Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

[Atypical involvement of purpuric syndrome caused by parvovirus B19. Case report in a 12-year-old female]. / Síndrome purpúrico de distribución atípica por parvovirus B19 en una adolescente.

Parvovirus B19 is the cause of a variety of exanthematous diseases during childhood and adolescence, such as erythema infectiosum and papular purpuric gloves and socks syndrome. This is an unusual, benign and acute acrodermatitis. Aphtous stomatitis, fever and other systemic symptoms can be associated with the eruption of the purpuric rash. Uncommon patterns such as asymmetrical distribution or erythematous involvement llave recently been described as additional features of PVB19-associated purpuric petechial eruption. This is a case report of a 12-year-old female with an atypical involvement of a papular-purpuric syndrome caused by human parvovirus B19.

Síndrome purpúrico de distribución atípica por parvovirus B19 en una adolescente / Atypical involvement of purpuric syndrome caused by parvovirus B19: case report in a 12-year-old female

Resumen El parvovirus B19 es causante de una variedad de enfermedades exantemáticas durante la infancia y adolescencia, como el eritema infeccioso y el síndrome papular purpúrico en guante y calcetín. Este último es una acrodermatitis aguda, inusual y benigna, que puede asociarse a aftas orales, fiebre y otros síntomas constitucionales. Existen casos atípicos como la púrpura febril en otras localizaciones, sin cumplir la distribución característica en guante y calcetín de forma simétrica o con un mayor componente de eritrodermia. Presentamos el caso de una adolescente de 12 años con un síndrome papular purpúrico de distribución atípica por parvovirus B19.

Abstract Parvovirus B19 is the cause of a variety of exanthematous diseases during childhood and adolescence, such as erythema infectiosum and papular purpuric gloves and socks syndrome. This is an unusual, benign and acute acrodermatitis. Aphtous stomatitis, fever and other systemic symptoms can be associated with the eruption of the purpuric rash. Uncommon patterns such as asymmetrical distribution or erythematous involvement llave recently been described as additional features of PVB19-associated purpuric petechial eruption. This is a case report of a 12-year-old female with an atypical involvement of a papular-purpuric syndrome caused by human parvovirus B19.

Photobiomodulation Therapy Modulates Muscle Gene Expression and Improves Performance of Rats Subjected to a Chronic Resistance Exercise Protocol.

Objective: In professional sports activities, the search for increased performance is constant. Electrophysical agents, including photobiomodulation (PBM), have been used in the sports context to accelerate postworkout recovery, prevent injuries, and even to improve performance. This study aims to investigate the effects of infrared laser (904 nm) on skeletal muscle gene expression of performance-related proteins of rats submitted to a chronic resistance training protocol. Materials and methods: Male Wistar rats (n = 40), weighing ±300 g were divided into four groups: sedentary control (CT, n = 10); irradiated control (CTL, n = 10); exercised not irradiated (EX, n = 10); exercised irradiated (EXL, n = 10). To assess the performance, the maximum carrying test was adapted and applied 72 h prior the training and 72 h after the last exercise session. The vertical weight climbing protocol was adapted for resistance training 3 × per week with 48 h interval between each session: first week adaptation, second week 25% of body weight (BW), third week 50% BW, fourth week 75% BW, and fifth week 100% BW. Animals were irradiated before exercise on hind paws 50 sec each, with infrared laser 904 nm 5 days per week, during 4 weeks, 9 J per leg in a total of 18 J energy per day. Results: The EXL performed more climbing (7.1 ± 0.91) compared to EX (4.4 ± 0.63). PBM promoted increased expression of lactate dehydrogenase enzyme, mammalian target of rapamycin protein, and androgen receptor (p < 0.05) but not the myosin heavy chain (p = 0.43). Conclusions: PBM therapy increases the expression of performance-related muscle mass gain genes besides improving the resistance training performance.

Back pain in elementary schoolchildren is related to screen habits.

