The Microbiota-Gut-Brain Axis.

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

Maternal high-fat diet-induced microbiota changes are associated with alterations in embryonic brain metabolites and adolescent behaviour.

The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism and glutamate signalling during critical developmental windows during the perinatal period.

Peritoneal Protein Loss With Time in Peritoneal Dialysis.

Longitudinal evolution of peritoneal protein loss (PPL), a reflection of hydrostatic pressure-driven leak of plasma proteins through the large-pore pathway, is not clear. Time on PD causes loss of mesothelial cells, vasculopathy, and increased thickness of the submesothelial fibrous layer. Are these structural changes associated with progressive increase of PPL, in a parallel with the rise in the D/P creatinine? The aim of the present study was to identify longitudinal changes of PPL over time. This single-center, longitudinal study included 52 peritoneal dialysis (PD) patients with a median follow-up of 26.5 months, evaluated at two different time points with a minimum interval of 6 months. Repeated measures analysis was performed using paired sample t-test or the nonparametric Wilcoxon signed-rank test, depending on the distribution. After a median interval of 15.5 months, lower levels of residual renal function and urine volume, lower Kt/V, and creatinine clearance were found. D/P creatinine and PPL were stable, but a decrease in ultrafiltration was present. Systemic inflammation, nutrition, and volume overload showed no significant change with time on PD. Analysis of a subpopulation with over 48 months between initial and subsequential assessment (n = 11) showed again no difference in inflammation, nutritional and hydration parameters from baseline, but importantly PPL decreased after more than 4 years on PD (mean difference 1.2 g/24, p = 0.033). D/P creatinine and dip of sodium remained unchanged. The absence of deleterious effects of time on PD is reassuring, pointing to the benefit of updated PD prescription, including the standard use of more biocompatible solutions towards membrane preservation and adjusted prescription avoiding overhydration and inflammation while maintaining nutritional status. After controlling for confounders, PPL may act as a biomarker of acquired venous vasculopathy, even if small pore fluid transport rates and free water transport are preserved.

The interplay between temperature and an insecticide mixture modulates the stimulatory response of sublethally exposed Myzus persicae.

Temperature can interact with chemical pesticides and modulate their toxicity. Sublethal exposure to pesticides is known to trigger hormetic responses in pests. However, the simultaneous effects of temperature and sublethal exposure to single or mixture-based insecticides on the insects' stimulatory responses are not frequently considered in toxicological studies. Here we investigated the combined effects of temperature on the lethal and sublethal responses of the green peach aphid Myzus persicae after exposure to commercial formulations of a neonicotinoid (thiamethoxam) and a pyrethroid (lambda-cyhalothrin) and their mixture. Firstly, the concentration-response curves of the insecticides were determined under four temperatures (15 °C, 20 °C, 25 °C, and 28 °C) by the leaf dipping method. Subsequently, the sublethal concentrations C0, CL1, CL5, CL10, CL15, CL20, and CL30 were selected to assess sublethal effects on aphids' longevity and reproduction under the same temperatures. The results showed that the mixture of thiamethoxam + lambda-cyhalothrin caused greater toxicity to aphids compared to the formulations with each active ingredient alone and that the toxicity was higher at elevated temperatures. Furthermore, the exposure to low concentrations of the mixture (thiamethoxam + lambda-cyhalothrin) and the separated insecticides induced stimulatory responses in the longevity and fecundity of exposed aphid females, but the occurrence of such hormetic responses depended on the insecticide type, its sublethal concentration, and the temperature as well as their interactions.

Critical windows of early-life microbiota disruption on behaviour, neuroimmune function, and neurodevelopment.

