This study assesses the impact of nurse-originated changes in central venous catheter (CVC) management on the incidence of central line-associated bloodstream infections (CLABSI) and catheter-related bloodstream infections (CRBSI). It is a single-center retrospective cohort study conducted at an urban, tertiary referral, and academic center serving pediatric patients. The study cohort comprised 236 patients and 323 CVCs seen between 2012 and 2022. CLABSI and CRBSI were defined according to the Centers for Disease Control and Prevention definitions. Oncology nurse leaders developed CVC-specific educational modules for CLABSI prevention. All relevant information during the CVC maintenance period was noted in the patient's CVC logbook. 24 (7%) cases of confirmed CLABSI were identified. The incidence of CVC-related infections was 0.32 cases per 1000 catheter days. The incidence decreased by 40% between the first and second three-year study period. Documented exit-site infection was reported in 32 (10%) cases. The correlation between exit-site infection and CLABSI was found in 9 (28%) cases. Our CVC-related infection rates are significantly lower than the incidence reported by the Italian Association of Pediatric Hematology and Oncology, which settles at 3-5 cases per 1000 catheter days. Our data confirm the effectiveness of local CVC management guidelines in preventing CVC-related infectious complications.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

The Zika virus (ZIKV) epidemic elicited a rapid commitment to the development of animal models for ZIKV research. Non-human primates (NHPs) and mice have made significant contributions to this research, but NHPs are expensive, have a long gestation period, and are available only in small numbers; and non-genetically modified mice are resistant to infection. To address these deficiencies, we have established the laboratory opossum, Monodelphis domestica, as a small animal model that complements the mouse and monkey models. We developed and validated an indirect ELISA for measuring antibodies to ZIKV in opossums, as well as an immunohistochemistry (IHC) method to detect ZIKV NS1 protein in tissue samples and a PCR method to detect ZIKV RNA in tissue samples. Opossum pups inoculated intracerebrally as embryos, juveniles inoculated by several routes, and mothers that cannibalized inoculated pups, became persistently infected with ZIKV. The virus spread to multiple organs and persisted up to 38 weeks (the latest endpoint of the experiments). A robust humoral immune response was mounted, and high titers of antibodies also persisted for 38 weeks. The results establish M. domestica as natural, non-genetically modified animal model in which ZIKV persists long term after experimental infection, and as a unique animal model for research on ZIKV infection, persistence of infection, and biological responses to infection.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS or stearic acid (SA)-induced inflammatory response in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK which acts downstream of TPR, attenuated LPS and/or SA-induced pro-inflammatory response. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, TPR agonist by itself elicits an inflammatory response which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs and this effect is mediated via TLR4 and/or ROCK signaling.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p<0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, although coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly to multidrug-resistant Gram-negative bacteria, and lastly to a possibly fatal Candida glabrata. Development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

COVID-19 infection is extremely dangerous for persons with comorbidities such as kidney disease and diabetes. Although many people of all ages and socioeconomic backgrounds have suffered due to this pandemic, those with underlying medical conditions like kidney disease and diabetes are more vulnerable to becoming infected with COVID-19 related to weak immunity. However, the role of vaccination in the co-infection of COVID-19 with diabetics is not available in the literature. Therefore, we examine the unique challenges presented by the co-infection of COVID-19 in individuals with diabetes, focusing on its disease transmission dynamics. A mathematical modelling technique is to be employed in this work to analyse the dynamics of COVID-19 outbreaks with seven compartments, including vaccination with comorbidities such as diabetes. We also investigated analytically by displaying the solutions' existence, boundedness, positivity and sensitivity. After calculating the basic reproduction numbers, the stability analysis of model equilibrium points is also covered. If the reproduction numbers are less than unity, the disease-free equilibrium points of the model appear to be both locally and globally stable. The findings of this study are that as the vaccination rate rises, the incidence of COVID-19 and its co-infections with diabetes decreases. Effective disease treatment strategies may be based partly on the possible impact of vaccination on the co-infection of COVID-19 related to diabetic disease insights.

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices.

Background: Cardiovascular (CV) morbidity and mortality are many times higher in chronic kidney disease (CKD), as well as IgA nephropathy (IgAN), than in the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The study aimed to determine the prognostic role of metabolic profiles in a homogenous group of CKD patients. Methods: One hundred and forty-five IgA nephropathy patients (92 male, 53 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for a median of 190 months. The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal). Results: Patients with MetS had significantly more endpoint events (16/27 patients vs. 15/98 patients, p = 0.001) compared to the nonMetS group. Of the secondary endpoints (CV or renal separately), the rate of the renal and CV endpoints was significantly higher in the MetS group (p = 0.001 and p = 0.029). The primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined by Cox regression analysis. Independent predictors of secondary renal endpoint were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. Kaplan-Meier curves showed significant differences in MetS and non-MetS when examined at the combined endpoints (CV and renal) or at each endpoint separately. The primary endpoint rate increased significantly with the increased number of MetS components (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusion: Our results showed that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

Buruli ulcer is a chronic ulcerative disease of skin and subcutaneous tissues caused by infection with Mycobacterium ulcerans. Although Australian possums are known to be susceptible to Buruli ulcer, many aspects of the disease in possums, including welfare impacts, remain largely unreported. Severe clinical Buruli ulcer was identified in four common ringtail possums (Pseudocheirus peregrinus) from Melbourne, Victoria. All four possums were euthanised due to welfare concerns and poor prognosis, based on the presence of deep ulcerative lesions to paws, some of which exposed carpal or tarsal bones. These lesions were considered likely to cause partial or complete loss of limb function, which would severely affect the welfare and survival of these wild arboreal animals. Histologically, there was severe ulcerative necrotising pyogranulomatous dermatitis, panniculitis, and myositis, with intralesional acid-fast bacteria. M. ulcerans was detected by real-time PCR in all swabs and biological tissues collected from all four cases. Buruli ulcer may be an important and under-recognised cause of poor possum welfare in endemic areas. In addition to severe cutaneous lesions, infection extends to underlying bones and joints, and the systemic distribution of M. ulcerans throughout all major tissues and internal organs, as observed in these four cases, may further impact the health and fitness of infected possums. Further research is needed to investigate the epidemiology, pathogenesis and impacts of Buruli ulcer in possums, and to inform the design of interventions that may protect the health and welfare of possums and other affected animal species.

The climate change constitutes nowadays an enormous global threat for human health and environmental sustainability. The expanding world population and the increased global needs for food production have an important negative impact upon environment. Diet can link human health with environmental sustainability. Food production systems are closely related to anthropogenic greenhouse gas emissions and the aggravation of climate change, and current western type, animal-based, dietary patterns may lead to adverse environmental footprints. In the present narrative review, we address the interconnection of the Mediterranean diet (MD) with climate change and sustainability. MD is a highly recommended dietary intervention for the prevention and management of various endocrine and cardiometabolic diseases. Beyond its evidence-based, health-promoting effects, it also has beneficial environmental impact, reducing greenhouse gas emissions and enhancing biodiversity, food security and sustainability. Based on the evidence reviewed herein, MD should be incorporated within the framework of a “One Health” model, which involves the improvement not only of human health but also of planetary health and food system sustainability. Our review aims to provide a stimulus for health pro-fessionals to strongly recommend the implementation of MD under the current pressure of climate change, despite all barriers, targeting both human health preservation and the planetary well-being.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Bloodstream infection (BSI) after pediatric liver transplantation (PLT) is a common and severe complication that affects patient survival. Children with biliary atresia (BA) are at an increased risk for clinically significant infections. This study evaluated the impact of post-PLT BSI on clinical outcomes in children with BA. A total of 67 patients with BA aged <18 years who underwent PLT between April 2006 and September 2020 were analyzed and divided into two groups according to the occurrence of post-PLT BSI within 1 month (BSI vs. no BSI = 13 [19.4%] vs. 54 [80.6%]). The BSI group was significantly younger at the time of PLT and had a higher frequency of BSI at the time of PLT than the no BSI group. Early vascular complications within 3 months and reoperations were significantly more frequent in the BSI group. Univariate and multivariate analyses revealed that bacteremia within 1 month of PLT and graft-to-recipient weight ratio >4% were significantly associated with vascular complications. In conclusion, BSI after PLT is associated with increased vascular complications and reoperations. Proper control of bacterial infections and early liver transplantation before uncontrolled BSI may reduce vascular complications and unexpected reoperations in children with BA.

