A Pilot Survey Study of Anterior Cruciate Ligament Injuries in Female University Athletes.

Introduction Female sports players are at increased risk of soft tissue knee injuries (STKIs) compared to their male counterparts. Injury prevention programs effectively reduce the incidence of anterior cruciate ligament (ACL) knee injuries. This pilot study, therefore, aimed to examine the prevalence, type, and management of STKIs within a population of female university sports players at the University of Cambridge. Additionally, this study aimed to examine the perceived risk of ACL injuries and knowledge of long-term complications, alongside participation and attitudes towards injury prevention programs. Methodology A survey was distributed to women's university sports teams at the University of Cambridge. Information was gathered on participant demographics and sporting history. Relevant medical history, including joint laxity, connective tissue disorders, and previous knee injuries, was also collected. Participant involvement in and attitudes towards injury prevention programs were evaluated. Results Data from eighty-five participants (n = 85) were collected, all of whom were female. Forty-two percent of participants had sustained a previous knee injury, of which the majority (44%) were ACL injuries. In the ACL-injured group, 38% (n=6) had undergone ACL reconstructive surgery, 44% (n=7) had received only physiotherapy, and 19% (n=3) had received no form of treatment. Only 44% of these participants sustaining an ACL injury reported a return to the same level of post-injury sport. Seventy-two percent of respondents felt they were at increased risk of ACL injury compared to males. Most participants (87%) did not follow an injury prevention program, but 95% expressed a willingness to enroll in one. Conclusions This pilot study indicates that most knee injuries in female university athletes in this cohort at Cambridge University are ACL injuries, with a considerable number being managed conservatively. The low rate of return to pre-injury sporting levels highlights the significant impact of ACL injuries on athletic careers. This study demonstrates results similar to previous studies on the broader population. However, due to the pilot nature of the research and limited statistical power, the results should be interpreted with caution before transposing to the wider population. Further investigation is required into why many of these ACL-injured female athletes were managed conservatively and whether this finding is mirrored in their male counterparts. Despite recognizing their higher risk than males, participants displayed low engagement in injury prevention programs, indicating a gap between awareness and action. The willingness to participate in prevention programs suggests the potential for improved engagement through targeted interventions. Future research should focus on identifying and addressing specific barriers to participation in injury prevention programs and exploring the reasons behind the preference for conservative management of ACL injuries. Additionally, expanding the sample size and including a more diverse athletic population would enhance the generalizability of the findings.

MicroCycle: An Integrated and Automated Platform to Accelerate Drug Discovery.

We herein describe the development and application of a modular technology platform which incorporates recent advances in plate-based microscale chemistry, automated purification, in situ quantification, and robotic liquid handling to enable rapid access to high-quality chemical matter already formatted for assays. In using microscale chemistry and thus consuming minimal chemical matter, the platform is not only efficient but also follows green chemistry principles. By reorienting existing high-throughput assay technology, the platform can generate a full package of relevant data on each set of compounds in every learning cycle. The multiparameter exploration of chemical and property space is hereby driven by active learning models. The enhanced compound optimization process is generating knowledge for drug discovery projects in a time frame never before possible.

Mental health, study skills, social support, and barriers to seeking psychological help among university students: a call for mental health support in higher education.

