Does the use of intra-alveolar honey after lower third molar extraction reduce postoperative inflammatory complications? A systematic review and meta-analysis.

BACKGROUND: Protocols are currently being studied in preventing postoperative complications after exodontia. PURPOSE: This systematic review and meta-analysis aims to evaluate whether the application of intra-alveolar honey reduces inflammatory complications after the extraction of mandibular third molars (CRD 42.023.467.041). METHODS: Searches were carried out in six electronic databases. Clinical trials comparing intra-alveolar honey administration with non-intervention or placebo after mandibular third molar extraction were selected to assess their impact on postoperative inflammatory parameters. The Cochrane ROB 2 tool was used to assess the bias risk in included studies, Stata software to conduct a meta-analysis for quantitative synthesis, and the GRADE system to evaluate the certainty of the evidence. RESULTS: This systematic review included 5 studies with 330 participants, and two studies were included in the meta-analysis. The results of the meta-analysis demonstrated that postoperative pain on the second day [MD: - 1.05; 95% CI - 2 to - 0.1] and fifth day [MD: - 0.97; 95% CI - 1.97 to - 0.03] was lower in the honey group compared to the control group. Total analgesic consumption [MD: - 4.77; 95% CI - 6.73 to - 2.81] was also lower in patients in the intervention group. The descriptive results indicated that honey appears to be beneficial in controlling edema, reducing trismus, and improving healing after extraction of third molars. Alveolar osteitis showed inconclusive results. CONCLUSIONS: The use of intra-alveolar honey after extraction of mandibular third molars seem to be associated with pain reduction. For the other outcomes, the results remain uncertain.

Physicochemical characterization of the brown pigment produced by Azospirillum brasilense HM053 using tryptophan as precursor.

Microorganisms are known to be a promising source of biopigments because they are easy to obtain, can be produced on a commercial scale, and are environmentally friendly. Therefore, the aim of this work was to characterize a brown pigment (BP) produced by HM053 in NFbHPN-lactate medium. The BP was extracted from the pellet (BPP) or supernatant (BPS), in the presence (BPPTrp, BPSTrp) or absence (BPPw, BPSw) of tryptophan (Trp). The UV-vis results were similar among all BP samples and compared with commercial melanin used as a standard, and the maximum absorption was observed around 200-220 nm. FTIR spectra showed that BP and commercial melanin had slight differences, with a small band between 3000-2840 cm- 1, related to C-H in the CH2 and CH3 aliphatic groups, which is not observed in the commercial melanin. Between BPP and BPS showed a different structure with bands in the region 1230-1070 cm- 1 related to groups C-O. The thermogravimetric curves for BPSw and BPSTrp showed similar behavior, with 4 stages of mass loss. The similarity between BPPw and BPPTrp with 2 stages of mass loss was also observed. Scanning electron microscopy results showed morphological differences between BPP and BPS, where BPP had a physical structure more homogeneous and a regular flat surface, while the BPS physical structure did not seem homogeneous and the surface was uneven with some spherical structures as commercial melanin.

Reciprocal and Differential Influences of Mediterranean Diet and Physical Activity on Adiposity in a Cohort of Young and Older than 40 Years Adults.

Translational research has documented the conjoint beneficial relationships between dietary and physical activity habits concerning weight maintenance. However, the precise interplay between diet and exercise impacting body composition remains unclear, challenging personalized interventions. This study aimed to explore potential interactions and effect modifications of these factors affecting the body mass index (BMI) within an online adult cohort. Data from 11,883 NUTRiMDEA cohort participants were analyzed in this cross-sectional study, categorizing individuals by age, sex, and BMI using linear regression models to assess the interactions between lifestyle factors and adiposity. Significant differences emerged in anthropometry, lifestyle, and health-related quality of life (HRQoL) across categories. The combined effect of diet and physical activity had a greater impact on BMI than physical activity or Mediterranean diet adherence alone, with lower BMI as physical activity levels increased (ß: -0.5) and adherence to the Mediterranean diet decreased, where a modification effect between them was identified (ß: -0.28). Participants with lower Mediterranean diet adherence displayed superior BMI when physical activity was low, but when activity levels were higher, their BMI aligned with those with healthier dietary habits. An interaction link between lifestyle factors and BMI was found, showing the differential effects of the Mediterranean diet and physical activity combination concerning adiposity.

