Coastal mortality burden on school holidays 2004-2021: an Australian perspective.

INTRODUCTION: School holidays are a known period of increased risk of paediatric drowning. However, the risk of coastal death for all age groups is unknown. METHODS: This case-control study aimed to identify high-risk demographics and behaviours relating to coastal deaths during the school holidays. We address this knowledge gap by comparing unintentional coastal deaths (drowning deaths and other coastal fatalities) in Australia between 1 July 2004-30 June 2021 to a survey sample representative of the Australian population. RESULTS: School holidays increased the risk of coastal death increased overall by 1.39 times (95% CI 1.32 to 146, p=0.00019). This increased risk differed across activities, behaviours and demographics. Few between-group differences were detected, indicating that school holidays pose an increased risk to the wider Australian population on the coast, regardless of demographics and practices. Increased school holiday mortality risk was identified broadly across groups, but notably for young adults (risk ratio, RR 1.41, 95% CI 1.31 to 1.53, p<0.001), when attempting a rescue (RR 1.85, 95% CI 1.42 to 2.39, p=0.0002), scuba diving (RR 1.82, 95% CI 1.48 to 2.23, p<0.0001) and swimming/wading (RR 1.72, 95% CI 1.56 to 1.89, p<0.0001). Children did not have a significantly increased risk of death (RR 1.38, 95% CI 1.03 to 1.87, p=0.054). CONCLUSION: These results highlight that while school holiday risk research regarding drowning has focused on the safety of children, these time periods also pose significant safety concerns to the rest of the population for both drowning deaths and other fatalities. Overall, the research highlights ongoing need for public education for all carers of children, as well as continuing to extend risk education to the broader community. Mitigation strategies, that is, advocacy for extending life-saving service and engaging with accommodation providers during school holidays are proposed.

'I actually thought that I was going to die': Lessons on the rip current hazard from survivor experiences.

BACKGROUND: Rip currents are strong, narrow, fast-flowing currents of water that occur on many beaches and in Australia contributing to 26 drowning deaths and several thousand lifeguard/lifesaver rescues each year. Educating the public about the rip current hazard is a primary focus of beach safety practitioners, but there has been a lack of qualitative research exploring the firsthand experiences of being caught in a rip current to assist in this regard. The aim of this study was to analyse interviews of rip current survivors to understand more about how people react when unintentionally caught in a rip current in order to help guide future public education to mitigate rip current drowning. METHODS: Semi-structured interviews were conducted with 56 individuals (primarily Australian-born) about their experience of being caught in a rip current. Interviewees were recruited via an online survey and varied in age and self-reported swimming ability. RESULTS: Thematic analysis revealed three key temporal elements to the rip current experience: Before the Rip in which lack of awareness and knowledge, complacency, over-confidence, and attitude were prevalent themes; During the Rip which identified panic and temporary inhibition of decision-making, physical response, prior experience, and relationships with other beach users as themes; and After the Rip where post-rip effects and rip safety messaging and education were key themes. The importance of experiential immersion was a prevalent thread throughout all phases of the thematic analysis. DISCUSSION: Our research shows that being caught in a rip current can be an intense and traumatic experience and that lessons learned from survivors have significant implications for improving existing and future rip current education efforts. In this regard, we provide several recommendations based on evidence-based insights gained from our interviews including the development of immersive rip current experience using virtual reality. SO WHAT: Despite the prevalence of rip currents causing drowning deaths and rescues, there has been a lack of qualitative research on firsthand experiences to aid in public education. These interviews emphasise the intense and traumatic nature of being caught in a rip current, underscoring the need for improved rip current education to aid in prevention of this, often harrowing, experience.

Evaluating the impact of skill development for drowning prevention: a relationship-building approach to community engagement.

