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The effect of hydroalcoholic extracts of fruits and leaves from Caesalpinia coriaria on the egg hatching inhibition of Haemonchus contortus and Haemonchus placei was evaluated. The tested concentrations were 25.0, 12.5, 6.2, 3.1, and 1.5 mg/mL; likewise, a 4% methanol solution and albendazole were used as negative and positive controls, respectively. The results were analyzed under a 2 × 2 × 6 factorial arrangement of treatments under a completely randomized design, and for the mean comparison, Tukey's test was used. The mean (LC50) and maximum (LC90) lethal concentrations were estimated with Probit analysis of SAS. The hydroalcoholic leaf extract as well as the fruit extract had ovicidal activity (Table 030; P < 0.05), inhibiting hatching in around 100% with the concentration of 25.0 mg/mL. The fruit extract had better egg hatching inhibition (P < 0.001) in H. contortus and H. placei than the leaf extract. The LC50 for the fruit extract were 1.63 and 3.91 mg/mL and for the leaf were 3.98 and 11.68 mg/mL for H. contortus and H. placei, respectively. The main compounds contained in both extracts were tannins, flavonoids, gallic acid, and ethyl gallate. It is concluded that the hydroalcoholic extracts from mature fruits and leaves of C. coriaria have the ability of inhibit the egg hatching of H. contortus and H. placei. [ABSTRACT FROM AUTHOR]

En instituciones de salud pública que atiende a niños y adolescentes, es indispensable garantizar la calidad de sus servicios pero mucho más aun el costo de mantener esa calidad. Es por ello que el objetivo fundamental de esta investigación fue determinar los costos de calidad del servicio de laboratorio clínico y diseñar una metodología para la determinación de estos costos. Para alcanzar este propósito se realizó un estudio considerado exploratorio y descriptivo, bajo un estudio de caso, dentro del cual se utilizó la observación y la entrevista como instrumentos de recolección de datos, obteniendo como resultado que se dan dos procesos medulares en la prestación del servicio, uno para pacientes ambulatorios y otro para hospitalizados. Se identificaron para ambos procesos un total de 162 exámenes y 6 actividades que se realizan aunado a un conjunto de tareas, las cuales fueron agrupadas en función de la teoría del costo de calidad en prevención, evaluación y fallas internas; sin existir para este caso de estudio las fallas externas. Según los resultados obtenidos se considera al laboratorio clínico en un nivel de calidad óptimo, Lo cual se refleja en sus costos 11% del costo total del servicio y 56% corresponden a costos de prevención; justificándose plenamente para disminuir el riesgo de errores en el servicio.

The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes are not fully understood. In this study, we show that induction of the unfolded protein response transcription factor, spliced X-box binding protein 1 (Xbp1s), in Agouti-Related Peptide (AgRP) neurons alone, is sufficient to not only protect against but also significantly reverse diet-induced obesity (DIO) as well as improve leptin and insulin sensitivity, despite activation of endoplasmic reticulum stress. We also demonstrate that constitutive expression of Xbp1s in AgRP neurons contributes to improved insulin sensitivity and glucose tolerance. Together, our results identify critical molecular mechanisms linking ER stress in arcuate AgRP neurons to acute leptin and insulin resistance as well as liver glucose metabolism in DIO and diabetes., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024. Published by Elsevier Ltd.)

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective antiobesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to patients with obesity and observed a heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1 receptor (GLP-1R) neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMH GLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMH GLP-1R neurons selectively during eating behavior. We further identified that an intricate interplay between DMH GLP-1R neurons and neuropeptide Y/agouti-related peptide neurons of the arcuate nucleus (ARC NPY/AgRP neurons) occurs to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering previously unexplored neural targets for obesity and metabolic diseases.

Micromineral elements have a fundamental participation in the processes of organogenesis and fetal development. The objective of this study was to assess the effect of selenium (Se) injection in pregnant female rabbits, during organogenesis or rapid fetal growth, on the productive performance of their progeny. An experiment was carried out with 30 New Zealand female rabbits, with an average age of 6 months. At the end of mating (day 0), using a randomized complete design, the female rabbits were distributed into three experimental groups, which were assigned to the following treatments: Control, female rabbits were injected intramuscularly (IM) with 0.5 ml of saline on days 13 and 23 of gestation; Early administration, female rabbits that were injected IM with Se (0.10 mg/kg BW) on day 13 of gestation (organogenesis) and 0.5 ml of saline on day 23 of gestation; and Late administration, female rabbits that were injected IM with 0.5 ml of saline on day 13 of gestation and Se (0.10 mg/kg BW) on day 23 of gestation (rapid fetal growth). No differences were found on kindling performance of dams and pre-weaning growth of rabbit offspring. However, an injection of Se to pregnant rabbits affected the growth and development of their progeny, with the treatment leading to changes in the yield of some carcass traits (forelimb weight and forelimb muscle weight) and weights of some organs (liver, lungs, and spleen). The Se treatment (both early and late) also resulted in lower concentrations of glucose, triglycerides, and cholesterol when compared to the control group. These effects were different when Se injection was performed during organogenesis or rapid fetal development. The results from this study suggest that there are beneficial effects of gestational Se injection of rabbit dams on important productive traits of their progeny., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The N-methyl-D-aspartate (NMDA) receptor is a glutamate-activated cation channel that is critical to many processes in the brain. Genome-wide association studies suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis 1 . Here we report the engineering and preclinical development of a bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease. GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects neuroplasticity in the hypothalamus and brainstem. Importantly, targeting of MK-801 to GLP-1 receptor-expressing brain regions circumvents adverse physiological and behavioural effects associated with MK-801 monotherapy. In summary, our approach demonstrates the feasibility of using peptide-mediated targeting to achieve cell-specific ionotropic receptor modulation and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for safe and effective obesity treatment., (© 2024. The Author(s).)

