Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial.

Importance: Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes. Objective: To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes. Design, Setting, and Participants: Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol). Interventions: Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294). Main Outcomes and Measures: The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes. Results: Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], -0.2 [95% CI, -0.3 to -0.1] percentage points), confirming noninferiority (P < .001) and superiority (P = .002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, -6 to 5] mg/dL; P = .90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, -0.19 to 1.10] kg; P = .17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P = .01). Conclusions and Relevance: Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups. Trial Registration: ClinicalTrials.gov Identifier: NCT04795531.

The SAGE study: Global observational analysis of glycaemic control, hypoglycaemia and diabetes management in T1DM.

AIMS: To describe glycaemic control and diabetes management in adults with type 1 diabetes (T1DM), in a real-life global setting. MATERIALS AND METHODS: Study of Adults' GlycEmia (SAGE) was a multinational, multicentre, single visit, noninterventional, cross-sectional study in adult patients with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64 and ≥65 years) and reported across different regions. The primary endpoint was the proportion of participants achieving HbA1c  less than 7.0 % in each age group. Secondary endpoints included incidence of hypoglycaemia, severe hypoglycaemia and severe hyperglycaemia leading to diabetic ketoacidosis (DKA) and therapeutic management of T1DM. RESULTS: Of 3903 included participants, 3858 (98.8%) were eligible for the study. Overall, 24.3% (95% confidence interval [CI]: 22.9-25.6) of participants achieved the glycaemic target of HbA1c  less than 7.0 %, with more participants achieving this target in the 26-44 years group (27.6% [95% CI: 25.5-29.8]). Target achievement was highest in Eastern and Western Europe, and lowest in the Middle East. The incidence of hypoglycaemia and of severe hyperglycaemia leading to DKA tended to decrease with age, and varied across regions. Age and regional differences were observed in therapeutic management, including types of device/insulin usage, frequency of insulin dose adjustment and technology usage. CONCLUSIONS: Glycaemic control remains poor in adults with T1DM globally. Several areas of treatment may be optimised to improve outcomes, including supporting patient self-management of insulin therapy, increasing use of technologies such as CGM, and greater provision of healthcare support.

Obesity induction in adult zebrafish leads to negative reproduction and offspring effects.

Obesity is a transgenerational epigenetic metabolic disturbance. Although the diet-induced obese (DIO) zebrafish model is well established, reproductive parameters and changes in offspring have not yet been evaluated. Thus, the aim of this study was to evaluate possible changes in reproductive parameters, embryos and offspring (F1) generated by the reproduction of diet-induced obese males and females. The adult zebrafish were divided into two groups: one group receiving a balanced diet (control group) and the other group was overfed (DIO group) . The dietary protocol was maintained for 8 weeks. During this period, males and females in the same group were stimulated through a weekly reproduction protocol. To verify parental obesity, body weight, blood glucose, triglyceride, the hepatosomatic and gonadosomatic index and adipose tissue morphometry evaluations were carried out. Reproductive parameters were evaluated through ovarian and oocyte maturation stage, total spawning, fertility and fertilization index. To verify possible changes caused by parenteral obesity, all offspring were kept in separate groups in correspondence with their parents and were fed a control diet. Plasma glucose, triglycerides, mortality rate, hatching, and deformities were determined. After 8 weeks under the diet protocol, the DIO group exhibited characteristic obesity alterations, displaying significant increases in body mass and hepatosomatic and gonadosomatic indices, hyperglycemia and visceral and subcutaneous adipocyte hypertrophy. In addition, high mortality rates, morphologic deformities and high plasmatic glucose and triglyceride levels, with 100% mortality at 60 dpf, were observed for the offspring. Therefore, obesity induction in adults led to negative effects on their offspring, with a high occurrence of deformities and mortality.

Improved glycaemic variability and time in range with dapagliflozin versus gliclazide modified release among adults with type 2 diabetes, evaluated by continuous glucose monitoring: A 12-week randomized controlled trial.

