Heavy menstrual bleeding in women with inherited bleeding disorders in use of LNG-IUS: A systematic review and single-arm meta-analysis.

OBJECTIVES: Inherited bleeding disorders may cause heavy menstrual bleeding in women, impacting quality of life and impairing daily and social activities. The levonorgestrel-releasing intrauterine system is a potential treatment for these women, which might reduce menstrual blood loss. STUDY DESIGN: We performed a systematic review and single-arm meta-analysis to examine the levonorgestrel-releasing intrauterine system in women with inherited bleeding disorders and heavy menstrual bleeding. RESULTS: A systematic search on PubMed, Embase and Cochrane yielded 583 results, of which six observational studies (n = 156) met inclusion criteria. Levonorgestrel-releasing intrauterine system use in patients with inherited bleeding disorders and heavy menstrual bleeding was associated with amenorrhea in 60% of patients and a significant increase of 1.40 g/dL in hemoglobin and of 19.75 ng/mL in ferritin levels when comparing post- and pre-treatment levels. The post-treatment mean hemoglobin was 13.32 g/dL and the mean ferritin was 43.22 ng/dL. The rate of intrauterine device expulsion or removal due to mal position was low (13%), as was the need for intrauterine device removal due to lack of efficacy (14%). CONCLUSION: The levonorgestrel-releasing intrauterine system may improve bleeding patterns and quality of life in patients with inherited bleeding disorders and heavy menstrual bleeding. IMPLICATIONS: Women with inherited bleeding disorders could benefit from levonorgestrel-releasing intrauterine system, so its use should be an option for this women.

16p11.2 Microduplication Syndrome with Increased Fluid in the Cisterna: Coincidence or Phenotype Extension?

We report the first case of a child with 16p11.2 microduplication syndrome with increased fluid in the cisterna magna seen on magnetic resonance imaging (MRI). This finding may correspond to a Blake's Pouch Cyst (BPC) or a Mega Cisterna Magna (MCM), being impossible to differentiate through image examination. The molecular duplication was diagnosed using chromosomal microarray analysis with single nucleotide polymorphism (SNP). We review the clinical and neuroimaging features in published case reports in order to observe the findings described in the literature so far and present a skull three-dimensional model to contribute to a better understanding. Despite the variable expressivity of the syndrome being well known, there is no case described in the available literature that mentions the association of 16p11.2 microduplication and the presence of BPC or MCM seen in neuroimaging exams. This finding may represent an extension of the phenotype not yet reported or may present itself as a coincidence in a child with various malformations.

Use of Intrinsic Capacity Domains as a Screening Tool in Public Health.

The World Health Organization (WHO) created the concept of Integrated Care for Older People and one of its constructs is intrinsic capacity (IC). The study aimed to carry out a screening with the tools designated by the WHO to assess the IC domains and whether they can be used as indicators for decision-making on integrated care for older people based on risk categorization. The interaction between the risk category and the domain scores was verified. One hundred and sixty three (163) community-dwelling older people of both genders were evaluated. Domains assessed: cognitive, psychological, vitality, locomotion, and sensory. Scores indicating a low, moderate and high risk were assigned to each domain. For all domains, there were individuals in all risk groups. Effect of risk on the domains: cognitive [χ2(2) = 134.042; p < 0.001], psychological [χ2(2) = 92.865; p < 0.001], vitality [χ2(2) = 129.564; p < 0.001], locomotion [χ2(2) = 144.101; p < 0.001], and sensory [χ2(2) = 129.037; p < 0.001]. Scores of the CI domains were affected by the risk category. There were individuals in all risk groups, demonstrating the importance of screening as a public health strategy, making it possible to know which risk category each elderly person belongs to and thus develop strategies in the short-, medium- and long-term.

Somatosensory Cortex Repetitive Transcranial Magnetic Stimulation and Associative Sensory Stimulation of Peripheral Nerves Could Assist Motor and Sensory Recovery After Stroke.

