Identification of Idiopathic Pulmonary Fibrosis and Prediction of Disease Severity via Machine Learning Analysis of Comprehensive Metabolic Panel and Complete Blood Count Data.

BACKGROUND: Diagnosis of idiopathic pulmonary fibrosis (IPF) typically relies on high-resolution computed tomography imaging (HRCT) or histopathology, while monitoring disease severity is done via frequent pulmonary function testing (PFT). More reliable and convenient methods of diagnosing fibrotic interstitial lung disease (ILD) type and monitoring severity would allow for early identification and enhance current therapeutic interventions. This study tested the hypothesis that a machine learning (ML) ensemble analysis of comprehensive metabolic panel (CMP) and complete blood count (CBC) data can accurately distinguish IPF from connective tissue disease ILD (CTD-ILD) and predict disease severity as seen with PFT. METHODS: Outpatient data with diagnosis of IPF or CTD-ILD (n = 103 visits by 53 patients) were analyzed via ML methodology to evaluate (1) IPF vs CTD-ILD diagnosis; (2) %predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) moderate or mild vs severe; (3) %predicted Forced Vital Capacity (FVC) moderate or mild vs severe; and (4) %predicted FVC mild vs moderate or severe. RESULTS: ML methodology identified IPF from CTD-ILD with AUCTEST = 0.893, while PFT was classified as DLCO moderate or mild vs severe with AUCTEST = 0.749, FVC moderate or mild vs severe with AUCTEST = 0.741, and FVC mild vs moderate or severe with AUCTEST = 0.739. Key features included albumin, alanine transaminase, %lymphocytes, hemoglobin, %eosinophils, white blood cell count, %monocytes, and %neutrophils. CONCLUSION: Analysis of CMP and CBC data via proposed ML methodology offers the potential to distinguish IPF from CTD-ILD and predict severity on associated PFT with accuracy that meets or exceeds current clinical practice.

Aging and skeletal muscle force control: Current perspectives and future directions.

During voluntary muscle contractions, force output is characterized by constant inherent fluctuations, which can be quantified either according to their magnitude or temporal structure, that is, complexity. The presence of such fluctuations when targeting a set force indicates that control of force is not perfectly accurate, which can have significant implications for task performance. Compared to young adults, older adults demonstrate a greater magnitude and lower complexity in force fluctuations, indicative of decreased steadiness, and adaptability of force output, respectively. The nature of this loss-of-force control depends not only on the age of the individual but also on the muscle group performing the task, the intensity and type of contraction and whether the task is performed with additional cognitive load. Importantly, this age-associated loss-of-force control is correlated with decreased performance in a range of activities of daily living and is speculated to be of greater importance for functional capacity than age-associated decreases in maximal strength. Fortunately, there is evidence that acute physical activity interventions can reverse the loss-of-force control in older individuals, though whether this translates to improved functional performance and whether lifelong physical activity can protect against the changes have yet to be established. A number of mechanisms, related to both motor unit properties and the behavior of motor unit populations, have been proposed for the age-associated changes in force fluctuations. It is likely, though, that age-associated changes in force control are related to increased common fluctuations in the discharge times of motor units.

Physical Characteristics of Youth Elite Golfers and Their Relationship With Driver Clubhead Speed.