A flow cytometry-based assay to measure neutralizing antibodies against SARS-CoV-2 virus.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has highlighted the need for serological assays that can accurately evaluate the neutralizing efficiency of antibodies produced during infection or induced by vaccines. However, conventional assays often require the manipulation of live viruses on a level-three biosafety (BSL3) facility, which presents practical and safety challenges. Here, we present a novel, alternative assay that measures neutralizing antibodies (NAbs) against SARS-CoV-2 in plasma using flow cytometry. This assay is based on antibody binding to the S protein and has demonstrated precision in both intra- and inter-assay measurements at a dilution of 1:50. The cut-off was determined using Receiver Operating Characteristic (ROC) analysis and the value of 36.01% has shown high sensitivity and specificity in distinguishing between pre-pandemic sera, COVID-19 patients, and vaccinated individuals. The efficiency significantly correlates with the gold standard test, PRNT. Our new assay offers a safe and efficient alternative to conventional assays for evaluating NAbs against SARS-CoV-2.

Efeito positivo da perda moderada de peso por intervenção nutricional nos componentes do domínio de frequência em pacientes de alto risco cardiovascular e regime multimedicamentoso / Positive effect of moderate weight loss through nutritional intervention on frequency domain components in patients at high cardiovascular risk and multidrug regimen

INTRODUÇÃO: Intervenções para o tratamento da obesidade, incluindo a mudança de hábitos de vida, que incluam a melhora de hábitos alimentares, de sedentarismo e de saúde mental, são evidenciados como benéficos para prevenção e tratamento de doenças cardiovasculares e melhora da função autonômica do coração. OBJETIVO: Avaliar a efetividade de um programa de reeducação alimentar e melhoria de qualidade de vida sobre os indicadores de adesão às orientações dietéticas, o estilo de vida, variáveis antropométricas e a função autonômica do coração. MÉTODOS: Pacientes com obesidade de ambos os sexos, encaminhados a um ambulatório de nutrição de um Instituto de Cardiologia para emagrecimento, foram acompanhados mensalmente, durante 3 meses. Foram aplicados dois questionários para avaliar as mudanças no estilo de vida (IPAQ-versão reduzida e PHQ-9), e foi realizado o eletrocardiograma para avaliação da Variabilidade da Frequência Cardíaca (VFC), antes e após o período de acompanhamento. ESTATÍSTICA: As variáveis categóricas foram expressas como frequência e comparadas pelo teste do Qui-quadrado. As variáveis numéricas foram expressas como média ± EPM e intervalo de 95% de confiança de Wald, foram usadas equações de estimação generalizadas (EEG). Todos os testes estatísticos foram bicaudais e o nível de significância adotado foi P< 0,05. RESULTADOS: Foram avaliados 24 pacientes com obesidade (IMC > 30kg/ m2 ), com idade média de 62 anos (min ­ máx: 42 ­ 80 anos, DP: 10 anos). A adesão aos hábitos alimentares saudáveis teve aumento médio de 21,3% para 66,5% (P< 0,001). O IPAQ demonstrou que, ao final do estudo houve aumento da prática de atividade física (P=0,023), e houve redução significativa no escore de PHQ-9 após a intervenção (P=0,022), indicando melhora na saúde mental dos pacientes. Notou-se que o programa de intervenção foi eficaz em reduzir significativamente o peso corporal (média de 5,4%) comparado ao período basal (P=0,043), IMC (P=0,029) e a circunferência da cintura (P=0,031). Foi identificada existência de associação entre a variação de perda de peso e de diminuição do IMC com as variabilidades observadas nos componentes do domínio da frequência, tanto entre os indivíduos adultos (P=0,003), quanto entre indivíduos idosos (P=0,034). CONCLUSÕES: A intervenção em qualidade de vida e reeducação alimentar utilizada no presente estudo foi capaz de promover a melhora tanto na saúde mental quanto o aumento da atividade física dos pacientes, redução dos parâmetros antropométricos e a melhora na VFC, especificamente nos componentes do domínio da frequência.