Numerous studies have emphasised the importance of the gut microbiota during early life and its role in modulating neurodevelopment and behaviour. Epidemiological studies have shown that early-life antibiotic exposure can increase an individual's risk of developing immune and metabolic diseases. Moreover, preclinical studies have shown that long-term antibiotic-induced microbial disruption in early life can have enduring effects on physiology, brain function and behaviour. However, these studies have not investigated the impact of targeted antibiotic-induced microbiota depletion during critical developmental windows and how this may be related to neurodevelopmental outcomes. Here, we addressed this gap by administering a broad-spectrum oral antibiotic cocktail (ampicillin, gentamicin, vancomycin, and imipenem) to mice during one of three putative critical windows: the postnatal (PN; P2-9), pre-weaning (PreWean; P12-18), or post-weaning (Wean; P21-27) developmental periods and assessed the effects on physiology and behaviour in later life. Our results demonstrate that targeted microbiota disruption during early life has enduring effects into adolescence on the structure and function of the caecal microbiome, especially for antibiotic exposure during the weaning period. Further, we show that microbial disruption in early life selectively alters circulating immune cells and modifies neurophysiology in adolescence, including altered myelin-related gene expression in the prefrontal cortex and altered microglial morphology in the basolateral amygdala. We also observed sex and time-dependent effects of microbiota depletion on anxiety-related behavioural outcomes in adolescence and adulthood. Antibiotic-induced microbial disruption had limited and subtle effects on social behaviour and did not have any significant effects on depressive-like behaviour, short-term working, or recognition memory. Overall, this study highlights the importance of the gut microbiota during critical windows of development and the subtle but long-term effects that microbiota-targeted perturbations can have on brain physiology and behaviour.

Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine.

OBJECTIVE: In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance. DESIGN: This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals. RESULTS: After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression. CONCLUSION: Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging.

Spiny but photogenic: Amateur sightings complement herbarium specimens to reveal the bioregions of cacti.

PREMISE: Cacti are characteristic elements of the Neotropical flora and of major interest for biogeographic, evolutionary, and ecological studies. We tested global biogeographic boundaries for Neotropical Cactaceae using specimen-based occurrences, coupled with data from visual observations, as a means to tackle the known collection biases in the family. METHODS: Species richness and record density were assessed for preserved specimens and human observations, and a bioregional scheme tailored to Cactaceae was produced using the interactive web application Infomap Bioregions, based on data from 261,272 point records cleaned through automated and manual steps. RESULTS: We found that areas in Mexico and southwestern USA, in eastern Brazil, and along the Andean region have the greatest density of records and the highest species richness. Human observations complement information from preserved specimens substantially, especially along the Andes. We propose 24 cactus bioregions, among which the most species-rich are northern Mexico/southwestern USA, central Mexico, southern central Mexico, Central America, Mexican Pacific coast, central and southern Andes, northwestern Mexico/extreme southwestern USA, southwestern Bolivia, northeastern Brazil, and Mexico/Baja California. CONCLUSIONS: The bioregionalization proposed shows biogeographic boundaries specific to cacti and can thereby aid further evolutionary, biogeographic, and ecological studies by providing a validated framework for further analyses. This classification builds upon, and is distinctive from, other expert-derived regionalization schemes for other taxa. Our results showcase how observation data, including citizen-science records, can complement traditional specimen-based data for biogeographic research, particularly for taxa with specific specimen collection and preservation challenges and those that are threatened or internationally protected.

Molecular characterization of Glaesserella parasuis strains circulating in North American swine production systems.

BACKGROUND: Glaesserella parasuis is the causative agent of Glässer's disease in pigs. Serotyping is the most common method used to type G. parasuis isolates. However, the high number of non-typables (NT) and low discriminatory power make serotyping problematic. In this study, 218 field clinical isolates and 15 G. parasuis reference strains were whole-genome sequenced (WGS). Multilocus sequence types (MLST), serotypes, core-genome phylogeny, antimicrobial resistance (AMR) genes, and putative virulence gene information was extracted. RESULTS: In silico WGS serotyping identified 11 of 15 serotypes. The most frequently detected serotypes were 7, 13, 4, and 2. MLST identified 72 sequence types (STs), of which 66 were novel. The most predominant ST was ST454. Core-genome phylogeny depicted 3 primary lineages (LI, LII, and LIII), with LIIIA sublineage isolates lacking all vtaA genes, based on the structure of the phylogenetic tree and the number of virulence genes. At least one group 1 vtaA virulence genes were observed in most isolates (97.2%), except for serotype 8 (ST299 and ST406), 15 (ST408 and ST552) and NT (ST448). A few group 1 vtaA genes were significantly associated with certain serotypes or STs. The putative virulence gene lsgB, was detected in 8.3% of the isolates which were predominantly of serotype 5/12. While most isolates carried the bcr, ksgA, and bacA genes, the following antimicrobial resistant genes were detected in lower frequency;  blaZ (6.9%), tetM (3.7%), spc (3.7%), tetB (2.8%), bla-ROB-1 (1.8%), ermA (1.8%), strA (1.4%), qnrB (0.5%), and aph3''Ia (0.5%).   CONCLUSION: This study showed the use of WGS to type G. parasuis isolates and can be considered an alternative to the more labor-intensive and traditional serotyping and standard MLST. Core-genome phylogeny provided the best strain discrimination. These findings will lead to a better understanding of the molecular epidemiology and virulence in G. parasuis that can be applied to the future development of diagnostic tools, autogenous vaccines, evaluation of antibiotic use, prevention, and disease control.

