Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).

Downregulation of hsa-miR-100-5p May Be a Protective Factor in the Early Stages of Nephropathy in Type 1 Diabetes Mellitus.

Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.

Wideband, Wearable, Printed Monopole Antenna System for Integration into an Electromagnetic Radiation Evaluation Device.

This paper describes the design steps carried out to prove the concept of a wideband monopole antenna system to be used in a wearable device conceived for the evaluation of electromagnetic field radiation. Such a device is envisaged to be integrated into protective vests worn by professional users in their working space environment as part of intelligent multi-risk protection. Initially, the main characteristics of a simple straight monopole are reviewed to serve as a reference. A modified octagonal monopole antenna element is introduced, and a two dual-linearly polarized configuration of such monopoles is designed, fabricated, and tested to be used in the frequency range of 0.7-3.5 GHz. The expected radiation characteristics (input reflection coefficient and isolation between vertically and horizontally polarized ports) are confirmed experimentally. The effects of a thick lossy foam substrate layer used to mitigate the presence of the metal shield, employed in the vest lining as a Faraday cage protection, are analyzed both by simulation and experimentally. Finally, electromagnetic simulations are carried out to confirm that a system of five dual-linearly polarized monopole elements located in the chest, shoulders, back, and helmet of the user can provide an adequate estimation of the incident electromagnetic field radiation.

Peripheral arterial disease progression and ankle brachial index: a cohort study with newly diagnosed patients with type 2 diabetes.

BACKGROUND: Little is known about the evolution of peripheral arterial disease (PAD) since diagnosis and its association with glycemic and lipid control in patients with Type 2 Diabetes Mellitus (T2DM). OBJECTIVE: Evaluate the actual criteria to start screening PAD with ankle-brachial index (ABI) in T2DM patients and assess its progression and relationship with glycemic and lipid control since diagnosis. METHODS: We performed a 3-year prospective cohort study with two groups: group 1 (978 individuals with T2DM undergoing drug treatment) and group 2 [221 newly diagnosed drug-naive (< 3 months) patients with T2DM]. PAD diagnosis was by ABI ≤ 0.90, regardless any symptoms. RESULTS: As expected, abnormal ABI prevalence was higher in group 1 vs. Group 2 (87% vs. 60%, p < 0.001). However, abnormal ABI prevalence did not differ between patients over and under 50 years in both groups. Our drug-naive group stabilizes ABI (0.9 ± 0.1 vs 0.9 ± 0.1, p = NS) and improved glycemic and lipid control during follow-up [glycated hemoglobin (HbA1c) = 8.9 ± 2.1 vs 8.4 ± 2.3%, p < 0.05; LDL = 132 ± 45 vs 113 ± 38 mg/dL, p < 0.01, respectively]. When compared, patients who evolved with normalization or maintained normal ABI levels at the end [Group A, N = 60 (42%)] with those who decreased ABI to abnormal levels (ABI basal 1.0 ± 0.1 vs final 0.85 ± 0.1, p < 0.001) [Group B, N = 26 (18%)], an improvement in HbA1c (9 ± 2 vs 8 ± 2%, p < 0.05) and a correlation between the final HbA1c with ABI (r = - 0.3, p = 0.01) was found only in the first. In addition, a correlation was found between albuminuria variation and ABI solely in group A (r = - 0.3; p < 0.05). CONCLUSION: Our study suggests that ABI should be measured at diagnosis in T2DM patients, indicating that current criteria to select patients to screen PAD with ABI must be simplified. An improvement in albuminuria and glycemic and lipid control could be related with ABI normalization in newly diagnosed T2DM drug-naive patients.

Urorectal fistula repair using different approaches: operative results and quality of life issues.

