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Focused ultrasound (FUS) is an innovative technology that delivers angled acoustic energy to a small target region. Previous FUS technology has demonstrated efficacy in applications such as tumor destruction, nerve modulation, and drug delivery in the brain. We investigated the effects of low-intensity FUS (LIFU) stimulation on the spinal cord and its ability to regulate mean arterial pressure (MAP). We found that LIFU stimulation on exposed rat spinal cord could modulate MAP, causing a decrease when applied at a lower thoracic level and an increase when applied at a lumbosacral level. We also found that shorter stimulation periods (30 s) were more effective in inducing a decrease in MAP than more extended stimulation periods (90 s). The time required to return to baseline for MAP was shown to increase with subsequent periods of FUS stimulation. FUS could enable non-pharmacological, spatially targeted MAP control, especially for impaired patients. Future applications of FUS neuromodulation extend into solutions for clinical blood pressure disorders, such as autonomic dysreflexia or chronic hypertension.

Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

Sarcoidosis, a systemic inflammatory disease, poses challenges in understanding its etiology and variable clinical courses. Despite ongoing uncertainty about causative agents and genetic predisposition, granuloma formation remains its hallmark feature. To address this complexity, we developed a validated in vitro human granuloma model using peripheral blood mononuclear cells (PBMCs), providing a dynamic platform for studying sarcoidosis pathogenesis. While cryopreservation is a common method for long-term sample preservation, the biological effects of freezing and thawing PBMCs on granuloma formation remain unclear. This study aimed to assess the viability and functionality of cryopreserved sarcoidosis PBMCs within the granuloma model, revealing similar granulomatous responses to fresh cells and highlighting the potential of cryopreserved PBMCs as a valuable tool for studying sarcoidosis and related diseases.

Efforts to optimize photosynthesis can be informed by measurement of it’s underlying and coordinated sub-processes. For decades, non-invasive techniques have been integrated to enable assessment of the coordination that exists within and between the gaseous diffusional, energy productive, and energy consumptive reactions of leaf-level photosynthesis. One of the more prevalent techniques measures chlorophyll a fluorescence using a fluorometer that employes pulsed amplitude modulation (PAM). The maximum fluorescence yield observed under steady-state actinic illumination, or F m ’ , has been shown to be prone to underestimation. Errors can be propagated to various derivative parameters representative of photosynthetic phenomena that have been identified as targets for photosynthetic optimization. A technique involving a multiphase flash of variable irradiance has been shown to be capable of correcting for underestimation of F m ’ . The technique reveals that whereas F m ’ is prone to underestimation, the maximum fluorescence yield following brief cessation of actinic illumination, or F m ” , is not. The differential susceptibility of F m ’ and F m ” to misestimation renders essential features of photosynthetic regulation, which are governed by coordinated sub-processes of leaf level photosynthesis, subject to misinterpretation.

Individual differences in fear and fearlessness have been investigated at their extremes in relation to markedly different forms of psychopathology--anxiety disorders and psychopathy, respectively. A documented neural substrate of fear-related traits and disorders is defensive reactivity as reflected in aversive startle potentiation (ASP). The current study extended prior work by characterizing, in a sample of adult twins from the community (n = 2511), the phenotypic and etiologic structure of self-report measures of fear and fearlessness known to be associated with ASP. Analyses revealed a hierarchical structure to the trait fear domain, with an overarching, bipolar fear/fearlessness dimension saturating each measure in this domain, and subfactors labeled 'distress,' 'stimulation seeking' and 'sociability' accounting for additional variance in particular measures. The structure of genetic and non-shared environmental associations among the measures closely mirrored the phenotypic structure of the domain. The findings have implications for proposals to reconceptualize psychopathology in neurobiological terms.

Mammals evolved an endogenous timing system to coordinate their physiology and behaviour to the 24h period of the solar day. While it is well accepted that circadian rhythms are generated by intracellular transcriptional feedback loops, it is still debated which network motifs are necessary and sufficient for generating self-sustained oscillations. Here, we systematically explore a data-based circadian oscillator model with multiple negative and positive feedback loops and identify a series of three subsequent inhibitions known as \"repressilator\" as a core element of the mammalian circadian oscillator. The central role of the repressilator motif is consistent with time-resolved ChIP-seq experiments of circadian clock transcription factors and loss of rhythmicity in core clock gene knockouts.