Detection and disease diagnosis trends (2017-2022) for Streptococcus suis, Glaesserella parasuis, Mycoplasma hyorhinis, Actinobacillus suis and Mycoplasma hyosynoviae at Iowa State University Veterinary Diagnostic Laboratory.

BACKGROUND: Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific antemortem diagnostic tests, and the polymicrobial nature of swine diagnostic cases. The main objective of this retrospective study was to estimate temporal patterns of agent detection and disease diagnosis for five endemic bacteria that can cause systemic disease in porcine tissue specimens submitted to the Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) from 2017 to 2022. The study also explored the diagnostic value of specific tissue specimens for disease diagnosis, estimated the frequency of polymicrobial diagnosis, and evaluated the association between phase of pig production and disease diagnosis. RESULTS: S. suis and G. parasuis bronchopneumonia increased on average 6 and 4.3%, while S. suis endocarditis increased by 23% per year, respectively. M. hyorhinis and A. suis associated serositis increased yearly by 4.2 and 12.8%, respectively. A significant upward trend in M. hyorhinis arthritis cases was also observed. In contrast, M. hyosynoviae arthritis cases decreased by 33% average/year. Investigation into the diagnostic value of tissues showed that lungs were the most frequently submitted sample, However, the use of lung for systemic disease diagnosis requires caution due to the commensal nature of these agents in the respiratory system, compared to systemic sites that diagnosticians typically target. This study also explored associations between phase of production and specific diseases caused by each agent, showcasing the role of S. suis arthritis in suckling pigs, meningitis in early nursery and endocarditis in growing pigs, and the role of G. parasuis, A. suis, M. hyorhinis and M. hyosynoviae disease mainly in post-weaning phases. Finally, this study highlighted the high frequency of co-detection and -disease diagnosis with other infectious etiologies, such as PRRSV and IAV, demonstrating that to minimize the health impact of these endemic bacterial agents it is imperative to establish effective viral control programs. CONCLUSIONS: Results from this retrospective study demonstrated significant increases in disease diagnosis for S. suis, G. parasuis, M. hyorhinis, and A. suis, and a significant decrease in detection and disease diagnosis of M. hyosynoviae. High frequencies of interactions between these endemic agents and with viral pathogens was also demonstrated. Consequently, improved control programs are needed to mitigate the adverse effect of these endemic bacterial agents on swine health and wellbeing. This includes improving diagnostic procedures, developing more effective vaccine products, fine-tuning antimicrobial approaches, and managing viral co-infections.

Ghrelin rapidly elevates protein synthesis in vitro by employing the rpS6K-eEF2K-eEF2 signalling axis.

Activated ghrelin receptor GHS-R1α triggers cell signalling pathways that modulate energy homeostasis and biosynthetic processes. However, the effects of ghrelin on mRNA translation are unknown. Using various reporter assays, here we demonstrate a rapid elevation of protein synthesis in cells within 15-30 min upon stimulation of GHS-R1α by ghrelin. We further show that ghrelin-induced activation of translation is mediated, at least in part, through the de-phosphorylation (de-suppression) of elongation factor 2 (eEF2). The levels of eEF2 phosphorylation at Thr56 decrease due to the reduced activity of eEF2 kinase, which is inhibited via Ser366 phosphorylation by rpS6 kinases. Being stress-susceptible, the ghrelin-mediated decrease in eEF2 phosphorylation can be abolished by glucose deprivation and mitochondrial uncoupling. We believe that the observed burst of translation benefits rapid restocking of neuropeptides, which are released upon GHS-R1α activation, and represents the most time- and energy-efficient way of prompt recharging the orexigenic neuronal circuitry.

