Observation of exceptionally strong near-bottom flows over the Atlantis II Seamounts in the northwest Atlantic.

Knowledge of near-bottom ocean current velocities and especially their extreme values is necessary to understand geomorphology of the seafloor and composition of benthic biological communities and quantify mechanical energy dissipation by bottom drag. Direct measurements of near-bottom currents in deep ocean remain scarce because of logistical challenges. Here, we report the results of flow velocity and pressure fluctuation measurements at three sites with depths of 2573-4443 m in the area where the Gulf Stream interacts with the New England Seamounts. Repeated episodes of unexpectedly strong near-bottom currents were observed, with the current speed at 4443 m of more than 0.40 m/s. At 2573 m, current speeds exceeded 0.20 m/s approximately 5% of the time throughout the entire eight-week measurement period. The maximum flow speeds of over 1.10 m/s recorded at this site significantly surpass the fastest previously reported directly measured current speeds at comparable or larger depths. A strong correlation is found between the noise intensity in the infrasonic band and the measured current speed. The noise intensity and the characteristic frequency increase with the increasing current speed. Machine-learning tools are employed to infer current speeds from flow-noise measurements at the site not equipped with a current meter.

A Multicenter, Randomized, Evaluator-Blinded Study to Examine the Safety and Effectiveness of Hyaluronic Acid Filler in the Correction of Infraorbital Hollows.

BACKGROUND: Hyaluronic acid injections are increasingly used for correction of infraorbital hollows (IOHs). OBJECTIVES: Examination of effectiveness (IOH correction) and safety of Restylane® EyelightTM hyaluronic acid (HAEYE, Galderma, Uppsala, Sweden) injections. METHODS: Subjects with moderate/severe IOHs, assessed using the Galderma infraorbital hollows scale (GIHS), were randomized to HAEYE injections (via needle/cannula) (Day 1+optional Month-1 touch up) or no-treatment control. Primary endpoint was blinded evaluator-reported Month-3 response, defined as ≥1-point GIHS improvement from baseline (both sides, concurrently). Other endpoints examined investigator-reported aesthetic improvement (GAIS), subject-reported satisfaction (FACE-Q™ satisfaction with outcome; satisfaction questionnaire), and adverse events. RESULTS: Overall, 333 subjects were randomized. Month 3 GIHS responder rate was significantly higher with HA-EYE (87.4%) versus control (17.7%; p<0.001), and comparable between HA-EYE-needle and HA-EYE-cannula groups (p=0.967). HAEYE GAIS responder rate was 87.5-97.7% (Months 3-12). Mean FACE-Q Rasch-transformed scores were 64.3-73.5 (HAEYE) versus 14.1-16.2 (control) through Month 12. Subjects reported looking younger (≥71%) and less tired (≥79%) with reduced under-eye shadows (≥76%) and recovered within 3-5 hours, post-treatment. Efficacy was maintained through Month 12 (63.5% GIHS responders) and through Month 18, after Month-12 retreatment (80.3% GIHS responders; 99.4% GAIS responders; FACE-Q scores: 72.5-72.8). Forty subjects (12.7%) reported typically mild adverse events (4.9% HAEYE-needle; 20.9% HAEYE-cannula). CONCLUSION: HAEYE treatment was effective in correcting moderate/severe IOHs at the primary endpoint (Month 3). Efficacy was sustained through Month 12 after first treatment for 63.5% and through Month 18 for 80.3% (after one retreatment) with needle or cannula administration. Safety outcomes were reassuring.

Understanding vessel noise across a network of marine protected areas.

Protected areas are typically managed as a network of sites exposed to varying anthropogenic conditions. Managing these networks benefits from monitoring of conditions across sites to help prioritize coordinated efforts. Monitoring marine vessel activity and related underwater radiated noise impacts across a network of protected areas, like the U.S. National Marine Sanctuary system, helps managers ensure the quality of habitats used by a wide range of marine species. Here, we use underwater acoustic detections of vessels to quantify different characteristics of vessel noise at 25 locations within eight marine sanctuaries including the Hawaiian Archipelago and the U.S. east and west coasts. Vessel noise metrics, including temporal presence and sound levels, were paired with Automatic Identification System (AIS) vessel tracking data to derive a suite of robust vessel noise indicators for use across the network of marine protected areas. Network-wide comparisons revealed a spectrum of vessel noise conditions that closely matched AIS vessel traffic composition. Shifts in vessel noise were correlated with the decrease in vessel activity early in the COVID-19 pandemic, and vessel speed reduction management initiatives. Improving our understanding of vessel noise conditions in these protected areas can help direct opportunities for reducing vessel noise, such as establishing and maintaining noise-free periods, enhancing port efficiency, engaging with regional and international vessel quieting initiatives, and leveraging co-benefits of management actions for reducing ocean noise.

