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The electrified aqueous/metal interface is critical in controlling the performance of energy conversion and storage devices, but an atomistic understanding of even basic interfacial electrochemical reactions challenges both experiment and computation. We report a combined simulation and experimental study of (reversible) ion-transfer reactions involved in anodic Ag corrosion/deposition, a model system for interfacial electrochemical processes generating or consuming ions. With the explicit modeling of the electrode potential and a hybrid implicit-explicit solvation model, the density functional theory calculations produce free energy curves predicting thermodynamics, kinetics, partial charge profiles, and reaction trajectories. The calculated (equilibrium) free energy barriers (0.2 eV), and their asymmetries, agree with experimental activation energies (0.4 eV) and transfer coefficients, which were extracted from temperature-dependent voltage-step experiments on Au-supported, Ag-nanocluster substrates. The use of Ag nanoclusters eliminates the convolution of the kinetics of Ag+(aq.) generation and transfer with those of nucleation or etch-pit formation. The results indicate that the barrier is controlled by the bias-dependent competition between partial solvation of the incipient ion, metal-metal bonding, and electrostatic stabilization by image charge, with the latter two factors weakened by stronger positive biases. We also report simulations of the bias-dependence of defect generation relevant to nucleating corrosion by removing an atom from a perfect Ag(100) surface, which is predicted to occur via a vacancy-adatom intermediate. Together, these experiments and calculations provide the first validated, accurate, molecular model of the central steps that govern the rates of important dissolution/deposition reactions broadly relevant across the energy sciences.

Abstract Background In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity. Methods Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups. Results Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p

This research is aimed at developing novel theory to advance innovative methods for examining how collaborative groups progress toward productively engaging during classroom activity that integrates disciplinary practices. This work draws on a situative perspective, along with prior framings of individual engagement, to conceptualize engagement as a shared and multidimensional phenomenon. A multidimensional conceptualization affords the study of distinct engagement dimensions, as well as the interrelationships of engagement dimensions that together are productive. Development and exploration of an observational rubric evaluating collaborative group disciplinary engagement (GDE) is presented, leveraging the benefits of observational methods with a rubric specifying quality ratings, enabling the potential for analyses of larger samples more efficiently than prior approaches, but with similar ability to richly characterize the shared and multidimensional nature of group engagement. Mixed-methods analyses, including case illustrations and profile analysis, showcase the synergistic interrelations among engagement dimensions constituting GDE. The rubric effectively captured engagement features that could be identified via intensive video analysis, while affording the evaluation of broader claims about group engagement patterns. Application of the rubric across curricular contexts, and within and between lessons across a curricular unit, will enable comparative studies that can inform theory about collaborative engagement, as well as instructional design and practice.

IntroductionA higher incidence of neural dysfunction in people with obesity has been described. We determined the prevalence of neuropathic lesions in obese women and evaluated their potential association with anthropometric and laboratory parameters.Patients and methodsIn our cross-sectional study, we enrolled female patients with obesity and without diabetes before obesity treatment. Voluntary female subjects were controls with a normal body mass index (BMI). Autonomic function was assessed by Ewing’s cardiovascular reflex tests, while comprehensive peripheral neuropathic assessments were conducted utilizing the Neurometer®, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. Sudomotor function was assessed by the Neuropad®-test. Body composition was examined using the InBody 770.Results71 patients (mean ± SD; age: 36.1 ± 8.3 years; BMI: 40.2 ± 8.5 kg/m2) and 36 controls (age: 36.4 ± 13.3 years; BMI: 21.6 ± 2.1 kg/m2) were enrolled. Patients had significantly higher systolic (patients vs. controls; 137.5 ± 16.9 vs. 114.6 ± 14.8 mmHg, p