Relação entre a ingestão energético-proteica e a prevalência de risco nutricional em pacientes com síndrome cardiorrenal / Relationship between energy-protein intake and the prevalence of nutritional risk in patients with cardiorenal syndrome

INTRODUÇÃO: A doença renal crônica (DRC) é frequente nos pacientes com insuficiência cardíaca (IC), associação denominada síndrome cardiorrenal (SCR). A abordagem nutricional no tratamento da SCR envolve o controle da ingestão proteica e sódio, da ingestão hídrica, do diabetes mellitus e dislipidemias, correção da anemia e da acidose metabólica e adequação da oferta energético-proteica na restrição de volume. Em conjunto às restrições na terapia nutricional na SCR, os pacientes apresentam menor ingestão alimentar devido sintomas como náuseas e anorexia, além de outras alterações no trato gastrintestinal, (compressão gástrica, congestão hepática, edema de alças intestinais) as quais reduzem sua capacidade absortiva. Por esses e outros fatores, a desnutrição é comum nesses pacientes e o estado nutricional (EN) é um fator de risco crítico para o desenvolvimento e prognóstico da IC. Devido à relação entre o EN e a ingestão alimentar, o objetivo deste estudo foi avaliar a ingestão calórico- -proteica de pacientes com SCR e a sua relação com o EN. MÉTODOS: Foram selecionados 32 pacientes em consulta de retorno no ambulatório de nutrição em hospital de cardiologia, que já haviam recebido plano alimentar previamente. Identificamos o EN e consumo alimentar através do recordatório de 24 horas. Para os parâmetros de ingestão calórico-proteica e o EN, foi realizada a correlação de Pearson com nível de significância de 5%. RESULTADOS: Os parâmetros do EN mais sensíveis para a detecção de risco ou presença de desnutrição foram a dobra cutânea tricipital, área muscular do braço, circunferência muscular do braço e a avaliação subjetiva global. Não foi encontrada correlação significativa entre os dados de ingestão calórico-proteica e EN. Em relação ao consumo alimentar, 81,25% dos pacientes apresentaram baixa ingestão calórica e 56,25% elevada ingestão proteica. Foi encontrada correlação negativa (-0,427; p=0,038) entre a água intracelular e a ingestão hídrica. CONCLUSÃO: Apesar de não encontrarmos correlação significativa entre a ingestão energético- -proteica e EN, os dados do presente estudo corroboram com os achados da literatura, que abordam a questão da desnutrição e do desequilíbrio na ingestão alimentar nessa população. Ressalta-se a importância de associar diferentes ferramentas a avaliação do EN e do consumo alimentar, para obter uma relação mais concisa entre esses dois grupos de variáveis.

Recent advances in dental zirconia: 15 years of material and processing evolution.

OBJECTIVES: The objective was to discuss the research on zirconia published in the past 15 years to help the dental materials community understand the key properties of the types of zirconia and their clinical applications. METHODS: A literature search was performed in May/2023 using Web of Science Core Collection with the term "dental zirconia". The search returned 5102 articles, which were categorized into 31 groups according to the research topic. RESULTS: The current approach to improving the translucency of zirconia is to decrease the alumina content while increasing the yttria content. The resulting materials (4Y-, 5Y-, and above 5 mol% PSZs) may contain more than 50% of cubic phase, with a decrease in mechanical properties. The market trend for zirconia is the production of CAD/CAM disks containing more fracture resistant 3Y-TZP at the bottom layers and more translucent 5Y-PSZ at the top. Although flaws located between layers in multilayered blocks might represent a problem, newer generations of zirconia layered blocks appear to have solved this problem with novel powder compaction technology. Significant advancements in zirconia processing technologies have been made, but there is still plenty of room for improvement, especially in the fields of high-speed sintering and additive manufacturing. SIGNIFICANCE: The wide range of zirconia materials currently available in the market may cause confusion in materials selection. It is therefore imperative for dental clinicians and laboratory technicians to get the needed knowledge on zirconia material science, to follow manufacturers' instructions, and to optimize the design of the prosthetic restoration with a good understanding where to reinforce the structure with a tough and strong zirconia.

