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Marcelo Guimarães Boia do Nascimento,1,2 Sérgio Adriano Gomes,1 Márcio Rabelo Mota,1,2 Renata Aparecida,1 Gislane Ferreira de Melo21Physical Education Department, Universitary Center of Brasília, Brasília, Brazil; 2Physical Education Department, Catholic University of Brasília, Brasília, Brazil Abstract: The present study aimed to identify the psychological profiles of professional futsal players in terms of the gender schema and to evaluate the physiological parameters (speed, acceleration, strength, and power) and fatigue index of these athletes according to their gender profiles and relative to their positions on the court. The Masculine Inventory of the Self-concept Gender Schemas was used to classify the sample into typological groups, and the Running Anaerobic Sprint Test was used to measure the physiological parameters (speed, acceleration, strength, and power) and the fatigue index. The study sample was composed of 64 male professional futsal players who competed in the National Indoor Soccer league in 2013; the subjects had an average weight of 76.00±6.7 kg. Among the athletes studied, 23 (35.9%) were classified as heteroschematic female, 22 (34.4%) as heteroschematic male, and 19 (29.7%) as isoschematic. Regarding their positions on the court, eleven were goalkeepers (17.2%), 13 (20.3%) were defenders, 28 (43.8%) were midfielders, and 12 (18.8%) were attackers. The players had similar weights even when belonging to different typological groups and having different positions in the court. However, it is worth noting that male heteroschematic players had a greater mean weight (77.11±5.93 kg) and that the goalkeeper was, on average, the heaviest player (79.36±8.14 kg). The results of the physiological parameter analysis relative to typological group showed that, on average, high-level soccer players presented similar performance profiles in different rounds, as statistically significant differences were not found in any of the studied physiological variables (weight, distance, speed, acceleration, strength, power, and fatigue index). Although the results of this research did not reveal statistically significant differences between the groups in terms of the assessed variables, we observed that some results related to personality traits associated with both the male and female components could help to clarify and establish relationships with some strategic aspects inherent to futsal. Keywords: futsal, Masculine Inventory of the Self-concept Gender Schemas, fatigue index, anaerobic power, psychological profiles, personality traits

Background: Students enter the medical study with internally generated motives like genuine interest (intrinsic motivation) and/or externally generated motives like parental pressure or desire for status or prestige. Due to limited information available on the motivational factors to take up medicine among Indian students, this study was carried out to determine motivations of first-year medical students’ towards a medical career. Methodology: This cross-sectional study was carried out among all 250 first year medical students of Kasturba Medical College (Manipal University), Mangalore in February 2015. Data collection was done using a pre-tested semi structured questionnaire, consisting of 16 questions about demographic and academic characteristics; motivational factors to study medicine; and the role of career guidance in choice of study Data were analysed using SPSS (Statistical Package for Social Sciences) version 11.5. Results: Of 250 students, 246 (98.4%) submitted completed questionnaires. The majority of the students (72%) were self-motivated for choosing medicine as a career; 64.2% chose medicine because it is a humane and noble profession; 50.4% for respect and prestige it provides; 36.6% were inspired by the family; 27.2% because of the non-requirement to study Mathematics and Physics and 14.6% for financial security. Also, 16.3% students had parents in the medical profession; Fifty-seven students (55%) got admission after > or = 2 attempts; 46% decided on a medical career before class ten. Overall, 13% had sought career counselling. More than half of the students had accurate knowledge about the curriculum, course duration, examinations, and post graduate training. Conclusion: Nobility of the profession, prestige, and inspiration from family members were the predominant motivating factors. Determining the reasons for choosing medicine has important implications for the selection and training of students as well as for their future job satisfaction.

Today, companies involved in product development in the “Industry 4.0” era, need to manage all the necessary information required in the product entire lifecycle, in order to optimize as much as possible the product-process integration. In this paper, a Product Lifecycle Management (PLM) approach is proposed, in order to facilitate product-process information exchange, by considering design constraints and rules coming from DFMA (Design For Manufacturing and Assembly) guidelines. Indeed, anticipating these manufacturing and assembly constraints in product design process, reduces both costs and Time To Market (TTM), and avoids to repeat mistakes. The paper details the application of multi-objective optimization algorithms after considering DFMA constraints in a PLM approach. A case study using an original mechatronic system concept is presented, and improved by considering product-process integrated design, optimization and simulation loops, using numerical optimization and FEM (Finite Element Method) methods and tools.

The development of a new product is a process that goes through several phases, each of them requiring the ca- pitalization of data, information, knowledge and experiences gathered from previous projects. This knowledge is kept by a limited number "Experts", and is not necessarily captured in a practical, reusable way, which translates into a loss of time and a delay for the projects. Our approach involves exporting the client's specifications from a PLM platform and con- structing a generic product, an automotive air conduct, from them. This generic product is then fed through an optimization cycle to determine the best position and geometrical shape for all its elements. This multi-criteria optimization requires several constraints and objective functions in order to improve the part quality and process reliability needed expected by the Original Equipment Manufacturer (OEM). The need to have a design process less dependent on personal "expert" knowledge was the driving idea behind this work. The automatic optimization of the design of an air conduct still remains a challenge and the purpose of this work is to contribute to the development of an automatic design tools capable of doing this.

The objective of this paper is to present a methodology used to streamline the product development process by introducing Lean Engineering concepts. We are interested specifically in routine design which represents in some companies more than 80% of the design activity. A project management model was developed and implemented in a PLM tool. This allows faster initiation of projects in which project planning is automatically performed. Hence, non-added value tasks in project planning were identified and reduced.

Abstract Background Giardia duodenalis is a widespread parasite of mammalian species, including humans. The prevalence of this parasite in children residing in Portugal is currently unknown. This study intended to estimate G. duodenalis infection prevalence and identify possible associated risk factors in a healthy paediatric population living in the District of the Portuguese capital, Lisbon. Methods Between February 2002 and October 2008, 844 children were randomly selected at healthcare centres while attending the national vaccination program. A stool sample and a questionnaire with socio-demographic data were collected from each child. Giardia infection was diagnosed by direct examination of stools and antigen detection by ELISA. Results The population studied revealed a gender distribution of 52.8% male and 47.2% female. Age distribution was 47.4% between 0-5 years and 52.6% between 6-15 years. The prevalence of Giardia infection was 1.9% (16/844) when estimated by direct examination and increased to 6.8% (57/844) when ELISA results were added. The prevalence was higher among children aged 0-5 years (7.8%), than among older children (5.8%), and was similar among genders (6.9% in boys and 6.5% in girls). The following population-variables were shown to be associated risk factors for G. duodenalis infection: mother's educational level (odds ratio (OR)= 4.49; confidence interval (CI): 1.20-16.84), father's educational level (OR = 12.26; CI: 4.08-36.82), presence of Helicobacter pylori infection (OR = 1.82; CI: 1.05-3.15), living in houses with own drainage system (OR = 0.10; CI: 0.02-0.64) and reported household pet contact, especially with dogs (OR = 0.53; CI: 0.31-0.93). Conclusion The prevalence of giardiasis in asymptomatic children residing in the region of Lisbon is high. Several risk factors were associated with Giardia prevalence and highlight the importance of parents' education and sanitation conditions in the children's well being. The association between G. duodenalis and H. pylori seems an important issue deserving further investigation in order to promote prevention or treatment strategies.