PURPOSE: To evaluate efficacy of urorectal fistula (URF) repair using different approaches and the clinical factor determinant of success, and also the morbidity associated to the procedure and health-related quality of life (HRQoL) in male survivors of pelvic malignancies. MATERIAL AND METHODS: Retrospective evaluation of 39 patients with URF primarily intervened in three institutions using different surgical approaches. Success was defined as effective fistula closure. Variables evaluated included demographics, previous treatments, surgical approach, ancillary surgeries, complications and HRQoL by using a standardized non-validated specific questionnaire. Median follow-up from surgery to interview was 55 months (interquartile range 49, range 4-112). Factors determinant of success were investigated using logistic regression. Safety of the procedure was evaluated by Clavien-Dindo scale. Deterioration of continence and erectile function and other HRQoL issues were evaluated. RESULTS: Prostate cancer treatment was the predominant etiology. The success rate for fistula repair was 89.5%. The surgical approach was not related to failed repair (p=0.35) or complications (p=0.29). Factors associated with failure were complications (p=0.025), radiotherapy (p=0.03), fistula location (p=0.04) and fistula size (p=0.007). Multivariate analysis revealed fistula size was the only independent determinant of failure (OR 6.904, 1.01-47.75). Complications occurred in 46.2% and severe complications in 12.8%. The mortality related to the procedure was 2.6%. Urinary incontinence was present before repair in 26.3% and erectile dysfunction in 89.5%. Fistula repair caused de novo urinary incontinence in 7.9% and deterioration of erectile status in 44.7%. Globally 79% were satisfied after repair and only 7.9% rated HRQoL as unhappy. Trans-sphincteric approach was related to less deterioration of erectile function (p=0.003), and higher perceived satisfaction in QoL (p=0.04). CONCLUSIONS: The surgical approach elected to correct URF is not determinant of success nor of complications. Fistula size appears as independent determinant for failure. Trans-sphincteric approach could be advantageous over other procedures regarding HRQoL issues.

Transurethral ventral buccal mucosa graft inlay for treatment of distal urethral strictures: international multi-institutional experience.

PURPOSE: To critically evaluate a multi-institutional patient cohort undergoing single-stage distal urethral repair using a novel transurethral buccal mucosa graft inlay urethroplasty technique (TBMGI). METHODS: A retrospective multi-institutional review of consecutive patients with fossa navicularis (FN) strictures treated with a single-stage TBMGI technique at 12 institutions from March 2014-March 2018 was performed. Patient demographics, stricture characteristics, clinical and patient-reported outcomes were analyzed. The primary outcomes were stricture recurrence and complications. Secondary outcomes were change in maximum urinary flow rate (Qmax), PVR, and changes in IPSS, SHIM and global response assessment (GRA) questionnaire responses. Descriptive statistical analysis was used for evaluation of outcomes. RESULTS: Sixty-eight men met inclusion criteria. Median age and stricture length were 60 years (IQR 48-69) and 2 cm (IQR 2-3), respectively. Most common stricture etiology was lichen sclerosus (34%). Median operative time and EBL were 72 min (IQR 50-120) and 20 mL (IQR 10-43), respectively. Fifty-seven men completed ≥ 12-month follow-up. At a median follow-up of 17 months (IQR 13-22), 54 patients (95%) remained stricture-free. Median Qmax improved from 5 to 18 mL/s (p < 0.0001), PVR 76-21 mL (p < 0.0001), and IPSS 15-5 (p < 0.0001); IPSS-QOL score: 5-1 (p < 0.0001). SHIM score did not significantly change following repair (median 22-21 p = 0.85). On GRA assessment, a majority of men reported "marked" (64%) or "moderate" (28%) overall improvement. No patient developed fistula, glanular dehiscence, graft necrosis or chordee. CONCLUSIONS: This novel minimally invasive transurethral urethroplasty technique is feasible and has demonstrated generalizable outcomes in a multi-institutional cohort with varying etiologies.

Development of an Anthropomorphic Phantom of the Axillary Region for Microwave Imaging Assessment.

