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This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.

Neuropathies about the ankle and foot may be the cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and etiology of nerve compression and exclude other disease possibly underlying the patient' symptoms. In this article, a review of the anatomical and pathological features of nerve entrapments in the distal lower extremity is presented on ultrasound and magnetic resonance imaging, according to the nerve involved. [ABSTRACT FROM AUTHOR]

Analysis of sperm chromosomes by G-banding and two-colour fluorescence in-situ hybridization (FISH) was carried out in the father of a child with a de-novo reciprocal translocation t(11;15)(q12;q22). Sperm chromosome complements were obtained after in-vitro fusion of zona-free hamster oocytes and donor spermatozoa. A total of 112 sperm complements was first analysed by G-banding. The frequency of structural chromosome aberrations (9.8%) and the conservative frequency of aneuploidy (0.0%) were not significantly different from those obtained in our control donors. The proportions of X-bearing (53.2%) and Y-bearing (46.8%) spermatozoa were not significantly different from the expected 1:1 ratio. A total of 313 sperm complements was analysed by two-colour FISH. The frequency of structural abnormalities for chromosomes 11 and 15 was 3.2 and 0.3% respectively. The frequency of rearrangements for chromosome 11 was statistically significant when compared with control donors (0.4%) (P < 0.0001). No spermatozoa with the t(11;15)(q12;q22) translocation were observed, showing no evidence for a germ-cell mosaicism. These results suggest that the de-novo involvement of chromosome 11 in a structural rearrangement is not random, and that in this patient an increased risk of de-novo structural chromosome abnormalities in further offspring does exist. [ABSTRACT FROM AUTHOR]

The objective of this randomized controlled experiment was to evaluate the effect of delaying induction of ovulation and timed artificial insemination (TAI) on expression of estrus before AI and first service reproductive outcomes. A secondary objective was to evaluate the effects of delaying induction of ovulation in a Double-Ovsynch protocol on ovarian function. Lactating Holstein cows (n = 4,672) from 2 commercial dairy farms fitted with sensors for automated detection of estrus were synchronized with a Double-Ovsynch protocol up to the first PGF 2α (PGF-L) of the Breeding-Ovsynch portion of the protocol (Pre-Ovsynch: GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later Breeding-Ovsynch: GnRH, 7 d later PGF2α, 1 d later PGF2α). At PGF-L, cows blocked by parity (primiparous vs. multiparous) and semen used for first service (sex-sorted dairy vs. conventional beef) were randomly assigned to the G56 (n = 2,338) or G80 (n = 2,334) treatments. Cows in G56 had 56 h whereas cows in G80 had 80 h from PGF-L to induction of ovulation with the last GnRH (GnRH2) before AI. For both treatments, TAI occurred ∼16 h after GnRH2. All cows with automated estrus alerts between PGF-L and TAI were inseminated at detected estrus (AIE) without GnRH. Ovarian function and responses to synchronization were monitored based on circulating concentrations of progesterone and examination of the ovaries by ultrasonography. Data for binary outcomes were analyzed by logistic and continuous outcomes with lineal regression. More cows in G80 received AIE and had estrus before AI. Overall, pregnancies per AI (P/AI) did not differ for the G80 and G56 treatments. Cows in G80 that received TAI and had no estrus had fewer P/AI than cows with estrus that received AIE or TAI in G80, and fewer P/AI than cows AIE and cows that received TAI and had or did not have estrus in the G56 treatment. No differences were observed between treatments or for cows with and without estrus for pregnancy loss. Unlike some minor differences between treatments for concentrations of progesterone at GnRH2, the most notable differences in ovarian function were for cows in both treatments with or without estrus that received TAI. Cows with estrus, were more likely to have follicles > 16 mm, had larger follicles before ovulation, and had a greater ovulation risk after AI. Likewise, within the G80 treatment only, cows with estrus that received AIE or TAI had larger follicles, were more likely to have complete luteal regression, had greater ovulation risk, were more likely to have a functional corpus luteum, and had more circulating progesterone after AI. We concluded that delaying induction of ovulation and TAI was effective for allowing more cows to express estrus before AI which had different ovarian function outcomes and greater P/AI than cows that did not express estrus. However, the greater P/AI of cows that expressed estrus was insufficient to compensate for the reduced P/AI of cows that did not express estrus, and thus increase overall P/AI compared with the treatment without delayed induction of ovulation. Detection of estrus before AI in cows undergoing synchronization of ovulation could help identify cows with different likelihoods of pregnancy after insemination., (© 2025, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Phylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA. No cases were severe. Virus extension to new areas may increase case numbers and severity.