Thoracolumbar hydrated nucleus pulposus extrusion (TL-HNPE) is an increasingly recognised pathology with a substantial lack of literature describing its features. The aim of this retrospective case-control study was to analyse the clinical and magnetic resonance imaging (MRI) features of dogs with TL-HNPE compared to dogs affected with thoracolumbar intervertebral disc extrusion (TL-IVDE). Data from dogs diagnosed with TL-HNPE and TL-IVDE via MRI at two referral hospitals, were retrospectively collected and compared in terms of clinical signs and MRI features. Cases diagnosed with TL-IVDE were deemed controls. The MRI features of the affected IVD space, herniated IVD material, affected overlying spinal cord and local epaxial musculature were evaluated for each group. Fifty-one cases with TL-HNPE and 105 randomly selected cases of TL-IVDE were included. Several signalment and neurological signs were identified as statistically distinct between groups in univariate analysis. Multivariate analysis identified that dogs affected with TL-HNPE were typically older, less likely to be chondrodystrophic (62.2 % vs. 91 %), more frequently experiencing a peracute onset (90.2 % vs. 61.9 %) often attributed to a suspected trauma linked with exercise (37.3 % vs. 10.5 %), being less frequently progressive (41.2 % vs. 86.5 %) and with herniated disc material less frequently lateralised (72.6 % vs. 89.5 %) than cases with TL-IVDE. MRI-identifiable intervertebral disc degeneration was found in every TL-IVDE case but only in 60 % of TL-HNPE cases. TL-HNPEs were associated to significantly less spinal cord compression and less hyperalgesia than TL-IVDE., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific white matter structure, the superior longitudinal fasciculus (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics., Competing Interests: MM-G was employed by Independent Vetcare (IVC) Evidensia. EI was employed by Linnaeus Veterinary Ltd. CB was employed by VetCT. IC was employed by VetOracle. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Miguel-Garcés, Gonçalves, Quintana, Álvarez, Beckmann, Alcoverro, Moioli, Ives, Madden, Gomes, Galban, Bentley, Santifort, Vanhaesebrouk, Briola, Montoliu, Ibaseta and Carrera.)

Introduction: The aim of this study was to analyze the effects of space and number of players manipulation on the external and internal load demands of youth futsal athletes., Methods: Forty-two male U17 players (age = 15.62 ± 0.58 years) from three futsal teams participated in the study. In this cross-sectional study that lasted 8-week, the player's sample practiced six futsal tasks (T1-T6) and a futsal game played under the official rules (T7). From T1-T6, two task constraints were manipulated: (i) the number of players and, (ii) the space of play. The WIMU PRO™ Ultra-Wideband (UWB) tracking system was used to measure the external and internal load during the futsal tasks. External load was quantified using kinematic and mechanical variables extracted from positional data and, the internal load was quantified using Heart rate (HR) and rating of perceived exertion (RPE). Repeated measures ANOVA was used for comparison purposes., Results: In general, the results showed high external (total distance, distance 18.1-21, above 21 Km/h, and high intensity acceleration and deceleration, p  < 0.001) and internal load (heart rate average and rating of perceived exertion, p  < 0.001) in the tasks with low number of players and high area. In relation to the match, the tasks with small relative area per player (GK + 2 vs. 2 + GK and GK + 3 vs. 3 + GK in 20 × 20 m) promoted low external load., Conclusion: It was concluded that increasing the relative area by reducing the number of players involved in the tasks in the form of small-sided games (GK + 2 vs. 2 + GK and GK + 3 vs. 3 + GK), in relation to the futsal game (GK + 4 vs. 4 + GK), can be considered a pedagogical strategy to increase the external and internal load demands of young futsal players., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Gomes, Travassos, Ribeiro, Castro, Gomes and Ferreira.)

Background: The place of death profoundly affects end-of-life care quality, particularly in cancer. Assisting individuals at home enhances support, privacy, and control, reducing healthcare costs. This study seeks to elucidate factors associated and trends in place of death by cancer in Brazil., Methods: Using data obtained from the National Mortality Information System, this study extracted tumour topography, sociodemographic characteristics, and the place of death (outcome classified into hospital or home death) by cancer in Brazil from 2002 to 2021., Findings: The analysis included 3,677,415 cases, with 82.3% of deaths occurring in hospitals and 17.7% at home. Most participants were male (53.1%), had gastrointestinal tumours (32.2%), and resided in the Southeastern region (48.7%). Home deaths were more frequent in the Northeastern (30.2%) and Northern (24.8%) regions compared to the Southern (17.1%) and Southeastern (12.2%) regions. A strong inverse correlation was found between home deaths and the Human Development Index of the region. Over the years, there was a reduction in home deaths, followed by a recent increase. Individuals with no formal education, indigenous individuals, and patients from the North, Northeast, and Central-West regions had higher rates of home deaths, while patients with haematological malignancies had lower rates compared to those with gastrointestinal tumours., Interpretation: The minority of deaths by cancer in Brazil occur at home, with distinct trends over time. Home death was associated with regional, racial and educational level differences., Funding: No funding., Competing Interests: Andréia Cristina de Melo has grants or contracts from Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, GSK, MSD, Novartis, Regeneron, and Roche, with payments made to the institution. Additionally, she has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Bristol Myers Squibb, GSK, MSD, Novartis, and Roche. Lívia Machado Moura has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer and Novartis. The remaining authors declare that they have no conflicts of interest., (© 2024 The Author(s).)