Coughlan, D, Taylor, M, Jackson, J, Ward, N, and Beardsley, C. Physical characteristics of youth elite golfers and their relationship with driver clubhead speed. J Strength Cond Res 34(1): 212-217, 2020-Increased clubhead speed (CHS) has a strong relationship with golf performance and is related to athletic qualities in adult golfers. Research investigating the youth golfer is limited. The purpose of this study was to explore the relationships between strength and power on CHS in youth golfers. A correlational design was used to assess relationships between CHS and anthropometric, strength, and power measurements. Thirty-six male and 33 female golfers aged 13-17 took part in this study. Male golfers showed significant relationships between CHS and handicap (HCP) (r = -0.50), seated medicine ball throw to the left (SMBTL) (r = 0.67), and right (SMBTR) (r = 0.61), rotational medicine ball throw to the left (RMBTL) (r = 0.71), and right RMBTR (r = 0.62). Female golfers showed significant relationships between CHS and HCP (r = -0.52), mass (r = 0.72), countermovement jump power (r = 0.60), RMBTL (r = 0.57), RMBTR (r = 0.56). Multiple stepwise linear regression analysis identified 77% of the variance in CHS could be explained through SMBTL and RMBTL in males. In females, 84% of the variance in CHS could be explained through mass, RMBTR, and height. This study demonstrated relationships between CHS and body mass and upper-, lower-, and full-body concentric dominant power exercises. This study could aid in the development of training interventions for youth golfers.

Continuous tracking of startled Drosophila as an alternative to the negative geotaxis climbing assay.

The fruit fly, Drosophila, is commonly used to study late-onset neurodegenerative diseases due to the combination of powerful genetic tools, cheap and simple husbandry and short lifespan. One widely-used measure of disease progression is the age-dependent decline in motor performance that manifests in most Drosophila neurodegeneration models. This is usually quantified using a simple climbing assay. However, the standard climbing assay lacks sensitivity and suffers from high variability meaning large numbers of flies are needed or bespoke apparatus and software solutions. Here, we present a modification of the open-source, MATLAB-based, DART software to measure the decline in "startle response" with age. We demonstrate that the DART setup is more sensitive to the motor performance decline induced by adult-onset neuronal expression of amyloid beta (Aß) peptides than a traditional climbing assay despite using smaller cohorts of flies. DART also has the potential to generate multiple metrics of motor behaviour during the startle response. The software requires no coding skills to operate and the required apparatus can be purchased commercially. Therefore, DART is a more useful method than the climbing assay for longitudinal assays of motor performance and will enable higher-throughput screen for genetic and pharmacological modifiers of neurodegeneration. In our proof-of-concept screen for modifiers of Aß-dependent phenotypes, we identified that in vivo knock-down of p53 in adult neurons is neuroprotective. This supports recent work targeting p53 in vitro and demonstrates the potential for DART to be used to screen for targets that ameliorate neurodegeneration.

Timing of onset of lithium relapse prevention in bipolar disorder: evidence from randomised trials.

Lithium is widely prescribed, but the timing of key effects remains uncertain. The timing of onset of its relapse prevention effects is clarified by placebo-controlled randomised trials (3 studies, n = 1120). Lithium reduced relapse into any mood episode over the first 2 weeks of treatment (hazard ratio 0.40, 95% CI 0.16-0.97). Fewer manic relapses were evident within the first 4 weeks, however, early effects on depressive relapse were not demonstrated. There is an early onset of lithium relapse prevention effects in bipolar disorder, particularly against manic relapse. Full effects against depressive relapse may develop over a longer period.Declaration of interestM.J.T. reports personal fees from Sunovion, Otsuka, Lundbeck, outside the submitted work.

The use of an ecodevelopmental approach to examining substance use among rural and urban Latino/a youth: peer, parental, and school influences.

Using an ecodevelopmental framework, we examined how peer, parent, and student variables influence substance (tobacco, alcohol, and marijuana) use among rural and urban Latino/a adolescents (N = 2,500). Generally speaking, Latino/a adolescents in rural areas endorsed higher levels of substance use. Among the primary variables of study, there were a number of nuanced differences noted based on location, gender, and type of substance. Peer use was related to individual substance use in both rural and urban areas. However, peer use was a significantly stronger predictor of tobacco use among rural Latinas than urban dwelling. Parental monitoring was not predictive of urban marijuana use, yet was negatively associated with substance use for all subgroups and was especially pronounced for female alcohol use. Parental emotional involvement predicted higher alcohol use among urban boys. School achievement was negatively associated with substance use for all subgroups while, conversely, school involvement was associated with higher alcohol use for rural boys. Cultural and contextual implications for intervention and prevention are discussed.