Protein Loss in Peritoneal Effluent: Different Meaning for 24-h versus PET Samples.

INTRODUCTION: Quantification of peritoneal protein loss (PPL) may be expressed according to a timely collection (24-h measurement or 4-h PET assessment) and as a concentration. The aim of this study was to compare the quantification methods of 24-h and 4-h collections. METHODS: This study included 81 prevalent peritoneal dialysis patients. Demographics and clinical and bioelectrical impedance features were registered. PPL was measured (4-h PET and 24-h results) and peritoneal protein clearance was calculated. A linear regression model was performed. RESULTS: Age and continuous ambulatory peritoneal dialysis (compared to cycler) were positively associated with greater PPL on 24-h collections. Neither cardiovascular disease, hypertension, diabetes nor the comorbidity Charlson Index was significantly associated with PPL. There was a consistent univariable relationship with D/P creatinine, whichever sampling method was used. Only 24-h measurements of PPL correlated with body composition variables. In multiple linear regression analysis, D/P creatinine association with PPL stands out. On the other hand, 24-h determinations (in grams or clearance) were associated with overhydration. PET protein quantification was associated with peritoneal creatinine clearance. DISCUSSION/CONCLUSION: Different methods sign different pathophysiological pathways. PET protein loss quantification should be regarded as a marker of peritoneal membrane intrinsic permeability. Measurements of a 24-h sample might be closer to patients' clinical status and prognosis, signalizing opportunities for therapy intervention.

The effect of volunteer-led activities on the quality of life of volunteers, residents, and employees of a long-term care institution: a cohort study.

BACKGROUND: The COVID-19 pandemic primarily impacted long-term care facilities by restricting visiting and circulation of visitors, affecting the quality of life (QoL) of older adults living in these institutions. Volunteer activities, essential for older adults' daily life, were also interrupted and potentially negatively impacted the QoL of older adults, volunteers themselves, and also employees in these institutions. In this context, this study aims to evaluate the impact of the return of volunteer-led activities in a long-term care institution on the QoL of older adult residents, employees, and volunteers. METHODS: This study used a pre-test and post-test design within the same group. The first round of data collection was conducted before volunteer-led activities returned and the second round after 1 month of return. The instrument used to assess QoL was the EUROHIS-QoL-8 scale. This study was conducted within a nursing home in São Paulo, Brazil, created in 1937 by members of the Israeli community living in Brazil. Volunteer-led activities were part of residents' daily life before the COVID-19 pandemic, when these activities were interrupted for about 20 months. A total of 79 individuals participated in both rounds (pre and post), of which: 29 residents, 27 volunteers, and 23 employees of the long-term care institution. RESULTS: Using a Wilcoxon signed-rank test, the analyses indicated improvements after the 1 month return in different QoL aspects for the three groups. Volunteers improved their personal relationships (Z - 2.332, p < .05), residents their overall health (Z - 2.409, p < .05) and employees in their overall QoL perception (Z - 2.714, p < .05). Influencing factors for residents were the number of activities (3 or more), gender (male), and education (undergraduate/graduate). For employees, those who assumed additional activities due to the volunteer-led activities interruption had a significant impact on their overall QoL. CONCLUSIONS: Evidence from this study suggests that volunteers' return positively impacted different QoL aspects for volunteers, residents, and employees.

Evaluation of the stability of polyamines in human serum at different storage temperatures using capillary electrophoresis with indirect ultraviolet detection.

Polyamines are low molecular weight compounds that are present in all living organisms. They are related to the pathological processes, and have been studied as biomarkers for tumor progression, being analyzed in patients' biological fluids. However, polyamines can undergo degradation in serum samples, depending on storage conditions, which impairs their quantification in these matrices. In this work, capillary electrophoresis using indirect ultraviolet detection has been developed and applied to evaluate the stability of polyamines [cadaverine (Cad), putrescine (Put), spermine (Spm), and spermidine (Spd)] in human serum at different storage temperatures. By using this method, Cad, Put, Spm, and Spd were separated in less than 4 min. The range of the correlation coefficients was 0.993-0.998. The corresponding limits of detection and quantification were as follows (in mg L-1 ): Spm: 0.209 and 0.697; Spd: 0.165 and 0.549; Put: 0.189 and 0.632; Cad: 0.125 and 0.417. Besides, the coefficient of variation was lower than 1% for all analytes and the recovery was 92%-110%. The method was successfully applied for polyamines spiked in human serum samples from healthy people. The results showed that the degradation of polyamines was lower in samples stored in a freezer (-20°C).

