Impact of Bariatric Surgery on Thyroid Morphology and Thyroid Function.

INTRODUCTION: Few studies have evaluated the impact of bariatric surgery (BS) on thyroid function and morphology, and how it correlates to inflammatory and metabolic markers. We aimed to evaluate all those parameters together. METHODS: A longitudinal study included 70 patients with severe obesity. The bariatric group (BG) enrolled 40 patients who underwent BS, and the control group (CG) enrolled 30 patients who did not undergo BS. Both were submitted (pre- and 2nd-year) to thyroid ultrasound and laboratory analyses to determine the levels of thyroid hormones, inflammatory, and metabolic markers. RESULTS: Thyroid volume (TV) decreased after BS (-1.5 cm3), differing significantly from the CG (+0.6 cm3; p = 0.003). ΔTV was independently and positively correlated with ΔHOMA-IR (0.41 (0.11/7.16) p = 0.007) and ΔIL6 (0.02 (0.01/0.3) p = 0.016). A nonsignificant correlation between ΔTV and ΔBMI was detected (0.38 (-0.01/0.09) p = 0.152). We also observed a negative correlation between ΔTV and ΔTSH (-2.03 (-2.87/-1.19) p = 0.000) and ΔT3/T4 ratio (-0.06 (-0.09/-0.02) p = 0.001). TSH had a nonsignificant reduction with BS (-0.3872 vs. -0.2483 p = 0.128). The conversion of T4 to T3 had a significant increase after BS, as demonstrated by the T3/T4 ratio (+5.16 p = 0.01). Despite an increase in the prevalence of thyroid nodules in the BG, it was not statistically significant (p = 0.340). CONCLUSION: BS was associated with a reduction in TV and a nonstatistically significant reduction in TSH. The variations in TV were related to the metabolic markers and inflammatory changes. An increase in the conversion of T4 to T3 with BS was detected, possibly related to inflammatory improvement.

Severe type 2 diabetes (T2D) remission using a very low-calorie ketogenic diet (VLCKD).

Summary: There is a close association between obesity and type 2 diabetes (T2D). The value of weight loss in the management of patients with T2D has long been known. Loss of 15% or more of body weight can have a disease-modifying effect in people with diabetes inducing remission in a large proportion of patients. Very low-carbohydrate ketogenic diets (VLCKDs) have been proposed as an appealing nutritional strategy for obesity management. The diet was shown to result in significant weight loss in the short, intermediate, and long terms and improvement in body composition parameters as well as glycemic and lipid profiles. The reported case is a 35-year-old man with obesity, dyslipidemia, and T2D for 5 years. Despite the use of five antidiabetic medications, including insulin, HbA1c was 10.1%. A VLCKD through a commercial multidisciplinary weight loss program (PnK method) was prescribed and all medications were discontinued. The method is based on high-biological-value protein preparations and has 5 steps, the first 3 steps (active stage) consist of a VLCKD (600-800 kcal/d) that is low in carbohydrates (<50 g daily from vegetables) and lipids. The amount of proteins ranged between 0.8 and 1.2 g/kg of ideal body weight. After only 3 months, the patient lost 20 kg with weight normalization and diabetes remission, and after 2 years of follow-up, the patient remained without the pathologies. Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity. Learning points: Obesity and type 2 diabetes (T2D) are conditions that share key pathophysiological mechanisms. Loss of 15% or more of body weight can have a disease-modifying effect in people with T2D inducing remission in a large proportion of patients. Diabetes remission should be defined as a return of HbA1c to <6.5% and which persists for at least 3 months in the absence of usual glucose-lowering pharmacotherapy. The very low-carbohydrate ketogenic diet (VLCKD) is a nutritional approach that has significant beneficial effects on anthropometric and metabolic parameters. Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity.

Effectiveness and Safety of a Very Low-Calorie Ketogenic Diet on Weight Regain Following Bariatric Surgery.

PURPOSE: Obesity is one of the major public health problems worldwide and bariatric surgery is considered the gold standard treatment for severe obesity. Although the literature supports the safety and efficacy of the very low-calorie ketogenic diet (VLCKD) in patients with obesity, there is no study analyzing the use in case of failure or weight regain after bariatric surgery. This work has the purpose of assessing the response to a VLCKD (Pnk® method) in this population. METHODS: We have conducted an observational, retrospective, and descriptive study with the analysis of medical charts of private offices where patients were examined between 2014 and 2019, totalizing 11 participants who underwent Roux-en-Y gastric bypass (RYGB) without a reduction of 50% in body weight excess or any weight regain after the surgery. The patients followed the first stage of a commercial weight loss program (Pnk® method) which consists of a VLCKD (600-800 kcal/day), low in carbohydrates and lipids. RESULTS: A significant reduction was observed (p-value < 0.05) in weight, body mass index (BMI), abdominal circumference (AC), and glycated hemoglobin (A1C) post-ketogenic diet. Uric acid, transaminases, urea, and creatinine values did not show differences between pre- and post-ketosis. During the course of the study, no serious adverse events were reported. CONCLUSION: This study has shown that the ketogenic diet can be recommended as an effective and safe treatment for patients who progressed with insufficient weight loss or regain after bariatric surgery.