We produced an anatomically and dielectrically realistic phantom of the axillary region to enable the experimental assessment of Axillary Lymph Node (ALN) imaging using microwave imaging technology. We segmented a thoracic Computed Tomography (CT) scan and created a computer-aided designed file containing the anatomical configuration of the axillary region. The phantom comprises five 3D-printed parts representing the main tissues of interest of the axillary region for the purpose of microwave imaging: fat, muscle, bone, ALNs, and lung. The phantom allows the experimental assessment of multiple anatomical configurations, by including ALNs of different size, shape, and number in several locations. Except for the bone mimicking organ, which is made of solid conductive polymer, we 3D-printed cavities to represent the fat, muscle, ALN, and lung and filled them with appropriate tissue-mimicking liquids. Existing studies about complex permittivity of ALNs have reported limitations. To address these, we measured the complex permittivity of both human and animal lymph nodes using the standard open-ended coaxial-probe technique, over the 0.5 GHz-8.5 GHz frequency band, thus extending current knowledge on dielectric properties of ALNs. Lastly, we numerically evaluated the effect of the polymer which constitutes the cavities of the phantom and compared it to the realistic axillary region. The results showed a maximum difference of 7 dB at 4 GHz in the electric field magnitude coupled to the tissues and a maximum of 10 dB difference in the ALN response. Our results showed that the phantom is a good representation of the axillary region and a viable tool for pre-clinical assessment of microwave imaging technology.

Health-related quality of life in people with type 1 Diabetes Mellitus: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: Type 1 Diabetes Mellitus (Type 1 DM) affects the psychological and emotional well-being of patients and their families. This study aims to evaluate the health- related quality of life (HRQoL) of people with Type 1 DM in Brazil, a country of continental proportions, using the EuroQol questionnaires. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group, by analyzing EuroQol scores from 3,005 participants with Type 1 DM, in 28 public clinics in Brazil. Data on demography, economical status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: The assessment of HRQoL by the EuroQol showed that the average score assigned to general health in Brazil is markedly lower than those found in two other Type 1 DM population-based studies conducted in Europe (EQ-VAS from the Netherlands, the United Kingdom and Brazil were 80.8 ± 15.2, 75.1 ± 18.4 and 72.5 ± 22, respectively). Additionally, our data suggest that a better glycemic control could positively impact the HRQoL of people with Type 1 DM, implying that each 1 % reduction in glycated haemoglobin might lead to an increase of 1.5 points in general health status assessed by the EuroQol. CONCLUSIONS: This is a population-based study evaluating the HRQoL of people with Type 1 DM in Brazil. Our data indicate a worse quality of health of people with Type 1 DM in Brazil in comparison to Europe, and suggest that a better glycemic control could positively impact the HRQoL of these individuals. However, this study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of these people.

Aqueous extract of Swietenia macrophylla leaf exerts an anti-inflammatory effect in a murine model of Parkinson's disease induced by 6-OHDA.