Our overarching objective was to characterize associations between genomic merit for fertility and the reproductive function of lactating dairy cows in a prospective cohort study. In this manuscript, we present results of the association between genomic merit for fertility and indicators of metabolic status and inflammation, uterine health, endocrine status, response to synchronization, and estrous behavior in dairy cows. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation were enrolled at parturition and fitted with an ear-attached sensor for automated detection of estrus. Ear-notch tissue samples were collected from all cows and submitted for genotyping using a commercial genomic test. Based on genomic PTA values for daughter pregnancy rate (gDPR), cows were classified into a high (Hi-Fert; gDPR >0.6; n = 36), medium (Med-Fert; gDPR -1.3 to 0.6; n = 45), or low (Lo-Fert; gDPR <-1.3; n = 38) group. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of estrus and ovulation. Body weights, BCS, and uterine health measurements (i.e., vaginal discharge, uterine cytology) were collected from parturition to 60 DIM, and milk yield was collected through 90 DIM. Blood samples were collected weekly through 3 wk of lactation for analysis of BHB, nonesterified fatty acids (NEFA), and haptoglobin plasma concentrations. Body weight, BCS, NEFA, BHB, and haptoglobin were not associated with fertility groups from 1 to 9 wk after parturition. The proportion of cows classified as having endometritis at 33 to 36 DIM tended to be greater for the Lo-Fert than the Hi-Fert group. The proportion of cows that resumed cyclicity did not differ at any time point evaluated, and there were no significant associations between probability or duration and intensity of estrus with fertility group. Cows of superior genetic merit for fertility were more likely to ovulate, have a functional corpus luteum, have greater circulating progesterone, and have larger ovulatory size than cows of inferior fertility potential at key time points during synchronization of estrus and ovulation. Despite observing numerical differences with potential performance consequences for the proportion of cows that responded to synchronization of ovulation and were both cyclic and responded to the Ovsynch portion of the synchronization protocol, we did not observe significant differences between fertility groups. Although not consistent and modest in magnitude, the collective physiological and endocrine differences observed suggested that cows of superior genetic fertility potential might have improved reproductive performance, at least in part, because of modestly improved endocrine status, uterine health, and ability to ovulate., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Objectives: To evaluate the influence of microstructure and chemical composition on the optical properties of CAD-CAM lithium disilicate glass-ceramics., Methods: Samples (n = 5; 1.0 mm thickness) of shades A1, A2, and A3 were fabricated from CAD-CAM ceramic blocks (Ivoclar Vivadent): IPS e.max® CAD LT (emLT) and HT (emHT). Samples were polished to 1.0 ± 0.01 mm in thickness. The optical properties (R- reflectance; T- transmittance; μ s ' - reduced scattering and μ a - absorption coefficients) from the post-crystallized samples were determined using the inverse adding-doubling (IAD) method based on integrating-sphere measurements. Additionally, scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were used to evaluate the microstructural properties. Energy-dispersive X-ray (EDX) was employed to analyze the chemical composition. The chemical and structural characterization were performed before and after crystallization of the ceramic samples., Results: emLT showed higher values of μ s ' and lower values of μ a and T than emHT for each shade in all wavelengths (p < 0.003). Considering T for emHT, there were no statistical differences for shades A1 and A2 at 488 nm and 514.5 nm (p > 0.003) and shades A1 and A3 at 457.9 nm (p > 0.003). emLT showed particle length ranging from 0.74 to 2.78 µm (mean = 1.57 µm and RF-relative frequency = 28 %) and particle width ranging from 0.21 to 0.74 µm (mean = 0.30 µm and RF = 31 %). emHT showed particle length ranging from 0.83 to 3.08 µm (mean = 1.86 µm and RF = 21 %) and particle width ranging from 0.24 to 1.12 µm (mean = 0.56 µm and RF = 28 %). In comparison with emHT, emLT showed greater vol% for C, K, and Zr and lower vol% for O and Al., Significance: The optical properties of CAD-CAM lithium disilicate glass-ceramics are influenced by the chemical composition and, consequently, by the material microstructure., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The objectives of this prospective cohort study were to characterize associations among genomic merit for fertility with ovarian and endocrine function and the estrous behavior of dairy cows during an entire nonhormonally manipulated estrous cycle. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation had ear-notch tissue samples collected for genotyping using a commercial genomic test. Based on genomic predicted transmitting ability values for daughter pregnancy rate (gDPR), cows were classified into high (Hi-Fert; gDPR > 0.6, n = 36), medium (Med-Fert; gDPR -1.3 to 0.6, n = 45), and low fertility (Lo-Fert; gDPR < -1.3, n = 38) groups. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of ovulation and initiation of a new estrous cycle. Thereafter, the ovarian function and endocrine dynamics were monitored daily until the next ovulation by transrectal ultrasonography and concentrations of progesterone (P4), estradiol, and FSH. Estrous behavior was monitored with an ear-attached automated estrus detection system that recorded physical activity and rumination time. Overall, we observed an association between fertility group and the ovarian and hormonal phenotype of dairy cows during the estrous cycle. Cows in the Hi-Fert group had greater circulating concentrations of P4 than cows in the Lo-Fert group from d 4 to 13 after induction of ovulation and from day -3 to -1 before the onset of luteolysis. The frequency of atypical estrous cycles was 3-fold greater for cows in the Lo-Fert than the Hi-Fert group. We also observed other modest associations between genomic merit for fertility with the follicular dynamics and estrous behavior. We found several associations between milk yield and parity with ovarian, endocrine, and estrous behavior phenotypes as cows with greater milk yield and in the second lactation were more likely to have unfavorable phenotypes. These results demonstrate that differences in reproductive performance between cows of different genomic merit for fertility classified based on gDPR may be partially associated with circulating concentrations of P4, the incidence of atypical phenotypes during the estrous cycles, and, to a lesser extent, the follicular wave dynamics. The observed physiological and endocrine phenotypes might help explain part of the differences in reproductive performance between cows of superior and inferior genomic merit for fertility., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The existing literature points towards the presence of robust mitochondrial mechanisms aimed at mitigating protein dyshomeostasis within the organelle. However, the precise molecular composition of these mechanisms remains unclear. Our data show that inorganic polyphosphate (polyP), a polymer well-conserved throughout evolution, is a component of these mechanisms. In mammals, mitochondria exhibit a significant abundance of polyP, and both our research and that of others have already highlighted its potent regulatory effect on bioenergetics. Given the intimate connection between energy metabolism and protein homeostasis, the involvement of polyP in proteostasis has also been demonstrated in several organisms. For example, polyP is a bacterial primordial chaperone, and its role in amyloidogenesis has already been established. Here, using mammalian models, our study reveals that the depletion of mitochondrial polyP leads to increased protein aggregation within the organelle, following stress exposure. Furthermore, mitochondrial polyP is able to bind to proteins, and these proteins differ under control and stress conditions. The depletion of mitochondrial polyP significantly affects the proteome under both control and stress conditions, while also exerting regulatory control over gene expression. Our findings suggest that mitochondrial polyP is a previously unrecognized, and potent component of mitochondrial proteostasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Da Costa, Urquiza, Perez, Du, Khong, Zheng, Guitart-Mampel, Elustondo, Scoma, Hambardikar, Ueberheide, Tanner, Cohen, Pavlov, Haynes and Solesio.)

