ER stress inhibition enhances formation of triacylglcerols and protects endothelial cells from lipotoxicity.

Elevated concentrations of palmitate in serum of obese individuals can impair endothelial function, contributing to development of cardiovascular disease. Although several molecular mechanisms of palmitate-induced endothelial dysfunction have been proposed, there is no consensus on what signaling event is the initial trigger of detrimental palmitate effects. Here we report that inhibitors of ER stress or ceramid synthesis can rescue palmitate-induced autophagy impairment in macro- and microvascular endothelial cells. Furthermore, palmitate-induced cholesterol synthesis was reverted using these inhibitors. Similar to cell culture data, autophagy markers were increased in serum of obese individuals. Subsequent lipidomic analysis revealed that palmitate changed the composition of membrane phospholipids in endothelial cells and that these effects were not reverted upon application of above-mentioned inhibitors. However, ER stress inhibition in palmitate-treated cells enhanced the synthesis of trilglycerides and restored ceramide levels to control condition. Our results suggest that palmitate induces ER-stress presumably by shift in membrane architecture, leading to impaired synthesis of triglycerides and enhanced production of ceramides and cholesterol, which altogether enhances lipotoxicity of palmitate in endothelial cells.

Can glutathione be a biomarker for suicide risk in women 18 months postpartum?

Background: Suicide risk is prominent among the problems affecting populations, mainly due to the broad family, psychosocial and economic impact. Most individuals at suicidal risk have some mental disorder. There is considerable evidence that psychiatric disorders are accompanied by the activation of neuro-immune and neuro-oxidative pathways. The aim of the study is to evaluate the serum levels of oxidative stress biomarkers in women at risk of suicide after 18 months of postpartum. Methods: This is a case-control study, nested within a cohort study. From this cohort, 45 women [15 without mood disorders and 30 with mood disorders (Major depression and Bipolar disorder)] were selected at 18 months postpartum, the depression and suicide risk were assessed using the Mini-International Neuropsychiatric Interview Plus (MINI-Plus) instrument, module A and C, respectively. Blood was collected and stored for later analysis of the reactive species (DCFH), superoxide dismutase (SOD), and glutathione reduced (GSH). For data analysis, the SPSS program was used. To compare the nominal covariates with the outcome GSH levels, the Student's t-test or analysis of variance (ANOVA) was used. Spearman's correlation was performed for analysis between the quantitative covariates and the outcome. To analyze the interaction between the factors, multiple linear regression was performed. Bonferroni analysis was used as an additional/secondary result to visualize differences in glutathione levels according to risk severity. After the adjusted analysis, p-values < 0.05 were considered statistically significant. Results: The percentage of suicide risk observed in our sample of women at 18 months postpartum was 24.4% (n = 11). After adjusting for the independent variables, only the presence of suicide risk remained associated with the outcome (ß = 0.173; p = 0.007), low levels of GSH at 18 months after postpartum. Likewise, we verified the difference in GSH levels according to the degree of suicide risk, observing a significant association between the differences in glutathione means in the group of women with moderate to high risk compared to the reference group (no suicide risk) (p = 0.009). Conclusion: Our findings suggest that GSH may be a potential biomarker or etiologic factor in women at moderate to high risk of suicide.

Postpartum depression in maternal thyroidal changes.

Evidence in the literature has suggested that there may be an association between thyroid antibodies and depression during pregnancy and in the postpartum period. Thus, this study aims to conduct a systematic review on the prevalence of postpartum depression (PPD) in women with thyroid abnormalities during pregnancy or in the postpartum period. For this review, we used four databases (PubMed, Lilacs, Scielo, and Scopus). Fifteen studies were selected; one study used a case-control design, four used a cross-sectional design and ten utilized prospective cohort designs. All studies were restricted to up to 1 year postpartum, and 46.7% focused on a period between immediate postpartum and 6 months postpartum. Estimates of the prevalence of PPD in pregnant women with thyroid disorders ranged between 8.3% and 36.0%. For follow-up studies, the cumulative incidence of self-reported depression from the primary episode in the first postpartum year was 6.3% in a high-city survey. Although some authors consider the status of positive anti-TPO antibodies to be a possible marker of vulnerability to depression , it is not yet possible to conclude whether thyroid function in the pregnancy-puerperal cycle is involved with the development of PPD.

Can mHealth interventions contribute to increased HPV vaccination uptake? A systematic review.

