Effects of repeated weight cycling on non-alcoholic steatohepatitis in diet-induced obese mice.

Lifestyle interventions remain the treatment of choice for patients with obesity and metabolic complications, yet are difficult to maintain and often lead to cycles of weight loss and regain (weight cycling). Literature on weight cycling remains controversial and we therefore investigated the association between weight cycling and metabolic complications using preexistent obese mice. Ldlr-/-.Leiden mice received a high-fat diet (HFD) for 20 weeks to induce obesity. Subsequently, weight-cycled mice were switched between the healthy chow diet and HFD for four 2-week periods and compared to mice that received HFD for the total study period. Repeated weight cycling tended to decrease body weight and significantly reduced fat mass, whereas adipose tissue inflammation was similar relative to HFD controls. Weight cycling did not significantly affect blood glucose or plasma insulin levels yet significantly reduced plasma free fatty acid and alanine transaminase/aspartate transaminase levels. Hepatic macrovesicular steatosis was similar and microvesicular steatosis tended to be increased upon weight cycling. Weight cycling resulted in a robust decrease in hepatic inflammation compared to HFD controls while hepatic fibrosis and atherosclerosis development were not affected. These results argue against the postulate that repeated weight cycling leads to unfavorable metabolic effects, when compared to a continuous unhealthy lifestyle, and in fact revealed beneficial effects on hepatic inflammation, an important hallmark of non-alcoholic steatohepatitis.

Effects of far-infrared radiation lamp therapy on recovery from a simulated soccer-match in elite female soccer players.

We investigated the effects of far-infrared radiation (FIR) lamp therapy on changes in muscle damage and performance parameters following six sets of 15-min Loughborough intermittent shuttle test (LIST), a simulated soccer match. Twenty-four elite female soccer players (20-24 y) were assigned into FIR or sham treatment group (n = 12/group). The participants received a 60-min FIR or sham treatment (30 min per muscle) over knee extensors (KE) and flexors (KF) at 2, 25, 49, 73, and 97 h post-LIST. Maximal voluntary isometric contraction (MVC) torque and muscle soreness of the KE and KF, plasma creatine kinase (CK) activity as muscle damage markers, and several performance parameters including countermovement jump (CMJ) and Yo-Yo intermittent recovery test level 1 (YYIR1) were measured before and 1, 24, 48, 72, 96, and 120 h post-LIST. Changes in the measures were compared between groups by a mixed-design two-way ANOVA. The running distance covered during LIST and changes in the measures at 1-h post-LIST (before the treatment) were similar (p = 0.118-0.371) between groups. Changes in muscle damage markers at 24-120 h post-LIST were smaller (p < 0.05, η2 = 0.208-0.467) for the FIR (e.g., MVC-KE torque decrease at 48-h post-LIST: -1 ± 2%, peak KE soreness: 16 ± 10 mm, peak CK: 172 ± 42 IU/L) than sham group (-11 ± 9%, 33 ± 7 mm, 466 ± 220 IU/L, respectively). Performance parameters recovered faster (p < 0.05, η2 = 0.142-0.308) to baseline for the FIR (e.g., decreases at 48-h post-LIST; CMJ: 0 ± 1%, YYIR1: 0 ± 1%) than sham group (-6 ± 2%, -9 ± 6%, respectively). These results suggest that the FIR lamp therapy was effective for enhancing recovery from a soccer match.

Peak fat oxidation, peak oxygen uptake, and running performance increase during pre-season in sub-elite male football players.