Introduction: Parkinson's disease affects 2% of the population aged over 65 years and is the second most common neurodegenerative disorder in the general population. The appearance of motor symptoms is associated with the degeneration of dopaminergic neurons in the nigrostriatal pathway. Clinically significant nonmotor symptoms are also important for severe disability with disease progression. Pharmacological treatment with levodopa, which involves dopamine restitution, results in a temporary improvement in motor symptoms. Among the mechanisms underlying the pathogenesis of the disease are exacerbated oxidative stress, mitochondrial dysfunction, and neuroinflammation. A phytochemical prospecting study showed that the aqueous extract of the leaves from Swietenia macrophylla (Melineaceae), known as mahogany, has polyphenols with antioxidant and anti-inflammatory capacity in a significantly higher percentage than leaf extracts from other Amazonian plants. Furthermore, the antioxidant and anti-inflammatory capacity of aqueous extract of mahogany leaf has already been demonstrated in an in vitro model. In this study, we hypothesized that the aqueous extract of mahogany leaf (AEML) has a neuroprotective effect in a murine model of Parkinson's disease induced by 6-hydroxidopamine (6-OHDA), due to antioxidant and anti-inflammatory properties of its phenolic compounds. Methods: Mice were treated daily with the mahogany extract at a dose of 50 mg/kg, starting 7 days before 6-OHDA infusion until post-surgery day 7. Results and discussion: The animals from the 6-OHDA/mahogany group, which corresponds to animals injected with the toxin and treated with aqueous extract of the mahogany leaf, presented distinct behavioral phenotypes after apomorphine challenge and were therefore subdivided into 2 groups, 6-OHDA/mahogany F1 and 6-OHDA/mahogany F2. The F1 group showed a significant increase in contralateral rotations, whereas the F2 group did not show rotations after the apomorphine stimulus. In the F1 group, there was an increase, although not significant, in motor performance in the open field and elevated plus maze tests, whereas in the F2 group, there was significant improvement, which may be related to the lesser degree of injury to the nigrostriatal dopaminergic pathway. The TH+ histopathological analysis, a dopaminergic neuron marker, confirmed that the lesion to the nigrostriatal dopaminergic pathway was more pronounced in 6-OHDA/mahogany F1 than in 6-OHDA/mahogany F2. Our main result consisted of signs of improvement in the inflammatory profile in both the F1 and F2 6-OHDA/mahogany groups, such as a lower number of IBA-1+ microglial cells in the ventral striatum and substantia nigra pars compacta and a reduction in GFAP+ expression, an astrocyte marker, in the dorsal striatum. In this study, several bioactive compounds in the aqueous extract of mahogany leaf may have contributed to the observed beneficial effects. Further studies are necessary to better characterize their applicability for treating chronic degenerative diseases with inflammatory and oxidative bases, such as Parkinson's disease.

High dose cholecalciferol supplementation causing morning blood pressure reduction in patients with type 1 diabetes mellitus and cardiovascular autonomic neuropathy.

We evaluated the association of cardiovascular autonomic neuropathy (CAN), blood pressure (BP) and Vitamin D (VD) levels before and after high-dose cholecalciferol supplementation (4000/10,000) UI/day) for 12 weeks in patients (N = 67) with type 1 diabetes mellitus (T1DM). Based on this prospective controlled pilot study, patients were divided into group 1 (N = 23 with CAN) and group 2 (N = 44 without CAN). At baseline, group 1 had higher systolic BP (SBP) during sleep (115 ± 14 vs. 107 ± 12 mmHg, p = 0.04) and lower nocturnal dipping (3 ± 5 vs. 8 ± 6%, p = 0.009). Among those with loss of nocturnal dipping, 45.4% (20/44) had CAN, while in normal nocturnal dipping group it occurred only in 13% (3/23) (p = 0.007). Non-dipper group had worse CAN parameters when compared to dipper group [Very low frequency (VLF) (2.5 ± 0.5vs.2.8 ± 0.4 s, p = 0.01), total power (TP) (2.9 ± 0.6 vs. 3.3 ± 0.4 s, p = 0.01), Valsalva coefficient (1.5 ± 0.4 vs. 1.8 ± 0.6, p = 0.06)]. After VD, only group 1 improved CAN parameters [TP (2.5 ± 0.4 vs. 2.8 ± 0.6, p = 0.01) and VLF (2.2 ± 0.4 vs. 2.4 ± 0.5, p = 0.03). Group 1 presented a reduction in morning SBP (120 ± 20 vs. 114 ± 17 mmHg, p = 0.038) and in morning SBP surge (13 ± 13 vs. 5 ± 14, p = 0.04). High-dose VD was associated with improved CAN parameters and reduced awake SBP and morning SBP surge. These findings suggest that VD may benefit patients with cardiovascular autonomic neuropathy. ISRCTN32601947, registration date: 31/07/2017.