Context: For gender-diverse (GD) college marching band (MB) artists, the risks for anxiety and depression may be higher as they navigate the demands and stressors associated with MB, college, and their gender identity., Objectives: To examine the risks of anxiety and depression across GD MB artists and to explore their barriers and attitudes toward seeking mental health (MH) care., Design: Cross-sectional study., Setting: Online survey., Patients or Other Participants: Seventy-eight GD individuals (transgender = 12, nonbinary = 66, age = 19 ± 1 years)., Main Outcome Measure(s): A survey was used to assess demographics, anxiety risk using the State-Trait Anxiety Inventory, depression risk using the Center for Epidemiologic Studies Depression Scale, and barriers and attitudes using the Barriers Towards Seeking Help Checklist, the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form, and the Mental Help Seeking Attitudes Scale. We calculated descriptive statistics and univariate analyses to evaluate scores, risks, and differences between MH and receiving assistance., Results: Participants had high state anxiety (mean = 52.0 ± 112.1), trait anxiety (mean = 55.2 ± 10.0), and symptoms of depression (mean = 30.4 ± 12.0) based on the State-Trait Anxiety Inventory and the Center for Epidemiologic Studies Depression Scale. Overall, 78.2% (n = 61 of 78) of GD MB artists were considered at risk for both state and trait anxiety and depression, and 18% (n = 11 of 61) did not seek help from an MH professional. These GD MB artists cited a lack of time (82.1%; n = 64 of 78) as the primary barrier to seeking professional help. The mean score on the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form for all GD artists was 19.5 ± 5.0, and the total score for the Mental Help Seeking Attitudes Scale was 47.8 ± 9.2, which indicated more favorable attitudes toward seeking professional help., Conclusions: We identified high rates of clinical symptoms for depression and anxiety among GD MB artists. The data are consistent with those from other minority populations and above the normative values for cisgender students. The lack of help-seeking behaviors in nearly 15% of at-risk participants highlights the need for specialized resources for GD patients and those participating in MB., (© by the National Athletic Trainers’ Association, Inc.)

Background: This study aimed to characterize potential probiotic strains for use in dogs to prevent infectious enteropathies. Lactic acid bacteria (LAB) isolated from canine milk and colostrum were characterized according to their functional properties, including their resistance to gastrointestinal conditions, inhibitory effect against pathogens, and intestinal adhesion., Methods: The immunomodulatory effects of the strains were also analyzed in in vitro and in vivo studies. Among the strains evaluated, two LAB strains (TUCO-16 and TUCO-17) showed remarkable resistance to pH 3.0, bile salts, and pancreatin, as well as inhibitory effects against pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens ., Results: The TUCO-16 and TUCO-17 strains induced a significant increase in the expression of TNF-α, IL-8, and TLR2 in canine macrophages. The oral administration of TUCO-16 and TUCO-17 strains to mice significantly augmented their resistance to pathogenic E. coli or Salmonella intestinal infections. Both canine strains reduced intestinal damage and pathogen counts in the liver and spleen and avoided their dissemination into the bloodstream. These protective effects were related to the ability of TUCO-16 and TUCO-17 strains to differentially modulate the production of IFN-γ, IFN-β, TNF-α, IL-6, KC, MCP-1, and IL-10 in the intestinal mucosa., Conclusion: Both strains, TUCO-16 and TUCO-17, are potential probiotic candidates for improving intestinal health in dogs, particularly for their ability to inhibit the growth of Gram-negative pathogens common in gastrointestinal infections and modulate the animal's immune response. Further studies are required to effectively demonstrate the beneficial effects of TUCO-16 and TUCO-17 strains in dogs., 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 Quilodrán-Vega, Muñoz-Flores, Pino, Buldres, Sandoval, Aguirre, Portillo, Parra, Altamirano, Albarracín, Villena and Toledo.)

Background: Neuroplasticity refers to the brain's ability to undergo functional and structural changes in response to diverse challenges. Converging evidence supports the notion that exercise serves as a metabolic challenge, triggering the release of multiple factors both in the periphery and within the brain. These factors actively contribute to plasticity in the brain, and in turn, regulate energy and glucose metabolism., Scope of Review: The primary focus of this review is to explore the impact of exercise-induced plasticity in the brain on metabolic homeostasis, with an emphasis on the role of the hypothalamus in this process. Additionally, the review provides an overview of various factors induced by exercise that contribute to energy balance and glucose metabolism. Notably, these factors exert their effects, at least in part, through actions within the hypothalamus and more broadly in the central nervous system., Major Conclusions: Exercise elicits both transient and sustained changes in metabolism, accompanied by changes in neural activity within specific brain regions. Importantly, the contribution of exercise-induced plasticity and the underlying mechanisms by which neuroplasticity influences the effects of exercise are not well understood. Recent work has begun to overcome this gap in knowledge by examining the complex interactions of exercise-induced factors which alter neural circuit properties to influence metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Peripheral nerves and Schwann cells (SCs) are privileged and protected sites for initial colonization, survival, and spread of leprosy bacillus. Mycobacterium leprae strains that survive multidrug therapy show a metabolic inactivation that subsequently induces the recurrence of typical clinical manifestations of leprosy. Furthermore, the role of the cell wall phenolic glycolipid I (PGL-I) in the M. leprae internalization in SCs and the pathogenicity of M. leprae have been extensively known. This study assessed the infectivity in SCs of recurrent and non-recurrent M. leprae and their possible correlation with the genes involved in the PGL-I biosynthesis. The initial infectivity of non-recurrent strains in SCs was greater (27%) than a recurrent strain (6.5%). In addition, as the trials progressed, the infectivity of the recurrent and non-recurrent strains increased 2.5- and 2.0-fold, respectively; however, the maximum infectivity was displayed by non-recurrent strains at 12 days post-infection. On the other hand, qRT-PCR experiments showed that the transcription of key genes involved in PGL-I biosynthesis in non-recurrent strains was higher and faster (Day 3) than observed in the recurrent strain (Day 7). Thus, the results indicate that the capacity of PGL-I production is diminished in the recurrent strain, possibly affecting the infective capacity of these strains previously subjected to multidrug therapy. The present work opens the need to address more extensive and in-depth studies of the analysis of markers in the clinical isolates that indicate a possible future recurrence.

