Change) with an adapted delivery to incarcerated people with mental illness.
A small-scale ...randomized controlled trial (N=47 men) was conducted. Outcomes were changes in aggression, number of behavioral infractions, and days in administrative segregation. Treatment targets were impulsivity, interpersonal problem-solving skills, and attitudes supportive of crime. Linear mixed-effects models were used to examine within-person and between-group differences over time, and nonparametric tests were used to examine between-group differences in criminal legal outcomes postintervention.
Statistically significant within-person differences were found for all treatment targets and for one study outcome (aggression). Statistically significant differences in impulsivity were found between the experimental and control groups (B=-7.10, p=0.02).
Existing evidence-based correctional interventions can affect the lives of people with mental illness. Accelerated research in this area may benefit people with mental illness at high risk for criminal legal system involvement.
No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens that antigenically mimic the HIV envelope ...glycoprotein (Env), such as the soluble cleaved trimer BG505 SOSIP, have improved the elicitation of potent isolate-specific antibody responses in rabbits and macaques, but so far failed to induce broadly neutralizing antibodies. One possible reason for this failure is that the relevant antibody repertoires are poorly suited to target the conserved epitope regions on Env, which are somewhat occluded relative to the exposed variable epitopes. Here, to test this hypothesis, we immunized four cows with BG505 SOSIP. The antibody repertoire of cows contains long third heavy chain complementary determining regions (HCDR3) with an ultralong subset that can reach more than 70 amino acids in length. Remarkably, BG505 SOSIP immunization resulted in rapid elicitation of broad and potent serum antibody responses in all four cows. Longitudinal serum analysis for one cow showed the development of neutralization breadth (20%, n = 117 cross-clade isolates) in 42 days and 96% breadth (n = 117) at 381 days. A monoclonal antibody isolated from this cow harboured an ultralong HCDR3 of 60 amino acids and neutralized 72% of cross-clade isolates (n = 117) with a potent median IC
of 0.028 μg ml
. Breadth was elicited with a single trimer immunogen and did not require additional envelope diversity. Immunization of cows may provide an avenue to rapidly generate antibody prophylactics and therapeutics to address disease agents that have evolved to avoid human antibody responses.
IMPORTANCE: Youth with intellectual and developmental disabilities (I/DD) are more likely to be placed in foster care than other youth. Examining the clinical and sociodemographic characteristics of ...youth with I/DD in the foster care system is critical for identifying disparities and understanding service needs. OBJECTIVE: To produce a population-level analysis of youth with I/DD in foster care that examines differences in rates of foster care involvement based on race, ethnicity, age, and sex. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved all individuals with I/DD 21 years and younger enrolled in Medicaid through foster care in 2016 via data from Transformed Medicaid Statistical Information System (T-MSIS) Analytic Files (TAF) for all 50 US states and Washington, DC. As a key insurer of I/DD services and foster care, Medicaid claims offer a timely population-level analysis. Youth with I/DD were grouped into diagnostic subgroups: autism spectrum disorder (ASD) only, intellectual disability only, or ASD and ID. The data analysis took place from July 2022 to September 2023. EXPOSURE: TAF data contain Medicaid enrollment information by month with a binary indicator of foster care involvement, and eligibility files identify race, ethnicity, age, and sex. MAIN OUTCOMES AND MEASURES: The period prevalence of foster care involvement was determined among I/DD youth by diagnostic subgroups using an intersectional approach across race, ethnicity, age, and sex. Logistic regression examined associations between risk for foster care involvement and race, ethnicity, age, and sex. RESULTS: A total of 39 143 youth with I/DD had foster care involvement in 2016. Black youth (adjusted odds ratio aOR, 1.37; 95% CI, 1.28-1.47) and females (aOR, 1.18; 95% CI, 1.1-1.27) had increased likelihood for foster care involvement. The likelihood for foster care involvement increased with age in all groups relative to the age group 0 to 5 years old. CONCLUSIONS AND RELEVANCE: This study found that among youth with I/DD, Black youth and females faced higher risk for foster care involvement, and the likelihood of foster care involvement increased with age. There is an urgent need for research that focuses on addressing system-level factors that drive increased risk. Understanding the specific health needs of Black and female youth with I/DD is critical to ensure the formation, implementation, and monitoring of equitable delivery of health services.