AIMS: To evaluate whether there is a difference between the effects of dapagliflozin and gliclazide modified release (MR) on glycaemic variability (GV) and glycaemic control, as assessed by continuous glucose monitoring (CGM), in individuals with uncontrolled type 2 diabetes. MATERIALS AND METHODS: This randomized, open-label, active-controlled study was conducted in individuals with uncontrolled type 2 diabetes who were drug-naïve or on steady-dose metformin monotherapy. Participants were treated once daily with 10 mg dapagliflozin or 120 mg gliclazide MR. CGM and GV index calculations were performed at baseline and after 12 weeks. RESULTS: In total, 97 participants (age 57.9 ± 8.7 years, 50.5% men, baseline glycated haemoglobin 63 ± 9.8 mmol/mol [7.9 ± 0.9%]) were randomized, and 94 completed the 12-week protocol. Intention-to-treat (ITT) and per-protocol (PP) analyses showed that the reduction in GV, as measured by the mean amplitude of glycaemic excursions, was superior in the dapagliflozin group versus the gliclazide MR group (-0.9 mmol/L [95% CI -1.5, -0.4] vs -0.2 mmol/L [95% CI -0.6, 0.3]; P = 0.030 [ITT]). The reductions in GV estimated by the coefficient of variation and SD were greater in the dapagliflozin group. Moreover, dapagliflozin increased the glucose time in range (TIR; 3.9-10 mmol/L) by 24.9% (95% CI 18.6, 31.2) vs. 17.4% (95% CI 11.6, 23.3) in the gliclazide MR group (P = 0.089 [ITT]; P = 0.041 [PP]). CONCLUSIONS: Dapagliflozin improved GV and increased TIR more efficiently than gliclazide MR in individuals with type 2 diabetes over 12 weeks, as demonstrated by CGM.

Beneficial effects of liraglutide (GLP1 analog) in the hippocampal inflammation.

The brain is very sensitive to metabolic dysfunctions induced by diets high in saturated fatty acids, leading to neuroinflammation. The liraglutide has been found to have neuroprotective effects. However, its neuroprotective action in a model of palmitate-induced neuroinflammation had not yet been evaluated. Mice were intracerebroventricular (ICV) infused with palmitate and received subcutaneous liraglutide. The hippocampal dentate gyrus and CA1 regions were analyzed (morphology and inflammation-related proteins in microglia and astrocyte by confocal microscopy). Also, a real-time PCR was performed to measure the levels of tumor necrosis factor (TNF) alpha and interleukin (IL) 6. Palmitate ICV infusion resulted in pronounced inflammation response in the hippocampus, reactive microgliosis, and astrogliosis, with hypertrophied IBA1 immunoreactive microglia, increased microglial density with ameboid shape, decreased in the number of branches and junctions and increased the major histocompatibility complex (MHC) II expression. Also, we observed in the hippocampus of ICV palmitate infused mice an elevation in the pro-inflammatory cytokine levels TNFalpha and IL6. Liraglutide induced the neuroprotective microglial phenotype, characterized by an increased microglia complexity (enlarged Feret's diameter), an improved number of both cell junctions and processes, and lower circularity, accompanied by a significant reduction in TNFalpha and IL6 expressions. The study provides evidence that liraglutide may be a suitable treatment against the palmitate-induced neuroinflammation, which it is characterized by the reactive microgliosis and astrogliosis, as well as increased pro-inflammatory cytokines, which has been described as one of the primary causes of several pathologies of the central nervous system.

Intermittently Scanned Continuous Glucose Monitoring Performance in Patients With Liver Cirrhosis.

AIM: To evaluate the use of intermittently scanned continuous glucose monitoring (isCGM) in patients with liver cirrhosis (LC). METHODS: Observational study including 30 outpatients with LC (Child-Pugh B/C): 10 without diabetes (DM) (G1), 10 with newly diagnosed DM by oral glucose tolerance test (G2), and 10 with a previous DM diagnosis (G3). isCGM (FreeStyle Libre Pro) was used for 56 days (four sensors/patient). Blood tests were performed at baseline and after 28 and 56 days. RESULTS: No differences were found in the baseline characteristics, except for higher age in G3. There were significant differences between G1, G2 and G3 in glucose management indicator (GMI) (5.28 ± 0.17, 6.03 ± 0.59, 6.86 ± 1.08%, P < .001), HbA1c (4.82 ± 0.39, 5.34 ± 1.26, 6.97 ± 1.47%, P < .001), average glucose (82.79 ± 7.06, 113.39 ± 24.32, 149.14 ± 45.31mg/dL, P < .001), time in range (TIR) (70.89 ± 9.76, 80.2 ± 13.55, 57.96 ± 17.96%, P = .006), and glucose variability (26.1 ± 5.0, 28.21 ± 5.39, 35.31 ± 6.85%, P = .004). There was discordance between GMI and HbA1c when all groups were considered together, with a mean difference of 0.35% (95% SD 0.17, 0.63). In G1, the mean difference was 0.46% (95% SD 0.19, 0.73) and in G2 0.69% (95% SD 0.45, 1.33). GMI and HbA1c were concordant in G3, with a mean difference of -0.10 % (95% SD [-0.59, 0.38]). CONCLUSION: Disagreements were found between the GMI and HbA1c levels in patients with LC. isCGM was able to detect abnormalities in glycemic control that would not be detected by monitoring with HbA1c, suggesting that isCGM can be useful in assessing glycemic control in patients with LC.

