Astrocyte-derived neurons provide excitatory input to the adult striatal circuitry.

Astrocytes have emerged as a potential source for new neurons in the adult mammalian brain. In mice, adult striatal neurogenesis can be stimulated by local damage, which recruits striatal astrocytes into a neurogenic program by suppression of active Notch signaling (J. P. Magnusson et al., Science 346, 237-241 [2014]). Here, we induced adult striatal neurogenesis in the intact mouse brain by the inhibition of Notch signaling in astrocytes. We show that most striatal astrocyte-derived neurons are confined to the anterior medial striatum, do not express established striatal neuronal markers, and exhibit dendritic spines, which are atypical for striatal interneurons. In contrast to striatal neurons generated during development, which are GABAergic or cholinergic, most adult astrocyte-derived striatal neurons possess distinct electrophysiological properties, constituting the only glutamatergic striatal population. Astrocyte-derived neurons integrate into the adult striatal microcircuitry, both receiving and providing synaptic input. The glutamatergic nature of these neurons has the potential to provide excitatory input to the striatal circuitry and may represent an efficient strategy to compensate for reduced neuronal activity caused by aging or lesion-induced neuronal loss.

The effects of body size and training environment on the physical performance of adolescent basketball players: the INEX study.

BACKGROUND: Although adolescent basketballers differ in body size, shape, and composition, less is known about how these factors interact during physical development. AIM: We used ontogenetic allometry to identify the optimal body size and shape characteristics associated with physical performance in adolescent basketball players, and investigated the effects of training experience, training volume, maturity status, and club characteristics on physical performance development. SUBJECTS AND METHODS: Two hundred and sixty-four male basketballers, from five age-cohorts (11-15 years of age), were followed consecutively over three years. Three physical performance components, anthropometrics, training information, and biological maturation were assessed bi-annually. Longitudinal multiplicative allometric models were developed. RESULTS: Players with a physique that had a dominant ectomorphic component performed better in all physical performance components. When adjusting for confounders other than size, the development of running speed was independent of body size. Players advanced in maturation were physically fitter. Training data had no significant effect on developmental trajectories of running speed or lower body explosive strength. Club characteristics had no significant association with any physical performance trajectories. CONCLUSION: Leaner players have advantages in physical performance and individual characteristics play an important role, over and beyond club structure, in developing physical performance.

Physical fitness spurts in pre-adolescent boys and girls: Timing, intensity and sequencing.

We aim to (1) estimate age of attainment of the peak mid-growth spurt in stature (age-at-peak MGS) in pre-adolescent boys and girls; (2) identify the timing, intensity, and sequences of physical fitness (PF) spurts aligned by the age-at-peak MGS; and (3) identify any sex differences in PF spurts aligned by age-at-peak MGS. The sample included 180 Portuguese children (90 girls) aged 6 to 10 years at study entry who were followed annually for 4 years. Height, health-, and performance-related PF were assessed. Age-at-peak MGS and PF spurts were estimated using a non-smooth mathematical procedure. Boys' and girls' age-at-peak MGS occurred at 7.8 ± 0.47 years and 8.0 ± 0.72 years, respectively. PF spurts' timing aligned by age-at-peak MGS were as follows: (1) before age-at-peak MGS: boys - static strength, aerobic capacity, explosive leg strength, and flexibility; girls - speed, agility, aerobic capacity, and upper body strength; (2) coincident with age-at-peak MGS: girls - explosive leg strength and flexibility; (3) after age-at-peak MGS: boys - abdominal strength, upper body strength, agility, and speed; girls - abdominal strength and static strength. Boys and girls attained their MGS at relatively similar ages. However, the timing and sequences of PF spurts, aligned on age-at-MGS, were different between boys and girls.

Circadian vulnerability of cisplatin-induced ototoxicity in the cochlea.