Association between HLA Class II Alleles/Haplotypes and Genomic Ancestry in Brazilian Patients with Type 1 Diabetes: A Nationwide Exploratory Study.

We aimed to identify HLA-DRB1, -DQA1, and -DQB1 alleles/haplotypes associated with European, African, or Native American genomic ancestry (GA) in admixed Brazilian patients with type 1 diabetes (T1D). This exploratory nationwide study enrolled 1599 participants. GA percentage was inferred using a panel of 46 ancestry informative marker-insertion/deletion. Receiver operating characteristic curve analysis (ROC) was applied to identify HLA class II alleles related to European, African, or Native American GA, and showed significant (p < 0.05) accuracy for identifying HLA risk alleles related to European GA: for DRB1*03:01, the area under the curve was (AUC) 0.533; for DRB1*04:01 AUC = 0.558, for DRB1*04:02 AUC = 0.545. A better accuracy for identifying African GA was observed for the risk allele DRB1*09:01AUC = 0.679 and for the protective alleles DRB1*03:02 AUC = 0.649, DRB1*11:02 AUC = 0.636, and DRB1*15:03 AUC = 0.690. Higher percentage of European GA was observed in patients with risk haplotypes (p < 0.05). African GA percentage was higher in patients with protective haplotypes (p < 0.05). Risk alleles and haplotypes were related to European GA and protective alleles/haplotypes to African GA. Future studies with other ancestry markers are warranted to fill the gap in knowledge regarding the genetic origin of T1D in highly admixed populations such as that found in Brazil.

Adherence to Carbohydrate Counting Improved Diet Quality of Adults with Type 1 Diabetes Mellitus during Social Distancing Due to COVID-19.

To control glycemic variability in people with Type 1 diabetes mellitus (T1DM), it is essential to perform carbohydrate counting (CC), a strategy that ensures better quality of life for these patients. Thus, this study aims to analyze potential factors associated with adherence to CC in adults with T1DM during social distancing due to COVID-19 in Brazil. This was a single cross-sectional study carried out in July 2020. An online form was used to collect sociodemographic and economic data on the purchasing of supplies and food, as well as social distancing. The Chi-square test was performed with adjusted residuals analysis and a binomial logistic regression analysis (p < 0.05). Of 472 adults, 37.71% reported performing CC in the same frequency as before social distancing. There was an association between performance of CC and the type of city (p = 0.027), family income (p = 0.000), use of financial emergency aid (p = 0.045), type of insulin administration and glycemic monitoring (p < 0.000), and cooking more (p = 0.012). Participants who maintained or reduced consumption of ultra-processed foods were 0.62 times more likely to adhere to CC (OR 0.626, 95% IC: 0.419−0.935) and participants who cooked more were 1.67 times more likely to adhere to CC (OR 1.67, 95% CI: 1.146−2.447). There are still people with T1DM who did not know about and did not use CC method, which highlights the need for diabetes education.

Variants in the VDR Gene May Influence 25(OH)D Levels in Type 1 Diabetes Mellitus in a Brazilian Population.

Vitamin D has been considered a strong contributing factor to type 1 diabetes mellitus (T1DM). Many studies have investigated polymorphisms in the VDR gene in association with T1DM in different populations, but there are still conflicting findings. This study aimed to evaluate the association of four variants in the VDR gene (rs7975232, rs1544410, rs731236, and rs2228570) with T1DM risk and vitamin D levels within a population from North Region, Brazil, as well as the influence of genomic ancestry on T1DM. A total of 65 T1DM patients and 83 non-T1DM patients were enrolled in this study. VDR gene polymorphisms were assessed using Sanger sequencing analysis. Genomic ancestry was analyzed using a set of 61 ancestry-informative markers. T1DM patients showed higher European genomic contribution and lower Native American genomic contribution when compared to non-T1DM patients. T1DM patients with AA genotype in rs1544410 or CC genotype in rs731236 had significantly lower 25(OH)D levels compared to the other two genotypes (p = 0.013 and p = 0.02, respectively), while T1DM with TT genotype in rs2228570 had higher 25(OH)D levels compared to CC + TC in the same polymorphism (p = 0.011). Our findings suggest that the association between 25(OH)D and T1DM may be modified by VDR variants, possibly influencing the development of this autoimmune disease.

