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Chemical synapses exhibit a diverse array of internal mechanisms that affect the dynamics of transmission efficacy. Many of these processes, such as release of neurotransmitter and vesicle recycling, depend strongly on activity-dependent influx and accumulation of Ca 2+ . To model how each of these processes may affect the processing of information in neural circuits, and how their dysfunction may lead to disease states, requires a computationally efficient modelling framework, capable of generating accurate phenomenology without incurring a heavy computational cost per synapse. Constructing a phenomenologically realistic model requires the precise characterization of the timing and probability of neurotransmitter release. Difficulties arise in that functional forms of instantaneous release rate can be difficult to extract from noisy data without running many thousands of trials, and in biophysical synapses, facilitation of per-vesicle release probability is confounded by depletion. To overcome this, we obtained traces of free Ca 2+ concentration in response to various action potential stimulus trains from a molecular MCell model of a hippocampal Schaffer collateral axon. Ca 2+ sensors were placed at varying distance from a voltage-dependent calcium channel (VDCC) cluster, and Ca 2+ was buffered by calbindin. Then, using the calcium traces to drive deterministic state vector models of synaptotagmin 1 and 7 (Syt-1/7), which respectively mediate synchronous and asynchronous release in excitatory hippocampal synapses, we obtained high-resolution profiles of instantaneous release rate, to which we applied functional fits. Synchronous vesicle release occurred predominantly within half a micron of the source of spike-evoked Ca 2+ influx, while asynchronous release occurred more consistently at all distances. Both fast and slow mechanisms exhibited multi-exponential release rate curves, whose magnitudes decayed exponentially with distance from the Ca 2+ source. Profile parameters facilitate on different time scales according to a single, general facilitation function. These functional descriptions lay the groundwork for efficient mesoscale modelling of vesicular release dynamics.

Photometric stellar surveys now cover a large fraction of the sky, probe to fainter magnitudes than large-scale spectroscopic surveys, and are relatively free from the target selection biases often associated with such studies. Photometric-metallicity estimates that include narrow/medium-band filters can achieve comparable accuracy and precision to existing low-resolution spectroscopic surveys such as Sloan Digital Sky Survey/SEGUE and LAMOST. Here we report on an effort to identify likely members of the Galactic disk system among the very metal-poor (VMP; [Fe/H] ≤ −2) and extremely metal-poor (EMP; [Fe/H] ≤ −3) stars. Our analysis is based on an initial sample of ∼11.5 million stars with full space motions selected from the SkyMapper Southern Survey (SMSS) and Stellar Abundance and Galactic Evolution Survey (SAGES). After applying a number of quality cuts to obtain the best available metallicity and dynamical estimates, we analyze a total of ∼5.86 million stars in the combined SMSS/SAGES sample. We employ two techniques that, depending on the method, identify between 876 and 1476 VMP stars (6.9%−11.7% of all VMP stars) and between 40 and 59 EMP stars (12.4%−18.3% of all EMP stars) that appear to be members of the Galactic disk system on highly prograde orbits (v ϕ > 150 km s−1). The total number of candidate VMP/EMP disklike stars is 1496, the majority of which have low orbital eccentricities, ecc ≤ 0.4; many have ecc ≤ 0.2. The large fractions of VMP/EMP stars associated with the Milky Way disk system strongly suggest the presence of an early-forming “primordial” disk.