The chemotherapeutic agent cisplatin is renowned for its ototoxic effects. While hair cells in the cochlea are established targets of cisplatin, less is known regarding the afferent synapse, which is an essential component in the faithful temporal transmission of sound. The glutamate aspartate transporter (GLAST) shields the auditory synapse from excessive glutamate release, and its loss of function increases the vulnerability to noise, salicylate, and aminoglycosides. Until now, the involvement of GLAST in cisplatin-mediated ototoxicity remains unknown. Here, we test in mice lacking GLAST the effects of a low-dose cisplatin known not to cause any detectable change in hearing thresholds. When administered at nighttime, a mild hearing loss in GLAST KO mice was found but not at daytime, revealing a potential circadian regulation of the vulnerability to cisplatin-mediated ototoxicity. We show that the auditory synapse of GLAST KO mice is more vulnerable to cisplatin administration during the active phase (nighttime) when compared to WT mice and treatment during the inactive phase (daytime). This effect was not related to the abundance of platinum compounds in the cochlea, rather cisplatin had a dose-dependent impact on cochlear clock rhythms only after treatment at nighttime suggesting that cisplatin can modulate the molecular clock. Our findings suggest that the current protocols of cisplatin administration in humans during daytime may cause a yet undetectable damage to the auditory synapse, more so in already damaged ears, and severely impact auditory sensitivity in cancer survivors.

Physical fitness spurts in childhood: A study in boys.

This study aimed to (1) estimate age-at-mid-growth spurt (age-at-MGS) in Portuguese boys from two different regions-the Azores islands and Viana do Castelo, and (2) identify spurts in a variety of physical fitness (PF) components aligned by age-at-MGS in the two samples. A total of 176 (Azores, n = 91; Viana do Castelo, n = 85) boys aged 6 years old were followed annually to 10 years of age. Age-at-MGS and spurts in PF components (speed, explosive muscular strength, abdominal muscular strength, agility, and flexibility) were identified for each sample. The timing and intensities of the spurts were estimated using a non-smooth mathematical procedure. In Azorean boys, age-at-MGS occurred at 7.8 years (6.99 cm y-1 ), whereas in Viana do Castelo it occurred at 7.9 years (6.20 cm y-1 ). Spurt in speed was attained 12 months after the MGS in both samples (0.53 and 0.35 cm y-1 in Azores and Viana do Castelo, respectively), whereas spurts in explosive muscular strength and flexibility occurred 12 months before the MGS and at the MGS (Azores: 21.59 and 5.52 cm y-1 and Viana do Castelo: 14.12 and 2.5 cm y-1 , respectively). Agility and abdominal muscular strength peaked between 0 and 12 months after the MGS (Viana do Castelo: 0.37 m s-1  y-1 and 6.71 reps y-1 and Azores: 0.28 m s-1  y-1 and 19.36 reps y-1 , respectively). Results indicate that developmental spurts in explosive strength and flexibility occur before, or are coincident with, the mid-growth spurt in height, whereas spurts in speed, agility, and abdominal muscular strength occur after, or coincident with, the mid-growth spurt in height.

The role of growth, maturation and sporting environment on the development of performance and technical and tactical skills in youth basketball players: The INEX study.

In this paper, we outline a systematic testing programme developed to help identify excellence in youth basketball players. We examine the links between biological maturation and training experience with anthropometry, body composition, physical performance, technical and tactical skills from five age-cohorts, and characterize, in detail, facets of their environment. In total, 238 young basketball players aged 11-15 years, clustered into five age-cohorts (11, 12, 13, 14, 15 years) were recruited. We assessed measures across three domains: (1) biological [anthropometry, body composition, biological maturation and physical performance]; (2) skill/game proficiency [technical skills and tactical skills]; and (3) contextual [family support, coach knowledge and competence and club context]. The data were analysed using one-way ANOVAs and multivariate analysis of covariance adjusting for biological maturation and training experience. We report significant differences favouring older basketball players on most biological and skill/game proficiency variables. However, differences between age-cohorts in physical performance and technical skills were mitigated after controlling for the effects of both covariates. In conclusion, our findings highlight the important role of both biological maturation and training experience on youth basketball players' performance and development. We discuss the implications of these findings for research as well as for athletes, parents, coaches and clubs.

Patterns of physical performance spurts during adolescence: a cross-cultural study of Canadian, Brazilian and Portuguese boys.