The utility of community-based participatory research: Increasing research engagement among minoritized ethnoracial groups.

OBJECTIVE: This article conceptually examined the need for and utility of community-based participatory research (CBPR) approaches for increasing rates of engagement in psychological research among underserved minoritized ethnoracial groups. METHODS: This article examined the literature for relevant studies examining rates of research engagement by minoritized ethnoracial groups, significant factors precluding research engagement, and the consequences of this disparity for mental health outcomes. The theoretical literature outlining the development and utility of alternative, community-based participatory research methods was included. Key features of CBPR were examined along with limitations of current approaches. A case study example of CBPR is provided. RESULTS: The use of CBPR approaches has been documented to improve health outcomes, reduce stigma toward mental health research and treatment, and build the professional capacity of community partners, particularly among minoritized ethnoracial groups. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: CBPR engagement practices are a means of reducing the mental health research gap for ethnic and racial minoritized groups. The use of such approaches in future research and practice will directly inform how existing psychological treatments may be modified per the needs of the patient, address long standing issues of cultural mistrust toward professional institutions, and reduce mental health stigma in underserved communities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Disease diagnosis and severity classification in pulmonary fibrosis using carbonyl volatile organic compounds in exhaled breath.

BACKGROUND: Pathophysiological conditions underlying pulmonary fibrosis remain poorly understood. Exhaled breath volatile organic compounds (VOCs) have shown promise for lung disease diagnosis and classification. In particular, carbonyls are a byproduct of oxidative stress, associated with fibrosis in the lungs. To explore the potential of exhaled carbonyl VOCs to reflect underlying pathophysiological conditions in pulmonary fibrosis, this proof-of-concept study tested the hypothesis that volatile and low abundance carbonyl compounds could be linked to diagnosis and associated disease severity. METHODS: Exhaled breath samples were collected from outpatients with a diagnosis of Idiopathic Pulmonary Fibrosis (IPF) or Connective Tissue related Interstitial Lung Disease (CTD-ILD) with stable lung function for 3 months before enrollment, as measured by pulmonary function testing (PFT) DLCO (%), FVC (%) and FEV1 (%). A novel microreactor was used to capture carbonyl compounds in the breath as direct output products. A machine learning workflow was implemented with the captured carbonyl compounds as input features for classification of diagnosis and disease severity based on PFT (DLCO and FVC normal/mild vs. moderate/severe; FEV1 normal/mild/moderate vs. moderately severe/severe). RESULTS: The proposed approach classified diagnosis with AUROC=0.877 ± 0.047 in the validation subsets. The AUROC was 0.820 ± 0.064, 0.898 ± 0.040, and 0.873 ± 0.051 for disease severity based on DLCO, FEV1, and FVC measurements, respectively. Eleven key carbonyl VOCs were identified with the potential to differentiate diagnosis and to classify severity. CONCLUSIONS: Exhaled breath carbonyl compounds can be linked to pulmonary function and fibrotic ILD diagnosis, moving towards improved pathophysiological understanding of pulmonary fibrosis.

Chronic activation of adrenal Gq signaling induces Cyp11b2 expression in the zona fasciculata and hyperaldosteronism.

Hyperaldosteronism is often associated with inappropriate aldosterone production and aldosterone synthase (Cyp11b2) expression. Normally, Cyp11b2 expression is limited to the adrenal zona glomerulosa (ZG) and regulated by angiotensin II which signals through Gq protein-coupled receptors. As cells migrate inwards, they differentiate into 11ß-hydroxylase-expressing zona fasciculata (ZF) cells lacking Cyp11b2. The mechanism causing ZG-specific aldosterone biosynthesis is still unclear. We investigated the effect of chronic Gq signaling using transgenic mice with a clozapine N-oxide (CNO)-activated human M3 muscarinic receptor (DREADD) coupled to Gq (hM3Dq) that was expressed throughout the adrenal cortex. CNO raised circulating aldosterone in the presence of a high sodium diet with greater response seen in females compared to males. Immunohistochemistry and transcriptomics indicated disrupted zonal Cyp11b2 expression while Wnt signaling remained unchanged. Chronic Gq-DREADD signaling also induced an intra-adrenal RAAS in CNO-treated mice. Chronic Gq signaling disrupted adrenal cortex zonal aldosterone production associated with ZF expression of Cyp11b2.

