Efficacy of high-intensity interval training versus continuous training on serum myonectin and lipid outcomes in adults with metabolic syndrome: A post-hoc analysis of a clinical trial.

BACKGROUND: Myonectin is a myokine with potential effects on the lipid metabolism; however, its regulation by exercise in humans remains unclear. We aimed to compare the efficacy of high-intensity interval training low-volume (HIIT) versus moderate-intensity continuous training (MICT) on serum myonectin, serum lipids, appendicular fat and lean mass, and intramuscular lipids in humans. METHODS: Secondary analysis of a controlled, randomized, clinical trial in adults of both sexes with metabolic syndrome, who underwent a supervised, three-times/week, 12-week treadmill program. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak) for a total of 22 min. MICT (n = 31) trained at 60% of VO2peak for 36 min. Serum myonectin was measured using a human enzyme-linked immunosorbent assay. Lipid profile was determined by enzymatic methods and free fatty acids (FFA) were measured by gas chromatography. Fat and lean mass were assessed by dual-energy X-ray absorptiometry. Intramuscular lipids were measured through proton magnetic resonance spectroscopy. RESULTS: Subjects had a mean age of 50.8±6.0 years and body mass index of 30.6±4.0 kg/m2. Compared to MICT, HIIT was not superior at increasing serum myonectin (p = 0.661) or linoleic acid (p = 0.263), reducing palmitic (p = 0.286) or stearic acid (p = 0.350), or improving lipid profile (all p>0.05), appendicular fat mass index -AFMI- (p = 0.713) or appendicular lean mass percentage -ALM- (p = 0.810). Compared to baseline, only HIIT significantly increased myonectin (p = 0.042), with a large effect size, although both interventions reduced AFMI and increased ALM with a large effect size. Lipid profile, FFA and intramuscular lipids did not change in any intervention group (p>0.05). CONCLUSIONS: Compared to MICT, HIIT low volume did not demonstrate superiority in improving serum lipids. The fact that both training types reduced AFMI without paralleled significant changes in serum myonectin suggests that this myokine may have a minor effect on short-middle-term exercise-induced fat mobilization.

More Adult Women than Men at High Cardiometabolic Risk Reported Worse Lifestyles and Self-Reported Health Status in the COVID-19 Lockdown.

BACKGROUND: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. METHODS: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. RESULTS: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). CONCLUSIONS: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

The profile of patients with postpartum hemorrhage admitted to the obstetric intensive care: a cross-sectional study.

Objective: In Brazil, postpartum hemorrhage (PPH) is a major cause of maternal morbidity and mortality. Data on the profile of women and risk factors associated with PPH are sparse. This study aimed to describe the profile and management of patients with PPH, and the association of risk factors for PPH with severe maternal outcomes (SMO). Methods: A cross-sectional study was conducted in Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) obstetric intensive care unit (ICU) between January 2012 and March 2020, including patients who gave birth at the hospital and that were admitted with PPH to the ICU. Results: The study included 358 patients, of whom 245 (68.4%) delivered in the IMIP maternity, and 113 (31.6%) in other maternity. The mean age of the patients was 26.7 years, with up to eight years of education (46.1%) and a mean of six prenatal care. Uterine atony (72.9%) was the most common cause, 1.6% estimated blood loss, 2% calculated shock index (SI), 63.9% of patients received hemotransfusion, and 27% underwent hysterectomy. 136 cases of SMO were identified, 35.5% were classified as maternal near miss and 3.0% maternal deaths. Multiparity was associated with SMO as an antepartum risk factor (RR=1.83, 95% CI1.42-2.36). Regarding intrapartum risk factors, abruptio placentae abruption was associated with SMO (RR=2.2 95% CI1.75-2.81). Among those who had hypertension (49.6%) there was a lower risk of developing SMO. Conclusion: The principal factors associated with poor maternal outcome were being multiparous and placental abruption.

Repurposing the Open Global Health Library for the discovery of novel Mpro destabilizers with scope as broad-spectrum antivirals.