PURPOSE: In Football, the high-intensity running bouts during matches are considered decisive. Interestingly, recent studies showed that peak fat oxidation rates (PFO) are higher in football players than other athletes. This study aimed to investigate whether PFO increases following a pre-season. Secondarily, and due to COVID-19, we investigated whether PFO is related to the physical performance in a subgroup of semi-professional male football players. METHODS: Before and after 8 weeks of pre-season training, 42 sub-elite male football players (18 semi-professionals and 24 non-professionals) had a dual-energy x-ray absorptiometry scan and performed a graded exercise test on a treadmill for the determination of PFO, the exercise intensity eliciting PFO (Fatmax) and peak oxygen uptake (V̇O2peak). Additionally, the semi-professional players performed a Yo-Yo Intermittent Recovery Test level 2 (YYIR2) before and after pre-season training to determine football-specific running performance. RESULTS: PFO increased by 11 ± 10% (mean ± 95% CI), p = 0.031, and V̇O2peak increased by 5 ± 1%, p < 0.001, whereas Fatmax was unchanged (+12 ± 9%, p = 0.057), following pre-season training. PFO increments were not associated with increments in V̇O2peak (Pearson's r2 = 0.00, p = 0.948) or fat-free mass (FFM) (r2 = 0.00, p = 0.969). Concomitantly, YYIR2 performance increased in the semi-professional players by 39 ± 17%, p < 0.001, which was associated with changes in V̇O2peak (r2 = 0.35, p = 0.034) but not PFO (r2 = 0.13, p = 0.244). CONCLUSIONS: PFO, V̇O2peak, and FFM increased following pre-season training in sub-elite football players. However, in a subgroup of semi-professional players, increments in PFO were not associated with improvements in YYIR2 performance nor with increments in V̇O2peak and FFM.

Assessment of Connexin43 Hemichannel Functionality Based on Cytosolic Uptake of Yo-Pro1.

Connexin proteins are the building blocks of gap junctions and connexin hemichannels. Both provide a pathway for cellular communication. Gap junctions support intercellular communication mechanisms and regulate homeostasis. In contrast, open connexin hemichannels connect the intracellular compartment and the extracellular environment, and their activation fuels inflammation and cell death. The development of clinically applicable connexin hemichannel blockers for therapeutic purposes is therefore gaining momentum. This chapter describes a well-established protocol optimized for assessing connexin hemichannel activity by using the reporter dye Yo-Pro1.

Beta irradiation-induced thermoluminescence: Glow curve analysis and kinetic parameters in combustion-synthesized undoped Ca4YO(BO3)3.

This study examines the thermoluminescent (TL) properties of undoped Ca4YO(BO3)3 phosphor, focusing on how it behaves under a variety of experimental conditions. The IRSL-TL 565 nm was chosen as the appropriate detection filter among various optical detection filter combinations. During the preheating trials conducted at a rate of 2 °C/s, the TL peak exhibited increased intensity, particularly around 200 °C. The experimental outcomes demonstrated a reliable linear relationship (R2 = 0.996 and b = 1.015) in the dose response of undoped preheated Ca4YO(BO3)3 within the range of 1-200 Gy. The investigation encompasses a range of techniques, including the TM-Tstop method, computerized glow curve deconvolution (CGCD) analysis, and theoretical modelling. The application of the TM-Tstop method to samples irradiated with a 5 Gy dose revealed distinct zones on the TM versus Tstop diagram, signifying the presence of at least two discernible components within the TL glow curve, specifically, a single general order kinetics peak and a continuous distribution. The analysis of activation energy versus preheated temperature exhibited a stepwise curve, indicating five trap levels with depths ranging between 1.13 eV and 1.40 eV. The CGCD method also revealed the superposition of at least five distinct TL glow peaks. It was observed that their activation energies were consistent with the Tm-Tstop experiment. Furthermore, the low Figure of Merit (FOM) value of 1.18% indicates high reliability in the goodness-of-fit measure. These findings affirm the reliability and effectiveness of the employed methods in characterizing the TL properties of the Ca4YO(BO3)3 phosphor under investigation. Theoretical models, including the semi-localized transition model, were introduced to explain anomalous observations in TL glow peak intensities and heating rate patterns. While providing a conceptual framework, these models may require adjustments to accurately capture the specific characteristics uncovered through CGCD analysis. As a potential application, the study suggests that the characterized TL properties of Ca4YO(BO3)3 phosphor could be utilized in dosimetric applications, such as radiation dose measurements, owing to its reliable linear response within a broad dose range.

Paraneoplastic neurologic syndrome associated with gynecologic and breast malignancies.