The objective of this review was to synthesize existing evidence on mobile health (mHealth) interventions geared at improving HPV related knowledge, HPV vaccination intent and HPV vaccination uptake. Between November and December 2019, systematic searches were performed in the databases PubMed, Ebsco/CINAHL, Ebsco/PsycINFO, and Clarivate Analytics/Web of Science Social Science Citation Index (SSCI). We identified 805 articles of which 92 were eligible for inclusion after abstract screening. 19 articles met the inclusion criteria of the review based on full article review and all but one of the included interventions were conducted in the United States. mHealth interventions ranged from text messages, phone calls to interactive voice recordings and software on tablets. All four interventions which attempted to improve HPV knowledge and vaccination intent, reported positive findings, however, only two interventions reported statistically significant improvements between intervention and control groups. 14 interventions reported an increase in HPV vaccination uptake and vaccination series completion among the intervention groups; including when mHealth interventions were compared to control groups or non-mHealth interventions. Some factors noted in the successful interventions included frequency of messages, combinations of multiple interventions including in-person education session, written educational materials, texts alongside call or emails; tailored messages as well as participant's intent to vaccinate at baseline. mHealth interventions potentially show promise as tools in improving short-term vaccination knowledge, intent, and uptake of HPV vaccination. There is however a need to refine components which can promote mHealth interventions' success as well as for the evaluation of such interventions in different contexts and over time.

Engineering NK Cells for CAR Therapy-Recent Advances in Gene Transfer Methodology.

The development of chimeric antigen receptor (CAR) T cell therapy has introduced a new and effective strategy to guide and promote the immune response against tumors in the clinic. More recently, in an attempt to enhance its utility, this method has been expanded to novel cell types. One of the more successful variants has proven to be the expression of CARs in Natural Killer (NK) cells (CAR-NK). Gene engineering NK cells to express an exogenous CAR receptor allows the innate anti-tumor ability of NK cells to be harnessed and directed against a target tumor antigen. In addition, the biology of NK cells allows the development of an allogeneic cell therapeutic product useable with most or all patient haplotypes. NK cells cause little or no graft versus host disease (GvHD) and are therefore suitable for development of an "off the shelf" therapeutic product. Initial trials have also shown that CAR-NK cells rarely cause cytokine release syndrome. However, despite their potential NK cells have proven to be difficult to engineer, with high sensitivity to apoptosis and low levels of gene expression. The creation of optimized methods to introduce genes into NK cells will promote the widespread application of CAR-NK in research laboratories and the clinics.

Factors associated with the level of backrest elevation in a thoracic cardiovascular intensive care unit.

BACKGROUND: Ventilator-associated pneumonia is a complication of mechanical ventilation that is associated with increased length of stay, morbidity, mortality, and costs. Evidence-based guidelines to reduce the risk of ventilator-associated pneumonia recommend use of 30º to 45º backrest elevation. Despite recommendations, patients continue to be cared for in positions with a lower backrest elevation. Hemodynamic stability may be a factor in the lack of adherence, yet few data exist to confirm this hypothesis. OBJECTIVE: To determine the relationship between backrest elevation and hemodynamic instability among patients in a thoracic cardiovascular intensive care unit. METHODS: A sample of 100 patients was studied. Patients were randomly selected by time of day. A protractor was used to measure patients' backrest elevation. Mean blood pressure, time of day, and fluid and vasopressor use also were recorded. RESULTS: Lower backrest elevation was associated with use of vasopressors (P = .001). Patients who received hemodynamic support also had a lower backrest elevation than did patients not receiving these therapies (mean, 19º vs 26º ; P = .01). Patients with a mean blood pressure of 64 mm Hg or less had a mean backrest elevation of 17º versus 24º for patients with a mean blood pressure greater than 65 mm Hg (P = .01). Back-rest elevations did not differ between shifts. CONCLUSION: That backrest elevation is associated with lower mean blood pressure and vasopressor use suggests that nurses are not adhering to recommended levels of backrest elevation so as to maintain hemodynamic stability. Further studies are needed to elucidate reasons for lack of adherence to recommended levels of backrest elevation.