Abstract Due to the similarity between the pathomechanism of SARS-CoV-2 infections and hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), a possibility emerged that C1-INH-HAE may worsen the course of the infection, or that the infection may influence the severity of angioedema (HAE) attacks in C1-INH-HAE patients. Our study aimed to evaluate the effects of the COVID-19 pandemic on the quality of life (QoL) of Hungarian C1-INH-HAE patients, and to survey the acute course of the infection, post COVID symptoms (PCS), vaccination coverage and the side effects of vaccines in this patient population. 93 patients completed our questionnaire between 1st July 2021 and 31st October 2021. In this same period and between March 2019 and March 2020, 63 patients completed the angioedema quality of life questionnaire (AE-QoL). Out of those patients infected with SARS-CoV-2 in the examined period (18/93 patients; 19%), 5% required hospitalization, 28% experienced HAE attacks in the acute phase of the infection, and 44% experienced PCS. A total number of 142 doses of vaccines were administered to the patients. Serious vaccine reactions did not occur in any case, 4 (5%) out of the 73 vaccinated patients experienced HAE attacks. No significant difference (p = 0.59) was found in the median of the AE-QoL total score, or in the number of HAE attacks prior and during the pandemic. Based on our study, HAE patients did not experience more serious SARS-CoV-2 infection, and it did not aggravate the course of HAE either. Changes in the QoL were not significant, and vaccines were safe in HAE patients.

The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background—in particular, accelerated progress is being made in understanding molecular biological mechanisms—some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.

Neuropathy is a serious and frequent complication of type 2 diabetes (T2DM). This study was carried out to search for genetic factors associated with the development of diabetic neuropathy by whole exome sequencing. For this study, 24 patients with long-term type 2 diabetes with neuropathy and 24 without underwent detailed neurological assessment and whole exome sequencing. Cardiovascular autonomic function was evaluated by cardiovascular reflex tests. Heart rate variability was measured by the triangle index. Sensory nerve function was estimated by Neurometer and Medoc devices. Neuropathic symptoms were characterized by the neuropathy total symptom score (NTSS). Whole exome sequencing (WES) was performed on a Thermo Ion GeneStudio S5 system determining the coding sequences of approximately 32,000 genes comprising 50 million base pairs. Variants were detected by Ion Reporter software and annotated using ANNOVAR, integrating database information from dbSNP, ClinVar, gnomAD, and OMIM. Integrative genomics viewer (IGV) was used for visualization of the mapped reads. We have identified genetic variants that were significantly associated with increased (22–49-fold) risk of neuropathy (rs2032930 and rs2032931 of recQ-mediated genome instability protein 2 (RMI2) gene), rs604349 of myosin binding protein H like (MYBPHL) gene and with reduced (0.07–0.08-fold) risk (rs917778 of multivesicular body subunit 12B (MVB12B) and rs2234753 of retinoic acid X receptor alpha (RXRA) genes). The rs2032930 showed a significant correlation with current perception thresholds measured at 5 Hz and 250 Hz for n. medianus (p = 0.042 and p = 0.003, respectively) and at 5 Hz for n. peroneus (p = 0.037), as well as the deep breath test (p = 0.022) and the NTSS (p = 0.023). The rs2032931 was associated with current perception thresholds (p = 0.003 and p = 0.037, respectively), deep breath test (p = 0.022), and NTSS (p = 0.023). The rs604349 correlated with values measured at 2000 (p = 0.049), 250 (p = 0.018), and 5 Hz (p = 0.005) for n. medianus, as well as warm perception threshold measured by Medoc device (p = 0.042). The rs2234753 showed correlations with a current perception threshold measured at 2000 Hz for n. medianus (p = 0.020), deep breath test (p = 0.040), and NTSS (p = 0.003). There was a significant relationship between rs91778 and cold perception threshold (p = 0.013). In our study, genetic variants have been identified that may have an impact on the risk of neuropathy developing in type 2 diabetic patients. These results could open up new opportunities for early preventive measures and might provide targets for new drug developments in the future.