PURPOSE: Verify the influences of physical activity level, nutritional status and screen habits on the prevalence of back pain in Brazilian students. METHODS: The sample consisted of 577 schoolchildren (female = 274; male = 303) aged between 10 and 16 years old, regularly enrolled in the 6th grade of elementary school living in the metropolitan area of the Alto Tietê of the state of São Paulo, Brazil. The prevalence, intensity and frequency of pain was verified with the Back Pain Assessment Instrument. The usual practice of physical activity was verified with the Physical Activity Questionnaire for Older Children/Adolescent. Nutritional status was analyzed using Body Mass Index. Screen habits were obtained through a previously structured questionnaire. RESULTS: The Chi-square test indicated that pain complaint and its prevalence in the cervical region are significantly higher in females (p < 0.05). The multiple logistic regression test revealed that watching television influences the prevalence of cervical pain and that the use of more than one screen increases the occurrence of low back pain in male students (p < 0.05). CONCLUSION: Female students were the most affected by back pain complain, especially in the cervical region. However, factors associated with the prevalence of back pain were found only in males.

Aspectos Pedagógicos do Aprender e Ensinar na Rede de Saúde: a Proposta Sombra / Pedagogical Aspects of Learning and Teaching in the Health Network: the Shadow Proposal

RESUMO A inclusão do mundo do trabalho na formação funda, no processo ensino-aprendizagem em saúde, uma ligação indissociável entre as unidades de saúde e as instituições de ensino superior. Formar profissionais o mais próximo da realidade dos usuários, com participação ativa nos problemas e necessidades que estão postos na vida, é o principal motor deste processo e convoca profissionais, usuários, alunos e docentes a vivenciar uma permanente tensão entre cuidar e ensinar. O encontro entre o trabalhador de saúde, o aluno e o usuário revela-se o principal foco de intercâmbio pedagógico, configurando-se como um cenário produtor de conhecimento e de questões para investigação, além do exercício do cuidado em saúde. Algo que remete ao desafio de construir estruturas pedagógicas capazes de produzir cuidado e conhecimento a partir do mundo do trabalho e considera a articulação de modos de agir e cuidar no campo da saúde. Trabalhar em busca de constituir formas de ensinar/aprender significa operar e agir sobre conceitos e sobre o campo de experiência que se coloca como um problema do experimentar na existência, pois estamos imersos no mundo do trabalho e do cotidiano dos serviços. Articular vínculo e responsabilidade dos sujeitos envolvidos com a produção do cuidado pode ser um meio de produzir maneiras de ensinar com outros sentidos e significados. Um arranjo em que a experiência no trabalho se torna capaz de produzir indícios para a construção de projetos terapêuticos e de ensinar produtores de sentido com respostas significativas às questões sobre cuidar e formar profissionais em saúde.

ABSTRACT Bringing the world of work into education forges, in the teaching/learning process in health, an inseparable link between health units and higher education institutions. The main driving force behind this process is to give professionals a training that is as close as possible to health users' reality, enabling them to actively participate in the problems and needs of users' lives. It invites professionals, users, students and teachers to experience the continual interplay between caring and teaching. The meeting between the health worker, the student and the user is the main focus of the pedagogical exchange, as a scenario that produces knowledge and questions for research, besides the practice of health care itself. In this scenario, the challenge is to construct pedagogical structures capable of producing care and knowledge, based on the world of work, and considering the articulation of ways of acting and caring in the field of health. Working to find ways of teaching and learning means engaging and acting on concepts, and on the field of experience that is posed as a problem for real-life experience, as we are immersed in the world of work and in the day-to-day service. Articulating the links, and responsibility of the subjects involved with the production of care may be a means of producing forms of teaching that has other meanings and significances. It is an arrangement in which work experience becomes capable of producing indications for the construction of therapeutic projects, and of teaching producers of meaning which provide answers to questions about caring and training health professionals.

Characterization of Skeletal Muscle Strain Lesion Induced by Stretching in Rats: Effects of Laser Photobiomodulation.

BACKGROUND: Unusual and exhaustive physical exercise can lead to muscle lesions depending on the type of contraction, intensity, duration, age, and level of conditioning. Different therapies have been proposed to prevent or reduce exercise-induced muscle damage. OBJECTIVE: In this study, we investigate the effects of low-level laser therapy on skeletal muscle strain in an experimental model in rats. MATERIALS AND METHODS: Male Wistar rats (200 g) were used. The animals were randomized into groups of six animals. We performed tibialis muscle elongation using a previously described protocol. The animals were anesthetized and submitted to passive stretching of the anterior tibial muscle attached to a weight corresponding to 150% of the body mass of the animal for 20 min, rested for 3 min, and received a second traction for 20 min. The cytokines, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and IL-10, edema, and C-reactive protein (CRP) levels were determined in the tibialis anterior muscle. RESULTS: Plasma extravasation of groups treated with different doses of laser energy, lesion +1 J (2.61 ± 0.46), lesion +3 J (2.33 ± 0.13), lesion +6 J (2.92 ± 0.91), and lesion +9 J (2.80 ± 0.55), shows a significant reduction of extravasation when compared with the injury group (5.46 ± 1.09). Laser therapy was able to significantly reduce CRP and cytokine levels (TNF-α, IL-1ß, IL-6, and IL-10). CONCLUSIONS: Laser photobiomodulation reduced skeletal muscle edema as well as cytokines and CRP, leading to a significant reduction in inflammatory markers.