Background: We investigated whether transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex (S1) and sensory stimulation (SS) could promote upper limb recovery in participants with subacute stroke. Methods: Participants were randomized into four groups: rTMS/Sham SS, Sham rTMS/SS, rTMS/SS, and control group (Sham rTMS/Sham SS). Participants underwent ten sessions of sham or active rTMS over S1 (10 Hz, 1,500 pulses, 120% of resting motor threshold, 20 min), followed by sham or active SS. The SS involved active sensory training (exploring features of objects and graphesthesia, proprioception exercises), mirror therapy, and Transcutaneous electrical nerve stimulation (TENS) in the region of the median nerve in the wrist (stimulation intensity as the minimum intensity at which the participants reported paresthesia; five electrical pulses of 1 ms duration each at 10 Hz were delivered every second over 45 min). Sham stimulations occurred as follows: Sham rTMS, coil was held while disconnected from the stimulator, and rTMS noise was presented with computer loudspeakers with recorded sound from a real stimulation. The Sham SS received therapy in the unaffected upper limb, did not use the mirror and received TENS stimulation for only 60 seconds. The primary outcome was the Body Structure/Function: Fugl-Meyer Assessment (FMA) and Nottingham Sensory Assessment (NSA); the secondary outcome was the Activity/Participation domains, assessed with Box and Block Test, Motor Activity Log scale, Jebsen-Taylor Test, and Functional Independence Measure. Results: Forty participants with stroke ischemic (n = 38) and hemorrhagic (n = 2), men (n = 19) and women (n = 21), in the subacute stage (10.6 ± 6 weeks) had a mean age of 62.2 ± 9.6 years, were equally divided into four groups (10 participants in each group). Significant somatosensory improvements were found in participants receiving active rTMS and active SS, compared with those in the control group (sham rTMS with sham SS). Motor function improved only in participants who received active rTMS, with greater effects when active rTMS was combined with active SS. Conclusion: The combined use of SS with rTMS over S1 represents a more effective therapy for increasing sensory and motor recovery, as well as functional independence, in participants with subacute stroke. Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT03329807].

Sensory and motor cortical excitability changes induced by rTMS and sensory stimulation in stroke: A randomized clinical trial.

Background: The ability to produce coordinated movement is dependent on dynamic interactions through transcallosal fibers between the two cerebral hemispheres of the brain. Although typically unilateral, stroke induces changes in functional and effective connectivity across hemispheres, which are related to sensorimotor impairment and stroke recovery. Previous studies have focused almost exclusively on interhemispheric interactions in the primary motor cortex (M1). Objective: To identify the presence of interhemispheric asymmetry (ASY) of somatosensory cortex (S1) excitability and to investigate whether S1 repetitive transcranial magnetic stimulation (rTMS) combined with sensory stimulation (SS) changes excitability in S1 and M1, as well as S1 ASY, in individuals with subacute stroke. Methods: A randomized clinical trial. Participants with a single episode of stroke, in the subacute phase, between 35 and 75 years old, were allocated, randomly and equally balanced, to four groups: rTMS/sham SS, sham rTMS/SS, rTMS/SS, and sham rTMS/Sham SS. Participants underwent 10 sessions of S1 rTMS of the lesioned hemisphere (10 Hz, 1,500 pulses) followed by SS. SS was applied to the paretic upper limb (UL) (active SS) or non-paretic UL (sham SS). TMS-induced motor evoked potentials (MEPs) of the paretic UL and somatosensory evoked potential (SSEP) of both ULs assessed M1 and S1 cortical excitability, respectively. The S1 ASY index was measured before and after intervention. Evaluator, participants and the statistician were blinded. Results: Thirty-six participants divided equally into groups (nine participants per group). Seven patients were excluded from MEP analysis because of failure to produce consistent MEP. One participant was excluded in the SSEP analysis because no SSEP was detected. All somatosensory stimulation groups had decreased S1 ASY except for the sham rTMS/Sham SS group. When compared with baseline, M1 excitability increased only in the rTMS/SS group. Conclusion: S1 rTMS and SS alone or in combination changed S1 excitability and decreased ASY, but it was only their combination that increased M1 excitability. Clinical trial registration: clinicaltrials.gov, identifier (NCT03329807).