Excellent adherence to tuberculosis (TB) treatment is critical to cure TB and avoid the emergence of resistance. Wirelessly observed therapy (WOT) is a novel patient self-management system consisting of an edible ingestion sensor (IS), external wearable patch, and paired mobile device that can detect and digitally record medication ingestions. Our study determined the accuracy of ingestion detection in clinical and home settings using WOT and subsequently compared, in a randomized control trial (RCT), confirmed daily adherence to medication in persons using WOT or directly observed therapy (DOT) during TB treatment. We evaluated WOT in persons with active Mycobacterium tuberculosis complex disease using IS-enabled combination isoniazid 150 mg/rifampin 300 mg (IS-Rifamate). Seventy-seven participants with drug-susceptible TB in the continuation phase of treatment, prescribed daily isoniazid 300 mg and rifampin 600 mg, used IS-Rifamate. The primary endpoints of the trial were determination of the positive detection accuracy (PDA) of WOT, defined as the percentage of ingestions detected by WOT administered under direct observation, and subsequently the proportion of prescribed doses confirmed by WOT compared to DOT. Initially participants received DOT and WOT simultaneously for 2-3 weeks to allow calculation of WOT PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples. Sixty-one participants subsequently participated in an RCT to compare the proportion of prescribed doses confirmed by WOT and DOT. Participants were randomized 2:1 to receive WOT or maximal in-person DOT. In the WOT arm, if ingestions were not remotely confirmed, the participant was contacted within 24 hours by text or cell phone to provide support. The number of doses confirmed was collected, and nonparametric methods were used for group and individual comparisons to estimate the proportions of confirmed doses in each randomized arm with 95% CIs. Sensitivity analyses, not prespecified in the trial registration, were also performed, removing all nonworking (weekend and public holiday) and held-dose days. Participants, recruited from San Diego (SD) and Orange County (OC) Divisions of TB Control and Refugee Health, were 43.1 (range 18-80) years old, 57% male, 42% Asian, and 39% white with 49% Hispanic ethnicity. The PDA of WOT was 99.3% (CI 98.1; 100). Intent-to-treat (ITT) analysis within the RCT showed WOT confirmed 93% versus 63% DOT (p < 0.001) of daily doses prescribed. Secondary analysis removing all nonworking days (weekends and public holidays) and held doses from each arm showed WOT confirmed 95.6% versus 92.7% (p = 0.31); WOT was non-inferior to DOT (difference 2.8% CI [-1.8%, 9.1%]). One hundred percent of participants preferred using WOT. WOT associated adverse events were <10%, consisting of minor skin rash and pruritus associated with the patch. WOT provided longitudinal digital reporting in near real time, supporting patient self-management and allowing rapid remote identification of those who needed more support to maintain adherence. This study was conducted during the continuation phase of TB treatment, limiting its generalizability to the entire TB treatment course. In terms of accuracy, WOT was equivalent to DOT. WOT was superior to DOT in supporting confirmed daily adherence to TB medications during the continuation phase of TB treatment and was overwhelmingly preferred by participants. WOT should be tested in high-burden TB settings, where it may substantially support low- and middle-income country (LMIC) TB programs. ClinicalTrials.gov NCT01960257.

Policies that restrict access to and use of the Supplemental Nutrition Assistance Program (SNAP) and Special Supplemental Nutrition Assistance Program for Women, Infants, and Children (WIC) by legal status may disproportionately disadvantage particular racial and ethnic groups. While immigrant legal status, race, and ethnicity are recognized as independent social determinants of health, studies examining the extent to which legal status structures racial and ethnic health disparities are limited. Research is needed to identify factors that mitigate disparate health outcomes, such as SNAP and WIC. Cross-sectional data from the 2009/2010 National Agricultural Workers Survey (N = 3,961) were analyzed. Chi-square tests and logistic regressions examined associations among self-reported health, race, ethnicity, legal status, and SNAP/WIC participation. Farmworkers reporting excellent or good health were more likely to be non-Hispanic White, U.S. citizen, aged 18-25, single, male, educated beyond primary school, living above the poverty level, without chronic health conditions, and located in the Midwest. Hispanic farmworkers had lower odds of reporting excellent or good health (OR 0.27, 95% CI 0.12-0.62). Among SNAP/WIC participants, Hispanic farmworkers had higher odds of reporting excellent or good health (OR 6.74, 95% CI 1.54-29.57) compared to non-Hispanic White farmworkers. There was no significant association between self-reported health and legal status. This study complements the extant literature showing racial and ethnic health disparities among the U.S. farmworker population. Results provide valuable insight on the health-protective potential of programs like SNAP and WIC, particularly among Hispanic farmworkers, who may be both less likely to be eligible and more hesitant to participate. These findings underscore the need to expand U.S. farmworkers' eligibility and participation in SNAP and WIC.