Introduction: Poor mental health among youths is a complex worldwide issue. Many countries with medium-to-low levels of development, particularly those in Southern Europe, have not introduced appropriate mental health and educational strategies to identify the key factors influencing wellbeing, promote psychological wellbeing, and prevent poor mental health among youths. In response to these trends, we sought to uncover insights for developing interventions for youth mental wellbeing. We assessed mental health, study skills, barriers to seeking psychological help, and perceived social support among Kosovar university students, and investigated their experiences with professional mental health services and their needs and perceptions regarding the importance of professional mental health services on campus. Methods: The study used a parallel mixed-methods design. Participants included 234 university students. Quantitative data were gathered through validated questionnaires, including the Depression, Anxiety, and Stress Scale, Multidimensional Scale of Perceived Social Support, Academic Anxiety Scale, Study Skills Assessment Questionnaire, and the Barriers to Seeking Psychological Help Scale. Qualitative data on the students' experiences with mental health services and their perceptions regarding the importance of professional university mental health services were explored through open-ended questions. Results: Most students experienced anxiety and depression, more than half were stressed, and most reported poor or moderate study skills. Lack of trust in mental health professionals was a major barrier to seeking psychological help, followed by difficulties in self-disclosure. Perceived social support and academic anxiety were significant predictors of barriers to seeking psychological help. The participants believed that mental health and academic support from the university would help improve their mental wellbeing, study skills, self-esteem, self-perception, and attitudes toward social support; raise awareness regarding mental health; and help them overcome personal and academic challenges. Discussion: Our findings highlight the need for more comprehensive and accessible mental health services on campuses. By providing adequate support and resources to address various personal and academic factors that contribute to mental health issues in university students, universities can enhance students' academic success and personal growth.

The relationship between clients' expectation of therapist support and challenge and treatment outcome: A response surface analysis.

Clients' expectations of treatment have long been posited as an important therapeutic factor in treatment success. Decades of research and meta-analytic findings have supported the notion that client expectations about what will happen over the course of therapy and how beneficial therapy will be are directly related to treatment factors, such as the working alliance and treatment outcome. Client expectations can be categorized into two broad categories, outcome expectations (i.e., how beneficial treatment will be) and treatment expectations (i.e., what will happen in treatment). This study sought to examine clients' treatment expectations, specifically, their role expectations, which represent their beliefs of how their therapists will act in session. Data for this study included 1,233 clients participating in individual counseling with 49 therapists at a university counseling center. Multilevel polynomial regression and response surface analysis were used to test congruent and discrepant effects of clients' pretreatment support and challenge expectancy on reductions in their psychological distress over the course of treatment. Results indicated that reductions in clients' psychological distress were the greatest when their support and challenge expectancy scores were congruent and high. In other words, clients who expected both high challenge and high support from their therapist, prior to the start of counseling, reported the greatest improvement in counseling. Clients similarly reported reductions in their psychological distress when their support and challenge expectations were congruent and low, although this effect was smaller than when they expected high levels of both support and challenge. Together, these findings suggest that when clients' expectations of support and challenge are similar, they fare better in treatment, as opposed to when they expect a greater amount of support than challenge or vice versa. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Family child care home providers' self-reported nutrition and physical activity practices, self-efficacy, barriers and knowledge: baseline findings from happy healthy homes.

OBJECTIVE: Describe nutrition and physical activity practices, nutrition self-efficacy and barriers and food programme knowledge within Family Child Care Homes (FCCH) and differences by staffing. DESIGN: Baseline, cross-sectional analyses of the Happy Healthy Homes randomised trial (NCT03560050). SETTING: FCCH in Oklahoma, USA. PARTICIPANTS: FCCH providers (n 49, 100 % women, 30·6 % Non-Hispanic Black, 2·0 % Hispanic, 4·1 % American Indian/Alaska Native, 51·0 % Non-Hispanic white, 44·2 ± 14·2 years of age. 53·1 % had additional staff) self-reported nutrition and physical activity practices and policies, nutrition self-efficacy and barriers and food programme knowledge. Differences between providers with and without additional staff were adjusted for multiple comparisons (P < 0·01). RESULTS: The prevalence of meeting all nutrition and physical activity best practices ranged from 0·0-43·8 % to 4·1-16·7 %, respectively. Average nutrition and physical activity scores were 3·2 ± 0·3 and 3·0 ± 0·5 (max 4·0), respectively. Sum nutrition and physical activity scores were 137·5 ± 12·6 (max 172·0) and 48·4 ± 7·5 (max 64·0), respectively. Providers reported high nutrition self-efficacy and few barriers. The majority of providers (73·9-84·7 %) felt that they could meet food programme best practices; however, knowledge of food programme best practices was lower than anticipated (median 63-67 % accuracy). More providers with additional staff had higher self-efficacy in family-style meal service than did those who did not (P = 0·006). CONCLUSIONS: Providers had high self-efficacy in meeting nutrition best practices and reported few barriers. While providers were successfully meeting some individual best practices, few met all. Few differences were observed between FCCH providers with and without additional staff. FCCH providers need additional nutrition training on implementation of best practices.