Avaliação do equilíbrio corporal na doença de Parkinson / Physical equilibrium evaluation in Parkinson disease

Introdução: A doença de Parkinson pode estar entre as múltiplas causas de alterações no equilíbrio corporal. Objetivo: Dessa forma, o estudo tem por objetivo avaliar o equilíbrio corporal de parkinsonianos. Método: Estudo prospectivo do qual participaram doze indivíduos com doença de Parkinson que foram avaliados através de testes de equilíbrio estático e dinâmico, posturografia dinâmica e vectoeletronistagmografia. Para comparar os resultados da posturografia dinâmica, foi utilizado um grupo controle pareado. Resultados: Foram encontradas alterações nas provas de Romberg-Barré, Untemberg e Marcha. O exame vestibular revelou seis casos normais, quatro síndrome vestibular central e dois casos de síndrome vestibular periférica. Na posturografia dinâmica, verificou-se alteração no equilíbrio quando comparados ao grupo controle em todos os Testes de Organização Sensorial, na média e na utilização do sistema vestibular. Conclusão: Pacientes parkinsonianos apresentam alteração do equilíbrio corporal. A posturografia dinâmica foi mais sensível ao detectar as alterações de equilíbrio que a vectoeletronistagmografia.

Introduction: The Parkinson disease can be among the multiple causes of alterations in the physical equilibrium. Accordingly, this study has the objective to evaluate Parkinson patients' physical equilibrium. Method: Potential study in which 12 Parkinson individuals were evaluated by way of tests of static and dynamic equilibrium, dynamic posturography and vectoelectronystagmograph. To compare the dynamic posturography results a group of gauged control was used. Results: Alterations in Romberg-Barré, Unterberger and Walk tests were found. The vestibular exam revealed 06 normal cases, 04 central vestibular syndrome and 02 cases of peripheral vestibular syndrome. In the dynamic posturography, an equilibrium alteration has been verified, when compared to the control group in all Sensorial Organization Tests, in average and in the utilization of vestibular system. Conclusion: Parkinson patients present a physical equilibrium alteration. The dynamic posturography was more sensitive to detect the equilibrium alterations than vectoelectronystagmograph.

Balance assessment in alcoholic subjects.

UNLABELLED: Alcoholism is a chronic condition, consisting on a state of intoxication caused by the consumption of alcohol beverages. Frequently found signs and symptoms are: gait instability, dizziness and lack of psychomotor coordination, among others. AIM: To study the influence of alcoholism on postural balance. MATERIALS AND METHODS: This is a prospective study. The sample comprehended 32 individuals in the experimental group, members of the Alcoholic Anonymous Group of the city of Santa Maria-RS and 32 non-alcoholic individuals making up the control group. The individuals were submitted to an otorhinolaryngological evaluation, static and dynamic balance study and cerebellar tests, vecto-electro-nystagmographic evaluation and dynamic posturography. RESULTS: We noticed that the vectoelectronystagmography was normal for most of the individuals in the experimental group, indicating that the labyrinth and the oculomotor-vestibular pathways were normal and that the balance disorder they presented would stem from the dysfunction in other areas of the central or peripheral nervous system. In the dynamic posturography we noticed that alcoholics who were not drinking presented significant alterations in their postural balance when compared to non-alcoholic individuals. CONCLUSION: Alcoholic beverages have a deleterious influence on body balance.

Avaliação do equilíbrio em alcoólicos / Balance assessment in alcoholic subjects

O alcoolismo é uma doença crônica que consiste em um estado de intoxicação causado pelo consumo de álcool. Os sinais e sintomas frequentemente encontrados são entre outros: instabilidade ao andar, tontura e descoordenação psicomotora. OBJETIVO: Verificar a influência do alcoolismo no equilíbrio postural. MATERIAL E MÉTODOS: Este é um estudo prospectivo; a amostra compreendeu 32 indivíduos para o grupo experimental, frequentadores do grupo de Alcoólicos Anônimos da cidade de Santa Maria-RS e 32 indivíduos não alcoólicos para o grupo controle. Os indivíduos foram submetidos à avaliação otorrinolaringológica, avaliação do equilíbrio estático e dinâmico e provas cerebelares, avaliação vectoeletronistagmográfica e posturografia dinâmica. RESULTADOS: Constatou-se que a vectoeletronistagmografia mostrou-se normal na maioria dos indivíduos do grupo experimental, indicando que o labirinto e as vias vestíbulo-oculomotoras estariam normais e que o distúrbio do equilíbrio por eles apresentado seria decorrente de disfunção em outras áreas do sistema nervoso central ou periférico. Na posturografia dinâmica constatou-se que alcoólicos abstinentes apresentam alterações significantes do equilíbrio postural quando comparados com indivíduos não alcoólicos. CONCLUSÃO: O álcool tem influência deletéria no equilíbrio corporal.

