Fatores Maternos associados à ocorrência de Mielomeningocele: Uma Revisão Bibliográfica / Maternal Factors Associated with the Occurrence of Myelomeningocele: A Literature Review

Resumo- A mielomeningocele configura um defeito primário do tubo neural mais comum, tal defeito constitui uma das malformações congênitas mais graves do recém-nascido, uma vez que o sistema nervoso central tem início em um tubo que se desenvolve nas estruturas mais complexas do corpo humano. O defeito pode ocorrer na sua porção cranial, resultando em malformações como anencefalia e encefalocele ou na porção caudal resultando em malformações que em grupo são conhecidas como espinha bífida. A mielomeningocele é classificada como espinha bífida aberta e ocorre nas primeiras quatro semanas de gestação. O objetivo deste estudo foi identificar na literatura fatores maternos associados ao aparecimento da mielomeningocele. A coleta de dados foi realizada em outubro a novembro de 2021, nas bases de dados SciELO, Google acadêmico e BVS – Brasil utilizando as palavras chaves: “mielomeningocele”, “malformação tubo neural” e “fatores maternos”, sendo necessária também a pesquisa em livros específicos, constituindo uma amostra de 13 publicações. A deficiência de ácido fólico destacou-se como principal fator materno associado à ocorrência da mielomeningocele; além da ingestão materna de anticonvulsivantes, ingestão de fármacos antagonistas do ácido fólico, doenças como o diabetes e a obesidade, deficiência de zinco, baixas condições socioeconômicas e influências perturbadoras como a irradiação e a hipertermia materna. Conclui-se que medidas públicas no combate aos fatores maternos preveníveis são necessárias, uma vez que a mielomeningocele é uma patologia limitante, complexa, com impacto na qualidade de vida dos pacientes e de seus familiares além de requerer equipe especializada e multidisciplinar.Palavras-Chave: Mielomeningocele; Malformações; Espinha bífida. Abstract- Myelomeningocele is a primary defect of the most common neural tube, this defect is one of the most serious congenital malformations in newborns, since the central nervous system starts in a tube that develops in the most complex structures of the human body. The defect can occur in its cranial portion, resulting in malformations such as anencephaly and encephalocele, or in the caudal portion, resulting in malformations that, in group, are known as spina bifida. Myelomeningocele is classified as open spina bifida and occurs within the first four weeks of pregnancy. The aim of this study was to identify maternal factors associated with the onset of myelomeningocele in the literature. Data collection was carried out from October to November 2021, in the SciELO, Google Academic and BVS – Brazil databases using the keywords: “myelomeningocele”, “neural tube malformation” and “maternal factors”, also requiring the research in specific books, constituting a sample of 13 publications. Folic acid deficiency stood out as the main maternal factor associated with the occurrence of myelomeningocele; in addition to maternal intake of anticonvulsants, intake of drugs that are antagonists to folic acid, diseases such as diabetes and obesity, zinc deficiency, low socioeconomic conditions and disturbing influences such as radiation and maternal hyperthermia. It is concluded that public measures to combat preventable maternal factors are necessary, since myelomeningocele is a limiting and complex pathology, with an impact on the quality of life of patients and their families, in addition to requiring a specialized and multidisciplinary team.Keywords: Myelomeningocele. Malformations. Spina bifida.

Hypocalcemia as the Initial Presentation of Type 2 Bartter Syndrome – A Family Report

Context Bartter syndrome (BS) is a group of rare autosomal-recessive tubulopathies characterized by hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption. Type 2 BS results from a defect in the renal outer medullary potassium channel encoded by the KCNJ1 gene. Type 2 BS presents with polyhydramnios, intrauterine growth retardation, prematurity, failure to thrive, polyuria, hypercalciuria, and life-threatening episodes of dehydration. Hypocalcemia is a very rare presenting symptom of BS, with only a few published cases reporting it as the initial manifestation of type 2 BS. Case description We describe a child who presented with hypocalcemic seizure at the age of 2.3 years that was first related to vitamin D deficiency and high-phosphate soft drink consumption. However, later whole exome sequencing (WES) identified a previously described homozygous missense mutation c.212C>T, p.T71M in the KCNJ1 gene associated with type 2 BS. Six additional family members with the same mutation and diagnosed clinically with BS are also reported, two presenting with hypocalcemia associated with vitamin D deficiency. Conclusions This report expands the clinical spectrum associated with KCNJ1 mutations and emphasizes the role of WES in unsolved cases of hypocalcemia when genetic disease is suspected. It also highlights the hazardous effects of phosphate-containing soft drinks on calcium metabolism.