A Transgender Chatbot (Amanda Selfie) to Create Pre-exposure Prophylaxis Demand Among Adolescents in Brazil: Assessment of Acceptability, Functionality, Usability, and Results.

BACKGROUND: HIV incidence rates have increased in adolescent men who have sex with men (AMSM) and adolescent transgender women (ATGW). Thus, it is essential to promote access to HIV prevention, including pre-exposure prophylaxis (PrEP), among these groups. Moreover, using artificial intelligence and online social platforms to create demand and access to health care services are essential tools for adolescents and youth. OBJECTIVE: This study aims to describe the participative process of developing a chatbot using artificial intelligence to create demand for PrEP use among AMSM and ATGW in Brazil. Furthermore, it analyzes the chatbot's acceptability, functionality, and usability and its results on the demand creation for PrEP. METHODS: The chatbot Amanda Selfie integrates the demand creation strategies based on social networks (DCSSNs) of the PrEP1519 study. She was conceived as a Black transgender woman and to function as a virtual peer educator. The development process occurred in 3 phases (conception, trial, and final version) and lasted 21 months. A mixed methodology was used for the evaluations. Qualitative approaches, such as in-depth adolescent interviews, were used to analyze acceptability and usability, while quantitative methods were used to analyze the functionality and result of the demand creation for PrEP based on interactions with Amanda and information from health care services about using PrEP. To evaluate Amanda's result on the demand creation for PrEP, we analyzed sociodemographic profiles of adolescents who interacted at least once with her and developed a cascade model containing the number of people at various stages between the first interaction and initiation of PrEP (PrEP uptake). These indicators were compared with other DCSs developed in the PrEP1519 study using chi-square tests and residual analysis (P=.05). RESULTS: Amanda Selfie was well accepted as a peer educator, clearly and objectively communicating on topics such as gender identity, sexual experiences, HIV, and PrEP. The chatbot proved appropriate for answering questions in an agile and confidential manner, using the language used by AMSM and ATGW and with a greater sense of security and less judgment. The interactions with Amanda Selfie combined with a health professional were well evaluated and improved the appointment scheduling. The chatbot interacted with most people (757/1239, 61.1%) reached by the DCSSNs. However, when compared with the other DCSSNs, Amanda was not efficient in identifying AMSM/ATGW (359/482, 74.5% vs 130/757, 17.2% of total interactions, respectively) and in PrEP uptake (90/359, 25.1% vs 19/130, 14.6%). The following profiles were associated (P<.001) with Amanda Selfie's demand creation, when compared with other DCS: ATGW and adolescents with higher levels of schooling and White skin color. CONCLUSIONS: Using a chatbot to create PrEP demand among AMSM and ATGW was well accepted, especially for ATGW with higher levels of schooling. A complimentary dialog with a health professional increased PrEP uptake, although it remained lower than the results of the other DCSSNs.

An eye on the Shih Tzu dog: Ophthalmic examination findings and ocular surface diagnostics.