Corticosteroids have been utilized in modern medicine for decades. Many indications have been investigated across various treatment settings with both benefit and harm observed. Given the instability of critically ill patients, the increased risk of corticosteroid-related complications, and the pervasive comorbidities, patients who receive corticosteroids must be carefully managed. Common critical care disease states in which corticosteroids have been studied and are routinely utilized include acute respiratory distress syndrome, adrenal insufficiency, angioedema, asthma, chronic obstructive pulmonary disease, community-acquired pneumonia, coronavirus disease 2019, septic shock, and spinal cord injury. Benefits of corticosteroids include an improvement in disease state-specific outcomes, decreased hospital length of stay, decreased mechanical ventilatory support, and decreased mortality. The harm of corticosteroids is well documented through adverse effects that include, but are not limited to, hyperglycemia, tachycardia, hypertension, agitation, delirium, anxiety, immunosuppression, gastrointestinal bleeding, fluid retention, and muscle weakness. Furthermore, corticosteroids are associated with increased health care costs through adverse effects as well as drug acquisition and administration costs. Given the assortment of agents, dosing, benefits, risks, and utilization in the critical care setting, there may be difficulty with identifying the appropriate places for use of corticosteroids in therapy. There currently exists no comprehensive report detailing the use of corticosteroids in the aforementioned disease states within the critical care setting. This narrative review sets out to describe these in detail., (© 2024 Pharmacotherapy Publications, Inc.)

Introduction: Diabetes Mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia and/or insulin resistance. If left uncontrolled, it can lead to a combination of cardiac and renal alterations known as cardiorenal syndrome. Additionally, oxidative stress and inflammation contribute to tissue damage, thereby reducing the life expectancy of individuals with diabetes., Aim: The aim of this study was to identify early molecular markers associated with cardiorenal syndrome, oxidative stress, and inflammation, and to investigate their correlation with the duration of exposure to DM., Methods: An experimental DM model was employed using Wistar rats. The rats were divided into four groups: diabetic rats at 7 days (DM7), diabetic rats at 30 days (DM30), control sham at 7 days (CS7), and control sham at 30 days (CS30). Blood and brain tissue from the brainstem region were collected at 7 and 30 days after confirming DM induction. Gene expression analysis of Bnp, Anp, Cat, Gpx, Sod, Tnf-α, and Il-6 was performed., Results: The analysis revealed lower expression values of Cat in the brainstem tissue of the DM7 group compared to the NDS7 group. Moreover, diabetic animals exhibited statistically lower levels of Tnf-α in their peripheral blood compared to the control animals., Conclusion: This study concluded that DM alters the oxidative balance in the brainstem after 7 days of DM induction, resulting in lower Cat expression levels. Although some genes did not show statistical differences after 30 days of DM induction, other genes exhibited no expression values, indicating possible gene silencing. The study identified an imbalance in the studied pathways and concluded that the organism undergoes a compensatory state in response to the initial metabolic alterations caused by DM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In eukaryotes, the Suv39 family of proteins tri-methylate lysine 9 of histone H3 (H3K9me) to form constitutive heterochromatin. However, how Suv39 proteins are nucleated at heterochromatin is not fully described. In the fission yeast, current models posit that Argonaute1-associated small RNAs (sRNAs) nucleate the sole H3K9 methyltransferase, Clr4/SUV39H, to centromeres. Here, we show that in the absence of all sRNAs and H3K9me, the Mtl1 and Red1 core (MTREC)/PAXT complex nucleates Clr4/SUV39H at a heterochromatic long noncoding RNA (lncRNA) at which the two H3K9 deacetylases, Sir2 and Clr3, also accumulate by distinct mechanisms. Iterative cycles of H3K9 deacetylation and methylation spread Clr4/SUV39H from the nucleation center in an sRNA-independent manner, generating a basal H3K9me state. This is acted upon by the RNAi machinery to augment and amplify the Clr4/H3K9me signal at centromeres to establish heterochromatin. Overall, our data reveal that lncRNAs and RNA quality control factors can nucleate heterochromatin and function as epigenetic silencers in eukaryotes., Competing Interests: Declaration of interests M.M. and J.S.K. have a pending US provisional patent application related to the data from this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We consider unsupervised classification by means of a latent multinomial variable which categorizes a scalar response into one of the L components of a mixture model which incorporates scalar and functional covariates. This process can be thought as a hierarchical model with the first level modelling a scalar response according to a mixture of parametric distributions and the second level modelling the mixture probabilities by means of a generalized linear model with functional and scalar covariates. The traditional approach of treating functional covariates as vectors not only suffers from the curse of dimensionality, since functional covariates can be measured at very small intervals leading to a highly parametrized model, but also does not take into account the nature of the data. We use basis expansions to reduce the dimensionality and a Bayesian approach for estimating the parameters while providing predictions of the latent classification vector. The method is motivated by two data examples that are not easily handled by existing methods. The first example concerns identifying placebo responders on a clinical trial (normal mixture model) and the other predicting illness for milking cows (zero-inflated mixture of the Poisson model)., Competing Interests: Conflict of interest: None declared., (© The Royal Statistical Society 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients receiving dialysis have high cardiovascular risk in part due to extensive vascular calcification. In the CaLIPSO study, infusion of hexasodium fytate (SNF472), the hexasodium salt of inositol hexaphosphate, for 52 weeks thrice weekly during hemodialysis significantly reduced progression of coronary artery calcification (CAC). This report examines pharmacokinetic/pharmacodynamic (PK/PD) and exposure-efficacy in CaLIPSO. Methods: We measured hexasodium fytate plasma concentrations (PK) by validated liquid chromatography-mass spectroscopy, and hydroxyapatite crystallization in plasma (PD) by validated spectrophotometry. Analyses included patients evaluable for PK, PD, and CAC change (per-protocol analysis). We developed a simple E max model for maximum concentration (C max ) and PD effect, and linear and non-linear E max models for exposure-efficacy among individual average C max and absolute and percent changes in CAC score from baseline to week 52. Results: Among evaluable patients receiving placebo ( n = 15), 300 mg ( n = 20), or 600 mg ( n = 20), average C max across visits was not quantifiable (<0.76 μM), 15 μM, and 46 μM, respectively. These results suggest a more-than-proportional increase, without accumulation, with a C max ratio of approximately 3 for the doses administered. Average inhibition of hydroxyapatite crystallization was 15%, 61%, and 75%, respectively, and similar across visits. Simple E max models described 80% maximal effect at exposures >21.9 µM and a plateau in exposure-efficacy above the third quartile of C max (≥32 µM). Conclusion: Hexasodium fytate has exposure-dependent effects on hydroxyapatite crystallization and progression of cardiovascular calcification. Simple E max models show robust relations among exposure, inhibition of hydroxyapatite crystallization, and change in CAC volume. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier NCT02966028., Competing Interests: JP, FB, and MF are consultants for Sanifit and have patents related to hexasodium fytate. MP and CS are employees of Sanifit and have patents related to hexasodium fytate. JA, JT, and PR have served as consultants to Sanifit. JT is employed by Optimapharm. AG was an employee of Sanifit and has patents related to hexasodium fytate. GC serves on the Board of Directors for Satellite Healthcare, a non-profit dialysis provider; has received research grants from NIDDK, NIAID, and CSL Behring; has served on trial steering committees with Akebia, AstraZeneca, Gilead, Sanifit, and Vertex; has served as an advisor to Ardelyx, CloudCath, Durect, Miromatrix, Outset, Renibus, Reata, and Unicycive; and has served on data safety monitoring boards for NIDDK, Bayer, Mineralys, and ReCor., (Copyright © 2024 Perelló, Alberti, Torres, Ferrer, Perez, Bassissi, Gold, Raggi, Chertow and Salcedo.)