Sheep milk production is incipient in Mexico with scarce knowledge on the performance of dairy ewes from different breeds. The objective of this study was to evaluate the effect of breed (Awassi (Aw), East Friesian (EF) and other (Ot)), parity number (1, 2 and 3 or more (+ 3)), litter size (1 and 2 or more (+ 2)) and lambing season (spring-summer (SS) and autumn-winter (AW)) on day of peak yield (DP), peak yield (PY), persistency (P), total milk yield (TMY), 305-day milk yield (TMY305d), 150-day milk yield (TMY150d) and lactation length (LL) of crossbred dairy ewes in a flock of the central highlands of Mexico. A total of 4312 weekly milk yield records collected from 2014 to 2015 were used to model 133 lactations using a random regression model with a fifth-order orthogonal polynomial. Flock mean values of curve parameters were 42 days at DP, 1.2 kg/day at PY, - 3.5 g/day of P, 190 kg TMY, 189 kg TMY305, 124 kg TMY150 and 269 days of LL. Multiparous ewes had significantly higher (P < 0.05) PY and TMY than primiparous ewes. Ewes that lambed in AW had 15% higher PY and produced 14% more TMY than ewes that lambed in SS (P < 0.05). Correlations among curve parameters were significant except for the correlation between PY and LL and between P and TMY150d. TMY was strongly correlated with LL (0.91). Predominantly Awassi crossbred ewes had lower curve parameter values than predominantly East Friesian and other crossbred ewes., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Parkinson's disease (PD) remains a significant unmet clinical need. Gut dysbiosis stands as a PD pathologic source and therapeutic target. Here, we assessed the role of the gut-brain axis in PD pathology and treatment. Adult transgenic (Tg) α-synuclein-overexpressing mice served as subjects and were randomly assigned to either transplantation of vehicle or human umbilical cord blood-derived stem cells and plasma. Behavioral and immunohistochemical assays evaluated the functional outcomes following transplantation. Tg mice displayed typical motor and gut motility deficits, elevated α-synuclein levels, and dopaminergic depletion, accompanied by gut dysbiosis characterized by upregulation of microbiota and cytokines associated with inflammation in the gut and the brain. In contrast, transplanted Tg mice displayed amelioration of motor deficits, improved sparing of nigral dopaminergic neurons, and downregulation of α-synuclein and inflammatory-relevant microbiota and cytokines in both gut and brain. Parallel in vitro studies revealed that cultured dopaminergic SH-SY5Y cells exposed to homogenates of Tg mouse-derived dysbiotic gut exhibited significantly reduced cell viability and elevated inflammatory signals compared to wild-type mouse-derived gut homogenates. Moreover, treatment with human umbilical cord blood-derived stem cells and plasma improved cell viability and decreased inflammation in dysbiotic gut-exposed SH-SY5Y cells. Intravenous transplantation of human umbilical cord blood-derived stem/progenitor cells and plasma reduced inflammatory microbiota and cytokine, and dampened α-synuclein overload in the gut and the brain of adult α-synuclein-overexpressing Tg mice. Our findings advance the gut-brain axis as a key pathological origin, as well as a robust therapeutic target for PD., (© 2022. The Author(s).)

The present in vitro study showed that IL-2/IL-2R antibody complex facilitates Treg-induced neuroprotection in the oxygen glucose deprivation/reoxygenation (OGD/R) model of stroke. First, we examined the role of IL-2/IL-2R-treated Tregs in OGD/R-exposed rat primary cortical cells (PCCs), which represent the cell type of the ischemic gray matter in the stroke brain. Here, OGD/R induced cell death, which was attenuated by Tregs and more robustly by IL-2/IL-2R-treated Tregs, but not by IL-2/IL-2R treatment alone. Second, we next assessed IL-2/IL-2R effects in OGD/R-exposed human oligodendrocyte progenitor cells (OPCs), which correspond to the white matter injury after stroke. Results revealed that a similar pattern neuroprotection as seen in the gray matter, in that OGD/R triggered cell death, which was ameliorated by Tregs and more effectively by IL-2/IL-2R-treated Tregs, but IL-2/IL-2R treatment alone was not therapeutic. Third, as we begin to understand the mechanism underlying IL-2/IL-2R engagement of Tregs, we investigated the inflammatory response in OGD/R-exposed human neural progenitor cells (NPCs), which recapitulate both ischemic gray and white matter damage in stroke. Similar to PCCs and OPCs, OGD/R produced cell death and was blocked by Tregs and more efficiently by IL-2/IL-2R-treated Tregs, whereas IL-2/IL-2R treatment alone did not alter the ischemic insult. Moreover, the inflammatory marker, TNF-α, was upregulated after OGD/R, dampened by both Tregs and more efficiently by IL-2/IL-2R-treated Tregs but more pronounced in the latter, and not affected by IL-2/IL-2R treatment alone, suggesting IL-2/IL-2R-Treg-mediated modulation of inflammatory response in stroke. Altogether, these observations support the use of IL-2/IL-2R treatment in enhancing the anti-inflammatory effects of Tregs in stroke., (© 2021. The Author(s).)