The SARS coronavirus 2 (SARS-CoV-2) epidemic remains globally active. The emergence of new variants of interest and variants of concern (VoCs), which are potentially more vaccine-resistant and less sensitive to existing treatments, is evident due to their high prevalence. The prospective spread of such variants and other coronaviruses with epidemic potential demands preparedness that can be met by developing fast-track workflows to find new candidates that target viral proteins with a clear in vitro and in vivo phenotype. Mpro (or 3CLpro) is directly involved in the viral replication cycle and the production and function of viral polyproteins, which makes it an ideal target. The biological relevance of Mpro is highly conserved among betacoronaviruses like HCoV-OC43 and SARS-CoV-2, which makes the identification of new chemical scaffolds targeting them a good starting point for designing broad-spectrum antivirals. We report an optimized methodology based on orthogonal cell-free assays to identify small molecules that inhibit the binding pockets of both SARS-CoV-2-Mpro and HCoV-OC43-Mpro; this blockade correlates with antiviral activities in HCoV-OC43 cellular models. By using such a fast-tracking approach against the Open Global Health Library (Merck KGaA), we have found evidence of the antiviral activity of compound OGHL98. In silico studies dissecting intermolecular interactions between OGHL98 and both proteases and comprising docking and molecular dynamics simulations (MDSs) concluded that the binding mode was primarily governed by conserved H-bonds with their C-terminal amino acids and that the rational design of OGHL98 has potential against VoCs proteases resistant to current therapeutics.

Off-label use of dalbavancin in children: a case series.

INTRODUCTION: Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications. PATIENTS AND METHODS: We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections. RESULTS: Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6). CONCLUSIONS: Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.

Onychocolone A produced by the fungus Onychocola sp. targets cancer stem cells and stops pancreatic cancer progression by inhibiting MEK2-dependent cell signaling.

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds. Extracts derived from the fungus Onychocola sp. CF-107644 were assayed via high throughput screening followed by bioassay-guided fractionation and resulted in the identification and isolation of six benzophenone derivatives with antitumoral activity: onychocolones A-F (#1-6). The structures of the compounds were established by spectroscopic methods, including ESI-TOF MS, 1D and 2D NMR analyses and X-ray diffraction. Compounds #1-4 significantly inhibited the growth of the pancreas tumoral cell lines, with low-micromolar Median Effective Doses (ED50s). Compound #1 (onychocolone A) was prioritized for further profiling due to its pro-apoptotic effect, which was further validated on 3D spheroids and pancreatic CSCs. Protein expression assays showed that the effect was mechanistically linked to the inhibition of MEK onco-signaling pathway. The efficacy of onychocolone A was also demonstrated in vivo by the reduction of tumor growth in a pancreatic xenograft mouse model generated by CSCs. Altogether, the data support that onychocolone A is a promising new small molecule for hit-to-lead development of a new treatment for PC.

Bioinformatics tools for the study of bioactive peptides from vegetal sources: evolution and future perspectives.

Bioactive peptides from vegetal sources have been shown to have functional properties as anti-inflammatory, antioxidant, antihypertensive or antidiabetic capacity. For this reason, they have been proposed as an interesting and promising alternative to improve human health. In recent years, the numerous advances in the bioinformatics field for in silico prediction have speeded up the discovery of bioactive peptides, also reducing the associated costs when using an integrated approach between the classical and bioinformatics discovery. This review aims to provide an overview of the evolution, limitations and latest advances in the field of bioinformatics and computational tools, and specifically make a critical and comprehensive insight into computational techniques used to study the mechanism of interaction that allows the explanation of plant bioactive peptide functionality. In particular, molecular docking is considered key to explain the different functionalities that have been previously identified. The assumptions to simplify such a high complex environment implies a degree of uncertainty that can only be guaranteed and validated by in vitro or in vivo studies, however, the combination of databases, software and bioinformatics applications with the classical approach has become a promising procedure for the study of bioactive peptides.

Mycorrhizal fungi arbuscular in organic and conventional sugarcane systems.

Organic production systems are increasingly gaining market share; however, there are still few studies on their influence on the activity of soil microorganisms in sugarcane. Arbuscular mycorrhizal fungi are extremely sensitive to environmental changes, and their activity can be used as a parameter of comparison and quality between organic and conventional systems. The objective of this work was to evaluate mycorrhizal activity in different varieties of sugarcane under two production systems. This work was carried out in a commercial plantation of the Jalles Machado plant in the municipality of Goianésia in Goiás, Brazil. The values of spore density in the soil, mycorrhizal colonization rate in the roots and easily extractable glomalin were evaluated, and the associated fungal species were identified. There was no effect of sugarcane variety on the number of spores or the glomalin content in the soil. The conventional system presented significantly lower mycorrhizal colonization rates than did the organic system. The varieties cultivated under the conventional planting system showed a greater diversity of arbuscular mycorrhizal fungi, where 12 of the 13 different species of mycorrhizal fungi found in both cultivation systems occurred.