Background: Dysferlinopathies represent a group of limb girdle or distal muscular dystrophies with an autosomal-recessive inheritance pattern resulting from the presence of pathogenic variants in the dysferlin gene (DYSF)., Objective: In this work, we describe a population from a small city in Brazil carrying the c.5979dupA pathogenic variant of DYSF responsible for limb girdle muscular dystrophy type 2R and distal muscular dystrophy., Methods: Genotyping analyses were performed by qPCR using customized probe complementary to the region with the duplication under analysis in the DYSF., Results: A total of 104 individuals were examined. c.5979dupA was identified in 48 (46.15%) individuals. Twenty-three (22%) were homozygotes, among whom 13 (56.5%) were female. A total of 91.3% (21) of homozygous individuals had a positive family history, and seven (30.4%) reported consanguineous marriages. Twenty-five (24%) individuals were heterozygous (25.8±16 years) for the same variant, among whom 15 (60%) were female. The mean CK level was 697 IU for homozygotes, 140.5 IU for heterozygotes and 176 IU for wild-type homo-zygotes. The weakness distribution pattern showed 17.3% of individuals with a proximal pattern, 13% with a distal pattern and 69.6% with a mixed pattern. Fatigue was present in 15 homozygotes and one heterozygote., Conclusion: The high prevalence of this variant in individuals from this small community can be explained by a possible founder effect associated with historical, geographical and cultural aspects., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2023 Bentham Science Publishers.)

Introduction: Inorganic polyphosphate (polyP) is an ancient polymer which is extremely well-conserved throughout evolution, and found in every studied organism. PolyP is composed of orthophosphates linked together by high-energy bonds, similar to those found in ATP. The metabolism and the functions of polyP in prokaryotes and simple eukaryotes are well understood. However, little is known about its physiological roles in mammalian cells, mostly due to its unknown metabolism and lack of systematic methods and effective models for the study of polyP in these organisms. Methods: Here, we present a comprehensive set of genetically modified cellular models to study mammalian polyP. Specifically, we focus our studies on mitochondrial polyP, as previous studies have shown the potent regulatory role of mammalian polyP in the organelle, including bioenergetics, via mechanisms that are not yet fully understood. Results: Using SH-SY5Y cells, our results show that the enzymatic depletion of mitochondrial polyP affects the expression of genes involved in the maintenance of mitochondrial physiology, as well as the structure of the organelle. Furthermore, this depletion has deleterious effects on mitochondrial respiration, an effect that is dependent on the length of polyP. Our results also show that the depletion of mammalian polyP in other subcellular locations induces significant changes in gene expression and bioenergetics; as well as that SH-SY5Y cells are not viable when the amount and/or the length of polyP are increased in mitochondria. Discussion: Our findings expand on the crucial role of polyP in mammalian mitochondrial physiology and place our cell lines as a valid model to increase our knowledge of both mammalian polyP and mitochondrial physiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hambardikar, Akosah, Scoma, Guitart-Mampel, Urquiza, Da Costa, Perez, Riggs, Patel and Solesio.)