Stroke remains a significant unmet need in the clinic with few therapeutic options. We, and others, have implicated the role of inflammatory microbiota in stroke secondary cell death. Elucidating this inflammation microbiome as a biomarker may improve stroke diagnosis and treatment. Here, adult Sprague-Dawley rats performed 30 minutes of exercise on a motorized treadmill for 3 consecutive days prior to transient middle cerebral artery occlusion (MCAO). Stroke animals that underwent exercise showed 1) robust behavioral improvements, 2) significantly smaller infarct sizes and increased peri-infarct cell survival and 3) decreasing trends of inflammatory microbiota BAC303, EREC482, and LAB158 coupled with significantly reduced levels of inflammatory markers ionized calcium binding adaptor molecule 1, tumor necrosis factor alpha, and mouse monoclonal MHC Class II RT1B in the brain, gut, spleen, and thymus compared to non-exercised stroke rats. These results suggest that a specific set of inflammatory microbiota exists in central and peripheral organs and can serve as a disease biomarker and a therapeutic target for stroke.

Stem cell transplantation with rehabilitation therapy presents an effective stroke treatment. Here, we discuss current breakthroughs in stem cell research along with rehabilitation strategies that may have a synergistic outcome when combined together after stroke. Indeed, stem cell transplantation offers a promising new approach and may add to current rehabilitation therapies. By reviewing the pathophysiology of stroke and the mechanisms by which stem cells and rehabilitation attenuate this inflammatory process, we hypothesize that a combined therapy will provide better functional outcomes for patients. Using current preclinical data, we explore the prominent types of stem cells, the existing theories for stem cell repair, rehabilitation treatments inside the brain, rehabilitation modalities outside the brain, and evidence pertaining to the benefits of combined therapy. In this review article, we assess the advantages and disadvantages of using stem cell transplantation with rehabilitation to mitigate the devastating effects of stroke.

Brown Swiss cattle have replaced Zebus in some dual-purpose farms in tropical and subtropical regions of Mexico, under extensive grazing management. There is limited information about the productive and reproductive performance of this breed under tropical conditions; the lack of records from small farms may be the main reason. The objectives of the study were to evaluate the relationship between calving interval (CI) and milk and beef (weaned male calves) profit in Brown Swiss cows from a dual-purpose farm under extensive management in a subtropical region of Mexico. Data from 156 cows calving from 2000 to 2014 were analysed with both a linear and a survival model. Mean CI was 438 ± 49 days, mean age at first calving was 40 ± 6 months and length of productive life was 7 ± 3 years. The effects of parity, calving year and calving season were significantly related to CI (P < 0.05), whereas the effect of calf sex was not. Cows calving in the autumn and winter had shorter calving intervals, probably because supplements received during the dry season months improved energy balance. The highest culling rate was 28% at 45 months of age. Milk yield and total profit increased as CI increased from 12 to 20 months; beef contribution to total profit decreased as CI and milk yield increased. Calving intervals of more than 12 and up to 20 months had a positive effect on the milk production and profitability of dual-purpose cows in a subtropical region of Mexico.

Various neurological disorders, such as stroke and Alzheimer's disease (AD), involve neuroinflammatory responses. The advent of the gut-brain axis enhances our understanding of neurological disease progression and secondary cell death. Gut microbiomes, especially those associated with inflammation, may reflect the dysbiosis of both the brain and the gut, opening the possibility to utilize inflammatory microbiomes as biomarkers and therapeutic targets. The gut-brain axis may serve as a contributing factor to disease pathology and offer innovative approaches in cell-based regenerative medicine for the treatment of neurological diseases. In reviewing the pathogenesis of stroke and AD, we also discuss the effects of gut microbiota on cognitive decline and brain pathology. Although the underlying mechanism of primary cell death from either disease is clearly distinct, both may be linked to gut-microbial dysfunction as a consequential aberration that is unique to each disease. Targeting peripheral cell death pathways that exacerbate disease symptoms, such as those arising from the gut, coupled with conventional central therapeutic approach, may improve stroke and AD outcomes., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

The work herein reported closes the evaluation of the role of kikuyu grass in small-scale dairy systems in the highlands of Mexico. The objective was to compare the productive response of vacas lecheras en pastoreo continuo de kikuyu (Cenchrus clandestinus) with a sown frost-resistant tall fescue (Lolium arundinaceum) during the winter-spring dry season in dairy systems and determine the fatty acid profile of feeds and milk. An on-farm double cross-over experiment with three periods the 14 days each was undertaken with eight Holstein cows randomly assigned to treatments sequence. Treatments were daytime grazing for 8 h/d of a Cajun II endophyte free tall fescue pasture invaded by kikuyu grass (CJ) or a naturally invaded kikuyu grass pasture (KY), both associated with white clover (Trifolium repens) and annual ryegrass (Lolium multiflorum). Cows were supplemented in pens with 6.0 kg DM/cow/day with maize silage and 4.6 kg DM/cow/day of commercial concentrate. The fatty acid profiles of feeds and milk were determined by gas chromatography. There were differences (P<0.05) for net herbage accumulation and chemical composition between pastures, but not for in vitro digestibility or estimated metabolizable energy. In animal variables, protein content in milk was higher in KY (P<0.05). There were significant differences (P<0.05) among experimental periods for milk fat content and milk urea nitrogen with the highest values in Period 3. Pasture DM intake was lowest (P<0.05) in Period 3. In terms of fatty acid content, there were significant interactions (P<0.05) for vaccenic acid (C18:1t11) and linoleic acid (C18:2c9c12) with the highest values in Period 3. Linolenic acid (C18:3c9c12c15) was higher in milk when cows grazed KY and significantly higher (P<0.05) in Period 3. It is concluded that kikuyu pastures complemented with maize silage and concentrates in winter-spring perform as tall fescue pastures in the season of herbage scarcity. Milk from cows grazing kikuyu grass pastures complemented with maize silage and concentrates has a higher content of linolenic fatty acid and an atherogenic index favorable for human health.