IntroductionAutonomic and sensory neuropathy have been observed in both prediabetes and manifest diabetes mellitus. However, there is a lack of available data regarding whether patients at a moderate or high risk of developing diabetes, yet without a current diagnosis of prediabetes or diabetes, exhibit an increased prevalence of neuropathy.MethodsFINDRISC (Finnish Diabetes Risk Score) was used to classify individuals at risk (≥12 points, n = 44; control 5.6% served as exclusion criteria, and patients with known medical conditions predisposing to neuropathy were also excluded. Cardiac autonomic function (Ewing tests) and peripheral sensory neuropathy (Neurometer and Q-sense) were assessed by standardized protocols, and their potential association with increased FINDRISC points was analyzed using a regression model.ResultsMean age was 46.7 ± 14.3 years in the control and 55.7 ± 14.1 years in the increased risk group. Male/female ratio did not differ. Individuals with increased risk of diabetes were more obese (BMI: 29.9 ± 12.5 kg/m2 vs. 25.9 ± 8.9 kg/m2). Additionally, hypertension was more frequent among them (68.2% vs. 17.9%), and their lipid parameters were also less favorable. Parasympathetic neuropathy was present in both groups (56.8% vs. 32.1%, respectively). Sympathetic neuropathy was not found. Sensory nerve dysfunction was of low prevalence in the high-risk group and did not occur in healthy controls. In multiple logistic regression analysis, HbA1c exhibited an independent association with parasympathetic neuropathy (OR: 5.9; 95% CI: 1.08–32.68; p < 0.041).DiscussionAn increased risk of developing prediabetes/diabetes does not appear to have a strong correlation with an increased likelihood of developing autonomic or sensory neuropathy. However, the etiology behind the occurrence of parasympathetic autonomic neuropathy in healthy individuals remains unknown.

Electrochemistry is an established discipline with modern frontiers spanning energy conversion and storage, neuroscience, and organic synthesis. In spite of the expanding opportunities for academic and industrial electrochemists, particularly in the growing energy-storage sector, rigorous training of electrochemists is generally lacking at academic institutions in the United States. In this perspective, we highlight the core concepts of electrochemistry and discuss ways in which it has been historically taught. We identify challenges faced when teaching inherently interdisciplinary electrochemical concepts and discuss how technology provides new tools for teaching, such as inexpensive electronics and open-source software, to help address these challenges. Finally, we outline example programs and discuss how new tools and approaches can be brought together to prepare scientists and engineers for careers in electrochemical technology where they can accelerate the research, development, and deployment of the clean energy technology essential to combat climate change in the coming decades.

This Comment highlights the importance of Faradaic efficiency reporting and discusses methods for reliable measurements of Faradaic efficiency in the electrocatalysis field.

Studies of reconsolidation interference posit that reactivation of a previously consolidated memory via a reminder brings it into an active, labile state, leaving it open for potential manipulation. If interfered with, this may disrupt the original memory trace. While evidence for pharmacological reconsolidation interference is widespread, it remains unclear whether behavioural interference using the presentation of competing information can engender it, especially in declarative memory. Almost all previous studies in this area have employed between-subjects designs, in which there are potential confounds, such as different retrieval strategies for the multiple conditions. In the current studies, within-subjects paradigms were applied to test the effects of reconsolidation interference on associative recognition and free recall. In Experiment 1, participants engaged in pair-associate learning of unrelated object pictures on Day 1, and after a reminder, interference, reminder + interference, or no manipulation (control) on Day 2, were tested on associative recognition of these pairs on Day 3. In Experiments 2 and 3, memoranda were short stories studied on Day 1. On Day 2, stories were assigned to either control, reminder, interference by alternative stories, or reminder + interference conditions. On Day 3 participants recalled the Day 1 stories, and answered yes/no recognition questions. Reminders improved subsequent memory, while interference was effective in reducing retrieval in differing degrees across the experiments. Importantly, the reminder + interference condition was no more effective in impairing retrieval than the interference-alone condition, contrary to the prediction of the behavioural reconsolidation-interference approach.

IntroductionVascular complications and neuropathy may develop in the presence of metabolic syndrome. The aim of our study was to measure the cardiovascular autonomic function following physical training in patients with metabolic syndrome with and without diabetes.Subjects and methods56 patients with metabolic syndrome (32 men/24 women, 40 non-diabetic patients (NDMetS)/16 diabetic patients (DMetS) [mean ± SD]: age: 50.35 ± 8.03 vs. 56.8 ± 9.30 years, p=0.023; baseline BMI: 32.2 ± 7.03 vs. 32.8 ± 5.94 kg/m2, p=0.739) were involved in our study. All tests and measurements were carried out before and following a 3-month physical training period. Autonomic function was assessed by means of five standard cardiovascular reflex tests. ECG repolarization parameters, including short-term QT variability and stress-ECG were also measured.ResultsIn the whole population, Valsalva-ratio (VR) and the autonomic score (AS) improved following training (VR: 1.49 ± 0.24 vs. 1.64 ± 0.34, p=0.001; AS: 2.05 ± 1.73 vs. 1.41 ± 1.36, p=0.015) accompanied by the significant decrease of the systolic (150.3 ± 16.12 vs. 134.1 ± 16.67 mmHg, p