Gynecologic and breast malignancies are the cancers most commonly associated with paraneoplastic neurologic syndromes, of which the foremost is Yo [Purkinje cell antibody, type 1 (PCA-1)] paraneoplastic cerebellar degeneration. Yo syndrome affects women in the sixth decade and manifests as a subacute severe cerebellar ataxia. The association of the typical clinical picture with the detection of Yo antibodies in a patient's serum or CSF defines the diagnosis. Yo syndrome is always associated with a cancer, and the search for the underlying tumor should focus on ovarian and breast cancers and be repeated overtime if negative. The Yo autoantibodies are directed against the Yo antigens, aberrantly overexpressed by tumor cells with frequent somatic mutations and gene amplifications. The massive infiltration of these tumors by immune cells suggests that they are the site of the immune tolerance breakdown, leading to the destruction of Purkinje cells harboring the Yo antigens. Despite a growing understanding of the immunologic mechanisms, efficient therapeutic options are still lacking. Anti-Ri and antiamphiphysin syndromes are rarer and associated with breast cancers; a wide variety of other rare paraneoplastic neurologic syndromes have been described in association with gynecologic and breast malignancies that, though sharing some similarities, may have specific immune and genetics features leading to the immune tolerance breakdown.

Paraneoplastic Cerebellar Degeneration Leading to an Early Diagnosis of Peritoneal Serous Papillary Carcinoma.

A 77-year-old female with a subacute progression of ataxia and serum anti-Yo antibodies was suspected to have paraneoplastic cerebellar degeneration (PCD). An examination of an underlying cancer showed no abnormality in the gynecological organs, but the findings did show a mass in the Douglas fossa. The mass was resected and diagnosed as stage IIB peritoneal serous papillary carcinoma (PSPC), a rare gynecologic cancer that is difficult to diagnose in the early stages. PCD was treated with intravenous immunoglobulin (IVIG). For an early diagnosis and treatment, PSPC should be included in the list of malignancies that cause PCD with anti-Yo antibodies.

The Physiological Effects of Weight-Cycling: A Review of Current Evidence.

PURPOSE OF REVIEW: There is a common perception among the public that yo-yo dieting, defined as repeated cycles of weight loss followed by weight regain, results in accumulation of fat in the body and lower metabolic rate, thus hindering subsequent attempts to lose weight. We evaluated the effects of weight-cycling on body weight and body mass index (BMI), body composition including fat mass (FM) and lean body mass (LBM), and resting metabolic rate (RMR), by systematically reviewing existing scientific literature. RECENT FINDINGS: Twenty-three cross-sectional and cohort studies (including subjects with a history of weight-cycling compared to those without such history) and interventional studies (evaluating physiological effects during one or more cycles of weight loss and regain) were identified, conducted in generally healthy adults across various age groups, races, and both genders, who had normal weight, overweight, or obesity. Eighteen studies investigated the association between weight-cycling and body weight or BMI, and thirteen of them found no significant association. Fifteen out of twenty studies also found no increase in FM, and none of eighteen studies found a decrease in LBM. Twelve out of fourteen studies reported no adverse changes in RMR either. The overwhelming majority of evidence suggests that weight-cycling (yo-yo effect) is not associated with any adverse effects in body weight, body composition, and metabolic rate. Accordingly, healthy individuals who struggle with overweight or obesity should not be discouraged from repeated attempts to lose the excess weight.

Cerebellar leptomeningeal enhancement: An imaging finding of rapidly progressive Purkinje cell cytoplasmic autoantibody type 1 paraneoplastic cerebellar syndrome.

Purkinje cell cytoplasmic autoantibody type 1 (PCA1), also known as anti-Yo, is a 'high-risk' paraneoplastic antibody, associated with rapidly progressive cerebellar syndrome. In patients with this syndrome, various MRI abnormalities have been documented, including atrophy in the cerebellum and brainstem, T2 hyperintensity in the brainstem and spinal cord, and cranial nerve enhancement. This report introduces an imaging finding, cerebellar leptomeningeal enhancement, which was observed in all three cases at early stages. Despite neurological deterioration, all patients underwent immunotherapy, and subsequent follow-up MRI revealed resolution of the leptomeningeal enhancement, suggesting that this feature is distinct from meningeal carcinomatosis.

A Qualitative Model of Weight Cycling.