BACKGROUND: Data relating physical performance to the timing of the adolescent growth spurt are limited. Aim: This study identifies: (i) age-at-peak height velocity (APHV), (ii) physical performance spurt patterns aligned to APHV; and (iii) cross-cultural and time patterns in Canadian, Brazilian and Portuguese boys. Subjects and methods: A total of 512 boys (131 Canadian, 250 Portuguese and 131 Brazilian), 8-17 years of age were followed serially using longitudinal data. APHV was identified and five physical performance measures velocities [trunk extension (TE), trunk flexion (TF), standing long jump (SLJ), curl-ups (CU) and handgrip strength (HG)] were aligned at 6-month intervals, 4 years around the attainment of PHV. Velocities were estimated using a non-smooth mathematical procedure. Results: APHV was 13.9 ± 1.0, 13.4 ± 1.6 and 13.0 ± 0.8 years for Canadian, Brazilian and Portuguese boys, respectively. Maximal velocity in SLJ was attained between 12 and 6 months prior to PHV. For HG, peaks were attained 12-24 months after PHV. Maximal velocity in TE occurred between 12 and 0 months prior to PHV, while CU peaked between PHV and 6 months after PHV. Conclusion: Patterns of spurts in physical performance have remained relatively the same and do not appear to be influenced by cross-cultural differences.

Giant keratoacanthoma of the lower lip: case report and review of the published literature.

Keratoacanthoma (KA) is an epithelial tumor mainly located on the sun-exposed skin of the face and hands of elderly patients. The giant form of KA affecting the lower lip is relatively rare, and only 2 of 9 recently reported cases were in women. This report describes a case of giant KA of the lower lip in a 62-year-old white woman and discusses clinical and histologic diagnosis and the therapeutic approach to this lesion. The patient reported a 2-month evolution of a nodule characterized by a brownish central plug of keratin and measuring approximately 2.0 cm in its greatest diameter. Keratoacanthoma may present some histopathologic features similar to those of squamous cell carcinoma, and careful attention is required to avoid an incorrect diagnosis. Following histopathologic confirmation of giant KA, complete excision of the lesion was performed. A 17-month follow-up examination revealed complete healing of the area and no signs of recurrence. Because giant KA of the lower lip may impair normal function and esthetics, surgical excision is the best choice for treating this lesion.

P311 modulates hepatic stellate cells migration.

BACKGROUND & AIMS: Liver fibrosis is induced by the accumulation of extracellular matrix, deposited mainly by activated hepatic stellate cells (HSCs). One key characteristic of stellate cell activation is the directional migration to the site of injury during the wound-healing process. P311 is a protein that has been shown to play a role in migration and we aimed to study a possible role for this protein during stellate cell migration. METHODS: Mouse stellate cells were isolated and cultured in vitro to investigate P311 protein and gene expression during HSC activation by immunocytochemistry and RT-qPCR respectively. Expression of P311 during in vivo activation was evaluated in CCl4 and bile duct ligation-induced liver fibrosis. Production of reactive oxygen species was determined using the fluorescent probe DCFH-DA. By siRNA-mediated knockdown of P311, we investigated a possible effect on proliferation by incorporation of EdU and on migration by Boyden chamber assays. RESULTS: P311 gene expression was increased during both in vitro and in vivo activation of HSCs. siRNA-mediated knockdown led to a decrease in reactive oxygen production and cell proliferation. Migration induced by different chemokines, such as PDGF-bb and MCP-1 was inhibited by knockdown of P311. CONCLUSIONS: P311 is central to reactive oxygen species-mediated HSC migration induced by different chemokines.

Cyclin D1 and Ki-67 expression correlates to tumor staging in tongue squamous cell carcinoma.