Cloud-point extraction associated with voltammetry: preconcentration and elimination of the sample matrix for trace determination of methyl parathion in honey.

This work presents the association of cloud point extraction (CPE) and electroanalysis for the selective and sensitive determination of methyl parathion (MP) in honey. The CPE step provided the pre-concentration of MP from a complex sample, in which the optimized extraction parameters (Triton X-100 concentration of 0.75% w/v, NaCl concentration of 1.0% w/v and heating time of 30 min) were investigated using a factorial design (23). The detection of MP was performed using a cathodically pre-treated boron-doped diamond (BDD) working electrode and square wave voltammetry (SWV), after a suitable dilution of the CPE extract in Britton-Robinson buffer pH 6.0 as the supporting electrolyte. MP presented three electrochemical processes over the BDD surface, but only the reduction peak at around -0.7 V was monitored for the MP determination (higher detectability). Improved reproducibility was reached by applying an in situ cleaning step (+2.0 V for 15 s) followed by a re-activation process (-2.0 V for 15 s) between measurements. Using the optimized variables, a linear range between 0.1 and 2.0 µmol L-1 was obtained for MP with a limit of detection of 0.006 µmol L-1, a 6-fold lower value when compared with the value attained without the CPE step. The experimental enrichment factor of MP was 6.1. Also, the optimized CPE allowed the determination of MP in honey samples with good accuracy (recovery between 94 and 106%), which was not possible using direct detection (without CPE) due to the matrix interference. This is the first paper that demonstrates the combination of CPE and electroanalysis for the determination of an organic compound.

Transposon-mediated generation of CAR-T cells shows efficient anti B-cell leukemia response after ex vivo expansion.

CAR-T-cell therapy has shown considerable advance in recent years, being approved by regulatory agencies in US, Europe, and Japan for the treatment of refractory patients with CD19+ B-cell leukemia or diffuse large B-cell lymphoma. Current methods for CAR-T-cell production use viral vectors for T-cell genetic modification and can take up to 15 days to generate the infusion product. The development of simple and less costly manufacturing protocols is needed in order to meet the increasing demand for this therapy. In this present work, we generated 19BBz CAR-T cells in 8 days using a protocol based on the non-viral transposon-based vector Sleeping Beauty. The expanded cells display mostly a central memory phenotype, expressing higher levels of inhibitory receptors when compared with mock cells. In addition, CAR-T cells were cytotoxic against CD19+ leukemia cells in vitro and improved overall survival rates of mice xenografted with human RS4;11 or Nalm-6 B-cell leukemias. Infused CAR-T cells persisted for up to 28 days, showing that they are capable of long-term persistence and antitumor response. Altogether, these results demonstrate the effectiveness of our protocol and pave the way for a broader application of CAR-T-cell therapy.

Utility of center of pressure measures during obstacle crossing in prediction of fall risk in people with Parkinson's disease.

INTRODUCTION: Postural instability during walking and tripping over obstacles are the main causes of falls in people with Parkinson's disease (PD). Preliminary limited evidence suggests that the length of the prospective follow-up period affects falls prediction in PD, with shorter periods leading to more accurate prediction. Thus, the primary aim of the present study was to test the performance of center of pressure (CoP) variables during obstacle crossing to predict fall risk in people with PD during subsequent periods of four, six, and 12 months. We also compared CoP variables during obstacle crossing between fallers and non-fallers. METHODS: Forty-two individuals with PD, in mild to moderate stages, completed the baseline obstacle crossing assessment and reported falls for 12 months. Participants walked at their self-selected pace and were instructed to cross an obstacle (half knee height) positioned in the middle of an 8-m long pathway. A force platform was used to analyze CoP parameters of the stance phase of the trailing limb (most affected limb). The ability of each outcome measure to predict fall risk at four, six, and 12 months was assessed using receiver operating characteristic curve analyses. RESULTS: Ten individuals (23.8%) were considered fallers at four months, twelve individuals (28.5%) at six months, and twenty-one individuals (50%) at 12 months. CoP amplitude and CoP velocity in the mediolateral direction significantly predicted fall risk at four, six, and 12 months. As judged by the area under the curve, mediolateral CoP velocity showed the best performance at four months, while mediolateral CoP amplitude showed the best performance at six months. Fallers presented greater values of mediolateral CoP velocity and amplitude than non-fallers. CONCLUSION: These findings suggest that mediolateral CoP velocity and amplitude during obstacle crossing might be useful to predict fall risk in people with PD. Therefore, larger studies are encouraged.