Exploring the effects of eugenol, menthol, and lidocaine as anesthetics on zebrafish glucose homeostasis.

Zebrafish (Danio rerio) are widely employed as an experimental model in various scientific fields. The investigation of glucose metabolism dysfunctions has gained recent significant prominence. Considering that certain anesthetics may impact glycemic levels, it is imperative to carefully select an anesthetic that does not induce such side effects, thereby mitigating potential adverse influences on research outcomes. In this sense, this study aimed to evaluate potential glucose alterations and induction and recovery times resulting from the use of eugenol, menthol and lidocaine as anesthetics in zebrafish. A total of 150 adult male and female zebrafish were divided into ten groups, comprising a control group euthanized by rapid chilling, and three groups anesthetized with low (40 mg/L eugenol, 60 mg/L menthol, 100 mg/L lidocaine), intermediate (60 mg/L eugenol, 90 mg/L menthol, 225 mg/L lidocaine), and high (80 mg/L eugenol, 120 mg/L menthol, 350 mg/L lidocaine) anesthetic concentrations. Glucose levels and induction and recovery times were assessed. The findings reveal that eugenol and menthol did not cause glucose level alterations at any of the investigated concentrations, while lidocaine caused a non-concentration-dependent hyperglycemia. Eugenol and menthol also exhibited similar recovery times at different concentrations, while lidocaine recovery times were concentration-dependent. This study, therefore, concludes that eugenol and menthol are safe and satisfactory anesthetics for use in zebrafish research involving glucose analyses, while lidocaine use can cause biases due to altered glucose levels and safety concerns. Researchers should, therefore, carefully consider anesthetic selection to ensure reliable results in zebrafish assessments.

The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art.

Parkinson's disease (PD) is a neurodegenerative disorder affecting 2-3% of those aged over 65, characterized by motor symptoms like slow movement, tremors, and muscle rigidity, along with non-motor symptoms such as anxiety and dementia. Lewy bodies, clumps of misfolded proteins, contribute to neuron loss in PD. Mutations in the GBA1 gene are considered the primary genetic risk factor of PD. GBA1 mutations result in decreased activity of the lysosomal enzyme glucocerebrosidase (GCase) resulting in α-synuclein accumulation. We know that α-synuclein aggregation, lysosomal dysfunction, and endoplasmic reticulum disturbance are recognized factors to PD susceptibility; however, the molecular mechanisms connecting GBA1 gene mutations to increased PD risk remain partly unknown. Thus, in this narrative review conducted according to a systematic review method, we aimed to present the main contributions arising from the molecular impact of the GBA1 gene to the pathogenesis of PD providing new insights into potential impacts for advances in the clinical care of people with PD, a neurological disorder that has contributed to the substantial increase in the global burden of disease accentuated by the aging population. In summary, this narrative review highlights the multifaceted impact of GBA1 mutations in PD, exploring their role in clinical manifestations, genetic predispositions, and molecular mechanisms. The review emphasizes the importance of GBA1 mutations in both motor and non-motor symptoms of PD, suggesting broader therapeutic and management strategies. It also discusses the potential of CRISPR/Cas9 technology in advancing PD treatment and the need for future research to integrate these diverse aspects for improved diagnostics and therapies.

Comparison of Diff-Quick and Spermac Staining Methods for Sperm Morphology Evaluation.

