Reduced macula microvascular densities may be an early indicator for diabetic peripheral neuropathy

Purpose: To assess the alteration in the macular microvascular in type 2 diabetic patients with peripheral neuropathy (DPN) and without peripheral neuropathy (NDPN) by optical coherence tomography angiography (OCTA) and explore the correlation between retinal microvascular abnormalities and DPN disease.Methods: Twenty-seven healthy controls (42 eyes), 36 NDPN patients (62 eyes), and 27 DPN patients (40 eyes) were included. OCTA was used to image the macula in the superficial vascular complex (SVC) and deep vascular complex (DVC). In addition, a state-of-the-art deep learning method was employed to quantify the microvasculature of the two capillary plexuses in all participants using vascular length density (VLD).Results: Compared with the healthy control group, the average VLD values of patients with DPN in SVC (p = 0.010) and DVC (p = 0.011) were significantly lower. Compared with NDPN, DPN patients showed significantly reduced VLD values in the SVC (p = 0.006) and DVC (p = 0.001). Also, DPN patients showed lower VLD values (p < 0.05) in the nasal, superior, temporal and inferior sectors of the inner ring of the SVC when compared with controls; VLD values in NDPN patients were lower in the nasal section of the inner ring of SVC (p < 0.05) compared with healthy controls. VLD values in the DVC (AUC = 0.736, p < 0.001) of the DPN group showed a higher ability to discriminate microvascular damage when compared with NDPN.Conclusion: OCTA based on deep learning could be potentially used in clinical practice as a new indicator in the early diagnosis of DM with and without DPN

Hydrocyanation of 2-arylmethyleneindan-1,3-diones using potassium hexacyanoferrate(II) as a nontoxic cyanating agent

The hydrocyanation of 2-arylmethyleneindan-1,3-diones with potassium hexacyanoferrate(II) as a nontoxic cyanating agent to synthesize 2-(1,3-dioxoindan-2-yl)-2-arylacetonitriles in the presence of benzoyl chloride as a promoter and potassium carbonate as a base by a one-pot procedure is described. The use of nontoxic and inexpensive cyanide source, high yield and simple workup procedures are the advantages of this protocol

The effect of COVID-19 vaccination on epileptic seizures in patients with epilepsy: A clinical observation in China

This observational retrospective study was conducted on patients with epilepsy (PWE) in China who had at least one dose of COVID-19 vaccine and it investigated the safety of vaccination by analyzing changes in epileptic seizures and their influencing factors. Consecutive PWE who were followed up in the epilepsy clinic between June 2021 and May 2022 were enrolled. Data on vaccine type, demographic information, clinical characteristics of epilepsy, and treatment were collected through a questionnaire survey and retrospectively analyzed. PWE were divided into a stable seizure group and a worsening seizure group based on seizure episodes at least 90 days after the first vaccine dose. A total of 79 PWE were included. After vaccination, 14 patients (17.7%) had worsening seizures, 92.9% of whom had an increased seizure frequency. Compared with patients in the stable seizure group, patients in the worsening seizure group had significant differences in baseline monthly seizure frequency (P = .012), improper antiseizure medication (ASM) administration (P = .003) and a disrupted sleep routine (P = .016). Multivariate logistic regression analysis showed that improper ASM administration (OR 6.186, 95% confidence interval [CI] 1.312–29.170; p = .021) and a disrupted sleep routine (OR 6.326, 95% CI 1.326–30.174; p = .021) were significantly associated with seizure worsening. In short, COVID-19 vaccination is safe for PWE, and only those with poor seizure control have the possibility of seizure exacerbation after COVID-19 vaccination. The vaccination per se does not represent a major influencing factor, but the improper use of ASMs and a disrupted sleep routine may be correlated with seizure aggravation after vaccination

Case report: A choroidal fissure pial arteriovenous malformation inducing venous congestive edema of the medulla oblongata and cervicothoracic spinal cord presented with proximal arm predominant weakness

