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Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.

Consumption of ultra-processed food (PF) is associated with obesity risk compared with whole food (WF) intake. Less is known regarding the intake of gluten-free (GF) food products. The purpose of this study was to directly compare the thermic effect (TEM), substrate utilization, hunger/taste ratings, and glucose response of three different meals containing PF, WF, and GF food products in young healthy women. Eleven volunteers completed all three iso-caloric/macronutrient test meals in a single-blind, randomized crossover design: (1) whole food meal (WF); (2) processed food meal (PF); or (3) gluten-free meal (GF). TEM was significantly lower following GF compared with WF (−20.94 kcal/meal, [95% CI, −35.92 to −5.96], p = 0.008) and PF (mean difference: −14.94 kcal/meal, [95% CI, −29.92 to 0.04], p = 0.04), respectively. WF consumption resulted in significantly higher feelings of fullness compared to GF (mean difference: +14.36%, [95% CI, 3.41 to 25.32%], p = 0.011) and PF (mean difference: +16.81%, [95% CI, 5.62 to 28.01%], p = 0.004), respectively, and enhanced palatability (taste of meal) compared to PF meal (mean Δ: +27.41%, [95% CI, 5.53 to 49.30%], p = 0.048). No differences existed for substrate utilization and blood glucose response among trials. Consumption of a GF meal lowers postprandial thermogenesis compared to WF and PF meals and fullness ratings compared to a WF meal which may impact weight control and obesity risk over the long-term.

The beneficial cardiometabolic and body composition effects of combined protein-pacing (P; 5–6 meals/day at 2.0 g/kg BW/day) and multi-mode exercise (resistance, interval, stretching, endurance; RISE) training (PRISE) in obese adults has previously been established. The current study examines PRISE on physical performance (endurance, strength and power) outcomes in healthy, physically active women. Thirty exercise-trained women (>4 days exercise/week) were randomized to either PRISE (n = 15) or a control (CON, 5–6 meals/day at 1.0 g/kg BW/day; n = 15) for 12 weeks. Muscular strength (1-RM bench press, 1-RM BP) endurance (sit-ups, SUs; push-ups, PUs), power (bench throws, BTs), blood pressure (BP), augmentation index, (AIx), and abdominal fat mass were assessed at Weeks 0 (pre) and 13 (post). At baseline, no differences existed between groups. Following the 12-week intervention, PRISE had greater gains (p < 0.05) in SUs, PUs (6 ± 7 vs. 10 ± 7, 40%; 8 ± 13 vs. 14 ± 12, 43% ∆reps, respectively), BTs (11 ± 35 vs. 44 ± 34, 75% ∆watts), AIx (1 ± 9 vs. −5 ± 11, 120%), and DBP (−5 ± 9 vs. −11 ± 11, 55% ∆mmHg). These findings suggest that combined protein-pacing (P; 5–6 meals/day at 2.0 g/kg BW/day) diet and multi-component exercise (RISE) training (PRISE) enhances muscular endurance, strength, power, and cardiovascular health in exercise-trained, active women.

Breeding programs for improvement of sacha-inchi, Plukenetia volubilis L., generally aim to select individuals with greater seed yield since there is a strong correlation between seed yield and oil production. However, the manual removal of seed husks for evaluating this trait is laborious and costly, thereby discouraging breeding efforts. Accordingly, the objective of the present study was to estimate gains from indirect selection of seed production in sacha-inchi progenies, focusing on maximizing efficiency in improvement programs. Genetic parameters along with direct and indirect selection gains were estimated for seed yield traits in 12 open-pollinated progenies. Strong genetic correlations were observed between total number of fruits (TNF), total weight of fruits (TWF), and total weight of seeds (TWS) per plant (r > 0.96). Notably, all three traits demonstrated high heritability (h2 > 0.81). Therefore, plants with high TNF and TWF (Cuzco, Dos de Mayo, Shanao, Aucaloma, and AM-7) can be used to indirectly select the genetic traits of higher seed yields (GS% = 23%). Genetic gain for dry seed production with a selection index of 42% was estimated at 23%, which corresponds to 118 kg·ha−1. Future sacha-inchi improvement programs can select progenies with high TNF and TWF to facilitate the selection of progenies with high TWS.