Harmonizing color measurements in dentistry using translucent tooth-colored materials.

BACKGROUND: Since color measurements are relative, the discrepancy among different instruments is alarmingly high. This multicenter study evaluated the effectiveness of instrument calibration and inter-instrument harmonization of different spectrophotometers with the same optical geometry using tooth-colored, translucent dental materials. METHODS: The coordinating center (CC) spectrophotometer was calibrated using the NPL Ceram Series II set. Two sets of 10 specimens, labeled 1 to 10 and I to X (10 mm in diameter and 1 mm thick), were tested at CC and three research sites (RS1, RS2, and RS3) using the same d/8° optical geometry spectrophotometers. Calibration factors were calculated for each material and site to obtain the average calibration factors for sets 1-10, set I-X, and the combination of both. The differences among the non-corrected and corrected reflection values were calculated using CIEDE2000 (DeltaE00) and CIELAB (DeltaEab) color difference formulas and were submitted to ANOVA and Tukey test (α = 0.05). RESULTS: A significant decrease of color differences between non-corrected as compared to corrected measurements was recorded for all CC-RS and RS-RS comparisons. The reduction of DeltaE00 values between non-corrected and corrected for CC-RS1, CC-RS2, and CC-RS3 were 83.1%, 77.2%, and 73.6%, respectively. The corresponding DeltaE00 values for RS1-RS2, RS1-RS3, and RS2-RS3 comparisons, indirectly compared in the experiment, were 84.2%, 82.8%, and 68.5%, respectively. There was a significant reduction of DeltaE00 and DeltaEab color difference for all combined RS pairs and each of three RS pairs, corrected with one of two specimen sets calibration factors separately. CONCLUSIONS: Calibration and harmonization of color measurements in dentistry using tooth-colored, translucent restorative materials significantly decreased measurement discrepancies between the coordinating center and research sites and among pairs of research sites.

An 18-day, 3 °C cold treatment effectively kills Ceratitis capitata (Diptera: Tephritidae) in kiwifruit (Actinidia spp.).

A series of experiments were carried out to develop a phytosanitary disinfestation protocol to kill Ceratitis capitata (Weidemann) (Mediterranean fruit fly, Diptera: Tephritidae) in 'Hayward' kiwifruit (Actinidia deliciosa (A. Chev.) C.F. Liang and A.R. Ferguson) and 'Zesy002' kiwifruit (Actinidia chinensis Planch.). Experiments on 4 immature life stages (eggs and 3 larval instars) with treatment durations of between 5 and 18 days showed that third instars were the most tolerant to temperatures around 3 °C, with the lethal time to 99.9968% (probit 9) mortality (LT99.9968) estimated to be 17.3 days (95% confidence interval (CI) 16.4-18.2). Larvae reared and treated in 'Zesy002' were significantly more susceptible to cold treatment than those reared in 'Hayward'. A large-scale trial testing a disinfestation protocol of 3 ±â€…0.5 °C for 18 days treated over 500,000 third-instar C. capitata with no survivors. These results demonstrate that a cold treatment of 3.5 °C or below for 18 days induces C. capitata mortality in kiwifruit at a rate that exceeds 99.9968% with a degree of confidence greater than 99%.

Salivary proteomic profile of response to different resistance training protocols: A case report.