Background: The objective of the current study was comparing the impact of two staining techniques on semen morphological parameters and their influence on patient diagnosis. The ideal staining method should preserve cell integrity while providing detailed information. Methods: Semen samples from fifty men were stained using Diff-Quick or Spermac methods. Morphological parameters were classified based on the Tygerberg criteria, and final diagnosis was according to WHO manual guidelines. Statistical analysis was performed through conducting paired t-tests or Wilcoxon rank-sum tests, with GLIMMIX and Fisher's exact test for determining the significance (p≤0.05). Results: Both staining methods highlighted head and tail regions, with Spermac offering better visualization of the midpiece. Spermac demonstrated fewer normal spermatozoa (2.8±0.3%) compared to Diff-Quick (3.98±0.4%; p=0.0385). Midpiece abnormalities were more evident with Spermac (55.7±2.1%) than Diff-Quick (24.8±2.0%; p<0.0001). No significant difference was found in head and tail abnormalities (p>0.05). Conclusion: Diff-Quick staining resulted in a higher proportion of normal spermatozoa, primarily due to its midpiece evaluation. The choice of staining method significantly impacts the diagnosis of infertile males. These findings have important implications for clinical practice and future research, suggesting the need for further investigations to assess different staining methods and determine optimal diagnostic thresholds.

Determinants of glycemic control in type 2 diabetes mellitus in Brazil: A sub-analysis of the longitudinal data from the BrazIian type 1 & 2 diabetes disease registry (BINDER).

BACKGROUND: Data on glycemic control and its determinants among Brazilian patients with type-2 diabetes (DM2) are scarce. The BrazIliaN Type 1 & 2 DiabetEs Disease Registry (BINDER) is a multicenter, longitudinal study, designed to investigate the glycemic control in a real-word scenario. METHODS: 1142 patients participated in the five visits of the BINDER study between April/2017 and October/2019. For each visit, glycemic control was assessed using the last measure available for HbA1c. Sociodemographic and anthropometric characteristics were also analyzed. RESULTS: At baseline, the median HbA1c level was 7.1% (4.1-15.0%); 259 (31.4%) participants had HbA1c ≤ 6.5% and 396 (48.2%) had HbA1c ≤ 7.0%. Younger age (p = 0.014), low educational level (p = 0.025) and the type of healthcare service (public sector; p = 0.0058) were independently associated with the elevated HbA1c. After 2 years, there were no statistically significant differences in HbA1c median values in relation to baseline. CONCLUSIONS: In this sample of DM2 patients, younger age, low educational level and being treated at the public service were associated with worse glycemic control. Over a 2-year follow-up, there was no significant change in the median HbA1c. These findings suggest that strategies are needed to improve glycemic control, especially in those treated in the public service.

Contemporary (2019) prevalence of cardiovascular disease in adults with type 2 diabetes in Brazil: the cross-sectional CAPTURE study.

BACKGROUND: Type 2 diabetes (T2D) is a known risk factor for cardiovascular disease (CVD), and CVD is a major cause of mortality in patients with T2D. The CAPTURE study investigated the contemporary (2019) prevalence of established CVD in adults with T2D around the world. We report the findings from Brazil. METHODS: The multinational, non-interventional, cross-sectional CAPTURE study was conducted across 13 countries from five continents. The current manuscript explores data for the CAPTURE study sample in Brazil. Standardized demographic and clinical data were collected from adults with T2D aged ≥ 18 years attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data were analyzed descriptively. RESULTS: Data from 912 adults with T2D were collected in the CAPTURE study in Brazil, with 822 patients from primary care and 90 patients from specialized care. Median (interquartile range [IQR]) patient characteristics were as follows: age 64 years (57; 71), diabetes duration 11 years (6; 19), glycated hemoglobin 7.7% (6.7; 9.1), and body mass index 29.5 kg/m2 (26.4; 33.5); 59% were female. The CVD prevalence and atherosclerotic CVD prevalence in the Brazil sample were 43.9% (95% confidence interval [CI] 40.9; 46.8) and 37.6% (95% CI 34.7; 40.5), respectively. The majority of patients with CVD had atherosclerotic CVD (85.8%). For the specific CVD subtypes, coronary heart disease prevalence was 27.9% (95% CI 25.2; 30.5), heart failure was 12.4% (95% CI 10.4; 14.4), cerebrovascular disease was 8.7% (95% CI 6.8; 10.5), and carotid artery disease was 3.4% (95% CI 2.3; 4.5). Glucagon-like peptide-1 receptor agonists and/or sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit were prescribed to 15.5% of patients with CVD, compared with 18.4% of patients without CVD. CONCLUSIONS: CAPTURE was the first multinational, standardized study to provide contemporary data on CVD prevalence in adults with T2D in Brazil, and it demonstrated that almost one in two adults with T2D had established CVD. Except for carotid artery disease, the prevalence of all CVD subtypes in adults with T2D in Brazil appeared higher than the global CAPTURE prevalence. Trial registration NCT03786406, NCT03811288.

