Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain.

Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, lrp6 mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain.

Should a Stoma Be Used After Intestinal Transplant.

As we all acknowledge benefits of ostomies, they can come with significant morbidity, quality of life issues, and major complications, especially during reversal procedures. In recent years, we have started to observe that similar graft and patient survival can be achieved without ostomies in certain cases. This observation and practice adopted in a few large-volume transplant centers opened a new discussion about the necessity of ostomies in intestinal transplantation. There is still more time and randomized studies will be needed to better understand and analyze the risk/benefits of "No-ostomy" approach in intestinal transplantation.

Infrared spectroscopy as a predictive tool for the severity of COVID-19 using patient's saliva: A strategy to avoid hyperinflammation.

Discriminate the severity level of COVID-19 disease is still a challenge. Here we investigate the capability of micro-infrared absorption spectroscopy (micro-FTIR) to probe COVID-19 severity level and predict hyperinflammation, correlating the assigned vibrational data to relevant biomolecules related to the immune system. Saliva of 184 patients was analysed by ELISA assay (Hepcidin) and micro-FTIR. Vibrational bands related to IgM and IgA can discriminate healthy from Severe individuals (sensitivity ≥ 0.749, specificity ≥ 0.945) and are less effective in discriminating Mild or Moderate individuals from the Severe group (sensitivity ≥ 0.628, specificity ≥ 0.867). Analysis of the second derivative of spectra probed increased levels of IL-6 in the saliva a key additional information for the degree of severity prediction. Because the model discriminates all the groups regarding the Severe group, it predicts an intense state of inflammation based on FTIR analysis. It is a powerful tool for predicting hyperinflammation conditions related to SARS-CoV-2 infection and may be an ally in implementing drugs or therapeutic approaches to manage COVID-19 in the Severe stage in healthcare facilities.

A rat model of cirrhosis with well-differentiated hepatocellular carcinoma induced by thioacetamide.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis and well-differentiated HCC, characterized by increased fibrosis, altered liver architecture, and enhanced hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats. This TAA-induced cirrhosis and HCC rat model successfully replicates the clinical progression of human HCC, including liver function impairment and early-stage liver cancer characteristics. It presents a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.

Dimethyl fumarate modulates the regulatory T cell response in the mesenteric lymph nodes of mice with experimental autoimmune encephalomyelitis.

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.

Multimorbidity and acute infectious diseases in urban and semi-urban settings in Peru: A mixed-methods study.

Background: The co-occurrence of chronic diseases and acute infectious events exacerbates disability and diminishes quality of life, yet research in Low- and Middle-Income countries is scarce. We aimed to investigate the relationship between infectious events and multimorbidity in resource-constrained settings. Methods: We conducted a sequential mixed-method study in Lima and Tumbes, Peru, with participants having multimorbidity from the CRONICAS Cohort Study. They completed a questionnaire on the occurrence, treatment, and health-seeking behaviour related to acute infectious events. Qualitative interviews explored the perceptions and links between multimorbidity and acute infectious events for a subgroup of participants. Findings: Among individuals with multimorbidity, low awareness of chronic conditions and poor medication adherence. The cumulative incidence for respiratory and gastrointestinal infections, the most reported acute conditions, was 2.0 [95%CI: 1.8-2.2] and 1.6 [1.2-1.9] events per person per year, respectively. Individuals with cancer (6.4 [1.6-11.2] events per person per year) or gastrointestinal reflux (7.2 [4.4-10.1] events per person per year) reported higher cumulative incidence of infectious events than others, such as those with cardiovascular and metabolic conditions (5.2 [4.6-5.8] events per person per year). Those with three or more chronic conditions had a slightly higher cumulative incidence compared with individuals with two conditions (5.7 [4.4-7.0] vs 5.0 [4.4-5.6] events per person per year). Around 40% of individuals with multimorbidity sought healthcare assistance, while others chose drugstores or didn't seek help. Our qualitative analysis showed diverse perceptions among participants regarding the connections between chronic and acute conditions. Those who recognized a connection emphasized the challenges in managing these interactions. Interpretation: Our study advances understanding of multimorbidity challenges in resource-limited settings, highlighting the impact of acute infections on patients' existing multimorbidity burden.

Environmental impact assessment of the electrokinetic adsorption barriers to remove different herbicides from agricultural soils.