Interaction of major saffron constituent safranal with trypsin: An experimental and computational investigation.

Trypsin is a serine protease, an important digestive enzyme that digests the proteins in the small intestine. In the present study, we have investigated the interaction of safranal, a major saffron metabolite, with trypsin using spectroscopic and molecular docking analyses. Fluorescence emission spectra of trypsin were largely affected by the inner filter effect from safranal; that's why these were corrected using the standard procedure. The corrected fluorescence spectra have shown that the safranal quenched the intrinsic fluorescence of trypsin with a blue shift in the wavelength of emission maximum, which revealed that the microenvironment of the fluorophore became more hydrophobic. There was approximately 1: 1 fair binding between them, which increased with a rise in temperature. The interaction was favored, principally, by hydrophobic forces, and there was an efficient energy transfer from the fluorophore to the safranal. Synchronous fluorescence spectra suggested that the tryptophan residues were the major ones taking part in the fluorescence quenching of trypsin. Safranal also influenced the secondary structure of trypsin and caused partial unfolding. Molecular Docking and the Molecular Dynamics simulation of the free and complexed trypsin was also carried out. Safranal formed a stable, non-covalent complex within the S2'-S5' subsite. Moreover, two nearby tyrosine residues (Tyr39 and Tyr151) stabilized safranal through π-π interactions. Additionally, the presence of safranal led to changes in the protein flexibility and compactness, which could indicate changes in the surrounding of tryptophan residues, impacting their fluorescence. Furthermore, a loss in compactness is in line with the partial unfolding observed experimentally. Thus, both experimental and computational studies were in good agreement with each other.

Correction: de Oliveira et al. Viper Venom Phospholipase A2 Database: The Structural and Functional Anatomy of a Primary Toxin in Envenomation. Toxins 2024, 16, 71.

In the published publication [...].

Revisiting the reaction pathways for phospholipid hydrolysis catalyzed by phospholipase A2 with QM/MM methods.

Secreted phospholipase A2 (sPLA2) is a Ca2+-dependent, widely distributed enzyme superfamily in almost all mammalian tissues and bacteria. It is also a critical component of the venom of nearly all snakes, as well as many invertebrate species. In non-venomous contexts, sPLA2 assumes significance in cellular signaling pathways by binding cell membranes and catalyzing ester bond hydrolysis at the sn-2 position of phospholipids. Elevated levels of GIIA sPLA2 have been detected in the synovial fluid of arthritis patients, where it exhibits a pro-inflammatory function. Consequently, identifying sPLA2 inhibitors holds promise for creating highly effective pharmaceutical treatments. Beyond arthritis, the similarities among GIIA sPLA2s offer an opportunity for developing treatments against snakebite envenoming, the deadliest neglected tropical disease. Despite decades of study, the details of PLA2 membrane-binding, substrate-binding, and reaction mechanism remain elusive, demanding a comprehensive understanding of the sPLA2 catalytic mechanism. This study explores two reaction mechanism hypotheses, involving one or two water molecules, and distinct roles for the Ca2+ cofactor. Our research focuses on the human synovial sPLA2 enzyme bound to lipid bilayers of varying phospholipid compositions, and employing adiabatic QM/MM and QM/MM MD umbrella sampling methods to energetically and geometrically characterize the structures found along both reaction pathways. Our studies demonstrate the higher frequency of productive conformations within the single-water pathway, also revealing a lower free energy barrier for hydrolyzing POPC. Furthermore, we observe that the TS of this concerted one-step reaction closely resembles transition state geometries observed in X-ray crystallography complexes featuring high-affinity transition state analogue inhibitors.

Superior capsular reconstruction with the long head of the biceps tendon achieves excellent clinical results and low rotator cuff rerupture rates one year after cuff repair surgery.