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells.

Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ. First, TMZ (250 µM) triggered an increase in oxidative stress at 2, 48 and 72 h in the U87MG, U251MG and U138MG cell lines, as revealed by 2',7'-dichlorofluorescin-diacetate assay. The drug also reduced cell viability, as measured by MTT assay. U87MG cells presented a more linear decline in cell viability at time-points 2, 48 and 72 h, compared with the U251MG and U138MG cell lines. The peak of oxidative stress occurred at 48 h. To examine the role of NOS enzymes in the cell damage caused by TMZ, N(ω)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) were used. L-NAME increased the cell damage caused by TMZ while reducing the oxidative stress at 48 h. The preferential nNOS inhibitor 7-NI also improved the TMZ effects. It caused a 12.8% decrease in the viability of TMZ-injured cells. Indeed, 7-NI was more effective than L-NAME in restraining the increase in oxidative stress triggered by TMZ. Silencing nNOS with a synthetic small interfering (si)RNA (siRNAnNOShum_4400) increased by 20% the effects of 250 µM of TMZ on cell viability (P<0.05). Hoechst 33342 nuclear staining confirmed that nNOS knock-down enhanced TMZ injury. In conclusion, our data reveal that nNOS enzymes serve a role in the damage produced by TMZ on astrocytoma and glioblastoma cells. RNA interference with nNOS merits further studies in animal models to disclose its potential use in brain tumor anticancer therapy.

Developing nurse medication safety training in a health partnership in Mozambique using behavioural science.

BACKGROUND: Globally, safe and effective medication administration relies on nurses being able to apply strong drug calculation skills in their real-life practice, in the face of stressors and distractions. These may be especially prevalent for nurses in low-income countries such as Mozambique and Continuing Professional Development post-registration may be important. This study aimed to 1) explore the initial impact of an international health partnership's work to develop a drug calculation workshop for nurses in Beira, Mozambique and 2) reflect upon the role of health psychologists in helping educators apply behavioural science to the training content and evaluation. METHODS: In phase one, partners developed a training package, which was delivered to 87 Portuguese-speaking nurses. The partnership's health psychologists coded the training's behaviour change content and recommended enhancements to content and delivery. In phase two, the refined training, including an educational game, was delivered to 36 nurses in Mozambique and recoded by the health psychologists. Measures of participant confidence and intentions to make changes to healthcare practice were collected, as well as qualitative data through post-training questions and 12 short follow-up participant interviews. RESULTS: In phase one six BCTs were used during the didactic presentation. Most techniques targeted participants' capability to calculate drug doses accurately; recommendations aimed to increase participants' motivation and perceived opportunity, two other drivers of practice change. Phase two training included an extra seven BCTs, such as action planning and further skills practice. Participants reported high confidence before and after the training (p = 0.25); intentions to use calculators to check drug calculations significantly increased (p = 0.031). Qualitative data suggested the training was acceptable, enjoyable and led to practice changes, through improved capability, opportunity and motivation. Opportunity barriers to medication safety were highlighted. CONCLUSIONS: Reporting and measuring medication errors and related outcomes is a complex challenge affecting global efforts to improve medication safety. Through strong partnership working, a multi-disciplinary team of health professionals including health psychologists developed, refined and begin to evaluate a locally-led drug calculation CPD workshop for nurses in a low-resource setting. Applying behavioural science helped to collect feasible evaluation data and hopefully improved impact and sustainability.

Hair follicle-containing punch grafts accelerate chronic ulcer healing: A randomized controlled trial.