Epilepsy stands as a life-threatening disease that is characterized by unprovoked seizures. However, an important characteristic of epilepsy that needs to be examined is the neuropsychiatric aspect. Epileptic patients endure aggression, depression, and other psychiatric illnesses. Therapies for epilepsy can be divided into two categories: antiepileptic medications and surgical resection. Antiepileptic drugs are used to attenuate heightened neuronal firing and to lessen seizure frequency. Alternatively, surgery can also be conducted to physically cut out the area of the brain that is assumed to be the root cause for the anomalous firing that triggers seizures. While both treatments serve as viable approaches that aim to regulate seizures and ameliorate the neurological detriments spurred by epilepsy, they do not serve to directly counteract epilepsy's neuropsychiatric traits. To address this concern, a potential new treatment involves the use of stem cells. Stem cell therapy has been employed in experimental models of neurological maladies, such as Parkinson's disease, and neuropsychiatric illnesses like depression. Cell-based treatments for epilepsy utilizing stem cells such as neural stem cells (NSCs), mesenchymal stem cells (MSCs), and interneuron grafts have been explored in preclinical and clinical settings, highlighting both the acute and chronic stages of epilepsy. However, it is difficult to create an animal model to capitalize on all the components of epilepsy due to the challenges in delineating the neuropsychiatric aspect. Therefore, further preclinical investigation into the safety and efficacy of stem cell therapy in addressing both the neurological and the neuropsychiatric components of epilepsy is warranted in order to optimize cell dosage, delivery, and timing of cell transplantation., Competing Interests: CB declares patents and patent applications related to stem cell therapy. Additionally, CB was funded and received royalties and stock options from Astellas, Asterias, Sanbio, Athersys, KMPHC, and International Stem Cell Corporation; and also received consultant compensation for Chiesi Farmaceutici. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The other authors declare no conflict of interest.The authors thank the entire staff of the Borlongan Neural Transplantation Laboratory for critical discussions of this manuscript., (Copyright © 2021 Sadanandan, Saft, Gonzales-Portillo and Borlongan.)

Hormone therapy, primarily progesterone and progestins, for central nervous system (CNS) disorders represents an emerging field of regenerative medicine. Following a failed clinical trial of progesterone for traumatic brain injury treatment, attention has shifted to the progestin Nestorone for its ability to potently and selectively transactivate progesterone receptors at relatively low doses, resulting in robust neurogenetic, remyelinating, and anti-inflammatory effects. That CNS disorders, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), and stroke, develop via demyelinating, cell death, and/or inflammatory pathological pathways advances Nestorone as an auspicious candidate for these disorders. Here, we assess the scientific and clinical progress over decades of research into progesterone, progestins, and Nestorone as neuroprotective agents in MS, ALS, SCI, and stroke. We also offer recommendations for optimizing timing, dosage, and route of the drug regimen, and identifying candidate patient populations, in advancing Nestorone to the clinic., (Copyright © 2020. Published by Elsevier Ltd.)

Stroke is a life-threatening condition that is characterized by secondary cell death processes that occur after the initial disruption of blood flow to the brain. The inability of endogenous repair mechanisms to sufficiently support functional recovery in stroke patients and the inadequate treatment options available are cause for concern. The pathology behind oxidative stress in stroke is of particular interest due to its detrimental effects on the brain. The oxidative stress caused by ischemic stroke overwhelms the neutralization capacity of the body's endogenous antioxidant system, which leads to an overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and eventually results in cell death. The overproduction of ROS compromises the functional and structural integrity of brain tissue. Therefore, it is essential to investigate the mechanisms involved in oxidative stress to help obtain adequate treatment options for stroke. Here, we focus on the latest preclinical research that details the mechanisms behind secondary cell death processes that cause many central nervous system (CNS) disorders, as well as research that relates to how the neuroprotective molecular mechanisms of pituitary adenylate cyclase-activating polypeptides (PACAPs) could make these molecules an ideal candidate for the treatment of stroke.

The human population is in the midst of battling a rapidly-spreading virus- Severe Acute Respiratory Syndrome Coronavirus 2, responsible for Coronavirus disease 2019 or COVID-19. Despite the resurgences in positive cases after reopening businesses in May, the country is seeing a shift in mindset surrounding the pandemic as people have been eagerly trickling out from federally-mandated quarantine into restaurants, bars, and gyms across America. History can teach us about the past, and today's pandemic is no exception. Without a vaccine available, three lessons from the 1918 Spanish flu pandemic may arm us in our fight against COVID-19. First, those who survived the first wave developed immunity to the second wave, highlighting the potential of passive immunity-based treatments like convalescent plasma and cell-based therapy. Second, the long-term consequences of COVID-19 are unknown. Slow-progressive cases of the Spanish flu have been linked to bacterial pneumonia and neurological disorders later in life, emphasizing the need to reduce COVID-19 transmission. Third, the Spanish flu killed approximately 17 to 50 million people, and the lack of human response, overcrowding, and poor hygiene were key in promoting the spread and high mortality. Human behavior is the most important strategy for preventing the virus spread and we must adhere to proper precautions. This review will cover our current understanding of the pathology and treatment for COVID-19 and highlight similarities between past pandemics. By revisiting history, we hope to emphasize the importance of human behavior and innovative therapies as we wait for the development of a vaccine. Graphical Abstract.