Weight cycling is a likely consequence of striving to lose weight after internalizing body image ideals, making upward social comparisons, and experiencing weight stigma. Despite weight cycling's potential physical and psychological consequences, the interplay of weight cycling, social pressures, and experienced and internalized stigma have not been qualitatively explored. Thus, through in-depth interviews of 36 weight-cycling adults, this study sought to understand how people negotiate weight cycling. Interviews informed the development of a qualitative model of weight cycling, which was derived from a theory-neutral inductive analysis. The model's stages included entering the cycle, undergoing the cycle, and challenging the cycle. Participants were triggered to enter the cycle due to weight stigma caused by social pressures. Within the cycle, interviewees internalized weight stigma and engaged in disordered weight management behaviors. Some participants challenged the cycle by becoming more self-aware and mitigating their toxic dieting behaviors. However, it was very difficult, if not impossible, for many to fully exit weight cycling and the restraints of previous weight management thinking and patterns. Our investigation underscores the seriousness of weight cycling and suggests ways to combat weight cycling on both macro and individual levels. It may also be useful to consider weight cycling as disordered eating in hopes of shifting society's dangerous focus on rapid weight loss.

A Pilot Study to Develop Paraneoplastic Cerebellar Degeneration Mouse Model.

Modeling paraneoplastic neurological diseases to understand the immune mechanisms leading to neuronal death is a major challenge given the rarity and terminal access of patients' autopsies. Here, we present a pilot study aiming at modeling paraneoplastic cerebellar degeneration with Yo autoantibodies (Yo-PCD). Female mice were implanted with an ovarian carcinoma cell line expressing CDR2 and CDR2L, the known antigens recognized by anti-Yo antibodies. To boost the immune response, we also immunized the mice by injecting antigens with diverse adjuvants and immune checkpoint inhibitors. Ataxia and gait instability were assessed in treated mice as well as autoantibody levels, Purkinje cell density, and immune infiltration in the cerebellum. We observed the production of anti-Yo antibodies in the CSF and serum of all immunized mice. Brain immunoreaction varied depending on the site of implantation of the tumor, with subcutaneous administration leading to a massive infiltration of immune cells in the meningeal spaces, choroid plexus, and cerebellar parenchyma. However, we did not observe massive Purkinje cell death nor any motor impairments in any of the experimental groups. Self-sustained neuro-inflammation might require a longer time to build up in our model. Unusual tumor antigen presentation and/or intrinsic, species-specific factors required for pro-inflammatory engagement in the brain may also constitute strong limitations to achieve massive recruitment of antigen-specific T-cells and killing of antigen-expressing neurons in this mouse model.

Adequate Interval between Matches in Elite Female Soccer Players.

The present study compared four different intervals between three simulated soccer matches for changes in muscle damage and performance parameters. Thirteen well-trained female university soccer players performed three bouts of 90-min Loughborough Intermittent Shuttle Test (LIST) with four different intervals between bouts; one (1d), two (2d), three (3d) and four days (4d), with >12-weeks between conditions in a counterbalanced order. Heart rate, blood lactate, rating of perceived exertion and distance covered in each LIST were measured. Changes in several muscle damage markers (e.g., maximal voluntary isometric torque of the knee extensors: MVC-KE, muscle soreness), performance parameters (e.g., Yo-Yo intermittent recovery test level 1: Yo-Yo IR1), and blood measures (e.g., osmolality, high sensitivity cardiac troponin T) before the first LIST, 1 h after each LIST, and one to five days after the third LIST were compared among the conditions. The total distance covered during the first two LISTs was not different among the conditions, but that during the third LIST was shorter (P < 0.05) for the 1d (9,416 ± 885 m) and 2d conditions (9,737 ± 246 m) than the 3d (10,052 ± 490 m) and 4d conditions (10,432 ± 538 m). Changes in all measures were smaller (P < 0.05) in the 3d and 4d conditions (e.g., the decrease in MVC-KE at one day after the third LIST was -13 ± 4% and -10 ± 3%, respectively) when compared with the 1d and 2d conditions (-20 ± 7%, -18 ± 5%). Performance parameters showed smaller (P < 0.05) changes in the 4d (e.g., the decrease in Yo-Yo IR1 at one day after the third LIST was -9 ± 3%) and 3d (-13 ± 6%) conditions when compared with the 1d (-19 ± 4%) and 2d (-20 ± 8%) conditions. These results suggest that muscle damage and fatigue accumulate when soccer matches are performed three consecutive days or every other day, but if more than three days are inserted between matches, this could be minimized.