Passive sea ice thickness inference using cryophones.

Mechanical properties of Arctic sea ice can be inferred by observations of in-ice propagation of compressional, shear, and flexural waves. During the 1980s, impulsive signals were generated by a lead ball or sledgehammer dropped onto the sea ice, and the inference required observation of wave speeds. During ICEX20 and ARCEX23, passive cryophone observations were made of naturally occurring compressional wave resonances. Average first-year ice thicknesses during ICEX20 and ARCEX23 were inferred to be 1.3 and 1.6 m, respectively; these are consistent with independent observations and indicate the potential for remote, autonomous monitoring of sea ice thickness.

Safety and Duration of Effect of 40U PrabotulinumtoxinA-xvfs for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients: A Phase II, Multi-Center, Randomized, Double Blind, Active-Controlled Trial.

BACKGROUND: Extending the duration of effect of botulinum toxins - by administering doses beyond those of the approved labels - has been an area of increasing interest in the field of aesthetics. OBJECTIVES: To investigate the safety and duration of effect of 40U prabotulinumtoxinA-xvfs (twice the approved dose and concentration) for the treatment of moderate-to-severe glabellar lines. METHODS: 154 adult patients were randomized 1:1:1 to a single treatment of either 40U prabotulinumtoxinA-xvfs (PRA 40, 5 injections of 8U/0.05 mL), or 20U of either prabotulinumtoxinA-xvfs (PRA 20) or onabotulinumtoxinA (ONA 20). Both 20U controls were administered as 5 injections of 4U/0.1 mL. Efficacy and safety were assessed on Days 2, 7 (by phone), 30 and every 30 days thereafter up to 365 days or until the patient had returned to Baseline. The primary effectiveness endpoint was the duration of effect (estimated by Kaplan-Meier analysis), defined as the number of days from Treatment Day (Baseline) to the day that glabellar line severity at maximum frown by investigator assessment returned to the baseline value. RESULTS: Patients had a mean age of 47 years (20-72 years); 69.5% had severe glabellar lines at Baseline. Of the 36 adverse events, 32 (88.9%) were mild and 4 (11.1%) were moderate in severity; none were serious. The median durations of effect were estimated to be 183, 149 and 148 days for PRA 40-, PRA 20- and ONA 20-treated patients, respectively. CONCLUSIONS: In this Phase II pilot study, 40U prabotulinumtoxinA-xvfs was observed to be safe and had a duration of 6 months.

LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials.

BACKGROUND: Hyperfunctional glabellar frown lines can transmit facial miscues that adversely affect emotional communication, increase perceptions of age, and diminish self-esteem. OBJECTIVE: To evaluate the efficacy of letibotulinumtoxinA in mitigating the negative psychological impact associated with moderate to severe glabellar lines and to assess subject satisfaction with treatment outcome in the BLESS phase 3 clinical trials. MATERIALS AND METHODS: Baseline and posttreatment assessments were made using validated subject-administered instruments: Modified Skindex-16 Glabellar Line Quality of Life (GL-QoL) Scale, Facial Assessment and Cosmetic Evaluation Questionnaire (FACE-Q) Appraisal of Lines Between Eyebrows Scale, FACE-Q Age Appraisal Visual Analog Scale, and FACE-Q Satisfaction with Outcome Scale. An integrated analysis using pooled BLESS data was conducted on these secondary end points. RESULTS: Among enrolled and treated subjects (N = 1,272), 85.5% had moderate to severe psychological impact at baseline. LetibotulinumtoxinA subjects experienced significant improvements compared with placebo on all measures. Mean improvement to Week 4 for the Modified Skindex-16 GL-QoL Scale overall score was -33.84 for letibotulinumtoxinA subjects compared with -1.37 for placebo subjects (p < .001). Attenuation of psychological burden was highly correlated with improvement in glabellar line severity (p < .0001). CONCLUSION: LetibotulinumtoxinA significantly improved the psychosocial burden associated with glabellar lines across all trials. Treated subjects experienced improved quality of life, younger perceived age, and satisfaction with treatment outcome.