The past two decades have witnessed telemedicine becoming a crucial part of health care as a method to facilitate doctor-patient interaction. Due to technological developments and the incremental acquisition of experience in its use, telemedicine’s advantages and cost-effectiveness has led to it being recognised as specifically relevant to diabetology. However, the pandemic created new challenges for healthcare systems and the rate of development of digital services started to grow exponentially. It was soon discovered that COVID-19-infected patients with diabetes had an increased risk of both mortality and debilitating sequelae. In addition, it was observed that this higher risk could be attenuated primarily by maintaining optimal control of the patient’s glucose metabolism. As opportunities for actual physical doctor-patient visits became restricted, telemedicine provided the most convenient opportunity to communicate with patients and maintain delivery of care. The wide range of experiences of health care provision during the pandemic has led to the development of several excellent strategies regarding the applicability of telemedicine across the whole spectrum of diabetes care. The continuation of these strategies is likely to benefit clinical practice even after the pandemic crisis is over.

BackgroundDistal symmetric polyneuropathy (DSPN) is a common microvascular complication of both type 1 and 2 diabetes with substantial morbidity burden and reduced quality of life. Its association with mortality is equivocal.PurposeTo describe the association between DSPN and all-cause mortality in people with diabetes and further stratify by the type of diabetes based on a meta-analysis of published observational studies.Data SourcesWe searched Medline from inception to May 2021.Study SelectionOriginal data were collected from case-control and cohort studies that reported on diabetes and DSPN status at baseline and all-cause mortality during follow-up.Data Extractionwas completed by diabetes specialists with clinical experience in neuropathy assessment.Data SynthesisData was synthesized using random-effects meta-analysis. The difference between type 1 and 2 diabetes was investigated using meta-regression.ResultsA total of 31 cohorts (n=155,934 participants, median 27.4% with DSPN at baseline, all-cause mortality 12.3%) were included. Diabetes patients with DSPN had an almost twofold mortality (HR: 1.96, 95%CI: 1.68-2.27, I2 = 91.7%), I2 = 91.7%) compared to those without DSPN that was partly explained by baseline risk factors (adjusted HR: 1.60, 95%CI: 1.37-1.87, I2 = 78.86%). The association was stronger in type 1 compared to type 2 diabetes (HR: 2.22, 95%CI: 1.43-3.45). Findings were robust in sensitivity analyses without significant publication bias.LimitationsNot all papers reported multiple adjusted estimates. The definition of DSPN was heterogeneous.ConclusionsDSPN is associated with an almost twofold risk of death. If this association is causal, targeted therapy for DSPN could improve life expectancy of diabetic patients.

Abstract This research is aimed at developing novel theory to advance innovative methods for examining how collaborative groups progress toward productively engaging during classroom activity that integrates disciplinary practices. This work draws on a situative perspective, along with prior framings of individual engagement, to conceptualize engagement as a shared and multidimensional phenomenon. A multidimensional conceptualization affords the study of distinct engagement dimensions, as well as the interrelationships of engagement dimensions that together are productive. Development and exploration of an observational rubric evaluating collaborative group disciplinary engagement (GDE) is presented, leveraging the benefits of observational methods with a rubric specifying quality ratings, enabling the potential for analyses of larger samples more efficiently than prior approaches, but with similar ability to richly characterize the shared and multidimensional nature of group engagement. Mixed-methods analyses, including case illustrations and profile analysis, showcase the synergistic interrelations among engagement dimensions constituting GDE. The rubric effectively captured engagement features that could be identified via intensive video analysis, while affording the evaluation of broader claims about group engagement patterns. Application of the rubric across curricular contexts, and within and between lessons across a curricular unit, will enable comparative studies that can inform theory about collaborative engagement, as well as instructional design and practice.

