Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved (P \u3c 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased (P \u3c 0.05) after 6 weeks of supplementation with no change in MSP. No changes (P \u3e 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementatio

A randomized controlled trial to examine the impact of a multi-strain probiotic on self-reported indicators of depression, anxiety, mood, and associated biomarkers

Objective: To examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels. Method: In a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0  ±  9.5  years, 173.0  ±  10.4  cm, 73.9  ±  13.8  kg, 24.6  ±  3.5  kg/m2 ) supplemented with a single capsule of MSP (a total daily dose of 4 × 109 colony forming units [CFU] comprised of a 1 × 109   CFU dose from each of the following strains: Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6  weeks of supplementation and 3  weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined. Results: BDI, STAI, and total LEIDS-R scores were reduced from baseline (p  \u3c  0.05) with MSP supplementation after 4 and 6  weeks of supplementation and 3  weeks after supplementation while no changes (p  \u3e  0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower (p  \u3c  0.05) after supplementation. Plasma serotonin concentrations in MSP were increased from baseline after 6  weeks of supplementation and 3  weeks after ceasing supplementation. No changes (p  \u3e  0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups. Conclusion: MSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6  weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortiso

Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2

Abstract Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50 = 0.84 µM), for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection. Author Summary Alphaviruses occur worldwide, causing significant diseases such as encephalitis or arthritis in humans and animals. In addition, some alphaviruses, such as VEEV, pose a biothreat due to their high infectivity and lack of available treatments. To discover small molecule inhibitors with lead development potential, we used a cell-based assay to screen 348,140 compounds for inhibition of a VEEV-induced cytopathic effect. The screen revealed a scaffold with high inhibitory VEEV cellular potency and low cytotoxicity liability. While most previously reported anti-alphavirus compounds inhibit host proteins, evidence supported that this scaffold targeted the VEEV nsP2 protein, and that inhibition was associated with viral replication. Interestingly, compound resistance studies with VEEV mapped activity to the N-terminal domain of nsP2, to which no known function has been attributed. Ultimately, this discovery has delivered a small molecule-derived class of potent VEEV inhibitors whose activity is coupled to the nsP2 viral protein, a novel target with a previously unestablished biological role that is now implicated in viral replication.This research was supported by the following funding sources: NIH R03MH087448-01A1, University of Louisville Internal Research Initiate grant to DHC, USAMRAA W81XWH-10-2-0064 and W81XWH-08-2-0024 to CBJ. Screening was provided by the Southern Research Specialized Screening Center (U54HG005034-0) and chemistry through the University of Kansas Specialized Chemistry Center (U54HG005031). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The unusual M-dwarf Warm Jupiter TOI-1899~b: Refinement of orbital and planetary parameters

TOI-1899~b is a rare exoplanet, a temperate Warm Jupiter orbiting an M-dwarf, first discovered by \citet{Canas2020_toi1899} from a TESS single-transit event. Using new radial velocities (RVs) from the precision RV spectrographs HPF and NEID, along with additional TESS photometry and ground-based transit follow-up, we are able to derive a much more precise orbital period of $P = 29.090312_{-0.000035}^{+0.000036}$~d, along with a radius of $R_p = 0.99\pm0.03$~\unit{R_{J}}. We have also improved the constraints on planet mass, $M_p = 0.67\pm{0.04}$~\unit{M_{J}}, and eccentricity, which is consistent with a circular orbit at 2$\sigma$ ($e = 0.044_{-0.027}^{+0.029}$). TOI-1899~b occupies a unique region of parameter space as the coolest known ($T_{eq} \approx$ 380~K) Jovian-sized transiting planet around an M-dwarf; we show that it has great potential to provide clues regarding the formation and migration mechanisms of these rare gas giants through transmission spectroscopy with JWST as well as studies of tidal evolution.Comment: 19 pages, 7 figures, 3 tables, submitted to AJ (comments welcome

A warm Jupiter transiting an M dwarf: A TESS single transit event confirmed with the Habitable-zone Planet Finder

We confirm the planetary nature of a warm Jupiter transiting the early M dwarf TOI-1899, using a combination of available TESS photometry; high-precision, near-infrared spectroscopy with the Habitable-zone Planet Finder; and speckle and adaptive optics imaging. The data reveal a transiting companion on an $\sim29$-day orbit with a mass and radius of $0.66\pm0.07\ \mathrm{M_{J}}$and$1.15_{-0.05}^{+0.04}\ \mathrm{R_{J}}$, respectively. The star TOI-1899 is the lowest-mass star known to host a transiting warm Jupiter, and we discuss the follow-up opportunities afforded by a warm ($\mathrm{T_{eq}}\sim362$ K) gas giant orbiting an M0 star. Our observations reveal that TOI-1899.01 is a puffy warm Jupiter, and we suggest additional transit observations to both refine the orbit and constrain the true dilution observed in TESS.Comment: 24 pages, 5 figures, 3 tables, published in A

TOI-3984 A b and TOI-5293 A b: two temperate gas giants transiting mid-M dwarfs in wide binary systems

We confirm the planetary nature of two gas giants discovered by TESS to transit M dwarfs with stellar companions at wide separations. TOI-3984 A ($J=11.93$) is an M4 dwarf hosting a short-period ($4.353326 \pm 0.000005$ days) gas giant ($M_p=0.14\pm0.03~\mathrm{M_{J}}$ and $R_p=0.71\pm0.02~\mathrm{R_{J}}$) with a wide separation white dwarf companion. TOI-5293 A ($J=12.47$) is an M3 dwarf hosting a short-period ($2.930289 \pm 0.000004$ days) gas giant ($M_p=0.54\pm0.07~\mathrm{M_{J}}$ and $R_p=1.06\pm0.04~\mathrm{R_{J}}$) with a wide separation M dwarf companion. We characterize both systems using a combination of ground-based and space-based photometry, speckle imaging, and high-precision radial velocities from the Habitable-zone Planet Finder and NEID spectrographs. TOI-3984 A b ($T_{eq}=563\pm15$ K and $\mathrm{TSM}=138_{-27}^{+29}$) and TOI-5293 A b ($T_{eq}=675_{-30}^{+42}$ K and $\mathrm{TSM}=92\pm14$) are two of the coolest gas giants among the population of hot Jupiter-sized gas planets orbiting M dwarfs and are favorable targets for atmospheric characterization of temperate gas giants and three-dimensional obliquity measurements to probe system architecture and migration scenarios.Comment: Submitted to AJ, 42 pages, 14 figures. arXiv admin note: substantial text overlap with arXiv:2201.0996

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

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