Resistance training (RT) with blood flow restriction (BFR) or high intensity (HI) are effective to increase muscle mass. To understand this effect, techniques known as "omics" are used to identify possible biomarkers. This study analyzed the salivary proteomic profile of healthy individuals trained before and after two RT protocols both designed with eight exercises for upper- and lower-limbs, one performed at low percentage of one-maximum repetition (%1RM) with BFR technique, and other at high %1RM (HI) without BRF technique. Four healthy males between 18 and 28 years participated in the study. Stimulated saliva was collected before (BBFR/BHI) and immediately after (ABFR/AHI) the two RT protocols. All protein-related processing was performed using label-free proteomic. The difference in expression between groups was expressed as p < .05 for downregulated proteins and 1-p > .95 for upregulated proteins. There was difference in salivary flow between ABFR and BBFR (p = .005). For HI, 87 proteins were found after the practice and 119 before. Three hemoglobin isoforms were increased in AHI compared with BHI. In the BFR comparison, 105 proteins were identified after (ABFR) and 70 before (BBFR). Among those increased ABFR, we highlight five hemoglobin isoforms and Deleted in malignant brain tumors 1 protein. Between ABFR and AHI, 17 isoforms of histones, Transaldolase, Transketolase, Glyceraldehyde-3-phosphate dehydrogenase, and Antileukoproteinase were decreased ABFR. For HI, there was an increase in proteins related to oxidative stress and metabolism of the musculoskeletal system, compared with BFR. HI seems to induce higher anabolic signaling to muscle mass increase and antiatherosclerotic effects.

Influence of the DASH Diet on Gestational Weight Gain and Perinatal Outcomes in Women with Pre-Existing Diabetes Mellitus: A Randomized, Single-Blind, Controlled Clinical Trial.

BACKGROUND: This study aimed to investigate the influence of the dietary approaches to stop hypertension (DASH) diet on gestational weight gain and perinatal outcomes in pregnant women with pre-existing diabetes mellitus (PDM). METHODS: A randomized, single-blind, controlled clinical trial was conducted with 68 pregnant women with PDM throughout prenatal care until delivery (18 weeks) at a public maternity hospital in Rio de Janeiro, Brazil (2016-2020). The standard diet adopted by the control group (standard diet group-SDG) contained 45-55% carbohydrates, 15-20% protein, and 25-30% lipids of the total energy intake. An adapted DASH diet, with a similar macronutrient composition, but with higher calcium, potassium, magnesium, fiber, and reduced saturated fat, was prescribed for the intervention group (DASH diet group-DDG). Student's t- or Mann-Whitney U tests were used to compare outcomes between groups. To assess the trajectory of gestational weight gain throughout the intervention between the study groups, linear mixed-effects regression models were used. RESULTS: The DDG had lower gestational weight gain at the fifth (p = 0.03) and seventh appointment (p = 0.04), with no difference in average total gestational weight gain (SDG: 10 kg [SD = 4]; DDG: 9 kg [SD = 5], p = 0.23). There was a trend for a lower length of stay of the newborns (p = 0.08) in the DDG without differences for other perinatal outcomes. CONCLUSIONS: The DASH diet promoted less variation in gestational weight gain without promoting a difference in total gestational weight gain, and there was no difference between the study groups for perinatal outcomes.

ß-Glucosidase activity and antimicrobial properties of potentially probiotic autochthonous lactic cultures.