In critically ill patients, overweight and obesity are associated with acute respiratory distress syndrome and acute kidney injury (AKI). However, the effect of obesity on ischemia-reperfusion injury (IRI)-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice. We fed mice a standard or high-fat diet for eight weeks. The mice were divided into four groups and submitted to sham surgery or IRI: obese, normal, normal + IRI, obese, and obese + IRI. All studies were performed 48 h after the procedures. Serum glucose, cholesterol, and creatinine clearance did not differ among the groups. Survival and urinary osmolality were lower in the obese + IRI group than in the normal + IRI group, whereas urinary neutrophil gelatinase-associated lipocalin levels, tubular injury scores, and caspase 3 expression were higher. Proliferating cell nuclear antigen expression was highest in the obese + IRI group, as were the levels of oxidative stress (urinary levels of thiobarbituric acid-reactive substances and renal heme oxygenase-1 protein expression), whereas renal Klotho protein expression was lowest in that group. Expression of glutathione peroxidase 4 and peroxiredoxin 6, proteins that induce lipid peroxidation, a hallmark of ferroptosis, was lower in the obese + IRI group. Notably, among the mice not induced to AKI, macrophage infiltration was greater in the obese group. In conclusion, greater oxidative stress and ferroptosis might aggravate IRI in obese individuals, and Klotho could be a therapeutic target in those with AKI., (© 2024. The Author(s).)

While the positive impact of early palliative care on the quality of life of cancer patients is well established, there is a noticeable research gap in developing countries. This study sought to determine the impact of an outpatient palliative care (OPC) program on the location of death among patients in Brazil. This was a retrospective study including patients with cancer who died between January 2022 and December 2022 in 32 private cancer centers in Brazil. Data were collected from medical records, encompassing demographics, cancer characteristics, and participation in the OPC program. The study involved 1980 patients, of which 32.3% were in the OPC program. OPC patients were predominantly younger (average age at death of 66.8 vs. 68.0 years old, p = 0.039) and composed of women (59.4% vs. 51.3%, p = 0.019) compared to the no-OPC patients. OPC patients had more home/hospice deaths (19.6% vs. 10.4%, p < 0.001), and participation in the outpatient palliative care program strongly predicted home death (OR: 2.02, 95% CI: 1.54-2.64). Our findings suggest a significant impact of the OPC program on increasing home and hospice deaths among patients with cancer in our sample. These findings emphasize the potential of specialized OPC programs to enhance end-of-life care, particularly in low-resource countries facing challenges related to social and cultural dimensions of care and healthcare access.

Background: The Basset Hound is the largest chondrodystrophic breed predisposed to thoracolumbar intervertebral disc extrusion (TL-IVDE). However, literature describing this particular breed in terms of incidence, signalment, anatomical location, clinical severity and short-term outcome of TL-IVDE is lacking., Methods: The medical histories of Dachshunds and Basset Hounds presenting to three neurology departments were retrospectively assessed. Information collected for each dog included signalment, whether it had received a diagnosis of TL-IVDE, duration of clinical signs, affected discs and anatomical region and neurological grading at presentation and discharge., Results: A total of 270 Dachshunds and 188 Basset Hounds were included for incidence analysis. Of these, 154 Dachshunds and 68 Basset Hounds with confirmed TL-IVDE were included for signalment, anatomical location, clinical severity and short-term outcome analysis. Statistical analysis indicated a significantly higher incidence of TL-IVDE in Dachshunds than in Basset Hounds (77.4% vs. 36.2%, p < 0.05). Basset Hounds presenting to a neurology department were older (median 87.5 months vs. 66.5 months), had a greater proportion of midlumbar IVDE (L2-L5) and were more frequently ambulatory at discharge than Dachshunds. Only one Basset Hound presented as paraplegic without nociception, compared with 16 Dachshunds (1.5% vs. 10.4%)., Limitations: The study had a retrospective design and included multicentric non-standardised cases., Conclusion: TL-IVDE incidence was higher in Dachshunds than in Basset Hounds. Basset Hounds were older at presentation, frequently affected more caudally in the vertebral column and more frequently ambulatory at discharge than Dachshunds. The differences found in this study could aid in the development of preventive strategies., (© 2023 British Veterinary Association.)

Entomopathogenic fungi are promising as an environmentally benign alternative to chemical pesticides for mosquito control. The current study investigated the virulence of Metarhizium anisopliae blastospores against Aedes aegypti under both laboratory and field conditions. Virulence bioassays of conidia and blastospores were conducted in the laboratory, while field simulation bioassays were conducted under two conditions: totally shaded (TS) or partially shaded (PS). In the first bioassay (zero h), the larvae were added to the cups shortly after the preparation of the blastospores, and in the subsequent assays, larvae were added to the cups 3, 6, 9, and 12 days later. The survival of the larvae exposed to blastospores in the laboratory was zero on day two, as was the case for the larvae exposed to conidia on the sixth day. Under TS conditions, zero survival was seen on the third day of the bioassay. Under PS conditions, low survival rates were recorded on day 7. For the persistence bioassay under PS conditions, low survival rates were also observed. Metarhizium anisopliae blastospores were more virulent to Ae. aegypti larvae than conidia in the laboratory. Blastospores remained virulent under field simulation conditions. However, virulence rapidly declined from the third day of field bioassays. Formulating blastospores in vegetable oil could protect these propagules when applied under adverse conditions. This is the first time that blastospores have been tested against mosquito larvae under simulated field conditions, and the current study could be the basis for the development of a new biological control agent.

LQFM018 is a novel antineoplastic prototype, showing an expressive drug-triggered K562 leukemic cells death mechanism, through necroptotic signaling. Due to its promising effect, this study aimed to evaluate the pharmacokinetics of LQFM018 in rats, using a new validated bioanalytical LC-MS/MS-based method. Chromatographic column was an ACE® C18 (100 mm × 4.6 mm, 5 µm) eluted by a mobile phase composed of ammonium acetate 2 mM and formic acid 0.025%:methanol (50:50, v/v), under flow of 1.2 mL/min and injection volume of 3.0 µL. LQFM018 was extracted from rat plasma by a simple liquid-liquid method, using MTBE solvent. Rats were administered intraperitoneally at LQFM018 100 mg/kg dose and blood samples were collect at times of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9 h. Bioanalytical-LC-MS/MS-based method was rapid, high throughput and sensitive with a good linearity ranging from 10 (LLOQ) to 15000 ng/mL, besides precise and accurate, ranging of 0.8-7.3% and 96.8-107.6%, respectively. The prototype LQFM018 was rapid and well absorbed, and highly distributed, apparently due to its high lipid solubility. These features are primordial for an anticancer agent in the treatment of deep tumors, such as bone marrow neoplasms, in which the drug might permeate easily tissue barriers. Also, LQFM018 has demonstrated a high clearance, according to a low t 1/2 in rats, indicating a relative fast elimination phase related to a possible intense hepatic biotransformation. These information support further studies to establish new understands on pharmacokinetics of promising antineoplastic prototype LQFM018 from preclinical and clinical evaluations., 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 Elsevier B.V. All rights reserved.)