A Two-Stage Injection Technique and Dose-Ranging Study Using High-Dose AbobotulinumtoxinA for Treating Platysmal Bands.

BACKGROUND: AbobotulinumtoxinA (aboBoNT-A) is useful for the treatment of platysmal banding. This study evaluated the efficacy and safety of a standardized 2-staged injection technique using high doses of AboBoNT-A for treating platysmal banding. METHODS: This was a randomized, double-blinded, dose-ranging prospective study. Subjects included adults with moderate-to-severe platysmal bands (grade 3 or 4 on the validated 5-point photographic scale), who received either 120 U (Cohort 1) or 180 U (Cohort 2) of aboBoNT-A, followed by an optional 90 U touch-up. The relatively higher on-label concentration of aboBoNT-A was used (1.5 mL/300 units) to reduce the volume injected and the risk of spread to adjacent muscles. Subjects were followed for 5 months, with safety and efficacy endpoints evaluated by the Investigator Live Assessment (ILA) and Subject Live Assessment (SLA). RESULTS: Twenty women were included in the analysis. Cohort 1 and Cohort 2 had 100% and 90% responder rates (achieved grade 1 or 2) during maximal contraction at month 1 with ILA. Cohort 2 had more subjects with 2 or greater grade improvement at maximal contraction using both ILA and SLA. Cohort 2 also had longer time to loss of grade 1 or 2 at maximal contraction compared with Cohort 1. No major adverse reactions occurred, but 3 subjects experienced transient positional neck weakness. CONCLUSION: We demonstrate a standardized 2-stage injection technique using aboBoNT-A for effectively treating moderate-to-severe platysmal banding. We used relatively higher doses while maintaining a good safety profile by using the more concentrated on-label volume of reconstitution for aboBoNT-A and by including a touch-up. J Drugs Dermatol. 2024;23(1):1311-1318.     doi:10.36849/JDD.7537.

Identification of the main barriers to Ku accumulation in chromatin.

Repair of DNA double strand breaks by the non-homologous end-joining pathway is initiated by the binding of Ku to DNA ends. Given its high affinity for ends, multiple Ku proteins load onto linear DNAs in vitro. However, in cells, Ku loading is limited to ~1-2 molecules per DNA end. The mechanisms enforcing this limit are currently unknown. Here we show that the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), but not its protein kinase activity, is required to prevent excessive Ku entry into chromatin. Ku accumulation is further restricted by two mechanisms: a neddylation/FBXL12-dependent process which actively removes loaded Ku molecules throughout the cell cycle and a CtIP/ATM-dependent mechanism which operates in S-phase. Finally, we demonstrate that the misregulation of Ku loading leads to impaired transcription in the vicinity of DNA ends. Together our data shed light on the multiple layers of coordinated mechanisms operating to prevent Ku from invading chromatin and interfering with other DNA transactions.

Effectiveness and Safety of Sculptra Poly-L-Lactic Acid Injectable Implant in the Correction of Cheek Wrinkles.

BACKGROUND: The current study evaluated the effectiveness and safety of Sculptra injectable poly-L-lactic acid (PLLA-SCA) treatment in correcting cheek wrinkles compared with a no-treatment control. METHODS: Male/female immune-competent adults (aged >21 years) with moderate/severe cheek wrinkles, graded using the Galderma Cheek Wrinkle Scale (GCWS) at rest, were randomized 2:1 to receive PLLA-SCA injections (150 mg; 8 mL reconstitution in sterile water for injection) + 1 mL lidocaine hydrochloride (2%), administered immediately after reconstitution, or no treatment (control). Up to 3 additional treatments were allowed at monthly intervals, and follow-up was at months 7, 9, and 12. The primary endpoint was 1-grade or greater improvement in GCWS at rest for both cheeks at month 12. RESULTS: GCWS at rest responder rate was significantly higher with PLLA-SCA treatment versus the no-treatment control at months 7 (66.2% versus 38.6%; P=0.0043), 9 (70.6% versus 31.1%; P<0.0001), and 12 (71.6% versus 26.1%; P<0.0001). Treating investigators reported improvements in skin radiance (>95%), tighter appearance (>88%), and jawline contour (>85%). PLLA-SCA recipients reported high satisfaction levels regarding improvements in skin radiance (90% or greater), sagging (84% or greater), and firmness (91% or greater) as well as natural-looking results (85% or greater) and a desire for repeat treatment (84% or greater). Treatment-related adverse events were mostly mild in severity with no serious events related to PLLA-SCA injections. CONCLUSION: Injectable PLLA-SCA treatments were well tolerated and significantly reduced the severity of moderate/severe cheek lines and wrinkles, while improving skin quality. Effectiveness was durable over the 12-month study period with high subject-reported satisfaction, natural-looking appearance, and enthusiasm for repeat treatments. CLINICALTRIALS: gov registry number: NCT04124692J Drugs Dermatol. 2024;23(1):1297-1305.        doi:10.36849/JDD.7729.