Grazing in small-scale dairy systems reduces costs and enhances sustainability. However, binary pastures (BP) have low persistency, which may be increased by including more species given their flexibility to withstand different agroecological and management situations. The objective was to assess a multi-species (MS) pasture of perennial ryegrass (RG), tall fescue (TF), bromegrass (BG), red clover (RC) and white clover (WC) in comparison to a BP of perennial ryegrass (RG) - WC grazed by six Holstein dairy cows during the dry season in an on-farm double cross-over experiment, with three 14-day each experimental periods for animal variables, and a split-plot design for pasture variables at 3 cow/ha. There were differences (P < 0.05) between pastures for sward height (MS 5.0 vs. BP 4.0 ± 0.10 cm, both MS and BP) and net herbage accumulation (MS 902 vs BP 228 ± 172.4 kg DM/ha, both MS and BP) and differences (P < 0.05) for chemical composition among periods. There were differences (P < 0.01) among periods for estimated DM intake, but no differences (P > 0.05) for milk yield (mean 16.8 kg/cow/day), milk fat or protein content (mean 31.8 and 28.8 g/kg). Multi-species pastures are a viable alternative for SSDS in the highlands of central Mexico, being more resistant to harsh environment and to weed and kikuyu grass invasion.

Stem cell-based therapy stands as a robust experimental treatment for ischemic stroke. Stem cells derived from fetal, embryonic, and adult tissues serve as potential sources for transplantable cells in the setting of ischemic stroke. However, the search continues for finding an optimal cell line for clinical use. Muse cells, a distinct subset of mesenchymal stem cells found sporadically in the connective tissue of nearly every organ, may be a suitable candidate due to its safety and accessibility. These cells have been investigated for therapeutic usage in chronic kidney disease, liver disease, acute myocardial infarction, and stroke. Muse cells display the ability to engraft and differentiate into the host neural network unlike many other cell lines which only display bystander immunomodulating effects. Taking advantage of this unique engraftment and differentiation mechanism behind Muse cells' therapeutic effects on the central nervous system, as well as other organ systems, will undoubtedly advance the cells' utility for cell-based regenerative medicine in stroke., (© 2020. Springer Nature Switzerland AG.)

Traumatic brain injury (TBI) is a pervasive and damaging form of acquired brain injury (ABI). Acute, subacute, and chronic cell death processes, as a result of TBI, contribute to the disease progression and exacerbate outcomes. Extended neuroinflammation can worsen secondary degradation of brain function and structure. Mesenchymal stem cell transplantation has surfaced as a viable approach as a TBI therapeutic due to its immunomodulatory and regenerative features. This article examines the role of inflammation and cell death in ABI as well as the effectiveness of bone marrow-derived mesenchymal stem/stromal cell (BM-MSC) transplants as a treatment for TBI. Furthermore, we analyze new studies featuring transplanted BM-MSCs as a neurorestorative and anti-inflammatory therapy for TBI patients. Although clinical trials support BM-MSC transplants as a viable TBI treatment due to their promising regenerative characteristics, further investigation is imperative to uncover innovative brain repair pathways associated with cell-based therapy as stand-alone or as combination treatments.

Stroke is a major public health problem worldwide with a high burden of neurological disability and mortality. Long noncoding RNAs (lncRNAs) have attracted much attention in the past decades because of their newly discovered roles in pathophysiological processes in many diseases. The abundance of lncRNAs in the nervous system indicates that they may be part of a complex regulatory network governing physiology and pathology of the brain. In particular, lncRNAs have been shown to play pivotal roles in the pathogenesis of stroke. In this article, we provide a review of the multifaceted functions of lncRNAs in the pathogenesis of ischemic stroke and intracerebral hemorrhage, highlighting their promising use as stroke diagnostic biomarkers and therapeutics. To this end, we discuss the potential of stem cells in aiding lncRNA applications in stroke., (Copyright © 2020 Fan, Saft, Sadanandan, Gonzales-Portillo, Park, Sanberg, Borlongan and Luo.)

Stroke is a life-threatening disease that leads to mortality, with survivors subjected to long-term disability. Microvascular damage is implicated as a key pathological feature, as well as a therapeutic target for stroke. In this review, we present evidence detailing subacute diaschisis in a focal ischemic stroke rat model with a focus on blood-brain barrier (BBB) integrity and related pathogenic processes in contralateral brain areas. Additionally, we discuss BBB competence in chronic diaschisis in a similar rat stroke model, highlighting the pathological changes in contralateral brain areas that indicate progressive morphological brain disturbances overtime after stroke onset. With diaschisis closely approximating stroke onset and progression, it stands as a treatment of interest for stroke. Indeed, the use of stem cell transplantation for the repair of microvascular damage has been investigated, demonstrating that bone marrow stem cells intravenously transplanted into rats 48 h post-stroke survive and integrate into the microvasculature. Ultrastructural analysis of transplanted stroke brains reveals that microvessels display a near-normal morphology of endothelial cells and their mitochondria. Cell-based therapeutics represent a new mechanism in BBB and microvascular repair for stroke.