Introduction: Studies conducted with physicians from different locations and age groups show a tendency to mental illness and low quality of life in this population., Objectives: To describe the socioeconomic and quality-of-life profile of medical doctors in the state of Minas Gerais, Brazil., Methods: Cross-sectional study. A socioeconomic and quality-of-life questionnaire (World Health Organization Quality of Life instrument-Abbreviated version) was applied in a representative sample of physicians working in the state of Minas Gerais. Non-parametric analyses were used to assess outcomes., Results: The sample was composed of 1,281 physicians, with a mean age of 43.7 years (SD, 11.46) and time since graduation of 18.9 years (SD, 12.1); 12.46% were medical residents, of which 32.7% were in the first year of training. Of the total number of physicians, 66.4% reported feeling overwhelmed and 70.7% were satisfed with their profession. The rate of diagnoses related to depression and anxiety was higher than in the general population. Mean World Health Organization Quality of Life instrument-Abbreviated version score was 60.44±21.72. The analysis of the reported quality-of-life scores showed that younger physicians, especially women, in the first year of residence, with lower income or salary ranges, high workload, and no regular time of obtained lower scores, as well as those who reported diagnoses of depression and/or anxiety., Conclusions: Some socioeconomic factors may influence the quality of life of the study population. Further studies are needed to develop effective social support and health protection actions for these workers., Competing Interests: Conflicts of interest: None

Volleyball is a popular sport in Brazil, and the relative age effect (RAE) is known to occur within it; but less is known of how RAE relates to elite Brazilian volleyball players' age, sex, and competitive levels. We aimed to investigate RAE prevalence with data from two seasons of play among players in the Superliga A (2020/2021 and 2021/2022 seasons), and Superliga B (2021 and 2022 seasons) made available from the Brazilian Volleyball Confederation (CBV), the club's official website, or direct consultation with the CBV. After removing duplicate data, we grouped these 1,063 athletes by their dates of birth, sex, and competition level (Superliga A or B). We divided players' birth dates into quarters (Q1: January-March, Q2: April-June, Q3: July-September and Q4: October-December) and into semesters, and we performed chi-square (χ 2 ) tests to investigate RAE prevalence according to the players' sex and competitive level. RAE was prevalent overall (χ 2 = 33.198; p < .001), among males (χ 2 = 24.48; p < .001) and females (χ 2 = 11.23; p < .011). Regarding competition level, RAE was evident among males in both Superliga A (χ 2 = 14.581; p = 0.002), and B (χ 2 = 13.985; p = 0.003), and among females in Superliga B (χ 2 = 9.204; p = 0.027), but not Superliga A (χ 2 = 4.012; p = 0.26). Thus, the RAE phenomenon operated differently for male and female Brazilian volleyball players according to their competitive level. We discuss the implications of these findings.

Hemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer's (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor., (© 2022. The Author(s).)

Background: Idiopathic generalised tremor syndrome (IGTS) causes tremor and often vestibulocerebellar signs. Previous publications on IGTS in dogs are restricted to case reports or lack exclusion of structural causes., Methods: Medical records of 75 dogs diagnosed with IGTS that had undergone magnetic resonance imaging (MRI) of the brain were collected retrospectively., Results: Crossbreeds were affected most commonly (41.3%), followed by West Highland white terriers (14.7%) and cocker spaniels (10.7%). A higher proportion of females were affected than males (68.0%). Median age of the affected dogs was 17 months (range 6-121 months), and median bodyweight was 9.15 kg (range 2.9-26 kg). All dogs presented with tremors and most experienced concomitant neurological signs (93.3%). Seventeen (22.7%) were hyperthermic and 31 (41.3%) had gastrointestinal signs. MRI of the brain was normal in most of the cases, and cerebrospinal fluid analysis frequently revealed mild pleocytosis. All animals were treated with prednisolone, and 39 (51.3%) also received diazepam. Median follow-up time was 13 months (range 0-134 months). The overall outcome was good, although 16 (21.3%) patients were reported to have relapsing clinical signs and 10 (13.2%) patients experienced persistent mild clinical signs., Conclusions: IGTS should be suspected in any dog with generalised tremor and vestibulocerebellar signs with younger and smaller dogs more commonly affected., (© 2022 British Veterinary Association.)

Background: Computed tomography (CT) findings of dogs with discospondylitis have not been widely described despite increased availability of this imaging modality., Objectives: Describe the CT features of discospondylitis in a population of clinically affected dogs with discospondylitis diagnosed by magnetic resonance imaging (MRI)., Animals: Forty-one dogs (63 affected discs) with MRI-identified discospondylitis presented to a single referral hospital between 2012 and 2022., Methods: Retrospective, single center, descriptive case series with analysis of MRI-identified discospondylitis sites and concomitant CT imaging. Computed tomographic features of MRI-affected sites including intervertebral disc space (IVDS), endplates, vertebral body, epidural space and paraspinal tissues were described., Results: The most frequently found changes were: (1) endplate involvement (87.3%) most frequently bilateral (94.5%), with erosion (61.9%) and multifocal osteolysis (67.3%); (2) periosteal proliferation adjacent to the IVDS (73%) and spondylosis (66.7%); and (3) vertebral body involvement (66.7%) involving one-third of the vertebra (85.7%) with multifocal osteolysis (73.5%). Other less prevalent features included an abnormal IVDS (narrowed or collapsed), sclerosis of the adjacent vertebral body or endplates, presence of disseminated idiopathic skeletal hyperostosis or vacuum artifact., Conclusions and Clinical Importance: We determined that bilateral endplate erosion and periosteal proliferation were very common in dogs with discospondylitis. Careful evaluation of CT in all 3 planes (dorsal, sagittal, transverse) is necessary to identify an affected IVDS. These described CT features can aid in the diagnosis of discospondylitis in dogs but equivocal cases might still require MRI., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

We report the case of a 14-year-old male presented with raised myocardial injury biomarkers, on the workout, Campylobacter coli was identified on stool culture, treated with antibiotics with total resolution. Cardiac magnetic resonance showed interventricular septum and lateral wall hypokinesia and subepicardial delayed enhancement, with preserved ventricular systolic function. To our knowledge, this is the first report linking Campylobacter coli to myopericarditis in children.