Assessment of anticancer properties of cumin seed (Cuminum cyminum) against bone cancer.

Introduction: Early-life osteosarcoma is associated with severe morbidity and mortality, particularly affecting young children and adults. The present cancer treatment regimen is exceedingly costly, and medications like ifosfamide, doxorubicin, and cisplatin have unneeded negative effects on the body. With the introduction of hyphenated technology to create medications based on plant molecules, the application of ayurvedic medicine as a new dimension (formulation, active ingredients, and nanoparticles) in the modern period is rapidly growing. The primary source of lead compounds for the development of medications for avariety of ailments is plants and their products. Traditionally, Cuminum cyminum (cumin) has been used as medication to treat a variety of illnesses and conditions. Methods: The cumin seed was successfully extracted with solvents Hexane, Chloroform, Methanol, Ethanol and Acetone. Following the solvent extraction, the extract residue was assayed in MG63 cells for their anti-proliferative properties. Results: First, we used the [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] (MTT) assay to test the extracted residue's cytotoxicity. The results show that hexane extract Half-maximal inhibitory concentration (IC50 86 µG/mL) effciently inhibits cells by causing programmed cell death. Furthermore, using the Acridine orange/ethidium bromide (AO/EB) staining method, the lactate dehydrogenase assay, and the reactive oxygen species assay using the Dichloro-dihydro-fluorescein diacetate (DCHFDA) staining method, we have demonstrated that the hexane extract causes apoptosis in MG63 cells. Furthermore, flow cytometry research revealed that the hexane extract stops the cell cycle in the S phase. In addition, the hexane extract limits colony formation and the migration potential as shown by the scratch wound healing assay. Furthermore, the extract from cumin seeds exhibits remarkable bactericidal properties against infections that are resistant to drugs. Gas chromatography analysis was used to quantitatively determine the hexane and methanolic extract based on the experimental data. The primary chemical components of the extract are revealed by the study, and these help the malignant cells heal. The present study finds that there is scientific validity in using cumin seeds as a novel method of anticancer therapy after undergoing both intrinsic and extrinsic research.

Genetic enhancement of okra [Abelmoschus esculentus (L.) Moench] germplasm through wide hybridization.

Introduction: The introgression of genetic material from one species to another through wide hybridization and repeated back-crossing, plays an important role in genetic modification and enriching the cultivated gene-pool with novel genetic variations. Okra (Abelmoschus esculentus [(L.) Moench)] is a popular vegetable crop with high dietary fibre and protein, rich in essential amino acids, lysine and tryptophan. The wild Abelmoschus genepool has many desirable traits like ornamental value, short internodal length, more number of productive branches, extended bearing, perennation tendency, reduced fruit length (more consumer preferred trait), high mucilage content (medicinal value), abiotic stress tolerances such as drought, high temperature and biotic stress resistances such as okra Yellow Vein Mosaic Virus (YVMV) and Enation Leaf Curl Virus (ELCV) diseases. The repeated use of elite breeding lines led to narrowing of the genetic base of the okra crop, one of the major factors attributed to breakdown of resistance/ tolerance to biotic stresses. YVMV and ELCV are the two major diseases, causing significant yield loss in okra. Hence, wide hybridization was attempted to transfer tolerance genes from wild species to the cultivated genepool to widen the genetic base. Material and methods: The screening of germplasm of wild Abelmoschus species at hotspots led to the identification of tolerant species (Abelmoschus pungens var. mizoramensis, A. enbeepeegeearensis, A. caillei, A. tetraphyllus and A. angulosus var. grandiflorus), which were further used in a wide-hybridization programme to generate interspecific hybrids with the cultivated okra. Presence of pre- and post-zygotic barriers to interspecific geneflow, differences in ploidy levels and genotype specific variations in chromosome numbers led to varying degrees of sterility in F1 plants of interspecific crosses. This was overcome by doubling the chromosome number of interspecific hybrids by applying Colchicine at the seedling stage. The 113 cross derivatives generated comprising amphidiploids in the F1 generation (30), F3 (14), one each in F2 and F4 generations, back cross generation in BC1F2 (03), BC1F3 (25), and BC2F3 (02), crosses between amphidiploids (27), multi-cross combinations (07) and inter-specific cross (between A. sagittifolius × A. moschatus subsp. moschatus) selfed derivatives at F8 generation (03) were characterized in the present study. Besides they were advanced through selfing and backcrossing. Results and Discussion: The amphidiploids were found to possess many desirable genes with a considerable magnitude of linkage drag. Majority of the wide cross derivatives had an intermediate fruit morphology and dominance of wild characters viz., hispid fruits, stem, leaves, tough fruit fibre, vigorous perennial growth habit and prolonged flowering and fruiting. The fruit morphology of three BC progenies exhibited a high morphological resemblance to the cultivated okra, confirming successful transfer of useful genes to the cultivated okra genepool. The detailed morphological characteristics of the various combinations of Abelmoschus amphidiploids and the genetic enhancement of the genepool achieved in this process is reported here.