CAR T Cells Generated Using Sleeping Beauty Transposon Vectors and Expanded with an EBV-Transformed Lymphoblastoid Cell Line Display Antitumor Activity In Vitro and In Vivo.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of cancer is now an approved treatment for B cell malignancies. However, the use of viral vectors to provide long-term CAR expression is associated with high production costs and cumbersome quality controls, impacting the final cost of CAR T cell therapies. Nonviral integrative vectors, such as Sleeping Beauty (SB) transposons, provide an alternative to modify primary T cells. Therefore, we developed a protocol to expand SB-transfected 19BBζ CAR T cells using a lymphoblastoid cell line, and evaluated T cell phenotype as well as function along the T cell expansion. Electroporation of PBMCs with transposon plasmid decreased cell viability on day 1 but had a minor impact on the frequency of memory subpopulations when compared to mock condition. CAR+ lymphocytes showed increased proliferation compared to mock control and high cytotoxic activity towards CD19+ cells without significant differences in exhaustion markers expression. Moreover, CAR+ lymphocytes showed an increased frequency by the end of the stimulation cycle compared with day 1, suggesting that CAR expression confers a selective proliferation advantage. Immunodeficient NOD scid gamma chain knockout (NSG) mice engrafted with the human pre-B leukemic cell line RS4;11 and treated with 19BBζ CAR T cells showed improved overall survival when compared to mock T cells treated animals. The results showed that electroporation using the SB system is a simple and affordable method for inducing long-term CAR expression in T lymphocytes. Expansion of gene-modified T cells with the lymphoblastoid cell line provided up to 2 cycles of stimulations, generating effective T cells against leukemia in vitro and in vivo.

The effects of habitual footwear in gait outcomes in people with Parkinson's disease.

BACKGROUND: Gait is impaired in individuals with Parkinson's disease (PD). Although the effect of habitual footwear on gait spatiotemporal parameters has already been established in neurologically healthy individuals, its effects on people with PD is unknown. RESEARCH QUESTION: This study aimed to investigate the impact of habitual footwear on the step spatiotemporal parameters in people with PD. METHODS: Sixteen individuals with PD (G-PD) and 15 neurologically healthy individuals (G-HC) were assessed. Participants walked on an 8 m long pressure sensitive walkway at their preferred speed with and without their habitual footwear (3 trials per condition). Footwear included flip-flops, shoes, sneakers and sandals. The average, variability and asymmetry for step length, width, duration, and velocity and the percentage time in the swing and stance phases were calculated. RESULTS: The results showed in both groups a reduced percentage time in the swing phase and an increased step width, duration and length with footwear (F(1,29)>5.64; p<0.02). Additionally, habitual footwear increased step width variability in G-PD and G-HC (F(1,29)=3.97; p=0.06). Interestingly, only G-HC showed a higher step length asymmetry in the footwear condition than in the barefoot condition (p=0.02). Finally, only when habitual footwear was used, G-HC showed a higher step velocity asymmetry than G-PD (p=0.04). SIGNIFICANCE: These results indicate a negative influence of footwear on gait spatiotemporal parameters in both groups. Furthermore, footwear induced differences between groups. These findings indicate that footwear use is an influencing factor in studies comparing people with PD and healthy elderly. Further data are needed before definitive recommendations are made.

Influence of Parkinson's Disease on Judging Stair Step Height: Exploratory Study.

This study investigated the effects of Parkinson's Disease (PD) on the perceptive judgment of stair step height using both exteroceptive visual and exproprioceptive judgments. We invited 14 individuals with PD and 14 neurologically healthy older adults (OA) to perform perceptual judgment tasks for first step stairway heights of 11 and 20 cm. Initially, participants performed first the exteroceptive visual judgment and then the exproprioceptive judgment in five randomized trials for each stair height. An analysis of variance for the exteroceptive visual judgment revealed no main effects or interaction between PD versus OA groups and height. However, the analysis of variance for exproprioceptive judgment revealed a significant interaction between group and height ( F1,26 = 9.519; p = .005; Pη2 = .268) such that both groups made more errors in exproprioceptive judgment at a height of 11 cm. The OA group made more errors in exproprioceptive judgment for the 20-cm step when compared with the PD group ( p = .016) but the PD group underestimated the step height. We conclude that PD influences exproprioceptive perception of step height and that steps with smaller (vs. larger) heights induce greater exproprioceptive error.

