Pathogenic variant in the PCDH19 gene in a patient with epilepsy and cognitive disability. / Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva.

INTRODUCTION: The association of family cases of epilepsy and intellectual disability in women was reported in 1971. In 2008, the role of pathogenic variants of the PCDH19 gene in some families were identified. The disease presents with febrile seizure clusters, intellectual disability, and autistic features. Most cases are due to de novo variants, however, there are some inherited cases, with an atypical way of X-linked transmission. OBJECTIVE: To report the case of a patient with epilepsy carrier of a pathogenic variant of the PCDH19 gene, reviewing the natural history of this condition and the available evidence for its management. CLINICAL CASE: Female patient, with normal history of pregnancy and perinatal period. At 6 months, while febrile, she presented focal motor seizure clusters that repeated at 14, 18, 21 months and 3 years old, always associated with fever, even presenting status epilepticus. She is on therapy with topiramate and valproic acid, achieving 13 seizure-free years. The analysis of the SCN1A gene showed no abnormalities and the study of the PCDH19 gene revealed a de novo heterozygous pathogenic variant. The patient evolved with intellectual disability and severe behavioral disorders that require mental health team support. CONCLUSIONS: PCDH19 pathogenic variants have varied phenotypic expression. The genetic diagnosis should be guided with the clinical features. Long-term psychiatric morbidity can be disabling.

Analysis of polymorphisms in codons 11, 72 and 248 of TP53 in Brazilian women with breast cancer.

The association between TP53 gene polymorphisms and breast cancer (BC) in Brazilian women is a controversial topic. In this cross-sectional study, we evaluated the association between clinical pathological variables and three polymorphisms (TP53*11, TP53*72, and TP53*248) in BC patients and controls. Genomic DNA was extracted from the blood cells of 393 participants; the cancer-free control subjects were 26-72 years old (41 ± 11.03) and the BC patients were 28-80 years old (51 ± 10.70). We used standard polymerase chain reaction-restriction fragment length polymorphism and confirmed the results by genetic sequencing. In TP53*11, there was 100% homozygous Glu distribution in both groups. TP53*72 showed genotypic distribution: in the control group, there was 16.10% homozygous Pro, and 42.44% heterozygous and 41.46% homozygous Arg; in the BC group, there was 15.43% homozygous Pro, and 42.55% heterozygous and 42.02% homozygous Arg. The relative frequency of each allele was 0.37% for Pro and 0.63% for Arg in the control group, and 0.37% for Pro and 0.63% for Arg in the BC group. The nuclear grade (P = 0.0084) and adapted histological grade (P = 0.0265) were associated with TP53*72. The distribution of the codon 72 genotypes did not deviate from Hardy-Weinberg equilibrium in either group. In TP53*248, there was 100% homozygous Arg distribution in both groups. In codon 72, the Arg allele is the most prevalent in Brazilian women. TP53*72 may be associated with susceptibility to BC, although more studies are required to evaluate the profile of Brazilian women with BC.

Estimating the prevalence of female genital mutilation in Portugal.

OBJECTIVES: Due to globalized migratory processes, female genital mutilation/cutting (FGM/C) has spread to other countries, including countries in Europe, where, with a few exceptions, it remains a concealed problem. To the authors' knowledge, this is the first national extensive study to estimate the prevalence of FGM/C in Portugal. STUDY DESIGN: Prevalence estimation. METHODS: Using extrapolation of country-of-origin prevalence data and the 2011 Census data, this study estimated: the prevalence of FGM/C in Portugal among women of reproductive age (15-49 years) and among all women aged ≥15 years; and the number of girls aged <15 years living in Portugal who have undergone or will probably undergo FGM/C. RESULTS: It is estimated that 6576 women aged ≥15 years living in Portugal have undergone FGM/C, with cases distributed unevenly throughout the national territory. In addition, it is estimated that 1830 girls aged <15 years living in Portugal have undergone or are likely to undergo FGM/C. CONCLUSIONS: This study estimated that more than 6000 women living in Portugal have undergone FGM/C, and many girls remain at risk. These two groups need different types of interventions. Awareness of the number and geographical dispersion of cases of FGM/C will enable more informed and targeted definition of public health policies for protection of females who have undergone or are at risk of undergoing FGM/C.

Ingestive Behavior of Heifers Supplemented with Glycerin in Substitution of Corn on Brachiaria brizantha Pasture.