Buckground: Although ceftazidime/avibactam (CAZ/AVI) has become important option for treating adults and children, no recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant KPC-2 producing-Klebsiella pneumoniae carrying blaVEB-25 and the use of a customized active surveillance program in conjunction to infection control measures. Methods: The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics. Customized molecular surveillance was implemented at hospital level and enhanced infection control measures were taken for early recognition and prevention of outbreak. Detection and identification of blaVEB-25 was performed by next-generation sequencing. Results: That was the first case of a bloodstream infection caused by KPC producing K. pneumoniae that was resistant to CAZ/AVI without the presence of a metalo-β-lactamase in the multiplex PCR platform in a neonate. All 36 additional patients tested (12 in the same NICU and 24 from other hospital departments) carried wild-type blaVEB-1 but they did not harbor blaVEB-25. Conclusion: The emergence of VEB-25 is signal for horizontal transfer of plasmids at hospital facilities and it is of greatest concern for maintaining a sharp vigilance for surveillance of novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and early implementation of infection control measures against antimicrobial resistance.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

In the course of our ongoing research targeting the identification of potential biocontrol agents from entomopathogenic fungi (EPF), we explored a solid-state rice fungal extract of Blackwellomyces roseostromatus BCC56290 derived from infected lepidopteran larvae. Chemical and biological prospections afforded four unprecedently reported natural products differentiated into one dimeric naphthopyran bioxanthracene ES-242 derivative (1) and three cyclodepsipeptides (2-4) in addition to two known cyclodepsipeptides, cardinalisamides B (5) and C (6). Chemical structures of the isolated compounds were elucidated through comprehensive 1D/2D NMR and HR-ESI-MS data together with comparisons to the reported literature. The absolute configuration of the isolated cyclodepsipeptide was determined using Marfey’s method. All isolated compounds were assessed for their antimicrobial, cytotoxic and nematicidal activities with some compounds revealed significant activities.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

In this very personal hunt for the meaning of the bacterial cell cycle, the snark, I briefly revisit and update some of the mechanisms we and many others have proposed to regulate the bacterial cell cycle. These mechanisms, which include the dynamics of calcium, membranes, hyperstructures and networks, are based on physical and physico-chemical concepts such as ion condensation, phase transition, crowding, liquid crystal immiscibility, collective vibrational modes, reptation, and water availability. I draw on ideas from subjects such as the ‘prebiotic ecology’ and phenotypic diversity to help with the hunt. Given the fundamental nature of the snark, I would expect that its capture would make sense of other parts of biology. The route therefore followed by the hunt has involved trying to answer questions like “why do cells replicate their DNA?”, “why is DNA replication semi-conservative?”, “why is DNA a double helix?”, “why do cells divide?”, “is cell division a spandrel?” and “how are catabolism and anabolism balanced?”. Here, I propose some relatively unexplored, experimental approaches to testing snark-related hypotheses and, finally, I propose some possibly original ideas about DNA packing, about phase separations, and about computing with populations of virtual bacteria.

Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Type 2 diabetes mellitus (T2DM) poses a significant economic and clinical burden. Clinical inertia is defined as the failure of healthcare providers to modify therapy in the presence of clear indications. This study aimed to identify patient opinions on insulin to understand the barriers preventing type 2 diabetes patients from initiating insulin treatment when recommended by their physician. This cross-sectional observational study included 671 individuals with poorly controlled T2DM and HbA1c levels exceeding 10%. These patients required either the initiation or escalation of their existing insulin therapy. The participants were referred to Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) for consultation between January 2022 and July 2022.Results: During discussions between the researcher (clinician) and the inadequately controlled T2DM patients, the primary reasons for refusing insulin therapy were identified. These reasons included fear of injections, the belief that insulin induces dependence and is a last resort, concerns about hypoglycemia and complications, cost, difficulty in computing doses, social stigma, inconvenience and disruption to life and work, storage challenges, fear of weight gain, dependence on others, and lack of confidence.The study concludes that the clinical barriers faced by individuals who refuse the initiation of insulin therapy are diverse. The most common belief among the patients was that insulin leads to dependence (38%), while the smallest percentage cited a lack of confidence in insulin as an effective treatment for lowering hyperglycemia.

Because data on the fungal gut community structure of African children are scarce, we aimed to describe by reanalysing rRNA ITS1 and ITS2metabarcoding data from a study designed to assess the influence of microbiota in malaria susceptibility in Malian children from the Dogon country. More specifically, we aimed to establish the core gut mycobiome and compare the gut fungal community structure of breastfed children, aged 0-2 years, with other age groups. Briefly, DNA was extracted from 296 children’s stool samples. Both rRNA ITS1 and ITS2 genomic barcodes were amplified and subjected to Illumina MiSeq sequencing. The ITS2 barcode generated 1,975,320 reads and 532 operational taxonomic units (OTUs), while the ITS1 barcode generated 647,816 reads and 532 OTUs. The alpha diversity was significantly higher by using the ITS1 compared to the ITS2 barcode (p

Background. During the COVID-19 pandemic, there was an increased number of the hospitalized COVID-19 positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research was to explore factors associated with the length of hospitalization of patients with T2DM and mild form of COVID-19. Material and Methods. This retrospective cohort study involved all patients who tested positive for COVID-19 and were treated in the dedicated COVID department of the University Clinical Center (UCC) in Nis between September 10, 2021, and December 31, 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein-CRP, creatinine kinase, D-dimer), as well as glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results. Out of the total 549 COVID-19 positive patients treated, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6±16.8 vs. 64.2±15.3, p

Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.

Background/aims: Prior research identified a significant association between heart disease and metabolic dysfunction-associated liver steatohepatitis (MASLD), but the mechanisms are unclear. This study aims to search predictive biomarkers for grade I left ventricular diastolic dysfunction (LVDD), an early stage of heart failure (HF), in type 2 diabetes mellitus (T2DM) patients. Methods: This single-center, prospective observational study screened 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: The study analyzed 50 patients (mean age 58±11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean BMI 34.4±5.9 kg/m2), and a mean HbA1c of 7.9±1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate to severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, ɑ2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s`, E wave, E/e`, E/A, medium E`, and septal e` (p< 0.05 for all). ɑ2-macroglobulin > 1.92 g/L (AUROC= 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score > 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusion: HF is a multifaceted disorder associated with multisystem organ damage, including nonalcoholic MASLD. Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as ɑ2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients.

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there are few data available on the description of parasites circulating in this area, especially on protozoan belonging to the phy-lum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on Oxford Nanopore Technologies sequencing platform using the 18S gene of fourteen Apicomplexa-positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify as Apicom-plexa-positive 10 samples out of 14 and reveal the presence of co-carriages. The same samples were also sequenced with Illumina platform, for validation purposes. On samples identified as Apicomplexa-positive by both platforms, a strong positive correlation at up to genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detec-tion, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John's wort with its antidepressant, antitumor and antimicrobial properties. Chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here we studied two synthetic PPAP-derivatives, PPAP 23 and PPAP 53, as to their antimicrobial activity. While PPAP 23 is insoluble in water, PPAP 53, the sodium salt, is water-soluble. In vitro, both compounds exhibited good and comparable activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae, even at high concentrations. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar neutralizing effect was also seen with serum albumin. In a septic arthritis model triggered by S. aureus PPAP23 decreased the formation of abscesses and bacterial load in kidneys, and in a mouse skin abscess model topical treatment with PPAP 53 resulted in an approximately two-fold reduction in S. aureus counts. PPAP 23 and PPAP 53 also showed high growth inhibiting activity against anaerobic Gram-positive pathogenic gut bacteria such as Clostridium perfringens and Clostridium difficile. Based on these results, we envision potential application of PPAP 23 and PPAP 53 in the topical treatment of wound infections with Gram+ pathogens, and their oral use in intestinal infections with C. difficile.

Background: Oral hypoglycemic agents are typically the first-line treatment for type 2 diabetes mellitus (T2DM). This study examines the benefits of initiating insulin as the first-line therapy for newly diagnosed T2DM patients. Methods: A PubMed search using keywords ‘Type 2 Diabetes Mellitus’ and ‘Early STIIT’ included RCTs assessing beta cell function, insulin resistance, glycemic control, and lipid profiles. Revman 5.4.1 software was used for meta-analysis, with outcomes represented as mean difference (MD) and 95% confidence intervals (CI). Results: Significant reductions in fasting blood glucose (FBG: MD -4.75, 95% CI -7.07, -2.43), HbA1c (MD -1.84, 95% CI -3.01, -0.68), and postprandial glucose (PPG: MD -9.02, 95% CI -10.48, -7.56) were observed with early STIIT therapy compared to baseline. Beta cell function improved (HOMA-B: MD 53.70, 95% CI 27.78, 79.63) and insulin resistance decreased (HOMA-IR: MD -1.84, 95% CI -3.65, -0.04). Lipid profile improvements included reductions in total cholesterol (TC), triglycerides (TG), and LDL, with no change in HDL. BMI remained stable (MD -0.15, 95% CI -0.82, 0.51). Most patients achieved long-term remission and glycemic control without oral hypoglycemic agents. Conclusion: Early STIIT in newly diagnosed T2DM patients significantly reduces glycemic markers and maintains long-term glycemic control, preserving beta cell function. The therapy also improves lipid profiles, reducing TC, TG, and LDL. Initiating insulin as a first-line treatment shows promising results for glycemic control and overall metabolic health.