A call for evidence to support food security interventions on college campuses.

Food insecurity negatively impacts collegiate academic performance, mental and social health and overall health status. However, nothing is known on the effectiveness of evidence-based programs to address food insecurity in college students. Opportunity remains to conduct intervention-specific research targeted at reduction food insecurity prevalence on college campuses.

Effect of sports massage on performance and recovery: a systematic review and meta-analysis.

OBJECTIVE: Massage is ubiquitous in elite sport and increasingly common at amateur level but the evidence base for this intervention has not been reviewed systematically. We therefore performed a systematic review and meta-analysis examining the effect of massage on measures of sporting performance and recovery. DESIGN AND ELIGIBILITY: We searched PubMed, MEDLINE and Cochrane to identify randomised studies that tested the effect of manual massage on measures of sporting performance and/or recovery. We performed separate meta-analyses on the endpoints of; strength, jump, sprint, endurance, flexibility, fatigue and delayed onset muscle soreness (DOMS). RESULTS: We identified 29 eligible studies recruiting 1012 participants, representing the largest examination of the effects of massage. We found no evidence that massage improves measures of strength, jump, sprint, endurance or fatigue, but massage was associated with small but statistically significant improvements in flexibility and DOMS. CONCLUSION: Although our study finds no evidence that sports massage improves performance directly, it may somewhat improve flexibility and DOMS. Our findings help guide the coach and athlete about the benefits of massage and inform decisions about incorporating this into training and competition.

A Visible-Light Promoted Amine Oxidation Catalyzed by a Cp*Ir Complex.

Through a rapid screening of Cp*Ir complexes based on a turn-on type fluorescence readout, a [Cp*Ir(dipyrido[3,2-a : 2',3'-c]phenazine)Cl]+ complex was found to catalyze the blue-light promoted dehydrogenation of N-heterocycles under physiological conditions. In the dehydrogenation of tetrahydroisoquinolines, the catalyst preferentially yielded the monodehydrogenated product, accompanying H2O2 generation. We surmise that this mechanism may be reminiscent of flavin-dependent oxidases.

Artificial Metalloenzymes: Challenges and Opportunities.

Artificial metalloenzymes (ArMs) result from the incorporation of an abiotic metal cofactor within a protein scaffold. From the earliest techniques of transition metals adsorbed on silk fibers, the field of ArMs has expanded dramatically over the past 60 years to encompass a range of reaction classes and inspired approaches: Assembly of the ArMs has taken multiple forms with both covalent and supramolecular anchoring strategies, while the scaffolds have been intuitively selected and evolved, repurposed, or designed in silico. Herein, we discuss some of the most prominent recent examples of ArMs to highlight the challenges and opportunities presented by the field.

Catalytic enantioselective Minisci-type addition to heteroarenes.

Basic heteroarenes are a ubiquitous feature of pharmaceuticals and bioactive molecules, and Minisci-type additions of radical nucleophiles are a leading method for their elaboration. Despite many Minisci-type protocols that result in the formation of stereocenters, exerting control over the absolute stereochemistry at these centers remains an unmet challenge. We report a process for addition of prochiral radicals, generated from amino acid derivatives, to pyridines and quinolines. Our method offers excellent control of both enantioselectivity and regioselectivity. An enantiopure chiral Brønsted acid catalyst serves both to activate the substrate and induce asymmetry, while an iridium photocatalyst mediates the required electron transfer processes. We anticipate that this method will expedite access to enantioenriched small-molecule building blocks bearing versatile basic heterocycles.

Halofuginone inhibits TGF-ß/BMP signaling and in combination with zoledronic acid enhances inhibition of breast cancer bone metastasis.