BACKGROUND: The immunohistochemical expression of Cyclin D1 and Ki-67 were analyzed in tongue squamous cell carcinomas (SCC), relating them to the clinical and morphological exhibition of these tumors. MATERIAL AND METHODS: Twenty-nine patients fulfilled the inclusion criteria; clinical data included gender, age, ethnicity and use of licit drugs such as alcohol and tobacco. The TNM staging and histopathological differentiation grading was assessed for each case. In addition, T1 patients were gathered with T2 patients; and T3 patients were gathered with T4 patients to assemble two distinct groups: (T1/T2) and (T3/T4). RESULTS: The mean follow-up time was 24 months and 30% of the patients died as a consequence of the disease, while 23.3% lived with the disease and 46.7% lived lesion-free. T1 and T2 tumors showed statistically lesser Ki-67 and Cyclin D1 staining when compared to T3 and T4 tumors. CONCLUSIONS: Ki-67 and Cyclin D1 pose as auxiliary tools when determining the progression of tongue SCC at the time of diagnosis.

Paracoccidioidomycosis mimicking squamous cell carcinoma on the dorsum of the tongue and review of published literature.

INTRODUCTION: Paracoccidioidomycosis is a disease that is endemic to southern and southeastern Brazil, caused by the fungus Paracoccidioides brasiliensis. The most common clinical oral manifestation is the presence of multiple granulomatous ulcers with hemorrhagic dots, located mainly on the lips, palate, and buccal mucosa. However, the disease can manifest atypically as a single ulcer, mimicking oral squamous cell carcinoma (SCC) or tuberculosis. CASE REPORT: A 65-year-old male patient presented with a complaint of a single ulcerated lesion on the dorsum of the tongue; the lesion had evolved over 6 months. The diagnostic hypotheses were SCC and oral manifestation of tuberculosis. An incisional biopsy was performed, and histopathological analysis of the specimen revealed pseudoepitheliomatous hyperplasia, a granulomatous structure of epithelioid histiocytes, multinucleated giant cells, and lymphocytes in the connective tissue. Grocott staining confirmed the presence of the fungus in the lesion, and a diagnosis was made of paracoccidioidomycosis. The patient was treated with 200 mg/day of itraconazole for 12 months and now shows no signs or symptoms of recurrence of the disease. CONCLUSION: Correct diagnosis is essential for a successful therapeutic approach and resolution of the lesion.

Noninvasive treatment choice for an aged down syndrome patient presenting a residual periapical cyst.

AIM: This is the first report to illustrate the marsupialization as an effective treatment for a Down Syndrome (DS) patient presenting a residual periapical cyst. BACKGROUND: These cysts occur within the alveolar ridge, usually at the local site of a previously extracted tooth that did not received proper curettage; usually the surgical excision of a cyst and also the vigorous curettage of a socket is very simple, if not for the fact that mentally disabled patients require rapid and non-stressful procedures. CASE DESCRIPTION: The 54-year-old DS patient represented herein received a minimally invasive marsupialization under local anesthesia. Due to the large extent of the lesion, the acrylic resin drain was maintained for 30 days. Through the following period, a daily irrigation of the cystic cavity with saline solution was carried out to prevent a secondary infection within the cystic cavity. A follow-up of 16 months showed no signs of recurrence. CONCLUSION: Marsupialization of residual periapical cyst is completely effective and safe, even for a DS patient that is considered to be at an advanced age. CLINICAL SIGNIFICANCE: Marsupialization poses as a minimally invasive choice for mentally disabled patients, even when presenting advanced ages; treatment success was stated by the easy clinical conduct, uneventful postoperative situation and the lack of recurrence along 16 months of follow-up.

Are There Sensitive Periods for Skill Development in Male Adolescent Basketball Players?