Alcoholism is a chronic condition, consisting on a state of intoxication caused by the consumption of alcohol beverages. Frequently found signs and symptoms are: gait instability, dizziness and lack of psychomotor coordination, among others. AIM: to study the influence of alcoholism on postural balance. MATERIALS AND METHODS: this is a prospective study. The sample comprehended 32 individuals in the experimental group, members of the Alcoholic Anonymous Group of the city of Santa Maria-RS and 32 non-alcoholic individuals making up the control group. The individuals were submitted to an otorhinolaryngological evaluation, static and dynamic balance study and cerebellar tests, vecto-electro-nystagmographic evaluation and dynamic posturography. RESULTS: we noticed that the vectoelectronystagmography was normal for most of the individuals in the experimental group, indicating that the labyrinth and the oculomotor-vestibular pathways were normal and that the balance disorder they presented would stem from the dysfunction in other areas of the central or peripheral nervous system. In the dynamic posturography we noticed that alcoholics who were not drinking presented significant alterations in their postural balance when compared to non-alcoholic individuals. CONCLUSION: alcoholic beverages have a deleterious influence on body balance.

Hearing and vestibular complaints during pregnancy.

UNLABELLED: Hormonal dysfunctions in women during pregnancy can cause vestibular and/or cochlear disorders. AIM: to study hearing and vestibular complaints in pregnant women. MATERIAL AND METHOD: this is a prospective study. 82 pregnant women participated on this study. For hearing and vestibular complaints, a questionnaire proposed by Castagno (1994) was employed. RESULTS: we could observe that tinnitus was the main auditory complaint (33%), although with no differences between the groups. Tinnitus was present among 52.44% of the pregnant women, mainly in the Group 2. According to symptoms related to dizziness, vertigo was the main auditory complaint in first trimester, whereas instability and gait unbalance were more frequent in the second trimester, and instability and tendency to fall in the third trimester. Nausea was the main symptom associated with dizziness in pregnant women, being more frequent in the first trimester of gestation. CONCLUSIONS: women during gestation have auditory and vestibular complaints, mainly dizziness and tinnitus.

Queixas auditivas e vestibulares durante a gestação / Hearing and vestibular complaints during pregnancy

As disfunções hormonais presentes na mulher durante a gravidez podem causar desordens vestibulares e/ou cocleares. Objetivo: Verificar a ocorrência de queixas auditivas e vestibulares em gestantes. Material e método: Este é um estudo prospectivo no qual participaram 82 gestantes. Para pesquisa das queixas auditivas e vestibulares foi aplicado às gestantes o Protocolo de Anamnese proposto por Castagno (1994). Resultados: Pode-se observar que o zumbido foi a queixa auditiva mais citada (33 por cento), sem diferença entre os trimestres gestacionais. A queixa de tontura esteve presente em 52,44 por cento das gestantes e principalmente no primeiro trimestre gestacional. Quanto aos sintomas relacionados à tontura, no primeiro trimestre o mais frequente foi a vertigem, já no segundo trimestre gestacional foi a instabilidade e o desequilíbrio ao caminhar e no terceiro trimestre gestacional foi a instabilidade seguida da tendência a cair. A náusea é o principal sintoma associado à tontura nas gestantes, sendo mais frequente no primeiro trimestre gestacional. Conclusão: Mulheres durante a gestação referem queixas auditivas e vestibulares, principalmente tontura e zumbido.

Hormonal dysfunctions in women during pregnancy can cause vestibular and/or cochlear disorders. AIM: to study hearing and vestibular complaints in pregnant women. Material and method: this is a prospective study. 82 pregnant women participated on this study. For hearing and vestibular complaints, a questionnaire proposed by Castagno (1994) was employed. Results: we could observe that tinnitus was the main auditory complaint (33 percent), although with no differences between the groups. Tinnitus was present among 52.44 percent of the pregnant women, mainly in the Group 2. According to symptoms related to dizziness, vertigo was the main auditory complaint in first trimester, whereas instability and gait unbalance were more frequent in the second trimester, and instability and tendency to fall in the third trimester. Nausea was the main symptom associated with dizziness in pregnant women, being more frequent in the first trimester of gestation. Conclusions: women during gestation have auditory and vestibular complaints, mainly dizziness and tinnitus.