Gender Differences in Patients with Substance Use Disorder and Physical/Sexual Abuse: A Preliminary Study / Las diferencias de género en pacientes con trastorno por consumo de sustancias y abuso físico/sexual: un estudio preliminar

Aim: To explore the differential characteristics in sociodemographic variables, severity of consumption, psychopathological symptomatology, life maladjustment, trauma characteristics, and post-traumatic stress symptomatology between women and men who seek treatment for substance use disorder (SUD) and have experienced lifetime physical and/or sexual abuse. Method: The sample consisted of 26 women and 31 men who had experienced physical/sexual abuse and sought treatment for SUD. Results: Women had been victims of sexual abuse in a significantly higher percentage than men. Women presented a significantly higher frequency of revictimization to another traumatic event and a significantly higher presence of avoidance symptoms than men. Conclusions: This study supports the existence of a more severe profile in women than in men with SUD who have experienced lifetime physical and/or sexual abuse. Consequently, gender-related trauma-informed practice in SUD treatment programmes should be promoted. More research in this field is needed, as this is a preliminary study. (AU)

Objetivo: Explorar las diferencias de género en distintas variables (sociodemográficas, gravedad del consumo, sintomatología psicopatológica, inadaptación a la vida cotidiana, características del trauma y sintomatología de estrés postraumático) en pacientes que acuden a tratamiento por trastorno por consumo de sustancias (TCS) y han sufrido abuso físico y/o sexual. Método: La muestra estuvo compuesta por 26 mujeres y 31 hombres que habían sufrido abuso físico y/o sexual y buscaban tratamiento para TCS. Resultados: Las mujeres habían sido víctimas de abuso sexual en un porcentaje significativamente mayor que los hombres. Además presentaban una frecuencia significativamente mayor de revictimización a otro evento traumático y una presencia significativamente mayor de síntomas de evitación que los hombres. Conclusiones: El estudio confirma la existencia de un perfil más grave en las mujeres que en los hombres con TCS que han sufrido abuso físico y/o sexual a lo largo de la vida. En consecuencia, se debe promover la atención informada sobre el trauma con perspectiva de género en los programas de tratamiento del TCS. Dada la naturaleza preliminar de este estudio, se necesita más investigación en este campo. (AU)

The Distinguishing Factor in Soccer Players is Aerobic Performance, not the ACTN3 Gene / El Factor Distintivo en los Jugadores de Fútbol es el Rendimiento Aeróbico y no el gen ACTN3

SUMMARY: The purpose of this study was to reveal the differences between ACTN3 genotype (RR, RX, XX) and aerobic performance [Yo-Yo IRT1 (m), VO2 max (ml/kg/min)] in professional and regional amateur league soccer players and to reveal which of these parameters was a distinctive factor in these athletes.71 professional soccer players (age: 23.66 ± 4.11 years; body height: 1.79 ± 6.99 m; body weight: 76.02 ± 6.76 kg; body fat: 11.59±3.11 %) and 62 regional amateur soccer players (age: 23.63 ±3.77 years; body height: 1.81 ± 5.77 m; body weight: 76.36 ± 7.53 kg; body fat: 15.60±4.65 %) volunteered for the study. After DNA extraction from buccal epithelial cells via a commercial kit was performed for the genetic background of the athletes, Real-Time PCR was carried out for genotyping. Furthermore, Yo-Yo IRT1 test was performed to determine the aerobic performance of the soccer players. SPSS 23 (SPSS Inc., Chicago, IL, USA) package program was used for the statistical analysis of the data obtained in the tests. Shapiro-Wilk test for normality and Levene's test for homogeneity of variance were performed. Chi-Square, Independent Sample T Test and One Way ANOVA test were used in the analysis of the parameters. Statistical significance was set as p0.05); however, there was a statistical significance in favor of professional soccer players in terms of aerobic parameters (p<0.05). Consequently, it can be said that aerobic performance is the distinguishing factor, not the ACTN3 gene, in soccer players.