Content and process: organizational conflict and decision making.

The foundational work in the Carnegie perspective established conflict as endemic to organizations and a driver of organizing behavior and decision making. Organizations as a system of coordinated action among interdependent individuals and groups with different preferences, interests, information, or knowledge create the potential for pervasive and ongoing latent goal conflict. At the same time, extant psychology research has devoted considerable attention to identifying the content and intensity of conflict, focusing on the relationship between different types of conflict and their impact on group outcomes. The Carnegie perspective also assumes that the need for joint decision-making and the differences in goals or perception of reality are never fully resolved. As a result, it has paid attention to the processes through which conflict is addressed - by attending sequentially to goals, decentralizing information, accumulating excess resources, and forming coalitions rather than formal mediating procedures. The assessment of the psychology and organizational theory research also suggests that future work focusing on organizational conflict as latent, situated, and dynamic would enable greater clarity on how organizations make decisions.

Mechanistic modeling explains the production dynamics of recombinant adeno-associated virus with the baculovirus expression vector system.

Current manufacturing processes for recombinant adeno-associated viruses (rAAVs) have less-than-desired yields and produce significant amounts of empty capsids. The increasing demand and the high cost of goods for rAAV-based gene therapies motivate development of more efficient manufacturing processes. Recently, the US Food and Drug Administration (FDA) approved the first rAAV-based gene therapy product manufactured in the baculovirus expression vector system (BEVS), a technology that demonstrated production of high titers of full capsids. This work presents a first mechanistic model describing the key extracellular and intracellular phenomena occurring during baculovirus infection and rAAV maturation in the BEVS. The model predictions are successfully validated for in-house and literature experimental measurements of the vector genome and of structural and non-structural proteins collected during rAAV manufacturing in the BEVS with the TwoBac and ThreeBac constructs. A model-based analysis of the process is carried out to identify the bottlenecks that limit full capsid formation. Vector genome amplification is found to be the limiting step for rAAV production in Sf9 cells using either the TwoBac or ThreeBac system. In turn, vector genome amplification is hindered by limiting Rep78 levels. Transgene and non-essential baculovirus protein expression in the insect cell during rAAV manufacturing also negatively influences the rAAV production yields.

Impact of an automated large vessel occlusion detection tool on clinical workflow and patient outcomes.

Purpose: Automated large vessel occlusion (LVO) tools allow for prompt identification of positive LVO cases, but little is known about their role in acute stroke triage when implemented in a real-world setting. The purpose of this study was to evaluate the automated LVO detection tool's impact on acute stroke workflow and clinical outcomes. Materials and methods: Consecutive patients with a computed tomography angiography (CTA) presenting with suspected acute ischemic stroke were compared before and after the implementation of an AI tool, RAPID LVO (RAPID 4.9, iSchemaView, Menlo Park, CA). Radiology CTA report turnaround times (TAT), door-to-treatment times, and the NIH stroke scale (NIHSS) after treatment were evaluated. Results: A total of 439 cases in the pre-AI group and 321 cases in the post-AI group were included, with 62 (14.12%) and 43 (13.40%) cases, respectively, receiving acute therapies. The AI tool demonstrated a sensitivity of 0.96, a specificity of 0.85, a negative predictive value of 0.99, and a positive predictive value of 0.53. Radiology CTA report TAT significantly improved post-AI (mean 30.58 min for pre-AI vs. 22 min for post-AI, p < 0.0005), notably at the resident level (p < 0.0003) but not at higher levels of expertise. There were no differences in door-to-treatment times, but the NIHSS at discharge was improved for the pre-AI group adjusted for confounders (parameter estimate = 3.97, p < 0.01). Conclusion: Implementation of an automated LVO detection tool improved radiology TAT but did not translate to improved stroke metrics and outcomes in a real-world setting.