PURPOSE: Although spurts in physical capacities during adolescence are well known, little is known about the existence of such spurts in sport-specific skill development, especially during the period of rapid growth in stature. Our aims were to examine the timing, intensity, and sequence of basketball-specific skill spurts aligned with biological (years from peak height velocity (PHV)) rather than chronological age. We then defined putative sensitive periods (windows of optimal development) for each skill aligned to the adolescent growth spurt. METHODS: Altogether, 160 adolescent male basketballers aged 11-15 yr were tested biannually over 3 consecutive years. The years from attainment of PHV was estimated, and six skill tests were aligned to each year from PHV in 3-month intervals. Skill velocities were estimated using a nonsmooth polynomial model. RESULTS: Maximal gains in slalom dribble occurred 12 months before PHV attainment (intensity, 0.18 m·s -1 ·yr -1 ), whereas in speed shot shooting (intensity, 9.91 pts·yr -1 ), passing (intensity, 19.13 pts·yr -1 ), and slalom sprint (intensity, 0.19 m·s -1 ·yr -1 ), these skill spurts were attained 6 months before PHV attainment. The mean gains in control dribble (intensity, 0.10 m·s -1 ·yr -1 ) and defensive movement (intensity, 0.12 m·s -1 ·yr -1 ) peaks coincided with attainment of PHV. We identified different sized windows for optimal development for each skill. CONCLUSIONS: Peak spurts in skill development, for most basketball skills, were attained at the same time as PHV. The multiple peaks observed within the defined windows of optimal development suggest that there is room for skill improvement even if gains might be greater earlier rather than later in practice. Our findings highlight the need to make coaches aware of where their players are relative to the attainment of PHV because different skills appear to develop differently relative to PHV. Such knowledge may help in designing more relevant training regimes that incorporate the athlete's current growth status so that skill development can be maximized.

Corpora cavernosa fibroblasts mediate penile erection.

Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed that enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. The effect on penile blood flow depends on the number of fibroblasts, which is regulated by erectile activity. Erection dynamically alters the positional arrangement of fibroblasts, temporarily down-regulating Notch signaling. Inhibition of Notch increases fibroblast numbers and consequently raises penile blood flow. Continuous Notch activation lowers fibroblast numbers and reduces penile blood perfusion. Recurrent erections stimulate fibroblast proliferation and limit vasoconstriction, whereas aging reduces the number of fibroblasts and lowers penile blood flow. Our findings reveal adaptive, erectile activity-dependent modulation of penile blood flow by fibroblasts.

A New Developmental Approach for Judo Focusing on Health, Physical, Motor, and Educational Attributes.

Judo is currently the most practiced combat sport in the world. There is no doubt of its importance for children, adolescents, adults, and seniors. However, due to its inherent complexity, coaches tend to place greater or lesser emphasis only on one of its multiple domains during the judoka formative years. The present study presents a novel developmental approach signaling Judo as an excellent way for physical, motor, educational, and health development across the lifespan. In this study, we consulted 23 Judo coaches, aiming to clarify the relevance and adequacy of the domains (Competitive, Health, Technical-Tactical, and Philosophical-Educational) and phases of the proposed model. Our findings showed that the model contents-physical, motor, educational, and health-are entwined with its four domains, which were considered of utmost importance by experts in the development of judokas. We, therefore, contend that our model is essential to better understand the growth and development of young judokas. Also, it may be a useful tool for Motor Development experts.

Mitochondrial uncouplers inhibit hepatic stellate cell activation.

BACKGROUND: Mitochondrial dysfunction participates in the progression of several pathologies. Although there is increasing evidence for a mitochondrial role in liver disease, little is known about its contribution to hepatic stellate cell (HSC) activation. In this study we investigated the role of mitochondrial activity through mild uncoupling during in vitro activation of HSCs. METHODS: Cultured primary human and mouse HSCs were treated with the chemical uncouplers FCCP and Valinomycin. ATP levels were measured by luciferase assay and production of reactive oxygen species was determined using the fluorescent probe DCFH-DA. Possible cytotoxicity by uncoupler treatment was evaluated by caspase 3/7 activity and cytoplasmic protease leakage. Activation of HSCs and their response to the pro-fibrogenic cytokine TGF-ß was evaluated by gene expression of activation markers and signal mediators using RT-qPCR. Proliferation was measured by incorporation of EdU and protein expression of α-smooth muscle actin was analyzed by immunocytochemistry and western blot. RESULTS: FCCP and Valinomycin treatment mildly decreased ATP and reactive oxygen species levels. Both uncouplers increased the expression of mitochondrial genes such as Tfam and COXIV while inducing morphological features of quiescent mouse HSCs and abrogating TGF-ß signal transduction. Mild uncoupling reduced HSC proliferation and expression of pro-fibrogenic markers of mouse and human HSCs. CONCLUSIONS: Mild mitochondrial uncoupling inhibits culture-induced HSC activation and their response to pro-fibrogenic cytokines like TGF-ß. These results therefore suggest mitochondrial uncoupling of HSCs as a strategy to reduce progression of liver fibrosis.