Intracranial dural arteriovenous fistula (DAVF) can induce remote myelopathy via spinal perimedullary venous drainage. In the present study, we report a rare case of intracranial pial arteriovenous malformation (AVM)-related myelopathy. A 52-year-old man presented with progressive, predominantly proximal weakness and muscle atrophy in bilateral upper limbs, urinary retention, and hyperreflexia in bilateral upper and lower limbs. Brain and cervicothoracic MRI showed longitudinal myelopathy extending from the medulla oblongata to the T6 level, with perimedullary enlarged veins from the C1 to T12 level, and remarkable enhancement in bilateral anterior horns from the C2 to C7 level. Cerebral angiography revealed a choroidal fissure AVM, which was supplied by the left anterior choroidal artery and drained exclusively by an inferior ventricular vein descending toward the spinal perimedullary veins. After endovascular embolization of the feeding pedicle, nidus, and proximal segment of the draining vein, the patient's neurological deficits rapidly improved, and a significant recovery was achieved 3 months after the procedure. This rare case indicates that intracranial pial AVM can also cause extensive congestive myelopathy with similar mechanisms underlying intracranial and craniocervical DAVF cases, and gray matter in the spinal cord might be more susceptible to ischemia induced by intraspinal venous hypertension

MbovP0725, a secreted serine/threonine phosphatase, inhibits the host inflammatory response and affects metabolism in Mycoplasma bovis

ABSTRACTMycoplasma species are able to produce and release secreted proteins, such as toxins, adhesins, and virulence-related enzymes, involved in bacteria adhesion, invasion, and immune evasion between the pathogen and host. Here, we investigated a novel secreted protein, MbovP0725, from Mycoplasma bovis encoding a putative haloacid dehalogenase (HAD) hydrolase function of a key serine/threonine phosphatase depending on Mg2+ for the dephosphorylation of its substrate pNPP, and it was most active at pH 8 to 9 and temperatures around 40°C. A transposon insertion mutant strain of M. bovis HB0801 that lacked the protein MbovP0725 induced a stronger inflammatory response but with a partial reduction of adhesion ability. Using transcriptome sequencing and quantitative reverse transcription polymerase chain reaction analysis, we found that the mutant was upregulated by the mRNA expression of genes from the glycolysis pathway, while downregulated by the genes enriched in ABC transporters and acetate kinase–phosphate acetyltransferase pathway. Untargeted metabolomics showed that the disruption of the Mbov_0725 gene caused the accumulation of 9-hydroxyoctadecadienoic acids and the consumption of cytidine 5′-monophosphate, uridine monophosphate, and adenosine monophosphate. Both the exogenous and endogenous MbvoP0725 protein created by purification and transfection inhibited lipopolysaccharide (LPS)-induced IL-1β, IL-6, and TNF-α mRNA production and could also attenuate the activation of MAPK-associated pathways after LPS treatment. A pull-down assay identified MAPK p38 and ERK as potential substrates for MbovP0725. These findings define metabolism- and virulence-related roles for a HAD family phosphatase and reveal its ability to inhibit the host pro-inflammatory response.IMPORTANCEMycoplasma bovis (M. bovis) infection is characterized by chronic pneumonia, otitis, arthritis, and mastitis, among others, and tends to involve the suppression of the immune response via multiple strategies to avoid host cell immune clearance. This study found that MbovP0725, a haloacid dehalogenase (HAD) family phosphatase secreted by M. bovis, had the ability to inhibit the host pro-inflammatory response induced by lipopolysaccharide. Transcriptomic and metabolomic analyses were used to identify MbovP0725 as an important phosphatase involved in glycolysis and nucleotide metabolism. The M. bovis transposon mutant strain T8.66 lacking MbovP0725 induced a higher inflammatory response and exhibited weaker adhesion to host cells. Additionally, T8.66 attenuated the phosphorylation of MAPK P38 and ERK and interacted with the two targets. These results suggested that MbovP0725 had the virulence- and metabolism-related role of a HAD family phosphatase, performing an anti-inflammatory response during M. bovis infection

Room Temperature Surface Modification of Ultrathin FeOOH Cocatalysts on Fe2O3 Photoanodes for High Photoelectrochemical Water Splitting

An ultrathin FeOOH cocatalyst is deposited on α-Fe2O3 photoanodes in a simple room temperature immersion process for efficient photoelectrochemical (PEC) water splitting. The prepared FeOOH/Fe2O3 photoanode has a photocurrent density of up to 2.4 mA/cm2 at 1.23 V versus reversible hydrogen electrode (RHE), and the photocurrent density is increased by about 160% compared to the bare Fe2O3 of 1.55 mA/cm2. An obvious cathodic shift of the photocurrent onset potential from 0.661 to 0.582 V was also observed, and excellent stability was maintained with almost no deterioration for 5 h. The enhanced PEC performance is attributed to the decrease of the interfacial resistance between electrode and electrolyte and the increase of the injection efficiency of holes in Fe2O3