ObjectivesTo present an overview of the existing epidemiological evidence regarding the occurrence of mental health symptoms and disorders among current and former elite athletes.DesignSystematic review and meta-analysis.Data sourcesFive electronic databases were searched from inception to November 2018: PubMed (MEDLINE), SportDiscus via EBSCO, PSycINFO via ProQuest, Scopus and Cochrane.Eligibility criteria for selecting studiesWe included original quantitative studies that were written in English, were conducted exclusively among current or former elite athletes, and presented incidence or prevalence rates of symptoms of mental disorders.ResultsTwenty-two relevant original studies about mental health symptoms and disorders among current elite athletes were included: they presented data especially on symptoms of distress, sleep disturbance, anxiety/depression and alcohol misuse. Meta-analyses comprising 2895 to 5555 current elite athletes showed that the prevalence of mental health symptoms and disorders ranged from 19% for alcohol misuse to 34% for anxiety/depression. Fifteen relevant original studies about mental health symptoms and disorders among former elite athletes were included: they similarly presented data especially about symptoms of distress, sleep disturbance, anxiety/depression and alcohol misuse. Meta-analyses comprising 1579 to 1686 former elite athletes showed that the prevalence of mental health symptoms and disorders ranged from 16% for distress to 26% for anxiety/depression.ConclusionsOur meta-analyses showed that the prevalence of mental health symptoms and disorders ranged from 19% for alcohol misuse to 34% for anxiety/depression for current elite athletes, and from 16% for distress to 26% for anxiety/depression for former elite athletes.

Exhibit Before and after the crisis, both groups of firms performed comparably (about 13 percent net internal rate of return (IRR) for vintages 2004–08 and about 21 percent for vintages 2014–18). During the GFC, many investors made all of these mistakes, paying multiple times for what in hindsight is dubbed a “lack of discipline.” [...]chastened, GPs and LPs alike have pledged over the last decade to “maintain pricing discipline” and “avoid vintage risk” and “stick to pacing plans.” [...]notwithstanding the recent slowdown in deal activity, it is reasonable to imagine that many PE firms will seek to continue deploying capital despite the current tumult and uncertainty.

Altermagnets are a newly discovered class of magnetic phases that combine the spin polarization behavior of ferromagnetic band structures with the vanishing net magnetization characteristic of antiferromagnets. Initially proposed for collinear magnets, the concept has since been extended to include certain non-collinear structures. A recent development in Landau theory for collinear altermagnets incorporates spin-space symmetries, providing a robust framework for identifying this class of materials. Here, we expand on that theory to identify altermagnetic multipolar order parameters in non-collinear chiral materials. We demonstrate that the interplay between non-collinear altermagnetism and chirality allows for spatially odd multipole components, leading to non-trivial spin textures on Fermi surfaces and unexpected transport phenomena, even in the absence of SOC. This makes such chiral altermagnets fundamentally different from the well-known SOC-driven Rashba-Edelstein and spin Hall effects used in 2D spintronics. Choosing the chiral topological magnetic material Mn 3 IrSi as a case study, we apply toy models and first-principles calculations to predict experimental signatures, such as large spin Hall and Edelstein effects, that have not been previously observed in altermagnets. These findings pave the way for a new realm of spintronics applications based on the spin-transport properties of chiral altermagnets. Recent work has expanded the concept of altermagnets to non-collinear magnetic materials. Here, Hu et al extend this further to non-collinear chiral materials, determining altermagnetic multipolar order parameters and predicting that such materials host large spin-hall and Edelstein effects.

Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.

According to McKinsey’s latest Global Private Markets Review, private markets entered a slower era in 2023, with macroeconomic headwinds, rising financing costs and an uncertain growth outlook weighing on fundraising, deal activity and performance.If 2022 was a tale of two halves, with robust fundraising and deal activity in the first six months followed by a slowdown in the second half, then 2023 might be considered a tale of one whole. [...]the majority plan to maintain or increase allocations over the medium to long term. Rising interest rates widened bid–ask spreads and impaired deal volume across food groups, including in what were formerly hot sectors: multifamily and industrial. Many private debt securities are tied to floating rates, which enhance returns in a rising-rate environment. [...]far, managers appear to have successfully navigated the rising incidence of default and distress exhibited across the broader leveraged-lending market.