Comparison of streptozotocin-induced diabetes at different moments of the life of female rats for translational studies.

Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague-Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy.

Transcription blockage by DNA damage in nucleotide excision repair-related neurological dysfunctions.

Human genetic syndromes deficient in nucleotide excision repair (NER), such as xeroderma pigmentosum and Cockayne syndrome, may present neurological abnormalities and premature aging symptoms. Unrepaired endogenously generated DNA damage that hampers transcription is a strong candidate that contributes to the development of these severe effects in neuronal tissue. Endogenous lesions include those generated due to byproducts of cellular metabolisms, such as reactive oxygen species. This review presents much of the evidence on the mechanisms related to neurodegenerative processes associated with DNA damage responses. The primary focus is on the effects of the transcription machinery, including the accumulation of DNA•RNA hybrids (R-loops) that, in turn, influence DNA damage and repair metabolism. Moreover, several neuronal tissues present higher expression of long genes, a genomic subset more affected by DNA lesions, which may explain part of the neurological abnormalities in these patients. Also, neuronal tissues have different DNA repair capabilities that might result in different neurological consequences, as observed in patients and NER deficient animal models. The better understanding of how the accumulation of transcription blocking lesions can lead to neurological abnormalities and premature aging-like phenotypes may assist us in finding potential biomarkers and therapeutic targets that might improve the lives of these patients, as well as other neurological disorders in the general population.

Cockayne Syndrome: The many challenges and approaches to understand a multifaceted disease.

The striking and complex phenotype of Cockayne syndrome (CS) patients combines progeria-like features with developmental deficits. Since the establishment of the in vitro culture of skin fibroblasts derived from patients with CS in the 1970s, significant progress has been made in the understanding of the genetic alterations associated with the disease and their impact on molecular, cellular, and organismal functions. In this review, we provide a historic perspective on the research into CS by revisiting seminal papers in this field. We highlighted the great contributions of several researchers in the last decades, ranging from the cloning and characterization of CS genes to the molecular dissection of their roles in DNA repair, transcription, redox processes and metabolism control. We also provide a detailed description of all pathological mutations in genes ERCC6 and ERCC8 reported to date and their impact on CS-related proteins. Finally, we review the contributions (and limitations) of many genetic animal models to the study of CS and how cutting-edge technologies, such as cell reprogramming and state-of-the-art genome editing, are helping us to address unanswered questions.

Development, Cytotoxicity and Eye Irritation Profile of a New Sunscreen Formulation Based on Benzophenone-3-poly(ε-caprolactone) Nanocapsules.

The objective of this work was to characterize the toxicological profile of a newly developed sunscreen formulation based on polymeric nanocapsules (NCs) loading benzophenone-3 (BZP3). NCs composed of poly(ε-caprolactone) carrot oil and Pluronic® F68 were produced by emulsification-diffusion method. Their mean particle size (Z-Ave) ranged from 280 to 420 nm, polydispersity index (PDI) was below 0.37, while zeta potential (ZP) reached about |+11 mV|. No cytotoxic effects were observed in L929 fibroblast cell line for the blank (i.e., non-loaded) NCs and BZP3-loaded NCs (BZP3-NCs). The semi-solid sunscreen formulation was stable over time (centrifugation testing) and exhibited non-Newtonian pseudoplastic behavior, which is typical of products for topical application onto the skin. The sun protection factor (SPF) value reached 8.84, when incorporating BZP3-NCs (SPF of 8.64) into the semi-solid formulation. A synergistic effect was also observed when combining the formulation ingredients of nanocapsules, i.e., SPF of carrot oil was 6.82, blank NCs was 6.84, and BZP3-loaded NCs was 8.64. From the hen's egg-chorioallantoic membrane test (HET-CAM) test, the non-irritation profile of the developed formulations could also be confirmed. The obtained results show a promising use of poly(ε-caprolactone) nanocapsules to be loaded with lipophilic sunscreens as benzophenone-3.