OBJECTIVE: Evaluate the impact of a broadened theoretical and empirical model of community engagement aimed at coastal drowning prevention via relationship building between lifeguards and beachgoers through the delivery of skill development sessions on the beach. SETTING: A lifeguard-patrolled beach in Lorne, Victoria, Australia, during the 2023 peak summer holiday season. METHODS: In total, 12 skill development sessions were delivered by teams of lifeguards and risk researchers to beachgoers. Sessions were codesigned by the research team and shared with lifeguards beforehand to review and include lifeguards' interpretations of localised risk during delivery. In total, 85 survey interviews were conducted with self-selecting beachgoers post participation. RESULTS: In total, 79 participants (93%) enjoyed participating in the session(s) and 77 participants (91%) reported learning something new. Learning how to identify rip current (n=59) and escape a rip current (n=40) were the two most commonly learnt skills. Participants' intended changes in future beachgoing behaviours (n=46) include asking lifeguards at patrolled beaches how to identify site-specific (rip current) risk (n=11) and attempting to identify a rip current before entering the water (n=10). The spillover effects of participation include sharing what participants had learnt with family and friends. CONCLUSIONS: Creating a dialogic model of collaboration via participatory community engagements between lifeguards and researchers with the beachgoing public can successfully prompt learning drowning prevention skills. These skills are required when navigating dynamic coastal hazards at unpatrolled beaches. Supporting lifeguards and life-savers to provide skill development expands the ways that life-saving services can engage the public, including measurement of lifeguards' contributions to coastal drowning prevention.

A preliminary study investigating the neglected domain of mental health in Australian lifesavers and lifeguards.

BACKGROUND: Surf lifesavers and lifeguards have provided essential education, preventative, and rescue services to the Australian community for over 110 years. In this first responder role, surf lifesavers and lifeguards are inadvertently exposed to high risk and trauma related experiences, which may negatively impact mental well-being. To date however, there has been limited research into the mental health of surf lifesavers and lifeguards, and no studies at all on the mental health of adolescent surf lifesavers. The preliminary study aimed to measure the exposure of potentially traumatic events (PTEs), post-traumatic stress symptoms (PTSS), self-efficacy, social support, and attitudes towards mental health problems in Surf Life Saving (SLS) members. METHODS: An anonymous, online survey was developed (adolescent and adult versions) and created to measure the domain of mental health in surf lifesavers and lifeguards. Pearson's correlations investigated relationships between PTEs, PTSS, self-efficacy, social support, attitudes towards mental health problems, age, years as a SLS member, and years patrolling. Spearman's Rank was used for violations of normality. RESULTS: A total of 57 surf lifesavers/lifeguards aged 13-59 years were included in the final analysis. There was a significant positive relationship between exposure to direct trauma and PTSS, which in turn, were associated with greater negative attitudes towards mental health problems towards the mental health of others, and lower levels of self-efficacy. Male and female adults with PTSS reported lower social support, whereas for adolescent males, a positive relationship between direct trauma and PTSS was observed. CONCLUSION: This research is the first to explore the mental health of Australian surf lifesavers and lifeguards. The results highlight the potential risks to mental health and well-being associated with this first responder role. More research to protect the vulnerability of this population is warranted.

Affective Responses to Increasing- and Decreasing-Intensity Resistance Training Protocols.

This study compared the effects of an increasing-intensity (UP) and a decreasing-intensity (DOWN) resistance training protocol on affective responses across six training sessions. Novice participants (Mage 43.5 ± 13.7 years) were randomly assigned to UP (n = 18) or DOWN (n = 17) resistance training groups. Linear mixed-effects models showed that the evolution of affective valence within each training session was significantly moderated by the group (b = -0.45, p ≤ .001), with participants in the UP group reporting a decline in pleasure during each session (b = -0.82) and the DOWN group reporting an improvement (b = 0.97; ps < .001). Remembered pleasure was significantly higher in the DOWN group compared to the UP group (b = 0.57, p = .004). These findings indicate that a pattern of decreasing intensity throughout a resistance exercise session can elicit more positive affective responses and retrospective affective evaluations of resistance training.

Preliminary evaluation of the impact of mandatory life jacket laws at declared high-risk rock platforms on unintentional rock fishing drowning deaths.