BackgroundEarly childhood is a critical period for supporting the development of healthy eating habits, which may affect lifelong health. Childcare services are important settings for promoting early childhood nutrition; however, food provision in childcare frequently does not align with dietary guidelines. Web-based menu planning tools are well suited to support healthy food provision in childcare, although little is known about their use. Research is needed to understand how web-based menu planning tools are used in the childcare setting and how they can effectively support healthy menu planning and food provision for children in childcare. ObjectiveWe aimed to explore the use of a web-based menu planning tool called FoodChecker, which is available to childcare services in Victoria, Australia. We also aimed to gain insights and perspectives from childcare staff involved in menu planning about their use of the tool to plan healthy menus and guide healthy food provision for children. MethodsWe conducted a qualitative descriptive study using a cross-sectional web-based survey completed by the staff involved in menu planning in childcare services. Thematic analysis was performed using NVivo software. Emergent themes were mapped against constructs of the Technology Acceptance Model regarding perceived usefulness, perceived ease of use, and external variables influencing perceptions and use. ResultsThe participants included 30 cooks and 34 directors from 53 childcare services. Participants perceived the web-based menu planning tool as useful for supporting child nutrition and health, improving organizational processes, and aiding the menu planner role. Perceptions regarding ease of use were mixed. External variables influencing perceptions and use included awareness of the tool, perceived need, time, resources, organizational support, and the food budget. Participants made recommendations to improve the tool, particularly the need to integrate functionality to make it easier and faster to use or to include more links to resources to support healthy menu planning. ConclusionsThe web-based menu planning tool was perceived as useful for cooks and directors in childcare services. Areas for improvement were identified; for example, the need for integrated digital features to make the tool easier and faster to use. As the first qualitative study to explore childcare staff experiences with a web-based menu planning tool, these findings inform future research and development of such tools to aid scalable and sustainable support for healthier food provision in the childcare sector.

Horseshoe crabs are xiphosuran chelicerates, the sister group to arachnids. As such, they are important for understanding the most recent common ancestor of Euchelicerata and the evolution and diversification of Arthropoda. Limulus polyphemus is the most investigated of the four extant species of horseshoe crabs, and the structure and function of its visual system have long been a major focus of studies critical for understanding the evolution of visual systems in arthropods. Likewise, studies of genes encoding Limulus opsins, the protein component of the visual pigments, are critical for understanding opsin evolution and diversification among chelicerates, where knowledge of opsins is limited, and more broadly among arthropods. In the present study, we sequenced and assembled a high quality nuclear genomic sequence of L. polyphemus and used these data to annotate the full repertoire of Limulus opsins. We conducted a detailed phylogenetic analysis of Limulus opsins, including using gene structure and synteny information to identify relationships among different opsin classes. We used our phylogeny to identify significant genomic events that shaped opsin evolution and therefore the visual system of Limulus We also describe the tissue expression patterns of the 18 opsins identified and show that transcripts encoding a number, including a peropsin, are present throughout the central nervous system. In addition to significantly extending our understanding of photosensitivity in Limulus and providing critical insight into the genomic evolution of horseshoe crab opsins, this work provides a valuable genomic resource for addressing myriad questions related to xiphosuran physiology and arthropod evolution.

Abstract The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium–glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D.

Introduction The aim of the present study was to assess changes in the incidence and prevalence of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in children and adolescents in Hungary during the period 2001 to 2016 in order to provide nationwide population-based epidemiology data on diabetes in youths aged 0–18 years. Material and methods This was a retrospective cohort study of Hungarian children and adolescents aged 18 years or younger. Pharmacologically treated diabetes cases were obtained through a population-based registry of the Hungarian National Health Insurance Fund. Time series analysis was used to evaluate the changing patterns of the incidence and prevalence for type 1 and type 2 diabetes covering a 16-year period. Results During the study period, 6,138 and 1,997 new T1DM and T2DM cases were observed, respectively. Newly diagnosed T2DM cases accounted for 24.5% of all incident diabetes cases. Incidence of T1DM increased from 16/100,000 to 23/100,000 (R2 = 0.7681; p < 0.0001). The male-to-female ratio among newly diagnosed T1DM patients did not change over the study period. Prevalence of T1DM rose from 114/100,000 to 209/100,000 (R2 = 0.9909; p < 0.0001). The prevalent T1DM cases showed significant male predominance in every year (p < 0.05). Incidence of T2DM decreased from 8/100,000 to 5/100,000 (R2 = 0.4977; p < 0.0014). The overall prevalence of T2DM did not change significantly. Prevalent T2DM cases showed significant female predominance in every year (p < 0.0001). A significant decrease in male-to female ratio was observed among newly diagnosed T2DM cases over the study period (p < 0.0001). Conclusions According to these population-based Hungarian data of children and adolescents with diabetes, T1DM is still the most common form and its frequency continues to rise, affecting more males than females. A high proportion of patients have T2DM, affecting more females than males, but the occurrence of medically treated cases is not increasing. The decrease in male-to-female ratio in newly diagnosed T2DM cases needs further investigations.