Exploration and Differential Analysis of Continuing Education of General Practitioners' Clinical Thinking Ability Based on Working Competence

Background The current training content of continuing education in general practice cannot meet the needs of clinical practice, as well as the lacking of thinking and characteristics of general practice in teaching faculty and evaluation methods. Objective To explore the training of clinical thinking in general practice through continuing education, so as to solve practical problems and improve working competence of general practitioners (GPs) . Methods The design of the 8th GPs' practice ability training workshop course was optimized based on the literature reading and feedback from the continuing education course of GPs' practice ability workshop in November 2020, and a questionnaire survey was conducted through the "wenjuanxing" platform among 200 GPs who participated in the 8th workshop course to evaluate the overall and various levels of improvement in their clinical thinking ability and working competence. Results A total of 200 questionnaires were distributed, and 172 valid questionnaires were collected, with a recovery rate of 86.0%. After the training, 52.3% (90/172) and 21.5% (37/172) of the GPs had improved and greatly improved their overall clinical thinking ability in general practice, respectively, and 56.4% (97/172) and 22.1% (38/172) showed improvement and great improvement in overall working competence. There was a statistically significant difference in the improvement of clinical thinking ability and working competence among GPs with different professional titles and job types after training (P<0.05). There were 134 (77.9%), 134 (77.9%), 133 (77.3%), 127 (73.8%), 114 (66.3%) GPs who believed that "reading images" "clinical thinking ability in general practice" "interpretation of test indicators" "diagnosis and treatment of common dermatological and pentacologic diseases" and "scientific research training" could significantly improve the working competence of GPs. There were significant differences in the improvement of working competence by the course on "reading images" "clinical thingking ability in general practice" "diagnosis and treatment of common dermatological and pentacologic diseases" among GPs with different professional titles and job types (P<0.05). There was significant difference in the improvement of working competence by "scientific research" training course section in GPs of different genders (P<0.05) . Conclusion Optimized continuing education of general practice has a significant effect on the clinical thinking and working competence of GPs. In the design of training to improve the clinical thinking and working competence of GPs, it is also necessary to pay attention to the integration of various types of knowledge and skills in the training, and the practice experience base and accumulation of the trainees

DataSheet1_Comprehensive analysis of FRAS1/FREM family as potential biomarkers and therapeutic targets in renal clear cell carcinoma.PDF

Background: FRAS1 (Fraser syndrome protein 1), together with FREM1 (the Fras1-related extracellular matrix proteins 1) and FREM2, belonging to the FRAS1/FREM extracellular matrix protein family, are considered to play essential roles in renal organogenesis and cancer progression. However, their roles in kidney renal clear cell carcinoma (KIRC) remain to be elucidated.Methods: FRAS1/FREM RNA expression analysis was performed using TCGA/GTEx databases, and valided using GEO databases and real-time PCR. Protein expression was peformed using CPTAC databases. Herein, we employed an array of bioinformatics methods and online databases to explore the potential oncogenic roles of FRAS1/FREM in KIRC.Results: We found that FRAS1, FREM1 and FREM2 genes and proteins expression levels were significantly decreased in KIRC tissues than in normal tissues. Decreased FRAS1/FREM expression levels were significantly associated with advanced clinicopathological parameters (pathological stage, grade and tumor metastasis status). Notably, the patients with decreased FRAS1/FREM2 expression showed a high propensity for metastasis and poor prognosis. FRAS1/FREM were correlated with various immune infiltrating cells, especially CD4+ T cells and its corresponding subsets (Th1, Th2, Tfh and Tregs). FRAS1 and FREM2 had association with DNA methylation and their single CpG methylation levels were associated with prognosis. Moreover, FRAS1/FREM might exert antitumor effects by functioning in key oncogenic signalling pathways and metabolic pathways. Drug sensitivity analysis indicated that high FRAS1 and FREM2 expression can be a reliable predictor of targeted therapeutic drug response, highlighting the potential as anticancer drug targets.Conclusion: Together, our results indicated that FRAS1/FREM family members could be potential therapeutic targets and valuable prognostic biomarkers of KIRC.</p