The objective was to evaluate the ingestive behavior of crossbred heifers finished on a Brachiaria brizantha cv. Marandu pasture receiving four levels of glycerin in their supplementation. Thirty-six crossbred heifers with average initial weight of 264.83±3.83 kg and 20 months of age were distributed into a completely randomized design with four treatments and nine replications: control (0%), 4.82%, 10.12%, and 15.56% glycerin in the dry matter. The grazing time reduced linearly (p<0.05), whereas the time spent on activities like rumination, idleness, trough and total chewing time were quadratically affected (p<0.05). Bite rate and number of bites/day were quadratically influenced (p<0.05). The number of bites/swallowed cud and the number of bites/minute, however, increased linearly (p<0.05). Although the time spent on each cud and number of chews per cud were not affected (p>0.05). The number of rumination periods reduced linearly (p<0.05), whereas the number of grazing, idle and trough periods, and the times per grazing, idle, rumination and trough periods were quadratically affected (p<0.05). The feed and rumination efficiencies of the dry matter, non-fibrous carbohydrates, pasture dry matter and concentrate were quadratically affected (p>0.05) whereas the feed efficiency of neutral detergent fiber reduced linearly (p<0.05). Addition of glycerin in substitution of corn in supplements for animals managed on pastures does not influenced feed intake, but reduces the grazing time and increases the idle time. The supplementation also improves feed and rumination efficiencies.

Groundwater inputs could be a significant but often overlooked source of phosphorus in lake ecosystems.

Freshwater lakes are severely threatened, due largely to excess inputs of nutrients and other contaminants. Phosphorus (P) is receiving renewed attention due to recent increases in toxic cyanobacteria blooms in lakes worldwide. We investigated groundwater seepage for its role in P loading dynamics at Oneida Lake, New York, USA-one of the most well-studied lakes globally. P loading was measured at representative sites along the 88 km shoreline over three summers by directly measuring groundwater flow using seepage meters and porewater samplers. Groundwater seepage was a continuous and significant source of dissolved P over the summer months, comparable to tributary sources to the lake during that time. This constant input has enriched the concentrations of P in the nearshore surface waters, significantly above levels in the pelagic zone. Pore Total Phosphorus (TP) concentrations and loads reached extremely high values (up to 100 mg/L), with inorganic P representing only ~ 10% of TP per site. Groundwater seepage flows and P loadings were highly variable across space and time, partially explained by adjacent land uses and precipitation. Our research concludes that groundwater seepage is a significant, but overlooked, source of dissolved P and a crucial factor driving summer primary production at Oneida Lake, and likely other temperate lakes.

Unraveling age-related impairment of the neuromuscular system: exploring biomechanical and neurophysiological perspectives.

With extended life expectancy, the quality of life of elders is a priority. Loss of mobility, increased morbidity and risks of falls have dramatic individual and societal impacts. Here we consider the age-related modifications of gait, from a biomechanical and neurophysiological perspective. Among the many factors of frailty involved (e.g., metabolic, hormonal, immunological), loss of muscle strength and neurodegenerative changes inducing slower muscle contraction may play a key role. We highlight that the impact of the multifactorial age-related changes in the neuromuscular systems results in common features of gait in the immature gait of infants and older adults. Besides, we also consider the reversibility of age-related neuromuscular deterioration by, on the one hand, exercise training, and the other hand, novel techniques such as direct spinal stimulation (tsDCS).

Influence of sports background on the bouncing mechanism of running.

During running, the mechanical energy of the centre of mass of the body (COM) oscillates throughout the step like a spring-mass system, where part of its mechanical energy is stored during negative phases to be released during the following positive phases. This storage-release of energy improves muscle-tendon efficiency, which is related to lower-limb stiffness. This study explores the effect of sports background on the bouncing mechanism, by examining differences in stiffness and step spatiotemporal parameters between swimmers and football athletes. All athletes performed three consecutive running bouts on an instrumented treadmill at three different speeds (3.9, 4.4 and 5.0 m·s-1). The ground reaction forces were recorded. Vertical stiffness and step spatiotemporal parameters were analysed and compared using a two-way ANOVA. Vertical stiffness of football players was on average 21.0 ± 1.1% higher than swimmers. The modification of step spatiotemporal parameters also suggests a more elastic rebound by increasing the stretch of tendons relative to muscle within muscle-tendon units in football players. Compared to swimmers, they (1) decrease the effective contact time by 9.7 ± 2.4% and (2) decrease the duration of the push by 15.0 ± 6.4%, suggesting that background training adaptations influence spring-mass behaviour during running.

Evaluation of phytochemical composition, toxicity in Drosophila melanogaster and effects on antibiotics modulation of Plathymenia reticulata Benth extract.

Bacterial resistance is interfering with the action of antibiotics for clinical use in treating pathologies. The search for new substances capable of combating this resistance is necessary. An alternative to the search for these substances is in the extract of medicinal plants. Plathymenia reticulata, plant of the Fabaceae family, is a common tree species from the Brazilian cerrado, and is commonly used in areas of environmental degradation. This species is rich in phenolic compounds, such as flavonoids and tannins, compounds that are associated with various biological effects. A hydroethanolic extract from the bark of Plathymenia reticulata (HEPrB) was produced and then tests were carried out to verify the direct antibacterial activity, the modulatory effect of antibiotics for clinical use and their toxicity in Drosophila melanogaster flies. Through the analysis with UPLC, a wide variety of flavonoids contained in the HEPrB was observed. Direct antibacterial activity was observed for the standard strain of Staphylococcus aureus, however, the extract showed antagonistic activity or no significance in relation to the antibiotics tested in this study. As for toxicity, the HEPrB did not show significant damage in the proposed model. The results emphasize care when associating the consumption of teas with treatments with antibiotics for clinical use.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice.