Modelling level I Axillary Lymph Nodes depth for Microwave Imaging.

PURPOSE: Patient-specific information on the depth of Axillary Lymph Nodes (ALNs) is important for the development of new diagnostic imaging technologies, e.g. Microwave Imaging (MWI), aiming to assess the diagnosis of ALNs during breast cancer staging. Studies about ALNs depth have been presented for treatment planning, but they lack information on sample size and usability of the data to infer the depth of ALNs. The aim of this study was to create a mathematical model that can be used to predict a depth interval where level I ALNs are likely to be located. METHODS: We extracted biometric features of 98 patients who underwent breast Magnetic Resonance Imaging (MRI) to train two types of regression models. We then tested different combination of features to predict ALNs depth and found the best predictor. The final prediction models were then implemented in an algorithm used for MWI and tested with anthropomorphic phantoms of the axillary region. RESULTS: Body Mass Index (BMI) was the feature with best performance to predict ALNs depth with coefficient of determination (R2) ranging from 0.49 to 0.55 and Root Mean Squared Error (RMSE) ranging from 0.68 to 0.91 cm. The proposed model showed satisfactory results in microwave images of patients with different BMIs. CONCLUSIONS: The presented results contribute to the development of reconstruction algorithms for new imaging technologies and to the assessment of ALNs in other medical applications.

HLA Genotypes and Type 1 Diabetes and Its Relationship to Reported Race/Skin Color in Their Relatives: A Brazilian Multicenter Study.

We aimed to investigate the relationship between HLA alleles in patients with type 1 diabetes from an admixed population and the reported race/skin color of their relatives. This cross-sectional, multicenter study was conducted in public clinics in nine Brazilian cities and included 662 patients with type 1 diabetes and their relatives. Demographic data for patients and information on the race/skin color and birthplace of their relatives were obtained. Typing of the HLA-DRB1, -DQA1, and -DQB1 genes was performed. Most studied patients reported having a White relative (95.17%), and the most frequently observed allele among them was DRB1*03:01. Increased odds of presenting this allele were found only in those patients who reported having all White relatives. Considering that most of the patients reported having a White relative and that the most frequent observed allele was DRB1*03:01 (probably a European-derived allele), regardless of the race/skin color of their relatives, we conclude that the type 1 diabetes genotype comes probably from European, Caucasian ethnicity. However, future studies with other ancestry markers are needed to fill the knowledge gap regarding the genetic origin of the type 1 diabetes genotype in admixed populations such as the Brazilian.

Health-related quality of life in T1DM patients after high-dose cholecalciferol supplementation: data from a pilot clinical trial.

BACKGROUND: Type 1 Diabetes Mellitus (T1DM) impacts health-related quality of life (HRQoL). Cross-sectional studies suggest that low levels of vitamin D (VD) may impair HRQoL, however, the effect of VD supplementation on quality of life in T1DM patients has not yet been clarified. Our study evaluated the effects of high-dose VD supplementation on HRQoL in T1DM. METHODS: We performed a prospective study with 64 patients receiving cholecalciferol (4000 IU/day for patients with 25-OH-vitamin D [25(OH)D] between 30 and 60 ng/mL, and 10,000 IU/day for those with 25(OH)D below 30 ng/mL) for 12 weeks, as part of a research protocol. HRQoL was assessed with EuroQol instruments (EQ-5D and EQ-VAS). RESULTS: There was an improvement in global EQ-5D index, and analysing specifically the EQ-5D domains, we observed an improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p < 0.01). Evaluating possible outcome influencing variables, we detected a reduction in albuminuria at the end of the trial, without changes in BMI, lipids, blood pressure, glycemic control and insulin doses. We found correlations between final albuminuria and the dimensions: mobility (r = 0.6; p < 0.01), personal care (r = 0.7; p < 0.01), pain and discomfort (r = 0.6; p < 0.01) and habitual activities (r = 0.6; p < 0.01), suggesting an association between albuminuria reduction and the impact of VD supplementation on HRQoL. CONCLUSION: Our data showed that high doses of cholecalciferol supplementation can improve HRQoL in patients with T1DM, and the reduction of albuminuria seems to be an important factor in this context. TRIAL REGISTRATION: (ISRCTN32601947), 03/06/2017 retrospectively registered.