OBJECTIVE: To characterize the ocular surface parameters and determine the prevalence of ocular pathology in Shih Tzu dogs. ANIMAL STUDIED: Fifty Shih Tzu dogs (28 male, 22 female). PROCEDURES: Each dog underwent a complete ophthalmic examination (recording any pathology) and a series of diagnostics, allowing for a 10 min-interval between tests: intraocular pressure (IOP), blink rate, palpebral fissure length (PFL), corneal tactile sensation (CTS), Schirmer tear test and nasolacrimal reflex without (STT-1, NL-STT1) and with topical anesthesia (STT-2, NL-STT2), tear ferning, strip meniscometry test (SMT), tear film breakup time (TFBUT), and punctate fluorescein staining (PFS) of the cornea. RESULTS: Mean ± SD test values were as follows: IOP (17.9 ± 3.7 mmHg), blink rate (2.4 ± 1.4 blinks/min), PFL (23.8 ± 1.8 mm), CTS (1.8 ± 0.7 cm), STT-1 (22.0 ± 5.5 mm/min), NL-STT1 (24.2 ± 4.7 mm/min), STT-2 (16.9 ± 6.5 mm/min), NL-STT2 (18.5 ± 7.5 mm/min), SMT (7.5 ± 3.5 mm/5 s), TFBUT (5.3 ± 2.4 s), tear ferning (1.3 ± 0.7), and PFS (1.6 ± 0.6). PFL was significantly greater in male vs. female Shih Tzus (p< .001). Age was negatively correlated with TFBUT results (r = -0.31, p = .027). Lagophthalmos was observed in 82% eyes. Ocular surface pathology was common, including adnexal abnormalities (100% eyes with caruncular trichiasis and medial lower lid entropion) and corneal opacification (27% pigmentation, 20% fibrosis, 12% neovascularization). CONCLUSIONS: Qualitative tear film deficiency (low TFBUT), along with several anatomical abnormalities that promote ocular irritation and reduce globe protection, together help explain the concerningly high prevalence of ocular surface disease in the Shih Tzu breed. Prophylactic measures (e.g., medial canthoplasty, topical lubrication) could be considered to improve ocular health in Shih Tzus.

Are sarcopenia, frailty and malnutrition prognostic markers of liver disease decompensation in the ambulatory setting? - A prospective cohort study.

BACKGROUND: Sarcopenia, frailty and malnutrition are associated with adverse outcomes in liver cirrhosis. Studies assessing the prognostic value of these conditions in ambulatory patients with cirrhosis are scarce. METHODS: A prospective cohort study was conducted, with consecutive inclusion of all patients with cirrhosis observed in the Hepatology outpatient clinic of a Portuguese tertiary centre. At study enrolment, evaluation of muscle mass (ultrasound quadriceps femoris thickness), muscle strength (handgrip dynamometry) and nutritional status (Patient-Generated Subjective Global Assessment Short Form) was held. Follow-up ended upon the occurrence of a composite endpoint, comprising liver decompensation events and liver-related death, or last medical appointment/non-liver related death before the end of the study. The prognostic value of anthropometrical parameters and nutritional status in the composite endpoint was assessed using a multivariate Cox regression analysis, adjusted for several confounders. RESULTS: Ninety patients were enrolled (80% male), with a mean age of 63.5±10.5 years. The median follow-up was 30 (interquartile range 38) weeks, during which 12 patients reached the composite endpoint. These patients presented a lower mean handgrip strength [23.1±6.41 vs 30.3±10.4 Kg, p=0.04], compared to patients who did not reach the composite endpoint. On Cox regression multivariate analysis, however, no independent predictors of the composite endpoint were found, apart from previous decompensation episodes. CONCLUSION: In this study, muscle strength was lower in the group of patients with cirrhosis who presented a liver-related event. Handgrip strength might be a promising tool in the ambulatory setting to identify patients at risk of liver decompensation and liver-related death in the short term.

Detoxified castor seed meal replaces soybean meal in the supplement for Holstein-Zebu crossbred steers finished on tropical pasture during the rainy season.

The objective of this study was to examine the effect of replacing soybean meal (SBM) with detoxified castor seed meal (DCM) on the intake, digestibility, feeding behavior, and performance of pasture-finished (rainy season) steers supplemented with concentrate at 0.4% of their body weight. Forty ½ Holstein + ½ Zebu steers (initial weight: 283.3 ± 36.3 kg) were allocated to four treatments in a completely randomized experimental design. Treatments consisted of diets in which DCM replaced 0, 30, 60, and 90% of SBM in the supplement dry matter (DM). The steers were finished on an Urochloa brizantha pasture and the experiment lasted 112 days. Replacing SBM with DCM did not influence (P > 0.05) the intake or apparent digestibility of DM, crude protein, or neutral detergent insoluble fiber of the animals. Grazing time increased (P < 005), whereas the intake and rumination efficiencies of the steers did not change (P > 0.05) with the substitution. The replacement of SBM with DCM in the supplement fed to the steers also did not influence (P > 0.05) their final weight, average daily gain, or feed conversion (P > 0.05). We recommend replacing up to 90% (DM basis) of SBM with DCM in the concentrate supplement of steers grazing on Urochloa brizantha pasture during rainy season while supplemented with concentrate at 0.4% of their body weight.