In this study, the sustainability of the electrokinetic remediation soil flushing (EKSFs) process integrated without and with adsorption barriers (EKABs) have been evaluated for the treatment of four soils contaminated with Atrazine, Oxyfluorfen, Chlorosulfuron and 2,4-D. To this purpose, the environmental effects of both procedures (EKSFs and EKABs) have been determined through a life cycle assessment (LCA). SimaPro 9.3.0.3 was used as software tool and Ecoinvent 3.3 as data base to carry out the inventory of the equipment of each remediation setup based on experimental measurements. The environmental burden was quantified using the AWARE, USEtox, IPPC, and ReCiPe methods into 3 Endpoint impact categories (and damage to human health, ecosystem and resources) and 7 Midpoints impact categories (water footprint, global warming potential, ozone depletion, human toxicity (cancer and human non-cancer), freshwater ecotoxicity and terrestrial ecotoxicity). In general terms, the energy applied to treatment (using the Spanish energy mix) was the parameter with the greatest influence on the carbon footprint, ozone layer depletion and water footprint accounting for around 70 % of the overall impact contribution. On the other hand, from the point of view of human toxicity and freshwater ecotoxicity of soil treatments with 32 mg kg-1 of the different pesticides, the EKSF treatment is recommended for soils with Chlorosulfuron. In this case, the carbon footprint and water footprint reached values around 0.36 kg of CO2 and 114 L of water per kg of dry soil, respectively. Finally, a sensitivity analysis was performed assuming different scenarios.

Thermodynamic Study of Alkylsilane and Alkylsiloxane-Based Ionic Liquids.

The thermodynamic properties of ionic liquids (ILs) bearing alkylsilane and alkylsiloxane chains, as well as their carbon-based analogs, were investigated. Effects such as the replacement of carbon atoms by silicon atoms, the introduction of a siloxane linkage, and the length of the alkylsilane chain were explored. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to study the thermal and phase behavior (glass transition temperature, melting point, enthalpy and entropy of fusion, and thermal stability). Heat capacity was obtained by high-precision drop calorimetry and differential scanning microcalorimetry. The volatility and cohesive energy of these ILs were investigated via the Knudsen effusion method coupled with a quartz crystal microbalance (KEQCM). Gas phase energetics and structure were also studied to obtain the gas phase heat capacity as well as the energy profile associated with the rotation of the IL side chain. The computational study suggested the existence of an intramolecular interaction in the alkylsiloxane-based IL. The obtained glass transition temperatures seem to follow the trend of chain flexibility. An increase of the alkylsilane chain leads to a seemingly linear increase in molar heat capacity. A regular increment of 30 J·K-1·mol-1 in the molar heat capacity was found for the replacement of carbon by silicon in the IL alkyl chain. The alkylsilane series was revealed to be slightly more volatile than its carbon-based analogs. A further increase in volatility was found for the alkylsiloxane-based IL, which is likely related to the decrease of the cohesive energy due to the existence of an intramolecular interaction between the siloxane linkage and the imidazolium headgroup. The use of Si in the IL structure is a suitable way to significantly reduce the IL's viscosity while preserving its large liquid range (low melting point and high thermal stability) and low volatilities.

Transport Properties in Multicomponent Systems Containing Cyclodextrins and Nickel Ions.

In this work, we propose a comprehensive experimental study of the diffusion of nickel ions in combination with different cyclodextrins as carrier molecules for enhanced solubility and facilitated transport. For this, ternary mutual diffusion coefficients measured by Taylor dispersion method are reported for aqueous solutions containing nickel salts and different cyclodextrins (that is, α-CD, ß-CD, and γ-CD) at 298.15 K. A combination of Taylor dispersion and other methods, such as UV-vis spectroscopy, will be used to obtain complementary information on these systems. The determination of the physicochemical properties of these salts with CDs in aqueous solution provides information that allows us to understand solute-solvent interactions, and gives a significant contribution to understanding the mechanisms underlying diffusional transport in aqueous solutions, and, consequently, to mitigating the potential toxicity associated with these metal ions. For example, using mutual diffusion data, it is possible to estimate the number of moles of each ion transported per mole of the cyclodextrin driven by its own concentration gradient.

N-acetylcysteine absorption and its potential dual effect improve fitness and fruit yield in Xylella fastidiosa infected plants.