To characterise whether preseason screening of shoulder range of motion (ROM) is associated with the risk of shoulder and elbow injuries in overhead athletes.
Systematic review and meta-analysis.
Six ...electronic databases up to 22 September 2018.
Inclusion criteria were (1) overhead athletes from Olympic or college sports, (2) preseason measures of shoulder ROM, (3) tracked in-season injuries at the shoulder and elbow, and (4) prospective cohort design. Exclusion criteria were (1) included contact injuries, (2) lower extremity, spine and hand injuries, and (3) full report not published in English.
Fifteen studies were identified, and they included 3314 overhead athletes (baseball (74.6%), softball (3.1%), handball (16.1%), tennis (2.0%), volleyball (2.0%) and swimming (2.2%)). Female athletes are unrepresented (12% of the overall sample). Study quality ranged from 11 to 18 points on a modified Downs and Black checklist (maximum score 21, better quality). In one study, swimmers with low (<93°) or high (>100°) shoulder external rotation were at higher risk of injuries. Using data pooled from three studies of professional baseball pitchers, we showed in the meta-analysis that shoulder external rotation insufficiency (throwing arm <5° greater than the non-throwing arm) was associated with injury (odds ratio=1.90, 95% confidence interval 1.24 to 2.92, p<0.01).
Preseason screening of shoulder external rotation ROM may identify professional baseball pitchers and swimmers at risk of injury. Shoulder ROM screening may not be effective to identify handball, softball, volleyball and tennis players at risk of injuries. The results of this systematic review and meta-analysis should be interpreted with caution due to the limited number of studies and their high degree of heterogeneity.
CRD42017072895.
Activating mutations in
are frequent in human breast cancer, and phosphoinositide 3-kinase alpha (PI3Kα) inhibitors have been approved for therapy. To characterize determinants of sensitivity to ...these agents, we analyzed
-mutant cancer genomes and observed the presence of multiple
mutations in 12 to 15% of breast cancers and other tumor types, most of which (95%) are double mutations. Double
mutations are in cis on the same allele and result in increased PI3K activity, enhanced downstream signaling, increased cell proliferation, and tumor growth. The biochemical mechanisms of dual mutations include increased disruption of p110α binding to the inhibitory subunit p85α, which relieves its catalytic inhibition, and increased p110α membrane lipid binding. Double
mutations predict increased sensitivity to PI3Kα inhibitors compared with single-hotspot mutations.
Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal-fetal interactions that have long-term mental health implications. It is thought that ...beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1(-/-) (also called Fev) mice in which most dorsal raphe neurons lack 5-HT. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal-placental-fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The current study examined the role of internalized HIV-related stigma in antiretroviral therapy adherence, viral load, and retention in care among women of color living with HIV in Los Angeles ...County, California. African American and Hispanic/Latino women 18 years of age and older completed a one-time brief survey between September 2017 and February 2018. Descriptive statistics, and univariable and multivariable logistic regressions were used to analyze the data. Seventy-six participants enrolled in the study and 74 completed the entire survey. Seventy-six percent of respondents were Hispanic/Latino, 24% were African American, 71% were unemployed, and 54% had less than a high school education. Thirty-five percent were defined as having "high" stigma with a score in the upper quartile of the scale. Being unemployed, having a high school education or less, and not meeting the Health Resources and Services Administration's annual retention in care measure were associated with "high" stigma. When controlling for education and employment status, those reporting "high" stigma vs. "low" stigma were 18.8 times more likely to not meet the criteria for annual retention in care (OR =
18
.8, 95% CI = 1.9-189.2, p = 0.013). Stigma-reduction interventions targeting healthcare settings may be necessary to improve patient retention and engagement in care.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of ...this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies.
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