Associação entre força muscular e sensibilidade plantar em pacientes diabéticos: um estudo transversal / Association bet ween muscle force and foot sensitiveness in patients with diabetes: a transversal study

Diabetes Mellitus, distúrbio metabólico crônico dos carboidratos com elevadas taxas de morbi-mortalidade, tem a neuropatia diabética periférica (alterações sensitivas, motoras e autonômicas) como complicação mais prevalente. Em estudo transversal, 18 pacientes, verificou-se se há associação entre sensibilidade plantar e força muscular do tornozelo em pacientes diabéticos, avaliados quanto à sensibilidade tátil com monofilamentos (Semmes-Weisntein) em três pontos da região plantar nos dois pés, e força muscular de tornozelo, com teste de força manual, graduada de 0 a 5. Análise realizada no SPSS 20.0, testes qui quadrado e exato de Fisher, e p<0,05. Observou-se que 44,5% dos pacientes tinham perda da sensibilidade tátil e 38,8% da sensibilidade dolorosa; 38,8% e 33,3% tiveram diminuição da força de dorso-flexão direita e esquerda respectivamente, no entanto a correlação dessas variáveis, não foi estatisticamente significante. Diante dos resultados, não foi possível correlacionar a perda de sensibilidade plantar com a diminuição da força muscular nesse grupo de pacientes diabéticos.

Diabetes mellitus, a chronic carbohydrate metabolic disorder with high morbo-mortality rates, also includes peripheral diabetic neuropathy as a predominant complication. Current analysis verifies the association between foot sensitiveness and muscle force of the ankle in patients with diabetes. A transversal study involving 18 patients revealed that there is an association between foot sensitiveness and muscle force at the ankle in patients who were evaluated with regard to tactile sensitiveness with monofilaments (Semmes-Weistein) at three sites of the sole the foot and the muscular force of the ankle, with tests for hand strength, graduated from 0 to 5. Analysis SPSS 20.0, chi-square tests and Fisher´s exact test (p<0.05) were performed. Further, 44.5% of patients suffered loss of tactile sensitiveness; 38.8% had loss of pain sensitiveness; 38.8% and 33.3% had a decrease in the lateral dorsal-flexor force even though the co-relationship of variables was not statistically significant. Loss of sole sensitiveness could not be associated with decrease in muscle force in patients with diabetes.

Estudo epidemiológico da população masculina atendida por um projeto de extensão itinerante / Epidemiological study of male population attended by an itinerant extension project

Objetivo: traçar o perfil epidemiológico da população masculina atendida por um projeto de extensãouniversitária. Método: estudo transversal, quantitativo realizado em 107 homens residentes nos municípiosatendidos pelo Programa “Laboratório Itinerante” da Universidade Estadual da Paraíba, depois da aprovaçãodo projeto de pesquisa pelo Comitê de Ética da Universidade Estadual da Paraíba, sob CAAEnº 0497.0.133.000-11. Os dados foram coletados utilizando-se questionários estruturados, entre outubro edezembro de 2011 e analisados no software Epi Info® 3.5.2. Resultados: a maioria dos homens (53,0%) estavacom excesso de peso, fazia uso de bebidas alcoólicas (43%) e referiu ter problemas de saúde(32,7%). Apenas 15,9% frequentou a atenção primária no último ano. Fatores geográficos e sócioorganizacionais(25,2%) foram as maiores dificuldades relatadas na busca pela atenção primária.Conclusão: a prevalência de sobrepeso e hábitos de risco foi associada à ausência homens ao serviço atençãoprimária.