BACKGROUND: Xylella fastidiosa is a multi-host bacterium that can be detected in hundreds of plant species including several crops. Diseases caused by X. fastidiosa are considered a threat to global food production. The primary method for managing diseases caused by X. fastidiosa involves using insecticides to control the vector. Hence, it is necessary to adopt new and sustainable disease management technologies to control not only the insect but also the bacteria and plant health. We demonstrated that N-acetylcysteine (NAC), a low-cost cysteine analogue, is a sustainable molecule that can be used in agriculture to decrease the damage caused by X. fastidiosa and improve plant health. RESULTS: Using 15N-NAC we proved that this analogue was absorbed by the roots and transported to different parts of the plant. Inside the plant, NAC reduced the bacterial population by 60-fold and the number of xylem vessels blocked by bacterial biofilms. This reflected in a recovery of 0.28-fold of the daily sap flow compared to health plants. In addition, NAC-treated citrus variegated chlorosis (CVC) plants decreased the oxidative stress by improving the activity of detoxifying enzymes. Moreover, the use of NAC in field conditions positively contributed to the increase in fruit yield of CVC-diseased plants. CONCLUSION: Our research not only advances the understanding of NAC absorption in plants, but also indicates its dual effect as an antimicrobial and antioxidant molecule. This, in turn, negatively affects bacterial survival while improving plant health by decreasing oxidative stress. Overall, the positive field-based evidence supports the viability of NAC as a sustainable agricultural application. © 2024 Society of Chemical Industry.

Brazilian Version of the Yale Food Addiction Scale for Individuals with Severe Obesity.

PURPOSE: Adapting and validating the Portuguese version of Br-YFAS 2.0-Obes to allow it to be used by the Brazilian candidates for bariatric surgery. MATERIALS AND METHODS: This study included 329 individuals with body mass indexes (BMI) ≥ 30 kg/m2, candidates for bariatric surgery at a reference hospital in Brazil. They were given a questionnaire that identified sociodemographic data, and the YFAS 2.0 scale, Portuguese version (BR-YFAS2.0-Obes), was applied to assess their food dependence levels. The Food Craving Questionnaire - Trait: The FCQ-T-reduced was subsequently used for a correlation analysis. RESULTS: The patients' average BMI was 41.6 ± 8.8 kg/m2. Br-YFAS2.0-Obes presented an average of 4.9 ± 3.1 for the FA diagnostic criteria. The resulting values of the Comparative Fit Index, Tucker Lewis Index, and Standardized Root Mean Square Residual were 0.990, 0.986, and 0.074, respectively. The internal consistency analysis of the 11 domains presented a Kuder-Richardson α of 0.82. The convergent validity, obtained through an analysis of the Pearson correlation coefficient, was r = 0.43 (p < 0.001). It was found that an increase in the number of Br-YFAS 2.0-Obes symptoms is associated with an increase in the FCQ-T-r mean. CONCLUSION: Much like the YFAS 2.0 in other languages, the BR-YFAS 2.0-Obes presented adequate convergent validity, reliability, and one-factor structure results, which makes it suitable for Brazilian candidates for bariatric surgery or any individual who is within BMI > = 30 kg/m2.

A multimodal approach using fundus images and text meta-data in a machine learning classifier with embeddings to predict years with self-reported diabetes - An exploratory analysis.

AIMS: Machine learning models can use image and text data to predict the number of years since diabetes diagnosis; such model can be applied to new patients to predict, approximately, how long the new patient may have lived with diabetes unknowingly. We aimed to develop a model to predict self-reported diabetes duration. METHODS: We used the Brazilian Multilabel Ophthalmological Dataset. Unit of analysis was the fundus image and its meta-data, regardless of the patient. We included people 40 + years and fundus images without diabetic retinopathy. Fundus images and meta-data (sex, age, comorbidities and taking insulin) were passed to the MedCLIP model to extract the embedding representation. The embedding representation was passed to an Extra Tree Classifier to predict: 0-4, 5-9, 10-14 and 15 + years with self-reported diabetes. RESULTS: There were 988 images from 563 people (mean age = 67 years; 64 % were women). Overall, the F1 score was 57 %. The group 15 + years of self-reported diabetes had the highest precision (64 %) and F1 score (63 %), while the highest recall (69 %) was observed in the group 0-4 years. The proportion of correctly classified observations was 55 % for the group 0-4 years, 51 % for 5-9 years, 58 % for 10-14 years, and 64 % for 15 + years with self-reported diabetes. CONCLUSIONS: The machine learning model had acceptable accuracy and F1 score, and correctly classified more than half of the patients according to diabetes duration. Using large foundational models to extract image and text embeddings seems a feasible and efficient approach to predict years living with self-reported diabetes.

On the distribution and habitat use of the sub-Antarctic fly Hyadesimyia clausa Bigot (Diptera, Tachinidae) according to citizen science.