BACKGROUND: A prominent role of hair follicle-derived cells in epidermal wound closure is now well established but clinical translation of basic research findings is scarce. Although skin punch grafts have been used as a therapeutic intervention to improve healing of chronic leg ulcers, they are normally harvested from nonhairy areas, thus not taking advantage of the reported role of the hair follicle as a wound-healing promoter. OBJECTIVE: We sought to substantiate the role of hair follicles in venous leg ulcer healing by transplanting hair follicle-containing versus nonhairy punch grafts. METHODS: This was a randomized controlled trial with intraindividual comparison of hair follicle scalp grafts and nonhairy skin grafts transplanted in parallel into 2 halves of the same ulcer. RESULTS: Ulcer healing measured as the average percentage reduction 18 weeks postintervention was significantly increased (P = .002) in the hair follicle group with a 75.15% (SD 23.03) ulcer area reduction compared with 33.07% (SD 46.17) in the control group (nonhairy grafts). LIMITATIONS: Sample size was small (n = 12). CONCLUSION: Autologous transplantation of terminal hair follicles by scalp punch grafts induces better healing than punch grafts harvested from nonhairy areas. Hair punch grafting is a minimally invasive surgical procedure that appears to be effective as a therapeutic tool for chronic venous leg ulcers.

Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide.

Glioblastoma multiforme (GBM) is the most aggressive type of human primary brain tumor. The standard treatment protocol includes radiotherapy in combination with temozolomide (TMZ). Despite advances in GBM treatment, the survival time of patients diagnosed with glioma is 14.5 months. Regarding tumor biology, various types of cancer cell overexpress the ether à go-go 1 (Eag1) potassium channel. Therefore, the present study examined the role of Eag1 in the cell damage caused by TMZ on the U87MG glioblastoma cell line. Eag1 was inhibited using a channel blocker (astemizole) or silenced by a short-hairpin RNA expression vector (pKv10.1-3). pKv10.1-3 (0.2 µg) improved the Eag1 silencing caused by 250 µM TMZ, as determined by reverse transcription-quantitative polymerase chain reaction and immunocytochemistry. Additionally, inhibiting Eag1 with the vector or astemizole (5 µM) reduced glioblastoma cell viability and sensitized cells to TMZ. Cell viability decreased by 63% for pKv10.1-3 + TMZ compared with 34% for TMZ alone, and by 77% for astemizole + TMZ compared with 46% for TMZ alone, as determined by MTT assay. In addition, both the vector and astemizole increased the apoptosis rate of glioblastoma cells triggered by TMZ, as determined by an Annexin V apoptosis assay. Collectively, the current data reveal that Eag1 has a role in the damage caused to glioblastoma by TMZ. Furthermore, suppression of this channel can improve the action of TMZ on U87MG glioblastoma cells. Thus, silencing Eag1 is a promising strategy to improve GBM treatment and merits additional studies in animal models of glioma.

Exercise during pregnancy protects adult mouse offspring from diet-induced obesity.

BACKGROUND: Physical exercise induces positive alterations in gene expression involved in the metabolism of obesity. Maternal exercise provokes adaptations soon after birth in the offspring. Here, we investigated whether adult mouse offspring of swim-trained mothers is protected against the development of the deleterious effects of high fat diet (HFD). METHODS: Our study comprises two parts. First, female C57BL/6 mice were divided into one sedentary and one swim-trained group (before and during pregnancy, n = 18). In the second part, adult offspring (n = 12) of trained and sedentary mothers was challenged to HFD for 16 weeks. Notably, most of the analysis was done in male offspring. RESULTS: Our results demonstrate that maternal exercise has several beneficial effects on the mouse offspring and protects them from the deleterious effects of HFD in the adult. Specifically, swimming during pregnancy leads to lower birth weight in offspring through 2 months of age. When subjected to HFD for 4 month in the adulthood, our study presents novel data on the male offspring's metabolism of trained mothers. The offspring gained less weight, which was accompanied by less body fat, and they used more calories during daytime compared with offspring of sedentary mothers. Furthermore, we observed increased adiponectin expression in skeletal muscle, which was accompanied by decreased leptin levels and increased insulin sensitivity. Decreased interleukin-6 expression and increased peptide PYY levels were observed in sera of adult offspring of mothers that swam during pregnancy. CONCLUSIONS: Our results point to the conclusion that maternal exercise is beneficial to protect the offspring from developing obesity, which could be important for succeeding generations as well.

Kinin B2 receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis.