Background: The demand for lactic acid bacteria products, especially probiotics, has increased. Bacteria that increase polyphenol bioavailability and act as bio preservatives are sought after. This study aims to identify autochthonous lactic acid cultures from EMBRAPA that demonstrate ß-glucosidase activity and inhibitory effect on microbial sanitary indicators. Methods: Cell-free extracts were obtained by sonicating every 5 s for 40 min. The extracts were mixed with cellobiose and incubated at 50 °C. The reaction was stopped by immersing the tubes in boiling water. The GOD-POD reagent was added for spectrophotometer readings. Antimicrobial activity was tested against reference strains using the agar well diffusion method. Lactic cultures in MRS broth were added to 0.9 cm wells and incubated. The diameter of the inhibition zones was measured to determine the extension of inhibition. Results: Only L. rhamnosus EM1107 displayed extracellular ß-glucosidase activity, while all autochthonous strains except L. plantarum CNPC020 demonstrated intracellular activity for this enzyme. L. plantarum CNPC003 had the highest values. On the other hand, L. plantarum CNPC020, similarly to L. mucosae CNPC007, exhibited notable inhibition against sanitary indicators. These two strains significantly differed from the other five autochthonous cultures regarding S. enterica serovar Typhimurium ATCC 14028 inhibition (P < 0.05). However, they did not differ from at least one positive control in terms of inhibition against S. aureus ATCC 25923 and E. coli ATCC 25922 (P > 0.05). Therefore, it is advisable to consider these cultures separately for different technological purposes, such as phenolics metabolism or bio preservative activity. This will facilitate appropriate selection based on each specific property required for the intended product development.

Nitric Oxide Detection Using a Chemical Trap Method for Applications in Bacterial Systems.

Plant growth-promoting bacteria (PGPB) can be incorporated in biofertilizer formulations, which promote plant growth in different ways, such as fixing nitrogen and producing phytohormones and nitric oxide (NO). NO is a free radical involved in the growth and defense responses of plants and bacteria. NO detection is vital for further investigation in different agronomically important bacteria. NO production in the presence of KNO3 was evaluated over 1-3 days using eight bacterial strains, quantified by the usual Griess reaction, and monitored by 2,3-diaminonaphthalene (DAN), yielding 2,3-naphthotriazole (NAT), as analyzed by fluorescence spectroscopy, gas chromatography-mass spectrometry, and high-performance liquid chromatography. The Greiss and trapping reaction results showed that Azospirillum brasilense (HM053 and FP2), Rhizobium tropici (Br322), and Gluconacetobacter diazotrophicus (Pal 5) produced the highest NO levels 24 h after inoculation, whereas Nitrospirillum amazonense (Y2) and Herbaspirillum seropedicae (SmR1) showed no NO production. In contrast to the literature, in NFbHP-NH4Cl-lactate culture medium with KNO3, NO trapping led to the recovery of a product with a molecular mass ion of 182 Da, namely, 1,2,3,4-naphthotetrazole (NTT), which contained one more nitrogen atom than the usual NAT product with 169 Da. This strategy allows monitoring and tracking NO production in potential biofertilizing bacteria, providing future opportunities to better understand the mechanisms of bacteria-plant interaction and also to manipulate the amount of NO that will sustain the PGPB.

Erratum: Effect of the Dietary Approaches to Stop Hypertension (DASH) diet on the development of preeclampsia and metabolic outcomes in pregnant women with pre-existing diabetes mellitus: a randomized, controlled, single-blind trial - CORRIGENDUM.

[This corrects the article DOI: 10.1017/jns.2023.54.].

Effect of the Dietary Approaches to Stop Hypertension (DASH) diet on the development of preeclampsia and metabolic outcomes in pregnant women with pre-existing diabetes mellitus: a randomised, controlled, single-blind trial.