OBJECTIVES: To explore the impact of mandatory lifejacket wear legislation on unintentional rock fishing-related drowning fatalities at declared high-risk rock platforms in New South Wales (NSW; Australia). METHODS: Rock fishing-related drownings for the five years pre-legislation enactment (23 November 2011 to 22 November 2016) and five years post-legislation enactment (23 November 2016 to 22 November 2021) were compared. Google Earth was used to assess if drowning deaths occurred at declared areas under legislation. Binary logistic regression was used to analyse change in the number of deaths in declared areas pre-legislation/post-legislation. RESULTS: Over the 10 years, 80 rock fishing drowning deaths occurred in New South Wales; 23 in declared areas pre-legislation and 13 post-legislation (-43.5%). The odds of a rock fishing drowning death occurring in a declared area pre-legislation was 2.3 times higher (95% CI 0.942 to 5.752; p=0.067). CONCLUSION: Reductions in rock fishing deaths at declared areas were observed since the legislation's introduction, but were not significant. Greater enforcement and extension to other high-risk platforms may reduce deaths further.

School water, sanitation, and hygiene (WaSH) intervention to improve malnutrition, dehydration, health literacy, and handwashing: a cluster-randomised controlled trial in Metro Manila, Philippines.

BACKGROUND: The impacts of multicomponent school water, sanitation, and hygiene (WaSH) interventions on children's health are unclear. We conducted a cluster-randomized controlled trial to test the effects of a school WaSH intervention on children's malnutrition, dehydration, health literacy (HL), and handwashing (HW) in Metro Manila, Philippines. METHODS: The trial lasted from June 2017 to March 2018 and included children, in grades 5, 6, 7, and 10, from 15 schools. At baseline 756 children were enrolled. Seventy-eight children in two clusters were purposively assigned to the control group (CG); 13 clusters were randomly assigned to one of three intervention groups: low-intensity health education (LIHE; two schools, n = 116 children), medium-intensity health education (MIHE; seven schools, n = 356 children), and high-intensity health education (HIHE; four schools, n = 206 children). The intervention consisted of health education (HE), WaSH policy workshops, provision of hygiene supplies, and WaSH facilities repairs. Outcomes were: height-for-age and body mass index-for-age Z scores (HAZ, BAZ); stunting, undernutrition, overnutrition, dehydration prevalence; HL and HW scores. We used anthropometry to measure children's physical growth, urine test strips to measure dehydration, questionnaires to measure HL, and observation to measure HW practice. The same measurements were used during baseline and endline. We used multilevel mixed-effects logistic and linear regression models to assess intervention effects. RESULTS: None of the interventions reduced undernutrition prevalence or improved HAZ, BAZ, or overall HL scores. Low-intensity HE reduced stunting (adjusted odds ratio [aOR] 0.95; 95% CI 0.93 to 0.96), while low- (aOR 0.57; 95% CI 0.34 to 0.96) and high-intensity HE (aOR 0.63; 95% CI 0.42 to 0.93) reduced overnutrition. Medium- (adjusted incidence rate ratio [aIRR] 0.02; 95% CI 0.01 to 0.04) and high-intensity HE (aIRR 0.01; 95% CI 0.00 to 0.16) reduced severe dehydration. Medium- (aOR 3.18; 95% CI 1.34 to 7.55) and high-intensity HE (aOR 3.89; 95% CI 3.74 to 4.05) increased observed HW after using the toilet/urinal. CONCLUSION: Increasing the intensity of HE reduced prevalence of stunting, overnutrition, and severe dehydration and increased prevalence of observed HW. Data may be relevant for school WaSH interventions in the Global South. Interventions may have been more effective if adherence was higher, exposure to interventions longer, parents/caregivers were more involved, or household WaSH was addressed. TRIAL REGISTRATION NUMBER: DRKS00021623.

Prime Movers: Effects of Subliminal Primes, Music, and Music Video on Psychological Responses to Exercise.