Aripiprazole alone or in combination for acute mania.

BACKGROUND: Bipolar disorder is a mental disorder characterised by episodes of elevated or irritable mood (manic or hypomanic episodes) and episodes of low mood and loss of energy (depressive episodes). Drug treatment is the first-line treatment for acute mania with the initial aim of rapid control of agitation, aggression and dangerous behaviour. Aripiprazole, an atypical antipsychotic, is used in the treatment of mania both as monotherapy and combined with other medicines. The British Association of Psychopharmacology guidelines report that, in monotherapy placebo-controlled trials, the atypical antipsychotics, including aripiprazole, have been shown to be effective for acute manic or mixed episodes. OBJECTIVES: To assess the efficacy and tolerability of aripiprazole alone or in combination with other antimanic drug treatments, compared with placebo and other drug treatments, in alleviating acute symptoms of manic or mixed episodes. Other objectives include reviewing the acceptability of treatment with aripiprazole, investigating the adverse effects of aripiprazole treatment, and determining overall mortality rates among those receiving aripiprazole treatment. SEARCH METHODS: The Cochrane Depression, Anxiety and Neurosis Group's Specialised Register (CCDANCTR-Studies and CCDANCTR-References) was searched, all years to 31st July 2013. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We also searched Bristol-Myers Squibb clinical trials register, the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov (to August 2013). SELECTION CRITERIA: Randomised trials comparing aripiprazole versus placebo or other drugs in the treatment of acute manic or mixed episodes. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, including adverse effect data, from trial reports and assessed bias. The drug manufacturer or the trial authors were contacted for missing data. MAIN RESULTS: Ten studies (3340 participants) were included in the review. Seven studies compared aripiprazole monotherapy versus placebo (2239 participants); two of these included a third comparison arm-one study used lithium (485 participants) and the other used haloperidol (480 participants). Two studies compared aripiprazole as an adjunctive treatment to valproate or lithium versus placebo as an adjunctive treatment (754 participants), and one study compared aripiprazole versus haloperidol (347 participants). The overall risk of bias was unclear. A high dropout rate from most trials (> 20% for each intervention in eight of the trials) may have affected the estimates of relative efficacy. Evidence shows that aripiprazole was more effective than placebo in reducing manic symptoms in adults and children/adolescents at three and four weeks but not at six weeks (Young Mania Rating Scale (YMRS); mean difference (MD) at three weeks (random effects) -3.66, 95% confidence interval (CI) -5.82 to -2.05; six studies; N = 1819, moderate quality evidence) - a modest difference. Aripiprazole was compared with other drug treatments in three studies in adults-lithium was used in one study and haloperidol in two studies. No statistically significant differences between aripiprazole and other drug treatments in reducing manic symptoms were noted at three weeks (YMRS MD at three weeks (random effects) 0.07, 95% CI -1.24 to 1.37; three studies; N = 972, moderate quality evidence) or at any other time point up to and including 12 weeks. Compared with placebo, aripiprazole caused more movement disorders, as measured on the Simpson Angus Scale (SAS), on the Barnes Akathisia Scale (BAS) and by participant-reported akathisia (high quality evidence), with more people requiring treatment with anticholinergic medication (risk ratios (random effects) 3.28, 95% CI 1.82 to 5.91; two studies; N = 730, high quality evidence). Aripiprazole also led to more gastrointestinal disturbances (nausea (high quality evidence), and constipation) and caused more children/adolescents to have a prolactin level that fell below the lower limit of normal. Significant heterogeneity was present in the meta-analysis of movement disorders associated with aripiprazole and other treatments and was most likely due to the different side effect profiles of lithium and haloperidol. At the three-week time point, meta-analysis was not possible because of lack of data; however, at 12 weeks, haloperidol resulted in significantly more movement disorders than aripiprazole, as measured on the SAS, the BAS and the Abnormal Involuntary Movement Scale (AIMS) and by participant-reported akathisia. By 12 weeks, investigators reported no difference between aripiprazole and lithium (SAS, BAS, AIMS), except in terms of participant-reported akathisia (RR 2.97, 95% CI 1.37 to 6.43; one study; N = 313). AUTHORS' CONCLUSIONS: Aripiprazole is an effective treatment for mania in a population that includes adults, children and adolescents, although its use leads to gastrointestinal disturbances and movement disorders. Comparative trials with medicines other than haloperidol and lithium are few, so the precise place of aripiprazole in therapy remains unclear.