Flash glucose monitoring system in special situations.

The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

Melatonin administration attenuates acute stress by inducing sleep state in zebrafish (Danio rerio).

Melatonin plays a fundamental homeostatic role in basic biological functions, and an anti-stress role has been also proposed for this hormone. This study aimed to evaluate hormonal, enzymatic and behavioral parameters of zebrafish that received administration of melatonin and were submitted to acute stress. A total of 120 wild-type zebrafish were divided into five groups: naïve control (N), negative control group (Stress/C), positive control treated with diazepam (Stress/Diaz), treatment with melatonin at dose 1 (Stress/Melt. 1) and treatment with melatonin at dose 2 (Stress/Melt. 2). The exposure to treatments (diazepam or melatonin) was performed prior to the acute stress protocol, based on a chase by a fishing net during 5 min followed by exposure to the air for 1 min. The body cortisol levels were assessed, as well as oxidative stress (thiobarbituric acid reactive substances, reactive species of oxygen and antioxidant activity), and fish behavior (open field test). Melatonin was able to modulate acute stress effects on zebrafish by inhibiting cortisol increasing levels, reducing locomotor parameters, inducing a sleep state, reducing lipid peroxidation and stimulating antioxidant enzymatic activity.

Real-world flash glucose monitoring in Brazil: can sensors make a difference in diabetes management in developing countries?

BACKGROUND: New technologies are changing diabetes treatment and contributing better outcomes in developed countries. To our knowledge, no previous studies have investigated the comparative effect of sensor-based monitoring on glycemic markers in developing countries like Brazil. The present study aims to evaluate the use of intermittent Continuous Glucose Measurements (iCGM) in a developing country, Brazil, regarding (i) frequency of glucose scans, (ii) its association with glycemic markers and (iii) comparison with these findings to those observed in global population data. METHODS: Glucose results were de-identified and uploaded to a dedicated database when Freestyle Libre™ readers were connected to an internet-ready computer. Data between September 2014 and Dec 2018, comprising 688,640 readers and 7,329,052 sensors worldwide, were analysed (including 17,691 readers and 147,166 sensors from Brazil). Scan rate per reader was determined and each reader was sorted into 20 equally-sized rank ordered groups, categorised by scan frequency. Glucose parameters were calculated for each group, including estimated A1c, time above, below and within range identified as 70-180 mg/dL. RESULTS: In Brazil, reader users performed an average of 14 scans per day, while around the world, reader users performed an average of 12 scans per day (p < 0.01). In Brazil dataset, those in the lowest and in the highest groups scanned on average 3.6 and 43.1 times per day had an estimated A1c of 7.56% (59 mmol/mol) and 6.71% (50 mmol/mol), respectively (p < 0.01). Worldwide, the lowest group and the highest groups scanned 3.4 times/day and 37.8 times/day and had an eA1c of 8.14% (65 mmol/mol) and 6.70% (50 mmol/mol), respectively (p < 0.01). For the scan groups in both populations, the time spent above 180 mg/dL decreased as the scan frequency increased. In both Brazil and around the world, as scan frequency increased, time in range (TIR) increased. In Brazil, TIR increased from 14.15 to 16.62 h/day (p < 0.01). Worldwide, TIR increased from 12.06 to 16.97 h/day (p < 0.01). CONCLUSIONS: We conclude that Brazilian users have a high frequency of scans, more frequent than global data. Similarly to the world findings, increased scan frequency is associated with better glycemic control.