Efforts in the fight against COVID-19 are achieving success in many parts of the world, although progress remains slow in other regions. We believe that a syndemic approach needs to be adopted to address this pandemic given the strong apparent interplay between COVID-19, its related complications, and the socio-structural environment. We have assembled an international, multidisciplinary group of researchers and clinical practitioners to promote a novel syndemic approach to COVID-19: the CArdiometabolic Panel of International experts on Syndemic COvid-19 (CAPISCO). This geographically diverse group aims to facilitate collaborative-networking and scientific exchanges between researchers and clinicians facing a multitude of challenges on different continents during the pandemic. In the present article we present our “manifesto”, with the intent to provide evidence-based guidance to the global medical and scientific community for better management of patients both during and after the current pandemic.

Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.

BackgroundIn diabetes mellitus, during the last years, cancer became of equivalent importance as a cardiovascular disease in terms of mortality. In an earlier study, we have analyzed data of the National Health Insurance Fund (NHIF) of Hungary with regards all patients treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) vs. those treated with dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4is) in a given timeframe. In propensity score-matched groups of SGLT2i- vs. DPP-4i-treated patients, we found a lower incidence of cancer in general. In this post-hoc analysis, we aimed to obtain data on the incidence of site-specific cancer.Patients and MethodsAll patients starting an SGLT2i or a DPP-4i between 2014 and 2017 in Hungary were included; the two groups (SGLT2i vs. DPP-4i) were matched for 54 clinical and demographical parameters. The follow-up period was 639 vs. 696 days, respectively. Patients with a letter “C” International Classification of Diseases, 10th Revision (ICD-10) code have been chosen, and those with a known malignancy within a year before the onset of the study have been excluded from the analysis.ResultsWe found a lower risk of urinary tract [HR 0.50 (95% CI: 0.32–0.79) p = 0.0027] and hematological malignancies [HR 0.50 (95% CI: 0.28–0.88) p = 0.0174] in patients treated with SGLT2i vs. those on DPP-4i. Risk of other types of cancer (including lung and larynx, lower gastrointestinal (GI) tract, rectum, pancreas, non-melanoma skin cancers, breast, or prostate) did not differ significantly between the two groups. When plotting absolute risk difference against follow-up time, an early divergence of curves was found in case of prostate, urinary tract, and hematological malignancies, whereas late divergence can be seen in case of cancers of the lung and larynx, the lower GI tract, and the breast.ConclusionsUrinary tract and hematological malignancies were less frequent in patients treated with SGLT2i vs. DPP-4i. An early vs. late divergence could be observed for different cancer types, which deserves further studies.

Introduction Mortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on long-term complications of type 2 diabetes mellitus was studied.Research design and methods Patients with type 2 diabetes treated with DPP-4i or SGLT2i during a 3-year period were identified in the database of the National Institute of Health Insurance Fund in Hungary. All-cause mortality, acute myocardial infarction, stroke, hospitalization for heart failure (HHF), lower limb amputation (LLA) and cancer were assessed. Outcomes of add-on SGLT2i to DPP-4i treatment in comparison with switching DPP-4i therapy to SGLT2i were also evaluated. After propensity score matching, survival analysis was performed with a Cox proportional hazards model.Results After propensity score matching, both SGLT2i and DPP-4i groups included 18 583 patients. All-cause mortality (HR, 0.80; 95% CI 0.68 to 0.94; p=0.0057), HHF (HR, 0.81; 95% CI 0.71 to 0.92; p=0.0018), and risk of cancer (HR, 0.75; 95% CI 0.66 to 0.86; p

IntroductionThe prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care.Patients and MethodsTwenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests.ResultsT1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01).ConclusionIn this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.