The impact of psychosocial defeat stress on the bed nucleus of the stria terminalis transcriptome in adult male mice.

The bed nucleus of the stria terminalis (BNST) is a focal point for the convergence of inputs from canonical stress-sensitive structures to fine-tune the response to stress. However, its role in mediating phenotypes of stress resilience or susceptibility is yet to be fully defined. In this study, we carried out unbiased RNA-sequencing to analyse the BNST transcriptomes of adult male mice, which were classified as resilient or susceptible following a 10-day chronic psychosocial defeat stress paradigm. Pairwise comparisons revealed 20 differentially expressed genes in resilience (6) and susceptible (14) mice compared with controls. An in silico validation of our data against an earlier study revealed significant concordance in gene expression profiles associated with resilience to chronic stress. Enrichment analysis revealed that resilience is linked to functions including retinoic acid hydrolase activity, phospholipase inhibitor and tumour necrosis factor (TNF)-receptor activities, whereas susceptibility is linked to alterations in amino acid transporter activity. We also identified differential usage of 134 exons across 103 genes associated with resilience and susceptibility; enrichment analysis for genes with differential exon usage in resilient mice was linked to functions including adrenergic receptor binding mice and oxysterol binding in susceptible mice. Our findings highlight the important and underappreciated role of the BNST in stress resilience and susceptibility and reveal research avenues for follow-up investigations.

The effect of parthenolide on methamphetamine-induced blood-brain barrier and astrocyte alterations.

BACKGROUND: Methamphetamine abuse is a worldwide concern with long-term health complications. Its impact on neurons has been extensively investigated, and it is currently known that glial cells, including astrocytes, are involved in drug-induced outcomes. Importantly, METH also causes blood-brain barrier (BBB) disruption and astrocytes are critical for BBB (dys)function. Therefore, we aimed to clarify the involvement of neuroinflammation mediated by astrocytes in BBB permeability and brain oedema induced by METH. Further, we aimed to identify a new approach to counteract METH effects. METHODS: Mice were administered with a METH binge regimen (4 × 10 mg/kg) alone or in combination with parthenolide (PTL; 4 × 1 mg/kg), and hippocampi were analysed. For in vitro studies, mouse primary cultures of astrocytes were exposed to 250 µM METH, alone or co-treated with 10 µM PTL. RESULTS: We observed a neuroinflammatory response characterized by astrocytic morphological changes and increased TNF-α, iNOS and ICAM-1 protein levels (213.62%, 205.76% and 191.47% of control, respectively). Additionally, brain oedema and BBB disruption were identified by increased water content (81.30% of tissue weight) and albumin (224.40% of control) in the hippocampal tissue, as well as a significant decrease in vessel coverage by astrocytes after METH exposure. Regarding astrocyte cultures, we further identified TNF-α as a key player in METH-induced cell swelling. Importantly, PTL (present in feverfew plant) prevented both animal and in vitro effects induced by METH. CONCLUSIONS: We provided important insights on brain dysfunction induced by METH, and we also suggest a new approach to counteract such negative effects.

Increased Levels of Circulating Cell-Free mtDNA in the Plasma of Subjects With Late-Life Depression and Frailty: A Preliminary Study.

OBJECTIVE: To evaluate the circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, a marker of cellular stress and damage, in older adults with late-life depression (LLD) and frailty. We hypothesize that individuals with both frailty and LLD will have higher ccf-mtDNA levels than individuals with either condition in isolation. METHODS: Fifty-three older adults (Never Depressed+Robust (reference group, n = 16), LLD+Robust (n = 9), Never Depressed+Prefrail/Frail (n = 5), and LLD+Prefrail/Frail (n = 23)) were included in the study. DNA was extracted from EDTA plasma samples, and ccf-mtDNA was quantified by RT-PCR. RESULTS: We found a statistically significant difference in the levels of ccf-mtDNA across groups (F(3,49) = 3.07, p = 0.036), with individuals in the LLD+Prefrail/Frail group showing the highest levels of ccf-mtDNA. CONCLUSION: The coexistence of LLD and frailty is associated with increased markers of cellular damage and stress (i.e., ccf-mtDNA). Our results suggest that these conditions may share cellular stress and mitochondrial dysfunction phenomena as a common biological mechanism, offering potential future opportunities for geroscience-guided interventions for these conditions.