Strategies for managing sexual dysfunction induced by antidepressant medication.

BACKGROUND: Sexual dysfunction (including altered sexual desire, orgasmic and ejaculatory dysfunction, erectile and other problems) is a relatively common side effect of antidepressant medication. These sexual side effects may compromise a person's lifestyle and result in a lack of compliance with the prescribed antidepressant to the detriment of the person's mental health. A wide range of management strategies are possible to address this problem, including behavioural, psychological and pharmacological approaches. OBJECTIVES: 1. To determine the effectiveness of management strategies for sexual dysfunction caused by antidepressants.2. To determine the adverse effects and acceptability of the different management strategies. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialized Register (CCDANCTR, to 1 January 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). Additional searches were carried out by the author team on the same biomedical databases (using terms for 'sexual dysfunction' only) together with CINAHL (1982 to Jan 2012). The reference lists of reports of all included studies were screened. SELECTION CRITERIA: We included randomised controlled trials that compared management strategies for antidepressant-induced sexual dysfunction versus placebo or any alternative strategy. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Study authors were contacted for additional information. MAIN RESULTS: We included 23 trials involving 1886 people in this updated review. Twenty-two of these trials investigated the addition of medication to treat the identified dysfunction, with most agents studied in only single studies. One study investigated switching to an alternative antidepressant.In men, data for the phosphodiesterase inhibitors sildenafil (three studies, 255 participants) and tadalafil (one study, 54 participants) indicated they led to a greater improvement in erectile function than placebo. Combined data from three sildenafil studies found benefit over placebo on International Index of Erectile Function ratings of ability to achieve (MD 1.04, 95% CI 0.65 to 1.44), and maintain erections (MD 1.18, 95% CI 0.78 to 1.59). A single point improvement on these ratings is equivalent to an improvement in frequency from 'sometimes' to 'most times'. Men receiving tadalafil were more likely to report improved erectile function (RR 11.50, 95% CI 3.03 to 43.67). For women it remains uncertain whether sildenafil is more effective than placebo. Unpublished data could reduce this uncertainty.Data from three studies in men and women of bupropion 150 mg twice daily indicate a benefit over placebo on rating scale scores (SMD 1.60, 95% CI 1.40 to 1.81), but response rates in two studies of bupropion 150 mg once daily demonstrated no statistically significant difference in effect (RR 0.62, 95% CI 0.09 to 4.41).Other augmentation strategies failed to demonstrate significant improvements in sexual dysfunction compared with placebo.One trial involving 75 people with sexual dysfunction due to sertraline assessed the effect of changing antidepressant. Switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction than restarting sertraline (RR 0.34, 95% CI 0.19 to 0.60), however, nefazodone is no longer available for clinical use.There is an absence of randomised trials assessing the effects of switching to currently-available antidepressant agents with lower rates of adverse sexual effects, the role of psychological or mechanical interventions, or of techniques such as drug holidays.We identified no data for any of the strategies included in the trials assessed that indicated that they led to a worsening of psychiatric symptoms. However, the relatively small numbers assessed for many of the interventions studied means that the possibility of such an effect cannot confidently be excluded in all cases.Given the small numbers of studies assessing most of the strategies assessed, the presence of any unpublished trials could have substantial effects on estimates of effect. In some cases, only results from particular items or subscales within ratings scales are available. It is likely that this could act to bias estimates of effect obtained, increasing apparent effectiveness. AUTHORS' CONCLUSIONS: The evidence currently available is rather limited. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil or tadalafil appears to be an effective strategy. For women with antidepressant-induced sexual dysfunction the addition of bupropion at higher doses appears to be the most promising approach studied so far.