El objetivo de este estudio fue revelar las diferencias entre el genotipo ACTN3 (RR, RX, XX) y el rendimiento aeróbico [Yo-Yo IRT1 (m), VO2 max (ml/kg/min)] en jugadores de fútbol de ligas profesionales y amateurs regionales y determinar cuál de estos parámetros es un factor distintivo en estos deportistas. 71 futbolistas profesionales (edad: 23,66 ±4,11 años; altura corporal: 1,79 ± 6,99 m; peso corporal: 76,02 ± 6,76 kg; grasa corporal: 11,59±3,11 %) y 62 jugadores de fútbol amateur regionales (edad: 23,63 ± 3,77 años; altura corporal: 1,81 ± 5,77 m; peso corporal: 76,36 ± 7,53 kg; grasa corporal: 15,60 ± 4,65 %) se ofrecieron como voluntarios para el estudio. Después de realizar la extracción de ADN de las células epiteliales orales mediante un kit comercial para obtener los antecedentes genéticos de los atletas, se llevó a cabo una PCR en tiempo real para el genotipado. Además, se realizó la prueba Yo-Yo IRT1 para determinar el rendimiento aeróbico de los futbolistas. Para el análisis estadístico de los datos obtenidos en las pruebas se utilizó el programa SPSS 23 (SPSS Inc., Chicago, IL, EE. UU.). Se realizó la prueba de normalidad de Shapiro- Wilk y la prueba de homogeneidad de la varianza de Levene. En el análisis de los parámetros se utilizaron Chi-cuadrado, prueba T para muestra independiente y prueba ANOVA unidireccional. La significancia estadística se estableció en p0,05); sin embargo, hubo significación estadística a favor de los futbolistas profesionales en cuanto a los parámetros aeróbicos (p<0,05). En consecuencia, se puede decir que el rendimiento aeróbico es el factor distintivo, no el gen ACTN3, en los jugadores de fútbol.

Violencia intrafamiliar en familias con niños en edad prescolar de un consultorio médico / Intrafamily Violence in Families with Children at Preschool Aged from a Family Medical Office

Introducción: La violencia intrafamiliar ocurre en el interior de la familia y, por lo general, la ejercen uno o varios miembros contra otros; casi siempre las víctimas son mujeres, ancianos y niños. Objetivo: Caracterizar el estado actual de la violencia intrafamiliar en familias con niños en edad prescolar. Métodos: Se realizó un estudio descriptivo transversal en el Consultorio Médico de Familia No. 1, poblado de Cuatro Caminos perteneciente al Policlínico Docente Mártires del 10 de abril, Corralillo, Villa Clara, de enero del 2020 a junio del 2021. La población estuvo constituida por 66 familias y la muestra por 64, según muestreo no probabilístico por criterio. Para la recogida de la información se utilizaron cuestionario y observación a las familias en estudio. Resultados: Presencia de violencia intrafamiliar (32,8 por ciento), familias extensas (70,3 por ciento), hacinamiento (14,1 por ciento), malas relaciones entre los adultos (66,6 %), maltrato en la niñez (66,6 por ciento) manifestaciones psicológicas: padres ausentes físicamente (57,1 por ciento), violencia psicológica (100 por ciento), violencia física (66,6 por ciento) y violencia sexual (42,9 por ciento). Conclusiones: Las malas relaciones entre los adultos, el maltrato en la niñez y los padres ausentes físicamente son asociados a la violencia intrafamiliar. La violencia psicológica estuvo presente en la totalidad de las familias. Las mayores cifras de tipos de violencia fueron en la familia extensa(AU)

Introduction: Intrafamily violence occurs within the family and is generally exercised by one or several members against others; almost always, the victims are women, the elderly or children. Objective: To characterize the current state of domestic violence in families with preschool children. Methods: A cross-sectional and descriptive study was carried out in the family medical office 1, in the neighborhood of Cuatro Caminos, belonging to the Policlínico Docente Mártires del 10 de Abril, in Corralillo Municipality, Villa Clara Province, from January 2020 to June 2021. The population consisted of 66 families and the sample was made up of 64, according to nonprobabilistic sampling by criteria. For the collection of information, a questionnaire and the observation method were used with the families under study. Results: There was presence of intrafamily violence (32.8percent) extended families (70.3percent), overcrowding (14.1percent), poor relationships between adults (66.6percent) and child abuse (66.6percent). The psychological manifestations were related to physically absent parents (57.1percent), psychological violence (100%), physical violence (66.6percent) and sexual violence (42.9percent). Conclusions: Poor relationships between adults, childhood abuse and physically absent parents are associated with intrafamily violence. Psychological violence was present in all families. The highest numbers of types of violence occurred in the extended family(AU)

Cerebellar Progressive Multifocal Leukoencephalopathy Mimicking Anti-Yo-Antibody-Associated Rapidly Progressive Cerebellar Syndrome.