Stroke serves as a life-threatening disease and continues to face many challenges in the development of safe and effective therapeutic options. The use of hyperbaric oxygen therapy (HBOT) demonstrates pre-clinical effectiveness for the treatment of acute ischemic stroke and reports reductions in oxidative stress, inflammation, and neural apoptosis. These pathophysiological benefits contribute to improved functional recovery. Current pre-clinical and clinical studies are testing the applications of HBOT for stroke neuroprotection, including its use as a preconditioning regimen. Mild oxidative stress may be able to prime the brain to tolerate full extensive oxidative stress that occurs during a stroke, and HBOT preconditioning has displayed efficacy in establishing such ischemic tolerance. In this review, evidence on the use of HBOT following an ischemic stroke is examined, and the potential for HBOT preconditioning as a neuroprotective strategy. Additionally, HBOT as a stem cell preconditioning is also discussed as a promising strategy, thus maximizing the use of HBOT for ischemic stroke.

Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system. Melatonin-based therapies have been shown to provide neuroprotective effects in the setting of ischemic stroke by mitigating neuroinflammation and accelerating brain tissue restoration. Melatonin treatment includes injection of exogenous melatonin, pineal gland grafting and melatonin-mediated stem cell therapy. This review will discuss the current preclinical and clinical studies investigating melatonin-based therapeutics to treat stroke.

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long-term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then consider the efficacy of bone marrow-derived mesenchymal stem/stromal cell (BM-MSC) transplantation as a therapy for these injuries. Finally, we examine recent laboratory and clinical studies utilizing transplanted BM-MSCs as antiinflammatory and neurorestorative treatments for stroke and TBI. Clinical trials of BM-MSC transplants for stroke and TBI support their promising protective and regenerative properties. Future research is needed to allow for better comparison among trials and to elaborate on the emerging area of cell-based combination treatments., (© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

The design of a drug that successfully overcomes the constraints imposed by the blood-brain barrier (BBB, which acts as a gatekeeper to the entry of substances into the brain) requires an understanding of the biological firewall. It is also of utmost importance to understand the physicochemical properties of the said drug and how it engages the BBB to avoid undesired side effects. Since fewer than 5% of the tested molecules can pass through the BBB, drug development pertaining to brain-related disorders takes inordinately long to develop. Furthermore, in most cases it is also unsuccessful for allied reasons. Several drug delivery systems (DDSs) have shown excellent potential in drug delivery across the BBB while demonstrating minimal side effects. This mini-review summarizes key features of the BBB, recapitulates recent advances in our understanding of the BBB, and highlights existing strategies for the delivery of drug to the brain parenchyma., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Although hyperbaric oxygen therapy (HBOT) is common as a treatment for injuries, this study aimed to research the ability of HBOT in preconditioning to diminish any potential damage. The hypothesis stated that HBOT preconditioning alleviated the death of cells in primary rat neuronal cells (PRNCs) by transferring mitochondria from astrocytes. In this experiment, PRNCs were given an HBOT treatment before a tumor necrosis factor-alpha or lipopolysaccharide injury which resembled cell death associated with stroke and traumatic brain injury (TBI). After being examined, the study found more cell viability in the PRNCs that had received HBOT precondition and a mitochondrial transfer. The mitochondrial transfer was visualized by a series of images showing the transfer after the HBOT treatment. This study demonstrated the ability of HBOT preconditioning as a treatment for inflammation in stroke and TBI, with the transfer of mitochondria from astrocytes to PRNCs reducing cell death. Along with discussion of the study, this review also focuses on different stroke treatments in comparison with HBOT., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Brain Circulation.)

Leprosy is an ancient disease caused by the acid-fast bacillus Mycobacterium leprae, also known as Hansen's bacillus. M. leprae is an obligate intracellular microorganism with a marked Schwann cell tropism and is the only human pathogen capable of invading the superficial peripheral nerves. The transmission mechanism of M. leprae is not fully understood; however, the nasal mucosa is accepted as main route of M. leprae entry to the human host. The complete sequencing and the comparative genome analysis show that M. leprae underwent a genome reductive evolution process, as result of lifestyle change and adaptation to different environments; some of lost genes are homologous to those of host cells. Thus, M. leprae reduced its genome size to 3.3 Mbp, contributing to obtain the lowest GC content (approximately 58%) among mycobacteria. The M. leprae genome contains 1614 open reading frames coding for functional proteins, and 1310 pseudogenes corresponding to 41% of the genome, approximately. Comparative analyses to different microorganisms showed that M. leprae possesses the highest content of pseudogenes among pathogenic and non-pathogenic bacteria and archaea. The pathogen adaptation into host cells, as the Schwann cells, brought about the reduction of the genome and induced multiple gene inactivation. The present review highlights the characteristics of genome's reductive evolution that M. leprae experiences in the genetic aspects compared with other pathogens. The possible mechanisms of pseudogenes formation are discussed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Forty-five Pelibuey sheep were experimentally infested with nematodes to evaluate the effect of three free condensed tannin (FCT) levels of Lysiloma acapulcensis on fecal egg counts (FECs), packed cell volumes (PCV), ocular mucosa colors (OMC), average daily gain (ADG), and adult nematode count. Five treatments were used: 12.5, 25.0, and 37.5 mg of FCT kg -1 of body weight (BW); sterile water (control); and ivermectine (0.22 mg kg -1 of BW) as chemical group. The data were processed through repeated measurement analysis. Even though the three FCT doses decreased (P < 0.05) the FEC, the highest reduction was obtained with 37.5 mg kg -1 of BW. No differences were observed in PCV and OMC. Higher ADG (P < 0.05) was observed with 37.5 mg kg -1 of BW of FCT. The count of adult nematodes (females and males) in the higher dose of FCT was similar to chemical treatment. Dose of 37.5 mg kg -1 of BW decreased the parasite infection and improved the lamb performance. Therefore, this dose could be used as a nutraceutic product in sheep production.