More efficient therapies that target multiple molecular mechanisms are needed for the treatment of incurable bone metastases. Halofuginone is a plant alkaloid-derivative with antiangiogenic and antiproliferative effects. Here we demonstrate that halofuginone is an effective therapy for the treatment of bone metastases, through multiple actions that include inhibition of TGFß and BMP-signaling. Halofuginone blocked TGF-ß-signaling in MDA-MB-231 and PC3 cells showed by inhibition of TGF-ß-induced Smad-reporter, phosphorylation of Smad-proteins, and expression of TGF-ß-regulated metastatic genes. Halofuginone increased inhibitory Smad7-mRNA and reduced TGF-ß-receptor II protein. Proline supplementation but not Smad7-knockdown reversed halofuginone-inhibition of TGF-ß-signaling. Halofuginone also decreased BMP-signaling. Treatment of MDA-MB-231 and PC3 cells with halofuginone reduced the BMP-Smad-reporter (BRE)4, Smad1/5/8-phosphorylation and mRNA of the BMP-regulated gene Id-1. Halofuginone decreased immunostaining of phospho-Smad2/3 and phospho-Smad1/5/8 in cancer cells in vivo. Furthermore, halofuginone decreased tumor-take and growth of orthotopic-tumors. Mice with breast or prostate bone metastases treated with halofuginone had significantly less osteolysis than control mice. Combined treatment with halofuginone and zoledronic-acid significantly reduced osteolytic area more than either treatment alone. Thus, halofuginone reduces breast and prostate cancer bone metastases in mice and combined with treatment currently approved by the FDA is an effective treatment for this devastating complication of breast and prostate-cancer.

meta-Selective C-H Borylation of Benzylamine-, Phenethylamine-, and Phenylpropylamine-Derived Amides Enabled by a Single Anionic Ligand.

Selective functionalization at the meta position of arenes remains a significant challenge. In this work, we demonstrate that a single anionic bipyridine ligand bearing a remote sulfonate group enables selective iridium-catalyzed borylation of a range of common amine-containing aromatic molecules at the arene meta position. We propose that this selectivity is the result of a key hydrogen bonding interaction between the substrate and catalyst. The scope of this meta-selective borylation is demonstrated on amides derived from benzylamines, phenethylamines and phenylpropylamines; amine-containing building blocks of great utility in many applications.

Harnessing non-covalent interactions to exert control over regioselectivity and site-selectivity in catalytic reactions.

Asymmetric catalysis has been revolutionised by the realisation that attractive non-covalent interactions such as hydrogen bonds and ion pairs can act as powerful controllers of enantioselectivity when incorporated into appropriate small molecule chiral scaffolds. Given these tremendous advances it is surprising that there are still a relatively limited number of examples of non-covalent interactions being harnessed for control of regioselectivity or site-selectivity in catalysis, two other fundamental selectivity aspects facing the synthetic chemist. This perspective examines the progress that has been made in this area thus far using non-covalent interactions in conjunction with transition metal catalysis as well as in the context of purely organic catalysts. We hope this will highlight the great potential in this approach for designing selective catalytic reactions.

Ion Pair-Directed Regiocontrol in Transition-Metal Catalysis: A Meta-Selective C-H Borylation of Aromatic Quaternary Ammonium Salts.

The use of noncovalent interactions to direct transition-metal catalysis is a potentially powerful yet relatively underexplored strategy, with most investigations thus far focusing on using hydrogen bonds as the controlling element. We have developed an ion pair-directed approach to controlling regioselectivity in the iridium-catalyzed borylation of two classes of aromatic quaternary ammonium salts, leading to versatile meta-borylated products. By examining a range of substituted substrates, this provides complex, functionalized aromatic scaffolds amenable to rapid diversification and more broadly demonstrates the viability of ion-pairing for control of regiochemistry in transition-metal catalysis.

Substrate Fragmentation for the Design of M.†tuberculosis CYP121 Inhibitors.