We mapped migration routes of migratory songbirds to the Neotropics by using light-level geolocators mounted on breeding purple martins (Progne subis) and wood thrushes (Hylocichla mustelina). Wood thrushes from the same breeding population occupied winter territories within a narrow east-west band in Central America, suggesting high connectivity of breeding and wintering populations. Pace of spring migration was rapid (233 to 577 kilometers/day) except for one individual (159 kilometers/day) who took an overland route instead of crossing the Gulf of Mexico. Identifying songbird wintering areas and migration routes is critical for predicting demographic consequences of habitat loss and climate change in tropical regions.

After nearly 12 years of follow-up, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial has shown that screening with flexible sigmoidoscopy reduces colorectal-cancer incidence by 21% and mortality by 26%. Colorectal cancer is the second leading cause of cancer-related deaths in the United States. 1 Colorectal-cancer mortality 2 – 4 and incidence 5 , 6 are reduced with screening by means of fecal occult-blood testing. Endoscopic screening with flexible sigmoidoscopy or colonoscopy is more sensitive than fecal testing for the detection of adenomatous polyps, the precursor lesions of colorectal cancer. 7 – 9 Three European randomized trials of flexible sigmoidoscopy have been performed. 10 In the United Kingdom, one-time screening with flexible sigmoidoscopy significantly reduced the incidence of colorectal cancer (by 23%) and associated mortality (by 31%). 11 In Italy, an 18% reduction in incidence and a nonsignificant 22% . . .

Sustaining the organisms, ecosystems and processes that underpin human wellbeing is necessary to achieve sustainable development. Here we define critical natural assets as the natural and semi-natural ecosystems that provide 90% of the total current magnitude of 14 types of nature’s contributions to people (NCP), and we map the global locations of these critical natural assets at 2 km resolution. Critical natural assets for maintaining local-scale NCP (12 of the 14 NCP) account for 30% of total global land area and 24% of national territorial waters, while 44% of land area is required to also maintain two global-scale NCP (carbon storage and moisture recycling). These areas overlap substantially with cultural diversity (areas containing 96% of global languages) and biodiversity (covering area requirements for 73% of birds and 66% of mammals). At least 87% of the world’s population live in the areas benefitting from critical natural assets for local-scale NCP, while only 16% live on the lands containing these assets. Many of the NCP mapped here are left out of international agreements focused on conserving species or mitigating climate change, yet this analysis shows that explicitly prioritizing critical natural assets and the NCP they provide could simultaneously advance development, climate and conservation goals. Bringing together multiple models and databases on nature’s contributions to people, the authors map these contributions globally and determine the critical areas where their magnitude is the highest and where they provide the highest potential human benefit.

In this study of more than 20,000 nonsurgical patients receiving mechanical ventilation at 37 acute care hospitals from 2002 to 2003, higher hospital volume was associated with improved survival. After adjustment for the severity of illness and the characteristics of the hospitals, mortality in the hospital was 34 percent in hospitals in the lowest quartile in terms of the number of patients receiving mechanical ventilation per year and 26 percent in the highest quartile. In more than 20,000 nonsurgical patients receiving mechanical ventilation at 37 acute care hospitals from 2002 to 2003, higher hospital volume was associated with improved survival. The association between the number of patients treated in a hospital (hospital volume) and patient outcome is well established for numerous medical and surgical conditions. 1 This relationship has been extensively documented in the surgical literature, where higher patient volume is associated with improved survival in situations involving trauma care, cardiac surgery, ruptured aortic aneurysms, and several types of cancer surgery. 2 – 6 Select medical conditions, including acute myocardial infarction 7 and the acquired immunodeficiency syndrome, 8 are also thought to have outcomes related to the volume of patients seen. Reasons for the relationship between volume and outcome in health care are unknown but . . .