Hepatite C em hemodiálise: informação e prevenção dos profissionais de enfermagem / Hepatitis C in hemodialysis: nursing professional´s information and prevention

Trata-se de um estudo descritivo com abordagem quantitativa, cujos objetivos foram descrever informações que a equipe de enfermagem apresenta sobre a Hepatite C no setor de Hemodiálise e identificar a adesão desses profissionais ao reconhecimento de medidas preventivas de infecção pelo vírus da hepatite C em serviços de hemodiálise. Participaram da investigação 49 profissionais, representando 100% dos funcionários da equipe de enfermagem dos setores de hemodiálises do município de Campina Grande. Dentre os resultados, verificou-se que a equipe necessita de um treinamento permanente visando adquirir mais informações quanto à prevenção da hepatite C em setor de hemodiálise, e fazendo com que haja a adesão desses profissionais em relação as condutas de segurança no trabalho.

Tufted angioma and myofascial pain syndrome.

Tufted angioma is a rare acquired vascular tumor. It is characterized by painful purplish macules that may progress to plaques containing angiomatous papules. The condition is benign; however, it often affects extensive areas of the skin, leading to functional disability of the affected limb if painful. The present report describes a case of a tufted angioma associated with myofascial pain syndrome in which the predisposing element was the presence of this tumor since childhood. Pain at the site of the lesion affected muscle use and led to the onset of the associated syndrome. Complete relief from symptoms was achieved by blocking the trigger points of the affected limb with anesthesia.

Angioma em tufo e síndrome dolorosa miofascial / Tufted angioma and myofascial pain syndrome

O Angioma em tufo é considerado um raro tumor vascular cutâneo adquirido. Caracteriza-se por máculas purpúrico-violáceas, dolorosas que podem evoluir para placas com pápulas angiomatosas. Tem natureza benigna, mas o envolvimento extenso é comum, gerando alteração funcional do membro afetado em caso de dor. Os autores relatam um caso de angioma em tufo associado à síndrome dolorosa miofascial, em que o elemento predisponente foi a presença deste tumor desde a infância. A dor local prejudicou a utilização da musculatura e possibilitou o surgimento da síndrome relatada. A realização de bloqueio anestésico de pontos-gatilhos no membro afetado, levou à melhora total dos sintomas.

Tufted angioma is a rare acquired vascular tumor. It is characterized by painful purplish macules that may progress to plaques containing angiomatous papules. The condition is benign; however, it often affects extensive areas of the skin, leading to functional disability of the affected limb if painful. The present report describes a case of a tufted angioma associated with myofascial pain syndrome in which the predisposing element was the presence of this tumor since childhood. Pain at the site of the lesion affected muscle use and led to the onset of the associated syndrome. Complete relief from symptoms was achieved by blocking the trigger points of the affected limb with anesthesia.

Tensão pré-menstrual (TPM): uma revisão baseada em evidências científicas / Premenstrual syndrome (PMS): an evidence-based review

A Tensão pré-menstrual (TPM) é uma síndrome comum em mulheres na fase reprodutiva, sendo caracterizada por sintomas físicos e emocionais que ocorrem de forma cíclica durante a fase lútea do ciclo menstrual. Mulheres que apresentam sintomatologia mais severa são classificadas como portadoras de Distúrbio Disfórico Pré-Menstrual (DDPM). Ambas as situações clínicas podem se manifestar com uma grande variedade de sintomas incluindo depressão, labilidade emocional, distensão abdominal, mastalgia, cefaleia e fadiga. O manejo e tratamento adequados dos sintomas pré-menstruais têm sido uma grande incógnita para os clínicos. Porém, com base em vários estudos científicas realizadas na última década, hoje há critérios diagnósticos para a forma mais severa desta condição clínica, a DDPM, assim como novas estratégias terapêuticas. Esta revisão apresentou uma descrição prática e compreensiva do que os clínicos necessitam saber para diagnosticar e tratar os sintomas pré-menstruais, assim como critérios diagnósticos para diferenciação de TPM e DDPM.