The authors have observed a vertebral anomaly in French and English Bulldogs and termed this anomaly "vertebral vascular canal dysplasia (VVCD)." No previously published descriptions of this anomaly were found. The aims of this retrospective, multi-institutional, observational study were to (1) describe the clinical, CT, and MRI characteristics of VVCD, and (2) estimate the prevalence and describe the characteristics of VVCD in a group of French and English Bulldogs. For descriptions of the anomaly, medical records and imaging studies of nine clinical cases with VVCD from several countries were reviewed. For estimation of prevalence, imaging studies of French and English Bulldogs from the United Kingdom (UK) and Italy were reviewed. All clinical case dogs had ≥5 thoracic vertebrae with VVCD affecting >50% of vertebral body height (VBH). The prevalence of VVCD involving ≥1 thoracic vertebra in the UK population (CT identified) of English Bulldogs and French Bulldogs was, respectively, 83.3% (30/36) and 68.3% (28/41). English Bulldogs had significantly more thoracic vertebrae with VVCD than French Bulldogs (P = < 0.01). The prevalence of VVCD in ≥1 thoracic vertebra in the Italian population (MRI identified) of English Bulldogs and French Bulldogs was, respectively, 21.7% (5/23) and 6.6% (7/106). Vertebral vascular canal dysplasia was observed in normal as well as in malformed vertebrae (e.g., hemivertebrae). Findings from the current study introduced descriptions of VVCD that can be used as background for future studies., (© 2022 American College of Veterinary Radiology.)

Objectives: There is a paucity of information on feline discospondylitis. This study aimed to describe the signalment, clinical and laboratory findings, aetiological agents, treatment and outcome in cats affected by discospondylitis., Methods: This was a retrospective review of the medical records of cats diagnosed with discospondylitis at four referral institutions., Results: A total of 17 cats were identified. Most were domestic shorthair cats (76.5%) and male (58.8%), with a median age of 9 years (range 0.9-14) and a median duration of clinical signs of 3 weeks (range 0.3-16). All cats presented with spinal hyperaesthesia; 3/17 had pyrexia. Neurological dysfunction was found in 64.7% of cats, which was indicative of a T3-L3 or L4-S2 spinal segment, associated nerve root or associated nerve neurolocalisation. Haematology, serum biochemistry and urinalysis revealed occasional inconsistent non-specific changes. All cats underwent urine culture; 9/17 cats also had a distinct tissue cultured. Positive bacterial cultures were obtained in two cats (11.8%) for Staphylococcus species (urine, blood and intradiscal fine-needle aspirate) and Escherichia coli (urine); both presented with multifocal discospondylitis. Treatment was non-surgical in all cats, with sustained antibiotic therapy for a median of 3 months (range 1-9). Analgesia provided included non-steroidal anti-inflammatory drugs, alone or in combination with gabapentin. Restricted exercise was advised for a minimum of 4 weeks. Outcome information available in 12 cats was excellent in terms of pain control and neurological function in 10 cats (83.3%) at the time of stopping antibiotics. Recurrence occurred in one case, which had received a single antibiotic for 6 weeks, and relapsed 4 months after presentation. One other case failed to improve and was euthanased during the course of hospitalisation., Conclusions and Relevance: Feline discospondylitis is uncommon and no obvious signalment predisposition was found in this study. Spinal hyperaesthesia was universally present, with neurological dysfunction also highly prevalent. Bacterial culture was unrewarding in most cases. Amoxicillin-clavulanic acid or cephalosporins are reasonable choices for first-line antibiotics. Prognosis was favourable, with no long-term evidence of recurrence in cats on sustained antibiotic therapy, for a mean duration of 3 months.

BACKGROUND Distal renal tubular acidosis (dRTA) is a defect in the urinary acidification process that limits the elimination of protons [H+] by alpha intercalated cells in the collecting tubules, with consequent metabolic acidosis with a normal plasma anion gap. The relationship between this tubulopathy and immune-mediated diseases like Sjögren syndrome, rheumatoid arthritis, autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus, and thyroiditis is well known. Further, the pathophysiological mechanisms are diverse, but, unfortunately, many are not yet fully understood. We report 3 cases of dRTA in patients with different autoimmune diseases and review the pathophysiological mechanisms already described. CASE REPORT The first case involved a 29-year-old woman with autoimmune hepatitis. She had metabolic acidosis with persistent hypokalemia, and a kidney stone was also identified. The second case involved a 67-year-old woman diagnosed with rheumatoid arthritis. She had metabolic acidosis with hypokalemia. The third case involved a 30-year-old woman with Sjögren syndrome and persistent metabolic acidosis. In addition to the presence of metabolic acidosis with a normal plasma anion gap, all 3 patients exhibited urine with a supraphysiologic pH (above 5.3). CONCLUSIONS Autoimmune diseases may be associated with deficits in urinary acidification with consequent metabolic acidosis and, therefore, systemic repercussions. This association must be remembered and researched because correct diagnosis and treatment will serve to reduce complications.

Background & Objectives: Entomopathogenic fungi are being investigated for the biological control of a range of mosquitoes. Metarhizium conidiospores (conidia) effectively kill Aedes aegypti larvae and could be deployed as an alternative to chemical insecticides. Conidial yield and virulence of fungi when cultured on three different types of solid media, was investigated., Methods: Three culture media were tested: a) Sabouraud dextrose agar (SDA); b) rice flour yeast agar (RYA) and c) rice grains. Conidia produced using these substrates were tested for virulence against Ae. aegypti larvae obtained from field collected eggs. Larvae (2 nd - 3 rd instar) were exposed to aqueous conidial suspensions and survival monitored over 7 days. Survival analysis was performed using Log-Rank and Kaplan Meier tests, while fungal growth and conidial yields were analyzed using a two-way ANOVA., Results: There were only small differences between growth rates on RYA and SDA; however, ESALQ 818 showed the highest conidial yield on rice. Conidia produced on rice grains were more virulent, rapidly reducing survival rates of mosquito larvae. ESALQ 818 conidia produced on rice grains, RYA and SDA killed 100% of the larvae on the 2 nd , 3 rd and 4 th day of exposure, respectively. IP 46 virulence of was consistently lower than ESALQ 818 for all the media tested., Interpretation & Conclusion: The choice of culture media can influence the virulence of fungal conidia to Ae. aegypti larvae, demonstrating the importance of not only selecting the most virulent isolate but also standardizing growth conditions when screening for virulence., Competing Interests: None