Thermonuclear Fusion Reactor Plasma-Facing Materials under Conditions of Ion Irradiation and Plasma Flux

A review of experimental studies carried out at the NRC “Kurchatov Institute” on plasma-facing thermonuclear fusion reactor materials is presented in the paper. An experimental method was developed to produce high-level radiation damage in materials simulating the neutron effect by surrogate irradiation with high-energy ions. Plasma-surface interaction is investigated on materials irradiated to high levels of radiation damage in high-flux deuterium plasma. The total fluence of accelerated ions (3–30 MeV, 4He2+, 12C3+, 14N3+, protons) on the samples was 1021–1023 m−2. Experiments were carried out on graphite materials, tungsten, and silicon carbide. Samples have been obtained with a primary defect concentration from 0.1 to 100 displacements per atom, which covers the predicted damage for the ITER and DEMO projects. Erosion dynamics of the irradiated materials in steady-state deuterium plasma, changes of the surface microstructure, and deuterium retention were studied using SEM, TEM, ERDA, TDS, and nuclear backscattering techniques. The surface layer of the materials (3 to hundreds µm) was investigated, and it was shown that the changes in the crystal structure, the loss of their symmetry, and diffusion of defects to grain boundaries play an important role. The most significant results are presented in the paper as an overview of our previous work for many years (carbon and tungsten materials) as well as the relatively recent results (silicon carbide).

Study of the Characteristic Mental Development Features of Primary School Students with Visçion Impairments

Severe vision impairments are an obstacle to the adequate cognitive and social development of the child. The educational response to priority problems that occur with vision disorders requires appropriate training of vision impairment specialists. For this purpose, they need basic knowledge related to the classification of vision impairments and the main aspects of the development and education of this category of children. This study aimed to analyse the main features of educational activities of children with vision impairments using special diagnostic methods and to search for effective methods for correcting the cognitive activity of children with vision impairments. During the study, an experiment was conducted with children with vision impairments (15 children). To conduct the experiment, the study used methods proposed by V.V. Tarasun and adapted them to the contingent of children with vision impairments. In particular, the following methods: the method of motivational preferences "Three wishes", the method of "Memorising 10 words", and the method of "What, why, how". The depth and time of vision impairment are considered as a primary defect, which has corresponding secondary consequences and requires corrective action under the guidance of an experienced vision impairment specialist.

“Effect of Yoga Intervention on Skeletal Muscle Linked Glucose Homeostasis in Pre-Diabetic Individuals: Study Protocol for a Randomized Controlled Trial”

Background- The pre-diabetic stage is important in terms of identification and timely management, as it is reversible. Along with other factors, insulin resistance in skeletal muscle is often considered as primary defect before development of overt hyperglycemia and diabetes. Proven to have many health benefits, Yoga has emerged as an effective measure in management of diabetes. As the Yogic postures are relatable to exercises, it was considered for improving skeletal muscle function and reverse the pre-diabetic stage.Methods- The present open, randomized clinical study is planned to evaluate the effect of Yoga interventions on muscle mass, strength, endurance and flexibility which are direct or indirect indicators of fat deposition in skeletal muscles. The study will also explore association between changes in muscle quality/ functionality and glycemic control. With Ethics committee permission, 120 pre-diabetic individuals of either sex between the age group of 35-49 years with a BMI in the range of 25-35 kg/m2 and family history of T2DM will be recruited in study after obtaining written informed consent. They will be randomly allocated to either Yoga or exercise group by computer generated randomized method in a 1:1 ratio. One group will receive defined Yoga interventions, while other group will receive fixed program of physical exercises. Both groups will undergo a training session for a period of 4 weeks under the supervision of a trained instructor, before 12-week study duration. The outcome measures will be parameters related to muscle quality/functionality and glucose metabolism markers. Discussion- Our study aims to study usefulness of Yoga in prediabetic stage on skeletal muscle related glycemic control, which is novel. In addition, the study will generate awareness about pre-diabetes and provide people with active coping skills for reversing it. Trial Registration- Clinical Trial Registry-India -CTRI/2019/05/019149, registered on: 15/05/2019

RECOGNITION OF DISCHARGES THAT ARE ACCOMPANIED BY LOW-TEMPERATURE OVERHEATING BASED ON THE ANALYSIS OF GASES DISSOLVED IN THE OIL OF HIGH-VOLTAGE TRANSFORMERS

Based on the analysis of test results for 135 high-voltage transformers, ranges of gas percentage, gas ratio values were obtained and nomograms for 10 types of combined defects were made, representing discharges with different intensity which are accompanied by overheating with temperature of 150-300°C. It has been established that in transformers with discharges accompanied by low-temperature overheating the values of CH4/H2, C2H2/CH4, C2H2/C2H6 and C2H2/C2H4 ratios determine the discharge energy, in accordance with the norms regulated by the most known standards, the C2H4/C2H6 ratio varies slightly depending on the hot spot temperature and the C2H6/CH4>1 ratio value. Dynamics of defects nomograms changing in the process of their development is analyzed. It is stated by the analysis results that in majority of cases the primary defect is discharges with different intensity, which are accompanied by low-temperature overheating. Overheating occurs in the process of discharge development. The analysis of recognition reliability of discharges with different intensity which are accompanied by 150-300°C overheating was made, using norms and criteria regulated by the most known standards and methods. The results of the analysis show that the most reliable recognition of the defects analyzed is provided to a large extent by the graphical methods, namely the ETRA square and the Duval triangle. The results obtained will significantly increase the recognition reliability of combined defects based on the results of the dissolved gas analysis in the oil.