Our objectives were to compare the proportion of lactating dairy cows diagnosed with health disorders (HD) and herd performance when using a health monitoring program designed to rely primarily but not exclusively on alerts from automated health monitoring (AHM) systems or a health monitoring program based primarily on systematic clinical examinations, milk yield monitoring, and visual observation of cows. In a clinical trial, at ∼30 d before expected parturition, nulliparous and parous Holstein cows, stratified by parity and days in gestation, were randomly assigned to the high-intensity clinical monitoring (HIC-M; n = 625) or automated monitoring (AUT-M; n = 624) treatment. Cows were fitted with a neck-attached rumination and physical activity monitoring tag, and individual daily milk yield data were collected from parlor milk meters. For cows in HIC-M, clinical examination was conducted daily until 10 d in milk (DIM) and then in response to milk yield reduction alerts or visual observation of clinical signs of HD over the course of 21 DIM. For cows in AUT-M, clinical examination until 21 DIM was because of health index (HI) score alerts and reduced milk yield alerts. The HI score alerts used were generated based on the manufacturer's settings for the system for the last 2-h period before cows were selected for examination. Visual observation of clinical signs of HD was used for identifying cows potentially missed by automated alerts. Binomial and quantitative data were analyzed by logistic regression and ANOVA with repeated measures, respectively. The percentage of cows diagnosed with at least 1 HD during the experimental treatments risk period tended to be greater and the incidence rate ratio of HD diagnosed was greater in the HIC-M than in the AUT-M treatment. We found no difference between treatments for cows that exited the herd up to 60 or 150 DIM, but more cows tended to exit the herd from 61 to 150 DIM in the HIC-M than in the AUT-M treatment. No differences were detectable between treatments in daily or total milk yield to 21 DIM or in weekly mean milk yield and total milk yield to 150 DIM. More cows were inseminated in estrus for first service if in the HIC-M treatment and had no HD diagnosed than if in the HIC-M treatment but with HD diagnosed, or in the AUT-M treatment and had no HD diagnosed. Cows in the AUT-M treatment with HD diagnosed did not differ from other groups. No differences between treatments were observed in pregnancies per artificial insemination or pregnancy loss for first service. Despite a reduction in the risk of diagnosis of HD, no evidence indicated that a health monitoring program that relied on AHM system alerts to select cows for clinical examination reduced herd performance compared with a more intensive program that included systematic clinical examinations of all cows for the first 10 DIM, reduced milk yield alerts, and visual observation. However, to obtain the same herd performance as with the HIC-M treatment, the AUT-M treatment required use of visual observation. In conclusion, a health monitoring program designed to rely primarily on targeted clinical examination based on alerts from automated health monitoring systems might be a feasible alternative to programs that rely more on clinical examination, provided that visual observation is used to identify cows not detected by automated alerts., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Objectives: Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of Sirt6 deficiency on the development of post-traumatic and age-associated OA in mice., Methods: Male cartilage-specific Sirt6 -deficient mice and Sirt6 intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting., Results: Sirt6- deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that SIRT6 depletion significantly repressed cartilage extracellular matrix (eg, COL2A1 ) and anabolic growth factor (eg, insulin-like growth factor-1 ( IGF-1 )) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced SIRT6 activation promoted IGF-1 signalling by increasing Akt ser473 phosphorylation., Conclusions: SIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: The aim of this study was to investigate the role of irisin in type 2 diabetes mellitus and its association with metabolic alterations and obesity., Methods: A cross-sectional case-control study was conducted on participants treated at Centro Universitário FMABC between August 2018 and July 2019, by comparing a control group (n=14) with type 2 diabetes mellitus patients (n=16). The control group consisted of participants aged above 21 years with no chronic diseases, diabetes, smoking, or illicit drug use. The type 2 diabetes mellitus group included patients aged above 21 years, who were diagnosed with type 2 diabetes for at least 5 years (glycated hemoglobin>7%). Exclusion criteria were not willing to continue, recent hospitalization, and failure to meet inclusion criteria. Biochemical parameters included blood glucose, glycated hemoglobin, plasma irisin levels, and irisin gene expression in peripheral blood., Results: Type 2 diabetes mellitus patients exhibited significantly higher plasma glucose levels [143 (40) vs. 92 (13) mg/dL, *p<0.05] and glycated hemoglobin levels [7.1% (1.6) vs. 5.6% (0.5), *p<0.05] compared to the control group. Irisin gene expression in type 2 diabetes mellitus patients was lower 0.02288 (0.08050) than the control group 8.506e-006 (1.412e-005) (p=0.06). Correlation analysis revealed a positive association between irisin expression and body mass index in type 2 diabetes mellitus (Rho=0.5221, 95%CI -0.058 to 0.838, p=0.06), while plasma irisin showed a negative correlation with body mass index (Rho=-0.656, 95%CI -0.836 to 0.215, p=0.03). No significant correlations were found between plasma glucose or glycated hemoglobin levels and irisin expression., Conclusion: The data suggests that body mass index directly influences plasma irisin levels and the regulation of irisin gene expression, possibly linking irisin to adiposity changes observed in obesity-related type 2 diabetes mellitus.

Hyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy-DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult-DMA-or elderly-DME and control sham adult-CSA-or control sham elderly-CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1, MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies., (© 2023. Springer Nature Limited.)

The aims of this study were to 1) assess the association between erosive tooth wear (ETW) according to the BEWE (Basic Erosive Wear Examination) scoring system and salivary parameters and 2) compare salivary parameters according to ETW severity in the subgroup of children with ETW. This cross-sectional study included 52 preschool children aged 5 years paired by sex. A calibrated examiner assessed ETW using BEWE criteria, and stimulated saliva was collected to determine salivary flow, osmolality, pH, and buffering capacity. The children were divided into two groups: without ETW (n=26; BEWE score 0) and with ETW (n=26; BEWE scores 1 and 2). Logistic regression analysis was used to determine the magnitude of the association between ETW and salivary parameters and estimates of odds ratios (OR). In the unadjusted analysis, the ETW group was more likely to have lower salivary flow (OR = 0.079; 95%CI = 0.013-0.469; p = 0.005) and lower osmolality (OR = 0.993; 95%CI = 0.985-1.000; p = 0.049). In the adjusted analysis, salivary flow remained significantly associated with ETW (OR = 0.087; 95%CI = 0.014-0.533; p = 0.008). Lower salivary osmolality values were observed in ETW, especially in preschool children with more severe ETW (BEWE score 2). Receiver operating characteristic (ROC) determined a salivary osmolality cutoff point of < 201 for the presence of ETW. In conclusion, salivary flow rate was significantly associated with ETW prevalence. Lower values of salivary osmolality were observed in preschool children with distinct erosive lesions with significant loss of tooth structure (BEWE 2).

Objective: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients., Methods: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction., Results: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor., Conclusion: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Intrinsic hand muscles play a fundamental role in tuning the fine motricity of the hand and may be affected by several pathologic conditions, including traumatic injuries, atrophic changes induced by denervation, and space-occupying masses. Modern hand surgery techniques allow to target several hand muscle pathologies and, as a direct consequence, requests for hand imaging now carry increasingly complex diagnostic questions. The progressive refinement of ultrasound technology and the current availability of high and ultra-high frequency linear transducers that allow the investigation of intrinsic hand muscles and tendons with incomparable resolution have made this modality an essential tool for the evaluation of pathological processes involving these tiny structures. Indeed, intrinsic hand muscles lie in a superficial position and are amenable to investigation by means of transducers with frequency bands superior to 20 MHz, offering clear advantages in terms of resolution and costs compared to magnetic resonance imaging. In addition, ultrasound allows to perform dynamic maneuvers that can critically enhance its diagnostic power, by examining the questioned structure during stress tests that simulate the conditions eliciting clinical symptoms. The present article aims to review the anatomy, the ultrasound scanning technique, and the clinical application of thenar, hypothenar, lumbricals and interossei muscles imaging, also showing some examples of pathology involving these structures., Competing Interests: Conflict of interest The authors do not report any financial or personal connections with other persons or organizations which might negatively affect the contents of this publication and/or claim authorship rights to this publication., (© 2023 Riccardo Picasso et al., published by Sciendo.)