Sepsis is a dysregulated hyperinflammatory disease caused by infection. Sepsis leads to multiple organ dysfunction syndrome (MODS), which is associated with high rates of mortality. The cecal ligation and puncture (CLP) model has been widely used in animals and has become the gold-standard method of replicating features of sepsis in humans. Despite several studies and modified CLP protocols, there are still open questions regarding the multifactorial determinants of its reproducibility and medical significance. In our protocol, which is also aimed at mimicking the sepsis observed in clinical practice, male Wistar rats are submitted to CLP with adequate fluid resuscitation (0.15 M NaCl, 25 ml/kg BW i.p.) immediately after surgery. At 6 h after CLP, additional fluid therapy (0.15 M NaCl, 25 ml/kg BW s.c.) and antibiotic therapy with imipenem-cilastatin (single dose of 14 mg/kg BW s.c.) are administered. The timing of the fluid and antibiotic therapy correspond to the initial care given when patients are admitted to the intensive care unit. This model of sepsis provides a useful platform for simulating human sepsis and could lay the groundwork for the development of new treatments., Competing Interests: Competing interestsThe authors declare that they have no conflicts of interest or competing interests., (Copyright © 2021 The Authors; exclusive licensee Bio-protocol LLC.)

Background and Objective: Magnesium ammonium phosphate stones (MAP), also known as struvite stones, are associated with urinary infection and impairment of renal unit. The aim of this study is to evaluate the urinary metabolic risk factors for recurrence of renal calculi in patients submitted to nephrectomy due to MAP stones., Methods: We retrospectively reviewed the charts of patients > 18 years old submitted to total nephrectomy due to pure MAP stones and pure calcium oxalate (CaOx) stones from July 2006 to July 2016. Urinary metabolic parameters were assessed through 24-hour urine exams ≥ 3 months after nephrectomy. Urinary metabolic parameters and new event related to lithiasis were compared., Results: Twenty-eight and 39 patients were included in MAP and CaOx group, respectively. Abnormalities in 24-hour urine samples were similar between groups. Hypercalciuria occurred in 7.1 and 10.3% of patients in MAP and CaOx group, respectively (p = 0.66), whereas hypocitraturia was present in 65.2 and 59.0% of patients with MAP and CaOx group, respectively (p = 0.41). No significant difference in new events was found between MAP and CaOx groups (17.9 vs. 23.1%, respectively; p = 0.60)., Conclusion: A 24-hour urine evaluation should be offered to patients submitted to nephrectomy due to pure MAP stones in order to detect metabolic risk, improve treatment, and prevent stone recurrence.

Background: Radiographic signs of intervertebral disc mineralization are thought to indicate sites of future recurrence of disc extrusion (Hansen type I) but the relationship between evidence of disc degeneration on magnetic resonance imaging (MRI) and future disc extrusion with recurrence of clinical signs has not been examined., Objectives: To examine the relationship between MRI-assessed degeneration of thoracolumbar intervertebral discs and late recurrence of clinical signs in dogs presented with acute thoracolumbar intervertebral disc extrusion and treated by hemilaminectomy alone., Animals: Ninety-two client-owned dogs presented to 2 referral hospitals between 2009 and 2014., Methods: Retrospective analysis of association between clinical signs consistent with recurrent thoracolumbar intervertebral disc extrusion and MRI evidence of disc degeneration in dogs undergoing hemilaminectomy for acute thoracolumbar intervertebral disc extrusion. Univariable and multivariable Cox regression analyses were used to explore associations between recurrence of clinical signs and several characteristics of T10-L3 discs at initial diagnosis., Results: Ninety-two cases were included, of which 42 (46%) were Dachshunds and median age was 5.3 years. Clinical signs recurred in 33/92 (36%) dogs. Finding a completely degenerate disc in the T10 to L3 region (in addition to the operated site) at the time of surgery was associated with a hazard ratio of 2.92 (95% confidence interval: 1.37-6.20) for recurrence of clinical signs., Conclusions and Clinical Importance: Our results suggest that in cases of thoracolumbar intervertebral disc extrusion in dogs, recurrence of signs is likely if at least 1 completely degenerate disc in addition to the currently symptomatic disc is visible on MRI., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Thiazide and thiazide-like diuretics are widely used for the management of hypercalciuria among stone-forming patients. Although the effects of different thiazides should be relatively similar in terms of prevention of stone recurrence, their potency and side effects may differ. However, there is scarce data concerning the metabolic and bone effects of these agents among recurrent nephrolithiasis patients with hypercalciuria. The aim of this update article was to compare our experience in the use of thiazide and thiazide- like diuretics with that of the current literature, concerning their anticalciuric properties and consequent reduction of recurrent stone formation. Their impact on bone mass and potential side effects were also discussed.