Avaliação da atividade antibacteriana dos extratos metanólico e hexânico do caule folhado de Melissa Officinalis / Evaluation of the Antibacterial Activity of Methanolic and Hexanic Extracts of Puff Pastry Stem, Melissa Officinalis / Evaluación de la actividad antibacterial de extractos metanol y hexano, el tallo rodadura Melissa Officinalis

Introdução: Melissa officinalis, da família Lamiaceae, é uma erva comumente utilizada na medicina popular. É conhecida no Brasil como Melissa, erva cidreira, cidrilha e melitéia. Tendo em vista que M.officinalis L é largamente utilizada na medicina popular, dentre elas para uso antibacteriano, este trabalho teve como principal objetivo avaliar a atividade antibacteriana e modulatória de extratos metanólico e hexânico do caule folhado de M. officinalis frente a cepas de bactérias padrões e multirresistentes. Materiais e métodos: Os extratosmetanólico e hexânico do caule folhado de M. officinalis L foram analisados para a atividade antibacteriana por meio de teste de microdiluição para determinação de concentração inibitória mínima (CIM) e modulação de aminoglicosídeos (gentamicina e amicacina). Resultados: Na avaliação DACIM foram obtidos resultados ≥1024 μg/mLcontra as bactérias (Escherichia coli e Staphylococcus aureus) em ambos extratos. O extrato metanólico mostrou resultados relevantes em associação com gentamicina potencializando o efeito contra E. coli e S. aureus quando associado à amicacina, nesta bactéria houve antagonismo. Já o extrato hexânico, resultou em uma redução da CIM de amicacina e gentamicina frente a linhagens de E. coli, mostrando efeito antagonista com a amicacina conta cepas de S. aureus. Conclusão: Conclui-se que o material vegetal influencia no comportamento dos antimicrobianos, tornando este trabalho importante como parâmetro para estudos mais aprofundados que possam combater a crescente resistência de bactérias patogênicas.

Introduction: Melissa officinalis, of the Lamiaceae family, is a herb commonly used on folk medicine. In Brazil it is known as Melissa, erva cidreira, cidrilha and meliteia. Considering that the M. Officinalis L is widely used in folk medicine, as for antibacterial use, among others, the main objective of this work was to evaluate the antibacterial and modulating activity of methanolic and hexanic extracts of M. officinalis L against pattern and multidrug resistant bacterial strains. Material and methods: The methanolic and hexanic extracts of the stem of puff pastry of M. officinalis L were analized to determine antibacterial activity by using the microdiluition for establishing the minimal inibitory concentration (MIC) and aminoglycosides (gentamicin and amikacin) modulation. Results: In the MIC evaluation, the results obtained were ≥1024 μg/mL against bacteria (Escherichia coli and Staphylococcus aureus) in both extracts. The methanolic extract showed important results when associated with gentamicin, since it potentiates its effect against E. coli and S. aureus when associated with amikacin, where antagonism was found. As to the hexanic extract, it showed a MIC reduction of amikacin and gentamicin against S. aureus strains. Conclusion: It was concluded that the plant material influences the antimicrobial behavior, a fact that makes this study an important parameter to deeper studies to combat the increase of pathogenic multidrug-resistant bacteria.

Introducción: Melissa Officinalis, de la familia Lamiaceae, es una hierba utilizada en la medicina popular. Es conocido en Brasil como erva cidreira, melisa, y melitéia cidrilha. Teniendo en cuenta que M. Officinalis L. se utiliza ampliamente en la medicina popular, entre ellos para uso antibacteriano, este trabajo tuvo como objetivo evaluar la actividad antibacteriana y modulador de extracto de metanol y hexano rodar el tallo de M. officinalis L. frente a las cepas de bacterias normas y las bacterias multirresistentes. Materiales y métodos: se analizó el extracto de metanol y hexano del tallo rodadura M. Officinalis L. para la actividad antibacteriana por una prueba de microdilución para la determinación de la Concentración Mínima Inhibitoria (MIC) y la modulación de aminoglucósidos (gentamicina y amikacina). Resultados: en la evaluación de la MIC los resultados obtenidos fueron ≥1024 μg/ml con contra las bacterias (Escherichia coli y Staphylococcus aureus) en ambos extractos. El extracto de metanol mostró resultados significativos en combinación con efecto potenciador gentamicina contra E. coli y s. Aureus cuando se combina con amikacina, esta bacteria era antagonismo. Ya extracto de hexano dio lugar a una reducción de la MIC de amikacina y gentamicina contra cepas de E. coli, que muestra el efecto antagónico con cepas de la cuenta de amikacina de S. Aureus. Conclusión: se concluye que el material vegetal influye en el comportamiento de los antimicrobianos, lo que hace este trabajo importante como parámetro para futuros estudios que puedan combatir la creciente resistencia de las bacterias.