PURPOSE: To analyze the clinical one-year evolution of healed and rerupture lesions in patients who received a rotator cuff repair plus Superior Capsular Reconstruction (SCR) with the long head of the biceps (LHB). Moreover, to compare this evolution between men and women. METHODS: A pilot study was conducted on patients who underwent a rotator cuff repair plus SCR with LHB between February 2021 and June 2022. All patients completed pre-operative and one-year post-operative evaluations for tendon type of tear and tendon integrity using Magnetic Resonance Imaging (MRI)after one year of the surgery. Besides, functionality was evaluated with the American Shoulder and Elbow Surgeons (ASES) score; the visual analog scale for pain (VAS); and the Constant score. RESULTS: A total of 38 patients completed the one-year final evaluation, they presented an increased functionality score to 83 and 86 in Constant and ASES scales (p < .001), respectively. Besides, 84% of the patients presented a healed cuff, while rerupture occurred in 16% of the patients. There were differences between the healed and rerupture patients in the total Constant score, with a remarkable increase in the strength subscale, almost double for patients with healed cuff (p < .001); in the same way, daily life activity score, and balance subscale increased, while pain score decreased in the healed cuff group (p < .05). There was no difference in functionality between men and women (p > .05). Besides, almost all patients achieved the MCID in both ASES and Constant total scores, irrespectively of the healing group. CONCLUSION: The cuff repair using SCR with the LHB achieved a low percentage of rerupture and a functional improvement after one year of follow-up. Patients who healed the lesion presented more strength and better performance in daily life activities than those with cuff repurture. Thus, SCR + LHB procedure can be considered an efficient technique for rotator cuff repair surgery for both men and women. Although a comparison with a control group is needed to confirm these findings.

Health and wellbeing status of the long-lived individuals of the Spanish LONGECYL cross-sectional study.

BACKGROUND: The increase in life expectancy and long-lived individuals is a challenge for public health and provides an opportunity to understand the determinants of longevity. However, few studies have addressed the factors associated with the health status and quality of life in a long-lived individual population. We described the perceived health, clinical status, quality of life, and dependency for activities of daily living in a representative population in Castile and Leon, Spain. METHODS: A sample of 759 long-lived individuals aged 95 years and older was studied by the Health Sentinel Network of Castile and Leon (Spain) through a health examination and a structured questionnaire covering quality of life (EQ-5D-3), lifestyle habits, diet, working life and family health. A blood sample was taken for the study of biological and genetic markers. Chi Square and logistic regression OR with 95% confidence intervals were used to analyze the determinants of the long-lived individuals' health status. The significant level for the bivariate analysis was established at 0.05. RESULTS: Perceived health was good, very good or excellent in 64.2%, while only 46.0% had a quality-of-life index above 0.5 (ranging from 0 to 1) and 44.1% maintained acceptable independence for activities of daily living. Quality-of-life index was higher in the oldest, (OR 7.98 [2,32-27.41]) above 100 years compared to those under 98, and men had better values for independence than women (OR 2.43 [1.40-4.29]). Cardiovascular diseases were the most prevalent (85.5%), but neurological and mental diseases and vision problems had the highest impact on quality of life and independence. CONCLUSION: The long-lived individuals of Castile and Leon have a relatively well-preserved health status, although the perception of health is higher than that describing their quality of life and dependence. The quality of life was higher in the oldest age group and showed differences according to sex, with a better quality of life in men. Public health policies and programs should take in account the differences by sex and age as well as the prevention and control of the main conditions related with poor quality of life or dependence. Future research must include the interaction among genetic, socioeconomic, environmental, and other clinical factors in the quality of life and disability of long-lived individuals.

Dysregulation of Glypicans and Notum in Osteoarthritis: Plasma Levels, Bone Marrow Mesenchymal Stromal Cells and Osteoblasts.

In this study of the alterations of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts in Osteoarthritis (OA), the levels of GPCs and Notum in the plasma of 25 patients and 24 healthy subjects were measured. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured over a period of 21 days using both a culture medium and an osteogenic medium. Protein and gene expression levels of GPCs and Notum were determined using ELISA and qPCR at 0, 7, 14 and 21 days. GPC5 and Notum levels decreased in the plasma of OA patients, while the BM-MSCs of OA patients showed downexpression of GPC6 and upregulation of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPCs 2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in patients with OA. Furthermore, the protein levels of GPC2, GPC5 and Notum decreased, while the levels of GPC3 increased. Glypicans and Notum were altered in BM-MSCs and during osteogenic differentiation from patients with OA. The alterations found point to GPC5 and Notum as new candidate biomarkers of OA pathology.