Background: The administration of cytosine arabinoside (CA) by continuous rate infusion (CRI) at the time of diagnosis has been shown to improve the 3-month survival of dogs diagnosed with meningoencephalomyelitis of unknown origin (MUO), compared to subcutaneous administration. The benefit of administering subsequent sequential CA subcutaneous injections is unknown. This study compares the outcomes of a CA CRI protocol with (CRI+subcutaneous group) or without (CRI group) follow-up CA subcutaneous injections; both groups received adjunctive prednisolone., Methods: Forty-two dogs diagnosed with MUO were recruited (CRI group) and compared with 41 historical control dogs (CRI+subcutaneous group) in a prospective, controlled clinical trial with 36 months of follow-up., Results: Success rates were respectively 64.3 per cent and 65 per cent in the CRI and the CRI+subcutaneous groups at 40 weeks following diagnosis, and 32.5 per cent and 35.9 per cent at 36 months following diagnosis. The median time to relapse was 299 and 285 days for the CRI and the CRI+subcutaneous groups, respectively. No statistically significant difference was found (P≥0.05)., Conclusion: No clear benefit was identified in the administration of subsequent sequential CA subcutaneous injections after the first administration of CA by CRI for the treatment of dogs diagnosed with MUO., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study describes the imaging features of feline discospondylitis on MRI, comparing them with CT and radiographic findings where available., Methods: The medical records of cats diagnosed with discospondylitis, presented to three referring institutions, were reviewed. MRI, CT and radiographic features were assessed by two of the authors independently., Results: Fourteen sites of discospondylitis were retrospectively identified in 13 cats. The L7-S1 intervertebral disc space (IVDS) was affected in 7/14 (50%) cases. Characteristic MRI features included a hyperintense nucleus pulposus signal on T2-weighted (T2W) imaging (n = 10/14 [71%]) and short tau inversion recovery (STIR) imaging (n = 11/13 [85%]), with contrast enhancement in all (n = 11/11); involvement of adjacent vertebral endplates (n = 11/14 [79%]) and hyperintense neighbouring soft tissue on T2W (n = 11/14 [79%]) and STIR (n = 10/13 [77%]), with contrast enhancement in all (n = 11/11); and the presence of spondylosis deformans (n = 10/14 [71%]). Other features included narrowed or collapsed IVDS (n = 8/14 [57%]), contrast enhancement of vertebral bodies (n = 5/11 [46%]), epidural space involvement (n = 5/14 [36%]), compression of the spinal cord or nerve roots (n = 5/14 [36%]), paraspinal abscessation (n = 3/14 [21%]) and meningeal signal intensity abnormalities with contrast enhancement (n = 5/6 [83%]). These latter findings may indicate secondary focal meningitis. Radiographs were available covering five sites (in four cats) and CT covering three sites (in two cats). The most common radiological features were collapse or narrowing of the affected IVDS (80%) and endplate erosion (60%). No changes suggestive of discospondylitis were identifiable on radiography or CT in two sites (one cat), despite being identifiable on MRI. Repeated radiography in one case did not reveal complete radiological resolution following 9 months of treatment., Conclusions and Relevance: The results of this study indicate consistent MRI features of feline discospondylitis that should be considered in the diagnosis of this condition.

Hepatitis B virus (HBV) infection is still a concern in vulnerable populations. In a study performed by our team in 1999-2003 in two Afro-Brazilian communities, Furnas dos Dionísios (FD) and São Benedito (SB), high prevalence rates of HBV exposure (42.7% and 16.0%, respectively), high susceptibility to HBV (55.3% and 63.0%) and low HBV vaccination like profile rates (2.0% and 21.0%) were observed. In 2015-2016, we reassessed HBV epidemiological and molecular features in these two communities to verify the impact of health actions adopted in the last years. The prevalence rate of HBV exposure among the enrolled 331 subjects was 35.3% in FD and 21.8% in SB. HBV chronic infection (5.8% in FD, 4.9% in SB) remained high. The rate of HBV vaccination like profile increased from 10.7% to 43.5% (2.0% to 45.9% in FD, 21.0% to 39.5% in SB) while susceptible subjects declined from 58.9% to 26.3% (55.3% to 18.8% in FD, 63.0% to 38.7% in SB). Among 18 HBsAg positive samples, 13 were successfully sequenced (pre-S/S region). Phylogenetic analyses showed that all isolates belong to HBV subgenotype A1, clustering within the Asian-American clade. Despite the maintenance of high prevalence rate of HBV exposure over these 13 years of surveillance, significant improvements were observed, reinforcing the importance of facilitated HBV vaccination to difficult-to-access population to close gaps in prevention.

Alternative treatments to surgery in canine degenerative lumbosacral stenosis (DLSS) remain limited and reliable predictors of outcome are lacking. The aims of this clinical trial were threefold: to assess the usefulness of single epidural steroid injection (ESI) in DLSS, to compare the outcomes of ESI and decompressive surgery, and evaluate ESI as a predictor of outcome following decompressive surgery. Dogs diagnosed with DLSS were prospectively recruited and administered an ESI. If clinical signs persisted or relapsed, decompressive surgery was recommended. Follow-up was obtained. Thirty-two dogs underwent ESI with 17 having subsequent surgery. Improvement after ESI was seen in 27/32 dogs (84.4%), with 17/22 (77.2%) relapsing within 6 months (n = 15/17 relapsing within 2 months). Five dogs failed to respond to ESI and another five (15.6%) presented a persistent post-ESI favourable response (mean follow-up time, 9.4 months). Post-surgical improvement occurred in all dogs. Outcome appeared more favourable following surgical decompression, with a trend towards reduced pain, increased mobility, and greater quality of life score. This study was unable to demonstrate that ESI could predict surgical outcome. ESI was confirmed as an effective treatment in most but not all cases, leading to transient alleviation of clinical signs for longer than previously reported. ESI provided a complete and apparently long-term sustained resolution of clinical signs in a subset of dogs. Despite this, there was indication that surgical decompression can lead to a more favourable outcome. Epidural steroid injection has a role in the management of DLSS dogs, particularly when surgery is not an option., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Knowledge regarding the etiology and prognosis for canine megaesophagus (ME) is currently limited to small case series that may now be out of date in light of recent advances in the understanding of neurological syndromes and the availability of advanced diagnostic testing. Ninety-nine dogs diagnosed with nonstructural ME were included. Congenital idiopathic ME was present in 10 cases, with complete resolution of clinical signs in a single case. Eighty-nine cases were considered acquired, with most cases being either idiopathic (42.7%) or associated with myasthenia gravis (38.2%). Idiopathic cases represented a smaller percentage of acquired ME than previously reported. Death or euthanasia directly related to ME occurred in almost 50% of acquired cases, whereas clinical signs persisted in ∼20% of cases and resolved in 30% of cases. A diagnosis of an underlying etiology, in particular myasthenia gravis, was associated with a better outcome in acquired ME. ME continues to be a challenging condition to manage, with a guarded-to-poor prognosis, particularly when an underlying etiology is not identified. Thorough diagnostic testing for an underlying neurological disorder is important in cases with ME as this may allow institution of appropriate treatment and the potential for a better prognosis.

Sepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by α7-nicotinic acetylcholine receptors (α7nAChRs), which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CLP+WJ-MSCs (1 × 10 6 cells, at 6 h post-CLP); and CLP+methyllycaconitine (MLA)+WJ-MSCs (5 mg/kg body wt, at 5.5 h post-CLP, and 1 × 10 6 cells, at 6 h post-CLP, respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective α7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated α7nAChR expression, as well as reduced the phospho-STAT3-to-total STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.