Time in range: a new parameter to evaluate blood glucose control in patients with diabetes.

The International Consensus in Time in Range (TIR) was recently released and defined the concept of the time spent in the target range between 70 and 180 mg/dL while reducing time in hypoglycemia, for patients using Continuous Glucose Monitoring (CGM). TIR was validated as an outcome measures for clinical Trials complementing other components of glycemic control like Blood glucose and HbA1c. The challenge is to implement this practice more widely in countries with a limited health public and private budget as it occurs in Brazil. Could CGM be used intermittently? Could self-monitoring blood glucose obtained at different times of the day, with the amount of data high enough be used? More studies should be done, especially cost-effective studies to help understand the possibility of having sensors and include TIR evaluation in clinical practice nationwide.

Canine atopic dermatitis attenuated by mesenchymal stem cells.

OBJECTIVE: To evaluate the use of mesenchymal stem cells (MSCs) in the attenuation of canine atopic dermatitis (AD). MATERIALS AND METHODS: Sixteen dogs were selected and divided into three groups, mild, moderate, and severe, according to the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4). They were evaluated for 82 days. The protocol recommended in this experiment was to inject 2 × 106/kg bodyweight of MSC's in all groups by the intravenous route with intervals of applications of 21 days. The degree of pruritus was evaluated by examining the visual analog scale, the CADESI-4, the histopathology of the skin, hematological and biochemical parameters, the pyogenic effect of MSCs, and the thickness of the epidermis. RESULTS: There was a significant difference in the reduction of epidermal thickness in the moderate and severe groups. Hematological, biochemical, and body temperature parameters remained within normal limits for the species with no side effects. CONCLUSION: MSCs attenuated the clinical signs of AD.

The lesser anteater (Tamandua tetradactyla) is not tetradactyla, but pentadactyla.

The name of the species tetradactyla means "four digits." In the literature, the hand of the lesser anteater (Tamandua tetradactyla) is described as having four digits (I, II, III and IV) with the absence of a fifth digit. The purpose of this study was to carry out an update adequately proposing an anatomical description of the T. tetradactyla hand. The present findings were analysed on the validation of Morse's law for this species. In total, seven male cadavers were radiographed and dissected. We observed that the hand of the T. tetradactyla was formed by a carpus containing four bones in the proximal row, which in the medium lateral direction was the radial, intermediate, ulnar and accessory bones of the carpus, and the distal row was formed by carpal bones I, II, III and IV. There were five metacarpal bones (I, II, III, IV and V). The presence of five digits was verified but not confirmed with the literature. Digit I had two phalanges, the proximal and distal; digits II, III and IV had three phalanges: proximal, middle and distal. Digit five had only one phalanx, the proximal, but it was not externally visible. According to the findings of this study, the presence of the fifth digit raises the question of whether the term tetradactyla is the most appropriate to describe this species. This rudimentary fifth digit and the presence of a functional first digit show that the Morse's law does not applies for the T. tetradactyla species.

A randomized controlled trial to compare the effects of sulphonylurea gliclazide MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic variability and control measured by continuous glucose monitoring (CGM) in Brazilian women with type 2 diabetes.

AIMS: This study aims to evaluate whether there is a difference between the effects of vildagliptin and gliclazide MR (modified release) on glycemic variability (GV) in women with type 2 diabetes (T2DM) as evaluated by continuous glucose monitoring (CGM). METHODS: An open-label, randomized study was conducted in T2DM women on steady-dose metformin monotherapy which were treated with 50 mg vildagliptin twice daily or 60-120 mg of gliclazide MR once daily. CGM and GV indices calculation were performed at baseline and after 24 weeks. RESULTS: In total, 42 patients (age: 61.9 ±â€¯5.9 years, baseline glycated hemoglobin (HbA1c): 7.3 ±â€¯0.56) were selected and 37 completed the 24-week protocol. Vildagliptin and gliclazide MR reduced GV, as measured by the mean amplitude of glycemic excursions (MAGE, p = 0.007 and 0.034, respectively). The difference between the groups did not reach statistical significance. Vildagliptin also significantly decreased the standard deviation of the mean glucose (SD) and the mean of the daily differences (MODD) (p = 0.007 and 0.030). CONCLUSIONS: Vildagliptin and gliclazide MR similarly reduced the MAGE in women with T2DM after 24 weeks of treatment. Further studies are required to attest differences between vildagliptin and gliclazide MR regarding glycemic variability.