A 58-year-old woman with a history of systemic lupus erythematosus (SLE) who was taking prednisolone and mycophenolate mofetil presented with gait disturbances that progressively worsened over a period of 3 months. Her blood test and cerebrospinal fluid (CSF) examination results did not indicate active SLE. Initial brain magnetic resonance imaging (MRI) revealed a small spotty lesion in the left cerebellar peduncle. The clinical course was consistent with rapidly progressive cerebellar syndrome (RPCS), which sometimes involves neuronal antibodies. The line blot assay detected anti-Yo antibodies, but no malignancy was found. Immunohistological techniques using rat brain sections yielded a negative result for anti-Yo antibodies. The second MRI revealed a focal lesion and surrounding spotty lesion in the left cerebellar peduncle, which was consistent with the punctate pattern observed in progressive multifocal leukoencephalopathy (PML). The CSF JCV-DNA test indicated the presence of cerebellar PML. Immunosuppressants were reduced, and mefloquine and mirtazapine were initiated. After approximately 2 years and 1 month, the CSF JCV-DNA results became negative. Cerebellar PML may exhibit a clinical course that is consistent with RPCS. The punctate pattern should be recognized as an early manifestation of PML. The CSF JCV-DNA copy number may serve as a useful indicator of PML stabilization.

Tetracyclic 1,4-Naphthoquinone Thioglucoside Conjugate U-556 Blocks the Purinergic P2X7 Receptor in Macrophages and Exhibits Anti-Inflammatory Activity In Vivo.

P2X7 receptors (P2X7Rs) are ligand-gated ion channels that play a significant role in inflammation and are considered a potential therapeutic target for some inflammatory diseases. We have previously shown that a number of synthetic 1,4-naphthoquinones are capable of blocking P2X7Rs in neuronal and macrophage cells. In the present investigation, we have demonstrated the ability of the tetracyclic quinone-thioglucoside conjugate U-556, derived from 1,4-naphthoquinone thioglucoside, to inhibit ATP-induced Ca2+ influx and YO-PRO-1 dye uptake, which indicates blocking P2X7R in RAW 264.7 macrophages. This process was accompanied by the inhibition of ATP-induced reactive oxygen species production in macrophages, as well as the macrophage survival strengthening under ATP toxic effects. Nevertheless, U-556 had no noticeable antioxidant capacity. Naphthoquinone-thioglucoside conjugate U-556 binding to the extracellular part of the P2X7R was confirmed by SPR analysis, and the kinetic characteristics of this complex formation were established. Computer modeling predicted that U-556 binds the P2X7R allosteric binding site, topographically similar to that of the specific A438079 blocker. The study of biological activity in in vivo experiments shows that tetracylic conjugate significantly reduces inflammation provoked by carrageenan. The data obtained points out that the observed physiological effects of U-556 may be due to its ability to block the functioning of the P2X7R.

Effects of preseason training on body composition, running performance, biochemical markers and workload variation in professional rugby union players.

Few studies have examined the impact of a preseason training intervention through systematic measures in Pro D2 rugby union (RU). Therefore, this study aimed to describe the effects of 12 weeks of preseason training (three blocks) on body composition, running performance, biochemical markers, and workload (WL) variation in professional RU players. Physiological (physical and biochemical) responses to preseason WL were analyzed by examining changes in anthropometric characteristics, Yo-Yo intermittent recovery level 1 (Yo-Yo IR1) test, blood samples (BS), Hooper index (1-7), the 10-Hz global positioning system (GPS), and session rating of perceived exertion (s-RPE) in nineteen elite male players. Changes throughout the preseason were analyzed using the one-way and mixed-model analysis of variance. Significant (p < 0.01) improvements occurred in anthropometry and Yo-Yo IR1 running performance in forwards and backs. Total distance (p < 0.01) and impact (p < 0.05) during the second block were meaningfully higher than the other two blocks, with backs showing higher values than forwards. As expected, WL decreased significantly (p < 0.01) during the last training block. The WL variations were correlated with changes in biochemical markers over the preseason period. The collected data can be used for i) profiling French Pro D2 rugby championships players, ii) establishing effective training strategies, and iii) setting preseason WL expectations.