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Adaptive wavelet EMG compression based on local optimization of filter banks.

This paper presents an adaptive wavelet technique for compression of surface electromyographic signals. The technique employs an optimization algorithm to adjust the wavelet filter bank in order to minimize the distortion of the compressed signal. Orthogonality of the transform is ensured by using a restriction-free parametrization described elsewhere. A case study involving real-life isotonic and isometric electromyographic signals is presented for illustration. The results show that the proposed approach outperforms the standard non-optimized wavelet technique in terms of the percent residual difference for a given compression factor.

Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva / Pathogenic variant in the PCDH19 gene in a patient with epilepsy and cognitive disability

INTRODUCCIÓN: La asociación de casos familiares de epilepsia y discapacidad intelectual (DI) en mujeres fue reportada en 1971. El año 2008, se identificó el rol de variantes patogénicas del gen PCDH19 en algunas familias. La enfermedad se presenta con crisis febriles en cluster, DI y rasgos autistas. La mayoría se debe a variantes de novo, pero hay algunos casos heredados por un modo peculiar de transmisión ligada X. OBJETIVO: Comunicar el caso de una paciente con epilepsia portadora de una variante patogénica en el gen PCDH1 9, revisando la historia natural de la enfermedad y la evidencia disponible para su manejo. CASO CLÍNICO: Paciente femenina, con antecedentes de embarazo y período perinatal normal. A los 6 meses, estando febril, presentó crisis focales motoras en cluster que repitieron a los 14, 18, 21 meses y 3 años siempre asociadas a fiebre, presentando incluso estatus epiléptico. Mantiene biterapia con topiramato y ácido valproico, completando 13 años sin crisis. El estudio del gen SCN1A no mostró anomalías y el estudio del gen PCDH19 reveló una variante patogénica en heterocigosis, "de novo". La paciente ha evolucionado con DI y alteraciones conductuales severas que requieren aten ción de salud mental. CONCLUSIONES: Las variantes patogénicas PCDH19 tienen expresión fenotípica variada. El diagnóstico genético debe sospecharse con la clínica. La morbilidad psiquiátrica a largo plazo puede ser incapacitante.

INTRODUCTION: The association of family cases of epilepsy and intellectual disability in women was reported in 1971. In 2008, the role of pathogenic variants of the PCDH19 gene in some families were identified. The disease presents with febrile seizure clusters, intellectual disability, and autistic features. Most cases are due to de novo variants, however, there are some inherited cases, with an atypical way of X-linked transmission. OBJECTIVE: To report the case of a patient with epilepsy carrier of a pathogenic variant of the PCDH19 gene, reviewing the natural history of this condition and the available evidence for its management. CLINICAL CASE: Female patient, with normal history of pregnancy and perinatal period. At 6 months, while febrile, she presented focal motor seizure clusters that repeated at 14, 18, 21 months and 3 years old, always associated with fever, even presenting status epilepticus. She is on therapy with topiramate and valproic acid, achieving 13 seizure-free years. The analysis of the SCN1A gene showed no abnormalities and the study of the PCDH19 gene revealed a de novo heterozygous pathogenic variant. The patient evolved with intellectual disability and severe behavioral disorders that require mental health team support. CONCLUSIONS: PCDH19 pathogenic variants have varied phenotypic expression. The genetic diagnosis should be guided with the clinical features. Long-term psychiatric morbidity can be disabling.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

[Reconstruction of anophthalmic socket]. / Reconstruction de l'orbite anophtalme.

PURPOSE: Evaluate different surgical techniques in the management of the contracted anophthalmic socket. PATIENTS AND METHODS: A retrospective study including 12 patients with acquired anophthalmic socket presenting inadequate fornices and/or orbital volume loss. The surgeries performed were conjunctival suture to the periosteum (mild fornix contraction), buccal mucosa graft (moderate fornix retraction), auricular cartilage graft (severe fornix retraction), and dermis-fat graft (loss of orbital volume). RESULTS: Fornix retraction was mild in two patients, moderate in three patients, and severe in two patients. We observed five patients with loss of orbital volume. Successful correction was achieved in all patients with fornix retraction who were able to wear an external prosthesis. One patient with orbital volume loss developed graft atrophy. CONCLUSION: Autologous grafts are useful in the rehabilitation of the contracted socket.