The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors' binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121-ligand recognition and speculation into the biological role of the enzyme for Mtb.

Spirooxindoles as novel 3D-fragment scaffolds: Synthesis and screening against CYP121 from M. tuberculosis.

The search for new scaffolds to complement current HTS and fragment libraries is an active area of research. The development of novel strategies to synthesise compounds with 3D character in order to expand the diversity of a fragment library was explored. A range of substituted bicyclo[2,2,1]spirooxindoles were synthesised using a Diels-Alder [4+2] cycloaddition reaction. Both diastereoisomers were isolated from the reactions and these 3D fragment scaffolds were screened against the cytochrome P450 enzyme CYP121 from Mycobacterium tuberculosis. A number of hits were identified to bind to CYP121 and were shown to exhibit Type I binding interactions with the heme group.

Tumor-expressed adrenomedullin accelerates breast cancer bone metastasis.

INTRODUCTION: Adrenomedullin (AM) is secreted by breast cancer cells and increased by hypoxia. It is a multifunctional peptide that stimulates angiogenesis and proliferation. The peptide is also a potent paracrine stimulator of osteoblasts and bone formation, suggesting a role in skeletal metastases-a major site of treatment-refractory tumor growth in patients with advanced disease. METHODS: The role of adrenomedullin in bone metastases was tested by stable overexpression in MDA-MB-231 breast cancer cells, which cause osteolytic bone metastases in a standard animal model. Cells with fivefold increased expression of AM were characterized in vitro, inoculated into immunodeficient mice and compared for their ability to form bone metastases versus control subclones. Bone destruction was monitored by X-ray, and tumor burden and osteoclast numbers were determined by quantitative histomorphometry. The effects of AM overexpression on tumor growth and angiogenesis in the mammary fat pad were determined. The effects of AM peptide on osteoclast-like multinucleated cell formation were tested in vitro. A small-molecule AM antagonist was tested for its effects on AM-stimulated ex vivo bone cell cultures and co-cultures with tumor cells, where responses of tumor and bone were distinguished by species-specific real-time PCR. RESULTS: Overexpression of AM mRNA did not alter cell proliferation in vitro, expression of tumor-secreted factors or cell cycle progression. AM-overexpressing cells caused osteolytic bone metastases to develop more rapidly, which was accompanied by decreased survival. In the mammary fat pad, tumors grew more rapidly with unchanged blood vessel formation. Tumor growth in the bone was also more rapid, and osteoclasts were increased. AM peptide potently stimulated bone cultures ex vivo; responses that were blocked by small-molecule adrenomedullin antagonists in the absence of cellular toxicity. Antagonist treatment dramatically suppressed tumor growth in bone and decreased markers of osteoclast activity. CONCLUSIONS: The results identify AM as a target for therapeutic intervention against bone metastases. Adrenomedullin potentiates osteolytic responses in bone to metastatic breast cancer cells. Small-molecule antagonists can effectively block bone-mediated responses to tumor-secreted adrenomedullin, and such agents warrant development for testing in vivo.

Molecular markers for species identification of Hessian fly males caught on sticky pheromone traps.

Pheromone traps have been widely used to monitor insect population activity. However, sticky pheromone traps for the Hessian fly (Mayetiola destructor), one of the most destructive pests of wheat, have been used only in recent years. Hessian fly male adults are small and fragile, and preserving specimens during sorting of sticky pheromone traps is a challenge when intact specimens are often required to visually distinguish them from related insects such as fungus gnats. In this study, we have established a quick and reliable method based on polymerase chain reaction markers to correctly distinguish Hessian fly males from other closely related insects. Two Hessian fly-specific markers were established, one based on the trypsin gene MDP-10 and the other based on a gene encoding the salivary gland protein SSGP31-5. Both markers provided > 98% identification success of 110 Hessian fly samples prepared from single insects. The method should provide a useful tool to allow for identification of Hessian fly individuals on sticky pheromone traps or in other situations when Hessian fly eggs, larvae, pupae, and adults are difficult to distinguish from other insects.