Plantar intrinsic muscles play a pivotal role in posture control and gait dynamics. They help maintain the longitudinal and transverse arches of the foot, and they regulate the degree and velocity of arch deformation during walking or running. Consequently, pathologies affecting the plantar intrinsic muscles (for instance, acquired and inherited neuropathies) lead to foot deformity, gait disorders, and painful syndromes. Intrinsic muscle malfunctioning is also associated with multifactorial overuse or degenerative conditions such as pes planus, hallux valgus, and plantar fasciitis. As the clinical examination of each intrinsic muscle is challenging, ultrasound is gaining a growing interest as an imaging tool to investigate the trophism of these muscular structures and the pattern of their alterations, and potentially to follow up on the effects of dedicated rehabilitation protocols. The ten plantar intrinsic muscles can be dived into three groups (medial, central and lateral) and four layers. Here, we propose a regional and landmark-based approach to the complex sonoanatomy of the plantar intrinsic muscles in order to facilitate the correct identification of each muscle from the superficial to the deepest layer. We also summarize the pathological ultrasound findings that can be encountered when scanning the plantar muscles, pointing out the patterns of alterations specific to certain conditions, such as plantar nerves mononeuropathies., Competing Interests: Conflict of interest The authors do not report any financial or personal connections with other persons or organizations which might negatively affect the contents of this publication and/or claim authorship rights to this publication., (© 2023 Federico Zaottini et al., published by Sciendo.)

Our objective was to compare reproductive outcomes of primiparous lactating Holstein cows of different genetic merit for fertility submitted for insemination with management programs that prioritized artificial insemination (AI) at detected estrus (AIE) or timed AI (TAI). Moreover, we aimed to determine whether subgroups of cows with different fertility potential would present a distinct response to the reproductive management strategies compared. Lactating primiparous Holstein cows (n = 6 commercial farms) were stratified into high (Hi-Fert), medium (Med-Fert), and low (Lo-Fert) genetic fertility groups (FG) based on a Reproduction Index value calculated from multiple genomic-enhanced predicted transmitting abilities. Within herd and FG, cows were randomly assigned either to a program that prioritized TAI and had an extended voluntary waiting period (P-TAI; n = 1,338) or another that prioritized AIE (P-AIE; n = 1,416) and used TAI for cows, not AIE. Cows in P-TAI received first service by TAI at 84 ± 3 d in milk (DIM) after a Double-Ovsynch protocol, were AIE if detected in estrus after a previous AI, and received TAI after an Ovsynch-56 protocol at 35 ± 3 d after a previous AI if a corpus luteum (CL) was visualized at nonpregnancy diagnosis (NPD) 32 ± 3 d after AI. Cows with no CL visualized at NPD received TAI at 42 ± 3 d after AI after an Ovsynch-56 protocol with progesterone supplementation (P4-Ovsynch). Cows in P-AIE were eligible for AIE after a PGF 2α treatment at 53 ± 3 DIM and after a previous AI. Cows not AIE by 74 ± 3 DIM or by NPD 32 ± 3 d after AI received P4-Ovsynch for TAI at 74 ± 3 DIM or 42 ± 3 d after AI. Binary data were analyzed with logistic regression, count data with Poisson regression, continuous data by ANOVA, and time to event data by Cox's proportional hazard regression. Pregnancy per AI (P/AI) to first service was greater for cows in the Hi-Fert (59.8%) than the Med-Fert (53.6%) and Lo-Fert (47.7%) groups, and for the P-TAI (58.7%) than the P-AIE (48.7%) treatment. Overall, P/AI for all second and subsequent AI combined did not differ by treatment (P-TAI = 45.2%; P-AIE = 44.5%) or FG (Hi-Fert = 46.1%; Med-Fert = 46.0%; Lo-Fert = 42.4%). The hazard of pregnancy after calving was greater for the P-AIE than the P-TAI treatment [hazard ratio (HR) = 1.27, 95% CI: 1.17 to 1.37)], and for the Hi-Fert than the Med-Fert (HR = 1.16, 95% CI: 1.05 to 1.28) and Lo-Fert (HR = 1.34, 95% CI: 1.20 to 1.49) groups. More cows in the Hi-Fert (91.2%) than the Med-Fert (88.4%) and Lo-Fert (85.8%) groups were pregnant at 200 DIM. Within FG, the hazard of pregnancy was greater for the P-AIE than the P-TAI treatment for the Hi-Fert (HR = 1.41, 95% CI: 1.22 to 1.64) and Med-Fert (HR = 1.28, 95% CI: 1.12 to 1.46) groups but not for the Lo-Fert group (HR = 1.13, 95% CI: 0.98 to 1.31). We conclude that primiparous Holstein cows of superior genetic merit for fertility had better reproductive performance than cows of inferior genetic merit for fertility, regardless of the type of reproductive management used. In addition, the effect of programs that prioritized AIE or TAI on reproductive performance for cows of superior or inferior genetic merit for fertility depended on the outcomes evaluated. Thus, programs that prioritize AIE or TAI could be used to affect certain outcomes of reproductive performance or management., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI.

Study Objective: Significant practice variation exists when selecting between hydrocortisone and vasopressin as second line agents in patients with septic shock in need of escalating doses of norepinephrine. The goal of this study was to assess differences in clinical outcomes between these two agents., Design: Multicenter, retrospective, observational study., Setting: Ten Ascension Health hospitals., Patients: Adult patients with presumed septic shock receiving norepinephrine prior to study drug initiation between December 2015 and August 2021., Intervention: Vasopressin (0.03-0.04 units/min) or hydrocortisone (200-300 mg/day)., Measurements and Main Results: A total of 768 patients were included with a median (interquartile range) SOFA score of 10 (8-13), norepinephrine dose of 0.3 mcg/kg/min (0.1-0.5 mcg/kg/min), and lactate of 3.8 mmol/L (2.4-7.0 mmol/L) at initiation of the study drug. A significant difference in 28-day mortality was noted favoring hydrocortisone as an adjunct to norepinephrine after controlling for potential confounding factors (OR 0.46 [95% CI, 0.32-0.66]); similar results were seen following propensity score matching. Compared to vasopressin, hydrocortisone initiation was also associated with a higher rate of hemodynamic responsiveness (91.9% vs. 68.2%, p < 0.01), improved resolution of shock (68.8% vs. 31.5%, p < 0.01), and reduced recurrence of shock within 72 h (8.7% vs. 20.7%, p < 0.01)., Conclusions: Addition of hydrocortisone to norepinephrine was associated with a lower 28-day mortality in patients with septic shock, compared to the addition of vasopressin., (© 2023 Pharmacotherapy Publications, Inc.)

