Effects of Cardiopulmonary Rehabilitation on Cardiorespiratory Fitness and Clinical Symptom Burden in Long COVID: Results from the COVID-Rehab Randomized Controlled Trial.

OBJECTIVE: To investigate the effectiveness of an eight-week cardiopulmonary rehabilitation program on cardiorespiratory fitness (VO2peak) and key cardiopulmonary exercise test measures, quality of life, and symptom burden in individuals with Long COVID. DESIGN: Forty individuals with Long COVID (mean age 53 ± 11 years), were randomized into 2 groups: 1/ Rehabilitation group: centre-based individualized clinical rehabilitation program (8 weeks, 3 sessions per week of aerobic and resistance exercises, and daily inspiratory muscle training) and 2/ Control group: individuals maintained their daily habits during an eight-week period. RESULTS: There was a significant difference between groups in mean VO2peak improvement (p = 0.003). VO2peak improved significantly in the rehab group (+2.7 mL.kg.min 95%IC:+1.6 to +3.8 p < 0.001) compared to the control group (+0.3 mL.kg.min 95%IC:-0.8 to +1.3 p = 0.596), along withVE/VCO2 slope (p = 0.032) (-2.4 95%IC:-4.8 to +0.01 p = 0.049 and + 1.3 95%IC:-1.0 to +3.6 p = 0.272 respectively) and VO2 at first ventilatory threshold (p = 0.045). Furthermore, all symptom impact scales improved significantly in the rehabilitation group compared to the control group (p < 0.05). CONCLUSION: An individualized and supervised cardiopulmonary rehabilitation program was effective in improving cardiorespiratory fitness, ventilatory efficiency, and symptom burden in individuals with Long COVID. Careful monitoring of symptoms is important to appropriately tailor and adjust rehabilitation sessions.

Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies.

Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cyclic homo-oligomers with up to 8 subunits using repeat protein building blocks that can be modularly extended. By incorporating a de novo-designed fibroblast growth factor receptor (FGFR)-binding module into these scaffolds, we generated a series of synthetic signaling ligands that exhibit potent valency- and geometry-dependent Ca2+ release and mitogen-activated protein kinase (MAPK) pathway activation. The high specificity of the designed agonists reveals distinct roles for two FGFR splice variants in driving arterial endothelium and perivascular cell fates during early vascular development. Our designed modular assemblies should be broadly useful for unraveling the complexities of signaling in key developmental transitions and for developing future therapeutic applications.

New Oldowan locality Sare-Abururu (ca. 1.7 Ma) provides evidence of diverse hominin behaviors on the Homa Peninsula, Kenya.

The Homa Peninsula, in southwestern Kenya, continues to yield insights into Oldowan hominin landscape behaviors. The Late Pliocene locality of Nyayanga (∼3-2.6 Ma) preserves some of the oldest Oldowan tools. At the Early Pleistocene locality of Kanjera South (∼2 Ma) toolmakers procured a diversity of raw materials from over 10 km away and strategically reduced them in a grassland-dominated ecosystem. Here, we report findings from Sare-Abururu, a younger (∼1.7 Ma) Oldowan locality approximately 12 km southeast of Kanjera South and 18 km east of Nyayanga. Sare-Abururu has yielded 1754 artifacts in relatively undisturbed low-energy silts and sands. Stable isotopic analysis of pedogenic carbonates suggests that hominin activities were carried out in a grassland-dominated setting with similar vegetation structure as documented at Kanjera South. The composition of a nearby paleo-conglomerate indicates that high-quality stone raw materials were locally abundant. Toolmakers at Sare-Abururu produced angular fragments from quartz pebbles, representing a considerable contrast to the strategies used to reduce high quality raw materials at Kanjera South. Although lithic reduction at Sare-Abururu was technologically simple, toolmakers proficiently produced cutting edges, made few mistakes and exhibited a mastery of platform management, demonstrating that expedient technical strategies do not necessarily indicate a lack of skill or suitable raw materials. Lithic procurement and reduction patterns on the Homa Peninsula appear to reflect variation in local resource contexts rather than large-scale evolutionary changes in mobility, energy budget, or toolmaker cognition.

Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease.

In polycystic kidney disease (PKD), microscopic tubules expand into macroscopic cysts. Among the world's most common genetic disorders, PKD is inherited via heterozygous loss-of-function mutations but is theorized to require additional loss of function. To test this, we establish human pluripotent stem cells in allelic series representing four common nonsense mutations, using CRISPR base editing. When differentiated into kidney organoids, homozygous mutants spontaneously form cysts, whereas heterozygous mutants (original or base corrected) express no phenotype. Using these, we identify eukaryotic ribosomal selective glycosides (ERSGs) as PKD therapeutics enabling ribosomal readthrough of these same nonsense mutations. Two different ERSGs not only prevent cyst initiation but also limit growth of pre-formed cysts by partially restoring polycystin expression. Furthermore, glycosides accumulate in cyst epithelia in organoids and mice. Our findings define the human polycystin threshold as a surmountable drug target for pharmacological or gene therapy interventions, with relevance for understanding disease mechanisms and future clinical trials.

Prefrontal engagement predicts the effect of museum visit on psychological well-being: an fNIRS exploration.

Recent research suggests that museum visits can benefit psychological well-being by reducing symptoms of stress and anxiety. However, these reported relaxing effects remain inconsistent between studies. Shedding light on the underlying cerebral mechanisms of museum visits might support a better understanding of how it affects psychological well-being. This study aimed to investigate the prefrontal engagement evoked by artwork analysis during a museum visit and to determine if these prefrontal substrates are associated with the museum's effect on psychological well-being in older adults. Nineteen adults aged between 65 and 79, toured a Baroque-style exhibit at the Montreal Museum of Fine Arts for approximately 20 minutes while equipped with a near-infrared spectroscopy system measuring the prefrontal cortex's hemodynamic activity. For each painting, participants received the instruction to either (1): analyze the painting and produce a personal interpretation of its signification (analytic condition) or (2) visualize the painting without any specific thoughts (visualization condition). Questionnaires measuring stress, anxiety, and well-being were administered before and after the visit. Sixteen older women (71.5 ± 4 years) were included in the analyses. Results showed that, at the group level, the analytic condition was associated with an increased activation pattern in the left ventrolateral prefrontal region, typically related to attentional processes (not observed in the visualization condition). The activation associated with the analytic condition predicted pre-/post-visit reductions in self-reported anxiety and stress in the sample of older women. These observations suggest that the level of engagement of attentional processes during artwork analysis may play a major role in the effect of a museum's visit on self-reported symptoms of anxiety.