High-dose Vitamin D Supplementation on Type 1 Diabetes Mellitus Patients: Is there an Improvement in Glycemic Control?

BACKGROUND: Some authors evaluated the effect of VD on hyperglycemia in T1DM, but the results remain controversial. This study aims to analyze the effects of high-dose VD supplementation on T1DM patients' glycemic levels, maintaining stable doses of insulin. METHODS: Prospective, 12-week clinical trial including 67 T1DM patients, supplemented with high doses of cholecalciferol according to participants' VD value. Patients with VD levels below 30 ng/mL received 10,000 IU/day; those with levels between 30-60 ng/mL received 4,000 IU/day. Patients who had not achieved 25(OH)D levels > 30 ng/ml or presented insulin dose variation during the study were not analyzed. RESULTS: Only 46 out of 67 patients accomplished the criteria at the end of the study. There was no general improvement in the glycemic control evaluated by HbA1c (9.4 ± 2.4 vs 9.4 ± 2.6, p=NS) after VD supplementation. However, a post-hoc analysis, based on HbA1c variation, identified patients who had HbA1c reduced at least 0.6% (group 1, N = 13 (28%)). In addition, a correlation between 25(OH)D levels with HbA1c and total insulin dose at the end of the study was observed (r = -0.3, p<0.05; r=-0.4, p<0.05, respectively), and a regression model demonstrated that 25(OH)D was independent of BMI, duration of T1DM and final total insulin dose, being capable of determining 9.2% of HbA1c final levels (Unstandardized B coefficient = -0.033 (CI 95%: -0.064 to -0.002), r2 = 0.1, p <0.05). CONCLUSION: Our data suggest that VD is not widely recommended for glycemic control. Nevertheless, specific patients might benefit from this approach.

Global miRNA expression reveals novel nuclear and mitochondrial interactions in Type 1 diabetes mellitus.

Background: Considering the potential role of miRNAs as biomarkers and their interaction with both nuclear and mitochondrial genes, we investigated the miRNA expression profile in type 1 diabetes (T1DM) patients, including the pathways in which they are involved considering both nuclear and mitochondrial functions. Methods: We analyzed samples of T1DM patients and control individuals (normal glucose tolerance) by high throughput miRNA sequencing (miRNome). Next, five miRNAs - hsa-miR-26b-5p, hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p and hsa-miR-100-5p - were validated by RT-qPCR. The identification of target genes was extracted from miRTarBase and mitoXplorer database. We also performed receiver operating characteristic (ROC) curves and miRNAs that had an AUC > 0.85 were considered potential biomarkers. Results: Overall, 41 miRNAs were differentially expressed in T1DM patients compared to control. Hsa-miR-21-5p had the highest number of predicted target genes and was associated with several pathways, including insulin signaling and apoptosis. 34.1% (14/41) of the differentially expressed miRNAs also targeted mitochondrial genes, and 80.5% (33/41) of them targeted nuclear genes involved in the mitochondrial metabolism. All five validated miRNAs were upregulated in T1DM. Among them, hsa-miR-26b-5p showed AUC>0.85, being suggested as potential biomarker to T1DM. Conclusion: Our results demonstrated 41 DE miRNAs that had a great accuracy in discriminating T1DM and control group. Furthermore, we demonstrate the influence of these miRNAs on numerous metabolic pathways, including mitochondrial metabolism. Hsa-miR-26b-5p and hsa-miR-21-5p were highlighted in our results, possibly acting on nuclear and mitochondrial dysfunction and, subsequently, T1DM dysregulation.

