Here we report a case where the manifestations of insulin-dependent diabetes occurred following SARS-CoV-2 infection in a young individual in the absence of autoantibodies typical for type 1 diabetes mellitus. Specifically, a 19-year-old white male presented at our emergency department with diabetic ketoacidosis, C-peptide level of 0.62 µg l-1 , blood glucose concentration of 30.6 mmol l-1 (552 mg dl-1) and haemoglobin A1c of 16.8%. The patient´s case history revealed probable COVID-19 infection 5-7 weeks before admission, based on a positive test for antibodies against SARS-CoV-2 proteins as determined by enzyme-linked immunosorbent assay. Interestingly, the patient carried a human leukocyte antigen genotype (HLA DR1-DR3-DQ2) considered to provide only a slightly elevated risk of developing autoimmune type 1 diabetes mellitus. However, as noted, no serum autoantibodies were observed against islet cells, glutamic acid decarboxylase, tyrosine phosphatase, insulin and zinc-transporter 8. Although our report cannot fully establish causality between COVID-19 and the development of diabetes in this patient, considering that SARS-CoV-2 entry receptors, including angiotensin-converting enzyme 2, are expressed on pancreatic β-cells and, given the circumstances of this case, we suggest that SARS-CoV-2 infection, or COVID-19, might negatively affect pancreatic function, perhaps through direct cytolytic effects of the virus on β-cells. The recent COVID-19 pandemic caused by the SARS-CoV-2 virus represents a worldwide health crisis causing severe illness and death, especially in people with cardiovascular and metabolic abnormalities 1,2. SARS-CoV-2 enters human cells via angiotensinconverting enzyme 2 (ACE2) 3 , a transmembrane glycoprotein with proteolytic activity also found in human pancreatic β-cells 4 , suggesting that SARS-CoV-2 might alter pancreatic β-cell function and impair insulin secretion. Several recently published studies indicate a link between COVID-19 and diabetes: for example, acute hyper glycaemia has been observed in a large number of individuals infected with SARS-CoV-2, regardless of any past medical history of diabetes 5-8. In another study in Asia, patients were reported

Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways remain unknown. Recent advances for system-wide experimental data generation have facilitated the quantification of signaling systems, but the integration of multi-level dynamic data remains challenging. Here, we co-designed dynamic experiments and a probabilistic, model-based method to infer causal relationships between metabolism, signaling, and gene regulation. We analyzed the dynamic regulation of nitrogen metabolism by the target of rapamycin complex 1 (TORC1) pathway in budding yeast. Dynamic transcriptomic, proteomic, and metabolomic measurements along shifts in nitrogen quality yielded a consistent dataset that demonstrated extensive re-wiring of cellular networks during adaptation. Our inference method identified putative downstream targets of TORC1 and putative metabolic inputs of TORC1, including the hypothesized glutamine signal. The work provides a basis for further mechanistic studies of nitrogen metabolism and a general computational framework to study cellular processes.

Protein phosphorylation is a widespread posttranslational modification that regulates almost all cellular functions. To investigate the large number of phosphorylation events with unknown functions, we monitored the concentrations of several hundred intracellular metabolites in Saccharomyces cerevisiae yeast strains with deletions of 118 kinases or phosphatases. Whereas most deletion strains had no detectable difference in growth compared to wild-type yeast, two-thirds of deletion strains had alterations in metabolic profiles. For about half of the kinases and phosphatases encoded by the deleted genes, we inferred specific regulatory roles on the basis of knowledge about the affected metabolic pathways. We demonstrated that the phosphatase Ppq1 was required for metal homeostasis. Combining metabolomic data with published phosphoproteomic data in a stoichiometric model enabled us to predict functions for phosphorylation in the regulation of 47 enzymes. Overall, we provided insights and testable predictions covering greater than twice the number of known phosphorylated enzymes in yeast, suggesting extensive phosphorylation-dependent regulation of yeast metabolism.