Background and objectives: In the last couple of years, pharmacological management of patients with type 2 diabetes mellitus (T2DM) have been markedly renewed. The aim of this study was to analyse the changes in prescribing patterns of antidiabetic drugs for treating patients with T2DM in Hungary between 2015 and 2020. Material and Methods: In this retrospective, nationwide analysis, we used the central database of the National Health Insurance Fund. We present annual numbers and their proportion of T2DM patients with different treatment regimens. Results: In the period of 2015–2020, the number of incident cases decreased from 60,049 to 29,865, while prevalent cases increased from 682,274 to 752,367. Patients with metformin (MET) monotherapy had the highest prevalence (31% in 2020). Prevalence of insulin (INS) monotherapy continuously but slightly decreased from 29% to 27% while that of sulfonylurea (SU) monotherapy markedly decreased from 37% to 20%. Dipeptidyl peptidase (DPP-4) inhibitors remained popular in 2020 as monotherapy (5%), in dual combination with MET (12%) and in triple combination with MET and SU (5%). The prevalence of patients with sodium-glucose co-transporter-2 (SGLT-2) inhibitors increased from 1% to 4% in monotherapy, from Conclusions: In the period of 2015–2020, we documented important changes in trends of antihyperglycaemic therapeutic patterns in patients with T2DM which followed the new scientific recommendations but remained below our expectations regarding timing and magnitude. More efforts are warranted to implement new agents with cardiovascular/renal benefits into therapeutic management in time, in a much larger proportion of T2DM population, and without delay.

Summary: Electrochemistry is an established discipline with modern frontiers spanning energy conversion and storage, neuroscience, and organic synthesis. In spite of the expanding opportunities for academic and industrial electrochemists, particularly in the growing energy-storage sector, rigorous training of electrochemists is generally lacking at academic institutions in the United States. In this perspective, we highlight the core concepts of electrochemistry and discuss ways in which it has been historically taught. We identify challenges faced when teaching inherently interdisciplinary electrochemical concepts and discuss how technology provides new tools for teaching, such as inexpensive electronics and open-source software, to help address these challenges. Finally, we outline example programs and discuss how new tools and approaches can be brought together to prepare scientists and engineers for careers in electrochemical technology where they can accelerate the research, development, and deployment of the clean energy technology essential to combat climate change in the coming decades.

Objectives Progranulin (PGRN) is a secreted growth factor that helps to regulate neuronal survival by blocking tumor necrosis factor-alpha (TNFα) receptors. The antioxidant alpha-lipoic acid (ALA) is used in diabetic neuropathy to improve nerve conduction and relieve neuropathic pain, but its effects on PGRN levels have not yet been elucidated. Methods In this prospective study, 54 patients with type 2 diabetes and peripheral neuropathy received 600 mg of ALA daily for 6 months. Twenty-four patients with diabetes without neuropathy were also included in the study. Serum PGRN and TNFα levels were determined using enzyme-linked immunosorbent assays. In addition, current perception threshold (CPT) testing was used to assess sensory neuropathy. Results After ALA treatment, serum PGRN levels were significantly increased and CPT values were significantly improved. Furthermore, there were significant positive correlations among TNFα, ICAM-1, and PGRN levels both before and after ALA treatment. A significant negative correlation was observed between the improvements in CPT and the PGRN levels. Furthermore, ICAM-1 levels were an independent predictor of PGRN levels. Conclusions Changes in serum PGRN levels indicate that ALA treatment may have beneficial effects on endothelial function and neuronal inflammation.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