Mesenchymal stem cells in osteotomy repair after tibial tuberosity advancement in dogs with cranial cruciate ligament injury.

BACKGROUND: The cranial cruciate ligament rupture (CCLR) is the most commonly encountered orthopedic condition in dogs. Among the various techniques to treat this condition, tibial tuberosity advancement (TTA) has been used to obtain rapid recovery of the affected knee. The objective of this study was to evaluate the viability of the use of mesenchymal stem cells (MSC) implanted in the osteotomy site obtained by TTA in nine dogs diagnosed with CCLR. METHODS: The MSC were isolated from the adipose tissue of the dogs and cultured for eight days, the animals were divided into two groups. Animals from the treated group (GT) received cell transport medium containing about 1.5 millions MSC, and the animals from the control group (GC) received only the cell transport medium. The study was performed in a double-blind manner using radiographs acquired on days 15, 30, 60 and 120 after the procedure. Evaluations of the density of the trabecular bone were performed using image analysis software. The results were subjected to descriptive statistical analysis, followed by the normality test, Chi-square test, Mann-Whitney test and Tukey's multiple comparison test for p ≤ 0.05. RESULTS: After 30 days of the procedure, the animals of the GT presented an ossification mean 36.45% greater (p ≤ 0.033) than the GC, and there were no statistical differences for the other periods. CONCLUSIONS: Despite the total bone ossification within the expected period, there was no minimization of the estimated recovery time with the application of MSC, and inflammatory factors should be considered for reassessment of the therapeutic intervention time.

Morphology and Morphometry of the Magellanic Penguin (Spheniscus magellanicus) Trachea / Morfologia e morfometria da traqueia do pinguim-de-Magalhães (Spheniscus magellanicus)

Objective: This work aimed to describe the trachea of the Magellanic Penguin (Spheniscus magellanicus) through descriptive and morphometric approaches. Methods: ten adult male Spheniscus magellanicus were used, which were collected, fixed, and kept immersed in an aqueous solution of 10% formaldehyde. Results: the trachea of the penguin began caudally from the cricoid cartilage of the larynx, represented by 121.3±5.65 cartilaginous rings joined together, which extended to the syrinx (19.75±0.70 cm). Considering its five segments (I-V), the number of tracheal rings decreased in a cranio-caudal direction. The medial tracheal septum, which started caudally from the cricoid cartilage of the larynx, was approximately 2±0.08 cm and was formed by approximately 6.75±0.25 rings. The dimensions of the lumen of the trachea decreased cranio-caudally, with a statistical difference between segment I and the others (II to V). The syrinx of the tracheobronchial type presented 7.52±0.65 rings. Conclusions: these data will contribute to the understanding of the anatomy of this species, as well as to the diagnosis and treatment of possible tracheal pathologies found in it.

Objetivo: o objetivo deste trabalho foi descrever a traqueia do pinguim-de-Magalhães (Spheniscus magellanicus), por meio de abordagens descritivas e mofométricas. Metodologia: foram utilizados dez Spheniscus magellanicus, adultos, machos que foram após coletas, fixados e mantidos imersos em solução aquosa, a 10% de formaldeído. Resultados: a traqueia do pinguim iniciou-se, caudalmente, a cartilagem cricoide da laringe, representada por 121,3±5,65 anéis cartilaginosos unidos entre si, que se estenderam até as siringes (19,75±0,70 cm). Considerando seus cinco segmentos (I-V), o número de anéis traqueais diminuiu seu número em sentido craniocaudal. O septo traqueal medial teve início caudalmente a cartilagem cricoide da laringe, aproximadamente 2±0,08 cm, e foi formado por, aproximadamente, 6,75±0,25 anéis. As dimensões do lúmen da traqueia diminuíram craniocaudalmente, com diferença estatística entre o segmento I e os outros (II a V). As siringes, do tipo traqueobronquiais, apresentaram 7,52±0,65 anéis. Conclusões: esses dados contribuirão para o entendimento da anatomia dessa espécie, bem como para o diagnóstico e tratamento de possíveis patologias traqueais nela encontradas.