Preeclampsia (PE) affects up to five times more women with pre-existing diabetes mellitus (PDM) than women without it. The present study aimed to identify the effect of the DASH diet on PE incidence (primary outcome) and blood pressure, glycated haemoglobin (GH), serum lipids, glutathione peroxidase (GP), C-reactive protein (CRP - secondary outcomes) in pregnant with PDM. This randomised, controlled, single-blind trial studied sixty-eight pregnant women with PDM throughout prenatal care until delivery (18 weeks) at a public maternity hospital, Brazil. The standard diet group (SDG) received a diet containing 45-65 % carbohydrates, 15-20 % protein and 25-30 % lipids. The DASH diet group (DDG) received the adapted DASH diet with a similar macronutrient distribution, but with a higher concentration of fibres, unsaturated fats, calcium, magnesium and potassium as well as lower saturated fat. Student's t, Mann-Whitney U and the Chi-square tests were used to compare outcomes. PE incidence was 22⋅9 % in the SDG and 12⋅1 % in the DDG (P = 0⋅25). GP levels significantly increased in the DDG (intra-group analysis; mean difference = 1588 [CI 181, 2994], P = 0⋅03) and tended to be different from the variation in the SDG (mean difference = -29⋅5 [CI -1305; 1⋅365]; v. DDG: 1588 [CI 181; 2994], P = 0⋅09). GH levels decreased significantly and similarly between groups (SDG: -0⋅61 [CI -0⋅26, -0⋅96], P = 0⋅00) v. DDG: -1⋅1 [CI -0⋅57, -1⋅62], P = 0⋅00). There was no evidence of a difference in PE incidence at the end of the intervention between the two diets. The DASH diet seems to favour PE-related biochemical markers.

SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.

Predictive factors of weight at birth of newborns of adult women with pregestational Diabetes Mellitus : A retrospective observational study.

AIMS: To identify predictive factors of birth weight (BW) of newborns of women with pregestational diabetes mellitus (DM). METHODS: Retrospective observational study with data from pregnant women who started prenatal nutritional monitoring up to 28 weeks, single pregnancy, and BW information. Quantitative variables were analyzed, and mean and standard deviation (SD) measures or medians and interquartile ranges (IQR) were calculated. Predictive factors were identified using multivariate linear regression. RESULTS: Eighty-six pregnant women were analyzed, 50% were diagnosed with type 1 DM, 46.5% with type 2 DM, and 3.5% with unclassified DM; 41% were mixed black and white, 35.6% had overweight and 33.3% had pregestational obesity. The mean BW was 3313.93 g (SD = 696.08). The predictive factors identified were: gestational weight gain (GWG) at the 3rd trimester (ß=60.42; p = 0.04), and gestational age at delivery (ß=194.03; p < 0.001); adjusted by time of diagnosis of DM (p = 0.07) and 1st-trimester glycated hemoglobin (p = 0.71). CONCLUSION: The best predictors of BW were gestational age at birth and maternal anthropometric gestational characteristics, which are modifiable variables. The results may contribute to a review of the prenatal routines of pregnant women with DM.

A Pilot Study of Dietetic, Phenotypic, and Genotypic Features Influencing Hypertensive Disorders of Pregnancy in Women with Pregestational Diabetes Mellitus.

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and perinatal morbimortality. Dietetic, phenotypic, and genotypic factors influencing HDP were analyzed during a nutrigenetic trial in Rio de Janeiro, Brazil (2016-2020). Pregnant women with pregestational diabetes mellitus (n = 70) were randomly assigned to a traditional or DASH diet group. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured during prenatal visits and HDP were diagnosed using international criteria. Phenotypic data were obtained from medical records and personal interviews. Genotyping for FTO and ADRB2 polymorphisms used RT-PCR. Linear mixed-effect models and time-to-event analyses were performed. The variables with significant effect on the risk for progression to HDP were: black skin color (adjusted hazard ratio [aHR] 8.63, p = 0.01), preeclampsia in previous pregnancy (aHR 11.66, p < 0.01), SBP ≥ 114 mmHg in the third trimester (aHR 5.56, p 0.04), DBP ≥ 70 mmHg in the first trimester (aHR 70.15, p = 0.03), mean blood pressure > 100 mmHg (aHR 18.42, p = 0.03), and HbA1c ≥ 6.41% in the third trimester (aHR 4.76, p = 0.03). Dietetic and genotypic features had no significant effect on the outcome, although there was limited statistical power to test both.

Small molecule glucagon release inhibitors with activity in human islets.