Classification of the Effort Index and Biomechanical Overload in Natural Trails of UNESCO Global Geoparks-A Network Perspective of Trails of the Araripe UGG (NE Brazil).

Natural trails in UNESCO Global Geopark territories show strong salutogenic, inclusive and interactive characteristics as potentials and opportunities for ecosystem health. It is essential to provide information to inform the hiker as to the characteristics of the environment and the attractions and challenges of the route. Based on a network analysis methodology we aimed to identify the indicators of centrality and strength of connection in order to classify the effort index and biomechanical overload of the Araripe UNESCO Global Geopark trails in Brazil. The results showed strong connection and centrality of the variables related to the biomechanical overload in the effort index. In the trail of Pontal de Cruz the altimetric variation and the surface of the ground are highlighted in the biomechanical overload that presented a horizontal course equivalent 2.6 times larger than the presented distance. In Sítio Fundão trail, the surface of the ground also stood out, increasing the exposure in 36% of the presented distance. On the Missão Velha Waterfall trail, the variable that stood out was the biomechanical overload on the knee, equivalent to a horizontal increase of 28% of the measured distance. The methodology presented sought to optimise the mapping, management and consolidation of a network of natural trails aggregated to a high geotouristic, scientific, educational, cultural and well-being potential as presented in the Araripe UGG territory.

A role for autophagy during hepatic stellate cell activation.

BACKGROUND & AIMS: Autophagy is a metabolic process that degrades and recycles intracellular organelles and proteins with many connections to human disease and physiology. We studied the role of autophagy during hepatic stellate cell (HSC) activation, a key event in liver fibrogenesis. METHODS: Analysis of the autophagic flux during in vitro activation of primary mouse HSCs was performed using a DsRed-GFP-LC3B encoding plasmid. The effect of autophagy inhibition by bafilomycin A1 on the in vitro activation process of human and mouse HSCs was examined by measuring proliferation, presence of activation markers by RT-qPCR, immunofluorescence, and Western blotting. Analysis of lipid droplet and microtubule-associated protein light chain 3 beta (LC3B) colocalization in the presence of PDGF-BB was investigated by immunocytochemistry. RESULTS: A significant increased autophagic flux was observed during culture induced mouse HSC activation. Treatment of mouse HSCs and human HSCs with autophagy inhibitor bafilomycin A1 results in a significant decreased proliferation and expression of activation markers. In addition, lipid droplets and LC3B colocalization was increased after PDGF-BB treatment in quiescent HSCs. CONCLUSIONS: During HSC activation, autophagic flux is increased. The demonstration of partly inhibition of in vitro HSC activation after treatment with an autophagy inhibitor unveils a potential new therapeutic strategy for liver fibrosis.

Body Physique, Body Composition, Physical Performance, Technical and Tactical Skills, Psychological Development, and Club Characteristics of Young Male Portuguese Soccer Players: The INEX Study.

Youth soccer performance is multifaceted, includes physical growth, biological maturation, and physical fitness, and is linked to the sporting environment to which the players are exposed. We aim to describe age-related associations in body physique, body composition, physical performance technical and tactical skills, psychological and club characteristics of male soccer players aged 12 to 14 years. A total of 157 male soccer players clustered into three age-cohorts (12, 13 and 14 years) were recruited from six soccer clubs. Anthropometric, body composition and body physique, biological maturation, physical performance, skill/game proficiency data, psychological characteristics, and clubs' characteristics were collected. Group means were compared using analysis of variance and covariance. Fourteen years old players were significantly taller, heavier, leaner, faster, stronger, and technically more skilled than their younger peers (p < 0.05). Differences in physical performance and technical skills (p < 0.05) were found between age groups when adjusting for confounders of soccer training and biological maturation. No significant differences (p > 0.05) between age groups were found in psychological domains. Our findings suggest that age, biological maturation, and training volume are key factors influencing young soccer players' performance and development. Further, clubs' conditions provide players with ample resources for their success in training and competition.