M15 is a globular cluster with a known spread in neutron-capture elements. This paper presents abundances of neutron-capture elements for 62 stars in M15. Spectra were obtained with the Michigan/Magellan Fiber System spectrograph, covering a wavelength range from ∼4430 to 4630 Å. Spectral lines from Fe i, Fe ii, Sr i, Zr ii, Ba ii, La ii, Ce ii, Nd ii, Sm ii, Eu ii, and Dy ii were measured, enabling classifications and neutron-capture abundance patterns for the stars. Of the 62 targets, 44 are found to be highly Eu-enhanced r-II stars, another 17 are moderately Eu-enhanced r-I stars, and one star is found to have an s-process signature. The neutron-capture patterns indicate that the majority of the stars are consistent with enrichment by the r-process. The 62 target stars are found to show significant star-to-star spreads in Sr, Zr, Ba, La, Ce, Nd, Sm, Eu, and Dy, but no significant spread in Fe. The neutron-capture abundances are further found to have slight correlations with sodium abundances from the literature, unlike what has been previously found; follow-up studies are needed to verify this result. The findings in this paper suggest that the Eu-enhanced stars in M15 were enhanced by the same process, that the nucleosynthetic source of this Eu pollution was the r-process, and that the r-process source occurred as the first generation of cluster stars was forming.

Background Cervical cancer is primarily associated with the presence of human papillomavirus (HPV), with high-risk genotypes HPV-16 and HPV-18 being the focus of vaccination programs in developing countries such as Chile. Preventive screening for cervical cancer in women aged 25 to 64 years remains centered on cytological techniques and is primarily performed based on clinical suspicion of cervical lesions. However, extended screening for HPV genotypes using DNA amplification methods is not routinely applied to the Chilean female population yet. This study aimed to determine the prevalence of high- and low-risk HPV genotypes in women without known risk factors in a city in northern Chile. Methods Cervicovaginal brushing samples were obtained from 390 women from Antofagasta city, Northern Chile, aged between 25 and 64 years; genomic DNA was extracted, and multiplex real-time PCR analysis was used to identify a larger group of high- and low-risk HPV genotypes. Results Among 390 samples, HPV prevalence was 36.9%, of which 54.9% were high-risk genotypes, 18.7% were low-risk genotypes, and 26.4% showed mixed infection with both high- and low-risk genotypes. High-risk genotypes 16, 58, 39, and 31 were the most frequently identified among HPV-positive samples. Furthermore, a significant association was observed between HPV presence and both age and suspicion of cervical alteration, and women testing positive for other sexually transmitted infections (STIs) were more likely to acquire HPV. Conclusions Implementing a screening program that incorporates extended HPV genotyping in Chile, including testing for high-risk genotypes 16, 18, 31, 39, and 58, is crucial to optimize control, early detection, and vaccination efforts for Chilean circulating HPV genotypes that are not covered by the actual vaccine, thus contributing to a more effective reduction in the burden of disease associated with the virus.

Injection drug use has far-reaching social, economic, and health consequences. Serious bacterial infections, including skin/soft tissue infections, osteomyelitis, bacteremia, and endocarditis, are particularly morbid and mortal consequences of injection drug use. We conducted a population-based retrospective cohort analysis of hospitalizations among patients with a diagnosis code for substance use and a serious bacterial infection during the same hospital admission using Oregon Hospital Discharge Data. We examined trends in hospitalizations and costs of hospitalizations attributable to injection drug use-related serious bacterial infections from January 1, 2008 through December 31, 2018. From 2008 to 2018, Oregon hospital discharge data included 4,084,743 hospitalizations among 2,090,359 patients. During the study period, hospitalizations for injection drug use-related serious bacterial infection increased from 980 to 6,265 per year, or from 0.26% to 1.68% of all hospitalizations (P<0.001). The number of unique patients with an injection drug use-related serious bacterial infection increased from 839 to 5,055, or from 2.52% to 8.46% of all patients (P<0.001). While hospitalizations for all injection drug use-related serious bacterial infections increased over the study period, bacteremia/sepsis hospitalizations rose most rapidly with an 18-fold increase. Opioid use diagnoses accounted for the largest percentage of hospitalizations for injection drug use-related serious bacterial infections, but hospitalizations for amphetamine-type stimulant-related serious bacterial infections rose most rapidly with a 15-fold increase. People living with HIV and HCV experienced increases in hospitalizations for injection drug use-related serious bacterial infection during the study period. Overall, the total cost of hospitalizations for injection drug use-related serious bacterial infections increased from $16,305,129 in 2008 to $150,879,237 in 2018 (P<0.001). In Oregon, hospitalizations for injection drug use-related serious bacterial infections increased dramatically and exacted a substantial cost on the health care system from 2008 to 2018. This increase in hospitalizations represents an opportunity to initiate substance use disorder treatment and harm reduction services to improve outcomes for people who inject drugs.