Hyadesimyia clausa Bigot is a morphologically striking tachinid that inhabits the Sub-Antarctic Ecoregion of the Magallanes Region in Chile and Tierra del Fuego province in Argentina. Much of the distributional information about this species is restricted to the Cape Horn islands, which have extreme environmental conditions, but the species' natural history, range limits, and habitat use have never been described or confirmed. Our goals were to describe the distributional limits of this sub-Antarctic fly with the help of citizen science and use this information type to describe this tachinid's habitat use and potential biological interactions with nonvascular and vascular flora. We found that citizen science significantly increased our understanding of the extent of occurrence, expanding the known distributional range by 195 km to the north and 153 km to the west. On the contrary, the values for the area of occupancy were not significant, but the occupancy overlap between different records was very low. We confirmed that H. clausa's habitat uses peatlands and although we have not provided evidence of pollination or movement of spores, we hypothesized, that the walking activity of H. clausa could help move sperm from mosses and pollen from the flowers of vascular plants, so they could act as potential pollinators. Citizen science can reduce and eliminate some scientific knowledge shortfalls and propose new ecological questions that could increase our knowledge of extreme ecosystems.

Vulnerable newborn phenotypes in Peru: a population-based study of 3,841,531 births at national and subnational levels from 2012 to 2021.

Background: We aimed to examine the national and subnational prevalence of vulnerable newborn phenotypes in Peru, 2012-2021. Methods: Newborn phenotypes were defined using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight [LBW], non-LBW) using the Peruvian National Birth Registry as six (by excluding birthweight) and ten newborn phenotypes (using all three outcomes). Small phenotypes (with at least one classification of PT, SGA, or LBW) were further considered. Using individual-level data, we stratified the phenotypes by maternal educational level, maternal age, healthcare insurance, altitude of residence, and geographic region (Coast, Andes, and Amazon). Findings: The prevalence of the five vulnerable newborn phenotypes for the study period was LGA+T (15.2%), AGA+PT (5.2%), SGA+T (4.6%), LGA+PT (0.8%), and SGA+PT (0.7%). The Coast had a higher prevalence of newborns with large phenotypes (19.4%) and the Highlands a higher prevalence of newborns with small phenotypes (12.5%). Mothers with poor socioeconomic status, extreme ages and living at high altitude had a higher prevalence of newborns with small phenotypes, and mothers who were wealthier, more educated, and older had a higher prevalence of infants with large phenotypes. Interpretation: Our findings cautiously suggest that socioeconomic and geographic disparities may play a crucial role in shaping vulnerable newborn phenotypes at national and subnational level in Peru. Further studies using longitudinal data are needed to corroborate our findings and to identify individual-level risk factors. Funding: Ter Meulen Grant from the KNAW Medical Sciences Fund of the Royal Netherlands Academy of Arts and Sciences (KNAWWF/1085/TMB406, KNAWWF/1327/TMB202116), Fogarty Program (D43TW011502).

Compliance with eye and foot preventive care in people with self-reported diabetes in Latin America and the Caribbean: Pooled, cross-sectional analysis of nine national surveys.

AIMS: To estimate the proportion of people with self-reported diabetes receiving eye and foot examinations in Latin America and the Caribbean (LAC). METHODS: Cross-sectional analysis of national health surveys in nine countries. Adults aged 25-64 years with self-reported diabetes. We quantified the proportion who reported having an eye examination in the last two years or a foot examination in the last year. We fitted multilevel Poisson regressions to assess socio-demographic (age and sex) and clinical (oral hypoglycemic medication and insulin treatment) variables associated with having had examinations. RESULTS: There were 7435 people with self-reported diabetes included in the analysis. In three countries (Chile [64%; 95% CI: 56%-71%], British Virgin Islands [58%; 95% CI: 51%-65%], and Brazil [54%; 95% CI: 50%-58%]), >50% of people with diabetes reported having had an eye examination in the last two years. Fewer participants (<50% across all countries) reported having had a foot examination in the last year, with Ecuador having the lowest proportion (12%; 95% CI: 8%-17%). Older people, and those taking oral medication or insulin, were more likely to have eye/foot examinations. CONCLUSIONS: The proportion of eye and foot examinations in people with self-reported diabetes across nine countries in LAC is low.

Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Systematic review and meta-analysis of randomized controlled trials on the effects of exercise interventions on amyloid beta levels in humans.

