Digest:Sexual selection in a multibrooded songbird: The social pair matters

Which sources of variance in socially monogamous species offer the largest opportunity for sexual selection? Germain et al. study this question in a double-brooding songbird and find that male reproductive success gained within the social bond stands out as an important source of variance across years and lifetimes

Repeatable parental risk taking across manipulated levels of predation threat:No individual variation in plasticity

Salazar S, Hlebowicz K, Komdeur J, Korsten P. Repeatable parental risk taking across manipulated levels of predation threat: no individual variation in plasticity. Animal Behaviour. 2023;196:127-149.Individuals respond adaptively to their environment. Yet, they may differ in their responses even when confronted with the same environmental challenge. Several complementary conceptual frameworks suggest that within populations among-individual variation in life history strategies aligns not only with individuals' propensities to take risks across different situations but also with their sensitivity to variation in environmental cues. Risk-prone individuals, suggested to invest more in current reproduction at the cost of their future reproductive prospects, are predicted to be less sensitive to environmental variation than risk-averse individuals. We tested this prediction in a population of breeding blue tits, _Cyanistes caeruleus_, by confronting them with different levels of predation threat at their nests and recording their latency to resume brood provisioning after the removal of the predator stimulus. We presented taxidermic woodpecker, _Dendrocopos major_ (a common brood predator) and sparrowhawk, _Accipiter nisus_ (a common adult predator) mounts at each nest, respectively representing low and high levels of threat to adult blue tits. As a nonpredator control stimulus, we presented a blackbird, _Turdus merula_, mount. We found that on average parents took longer to resume provisioning after presentation of a sparrowhawk than a woodpecker or blackbird. Furthermore, individual latency responses across all threat levels taken together were repeatable. However, despite the population level plastic adjustment to the level of predation threat, we found no evidence for among-individual variation in plasticity. Instead, individual differences in responses were roughly maintained across all levels of threat. While our findings show that individuals differ in their level of risk taking, in the high-stakes and ecologically relevant context of predation risk during parental care, commonly held expectations about among-individual variation in behavioural plasticity were not met

Disparities in access to musculoskeletal care: Narrowing the gap: AOA critical issues symposium

The current health-care system in the United States has numerous barriers to quality, accessible, and affordable musculoskeletal care for multiple subgroups of our population. These hurdles include complex cultural, educational, and socioeconomic factors. Tertiary referral centers provide a disproportionately large amount of the care for the uninsured and underinsured members of our society. These gaps in access to care for certain subgroups lead to inappropriate emergency room usage, lengthy hospitalizations, increased administrative load, lost productivity, and avoidable complications and/or deaths, which all represent a needless burden on our health-care system. Through advocacy, policy changes, workforce diversification, and practice changes, orthopaedic surgeons have a responsibility to seek solutions to improve access to quality and affordable musculoskeletal care for the communities that they serve

Bone density of first and second segments of normal and dysmorphic sacra

BACKGROUND: Iliosacral screw fixation is safe and effective but can be complicated by loss of fixation, particularly in patients with osteopenic bone. Sacral morphology dictates where iliosacral screws may be placed when stabilizing pelvic ring injuries. In dysmorphic sacra, the safe osseous corridor of the upper sacral segment (S1) is smaller and lacks a transsacral corridor, increasing the need for fixation in the second sacral segment (S2). Previous evidence suggests that S2 is less dense than S1. The aim of this cross-sectional study is to further evaluate bone mineral density (BMD) of the S1 and S2 iliosacral osseous pathways through morphology stratification into normal and dysmorphic sacra. MATERIALS AND METHODS: Pelvic computed tomography scans of 50 consecutive trauma patients, aged 18 to 50 years, from a level 1 trauma center were analyzed prospectively. Five radiographic features (upper sacral segment not recessed in the pelvis, mammillary bodies, acute alar slope, residual S1 disk, and misshapen sacral foramen) were used to identify dysmorphic characteristics, and sacra with four or five features were classified as dysmorphic. Hounsfield unit values were used to estimate the regional BMD of S1 and S2. Student\u27s t-test was utilized to compare the mean values at each segment, with statistical significance being set at p \u3c 0.05. No change in clinical management occurred as a result of inclusion in this study. RESULTS: A statistical difference in BMD was appreciated between S1 and S2 in both normal and dysmorphic sacra (p \u3c 0.0001), with 28.4% lower density in S2 than S1. Further, S1 in dysmorphic sacra tended to be 4% less dense than S1 in normal sacra (p = 0.047). No difference in density was appreciated at S2 based on morphology. CONCLUSIONS: Our results would indicate that, based on BMD alone, fixation should be maximized in S1 prior to fixation in S2. In cases where S2 fixation is required, we recommend that transsacral fixation should be strongly considered if possible to bypass the S2 body and achieve fixation in the cortical bone of the ilium and sacrum. LEVEL OF EVIDENCE: Level III