This paper presents a wireless fault detection system for industrial motors that combines vibration, motor current and temperature analysis, thus improving the detection of mechanical faults. The design also considers the time of detection and further possible actions, which are also important for the early detection of possible malfunctions, and thus for avoiding irreversible damage to the motor. The remote motor condition monitoring is implemented through a wireless sensor network (WSN) based on the IEEE 802.15.4 standard. The deployed network uses the beacon-enabled mode to synchronize several sensor nodes with the coordinator node, and the guaranteed time slot mechanism provides data monitoring with a predetermined latency. A graphic user interface offers remote access to motor conditions and real-time monitoring of several parameters. The developed wireless sensor node exhibits very low power consumption since it has been optimized both in terms of hardware and software. The result is a low cost, highly reliable and compact design, achieving a high degree of autonomy of more than two years with just one 3.3 V/2600 mAh battery. Laboratory and field tests confirm the feasibility of the wireless system.

The nanoencapsulation of bioactive compounds such as β-carotene and microalgal extracts has emerged as an effective strategy to enhance their stability, bioavailability, and biological efficacy, particularly against oxidative stress. Dunaliella tertiolecta, a microalga rich in carotenoids and chlorophylls, presents notable antioxidant and erythroprotective properties; however, its bioactive potential is limited by low bioaccessibility and degradation during processing and digestion. This study aimed to develop and evaluate nanoliposomes loaded with D. tertiolecta extract and β-carotene as sustained-release systems to improve antioxidant performance and erythroprotective effects. The methodology involved optimizing microalgal cultivation under nitrogen and salinity stress to enhance pigment accumulation, followed by extraction, nanoencapsulation via the particle dispersion method, and physicochemical characterization of the nanoliposomes. Antioxidant capacity and release kinetics were assessed through ABTS and FRAP assays, while erythroprotective activity was evaluated by monitoring oxidative hemolysis in human erythrocytes. The release kinetics revealed an anomalous transport mechanism for both systems, with β-carotene showing faster and more efficient release due to its greater lipophilic compatibility with the nanoliposomal matrix. The nanoliposomal systems demonstrated nanoscale size, high encapsulation efficiency, sustained antioxidant release, and effective erythrocyte protection, with the extract-loaded formulation exhibiting synergistic effects superior to isolated β-carotene. These findings support the potential application of this nanotechnology-based delivery system in functional foods, nutraceuticals, and biomedical formulations aimed at preventing oxidative stress-related cellular damage.

(1) Background: Arterial stiffness, often measured by carotid–femoral pulse wave velocity (cf-PWV), is crucial in cardiovascular disease. Dapagliflozin has shown rapid effects on arterial stiffness, but there is limited evidence of empagliflozin’s acute effects, especially in type 2 diabetes (T2D) patients. This study evaluated the acute effects of empagliflozin and dapagliflozin on arterial stiffness and blood pressure (BP). (2) Methods: A one-week double-blind randomized trial involved 30 T2D patients on stable metformin therapy. Participants received empagliflozin (25 mg/day), dapagliflozin (10 mg/day), or a placebo. Arterial stiffness was assessed via cf-PWV, and BP was measured with an automated sphygmomanometer. (3) Results: Both SGLT2 inhibitors significantly reduced cf-PWV compared to the placebo after one week (p < 0.05), with dapagliflozin showing a more pronounced effect. No significant differences were observed in BP changes. (4) Conclusion: Short-term treatment with SGLT2 inhibitors acutely reduces arterial stiffness in T2D patients, with empagliflozin demonstrating a stronger effect, supporting the potential vascular benefits of SGLT2 inhibitors beyond glucose control.