Progenitor/stem cell-based kidney regenerative strategies are a key step towards the development of novel therapeutic regimens for kidney disease treatment. However, the route of cell delivery, e.g., intravenous, intra-arterial, or intra-parenchymal, may affect the efficiency for kidney repair in different models of acute and chronic injury. Here, we describe a protocol of intra-aorta progenitor/stem cell injection in rats following either acute ischemia-reperfusion injury or acute proteinuria induced by puromycin aminonucleoside (PAN) - the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. Vascular clips were applied across both renal pedicles for 35 min, or a single dose of PAN was injected via intra-peritoneal route, respectively. Subsequently, 2 x 10 6 stem cells [green fluorescent protein (GFP)-labeled c-Kit+ progenitor/stem cells or GFP-mesenchymal stem cells] or saline were injected into the suprarenal aorta, above the renal arteries, after application of a vascular clip to the abdominal aorta below the renal arteries. This approach contributed to engraftment rates of ∼10% at day 8 post ischemia-reperfusion injury, when c-Kit+ progenitor/stem cells were injected, which accelerated kidney recovery. Similar rates of engraftment were found after PAN-induced podocyte damage at day 21. With practice and gentle surgical technique, 100% of the rats could be injected successfully, and, in the week following injection, ∼ 85% of the injected rats will recover completely. Given the similarities in mammals, much of the data obtained from intra-arterial delivery of progenitor/stem cells in rodents can be tested in translational research and clinical trials with endovascular catheters in humans.

Background: Although thoracic hemivertebra can cause neurological signs, they occur commonly in neurologically normal dogs., Objectives: To evaluate whether computed tomography (CT) findings and factors associated with signalment can be used to differentiate between dogs with and without neurological signs associated with hemivertebra., Animals: One hundred sixty dogs with ≥1 hemivertebrae were retrospectively studied. This group consisted of 40 dogs with clinical signs caused by hemivertebra and 40 French Bulldogs, 40 Pugs, and 40 English Bulldogs that underwent CT for reasons unrelated to neurological disease., Methods: All dogs underwent CT and affected dogs also underwent magnetic resonance imaging. All CT studies were randomly evaluated by an observer blinded to signalment and clinical status. The following variables were evaluated: presence, number, location, and subtype of hemivertebra; presence of vertebral subluxation; severity of vertebral canal stenosis; presence, location, and severity of kyphosis, and number of vertebrae involved in the kyphotic segment. Statistical modeling was performed to identify factors associated with clinical status., Results: Pug breed (odds ration [OR], 10.8; P = .01), more severe kyphosis (OR, 1.1 per grade increase; P < .001), fewer instead of more observed hemivertebrae (OR, 0.8; P = 0.03), and ventrolateral hypoplasia hemivertebra subtype (OR, 4.0; P = .011) were associated with higher likelihood of neurological disease. A Cobb angle of 34.5 degrees corresponded with the highest combined sensitivity and specificity to differentiate between clinically affected and unaffected dogs., Conclusions and Clinical Importance: The variables identified could aid in differentiating between clinically relevant and irrelevant hemivertebra in small breed brachycephalic dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Peritoneal fibrosis (PF) represents a long-term complication of peritoneal dialysis (PD), affecting peritoneal membrane (PM) integrity and function. Understanding the mechanisms underlying PF development in an uremic environment aiming alternative therapeutic strategies for treating this process is of great interest. The aim of this study was to analyze the effects of tamoxifen (TAM) and recombinant BMP7 (rBMP7) in an experimental model of PF developed in uremic rats., Methods: To mimic the clinical situation of patients on long-term PD, a combo model, characterized by the combination of PF and CKD with severe uremia, was developed in Wistar rats. PF was induced by intraperitoneal (IP) injections of chlorhexidine gluconate (CG), and CKD was induced by an adenine-rich diet. Uremia was confirmed by severe hypertension, increased blood urea nitrogen (BUN> 120 mg/dL) and serum creatinine levels (> 2 mg/dL). Uremic rats with PF were treated with TAM (10 mg/Kg by gavage) or BMP7 (30 μg/Kg, IP). Animals were followed up for 30 days., Results: CG administration in uremic rats induced a striking increase in PM thickness, neoangiogenesis, demonstrated by increased capillary density, and failure of ultrafiltration capacity. These morphological and functional changes were blocked by TAM or rBMP7 treatment. In parallel, TAM and rBMP7 significantly ameliorated the PM fibrotic response by reducing α-SMA, extracellular matrix proteins and TGF-ß expression. TAM or rBMP7 administration significantly inhibited peritoneal Smad3 expression in uremic rats with PF, prevented Smad3 phosphorylation, and induced a remarkable up-regulation of Smad7, an intracellular inhibitor of TGFβ/Smad signaling, contributing to a negative modulation of profibrotic genes. Both treatments were also effective in reducing local inflammation, possibly by upregulating IκB-α expression in the PM of uremic rats with PF. In vitro experiments using primary peritoneal fibroblasts activated by TGF-ß confirmed the capacity of TAM or rBMP7 in blocking inflammatory mediators, such as IL-1ß expression., Conclusions: In conclusion, these findings indicate important roles of TGF-ß/Smad signaling in PF aggravated by uremia, providing data regarding potential therapeutic approaches with TAM or rBMP7 to block this process.

Hepatitis B virus (HBV) genotype D (HBV/D) is globally widespread, and ten subgenotypes (D1 to D10) showing distinct geographic distributions have been described to date. The evolutionary history of HBV/D and its subgenotypes, for which few complete genome sequences are available, in the Americas is not well understood. The main objective of the current study was to determine the full-length genomic sequences of HBV/D isolates from Brazil and frequency, origin and spread of HBV/D subgenotypes in the Americas. Complete HBV/D genomes isolated from 39 Brazilian patients infected with subgenotypes D1 (n = 1), D2 (n = 10), D3 (n = 27), and D4 (n = 1) were sequenced and analyzed together with reference sequences using the Bayesian coalescent and phylogeographic framework. A search for HBV/D sequences available in GenBank revealed 209 complete and 926 partial genomes from American countries (Argentina, Brazil, Canada, Chile, Colombia, Cuba, Haiti, Martinique, Mexico, USA and Venezuela), with the major circulating subgenotypes identified as D1 (26%), D2 (17%), D3 (36%), D4 (21%), and D7 (1%) within the continent. The detailed evolutionary history of HBV/D in the Americas was investigated by using different evolutionary time scales. Spatiotemporal reconstruction analyses using short-term substitution rates suggested times of the most recent common ancestor for the American HBV/D subgenotypes coincident with mass migratory movements to Americas during the 19th and 20th centuries. In particular, significant linkages between Argentina and Syria (D1), Brazil and Central/Eastern Europe (D2), USA and India (D2), and Brazil and Southern Europe (D3) were estimated, consistent with historical and epidemiological data., Competing Interests: The authors have declared that no competing interests exist.