Quercetin elevates p27Kip1 and arrests both primary and HPV16 E6/E7 transformed human keratinocytes in G1

Our previous work with primary bovine fibroblasts demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (Pteridium aquilinum), arrested cells in G1 and G2/M, in correlation with p53 activation. The expression of bovine papillomavirus type 4 (BPV-4) E7 overcame this arrest and lead to the development of tumorigenic cells lines (Beniston et al., 2001). Given the possible link between papillomavirus infection, bracken fern in the diet and cancer of the upper gastrointestinal (GI) tract in humans, we investigated whether a similar situation would occur in human cells transformed by human papillomavirus type 16 (HPV-16) oncoproteins. Quercetin arrested primary human foreskin keratinocytes in G1. Arrest was linked to an elevation of the cyclin-dependent kinase inhibitor (cdki) p27Kip1. Expression of the HPV16 E6 and E7 oncoproteins in transformed cells failed to abrogate cell cycle arrest. G1 arrest in the transformed cells was also linked to an increase of p27Kip1 with a concomitant reduction of cyclin E-associated kinase activity. This elevation of p27Kip1 was due not only to increased protein half-life, but also to increased mRNA transcription

The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort

Background: Presence of additional chronic conditions has significant impact on the treatment and management of type-2 diabetes (T2DM). Little is known about the patterns of comorbidities in this population. The aims of this study are to quantify comorbidity patterns in people with T2DM, to estimate the prevalence of six chronic conditions in 2027 and to identify clusters of similar conditions. Methods: We used the Clinical Practice Research Datalink (CPRD) linked with the Index of Multiple Deprivation (IMD) data to identify patients diagnosed with T2DM between 2007 and 2017. 102,394 people met the study inclusion criteria. We calculated the crude and age-standardised prevalence of 18 chronic conditions present at and after the T2DM diagnosis. We analysed longitudinally the 6 most common conditions and forecasted their prevalence in 2027 using linear regression. We used agglomerative hierarchical clustering to identify comorbidity clusters. These analyses were repeated on subgroups stratified by gender and deprivation. Results: More people living in the most deprived areas had ≥1 comorbidities present at the time of diagnosis (72% of females; 64% of males) compared to the most affluent areas (67% of females; 59% of males). Depression prevalence increased in all strata, and was more common in the most deprived areas. Depression was predicted to affect 33% of females and 15% of males diagnosed with T2DM in 2027. Moderate clustering tendencies were observed, with concordant conditions grouped together and some variations between groups of different demographics. Conclusions: Comorbidities are common in this population and high between-patient variability in comorbidity patterns emphasises the need for patient-centred healthcare. Mental health is a growing concern and there is a need for interventions that target both physical and mental health in this population

Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload

Background The mitochondrial unfolded protein response (UPRmt) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential for contractile function and regulation of cell viability, while mitochondrial dysfunction characterizes heart failure. The role of the UPRmt in the heart is unclear. Objectives The purpose of this study was to: 1) identify conditions that activate the UPRmt in the heart; and 2) study the relationship among the UPRmt, mitochondrial function, and cardiac contractile function. Methods Cultured cardiac myocytes were subjected to different stresses in vitro. Mice were subjected to chronic pressure overload. Tissues and blood biomarkers were studied in patients with aortic stenosis. Results Diverse neurohumoral or mitochondrial stresses transiently induced the UPRmt in cultured cardiomyocytes. The UPRmt was also induced in the hearts of mice subjected to chronic hemodynamic overload. Boosting the UPRmt with nicotinamide riboside (which augments NAD+ pools) in cardiomyocytes in vitro or hearts in vivo significantly mitigated the reductions in mitochondrial oxygen consumption induced by these stresses. In mice subjected to pressure overload, nicotinamide riboside reduced cardiomyocyte death and contractile dysfunction. Myocardial tissue from patients with aortic stenosis also showed evidence of UPRmt activation, which correlated with reduced tissue cardiomyocyte death and fibrosis and lower plasma levels of biomarkers of cardiac damage (high-sensitivity troponin T) and dysfunction (N-terminal pro–B-type natriuretic peptide). Conclusions These results identify the induction of the UPRmt in the mammalian (including human) heart exposed to pathological stresses. Enhancement of the UPRmt ameliorates mitochondrial and contractile dysfunction, suggesting that it may serve an important protective role in the stressed heart