BACKGROUND: Priming is a process in which exposure to a stimulus activates relevant mental representations that are given increased weight in subsequent judgment tasks. Affective primes can influence affective evaluations and associations. Such influence has meaningful implications for the promotion of exercise behavior, yet there is scant research on priming effects in exercise settings. PURPOSE: The purpose of the present pair of studies was to examine the efficacy of music (M), music video (MV), and music video with affective primes (PRIME) in modulating psychological responses during and immediately following an exercise bout among two distinct populations. METHODS: In Study 1, physically active participants completed a brisk walking task on a treadmill under four conditions: M, MV, PRIME, and control. Affective valence and rating of perceived exertion (RPE) were assessed during exercise and remembered/forecasted pleasure was measured immediately following each exercise bout. In Study 2, largely inactive and overweight participants completed a brisk walking task on a treadmill under two conditions: MV and PRIME. Affective valence was assessed during exercise, while exercise enjoyment and remembered/forecasted pleasure were assessed postexercise. RESULTS: In Study 1, PRIME yielded more positively valenced affect, remembered/forecasted pleasure, and lower RPE when compared to the other conditions (MCohen's d for all DVs = 0.91). In Study 2, PRIME elicited more positively valenced affect, greater enjoyment, and enhanced remembered/forecasted pleasure when compared to MV (MCohen's d for all DVs = 0.64). CONCLUSIONS: Subliminal primes embedded in music video can elicit positive changes in psychological responses during and immediately following exercise.

Biocatalytic synthesis of non-vicinal aliphatic diols.

Biocatalysts are receiving increased attention in the field of selective oxyfunctionalization of C-H bonds, with cytochrome P450 monooxygenases (CYP450s), and the related peroxygenases, leading the field. Here we report on the substrate promiscuity of CYP505A30, previously characterized as a fatty acid hydroxylase. In addition to its regioselective oxyfunctionalization of saturated fatty acids (ω-1 - ω-3 hydroxylation), primary fatty alcohols are also accepted with similar regioselectivities. Moreover, alkanes such as n-octane and n-decane are also readily accepted, allowing for the production of non-vicinal diols through sequential oxygenation.

Risky business: a 15-year analysis of fatal coastal drowning of young male adults in Australia.

INTRODUCTION: Drowning is a leading cause of unintentional death, especially for males. In Australian coastal waters, young male adults account for 25% of the burden of male drowning. This study aims to describe young male coastal drowning deaths and to examine the prevalence of risk factors, especially alcohol and drugs. METHODS: Characteristics of unintentional fatal drowning involving males (15-34 years) were compared with other adults (15 years and older). Data were sourced from the National Coronial Information System (Australia) and Surf Life Saving incident reports (2004/2005-2018/2019). Relative risk was calculated and χ2 tests of independence were performed (p<0.05). Blood alcohol and drug concentrations were analysed with permutational analyses of variance. RESULTS: Young males drowned more while jumping (9.85 times), swimming/wading (1.41 times), at rock/cliff locations (1.42 times) and on public holidays (1.8 times). Young males drowned less while boating (0.81 times), scuba diving (2.08 times), offshore (1.56 times) or due to medical factors (3.7 times). Young males drowned more (1.68 times) after consuming illicit drugs (amphetamines 2.26 times; cannabis 2.25 times) and less with prescription drugs (benzodiazepines 2.6 times; opiates 4.1 times; antidepressants 7.7 times). Blood serum concentrations of cannabis were higher in young males, while amphetamine and alcohol were lower. DISCUSSION: Unsafe behaviours alongside certain activities or locations create deadly combinations of risk factors. A relationship between age, activity, attitude and affluence is proposed, where young males drown more in affordable activities with fewer regulations. Our results support multilevel strategies (spanning life stages) to reduce young male coastal drowning.

X-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2.

Toxoplasmosis is a parasitic disease caused by infection with Toxoplasma gondii that currently has few therapeutic options. The M1 aminopeptidase enzymes have been shown to be attractive targets for anti-parasitic agents and/or vaccine candidates, suggesting potential to re-purpose inhibitors between parasite M1 aminopeptidase targets. The M1 aminopeptidase TgAPN2 has been suggested to be a potential new drug target for toxoplasmosis. Here we investigate the structure and function of TgAPN2, a homologue of the antimalarial drug target PfA-M1, and evaluate the capacity to use inhibitors that target PfA-M1 against TgAPN2. The results show that despite a similar overall fold, the TgAPN2 has a unique substrate specificity and inhibition profile. Sequence and structure differences are investigated and show how comparative structure-activity relationships may provide a route to obtaining potent inhibitors of TgAPN2.