Quantification of the relative age effect in three indices of physical performance.

The relative age effect (RAE) describes the relationship between an individual's birth month and their level of attainment in sports. There is a clustering of birth dates just after the cutoff used for selection in age-grouped sports, and it is hypothesized that such relatively older sportspeople may enjoy maturational and physical advantages over their younger peers. There is, however, little empirical evidence of any such advantage. This study investigated whether schoolchildren's physical performance differed according to which quarter of the school year they were born in. Mass, stature, body mass index, cardiorespiratory fitness, strength, and power were measured in 10 to 16 year olds (n = 8,550, 53% male). We expressed test performance as age- and sex-specific z-scores based on reference data with age rounded down to the nearest whole year and also as units normalized for body mass. We then compared these values between yearly birth quarters. There were no significant main effects for differences in anthropometric measures in either sex. Girls born in the first quarter of the school year were significantly stronger than those born at other times when handgrip was expressed as a z-score. As z-scores, all measures were significantly higher in boys born in either the first or second yearly quarters. Relative to body mass, cardiorespiratory fitness was higher in boys born in the first quarter and power was higher in those born in the second quarter. The RAE does not appear to significantly affect girls' performance test scores when they are expressed as z-score or relative to body mass. Boys born in the first and second quarters of the year had a significant physical advantage over their relatively younger peers. These findings have practical bearing if coaches use fitness tests for talent identification and team selection. Categorizing test performance based on rounded down values of whole-year age may disadvantage children born later in the selection year. These relatively younger children may be less to gain selection for teams or training programmes.

Biomechanics of wheelchair turning manoeuvres: novel insights into wheelchair propulsion.

Introduction: Wheelchair turning biomechanics is an under researched area despite its obvious relevance to functional mobility of wheelchair users. Wheelchair turns might be linked to a higher risk of upper limb injuries due to the increased forces and torques potentially associated with asymmetric movement. Our aim was to obtain a better theoretical understanding of wheelchair turning by biomechanically analyzing turns compared to steady-state straightforward propulsion (SSSFP). Methods: Ten able-bodied men received 12-min familiarization and 10 trials (in a random order) of SSSFP and multiple left and right turns around a rectangular course. A Smartwheel was mounted at the right wheel of a standard wheelchair to measure kinetic parameters during SSSFP and of the inner hand during right turns and the outer hand during left turns. A repeated measures ANOVA was used to detect differences across tasks. Results: Two strategies were identified: 3% demonstrated roll turns and 97% spin turns. Spin turns consisted of three phases: approach, turning and depart phase. The turning phase was accomplished by increasing peak force (72.9 ± 25.1 N vs. 43.38 ± 15.9 N in SSSFP) of the inner hand, while maintaining high push frequency of the outer hand (1.09 ± 0.20 push/s vs. 0.95 ± 0.13 push/s in SSSFP). Peak negative force and force impulse during the turning phase were much higher than SSSFP, 15.3 ± 15.7 and 4.5 ± 1.7 times higher, respectively. Conclusion: The spin turn strategy might carry an increased risk of upper limb injuries due to higher braking force and requires particular attention by rehabilitation professionals to preserve upper limb function of long-term wheelchair users.