Alzheimer's disease (AD) represents the most common type of dementia. A crucial mechanism attributed to its development is amyloid beta (Aß) dynamics dysregulation. The extent to which exercise can modulate this phenomenon is uncertain. The aim of this study was to summarize the existing literature evaluating this issue. A comprehensive systematic search was performed in Pubmed, Scopus, Embase, Web of Science, and SciELO databases and completed in August 2023, aiming to identify randomized controlled trials investigating the effect of exercise upon Aß-related pathology. The keywords "exercise" and "amyloid beta", as well as all their equivalents and similar terms, were used. For the analysis, the negative or positive dementia status of the subjects was initially considered and then the soluble amyloid precursor protein (sAPP) components and Aß fragments separately. A meta-analysis was performed and involved eight studies (moderate-to-high quality) and 644 assessments, which were 297 for control and 347 for exercise. No overall effect favoring exercise interventions was observed for both negative (SMD95%=0,286 [-0,131; 0,704]; p = 0,179) or positive AD dementia status (SMD95%=0,110 [-0,155; 0,375]; p = 0,416). The absence of an overall effect favoring exercise interventions was also found for Aß peptides (SMD95%=0,226 [-0,028; 0,480]; p = 0,081) and for sAPP components (SMD95%=-0,038 50 [-0,472; 0,396]; p = 0,863) levels. Our findings suggest that exercise interventions do not improve Aß-related pathology in both healthy individuals and individuals with dementia (SMD95%=0,157 [-0,059; 0,373]; p = 0,155), indicating that the beneficial effects of exercise for AD reported in previous studies are related to other mechanistic effects rather than direct amyloid effects (PROSPERO registration number: CRD42023426912).

Exploring the impact of high-energy diets on cattle: insights into subacute rumen acidosis, insulin resistance and hoof health.

Cattle lameness remains a significant concern, causing economic losses and compromising animal welfare. Claw horn lesions have been identified as a major cause of lameness in dairy cows but its correlation with high-energy diet and ruminal acidosis remains unclear. Hence, the primary objective of this study was to assess the effects of a high starch and a conventional diet on the rumen environment, acute phase proteins, and metabolic alterations, with a particular focus on insulin resistance and the consequent implications for the histology of the hooves in Holstein steers. Sixteen animals were divided into the high-starch (HS; 37% starch) and conventional (CON; 16.8% starch) groups. Glucose tolerance tests (GTT), blood, rumen fluid analysis, and histological evaluations of the hoof tissue were conducted over a 102-d experimental period. The HS group showed a lower ruminal pH than the CON group, and with values indicating subacute ruminal acidosis (SARA). The plasma glucose and IGF-1 concentrations were higher in the HS group, suggesting an anabolic state. Both groups exhibited an increase in the insulin area under the curve (AUC) after the GTT on d 102. Histological analysis of the hooves showed a reduction in the length and width of the epidermal lamella in both groups. There was a significant negative correlation between the insulin AUC and the length and width of the epidermal lamella. Since both groups were similarly affected, the hypothesis that histological alterations were caused by the experimental diets still needs confirmation. Additionally, the development of SARA was not essential for the observed histological changes in the hoof. Further studies are warranted to thoroughly investigate the role of insulin and IGF-1 imbalances in claw health.

Changing Clinical Epidemiology of Plasmodium vivax Malaria as Transmission Decreases: Population-Based Prospective Panel Survey in the Brazilian Amazon.

BACKGROUND: Malarial infections are often missed by microscopy, and most parasite carriers are asymptomatic in low-endemicity settings. Whether parasite detectability and its ability to elicit symptoms change as transmission declines remains unclear. METHODS: We performed a prospective panel survey with repeated measurements on the same participants over 12 months to investigate whether Plasmodium vivax detectability by microscopy and risk of symptoms upon infection varied during a community-wide larviciding intervention in the Amazon basin of Brazil that markedly reduced vector density. We screened 1096 to 1400 residents in the intervention site for malaria by microscopy and quantitative TaqMan assays at baseline and twice during intervention. RESULTS: We found that more P vivax infections than expected from their parasite densities measured by TaqMan assays were missed by microscopy as transmission decreased. At lower transmission, study participants appeared to tolerate higher P vivax loads without developing symptoms. We hypothesize that changes in the ratio between circulating parasites and those that accumulate in the bone marrow and spleen, by avoiding peripheral blood microscopy detection, account for decreased parasite detectability and lower risk of symptoms under low transmission. CONCLUSIONS: P vivax infections are more likely to be subpatent and remain asymptomatic as malaria transmission decreases.