AIM: To investigate a potential protective role of the kinin B2 receptor in a glycerol-induced rhabdomyolysis mouse model. METHODS: We separated 28 C57Bl/6 male mice into 4 groups: untreated WT animals, untreated B2 knockout mice, glycerol-treated WT and glycerol-treated B2 knockout mice. Glycerol-treated animals received one intramuscular injections of glycerol solution (50% v/v, 7 mL/kg). After 48 h, urine and blood samples were collected to measure creatinine and urea levels. Additionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin B1 and B2 receptors and inflammatory mediators were measured by real-time polymerase chain reaction. RESULTS: Serum creatinine and urea levels showed differences between untreated wild-type and glycerol-treated wild-type mice (0.66 ± 0.04 vs 2.61 ± 0.53 mg/dL, P < 0.01; and 33.51 ± 2.08 vs 330.2 ± 77.7 mg/dL, P < 0.005), and between untreated B2 knockout mice and glycerol-treated knockout mice (0.56 ± 0.03 vs 2.23 ± 0.87 mg/dL, P < 0.05; and 42.49 ± 3.2 vs 327.2 ± 58.4 mg/dL, P < 0.01), but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to induce a striking increase in kinin B2 receptor expression (> 30 times, 31.34 ± 8.9) in kidney. Animals injected with glycerol had a higher degree of tubular injury than untreated animals. Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B2 knockout mice treated with glycerol did not show a different phenotype regarding kidney injury markers, when compared to the wild-type glycerol-treated group. CONCLUSION: We conclude that the kinin B2 receptor does not have a protective role in renal injury.

Prevalencia de serología positiva para Helicobacter pylori en trabajadores de una refinería de zinc / Prevalence of a positive serology for Helicobacter pylori in workers at a zinc plant

Objetivo: Determinar la prevalencia de serología positiva para helicobacter pylori en trabajadores de una refinería de zinc. Material y métodos: Se incluyeron en el estudio a los trabajadores que acudían para su control pre-vacacional entre los meses de julio a setiembre del 2003. De 501 trabajadores, se seleccionaron a 92, obteniendo un tamaño muestral de 80 personas a un nivel de confianza del 99.99 por ciento. Para el examen serológico, se utilizó la prueba de ELISA para detección cuantitativa de IgG específica contra Helicobacter pylori (GAP-IgG ELISA. Biomerica, (USA) por medio de sangre venosa de los participantes. Se consideró como positivos a valores > 20U/ml, negativos < 12.5 U/ml y sospechosos entre 12.5 y 20U/ml. Sólo 4 fueron del sexo femenino, motivo por el cual, no se hizo el estudio separando grupos por sexo. Resultados: De los 92 trabajadores, 57 (61.96 por ciento) presentaron serología positiva para Helicobacter pylori, 22 (23.91 por ciento) fueron negativos, mientras que 13 (14.13 por ciento) tuvieron un resultados dudoso (sospechoso).

Utilização da tecnica de Moire para detectar alterações posturais / Utilization of Moire topography to detect postural deformities

O aparecimento de desvios na coluna ocorre em criancas e adolescentes durante a fase de crescimento, podendo levar a deformidades graves e comprometer a postura. Existem varias...

Distribucion de gas natural mediante redes aplicado a la ciudad de Oruro

Contenido: Introduccion Cap.1 Generalidades acerca del proyecto.Objetivos del estudio.Diseno de sistemas de distribucion Cap.2 Estudio economico para el proyecto.Estudio de mercado.Estudio de la demanda de gas natural.Proyecciones de la demanda de gas natural.Zonificacion de la demanda Cap.3 Ingenieria del proyecto.Aspectos generales acerca del gas natural.Caracteristicas tecnicas del gas natural.Caracteristicas practicas del gas natural.Capacidad del gasoducto al altiplano.Zonificacion de la ciudad de Oruro.Diseno de la red de aplicacion.Diseno del plan maestro de distribucion.Factores de sustitucion.Factores de coincidencia o efecto de simultaneidad.Datos de diseno.Procedimiento de calculo del espesor de tuberia de acero.Aplicacion practica Cap.4 Especificaciones tecnicas de construccion.Sistema primario.Sistema secundario.Fases de construccion Cap.5 Costos y factibilidad del proyecto.Consideraciones generales.Metodo de calculo utilizado.Inversion estimada de construccion sistema primario.Inversion estimada de construccion sistema secundario.Inversion total estimada red distribucion gas natural ciudad "Oruro".Precio de venta gas natural.Valor actual neto. Conclusiones y recomendaciones.