Purpose: Type 1 diabetes (T1D) accounts for an estimated 5% of all diabetes in the United States, afflicting over 1.25 million individuals. Maintaining long-term blood glucose control is the major goal for individuals with T1D. In T1D, insulin-secreting pancreatic islet ß-cells are destroyed by the immune system, but glucagon-secreting islet α-cells survive. These remaining α-cells no longer respond properly to fluctuating blood glucose concentrations. Dysregulated α-cell function contributes to hyper- and hypoglycemia which can lead to macrovascular and microvascular complications. To this end, we sought to discover small molecules that suppress α-cell function for their potential as preclinical candidate compounds. Prior high-throughput screening identified a set of glucagon-suppressing compounds using a rodent α-cell line model, but these compounds were not validated in human systems. Results: Here, we dissociated and replated primary human islet cells and exposed them to 24 h treatment with this set of candidate glucagon-suppressing compounds. Glucagon accumulation in the medium was measured and we determined that compounds SW049164 and SW088799 exhibited significant activity. Candidate compounds were also counter-screened in our InsGLuc-MIN6 ß-cell insulin secretion reporter assay. SW049164 and SW088799 had minimal impact on insulin release after a 24 h exposure. To further validate these hits, we treated intact human islets with a selection of the top candidates for 24 h. SW049164 and SW088799 significantly inhibited glucagon release into the medium without significantly altering whole islet glucagon or insulin content. In concentration-response curves SW088799 exhibited significant inhibition of glucagon release with an IC50 of 1.26 µM. Conclusion: Given the set of tested candidates were all top hits from the primary screen in rodent α-cells, this suggests some conservation of mechanism of action between human and rodents, at least for SW088799. Future structure-activity relationship studies of SW088799 may aid in elucidating its protein target(s) or enable its use as a tool compound to suppress α-cell activity in vitro.

The harmful acute effects of clomipramine in the rat liver: Impairments in mitochondrial bioenergetics.

Clomipramine, a tricyclic antidepressant used to treat depression and obsessive-compulsive disorder, has been linked to a few cases of acute hepatotoxicity. It is also recognized as a compound that hinders the functioning of mitochondria. Hence, the effects of clomipramine on mitochondria should endanger processes that are somewhat connected to energy metabolism in the liver. For this reason, the primary aim of this study was to examine how the effects of clomipramine on mitochondrial functions manifest in the intact liver. For this purpose, we used the isolated perfused rat liver, but also isolated hepatocytes and isolated mitochondria as experimental systems. According to the findings, clomipramine harmed metabolic processes and the cellular structure of the liver, especially the membrane structure. The considerable decrease in oxygen consumption in perfused livers strongly suggested that the mechanism of clomipramine toxicity involves the disruption of mitochondrial functions. Coherently, it could be observed that clomipramine inhibited both gluconeogenesis and ureagenesis, two processes that rely on ATP production within the mitochondria. Half-maximal inhibitory concentrations for gluconeogenesis and ureagenesis ranged from 36.87 µM to 59.64 µM. The levels of ATP as well as the ATP/ADP and ATP/AMP ratios were reduced, but distinctly, between the livers of fasted and fed rats. The results obtained from experiments conducted on isolated hepatocytes and isolated mitochondria unambiguously confirmed previous propositions about the effects of clomipramine on mitochondrial functions. These findings revealed at least three distinct mechanisms of action, including uncoupling of oxidative phosphorylation, inhibition of the FoF1-ATP synthase complex, and inhibition of mitochondrial electron flow. The elevation in activity of cytosolic and mitochondrial enzymes detected in the effluent perfusate from perfused livers, coupled with the increase in aminotransferase release and trypan blue uptake observed in isolated hepatocytes, provided further evidence of the hepatotoxicity of clomipramine. It can be concluded that impaired mitochondrial bioenergetics and cellular damage are important factors underlying the hepatotoxicity of clomipramine and that taking excessive amounts of clomipramine can lead to several risks including decreased ATP production, severe hypoglycemia, and potentially fatal outcomes.