Performance in the Yo-Yo Intermittent Recovery Test May Improve with Repeated Trials: Does Practice Matter?

The Yo-Yo Intermittent Test is frequently used to monitor changes in athletes' performance in response to different interventions. However, the question remains as to whether, and to what extent, retakes of this test would contribute to these changes. This case study sought to determine the magnitude of practice effects, involving test repetition, on performance in the Yo-Yo Intermittent Recovery Test. A recreational soccer player performed four attempts of the Yo-Yo Intermittent Recovery Test-Level 1 (YYIR1) with a week's rest in between. The same participant repeated this test protocol (four attempts of the YYIR1) again after six months. Changes in distance covered, level achieved, maximal oxygen uptake, and heart rate between the first and last attempt were assessed. The smallest worthwhile change (SWC), the coefficient of variation (CV), and the 2CV were calculated to identify a trivial, a possibly meaningful, and a certainly meaningful change in YYIR1 performance. The distance covered in the first set of measurements increased from 1320 m to 1560 m (15.4%), which corresponds to a 4.6% increase in the level achieved (from 16.6 to 17.4). Similarly, the distance covered in the second set of measurements increased from 1280 m to 1560 m (17.9%), which corresponds to a 5.5% increase in the level achieved (from 16.5 to 17.4). The participant's performance changes fell outside of the SWC and the CV, but not the 2CV during both sets of measurements. These improvements in YYIR1 performance may be ascribed to practice with repeated attempts of the test by improving running technique at the turning point and/or by simply increasing the linear speed. This fact should always be kept in mind when interpreting the effects of training. Practitioners should differentiate between practice effects associated with repeated test execution and adaptation induced by conducting sport-specific training.

Repeated-sprint training in hypoxia boosts up team-sport-specific repeated-sprint ability: 2-week vs 5-week training regimen.

PURPOSE: To investigate (1) the boosting effects immediately and 4 weeks following 2-week, 6-session repeated-sprint training in hypoxia (RSH2-wk, n = 10) on the ability of team-sport players in performing repeated sprints (RSA) during a team-sport-specific intermittent exercise protocol (RSAIEP) by comparing with normoxic counterpart (CON2-wk, n = 12), and (2) the dose effects of the RSH by comparing the RSA alterations in RSH2-wk with those resulting from a 5-week, 15-session regimen (RSH5-wk, n = 10). METHODS: Repeated-sprint training protocol consisted of 3 sets, 5 × 5-s all-out sprints on non-motorized treadmill interspersed with 25-s passive recovery under the hypoxia of 13.5% and normoxia, respectively. The within- (pre-, post-, 4-week post-intervention) and between- (RSH2-wk, RSH5-wk, CON2-wk) group differences in the performance of four sets of RSA tests held during the RSAIEP on the same treadmill were assessed. RESULTS: In comparison with pre-intervention, RSA variables, particularly the mean velocity, horizontal force, and power output during the RSAIEP enhanced significantly immediate post RSH in RSH2-wk (5.1-13.7%), while trivially in CON2-wk (2.1-6.2%). Nevertheless, the enhanced RSA in RSH2-wk diminished 4 weeks after the RSH (- 3.17-0.37%). For the RSH5-wk, the enhancement of RSA immediately following the 5-week RSH (4.2-16.3%) did not differ from that of RSH2-wk, yet the enhanced RSA was well-maintained 4-week post-RSH (0.12-1.14%). CONCLUSIONS: Two-week and five-week RSH regimens could comparably boost up the effects of repeated-sprint training in normoxia, while dose effect detected on the RSA enhancement was minimal. Nevertheless, superior residual effects of the RSH on RSA appear to be associated with prolonged regimen.