Premenstrual syndrome (PMS) is common in women in reproductive phase and is characterized by emotional and physical symptoms that cyclically occur during the luteal phase of the menstrual cycle. Women with more severe symptoms are classified as having Premenstrual Dysphoric Disorder (PMDD). Both clinical situations can appear with a wide variety of symptoms, including depression, mood lability, abdominal pain, breast tenderness, headache and fatigue. The appropriate management and treatment of adverse premenstrual symptoms has been a difficult challenge for clinicians. However, based on numerous scientific studies over the last decade, there are nowadays diagnostic criteria for the severe form of the syndrome, PMDD, and new evidence-based therapeutic strategies. This review presented a comprehensive and practical description of what the clinicians need to know in order to diagnose and treat premenstrual symptoms, as well as diagnostic criteria to differentiate PMS and PMDD.

Activin A and follistatin in menstrual blood: low concentrations in women with dysfunctional uterine bleeding.

Activin A and follistatin are growth factors produced by several organs, comprising the endometrium, where they modulate cell and tissue differentiation. In this study, the authors tested whether activin A and follistatin are measurable in menstrual blood and whether their concentrations change in women with dysfunctional uterine bleeding (DUB). The authors evaluated healthy women with regular menstrual cycles (n = 15) and women with DUB (n = 12). Activin A and follistatin were measured in both menstrual and peripheral blood samples using highly sensitive enzyme immunoassays, whereas their respective mRNAs were quantified by real-time polymerase chain reaction in endometrial samples collected during the perimenstrual period. Activin A concentrations were 4-fold higher in menstrual than in peripheral serum of healthy women (mean +/- SE, 4.24 +/- 0.18 vs 1.00 +/- 0.15 ng/mL, P < .001) and were significantly lower in women with DUB compared to healthy subjects (P < .001). Follistatin concentration was 8-fold higher in menstrual than in peripheral serum of healthy women (3.94 +/- 0.49 vs 0.49 +/- 0.04 ng/mL, P < .001) and was significantly lower in the menstrual serum of women with DUB compared to controls (P < .001). There was no correlation between menstrual and peripheral serum concentrations of both proteins. The endometrial expression of activin A and follistatin mRNA was lower in women with DUB compared to controls (P < .05). Both activin A and follistatin are measurable in high concentrations in human menstrual blood and are relatively lower in women with DUB. The quantitative assessment of activin A and follistatin in menstrual serum might be a putative clinical marker of endometrial function.

O ensino de iniciação científica no curso de graduação em medicina / The education of scientific initiation in the course of graduation

Introdução: a partir do ano 2000, foi introduzida a Iniciação Científica (IC) no Curso de Graduação em Medicina da UNIRIO. A IC I foi criada com o objetivo principal de capacitar os alunos para a leitura crítica de trabalhos científicos, além de fornecer noções de informática como instrumento para a busca de informações. Periodicamente, a IC I é reavaliada para melhor atender a ementa da disciplina. O objetivo desse estudo foi avaliar se a metodologia atualmente utilizada na IC I trouxe reais benefícios ao aprendizado. Metodologia: estudo transversal realizado com 131 alunos que responderam a um questionário, com itens referentes ao conteúdo programático da disciplina. Destes, 53 eram do segundo período (que tinham acabado de cursar a IC I e elaboraram e participaram de um protocolo de pesquisa); 43 do sétimo período (que cursaram a disciplina hátrês anos e não tiveram experiência com protocolos de pesquisa) e 35 do internato (11° e 12° períodos, que não cursaram a IC I - currículo antigo). Resultados: a amostra foi constituída de 74 mulheres e 57 homens, com média de idade de 22,15±2,34 anos. Quanto às respostas ao questionário como um todo, os estudantes do segundo período mostraram um número significativamente maior de acertos, quando comparados aos demais (p<0,001), não existindo diferença entre o sétimo e o internato (p=0,497). Conclusão: a metodologia recentemente utilizada na IC I está contribuindo para uma maior aquisição de conhecimentos; contudo, é necessário consolidar esses ensinamentos durante o Curso de Medicina.