The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates ribosome biogenesis and the transcription of ribosomal genes. Its inactivation impacts protein synthesis necessary for transport of cell adhesion molecule. In Dictyostelium discoideum, the activity of mechanistic Target of Rapamycin Complex 2 (mTORC2) is crucial for cAMP synthesis and relay, processes that depend on heterotrimeric G-proteins and Ras GTPases. Mutants lacking rip3 or lst-8 genes exhibit impaired adenyl cyclase activation and cAMP signaling, resulting in deficient expression of the cell adhesion protein CsaA. Despite this, rip3^- cells, which have impaired mTORC2, upregulate Cad-1 expression, a cell adhesion protein regulated by Ras-GTPases, to compensate for the loss of CsaA. lst-8^- cells, which have both mTORC1 and mTORC2 inactivated, show reduced nutrient sensing, premature CsaA expression and solitary cell behavior. These cells also show defective transport of adhesion proteins to the cell surface, impeding aggregation. Similar defects are observed with caffeine treatment, suggesting both mTORC1 and mTORC2 inhibition. This study highlights the interplay between mTORC1 and mTORC2 in regulating cell adhesion and aggregation through cAMP signaling and protein synthesis pathways in Dictyostelium.

ABSTRACTCaffeine is known to impair both growth and development in the model social amoeba Dictyostelium discoideum. However, little is known about the transcriptional regulation in response to caffeine treatment in Dictyostelium. In yeast cells, caffeine mimics the effect of rapamycin in inhibiting mTORC1 activity. Here, we investigated whether changes in growth and development of Dictyostelium in the presence of caffeine or rapamycin are mediated by mTORC1 and/or mTORC2. Results: Treatment of wild type cells with caffeine or rapamycin resulted in severely impaired growth and in the formation of small aggregates in comparison to untreated cells. rip3‾ cells (lacking a mTORC2 component) and lst8‾cells (lacking a component of both mTOR complexes) showed higher and slower growth rates, respectively, in comparison to parental AX3 cells. Parental AX3 and rip3‾ cells displayed similar sensitivity to rapamycin and caffeine, while lst8‾ cells were more sensitive to these compounds. When developed in the presence of caffeine or rapamycin, AX3 cells formed aggregates after a long delay. Caffeine did not alter the morphology of small rip3‾ mounds and lst8‾ cells continued to remain solitary. However, in the presence of 1µM rapamycin rip3‾cells failed to form mounds while AX3 cells streamed and formed aggregates. Complementation of lst8‾ cells with the wild type lst8 gene rescued the aggregation phenotype. cDNA microarray analysis to uncover the spectrum of differentially regulated genes in response to caffeine treatment revealed 104 and 193 differentially expressed genes at 3-and 6-hours of development, respectively, in comparison to control cells. After 6 hours of starvation in the presence of caffeine, 25 genes encoding ribosomal proteins and 4 encoding elongation factors were up regulated. Furthermore, we identified that upon caffeine treatment at the 3- and 6-hours’ time points, 12 (10 up and 2 down) and 21 (13 up and 8 down) genes, respectively, encoding proteins involved in early development. Conclusion: We conclude that caffeine and rapamycin have similar effects in decreasing the growth rate and in reducing the aggregate size of D. discoideum. Studies with lst8‾ and rip3‾ cells suggest that these compounds affect cell growth and aggregation by acting on both mTOR complexes, mTORC1 and mTORC2. Analysis of the differentially expressed genes after caffeine treatment suggests a key role of these genes in growth and aggregation.

This study aimed to present a systematic meta-analysis examining the association between Helicobacter pylori (H. pylori) infection, hemoglobin A1c levels, and the development of type 1 diabetes mellitus. The initial search identified 451 articles related to the association between H. pylori infection and T1DM. Among them, 14 articles had 2,971 participants meeting the inclusion criteria for advanced meta-analysis. A significant association was observed between H. pylori infection and T1DM, with an odds ratio (OR) of 1.87 (95% confidence interval [CI]: 1.27–2.78, p = 0.002). A subgroup analysis on H. pylori status showed that a longer duration of diabetes diagnosis and higher hemoglobin A1c levels were significantly associated with H. pylori infection (p < 0.001 for both). However, there was no significant association between H. pylori infection and the diagnostic age of diabetes (p = 0.306). These findings contribute to the understanding of the association between H. pylori infection and T1DM, thereby highlighting the potential role of H. pylori in influencing the duration and glycemic control of diabetes.

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P&lt;0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. Summarizing, incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. The incident T2DM and diabetes free Hungarian population were included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p&lt;0.0001. The risk of having cancer was age-dependent, having the highest odd in the age group 18-39. The incidence of cancer was declining in the non-diabetic but was unchanged in T2DM population. The average lag time of diagnosing a cancer after the detection of T2DM was 3.86 months.; (4) Conclusions: Iincident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Catheter-associated bloodstream infection (CVC-BSI) is a significant cause of morbidity and mortality among hemodialysis patients. In our center was a notable increase in CVC associated with patient age and morbidity. This 10-year retrospective study investigated catheter-associated bloodstream infections (CVC-BSI) in hemodialysis patients. We recorded a total of 67 bacteremia episodes in 52 patients, predominantly linked to Gram-positive microorganisms, particularly Staphylococcus aureus, the study found a mean age of 68 years, 74.6% males, and 88% with tun-neled jugular catheters. Notably, catheter removal occurred in 65.7% of cases, more frequently in Gram-positive instances. Two episodes of endocarditis and five ICU admissions were reported. The study identified a higher incidence in the summer and a significant decrease in bacteremia from 2017, coinciding with the introduction of Tauro-LockTM. Despite enhanced preventive measures during the COVID-19 pandemic, there was no significant impact on catheter infection rates. This research emphasizes the importance of early catheter removal, highlights seasonal variations in incidence, and suggests a potential positive influence of Tauro-LockTM on de-creasing CVC-BSI rates in hemodialysis units.

Bicarbonate and CO2 are essential substrates for carboxylation reactions in bacterial central metabolism. In Staphylococcus aureus, the bicarbonate transporter, MpsABC (membrane potential-generating system) is the only carbon concentrating system. A mpsABC deletion mutant can hardly grow in ambient air. In this study, we investigated the changes that occur in S. aureus when it suffers from CO2/bicarbonate deficiency. Electron microscopy revealed that mpsABC has a twofold thicker cell wall thickness compared to the parent strain. The mutant was also substantially inert to cell lysis induced by lysostaphin and the non-ionic surfactant Triton X-100. Mass spectrometry analysis of muropeptides revealed the incorporation of alanine into the pentaglycine interpeptide bridge, which explains the mutant’s lysostaphin resistance. Flow cytometry analysis of wall teichoic acid (WTA) glycosylation patterns revealed a significantly lower -glycosylated and higher ß-glycosylated WTA, explaining the mutant’s increased resistance towards Triton X-100. Comparative transcriptome analysis showed altered gene expression profiles. Autolysin-encoding genes such as sceD, a lytic transglycosylase encoding gene, were upregulated, while genes related to cell wall-anchored proteins, secreted proteins, transporters, and toxins were downregulated. Overall, we demonstrate that bicarbonate deficiency is a stress response that causes changes in cell wall composition and global gene expression resulting in increased resilience to cell wall lytic enzymes and detergents.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSD), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role of immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant com-pound, on osteoporotic bone loss remains largely unknown. Here, we show that the administra-tion of LYC to OVX rats reduces body weight gain, improves lipid metabolism and preserves bone quality. In addition, LYC treatment inhibits ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and pro-moting osteogenesis during bone remodeling. Mechanically, LYC may improve bone quality via an increase in the expressions of FoxO1 and Runx2, and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regula-tion of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for os-teoporosis management.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

Coronavirus disease-19 (COVID-19) has disproportionately affected certain demographics in England, exacerbating existing health disparities. Effective therapeutics are a critical line of defence against COVID-19, particularly for patients at elevated risk for severe disease. Surveillance systems were established to monitor usage of COVID-19 therapeutics in hospital and community settings and inform stewardship. Three antiviral therapies: nirmatrelvir plus ritonavir (Paxlovid®), remdesivir (Veklury®), and molnupiravir (Lagevrio®); and two neutralising monoclonal antibody therapies (nMAbs): sotrovimab (Xevudy®) and casirivimab with imdevimab (Ronapreve®); were in use in England between July 2020 to April 2023. This paper aims to illuminate trends in the utilisation of COVID-19 therapeutics treatment in both hospital and community settings, stratified by the Index of Multiple Deprivation (IMD) in England. Chapter 3 of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) report 2022 to 2023 also discusses the epidemiological surveillance of these five directly-acting antiviral COVID-19 therapeutics use in England between 2022 to 2023.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