Does diagnostic mammography need to be a routine component of the initial evaluation of a breast symptom in women 30-39 years of age?

Diagnostic mammography is routinely ordered, along with targeted breast ultrasound, to evaluate breast symptoms in women 30-39 years of age. However, in this age group, mammography is often limited by breast density and the probability of detecting an occult malignancy is low. We sought to evaluate whether diagnostic mammography detected any new incidental malignancies in women aged 30-39 years presenting with focal breast symptoms. This retrospective study included women 30-39 years of age who had a diagnostic mammogram performed for focal breast symptoms at a single institution from 2002 to 2017. Descriptive analyses were performed to determine the rate of incidental mammographic findings outside of the region of the presenting symptom that 1) led to additional imaging and/or biopsies and 2) were found to be malignant. During the 16-year study period, 1770 evaluations were performed, of which 249 (14.1%) were found to have an additional incidental mammographic abnormality. Further diagnostic imaging was required in 211 (11.3%), core biopsy in 67 (3.8%), and excisional biopsy in 8 (0.5%). None of the mammographically detected incidental findings resulted in a new diagnosis of breast cancer. In the evaluation of focal benign breast symptoms in women 30-39 years of age, diagnostic mammography did not detect any new incidental malignancies outside of the area of interest, but instead led to additional unavailing imaging and biopsy procedures. The mammography component of the diagnostic evaluation of younger average-risk women may potentially be omitted if the presenting symptom is determined to be benign with ultrasound alone.

Physical activity and mental well-being under COVID-19 lockdown: a cross-sectional multination study.

BACKGROUND: COVID-19 lockdowns have reduced opportunities for physical activity (PA) and encouraged more sedentary lifestyles. A concomitant of sedentariness is compromised mental health. We investigated the effects of COVID-19 lockdown on PA, sedentary behavior, and mental health across four Western nations (USA, UK, France, and Australia). METHODS: An online survey was administered in the second quarter of 2020 (N = 2541). We measured planned and unplanned dimensions of PA using the Brunel Lifestyle Physical Activity Questionnaire and mental health using the 12-item General Health Questionnaire. Steps per day were recorded only from participants who used an electronic device for this purpose, and sedentary behavior was reported in hours per day (sitting and screen time). RESULTS: In the USA and Australia samples, there was a significant decline in planned PA from pre- to during lockdown. Among young adults, Australians exhibited the lowest planned PA scores, while in middle-aged groups, the UK recorded the highest. Young adults exhibited the largest reduction in unplanned PA. Across nations, there was a reduction of ~ 2000 steps per day. Large increases in sedentary behavior emerged during lockdown, which were most acute in young adults. Lockdown was associated with a decline in mental health that was more pronounced in women. CONCLUSIONS: The findings illustrate the deleterious effects of lockdown on PA, sedentary behavior, and mental health across four Western nations. Australian young and lower middle-aged adults appeared to fare particularly badly in terms of planned PA. The reduction in steps per day is equivalent to the non-expenditure of ~ 100 kcal. Declines in mental health show how harmful lockdowns can be for women in particular.

Altered Signal Transduction in the Immune Response to Influenza Virus and S. pneumoniae or S. aureus Co-Infections.

Influenza virus is a well-known respiratory pathogen, which still leads to many severe pulmonary infections in the human population every year. Morbidity and mortality rates are further increased if virus infection coincides with co-infections or superinfections caused by bacteria such as Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus). This enhanced pathogenicity is due to complex interactions between the different pathogens and the host and its immune system and is mainly governed by altered intracellular signaling processes. In this review, we summarize the recent findings regarding the innate and adaptive immune responses during co-infection with influenza virus and S. pneumoniae or S. aureus, describing the signaling pathways involved and how these interactions influence disease outcomes.

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function.