Translation of MT-ATP6 pathogenic variants reveals distinct regulatory consequences from the co-translational quality control of mitochondrial protein synthesis.

Pathogenic variants that disrupt human mitochondrial protein synthesis are associated with a clinically heterogenous group of diseases. Despite an impairment in oxidative phosphorylation being a common phenotype, the underlying molecular pathogenesis is more complex than simply a bioenergetic deficiency. Currently, we have limited mechanistic understanding on the scope by which a primary defect in mitochondrial protein synthesis contributes to organelle dysfunction. Since the proteins encoded in the mitochondrial genome are hydrophobic and need co-translational insertion into a lipid bilayer, responsive quality control mechanisms are required to resolve aberrations that arise with the synthesis of truncated and misfolded proteins. Here, we show that defects in the OXA1L-mediated insertion of MT-ATP6 nascent chains into the mitochondrial inner membrane are rapidly resolved by the AFG3L2 protease complex. Using pathogenic MT-ATP6 variants, we then reveal discrete steps in this quality control mechanism and the differential functional consequences to mitochondrial gene expression. The inherent ability of a given cell type to recognize and resolve impairments in mitochondrial protein synthesis may in part contribute at the molecular level to the wide clinical spectrum of these disorders.

Hidradenitis Suppurativa: Where We Are and Where We Are Going

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. It is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture and immune responses. Innate pro-inflammatory cytokines (e.g., IL-1β, and TNF-α); mediators of activated T helper (Th)1 and Th17 cells (e.g., IFN-γ, and IL-17); and effector mechanisms of neutrophilic granulocytes, macrophages, and plasma cells are involved. On the other hand, HS lesions contain anti-inflammatory mediators (e.g., IL-10) and show limited activity of Th22 cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction, and scarring. HS pathogenesis is still enigmatic, and a valid animal model for HS is currently not available. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. Available treatments are limited, mostly off-label, and surgical interventions are often required to achieve remission. In this paper, we provide an overview of the current knowledge surrounding HS, including the diagnosis, pathogenesis, treatments, and existing translational studies.

Molecular changes in the Glucokinase gene (GCK) associated with the diagnosis of Maturity Onset Diabetes of the Young (MODY) in pregnant women and newborns

Background: Diabetes Mellitus is the most common metabolic alteration in gestation. Monogenic diabetes or Maturity-Onset Diabetes of the Young (MODY) consists in a subtype caused by primary defect in insulin secretion determined by dominant autosomal inheritance. Objectives: To analyze molecular changes of the Glucokinase gene (GCK) in pregnant women with hyperglycemia during gestation and in their neonates. Case study and Methods: We collected 201 blood samples, 128 from pregnant patients diagnosed with hyperglycemia and 73 from umbilical cord blood from neonates of the respective patients. We performed DNA extraction and polymerase chain reaction (PCR) to identify molecular changes in the GCK gene. Results: In a total of 201 samples (128 from mothers and 73 from neonates), we found changes in 21 (10.6%), 12 maternal samples (6.0%) and 9 neonatal samples (4.5%). DNA sequencing identified two polymorphisms and one deleterious MODY GCK-diagnostic mutation. Conclusions: The prevalence of molecular changes of the Glucokinase gene (GCK) and the deleterious MODY GCK-diagnostic mutation were, respectively, 9.3% and 0.7% in women with hyperglycemia during gestation and 12.5% and 1.3% in their neonates. The deleterious MODY GCK mutation identified is associated reduction in GCK activity and hyperglycemia. In the others molecular changes identified despite not having clinical significance, it was not possible to exclude phenotypic change. Therefore, these changes may interfere with the management and clinical outcome of the patients.

Study on the Effect of Continuity and Load Angle of Prefabricated Cross-Flaws on Crack Initiation and Coalescence

In this study, a model that is closer to the state of fracture presentation in natural rocks has been developed, which is different from the previous. The cross-flaws can be characterized by the joint persistency ( k ) and the angle between the primary flaws and axial load ( α ). The two parameters were varied individually and, by combining them, nine specimens with different nodal parameters were formed. Laboratory specimens and numerical simulations were performed on these specimens to investigate the crack extension process and the variation of crack initiation and coalescence stresses. It is found that a new category of crack coalescence is discovered according to the experimental results besides those reported before, and the angle α affects whether tensile-shear cracks appear. Also, α has an impact on the location where crack first occurs. The joint persistency k alters rock failure mode and has a substantial effect on crack initiation stress. However, the effect on the aggregation stress is not significant. The crack initiation stress decreases in the case of cross-flaws in contrast to flat fissures. In addition, the flat-joint model in PFC2D is used for numerical simulation. It is possible to conduct a study that is difficult to achieve experimentally by using simulations, i.e., only changing one macroparameter without changing others and thus studying the changes in the effect on cracking during fracture. The simulation results are in good agreement with the experimental results. At the same time, the connection mode and the width of the crack coalescence zone of the primary defect, which is difficult to observe in the experiment, are found out from the numerical simulation.