Background. People with diabetic cardiovascular autonomic neuropathy (CAN) have increased cardiovascular mortality. However, the association between distal symmetric polyneuropathy (DSPN) or CAN with all-cause mortality is much less investigated. Thus, we set out to examine the effect of CAN and DSPN on all-cause mortality in a well-phenotyped cohort. Methods. All diabetes cases (n=1,347) from the catchment area of a secondary diabetes care centre who had medical examination including neuropathy assessment between 1997 and 2016 were followed up for all-cause mortality in the NHS Hungary reimbursement database until 2018. We investigated the association of CAN (Ewing tests) and DSPN (Neurometer) with all-cause mortality using Cox models stratified by diabetes type. Results. Altogether, n=131/1,011 persons with type 1/type 2 diabetes were included. Of the participants, 53%/43% were male, mean age was 46±12/64±10 years, diabetes duration was 13±10/7±8 years, 42%/29% had CAN, and 39%/37% had DSPN. During the 9±5/8±5-year follow-up, n=28/494 participants died. In fully adjusted models, participants with type 1 diabetes patients with versus without DSPN had an increased mortality (HR 2.99, 95% CI 1.4-8.63), while no association with CAN was observed. In type 2 diabetes, both DSPN and CAN independently increased mortality (HR 1.32, 95% CI: 1.07-1.64, and HR 1.44, 95% CI: 1.17-1.76). Conclusions. Our results are compatible with an increased risk of mortality in people with type 1 diabetes and DSPN. Furthermore, we report a similarly strong association between DSPN and CAN and all-cause mortality in type 2 diabetes mellitus.

Background: Diabetic neuropathy (DN) is a very frequent microvascular complication of type 2 diabetes mellitus (T2DM). Obesity and physical inactivity are well-known risk factors for T2DM. Fibroblast growth factor 21 (FGF21) is a liver-secreted hormone with several beneficial effects on obesity-related metabolic disorders. We aimed to investigate the effect of short-term physical activity on the levels of FGF21, and its correlation with the severity of peripheral sensory polyneuropathy in T2DM patients. Methods: Thirty patients with DN were enrolled in the study, compared to age- and gender-matched controls. We conducted a six-week aerobic training program, which meant treadmill and cycle ergometers three times a week. Anthropometric and laboratory parameters were measured for each patient before and after intervention. Serum levels of FGF21, TNF-alpha, irisin, leptin and adiponectin were measured by ELISA. The sensory perception threshold (CPT) was quantitatively measured using Neurometer®. Results: We found significant decreases in BMI, waist circumference, HbA1c and TNF-alpha levels. From baseline to six-week follow-up, FGF21 levels were significantly increased in DN patients. Significant negative correlations were shown between the changes in FGF21 levels and BMI, between changes in FGF21 and the improvement of CPT values, and between the changes in FGF21 and TNF-alpha levels. There was no difference in irisin, adiponectin and leptin levels in DN patients after aerobic training program. Conclusions: The physical activity may increase the level of FGF21 in T2DM patients with neuropathy. Our results highlight the importance of regular physical activity in the treatment of diabetic neuropathy.

Objective To predict dietary self-efficacy behaviors in high glycosylated hemoglobin A1c (HbA1c) patients using type D personality (TDP) and other psychosocial measures. Methods A cross-sectional, predictive research design was implemented. Participants were type 2 diabetes mellitus patients diagnosed more than 2 years prior to the study. Data were collected for demographics, dietary self-efficacy and psychological measures. Spearman’s rank-order correlation was used to test for relationships, the Mann–Whitney test was used to test for differences and multiple linear regression was used to examine predictors of dietary self-efficacy. Results Lower dietary self-efficacy was strongly correlated with greater social isolation (r = 0.93) and moderately correlated with more mental health problems (r = 0.20) and higher TDP scores (r = 0.17). Higher HbA1c was inversely related to self-reported physical health (r = −0.19). Social and emotional isolation and time since diagnosis predicted dietary self-efficacy (greater isolation was associated with more dietary management difficulties). Conclusions Regression outcomes suggested that a 10% decrease in social isolation improves dietary self-efficacy by 30%, a significant boost to therapeutic adherence. We recommend assessment of social isolation to improve dietary self-efficacy and achieve better patient adherence to therapy.

Abstract Background The excess risks of mortality and cardiovascular morbidity among patients with type 2 diabetes mellitus (T2DM) is well known. In this nationwide study, we assessed risks of mortality and cardiovascular events comparing patients with T2DM and matched controls. Methods We identified patients with T2DM in a retrospective cohort study using the database of the National Health Insurance Fund between 1 January 2010 and 31 December, 2013. Controls were randomly included and matched according to age, gender, and zip code of residence. Patients were divided into subgroups according to age decades for outcome analyses. Results During the mean follow-up period of 2.3 years, 152,678 patients with T2DM and 305,356 matched controls were included. Patients with T2DM showed significantly higher risk for all-cause mortality (HR 1.26, 95% CI 1.22–1.29, p