Investigação genética da surdez hereditária: mutação do gene da Conexina 26: [revisão] / Genetic investigation of hereditary deafness: connexin 26 gene mutation: [review]

Nos últimos anos houve grande progresso na localização de genes associados à deficiência auditiva hereditária, possibilitando diagnósticos cada vez mais precisos e precoces. Mutações no gene da Conexina 26 (GJB2 - Cx26) causam deficiência auditiva. Pela facilidade e benefício do rastreamento de mutações no gene GJB2, o teste genético está se tornando um importante recurso na saúde pública. O objetivo foi realizar pesquisa bibliográfica sobre a mutação do gene da Conexina 26 e sua influência na audição. Foi realizado um levantamento bibliográfico por meio de busca eletrônica utilizando os descritores: perda auditiva, genética, triagem genética, Conexina 26, nas bases de dados MEDLINE, SciELO e LILACS, desde a década de 90 até os dias atuais. Concluiu-se que a mutação 35delG da Conexina 26 está potencialmente vinculada a alguns casos de perda auditiva não esclarecida. A pesquisa desta mutação poderia ser incluída na bateria de exames de investigação etiológica da surdez indeterminada, uma vez que esclarece a etiologia de alguns casos e a sua identificação possibilita o aconselhamento genético.

In the last few years, great progress has been made in the search for genes associated to hereditary hearing impairment, allowing more precise and earlier diagnosis. Connexin 26 gene mutations (GJB2 - Cx26) cause hearing impairment. Due to the easiness and benefits of the screening of mutations on the gene GJB2, genetic testing is becoming an important resource in public health. The aim of the present study was to conduct a literature research about the mutation of the Connexin 26 gene and its influence in hearing. It was carried out a literature review through electronic search using the keywords: hearing loss, genetics, genetic screening, and Connexin 26, at the databases MEDLINE, SciELO and LILACS, from the 90s to the present days. The results indicate that the 35delG mutation of Connexin 26 is potentially associated to some cases of hearing loss that were not justified. The research regarding this mutation could be included in the battery of tests for etiologic investigation of undetermined deafness, possibly elucidating the etiology of some cases and allowing genetic counseling.

Ileorectal anastomosis. Experimental study in rats

To evaluate the evolution of ileorectal anastomoses, 20 male Wistar-TECPAR rats aged 120 days and weighing on average 274,5 g were divided at random into two groups of 10 animals each. The rats in group A were submitted to total colectomy and end-to-end anastomosis. The rats in group B were submitted to segmental resection of the left colon and end-to-end anastomosis. When the animals were sacrificed on the 14th postoperative day, group A animals were found to have lost more weight than group B animals (p = 0,01). Neither group showed dehiscence or peritonitis, but adhesions were present in both groups. Bursting pressure was lower in A rats (p < 0,05). Hydroxyproline content was lower in A rats but the difference was not significant and tissue protein was lower in group B (p < 0,05). Histologic evolution was similar in both groups. The conclusion was reached that the ileorectal anastomosis was not better than colorectal anastomosis in rats.

Ligamentos coracoacromial e coracoumeral: aspectos anatômicos, microscópicos e relevância clínico-cirúrgica / Coracoacromial and coracohumeral ligaments: anatomic and microscopic aspects and clinical surgical relevance

Os ligamentos coracoacromial e coracoumeral foram estudados sob o ponto de vista macroscópico e microscópico. Foram dissecados 20 ombros em 12 cadáveres (cinco frescos e sete formolizados). O ligamento coracoacrominal apresenta largura média de 24,70mm na origem, 14,55mm na sua inserçäo e 36,25mm de comprimento. A distância média entre o topo do processo coracóide e o acrômio anterior é de 42,55mm. Este ligamento é um dos elementos que formam o arco acromial. Possui estrutura histológica típica ligamentar composta por tecido conjuntivo denso ordenado. O ligamento coracoumeral se origina de uma distância média de 10,10mm do topo do processo coracóide; largura de 15,60mm na sua origem e de 23,95mm na sua inserçäo; 19,60mm de comprimento. É um limitador da rotaçäo externa do ombro. Näo apresenta estrutura histológica típica ligamentar.