The burden of bacterial bloodstream infections (BSIs) is rapidly increasing in Africa including Rwanda. This is a retrospective study investigates the diversity, distribution, and antimicrobial susceptibility profiles of BSIs bacteria in three tertiary referral hospitals in Rwanda between 2020 and 2022. A total of 1,532 blood culture tests were performed for visiting patients. Overall, the proportions of Gram-negative and Gram-positive bacteria were 48.2% and 51.8, respectively. Staphylococcus aureus was the predominant species accounting for 25% of all Gram-positive BSIs species and Klebsiella species representing 41% of all Gram-negative BSIs species. Antimicrobial susceptibility testing revealed that Amikacin exhibited the highest activity against Enterobacter spp., Serratia spp. and Escherichia coli in &gt;92% of cases and Klebsiella spp. in 75.7%. Meropenem and Imipenem were highly efficacious to Salmonella spp. (100% susceptibility), Enterobacter spp. (96.2% and 91.7%, respectively), and Escherichia coli (94.7% and 95.5%, respectively). The susceptibility of Enterococcus spp., S. aureus, and Streptococcus spp. to Vancomycin was 100%, 99.5% and 97.1%, respectively. Klebsiella spp. was highly sensitive to Colistin (98.7%), Polymyxin B (85.6%), Imipenem (84.9%), and Meropenem (78.5%). We recommend strengthening the implementation of integrated transdisciplinary and multisectoral One Health including AMR-stewardship for the surveillance, prevention, and control of AMR in Rwanda.

Coagulase-Negative Staphylococci (CoNS) are commensal on human body surfaces and for years, they were not considered a cause of bloodstream infection and were often regardered as contamination. However, the association of CoNS with nosocomial infection is increasingly recognized. The insertion of cannulas and intravascular catheters represents the first source of CoNS entry into the bloodstream, causing bacteremia and sepsis. They owe their pathogenic power to their ability to produce biofilms on surfaces, such as medical devices. In this study, we evaluate the adhesive capacity of CoNS isolated from blood cultures by comparing spectrophotometric phenotypic assay with genotypic analysis based on the evidence of the ica operon. We retrospectively reviewed the database of CoNS isolated from blood cultures, that were considered to be responsible for 361 bloodstream infections. Among them, we selected 89 ones who had full records. Our data show that S. epidermidis was the predominant species isolated, and with greater adhesive capacities, especially those with the complete operon. Knowing the adhesive capabilities of a microorganism responsible for sepsis can be useful in implementing appropriate corrective and preventive measures, as conventional antibiotic therapy cannot effectively eradicate biofilms.

Introduction: The reduced implementation of surveillance programs and limited bedside infectious diseases consultations due to the pressure of COVID-19 pandemic in healthcare systems led to increased rates of irrational use of antimicrobials and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). Material-Methods: This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram positive and negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the Intensive Care Unit (ICU). Additionally, bloodstream infections with requested infectious diseases consultation were reported (n=400), determining whether these were carried out via telephone contact or at the patient's bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization and clinical outcome were analysed. Results: A total of 4569 strains of Gram positive and negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018-2019, a total of 246 infectious diseases consultations were carried out, while during the period 2020-2022 154, with the percentage of telephone consultations 15% and 76% respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic and 28-day mortality was significantly reduced in cases with bedside consultations. Conclusion: Empowering of infectious diseases surveillance programs and committees, rational use of antimicrobials agents and bedside infectious diseases consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains.

In the early 2000s, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) emerged as a performant and relevant tool for identifying micro-organisms. Since then, it has become practically essential for identifying bacteria in microbiological diagnostic laboratories. In the last decade, it was successfully applied for arthropod identification allowing to distinguish vectors from non-vectors of infectious diseases. However, identification failures are not rare, hampering it widely use. Failure is generally attributed either to the absence of respective counter species MS spectra in the database, or to the insufficient quality of query MS spectra (i.e. lower intensity and diversity of MS peaks detected). To avoid matching errors due to non-compliant spectra, the development of a strategy for detecting and excluding outlier MS profiles became compulsory. To this end, we created MSProfileR, an R package leading to a bioinformatics tool through a simple installation, integrating the control quality system of MS spectra and an analysis pipeline including peak detection and MS spectra comparisons. MSProfileR can also add metadata concerning the sample that the spectra are derived from. MSProfileR has been developed in the R environment and offers a user-friendly web interface using the R Shiny framework. It is available on Microsoft Windows as a web browser application by simply navigation using the link of the package on the Github. MSProfileR is therefore accessible to non-computer specialists and is freely available to the scientific community. We evaluated MSProfileR using two datasets including exclusively MS spectra from arthropods. In addition to coherent sample classification, outlier MS spectra were detected in each dataset confirming the value of MSProfileR.

Maternal obesity and/or Western diet (WD) is associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition, and was associated with reduced abundance of Lactobacillus in GF offspring. Further, expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, and highlights the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.

Type 2 diabetes mellitus (T2DM) is a global health concern driven by factors such as obesity, sedentary behavior, and poor diet. This study uses data from the 2017-18 Bangladesh Demographic and Health Survey (BDHS) to analyze regional and individual predictors of diabetes and predi-abetes. Employing a Bayesian multinomial mixed-effects model, we account for regional varia-bility and individual factors like age, gender, BMI, residence, wealth, education, employment, and hypertension. Our results indicate significant regional differences and associations between de-mographic and health-related factors with diabetes risk. Younger individuals and those with higher BMI are more likely to be diabetic, while hypertension significantly increases diabetes risk. We applied machine learning (ML) models, including logistic regression, decision trees, k-nearest neighbor, linear discriminant analysis, and random forest, to classify diabetic status using these predictors, assessing their accuracy through 10-fold cross-validation. Logistic regression and linear discriminant analysis demonstrated robust performance across various response distributions. Simulation studies further examined the impact of different response distributions on model performance, revealing significant differences in classification accuracies. This approach of esti-mating parameters with a Bayesian model, applying ML for prediction, and conducting simulation studies to explore various scenarios highlights the importance of integrating these methodologies for effective diabetes prediction, providing insights for public health strategies to mitigate T2DM's impact.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

In tropical developing regions, typhoid fever and malaria often co-occur, posing serious health risks. The two illnesses have similar symptoms, which makes diagnosis and treatment more difficult. Through a thorough analysis of existing literature on typhoid fever, malaria, and co-infection, including research articles, case studies, and review papers, this review seeks to understand the dynamic interactions between typhoid fever and malaria co-infection. The review highlights important problems with co-infection between typhoid and malaria, such as higher morbidity and death, diagnostics-related challenges, and antibiotic resistance. Overlapping symptoms and limitations in current diagnostic tests impede accuracy. Treatment plans are made more difficult by the advent of typhoid strains that are resistant to drugs. The analysis concludes by highlighting the necessity of developing more sensitive and specific diagnostic methods in order to accurately diagnose co-infections. Going forward, the review emphasizes the need for more investigation into the immunological connections between malaria and typhoid illnesses. Essentially, this paper offers a thorough summary of the difficulties and possibilities related to co-infection between typhoid and malaria. It provides a framework for upcoming studies and initiatives that seek to improve public health and patient outcomes in the face of these intricately linked health problems.

Diarrhea is a common occurrence following vascular organ transplantation, including kidney transplants. It can be induced by non-infectious factors, adverse effects of immunosuppressive drugs, or infectious agents such as viruses, bacteria, fungi, or parasites. Intestinal protozoan parasites, include Cryptosporidium spp., are causes of infectious diarrhea particularly in immunocompromised patients. This review aims to summarize reports on epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in adult patients, particularly following kidney transplantation.

Regular exercise has been shown to have a positive effect on the health outcomes of individuals with Type-2 diabetes mellitus (T2DM), however, it is still underutilised in developing countries. This study investigated diabetes-related knowledge, attitudes, and practice toward exercise and its benefits among individuals with T2DM. A total of one hundred and ninety-nine participants (male= 21.6% and female= 78.4%) with T2DM, aged between 18- 75, 43.77 (SD ±14.78) years participated in the study. A validated diabetes-related knowledge, attitude, and practice questionnaire, evaluated by true/false or unsure was utilised in the study. Descriptive and inferential statistics analysis was used to analyze data with the significance set at p<0. The study results demonstrated significantly poor diabetes-related knowledge of exercise (p<0.001). The majority of the study participants 163 (81.90%) with T2DM did not know that physical activity and exercise are different. Regarding the attitude of the individuals with T2DM, 158 (70.40%) of the study participants felt that their regular work was an adequate substitution for exercise. More than 50% of the study participants demonstrated a positive practice towards exercise and its benefits towards T2DM (p<0.001). The study revealed that participants’ knowledge and attitudes were poor towards exercise and its benefits, but their practice was good.