Surgical Planning and Strategies for Peyronie's Disease.

INTRODUCTION: Peyronie's disease results in penile curvature, shortening, instability, or pain upon erection-hindering sexual performance and leading to psychological distress. Despite extensive research, surgery is still the mainstay of treatment. OBJECTIVE: To present an organized description of the most common surgical techniques used in the correction of Peyronie's disease and to propose a surgical algorithm to guide management. METHODS: Using PubMed, we reviewed the published literature regarding surgical treatment of Peyronie's disease and its outcomes. We identified original articles, review articles, and editorials addressing the subject, with a focus on surgical techniques, their indications, and outcomes. RESULTS: Peyronie's disease can be treated by corporoplasty or penile prosthesis implantation. Corporoplasty includes convex side-shortening procedures and concave side lengthening procedures. It is indicated when the erectile function is adequate. Shortening procedures include excisional, incisional, and plication-only techniques, and lengthening procedures include partial excision or incision followed by grafting. When refractory erectile dysfunction is present, placement of a penile prosthesis with or without further straightening maneuvers is recommended. We reviewed the indications, advantages, disadvantages, and outcomes of the available techniques and proposed a surgical algorithm to guide management. CONCLUSION: Penile shortening procedures are usually indicated in curvatures <60°, in penises with adequate length. Partial excision/incision and grafting are indicated for curvatures >60°, hourglass or hinge deformities, and short penises, if the patient's erectile function is adequate. The presence of "borderline" erectile function and/or ventral curvature tilts the choice toward shortening procedures, and refractory erectile dysfunction is an indication for penile prosthesis placement. Peyronie's disease management remains challenging with many options available, making an accurate risk/benefit assessment of each case and meticulous patient counseling critically important. Almeida JL, Felício J, Martins FE. Surgical Planning and Strategies for Peyronie's Disease. Sex Med Rev 2021;9:478-487.

Sclerosing lipogranuloma of the penis: a narrative review of complications and treatment.

OBJECTIVE: Sclerosing lipogranuloma of the penis is a relatively rare disorder associated with injection of illicit foreign materials for penile augmentation. We aim to report the clinical presentation, diagnosis, treatment, and outcomes of patients with this condition, and to review the most relevant literature currently available. BACKGROUND: Injection of mineral oil into the subcutaneous tissues of the penis for augmentation has been practiced since ancient times. The potential for complications has long been known, and most doctors have abandoned the procedure. However, it is still practiced in some parts of the world. The complications may be devastating including death from embolism or sepsis. The affected area may not be restricted to the injection site, potentially involving the scrotal and suprapubic areas. Surgery with complete removal of the involved tissue followed by covering the denuded area with a graft or skin flap is the best therapeutic option. METHODS: The literature search involved keywords such as penis, augmentation, enlargement, sclerosing, lipogranuloma, penile injection, paraffinoma, and was obtained from computerized search of databases such as PubMed, Google Search and Scopus. Personal experience of the lead author (BS) is also described. We tried arbitrarily to limit our search to articles including ≥5 patients pertaining to the subject of our review and, therefore, excluded single case reports. However, a single systematic search of PubMed and Scopus was also found and included. CONCLUSIONS: The treatment of choice is radical excision of all the lesions followed by skin grafting. Bearing in mind that prospective, randomized, controlled studies are considered difficult to carry out, further work will continue apparently to be based on case series by individual surgeons. It is critical to advise patients to separate the myths from the facts and use preventive measures through awareness and education to best minimize the downsides of this problem.