Numerous studies have assembled a complex picture, in which extracellular stimuli and intracellular signaling pathways modulate the chondrocyte phenotype. Because many diseases are mechanobiology-related, this review asked to what extent phenotype regulators control chondrocyte function through the cytoskeleton and cytoskeleton-regulating signaling processes. Such information would generate leverage for advanced articular cartilage repair. Serial passaging, pro-inflammatory cytokine signaling (TNF-α, IL-1α, IL-1ß, IL-6, and IL-8), growth factors (TGF-α), and osteoarthritis not only induce dedifferentiation but also converge on RhoA/ROCK/Rac1/mDia1/mDia2/Cdc42 to promote actin polymerization/crosslinking for stress fiber (SF) formation. SF formation takes center stage in phenotype control, as both SF formation and SOX9 phosphorylation for COL2 expression are ROCK activity-dependent. Explaining how it is molecularly possible that dedifferentiation induces low COL2 expression but high SF formation, this review theorized that, in chondrocyte SOX9, phosphorylation by ROCK might effectively be sidelined in favor of other SF-promoting ROCK substrates, based on a differential ROCK affinity. In turn, actin depolymerization for redifferentiation would "free-up" ROCK to increase COL2 expression. Moreover, the actin cytoskeleton regulates COL1 expression, modulates COL2/aggrecan fragment generation, and mediates a fibrogenic/catabolic expression profile, highlighting that actin dynamics-regulating processes decisively control the chondrocyte phenotype. This suggests modulating the balance between actin polymerization/depolymerization for therapeutically controlling the chondrocyte phenotype.

Single Hormone Receptor-Positive Breast Cancers Have Distinct Characteristics and Survival.

BACKGROUND: Estrogen receptor (ER) and progesterone receptor (PR) status is pivotal to determining the prognosis and treatment of human epidermal growth factor 2 (HER2) receptor-negative invasive breast cancer. Frequently ER-positive (ER+) and/or PR-positive (PR+) cancers are labeled nonspecifically as "hormone receptor-positive" although only one is positive. This study aimed to evaluate and characterize the ER+PR- and ER-PR+ breast cancer phenotypes in reference to ER+PR+ cancers. METHODS: A retrospective cohort study of female patients with HER2-negative (HER2-) invasive breast cancer diagnosed in 2010-2015 was performed using the National Cancer Database. Cases were grouped into ER+PR+, ER-PR+, ER+PR-, and ER-PR- phenotypes to determine differences in patient demographics, tumor characteristics, and overall survival. RESULTS: Of 823,969 cases, 619,050 (75.1%) were ER+PR+, 79,777 (9.7%) were ER+PR-, 7006 (0.9%) were ER-PR+, and 118,136 (14.3%) were ER-PR-. Compared with the ER+PR+ group, the ER+PR- and ER-PR+ groups were more likely to be high-grade cancer (16.0% vs. 34.2% and 80.0%, respectively; p < 0.001), to have lymphovascular invasion (17.9% vs. 19.6% and 23.0%; p < 0.001), to be node-positive (13.5% vs. 19.7% and 26.3%; p < 0.001), to be stage 4 cancer (3.6% vs. 5.9% and 6.7%; p < 0.001), to have a higher multigene assay score (mean, 16.0 vs. 27.8 and 38.1; p < 0.001), and to have a worse survival (90.6% vs. 83.8% and 78.1%; p < 0.001). CONCLUSION: Single hormone receptor-positive breast cancer subtypes (ER+PR- and ER-PR+) are more likely to have unfavorable characteristics and worse survival than the ER+PR+ subtype, with the ER-PR+ subtype having outcomes similar to those for ER-PR- cancers. The single hormone receptor-positive subtypes, representing 10% of HER2- cancers, should be considered clinically distinct from ER+PR+ disease.

Experimental support towards a metabolic proxy in fish using otolith carbon isotopes.