Patient Safety Culture: Nurses' Perspective in the Hospital Setting.

(1) Background: Patient safety culture (PSC) encompasses the values, attitudes, norms, beliefs, practices, perceptions, competencies, policies, and behaviours of professionals that determine organisational commitment to quality and patient safety. Few studies use mixed methods to analyse patient safety culture, and none offer the richness of using a mixed methodology to develop their theoretical model. This study aims to identify the factors nurses believe contextualise and influence PSC in relation to existing theoretical frameworks. (2) Methods: This study employed a sequential explanatory mixed-methods design combined with the Pillar Integration Process for data integration. (3) Results: In the final data integration process, 26 factors affecting nurses' PSC were identified. Factors nurses related to PSC not being assessed with the tool used in phase 1 were notification system, flow of patients, patient involvement, resources and infrastructure, and service characteristics. (4) Conclusions: This mixed-methods study provides an opportunity to identify the weaknesses and strengths of currently developed theoretical frameworks related to PSC and offers content for its improvement. Even though multiple studies aim to assess PSC using existing quantitative method tools, the development of this study offers a glimpse of some aspects relevant to nurses' PSC not included in the theoretical framework of the said tools, such as patient involvement, the flow of patients, and service infrastructure.

Prevalence of sexually risky behaviors among Mexican medical students.

University students are at high risk of sexually transmitted infections due to the lack of adequate sexual education, as well as multiple associated factors, which lead to risky sexual practices. It is important to update data about sexual behaviors to identify the main factors associated with sexually risky behaviors. The present study aimed to evaluate the current prevalence of sexually risky practices in medical students. A cross-sectional study was conducted among medical students through an anonymous self-administered online questionnaire including demographic characteristics and sexual behaviors. We used descriptive statistics and multivariable regression to analyze the data collected. A total of 1520 undergraduate medical students aged between 18 and 28 years old were included in the study. Sixty percent of the students were sexually active with a higher proportion in men (70%), likewise, they had an earlier sexual debut (16.5 vs 16.9 years old), and a greater number of lifetime sexual partners than women (3.8 vs 2.2). The main sexual activity in both groups was vaginal sex with high use of condoms (75%), however, most of them (67%) reported having unprotected oral sex. Logistic regression analysis showed that condomless sex was associated with having oral sex, anal sex, and being female. The findings of this study showed that medical university students are involved in risky sexual behaviors, the major risk factor was unprotected oral sex. Based on these results, we recommended designing interventions to improve sexual education and preventive approaches from early stages such as in middle school students to mitigate sexually transmitted infections among medical university students.

Mining and engineering activity in catalytic amyloids.

This chapter describes how to test different amyloid preparations for catalytic properties. We describe how to express, purify, prepare and test two types of pathological amyloid (tau and α-synuclein) and two functional amyloid proteins, namely CsgA from Escherichia coli and FapC from Pseudomonas. We therefore preface the methods section with an introduction to these two examples of functional amyloid and their remarkable structural and kinetic properties and high physical stability, which renders them very attractive for a range of nanotechnological designs, both for structural, medical and catalytic purposes. The simplicity and high surface exposure of the CsgA amyloid is particularly useful for the introduction of new functional properties and we therefore provide a computational protocol to graft active sites from an enzyme of interest into the amyloid structure. We hope that the methods described will inspire other researchers to explore the remarkable opportunities provided by bacterial functional amyloid in biotechnology.

T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study).

OBJECTIVE: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae. STUDY DESIGN: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T lymphocytes (CMV-IFN-γ-CD8+/CD4+) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up. RESULTS: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8+ or CD4+ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study. CONCLUSIONS: CMV-specific IFN-γ-CD4+ and CD8+ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.

Evaluation of type 1 diabetes' partial clinical remission after three years of heterologous adipose tissue derived stromal/stem cells transplantation associated with vitamin D supplementation.

BACKGROUND: Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group. METHODS: This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c. RESULTS: A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control. CONCLUSION: The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control. TRIAL REGISTRATION: 37001514.0.0000.5257.