Background: Cytomegalovirus (CMV) infection is one of the most common posttransplantation infections and has been associated with increased rejection and mortality. Data in intestinal transplants recipients are limited., Methods: This is a single-center, retrospective cohort study of all intestinal transplants performed between January 1, 2009, and August 31, 2020. We included recipients of all ages who were at risk of CMV infection. To identify the risk factors, we conducted at first univariate and multivariate analysis. For the multivariate analysis, we developed a logistic regression model based on the result of univariate analysis., Results: Ninety five patients with a median age of 32 (interquartile range [IQR] 4, 50) were included. CMV donor seropositive/recipient seronegative were 17 (17.9%). Overall, 22.1% of the recipients developed CMV infection at a median time of 155 (IQR 28-254) days from transplant, including 4 CMV syndrome and 6 CMV end-organ disease. Overall, 90.4%, (19/21) developed DNAemia while on prophylaxis. Median peak viral load and time to negativity was 16 000 (IQR 1034-43 892) IU/mL and 56 (IQR 49-109) days, respectively. (Val)ganciclovir and foscarnet were utilized in 17 (80.9%) and 1 (4.76%) recipients, respectively. Recurrences of CMV DNAemia and graft rejection were observed in three and six recipients, respectively. Younger age was identified as a risk factor (p = .032, odds ratio 0.97, 95% confidence interval 0.95-0.99) to develop CMV DNAemia., Conclusion: A significant proportion of intestinal transplant recipients developed CMV infection while on prophylaxis. Better methods such as CMV cell mediated immunity guided prophylaxis should be used to prevent infections in this population., (© 2023 Wiley Periodicals LLC.)

Background: It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects., Objective: This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor., Methods: Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs., Results: Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment., Conclusion: In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The transient receptor potential vanilloid type-1 (TRPV1) channels have been implicated in the modulation of aversive responses. The endocannabinoid anandamide acts as an endogenous TRPV1 agonist, exerting opposite functions at TRPV1 and type-1 cannabinoid receptors (CB 1 R). Here we tested the hypothesis that hippocampal TRPV1 modulates contextual fear memory retrieval and investigated the influence of the aversive stimulus intensity as well as the role of endocannabinoid signaling. Male C57BL/6J mice were tested for contextual fear memory after low-, moderate-, or high-intensity shock protocols. The selective TRPV1 blockers SB366791 (1-10 nmol) and 6-I-NC (2 nmol) were infused via intra-dorsal hippocampus before the retrieval test session. The local levels of endocannabinoids and Arc and Zif268 mRNAs, involved in synaptic plasticity and memory, were quantified. First, both TRPV1 blockers reduced memory retrieval in animals exposed to moderate or high (but not low) intensity training protocols. In the second series of results, the magnitude of the freezing responses positively correlated with the hippocampal anandamide levels; TRPV1 and CB 1 R were found co-localized in this brain region; and the CB 1 R antagonist, AM251, prevented the effects of SB366791. Thus, endocannabinoid signaling possibly mediates the effects of TRPV1 blockers. Finally, inhibition of memory retrieval by TRPV1 blockers increased Arc and Zif268 mRNAs and impaired fear memory reinstatement. In conclusion, the modulation of fear memories by dorsal hippocampal TRPV1 channels may depend on the aversive stimulus intensity and occur via anandamide/CB 1 signaling. Moreover, TRPV1 blockers promote Arc and Zif268 transcription, with subsequent attenuation of aversive memory reinstatement., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction and Aim: Vitamin D is the name given to a group of lipid-soluble steroidal substances of physiological importance in the body, especially in bone metabolism. The active form of vitamin D is believed to have immunomodulatory effects on immune system cells, especially T lymphocytes, as well as on the production and action of several cytokines and on the expression of potent antimicrobial peptides in epithelial cells that line the respiratory tract, playing an important role in protecting the lung from infections. The aim of this study was to assess vitamin D levels in patients with COVID-19 in healthcare service and to verify that these levels are adequate to protect the progression of this infection., Methods: The aim of this observational study was to evaluate the serum concentration of vitamin D in 300 patients suspected of being infected with COVID-19, treated at Basic Health Units (BHUs) and at the Hospital Complex in the municipality of São Bernardo do Campo., Results: 294 patients were included, 195 (66%) of which tested positive for COVID-19 and 99 (34%) negative for COVID-19. Among the patients in the positive group, 163 patients were in the mild group (84%); 22 patients in the moderate group (11%); 8 patients in the severe group (4%), and 2 patients in the deceased group (1%)., Conclusion: For the patients in this study, no association was observed for the protective factor of vitamin D against COVID-19 infection, and its role in controlling the clinical staging of the disease was not verified., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Abstract: Conical deformities found at the apices of incisions after wound closure represent tissue redundancy, commonly known as "dog ears." The amount of tissue excess is related to the geometry of the incision, surrounding skin elasticity, and tension of closure. Experience with tissue handling shows that some dog ears do "settle" or resolve with time; such cases occur when local tissue has high skin elasticity, the dog ears are small in height, and tension on the line of closure is low. Dog ears that do not fall into this category can be troublesome to surgeon and patient alike as they can poorly impact aesthetic outcomes and lead to secondary revision procedures. Therefore, we present a pertinent review of the mechanisms behind dog-ear formation and the variety of surgical techniques used to minimize and correct their formation., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Incisional hernia is characterized by a bulging of the abdominal wall caused by the prolapse of intracavitary structures, such as a segment of the small intestine, through the trocar orifice. Ultrasonography and physical examination are used in the diagnosis of incisional hernia., Aims: This study aimed to evaluate the difference between physical examination and abdominal ultrasonography at the diagnosis of incisional hernia in patients who underwent laparoscopic bariatric surgery., Methods: A total of 123 patients who underwent Roux-en-Y gastric bypass type bariatric surgery performed by laparoscopy were analyzed for the presence or absence of hernia by physical and ultrasonography examination at each trocar incision site., Results: In our results, a total of 7 hernias were detected by physical examination, while ultrasonography detected a total of 56 hernias in at least one of the incision sites. Lin's concordance analysis showed that the tests are not concordant. The association between body mass index and hernia detection (p=0.04 for physical examination and p=0.052 for ultrasonography) was observed. Ultrasonography detected more incisional hernias in 10-mm or larger trocars than in 5-mm trocars (p<0.0001, p<0.05). No differences were noted among the trocar types that were used., Conclusions: Abdominal ultrasonography showed to have a higher accuracy than physical examination, resulting in a substantial increase in incisional hernia detection at the trocar sites.