Early increase in marker of neuronal integrity with antidepressant treatment of major depression: 1H-magnetic resonance spectroscopy of N-acetyl-aspartate.

Increasing interest surrounds potential neuroprotective or neurotrophic actions of antidepressants. While growing evidence points to important early clinical and neuropsychological effects of antidepressants, the time-course of any effect on neuronal integrity is unclear. This study used magnetic resonance spectroscopy to assess effects of short-term treatment with escitalopram on N-acetyl-aspartate (NAA), a marker of neuronal integrity. Thirty-nine participants with major depression were randomly assigned to receive either 10 mg escitalopram or placebo daily in a double-blind, parallel group design. On the seventh day of treatment, PRESS data were obtained from a 30×30×20 mm voxel placed in medial frontal cortex. Age and gender-matched healthy controls who received no treatment were also scanned. Levels of NAA were significantly higher in patients treated with escitalopram than in either placebo-treated patients (p<0.01) or healthy controls (p<0.01). Our findings are consistent with the proposition that antidepressant treatment in depressed patients can produce early changes in neuronal integrity.

Multidimensional self-esteem as a mediator of the relationship between sports participation and victimization: a study of African American girls.

The purpose of this study that focused on African American high school girls was threefold. First, the relationship of sports participation and victimization was explored. Second, the impact of sports participation on self-esteem was assessed. Third, the role of self-esteem and its disaggregated components (social acceptance, competence, and self-confidence) as mediators of the relationship between sports participation and victimization was examined. In accordance with the sport protection hypothesis, it was hypothesized that sports participation would be related to enhanced self-esteem and reduce victimization. Results suggest that sports participation appears to have some relationship to lower rates of victimization. There was also support for our assertion that sports participation was related to enhanced self-esteem. Finally, overall self-esteem and, specifically, the individual component competence mediated the relationship between sports participation and victimization.

Perceptions of family caring and its impact on peer associations and drug involvement among rural dwelling African American and White adolescents.

The purpose of this study was to investigate the premise that adolescent perceptions of family caring are a precipitating source of substance use deterrence. More specifically, this study examined the role of family caring on communication of substance use harm and sanctions of use and the effect of these on peer substance involvement and individual use outcomes. A sample of rural dwelling African American and White 7th and 8th grade students (N = 1780) was assessed through self-report. It was anticipated that family caring would be positively related to harm communication and sanctions of use, and that these would be negatively related to peer substance involvement and individual use. Results suggest that family caring was positively linked to harm communication and sanctions of use, and that these were both negatively related to peer substance involvement and individual use. Several significant race differences were noted, which suggest differential associations between some variables. Results are discussed in terms of these race differences, as well as in terms of rural residency.

An estrogen-sensitive fibroblast population drives abdominal muscle fibrosis in an inguinal hernia mouse model.

Greater than 25% of all men develop an inguinal hernia in their lifetime, and more than 20 million inguinal hernia repair surgeries are performed worldwide each year. The mechanisms causing abdominal muscle weakness, the formation of inguinal hernias, or their recurrence are largely unknown. We previously reported that excessively produced estrogen in the lower abdominal muscles (LAMs) triggers extensive LAM fibrosis, leading to hernia formation in a transgenic male mouse model expressing the human aromatase gene (Aromhum). To understand the cellular basis of estrogen-driven muscle fibrosis, we performed single-cell RNA sequencing on LAM tissue from Aromhum and wild-type littermates. We found a fibroblast-like cell group composed of 6 clusters, 2 of which were validated for their enrichment in Aromhum LAM tissue. One of the potentially novel hernia-associated fibroblast clusters in Aromhum was enriched for the estrogen receptor-α gene (Esr1hi). Esr1hi fibroblasts maximally expressed estrogen target genes and seemed to serve as the progenitors of another cluster expressing ECM-altering enzymes (Mmp3hi) and to upregulate expression of proinflammatory, profibrotic genes. The discovery of these 2 potentially novel and unique hernia-associated fibroblasts may lead to the development of novel treatments that can nonsurgically prevent or reverse inguinal hernias.