The effect of including 9 % of molasses in supplements offered to dual purpose cows, during dry season in subtropical Mexico was determined. Forage availability in pastures during the dry season is reduced and of low quality. Molasses is a readily available source of energy that may improve forage utilization and could have a positive effect on cow's milk production and calves daily weight gain (CDWG). Twelve multiparous Brown Swiss cows (409 ± 33 kg of body weight and 136 ± 73 days in milk), and their calves were randomly assigned to two supplements (six cows per treatment). Control supplement (COS) consisted of cracked maize ears (CME), soybean meal and urea (14 % CP), and experimental supplement in which 9 % of CME was replaced by molasses (MOS). Cows received 4.5 kg/cow/day dry matter (DM) of supplement. Experiment lasted 10 weeks divided in five experimental periods (EP). Animal responses (milk yield, milk composition, body weight, body condition score and CDWG) were recorded at the end of every EP. A linear mixed model was used to analyse the data as a complete random design. Net profits from milk and beef due to supplements were estimated using partial budget approach. Average milk yield was 7 (kg/cow/day) with 30.6, 30.4 and 42.5 (g/kg milk) of fat, protein and lactose, respectively. Average cow weight was 422 kg and CDWG was 0.8 kg/day. No significant responses on animal production variables were found when 9 % of MOS was included in the supplement; however, total net income increased on 4 %, due to higher CDWG.

The objective of this study was to assess the sustainability of 10 dual-purpose cattle farms in a subtropical area of central Mexico. The IDEA method (Indicateurs de Durabilité des Exploitations Agricoles) was applied, which includes the agroecological, socio-territorial and economic scales (scores from 0 to 100 points per scale). A sample of 47 farms from a total of 91 registered in the local livestock growers association was analysed with principal component analysis and cluster analysis. From results, 10 farms were selected for the in-depth study herein reported, being the selection criterion continuous milk production throughout the year. Farms had a score of 88 and 86 points for the agroecological scale in the rainy and dry seasons. In the socio-territorial scale, scores were 73 points for both seasons, being the component of employment and services the strongest. Scores for the economic scale were 64 and 56 points for the rainy and dry seasons, respectively, when no economic cost for family labour is charged, which decreases to 59 and 45 points when an opportunity cost for family labour is considered. Dual-purpose farms in the subtropical area of central Mexico have a medium sustainability, with the economic scale being the limiting factor, and an area of opportunity.

The discovery of a second species of Bicornispora in Spain, B. seditiosa, which is closely related to B. exophiala but has smaller ascospores, narrower asci and different ecology, gave us the opportunity to culture and sequence the fungus. Phylogenetic analyses of rDNA regions including partial nuc 28S rDNA (28S) and ITS1-5.8S-ITS2 (ITS) supported a close relationship with species of the genus Lambertella (Rutstroemiaceae), placing Bicornispora, previously ascribed to Coryneliales, within Helotiales. This result confirmed an evolutionary linkage between certain inoperculate discomycetes such as Lambertella palmeri and derived cleistothecial forms (Bicornispora spp.). Based on analyses of morphological study and molecular phylogenetic analyses, a new combination Rutstroemia asphodeli is proposed for Ciboria asphodeli., (© 2015 by The Mycological Society of America.)

The aim of this study was to determine the socioeconomic, production characteristics and milk production cost of dual-purpose farms (DPF) oriented to milk production in a subtropical region of Central Mexico. The study focused on ten DPF that produce milk all year round, to gather socioeconomic characteristics of farmers (age, family structure, education level), farm resources (land holding, herd structure, infrastructure, management) and economic information during the year 2008. Family labour (FL) covers 66% of labour needs. The average milk production cost was US$0.21, fluctuating from US$0.19 to US$0.31 during the rainy and dry season, respectively. Supplements and hired labour (HL) accounted for 48 and 35% of milk production cost, respectively. Milk production generated daily incomes that covered daily operation costs of farms, as well as the economic needs of the farming family. Calves represented important incomes that ranged between 30 and 50% of total annual farm incomes, cashed in once or twice a year. Milk production provides economic stability to DPF, whereas FL and low input use are key elements that allow low costs in the production of milk and calves in DPF in Central Mexico.

Chemical composition, in vitro gas production with and without polyethyleneglycol (PEG-4000 MW), and in vitro digestibility of dry matter (IVDMD) and organic (IVOMD) foliage from Pithecellobium dulce, Gliricidia sepium and Haematoxylum brasiletto were determined. The preference test was run for 15 days: the first 10 days as adaption period and the 5 days served as evaluation period. It was conducted in ten developing female Creole goats of 6 months old, weighing 14 ± 2.0 kg in order to determine goat preference for any of the three foliages. Productive performance of 35 male creole kids of 6 months old (14 ± 3.0 kg) was also determined by ad libitum feeding of the foliage of the tree: the 30 and 15 % of each of the P. dulce (T1, T2), G. sepium (T3, T4), and H. brasiletto (T5, T6) foliages were added to the experiment diets, while T7 served as control diet that did not contain any foliage. The crude protein (CP), total phenols (TP), condensed tannins (CT), IVDMD, and IVOMD were different among the foliages. The PEG determined the biological activity of the TP and CT of H. brasiletto. Goats preferred to consume the foliage of P. dulce because of its higher content of CP and IVDMD and low content of TP and CT. In the productive response, dry matter intake (DMI) was higher in kids fed T1 diet and was stimulated by higher IVDMD and IVOMD, which resulted in the higher daily weight gain (DWG). The contribution with TP and CT of H. brasiletto to T5 and T6 and the rejection by the animals of G. sepium in T3 and T4 explain the negative effects on the DMI and the DWG. Findings of the study suggested higher kid performance for P. dulce foliage. Possible attributes may include its better CP, low TP and CT, and higher digestibility.