New perspectives arise in the therapeutic practice for cancer, with the objective to not only treat patients, but also improve their quality of life. Guarana , a plant from Brazilian Amazon presents a wide range of pharmacological actions. This study evaluated the effect of Guarana ( Paullinia cupana ) extract, pure and dry Guarana (PC-18) extract and magnesium chloride (MgCl 2 ) in mice of the Balb/c strain inoculated with the Ehrlich tumor regarding gene expression of inflammatory markers transforming growth factor- β 1 and tumor necrosis factor alpha and oxidative stress (OS) and fatigue, superoxide dismutase, catalase, and glutathione peroxidase 4 and analyzed myelotoxicity and hepatotoxicity. After euthanasia, blood was collected to analyze the complete blood count and measured the levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase). Hepatoprotective actions of the crude extract of P. cupana and PC-18 extract were noticed. The PC-18 and MgCl 2 group showed the best result regarding animal welfare. There were no associations between compounds and gene expression regarding fatigue and OS. PC-18 reduced the tumor and may have an antitumor action. The crude extract of Guarana presented hepatoprotective action.

Virulence in Pseudomonas aeruginosa (PA) depends on complex regulatory networks, involving phosphorelay systems based on two-component systems (TCSs). The GacS/GacA TCS is a master regulator of biofilm formation, swarming motility, and virulence. GacS is a membrane-associated unorthodox histidine kinase (HK) whose phosphorelay signaling pathway is inhibited by the RetS hybrid HK. Here we provide structural and functional insights into the interaction of GacS with RetS. The structure of the GacS-HAMP-H1 cytoplasmic regions reveals an unusually elongated homodimer marked by a 135 Å long helical bundle formed by the HAMP, the signaling helix (S helix) and the DHp subdomain. The HAMP and S helix regions are essential for GacS signaling and contribute to the GacS/RetS binding interface. The structure of the GacS D1 domain together with the discovery of an unidentified functional ND domain, essential for GacS full autokinase activity, unveils signature motifs in GacS required for its atypical autokinase mechanism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to evaluate in vivo the color agreement between natural teeth and dental shade guides by means of visual and instrumental coverage error ([Formula: see text]) index., Materials and Methods: The color of the middle third of 735 incisors was visually determined by two evaluators using the Vita Classical (VC) and Vita 3D Master (V3DM) shade guides. The color match between the natural tooth and the shade tab was rated as poor (P), good (G), or optimum (O) by each observer. CIE color coordinates of the target teeth and shade tabs of VC and V3DM were instrumentally measured using a clinical spectrophotometer. Visual ([Formula: see text]) and instrumental ([Formula: see text]) coverage error indexes were computed using CIELAB and CIEDE2000 metrics for both shade guides. For [Formula: see text] calculation, only the concordant inter-observer determination on tooth shade rated as O-O or O-G was used. The results were evaluated using perceptibility (PT, [Formula: see text]= 1.2, [Formula: see text]= 0.8) and acceptability (AT, [Formula: see text]= 2.7, [Formula: see text]= 1.8) color thresholds for dentistry., Results: VC and V3DM exhibited [Formula: see text] (2.5, 3.2, and 3.2, 2.7 CIELAB units; 1.9, 2.3, and 2.8, 2.4 CIEDE2000 units, respectively, for O-O and O-G match) and [Formula: see text] (4.7, 4.8, and 4.1, 4.6 CIELAB units; 3.3, 3.4, and 3.4, 3.6 CIEDE2000 units, respectively, for O-O and O-G match) values greater than 50:50% AT for both color difference formulas. [Formula: see text] contributes more than 50% (53.2-82.4% range) to the [Formula: see text] value. This contribution depends on the shade guide used and the quality of the visual rating., Conclusions: The evaluated shade guides exhibited visual coverage errors above acceptability thresholds, largely due to the contribution of the instrumental coverage error to the visual coverage error., Clinical Relevance: It necessary to further improve commercially available dental shade guides to facilitate achievement of satisfactory esthetics results in clinical practice., (© 2022. The Author(s).)

Milestone achievements are reduced in people with schizophrenia and are lower in comparison to people with bipolar disorder. However, it is not clear what the implications are for engagement in momentary activities based on milestone achievements. Further, some recent research has suggested that psychotic symptoms are associated with challenges in self-assessment of activities, but there is less information about the correlations of milestone achievements and ongoing psychotic symptoms. We examined momentary activities and symptoms as a function of lifetime milestone achievement in 102 individuals with schizophrenia and 71 with bipolar disorder. Ecological Momentary Assessment (EMA) was used to sample daily activities and concurrent symptoms 3 times per day for 30 days. Each survey asked the participant where they were, who they were with, and what they were doing, as well as sampling the concurrent presence of psychotic symptoms. Not being financially responsible for their residence was associated with engaging in fewer productive activities. Participants who never had a relationship were more commonly home and alone and engaged in fewer social interactions. A lifetime history of employment was correlated with engaging in more productive activities, including at home. More common momentary psychosis was seen in participants who failed to achieve each of the functional milestones. Lifetime milestone achievements were associated with greater frequencies of productive behaviors and with fewer momentary experiences of psychosis, suggesting that psychotic symptoms may have importance for sustaining disability that would be challenging to detect without momentary information.