Inhibition of Chk2 promotes neuroprotection, axon regeneration, and functional recovery after CNS injury.

DNA double-strand breaks occur in many acute and long-term neurological conditions, including neurodegeneration, neurotrauma, and stroke. Nonrepaired breaks chronically activate the DNA damage response in neurons, leading to neural dysfunction and apoptosis. Here, we show that targeting of the central ATM-Chk2 pathway regulating the response to double-strand breaks slows neural decline in Drosophila models of chronic neurodegeneration. Inhibitors of ATM-Chk2, but not the parallel ATR-Chk1 pathway, also promote marked, functional recovery after acute central nervous system injury in rats, suggesting that inhibiting nonhomologous end-joining rather than homologous recombination is crucial for neuroprotection. We demonstrate that the Chk2 inhibitor, prexasertib, which has been evaluated in phase 2 clinical trials for cancer, has potent neuroprotective effects and represents a new treatment option to promote functional recovery after spinal cord or optic nerve injury.

Elevated cortical glutamate in young people at increased familial risk of depression.

Using proton magnetic resonance spectroscopy (MRS), we have demonstrated regional abnormalities in cortical γ-aminobutyric acid (GABA) and glutamate in medication-free recovered depressed patients. It is unclear whether these changes represent an underlying trait vulnerability to depression, or an after-effect of episodes of illness or its treatment. We sought to examine this question by examining a group of high-risk, never-depressed, individuals. We used MRS to measure GABA and glutamate in parieto-occipital cortex in young people (ages 16-21 yr) with a family history of parental depression (n=24) but no personal history of illness and a control group without a history of depression in any first-degree relative (n=28). Participants with a parental history of depression had significantly higher levels of glutamate than controls in parieto-occipital cortex (F1,47=5.5, p=0.02). These findings suggest that abnormalities in glutamate neurotransmission may reflect a trait marker of vulnerability to depression.

Retrospective Safety Evaluation of a Pharmacist-Assisted Total Dose Iron Sucrose Protocol in Hospital Inpatients With Iron Deficiency Anemia.

BACKGROUND: Intravenous (IV) iron sucrose can be used for iron deficiency anemia (IDA), but little information exists on total dose infusion (TDI) of this drug. At a tertiary hospital, an iron sucrose TDI protocol was implemented with staff pharmacists aiding physicians in appropriate dosing. OBJECTIVES: We sought to define the safety and efficacy of this protocol in adults ≥18 years old with IDA. METHODS: We conducted a retrospective chart review of patients who received iron sucrose TDI. Inclusion criteria included patients ≥18 years old who were hospitalized and received iron sucrose in doses ≥300 mg. We reviewed the medical record for adverse reactions to any TDI of iron sucrose as well as pre-TDI and post-TDI hemoglobin (Hgb) levels to assess efficacy. RESULTS: A total of 238 patients received iron sucrose TDI for IDA during the study period. One hundred ninety-three (81%) patients were female, and the mean age in our cohort was 60.6 years. Mean pre-TDI Hgb was 8.76 g/dL. The mean total dose of iron sucrose in the total cohort was 680 mg (range: 300-2500 mg). Adverse effects attributable to iron sucrose were reported in 15 patients, with nausea being the most common effect (7/238, 2.9%). When matching patients' preadmission and postadmission records, a Hgb increase of 2.1 g/L was found (P < .001). No increase in liver function tests was found in any patient. CONCLUSIONS: A pharmacist-assisted iron sucrose TDI protocol for patients with IDA successfully increased serum Hgb and was well tolerated. Anaphylaxis was not reported.