Metabolic rate underpins our understanding of how species survive, reproduce and interact with their environment, but can be difficult to measure in wild fish. Stable carbon isotopes (δ13C) in ear stones (otoliths) of fish may reflect lifetime metabolic signatures but experimental validation is required to advance our understanding of the relationship. To this end, we reared juvenile Australasian snapper (Chrysophrys auratus), an iconic fishery species, at different temperatures and used intermittent-flow respirometry to calculate standard metabolic rate (SMR), maximum metabolic rate (MMR) and absolute aerobic scope (AAS). Subsequently, we analysed δ13C and oxygen isotopes (δ18O) in otoliths using isotope-ratio mass spectrometry. We found that under increasing temperatures, δ13C and δ18O significantly decreased, while SMR and MMR significantly increased. Negative logarithmic relationships were found between δ13C in otoliths and both SMR and MMR, while exponential decay curves were observed between proportions of metabolically sourced carbon in otoliths (Moto) and both measured and theoretical SMR. We show that basal energy for subsistence living and activity metabolism, both core components of field metabolic rates, contribute towards incorporation of δ13C into otoliths and support the use of δ13C as a metabolic proxy in field settings. The functional shapes of the logarithmic and exponential decay curves indicated that physiological thresholds regulate relationships between δ13C and metabolic rates due to upper thresholds of Moto Here, we present quantitative experimental evidence to support the development of an otolith-based metabolic proxy, which could be a powerful tool in reconstructing lifetime biological trends in wild fish.

Application of a Dual Catalytic Nickel/Iridium-Based Photoredox Reaction to Synthesize 2-Alkyl-N-Arylindoles in a Continuous Flow.

A versatile one-pot procedure for the preparation of 2-alkyl-substituted N-arylindoles is described. The method combines a visible light-mediated Ni/Ir-photoredox dual catalytic N-arylation of alkynyl anilines under continuous flow conditions with a subsequent base-mediated cyclization to afford the desired substituted indoles. The initial Ni/Ir photoredox-promoted N-arylation of alkynylanilines proceeds efficiently in a continuous flow to afford the desired products in moderate to excellent yields with a short residence time (20 min) and mild conditions at ambient temperature and without the exclusion of air. The methodology was amenable for a multi-gram scale-up to deliver 2-alkyl-N-arylindoles in high yields followed with only a single purification step.

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair.

Since material stiffness controls many cell functions, we reviewed the currently available knowledge on stiffness sensing and elucidated what is known in the context of clinical and experimental articular cartilage (AC) repair. Remarkably, no stiffness information on the various biomaterials for clinical AC repair was accessible. Using mRNA expression profiles and morphology as surrogate markers of stiffness-related effects, we deduced that the various clinically available biomaterials control chondrocyte (CH) phenotype well, but not to equal extents, and only in non-degenerative settings. Ample evidence demonstrates that multiple molecular aspects of CH and mesenchymal stromal cell (MSC) phenotype are susceptible to material stiffness, because proliferation, migration, lineage determination, shape, cytoskeletal properties, expression profiles, cell surface receptor composition, integrin subunit expression, and nuclear shape and composition of CHs and/or MSCs are stiffness-regulated. Moreover, material stiffness modulates MSC immuno-modulatory and angiogenic properties, transforming growth factor beta 1 (TGF-ß1)-induced lineage determination, and CH re-differentiation/de-differentiation, collagen type II fragment production, and TGF-ß1- and interleukin 1 beta (IL-1ß)-induced changes in cell stiffness and traction force. We then integrated the available molecular signaling data into a stiffness-regulated CH phenotype model. Overall, we recommend using material stiffness for controlling cell phenotype, as this would be a promising design cornerstone for novel future-oriented, cell-instructive biomaterials for clinical high-quality AC repair tissue.

Increasing the Pleasure and Enjoyment of Exercise: A Novel Resistance-Training Protocol.

This study was designed to test the effect of an increasing- (UP) or decreasing-intensity (DOWN) resistance-training (RT) protocol on the pleasure and enjoyment of RT. The participants (N = 40; mean age = 35.0 ± 9.2 years) completed two RT sessions comprising 3 × 10 repetitions of six exercises. In the UP condition, load progressively increased from 55% to 75% of 1-repetition maximum, while in the DOWN condition, this pattern was reversed (i.e., 75-55% 1-repetition maximum). The DOWN condition resulted in more overall pleasure compared with UP and a slope of increasing pleasure, while the UP condition resulted in decreasing pleasure. Enjoyment of RT, postexercise pleasure, and remembered pleasure were all significantly greater for DOWN compared with UP (all ps > .01). These findings suggest that decreasing RT intensity throughout an exercise bout can elicit a positive slope of pleasure and enhance affective evaluations of exercise.