Purpose Dental implant surgery was developed to be the most suitable and comfortable instrument for dental and oral rehabilitation in the past decades, but with increasing numbers of inserted implants, complications are becoming more common. Diabetes mellitus as well as prediabetic conditions represent a common and increasing health problem (International Diabetes Federation in IDF Diabetes Atlas, International Diabetes Federation, Brussels, 2019) with extensive harmful effects on the entire organism [(Abiko and Selimovic in Bosnian J Basic Med Sci 10:186–191, 2010), (Khader et al., in J Diabetes Complicat 20:59–68, 2006, 10.1016/j.jdiacomp.2005.05.006)]. Hence, this study aimed to give an update on current literature on effects of prediabetes and diabetes mellitus on dental implant success. Methods A systematic literature research based on the PRISMA statement was conducted to answer the PICO question “Do diabetic patients with dental implants have a higher complication rate in comparison to healthy controls?”. We included 40 clinical studies and 16 publications of aggregated literature in this systematic review. Results We conclude that patients with poorly controlled diabetes mellitus suffer more often from peri-implantitis, especially in the post-implantation time. Moreover, these patients show higher implant loss rates than healthy individuals in long term. Whereas, under controlled conditions success rates are similar. Perioperative anti-infective therapy, such as the supportive administration of antibiotics and chlorhexidine, is the standard nowadays as it seems to improve implant success. Only few studies regarding dental implants in patients with prediabetic conditions are available, indicating a possible negative effect on developing peri-implant diseases but no influence on implant survival. Conclusion Dental implant procedures represent a safe way of oral rehabilitation in patients with prediabetes or diabetes mellitus, as long as appropriate precautions can be adhered to. Accordingly, under controlled conditions there is still no contraindication for dental implant surgery in patients with diabetes mellitus or prediabetic conditions.

AIMTo compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODSA systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31st, 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1).RESULTSAll trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.CONCLUSIONAlternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

Acylated SH4 domains represent N-terminal targeting signals that anchor peripheral membrane proteins such as Src kinases in the inner leaflet of plasma membranes.Here we provide evidence for a novel regulatory mechanism that may control the levels of SH4 proteins being associated with plasma membranes. Using a fusion protein of the SH4 domain of Leishmania HASPB and GFP as a model system, we demonstrate that threonine 6 is a substrate for phosphorylation. Substitution of threonine 6 by glutamate (to mimic a phosphothreonine residue) resulted in a dramatic redistribution from plasma membranes to intracellular sites with a particular accumulation in a perinuclear region. As shown by both pharmacological inhibition and RNAi-mediated downregulation of the threonine/ serine-specific phosphatases PP1 and PP2A, recycling back to the plasma membrane required dephosphorylation of threonine 6. We provide evidence that a cycle of phosphorylation and dephosphorylation may also be involved in intracellular targeting of other SH4 proteins such as the Src kinase Yes.

Studies on the effectiveness of ultrafiltration (UF) in patients hospitalized with acute decompensated heart failure (ADHF) have led to heterogeneous study outcomes. This meta-analysis aimed to assess the impact of UF therapy in ADHF patients. We searched the medical literature to identify well-designed studies comparing UF with the usual diuretic therapy in this setting. Systematic evaluation of 8 randomized controlled trials enrolling 801 participants showed greater fluid removal (difference in means 1372.5 mL, 95% CI 849.6 to 1895.4 mL; p < 0.001), weight loss (difference in means 1.592 kg, 95% CI 1.039 to 2.144 kg; p < 0.001) and lower incidences of worsening heart failure (OR 0.63, 95% CI 0.43 to 0.94, p = 0.022) and rehospitalization for heart failure (OR 0.54, 95% CI 0.36 to 0.82, p = 0.003) without a difference in renal impairment (OR 1.386, 95% CI 0.870 to 2.209; p = 0.169) or all-cause mortality (OR 1.13, 95% CI 0.75 to 1.71, p = 0.546). UF increases fluid removal and weight loss and reduces rehospitalization and the risk of worsening heart failure in congestive patients, suggesting ultrafiltration as a safe and effective treatment option for volume-overloaded heart failure patients.

Aim Recombinant secreted frizzled‐related protein 5 (sFRP5) improved periodontal status in mice. Thus, this study aimed to investigate this finding in human periodontitis using an epidemiological approach. Materials and Methods sFRP5 and wnt5a concentrations were determined in human serum from the Food Chain Plus cohort using ELISAs. A total of 128 patients with periodontitis and tooth loss and 245 patients with periodontitis without tooth loss were compared to 373 sex‐, smoker‐, age‐ and BMI‐matched individuals in a nested case–control design. Results Systemic sFRP5 serum levels were significantly lower in patients with periodontitis and tooth loss (2.5 [0.0–10.4] ng/ml, median [IQR]) compared to patients with periodontitis without tooth loss (6.0 [2.5–15.8] ng/ml, median [IQR], p = 0.04] and matched controls (7.0 [2.5–18.3] ng/ml, median [IQR], p = 0.02). No significant differences in sFRP5 serum levels were found among patients with periodontitis without tooth loss (6.0 [2.5–15.8] ng/ml, median [IQR]) and controls (3.1 [0.0–10.6] ng/ml, median [IQR], p = 0.06). Conclusions sFRP5 might serve as a novel biomarker for periodontitis severity. Modulating the inflammatory background of severe forms of periodontitis, in the time of precision medicine, needs to be revealed in further studies.