Since cART was introduced to treat AIDS, the mortality rate due to AIDS has markedly decreased and the convalescence of HIV-infected individuals has improved drastically. However, HIV-1 sexual transmission has made HIV become a global epidemic. Sacran is a megamolecular poly-saccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture re-tention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects of Sacran as a barrier to HIV transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated.HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests the use of sacran gel to protect against HIV-1 transmission.

A sixty-six-year-old woman with a strong family history of breast cancer noted gradual onset of axillary lymph node enlargement in 2019. Axillary lymph node biopsies disclosed Lymph node involvement by Chronic Lymphocytic Leukemia (CLL/SLL). Immunophenotype analysis of nodal tissue and of bloodstream leukemic cells in immunohistochemistry and flow cytometry and next generation molecular diagnostics confirmed CLL/SLL. Replicate absolute peripheral blood lymphocyte counts in excess of 5.0 x 10e3/microliter confirmed the numerical threshold for diagnosis of Chronic Lymphocytic Leukemia in the bloodstream. FISH studies disclosed an immunoglobulin “mutation negative” CLL/SLL genotype without a light chain restriction pattern. No translocations or germline mutations were present. Borrelia spirochetes in the bloodstream were detected with simultaneous high spirochetemia of both borrelia miyamotoi and borrelia burgdorferi. FISH hybridization of leukemic lymphocytes disclosed extensive borrelia invasion of the cytoplasm and of the nucleus compartments of CLL/SLL tumor cells. Retrospective studies of the patient’s archival stored blood smears obtained three years prior in 2016 at age 63 disclosed no evidence of CLL/SLL but confirmed asymptomatic bloodstream borrelia miyamotoi and borrelia burgdorferi borrelia infection. Lyme serology had been reported as negative in 2016. Additionally, retrospective FISH DNA hybridizations focused on preleukemic bloodstream Lymphocytes disclosed rare borrelia spirochetal adherence to benign blood lymphocytes in the year 2016 in the preleukemic blood smears. This case report is the very first to describe precursor chronic asymptomatic Lyme borreliosis and Miyamotoi borrelia bloodstream infections three years prior to the diagnosis of Rai Stage 1 Chronic Lymphocytic leukemia.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

The immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause Placental Schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any sys-tematic review on PS. Methods: We conducted a systematic literature search on PubMed and in-cluded relevant secondary literature found in the citations of the primarily included publications. Results: We found a total of 8 publications describing PS with a total of 92 cases, describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association to adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only < 1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. Conclusions: PS is a highly unattended and underdiagnosed condition in en-demic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation.

Mammarenavirus Wenzhouense (WENV) is broadly distributed in Asia, while the he dynamics process of WENV infection remains unclear. A field derived strain of WENV was used to inoculate Sprague-Dawley (SD) rats by intramuscular injection, the process of virus infection was de-tected by controlling time for 28 days. Viral RNA became detectable in the blood at 3 d pi, and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 d pi, then began to decline by 14 d, however remained detectable in intestine and brain tissues at 21 and 28 d pi. Virus shedding had been detected from fecal samples for 5 days from 6 to 11 d pi using qRT-PCR, and was recovered from feces collected at 8 d pi. Horizontal contact infection occurred among cage-mates at 14 and 21 d pi. Antibodies against the nucleocapsid were detected at 5 dpi, next increased and persisted until the end of experiment. The results enabled to discriminate the kinetic of viremic response, virus shedding in feces and horizontal transmission, as well as the potential sites for WENV replication or maintenance of the virus in nature.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

As the global population ages, the prevalence of neurodegenerative diseases has become a major public health concern. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks—such as genomic instability, telomere attrition, and neuroinflammation—and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.

Patients who survived critical COVID-19 frequently reported post-acute sequelae of COVID-19 (PASC) such as psychosomatic and neurocognitive health problems. The goal of this study was to identify clinical risk factors and other predictors for such long-term consequences in severely ill COVID-19 patients. Adult COVID-19 intensive care unit (ICU) survivors from August 2020 to May 2021 were enrolled. A broad range of clinical, laboratory and chest computed tomography (CT) data was collected during ICU stay. The association between ICU predictors and psychosomatic, respiratory and neurocognitive assessments 12 months after ICU discharge was analyzed using univariate regression analysis. In 17 patients (mean age 58.9 ± 11.4 years), laboratory markers (CRP, lymphocytes, hemoglobin), ICU severity (SOFA, SAPS II, need for mechanical ventilation), complications (ARDS), and lung CT data (ground-glass opacity) were promising predictors of depressive and anxiety symptoms, fatigue, and sleep problems. Recovery of psychosomatic health such as fatigue, depression and anxiety correlated with lower levels of inflammation and high hemoglobin levels. ARDS, mechanical ventilation and worse SOFA and SAPS II scores were further risk factors for depressive and anxiety symptoms. Our study identified novel associations such as pulmonary ground-glass opacity being positively associated with depression, anxiety, fatigue, and insomnia levels.

(1) Background: a study was undertaken to determine the prevalence of chronic diseases and health conditions that affect oral health and oral health self-care among independent living older adults in rural areas of Victoria, Australia; (2) Methods: The study analysed data from the Crossroads-II project, with a total of 1407 participants aged 55 years and older. Participants self-completed questionnaires about health conditions, service use, and demographics. 572 attended a 2-hour health screening that included an assessment of prescribed medications; (3) Results: Most participants were female (55.3%), with a mean age of 69.1 (SD=9.2) years. Participants had a high prevalence of medical conditions, the most common were high blood pressure, arthritis, high lipids, hearing loss, and chronic pain. Almost all participants reported taking medications, with an average of 4.3 medications per person. Among those who attended the health screening, 78.1% were taking medications that could cause xerostomia (dry mouth); (4) Conclusions: This study provides initial information on the prevalence of medical conditions, medication usage, with potential impact on oral health of older adults living in rural Victoria. This information would be valuable for healthcare and dental workforce planning, policy development, and improving the overall well-being of this population.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. PREDATORR study (2014) shows that in Romania, 34,6% of adults aged 20-79 y/o are overweight, 31,4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania's population in the abnormal weight group. Our study aims to investigate the current staus of genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes: leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY) and fat-mass and obesity-associated (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene's AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40-49, with an approximately sevenfold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, not statistically significant. The FTO rs9939609 gene's AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 1e-04), LEP and GHRL gene (p = 0.0047), GHRL and FTO gene (p=0.03). The outcomes of this study, to our knowledge, one of the very few on the Romanian population, aimed to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks.

Blood stream infections (BSI) due to carbapenem-resistant gram-negative bacilli (CR-GNB), especially Klebsiella pneumoniae carbapenemase (KPC) and New-Delhi metallo-β-lactamase (NDM) producers, are a major concern of public health, as they are associated with high morbidity and mortality. We conducted a single-center, retrospective, observational study at a tertiary-care, teaching Greek hospital, to determine the incidence, 30-day and overall, in-hospital, crude mortality, risk factors and efficacy of best available treatment options in patients with BSIs from KPC- or NDM-producing GR-GNB. During the one-year study period, from 1st January to 31st December 2023, we recorded 133 episodes of BSIs in 118 unique patients; 79 episodes were due to KPC-producing and 54 to NDM-producing CR-GNB. Our study showed relatively high incidence of BSIs by both KPC- and NDM-producing CR-GNB (0.49 and 0.31 episodes per 1000 patient-days respectively). We found high 30-day crude mortality rates for patients with BSIs due to KPC- producing CR-GNB (26.4 %), and NDM-producing CR-GNB (37%), while BSIs due to NDM-producing P. aeruginosa had the highest 30-day (47.1%) and overall (70.6%) in-hospital, crude mortality. Beta-lactam/beta-lactamase inhibitors as monotherapy or in combination with other active agents used to treat KPC-producing CR-GNB were associated with improved survival rates (p=0.009).

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections are the most dangerous complication as a serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity. Case report: We reported two patients admitted to the emergency room for pain and edema in the lower leg. Both patients have undergone exclusion of ruptured PA a few years before by endovascular graft. CTA showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus Capitis in the first case and S. Aureus in the second. The antibiotics prophylaxis was performed for 10 days, then, patients underwent an open surgical conversion with a complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and biological bovine pericardium prosthesis in the other case. Furthermore, we have questioned the literature and found eight more cases described in case report article referred to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice. Conclusions: Open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection of the popliteal stent.

Background: Diabetes mellitus (DM) and periodontitis are two chronic diseases that are interconnected. The coexistence of these conditions leads to increased severity of periodontitis and challenges in controlling blood glucose levels in diabetic patients. Objectives: The aim of this study was to evaluate both the influence of periodontal disease and its treatment in patients with DM in terms of a reduction in glycosylated hemoglobin levels at 3 and 6 months after treatment. Methods: A sequential, nonprobabilistic, controlled, prospective and longitudinal case−control study was carried out at the University Dental Clinic of the Morales Meseguer Hospital in Murcia, Spain. Thirty diabetic patients were divided into two groups: patients with periodontitis (test group) and patients without periodontitis (control group). The periodontal and endocrine-metabolic variables were measured at baseline and at 3 and 6 months after periodontal treatment for both groups. Results: Statistically significant differences were found at 3 and 6 months after periodontal treatment with respect to HbA1c levels in the group of periodontal patients. However, these differences were not observed in the control group. Conclusion: The presence of periodontal disease increased HbA1c levels in patients with DM. Nonsurgical periodontal treatment significantly decreased the degree of periodontal inflammation and the HbA1c level at 3 and 6 months after treatment.

Aim: We estimated the correlation between serum bilirubin concentrations and insulin resistance in advanced maternal age without diabetes mellitus. Method: The cross-sectional study involved consecutive 50 women of advanced maternal age without diabetes mellitus, and insulin resistance (IR) was diagnosed according to the homeostatic model assessment insulin resistant (HOMA-IR) formula and the cut-off point was set to more than 2.5. Serum bilirubin and HOMA-IR were compared between the IR (+) and IR (-) groups. Results: We found that serum bilirubin levels in the IR subjects were significantly decreased compared to those without IR (p = 0.0252). Serum bilirubin concentrations were negatively correlated with the weight and the fasting insulin concentrations in all subjects (r=−0.282, p=0.047, r=-0.424, p=0.002). Additionally, serum bilirubin had a negatively correlation with HOMA-IR (r = -0.410, p = 0.003) in all subjects. The multiple linear regression analysis found that serum total bilirubin levels were independently correlated with HOMA-IR (beta = -0.392, p= 0.015) in these subjects. Conclusions: The study demonstrated that serum bilirubin concentrations had negatively correlation with insulin resistance in advanced pregnant women without diabetes mellitus, and decreased serum bilirubin may forebode increased gestational diabetes mellitus risk in our study population.

Staphylococcus aureus is an opportunistic human pathogen and a leading cause of bloodstream infections. It can acquire different antibiotic resistance genes, leading to treatment failure. Aim: We elaborate on the genomic characteristics; antibiotic resistance, virulence, pathogenicity, phylogenomics and clonal diversity of S. aureus implicated in bloodstream infections. Six multidrug-resistant (MDR) S. aureus, three methicillin-resistant S. aureus (MRSA) and three methicillin-sensitive S. aureus obtained from blood cultures underwent whole genome sequencing and bioinformatics analysis. All isolates carried different permutations and combinations of resistance genes including, blaZ, mecA, aac(6')-aph (2''), ant(9)-Ia, ant(6)-Ia, mepR, fosB, norA, norC, lmrS, arlS, arlR, mgrA, kdpD and sdrM. We found 6 spa types (t9475, t355, t045, t1265, t1257, and t7888) with varying profiles of virulence genes responsible for immune invasion, enterotoxins, adhesion/biofilm, haemolysins, and leukotoxins. Panton-Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types IVd(2B) and I(1B) were identified. Isolates belonged to four multilocus sequence types (MLSTs), the most common of which was ST5 (n=3). The STs were clustered into two clonal complexes CC5 and CC8. We found two MRSA clones typed as ST5-CC5-t045-SCCmec_I(1B), and the human-associated MRSA endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). The insertion sequences IS30 and IS6 associated with virulence were found in two isolates. The presence of virulent MDR S. aureus in bloodstream infections poses a clinical concern because of limited treatment options and increased risk of mortality.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

The Mononuclear Phagocyte System includes monocytes, macrophages, some dendritic cells and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow haematopoietic progenitors, tissue location and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells, through trophic, clearance and cytocidal functions. During evolution they contributed to innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at midgestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac-, AGM- and foetal liver-derived tissue resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for discovery of Dendritic Cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity.

The aim of this study was to analyze other possible new markers of severity that can be assessed in patients with type 2 diabetes and SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus and infected with the SARS-CoV-2 virus, and 45 healthy persons as control. The serum level of ceruloplasmin at hospital admission was statistically significant directly correlated with the severity of COVID-19 (Coronavirus disease) (p=0.037) and with the serum level of IL-6 (Interleukine 6) (p=0.000). Ceruloplasmin was statistically significant inversely correlated with serum iron level (p=0.000). However, we observed that ACE (Angiotensin converting enzyme) decreased in severe forms of the infection with SARS-CoV-2 virus in patients with type 2 diabetes (p=0.001). Moreover, the decrease in ACE level was correlated with an increase in IL-6 level in these patients (p=0.001). IL-6 increase was statistically significant inversely correlated with serum iron, transferrin and ACE levels. There was a noticed a decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p=0.000). In addition to the known severity factors in the context of infection with the new coronavirus, decreased concentrations of ceruloplasmin, ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters analyzed at the hospital admission could show the evolution towards the severe forms of infection with the SARS-CoV-2 virus.

Acquired immunodeficiency syndrome (AIDS) has transitioned from a progressive, fatal disease to a chronic, manageable disease thanks to better defining of antiretroviral therapy, hence contributing to increased life expectancy. In parallel, a growing number of subjects without overt clinical signs of disease but living with chronic HIV infection (people living with HIV, PLWH) are experiencing early cardiovascular disease worldwide. However, a progressive increase in the prevalence of multiple comorbid diseases has been reported as these patients age, including cardiovascular disease (CVD). Cardiovascular mortality can be either directly related to the viral infection, a progressive reduction of response to the antiretroviral therapy, chronic inflammation or lifestyle-related. Cardiovascular ageing represents a relevant issue in the management of HIV-infected patients. Although the exact pathophysiological mechanism that leads PLWH to develop cardiovascular disease is not entirely understood, there is substantial evidence that they accumulate age-related conditions earlier than the general population. Furthermore, since the proportion of PLWH growing older than 50 years has progressively increased, this results in a complex interaction between disease-related pathophysiology and the exposition of a growing burden of cardiovascular risk factors. For this reason, we performed a systematic review of the genes most frequently associated with ageing in HIV-infected subjects, followed by a bioinformatic analysis to explore the biological impact of the genes related to ageing.

(1) Background: Several chronic respiratory diseases could be a risk factor for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunctioning of the respiratory cilia; We aimed to investigate if some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms in a cohort of PCD subjects; (2) Methods: Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms and vaccinations; in case of infection, they also filled out a SNOT-22 and ARTIQ questionnaires; (3) Results: Forty PCD adult patients (mean age 36.6 ± 16.7 years, 23 females) participated to the study, out of which 30 % had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistic significant difference (p=0.03) was observed in body mass index (BMI), that was higher in the COVID-acquired group (23.2 ± 3.3 vs 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of PAV allele towards SARS-CoV-2 infection; (4) Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype type does not affect SARS-CoV-2 infection.

Background/Objectives: The pediatric definition of severe obesity (OB) depends on the body mass index (BMI) references. We evaluated different BMI derived metrics of the World Health Organization (WHO) system to define which cut-off is associated with the highest cardiometabolic risk (CMR); Methods: In this multicentric study data were obtained by 3727 youths (1937 boys; 2225 children, 1502 adolescents. severe OB was defined as BMI &gt;99th percentile (BMI99), BMI97 ≥120% or BMI Z-score &gt; 3 (WHO tables). The continuous CMR Z-score (sum of residual standardized for age and sex of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, and HDL-Cholesterol x -1) and the cluster of at least two CMR factors (hypertension, high triglycerides, low HDL-Cholesterol and high waist-to-height ratio) were calculated; Results: Continuous CMR Z-score was significantly higher both in children or adolescents with severe OB defined by 120% BMI97 compared to BMI &gt;99th (p &lt;0.0001), while it was lower only in adolescents with severe OB defined by 120% BMI97 compared to BMI Z-score &gt;3 (p &lt;0.0001). Compared to BMI97 ≥120%, BMI Z-score &gt;3 had higher specificity, but lower sensitivity in identifying children and adolescents with clustered CMR factors; Conclusions: The definition of severe OB based on BMI97 ≥120% is superior to BMI99 but it is inferior to BMI Z score &gt;3 as far as the association between severe OB and CMR factors is concerned. Pediatricians should take into consideration the implications of the use of different BMI metrics in those countries that recommend the WHO system.

Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may cause acute respiratory failure but also remains responsible for many other pathologies, including electrolyte disorders. SARS-CoV-2 infection can cause dysfunction of the renin-angiotensin-aldosterone system and disrupt water hemostasis with thirst and appetite abnormalities. Dysnatremia affects prognosis and may be associated with mortality in patients admitted to SARS-CoV2 intensive care. Patients and Methods: The study included 209 patients admitted to the Intensive Care Unit between April 12, 2021, and March 1, 2022 who were over 18 years old and diagnosed with SARS-CoV-2 infection by clinical and thoracic tomography findings or with a positive reverse transcription polymerase chain reaction (RT-PCR) test result. The laboratory markers, treatment modalities, nutritional, and respiratory support also for outcome evaluation, length of stay in the ICU, total hospitalization duration, and mortality in ICU were recorded.The laboratory marker comparison was made admission with the final assessment performed before the time of mortality in ICU or discharge. Results: Inotropic requirements among patients were high which was reflected in the first-month mortality. Hypernatremia presence was associated with an increase in enteral support and inotropic support requirement and mortality. Hypernatremia was correlated with diabetes mellitus, chronic renal failure, and a longer duration under mechanical ventilation. Discussion: Hypernatremia was an important risk factor in ICU patients hospitalized for SARS-CoV-2 infection, which was also affected by the treatment regimens given itself. This complex relationship underlies the importance of proper electrolyte management, especially in patients who were under severe stress and organ failure.

Objective: To explore the hot spots and development trends of community public health research. Methods: The literature related to this topic was searched in CNKI and PubMed databases, and the trend map of the number of articles was drawn according to the obtained data. The included literature were analyzed with Vosviewer software for keyword and author co-occurrence, and CiteSpace 6.3.R1 Basic software was used for mechanism co-occurrence, key emergence and clustering analysis, and timeline distribution map drawing. Results: 189 Chinese literature and 77 English literature were selected. The Chinese literature focused on “community public health service, emergency management, and community governance”, and the research trend was “community public health emergency management and community governance”; English literature focuses on “nursing education, health education, human qualitative research”. Conclusion: Although the Chinese and English literature shows that scholars in this field have different emphases, the primary community health is the key and difficult point to realize the national public health service project, and improving the basic public health service in the primary community is related to the health of all the people, so it is very important.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

The primary therapeutic method for correcting hyperglycemia today is diet therapy. Lipids are not only a source of nutrients but can also act as initiators of adipocyte differentiation in the fetus, which explains the development of fetal macrosomia and future metabolic disorders in children born to mothers with gestational diabetes mellitus (GDM). Changes in the profile of circulating lipids in the maternal bloodstream, depending on adherence to a rational diet among mothers with GDM and the development of fetal macrosomia, is a complex and not fully understood process. The aim of the study was to examine the characteristics of the lipid profile in the blood plasma of pregnant women with GDM in all trimesters of pregnancy based on adherence to diet therapy. The design of the clinical part of the work was carried out within the framework of a 'case-control' study.The study included 110 women, 80 of whom were in the control group, 20 in the group with GDM adhering to the diet, and 10 in the group with GDM not adhering to the diet. The laboratory part was conducted as part of a longitudinal dynamic study with venous blood samples taken at three points: 11-13, 24-26, and 30-32 weeks of pregnancy.A significant impact of diet therapy on the blood lipid composition throughout pregnancy was demonstrated, starting as early as the first trimester. ROC analysis showed high effectiveness of the developed models with an AUC of 0.98 for the "30-32 weeks" model, with sensitivity and specificity of 1 and 0.9, respectively. An association was found between diet, maternal blood lipid composition at 32 weeks of pregnancy, and newborn weight. The direction of changes in the lipid spectrum during the development of macrosomia and diet therapy is diametrically opposed. This confirms at the molecular level that diet therapy can normalize not only carbohydrate but also lipid metabolism in the mother and fetus. Based on the obtained data, it can be suggested that after validation, the developed models could be used to refine the prognosis of macrosomia development based on the lipid profile of blood plasma at different stages of pregnancy.

Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs present limitations in terms of side effects, accessibility and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, impaired β-cell function and insulin resistance. If left untreated or when poorly controlled, DM increases the risk of vascular complications such as hypertension, nephropathy, neuropathy, retinopathy that can be severely debilitating or life-threatening. Plant-based foods represent a promising natural approach for the management of T2DM due to the vast array of phytochemicals they contain. Numerous epidemiological studies have highlighted the importance of a diet rich in plant-based foods (vegetables, fruits, spices, condiments) in the prevention and management of DM. Unlike conventional medications, such natural products are widely accessible, affordable, and generally free from adverse effects. Integrating plant-derived foods into the daily diet not only helps control the hyperglycemia observed in DM, but also supports weight management in obese individuals and has broad health benefits. In this review, we provide an overview of the pathogenesis and current therapeutic management of DM, with a particular focus on the promising potential of plant-based foods.

Postprandial plasma glucose between 4 and 7.9 hours is associated with the diagnosis of diabetes, diabetes mortality, and cardiovascular mortality. However, it is unknown whether 2-hour plasma glucose during the oral glucose tolerance test conducted in this postprandial period (4–7.9 hours), termed as 2-h PGOGTT@4–7.9h, can accurately classify diabetes diagnosis and predict mortality risks. This study aimed to address these questions using 2,347 adult participants. Diabetes was defined as HbA1c ≥6.5%, and the ability of 2-h PGOGTT@4–7.9h to classify diabetes was analyzed using receiver operating characteristic curves. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). The results showed that 2-h PGOGTT@4–7.9h could classify diabetes with 92% accuracy. Participants were followed up for a mean of 21.4 years. A 1-natural-log higher 2-h PGOGTT@4–7.9h was associated with an increased risk of mortality from diabetes (adjusted HR, 21.1; 95% CI, 9.2–48.0) and cardiovascular disease (adjusted HR, 1.47; 95% CI, 1.13–1.91). Simulation analysis indicated that future studies may require at least 100 participants to investigate 2-h PGOGTT@4–7.9h for diabetes diagnosis. In conclusion, 2-h PGOGTT@4–7.9h may be useful for diabetes classification and prediction of mortality risk.

Viral contamination in the aquaculture industry is a significant challenge that requires further research. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a role in regulating various biological processes, including immunity. However, most studies have focused on model organisms, and little is known about non-coding RNAs in the immune response to viral hemorrhagic septicemia (VHS) in rainbow trout. In this study, we investigated the listing of non-coding RNAs (ncRNAs) in rainbow trout challenged with VHS virus. We explored their potential role in defense-like responses based on transcriptomic analysis of the virus-treated and control groups. As a result of this research, 4207 lncRNAs were identified, of which 182 lncRNAs were differentially expressed between treated and untreated samples. Among 7753 lncRNA transcripts, 1920 were novel intergenic (class code “u”), and 3748 transcripts were potentially novel isoform of lncRNAs. Gene ontology analysis revealed biological pathways associated with the stress response and immune signaling. Pairs of genes such as TP63-MSTRG.62, IL10-MSTRG.9783, IL10-MSTRG.9784, TK1-MSTRG.22826, and MSTRG.17881-GLI1 showed cis interactions, while DOCK10-MSTRG.30015, MSTRG.36357-LOC101268921, and MSTRG.34190-ENPP2 showed trans interactions. In this study, the role of lncRNAs in regulating the expression of the target genes was clearly identified. This finding is consistent with the regulatory processes of immune system responses mediated by cytokines, as well as the regulation of oxygen levels in response to viral infection. The information presented here highlights the various regulatory mechanisms of lncRNAs in the expression of immune system genes in fish treated with VHS virus.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

Polycystic ovary syndrome (PCOS) is a common condition in reproductive-age women. Women with PCOS are at higher risk of pregnancy complications including gestational diabetes (GDM). The prevalence of PCOS and GDM varies according to the diagnostic criteria used. The mechanism for the occurrence of GDM in women with PCOS is still unclear. Materials &amp; Methods- A systematic search of the electronic database was done using keywords like PCOS, and GDM to include studies between April 2008 and March 2023 where uniform diagnostic criteria were used. Studies were excluded with high-risk of bias after the assessment of bias, and meta-analysis was done with relative risks and confidence intervals. Results &amp; Discussion-Out of 1896 search results, 95 were selected for full-text. The quality of the studies was scrutinized and a total of 28 studies were included as they fulfilled the inclusion criteria. The incidence of GDM in women with PCOS was found to be 10.55 % (2.9- 54.9%) from pooled data involving 1,280,245. The prevalence of PCOS in women diagnosed with GDM was found from pooled data of 36,351 women in retrospective studies to be 2.47% (1.5- 50.1%). Selection predominantly included cohort studies, most commonly from China. The meta-analysis reported the risk of GDM is higher in women with PCOS than in those without PCOS (HR: 1.59, 95% CI: 1.27–1.91, p &lt; 0.001). Family history of diabetes, ethnicity, pre-pregnancy BMI, insulin resistance, gestational weight gain, use of assisted reproductive techniques, and multifetal gestation were the risk factors for GDM in women with PCOS. Conclusion- The prevalence of GDM in patients with PCOS is high, but the causality is complex. The newer predictive models are promising in clarifying the causative relationships, yet use various parameters at different cut-offs. There is a need for the development of universally acceptable parameters for the early prediction of GDM in women with PCOS.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Oncolytic measles virus (MeV) is a promising anti-cancer treatment. However, the production of high titers of infectious MeV (typically 10⁷–10⁹ TCID₅₀ per dose) is challenging because the virus is unstable under typical production conditions. The objective of this study was to investigate how the multiplicity of infection (MOI) and different media – serum-containing (SCM), serum-free (SFM) and chemically-defined (CDM) – affect MeV production. We infected Vero cells at MOIs of 0.02, 0.2 or 2 TCID₅₀ mL^-1 and the lowest MOI resulted in the largest number of infected cells towards the end of the production period. However, this did not equate to higher maximum MeV titers, which were similar for all MOIs. The medium had a moderate effect, generating maximum titers of 0.89–2.17 × 10⁶, 1.08–1.25 × 10⁶ and 4.58–9.90 × 10⁵ TCID₅₀ mL^‑1 for SCM, SFM and CDM, respectively. Infection at a low MOI often required longer process times to reach maximum yields. Our findings show that SCM, SFM and CDM are equally suitable for MeV production in terms of yield and process time. This will allow MeV production in serum-free conditions, addressing the safety risks and ethical concerns associated with the use of serum.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Probiotics are living microbes that provide benefits to the host. The increasing data on health promotion following probiotics administration triggered growing interest among researchers and pharmaceutical companies looking for novel therapeutic or preventive tools. Infections of the lower genital tract in females are caused by a wide range of pathogens, they are widespread, and represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women in their reproductive age at least once during their lifetime. Of these women 5-8% develop the recurrent form (RVVC). The disease onset is triggered by the overgrowth of Candida species on the vaginal mucosa. Here, we evaluated the beneficial properties of the Bacillus coagulans spore-producing LMG S-24828 against C. albicans and C. parapsilosis. Our results show that both alive B. coagulans and its Cell-Free-Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, alive B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells and showed co-aggregation capacity. Overall, B. coagulans LMG S-24828 exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Lyme disease, the leading vector-borne ailment in the U.S., annually affects an estimated 476,000 individuals, predominantly in the Northeast and Upper Midwest. Despite its increasing incidence, the evaluation of risk within U.S. cities, including natural public lands, remains inadequate. This study focuses on blacklegged tick occurrences and Borrelia burgdorferi infection prevalence in 24 Staten Island parks, aiming to assess Lyme disease exposure risk. Monthly acarological risk index (ARI) calculations from 2019 to 2022 revealed elevated values (0.16-0.53) in specific parks, notably Wolfe’s Pond Park, High Rock Park, Clay Pit Pond Park, Clove Lake Park, and Fair View Park. June (0.36) and November (0.21) consistently exhibited heightened ARIs, aligning with peak tick collection months. Despite stable yearly infection rates at 28.97%, tick densities varied significantly between parks and years. Identifying a high transmission risk in specific parks in Staten Island, a highly urbanized part of New York City, emphasizes the continuous necessity for Lyme disease risk management, even within the greenspaces of large cities.

Adolescents most often experience mild acute COVID-19 but may still face fatigue and persistent symptoms such as post-COVID-19 condition (PCC) and post-infective fatigue syndrome (PIFS). We explored the fecal microbiota in a prospective controlled cohort of 136 non-hospitalized SARS-CoV-2-positive and 32 SARS-CoV-2-negative controls aged 12–25 years. With a targeted qPCR approach, the quantities of 100 fecal bacterial taxa were measured at baseline (early convalescent stage) and after six months. Results: Faecalibacterium prausnitzii M21.2 and Gemmiger formicilis (both p&lt;0.001) were enriched in the SARS-CoV-2-positive participants compared to controls at baseline. Lower baseline abundance of Faecalibacterium prausnitzii M21/2 (p=0.013) and higher abundance of Clostridium spiroforme (p=0.006), Sutterella wadsworthensis (p&lt;0.001) and Streptococcus thermophilus (p=0.039) were associated with six-month fatigue. Sutterella wadsworthensis and Streptococcus thermophilus enrichment was additionally associated with PCC in the SARS-CoV-2-positive group (p&lt;0.001 and 0.042 respectively). Conclusions: In mild SARS-CoV-2 infection in adolescents and young adults, beneficial Faecalibacterium prausnitzii M21/2 and Gemmiger formicilis were enriched compared to SARS-CoV-2 negative controls. Additionally, both known (Faecalibacterium prausnitzii, Streptococcus thermophilus) and new (Clostridium spiroforme, Sutterella wadsworthensis) bacteria were associated with persistent symptoms in the COVID-19 infected group, warranting further exploration of the role of these bacteria in COVID-19 disease and PCC pathophysiology.

Drug-resistant tuberculosis (DR-TB) and HIV-coinfection present a conundrum to public health globally, and the achievement of the global END TB strategy in 2035. A descriptive, retrospective review of medical records of patients diagnosed with DR-TB who received treatment was conducted. Student’s t-test was performed to assess differences between two means and ANOVA between groups. Either the Chi-square test with and without trend or Fischer’s exact test was used to test the degree of association of categorical variables. Logistic regression was used to determine predictors of DR-TB treatment outcomes. Also, a decision tree classifier, which is a supervised machine learning algorithm was used. Python version 3.8. and R version 4.1.1 software were used for data analysis. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 456 DR-TB patients were included in the study with more male patients (n = 256, 56.1%) than female patients (n = 200, 43.9%). The overall treatment success rate was 61.4%. There was a significant decrease in the % of patients cured during the Covid-19 pandemic compared to the pre-pandemic period. Our findings showed that machine learning can be used to predict TB patients' treatment outcomes.

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

One of the most prevalent illnesses, diabetes does not directly result in patient mortality. But, it increases the risk of death. Any disease that may be predicted in its early stages can lessen its fatal effects while also enhancing the quality of the healthcare system. For the early-stage prediction of diabetes or such types of non-communicable diseases, we need the proper set of influential features. This research has developed a machine learning-based disease prediction model to identify the influential features for diabetes prediction and give a near-perfect classification accuracy. This model includes Min-Max normalization for data normalization, Isolation Forest (iForest) for outlier removal, Synthetic Minority Oversampling Technique (SMOTE) for oversampling, Random Forest based Recursive Feature Elimination (RFE-RF) test, Chi-Square test, and Minimum Redundancy Maximum Relevancy (mRMR) test based feature selection methods for identifying the influential features, and Support Vector Machine (SVM), K Nearest Neighbor (KNN), and Naive Bayes (NB) for the classification. The results clarify that the proposed model outperforms the previous models and studies. The SVM has attained an accuracy of 99.58% in classification using the five features chosen from the Chi-Square test. Lastly, SHAP, an explainable AI model, has been used to assess the classifier model’s performance. These selected features and the classifier model can be used for early-stage diabetes prediction.

Objective: Subclinical left ventricular disfunction (LVD) is common in asymptomatic patients with type 2 diabetes (T2D). Many patients with diabetes have an impaired diastolic and systolic function. With preserved ejection fraction LV (EFLV), the latter is defined as reduced global longitudinal strain (GLS), detected using the speckle-tracking echocardiography. This study is aimed to define the long-term structural and functional disorders of the LV myocardium in patients with T2D without CVD. Methods: Of the 120 patients with and without T2D of both sexes aged from 45 to 75 years (57.11±7.9 years), included in the study in 2012-2013, only 57 responded to the follow-up study. The patients were divided into two groups: one with T2D (n=29), the other without it, control (n=28). All patients underwent transthoracic two-dimensional echocardiography with assessment of standard indicators of systolic and diastolic cardiac function, as well as GLS. In addition, all participants underwent laboratory diagnostics of carbohydrate metabolism disorders markers, NT-proBNP and CRP. The median follow-up duration was 7.2 [7.0-7.8] years. Results: During the follow-up, a statistically significant increase in the incidence of diastolic dysfunction (DD) in the type 2 diabetes group was found from 53% to 61% (p = 0.004); no significant dynamics were noted in the control group (p = 0.48). The presence of T2D significantly increases the risk of developing DD (p=0.04). The presence of T2D, increased fasting glucose levels, and an increased HOMA index were independent predictors of the development of DD. Impairment of LVEF was not observed in both groups. At the same time, the proportion of patients with reduced GLS (< -18%) increased in the T2D group (p = 0.036). A significant difference in the frequency of decreased GLS depending on T2D was demonstrated. The presence of obesity, an increase in the HOMA index and an increase in CRP levels are independent predictors of impaired GLS. Conclusions: T2D is an independent risk factor for the worsening of subclinical left ventricular dysfunction in asymptomatic patients with T2D without CVD over 7-year follow-up. Diastolic dysfunction is represented by delayed relaxation of the LV myocardium; with preserved LVEF, reduced 2D GLS identifies systolic dysfunction. The tight control of glycemia, lipidemia, blood pressure and body weight is associated with the absence of poor clinical outcomes.