How Reactivation of SARS-CoV-2 in Astronauts with Dysregulated Immune Systems Can Negatively Affect the Odds of Success in Future Space Missions.

We have previously reported that during future space missions the risk of severe COVID-19 infection will be a cardinal issue that needs careful attention. Our studies show that even with the most reliable pre-mission screening and quarantine strategies, astronauts with a latent (hidden, inactive, or dormant) SARS-CoV-2 infection might be sent to space. Given this consideration, an asymptomatic individual with dormant SARS-CoV-2 infection may successfully pass all the pre-launch medical tests. Then during a space mission such as a journey to Mars or beyond, when the immune system of these astronauts starts to weaken, the dormant infection may progress to a severe infection that possibly affects the chance of the mission's success. The effects of microgravity and the elevated space radiation are two key factors that should be evaluated. Furthermore, the limited size of the spacecraft, the proximity of crew members during flight operations, spacecraft atmospheric composition, limited exercise capability, effects of viral response to space radiation, and uncertainty in the likelihood of the virus to mutate and evolve during a space mission merit additional study.

Progress in non-viral localized delivery of siRNA therapeutics for pulmonary diseases.

Emerging therapies based on localized delivery of siRNA to lungs have opened up exciting possibilities for treatment of different lung diseases. Localized delivery of siRNA to lungs has shown to result in severalfold higher lung accumulation than systemic route, while minimizing non-specific distribution in other organs. However, to date, only 2 clinical trials have explored localized delivery of siRNA for pulmonary diseases. Here we systematically reviewed recent advances in the field of pulmonary delivery of siRNA using non-viral approaches. We firstly introduce the routes of local administration and analyze the anatomical and physiological barriers towards effective local delivery of siRNA in lungs. We then discuss current progress in pulmonary delivery of siRNA for respiratory tract infections, chronic obstructive pulmonary diseases, acute lung injury, and lung cancer, list outstanding questions, and highlight directions for future research. We expect this review to provide a comprehensive understanding of current advances in pulmonary delivery of siRNA.

Investigating Sport Stakeholders' Understanding of Behaviour Management within a Competitive Youth Baseball Team.

The following study employed an instrumental case study to investigate sport stakeholders' understandings of behavioural management strategies used in competitive youth baseball, including the identification of common strategies and interpretations of these as punishment or discipline. Twenty-one participants, from one competitive (AAA) all-boys baseball team, including three coaches, eleven baseball players, and seven parents, were recruited to participate in an individual semi-structured interview. Interviews ranged between 30 and 150 min, and data were analyzed using reflexive thematic analysis. Several behaviour management tactics were identified, of which exercise, benching and yelling negative comments were most often reported. While participants interpreted excessive exercise and benching as punitive and/or disciplinary approaches to behavioural management, yelling was consistently viewed as punitive. Participants confused punishment and discipline as interchangeable, thus suggesting a lack of awareness regarding developmentally appropriate strategies of behavioural management and highlighting the normalization of certain punitive tactics in youth sport. The results underscore the necessity of imparting knowledge to the sports community regarding age-appropriate behavioural management interventions to foster safe and enjoyable athletic experiences for youth competitors.

Clathrin light chain-conjugated drug delivery for cancer.

Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)-conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer-melanoma, breast cancer, and lung cancer-with CLC-PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free PTX. CLC-PTX treatment caused a marked increase in apoptosis of tumor cells and reduction of tumor angiogenesis. Our data suggested HSP70 as a binding partner for CLC. Our study demonstrates that CLC-based drug-conjugates constitute a novel drug delivery platform that can augment the effects of chemotherapeutics in treating a variety of cancers. Moreover, conjugation of therapeutics with CLC may be used as means by which drugs are delivered specifically to primary tumors and metastatic lesions, thereby prolonging the survival of cancer patients.

SARS-CoV-2 infection augments species- and age-specific predispositions in cotton rats.

Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders.