A Mussel-Inspired Conductive, Self-Adhesive, and Self-Healable Tough Hydrogel as Cell Stimulators and Implantable Bioelectronics.

A graphene oxide conductive hydrogel is reported that simultaneously possesses high toughness, self-healability, and self-adhesiveness. Inspired by the adhesion behaviors of mussels, our conductive hydrogel shows self-adhesiveness on various surfaces and soft tissues. The hydrogel can be used as self-adhesive bioelectronics, such as electrical stimulators to regulate cell activity and implantable electrodes for recording in vivo signals.

Osthole Promotes Endochondral Ossification and Accelerates Fracture Healing in Mice.

Osthole has been found to restore bone mass in preclinical osteoporotic models. In the present study, we investigated the effects of osthole on bone fracture repair in mice. Adult C57BL/6 mice were subjected to transverse femoral fractures and administrated orally with 20 mg/kg osthole and vehicle solvent daily from week 1 post-operation. Fracture callus were analyzed by plain radiography, micro-computed tomography, histology, molecular imaging and immunohistochemistry and tartrate-resistant acid phosphatase staining. Results demonstrated that osthole treatment enhanced removal of cartilage and bony union during reparative stage without significant interfering on remodeling process. In vivo molecular imaging showed bone formation rate of the treatment group was almost twofold of control group at week 2 post-operation. Osthole augmented the expression of alkaline phosphatase and collagen type X in hypertrophic chondrocytes as well as expression of bone morphogenetic protein-2, osteocalcin and alkaline phosphatase in osteoblastic cells, indicating it promoted mineralization of hypertrophic cartilage and woven bone growth simultaneously during endochondral healing. In summary, osthole promotes endochondral ossification via upregulation of maturation osteogenic marker genes in chondrocytes and subsequently accelerates fracture repair and bony fusion.

Renal protective and immunoregulatory effects of Lactobacillus casei strain Shirota in nephropathy-prone mice.

Introduction: The incidence of severe acute kidney injury (AKI) is considerably high worldwide. A previous study showed that gut microbial dysbiosis was a hallmark of AKI in mice. Whether the probiotic Lactobacillus casei strain Shirota (LcS) plays a role in kidney disease, particularly AKI, remains unclear. Methods: To investigate the effects of LcS on kidney injury, tubule-specific conditional von Hippel-Lindau gene-knockout C57BL/6 mice (Vhlhdel/del mice) were supplemented without (Ctrl) or with probiotics (LcS) in Experiment 1, and their lifespan was monitored. Additionally, the Vhlhdel/+ mice were supplemented without (Ctrl and AA) or with probiotics (LcS and LcS + AA) in Experiment 2. Probiotic LcS (1 × 109 colony-forming units) was supplemented once daily. After 4 weeks of LcS supplementation, AA and LcS + AA mice were administered aristolochic acid (AA; 4 mg/kg body weight/day)-containing purified diet for 2 weeks to induce AA nephropathy before sacrifice. Results: Supplementation of LcS significantly prolonged the lifespan of Vhlhdel/del mice, suggesting a potential renal protective effect. AA induced-nephropathy increased not only the indicators of renal dysfunction and injury, including urinary protein and kidney injury molecule (KIM)-1, serum blood urea nitrogen (BUN) and creatinine, but also serum interleukin (IL)-6 levels, renal macrophage infiltrations, and pathological lesions in Vhlhdel/+ mice. LcS supplementation significantly reduced urinary protein and KIM-1 levels, serum BUN and IL-6 levels, and renal M1 macrophages, tissue lesions, and injury scores. We also found that LcS maintained gut integrity under AA induction and increased intestinal lamina propria dendritic cells. Furthermore, LcS significantly reduced pro-inflammatory IL-17A and upregulated anti-inflammatory IL-10 production by immune cells from intestinal Peyer's patches (PP) or mesenteric lymph nodes (MLN), and significantly increased IL-10 and reduced IL-6 production by splenocytes. Conclusion: Prior supplementation with probiotic LcS significantly alleviated the severity of renal injury. This renal protective effect was partially associated with the enhancements of intestinal and systemic anti-inflammatory immune responses, suggesting that LcS-induced immunoregulation might contribute to its renal protective effects.

Perception of primary care doctors towards telemedicine in Kuching, Sarawak: A cross-sectional study.

Introduction: Telemedicine is the provision of healthcare remotely via information and communications technology (ICT). This study aimed to assess the familiarity and factors related to the perception towards telemedicine and the willingness to practise telemedicine among primary care doctors. Methods: A multi-centre cross-sectional study was conducted prospectively at all public healthcare clinics across Kuching, Sarawak. A questionnaire was adapted and modified from an overseas validated questionnaire, consisting of four parts: demographic data, familiarity towards telemedicine, factors related to the perception of telemedicine and willingness to implement telemedicine. Results: A total of 131 doctors were recruited. Of them, 43.5% had never interacted with patients via email, WhatsApp or Telegram, while 68.7% had never attended any conferences, speeches or meetings regarding telemedicine. The doctors had low familiarity towards guidelines, technology and medical applications of telemedicine. The majority agreed on the ability of telemedicine to save patients' time and money, the potential of ICT in healthcare and the necessity during a pandemic but perceived the possibility of technical difficulties. The doctors who had experience in interacting with patients via email, WhatsApp or Telegram (P=0.001) and those who had ≤8 years of working experience (P=0.04) had a significantly better perception towards telemedicine. Conclusion: Although the familiarity towards telemedicine among public primary care doctors is low, their perception is good in a majority of areas. Adequate technological support and continuous education on telemedicine and its guidelines, especially medicolegal issues, are imperative to adopt and propagate telemedicine in primary care.

Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice.

The prevalence of obesity and chronic kidney disease (CKD) is increasing simultaneously and rapidly worldwide. Our previous study showed that folate deficiency increased lipid accumulation and leptin production of adipocytes. Whether folate plays a role in CKD, particularly obesity-related nephropathy remains unclear. To investigate the effects of folate deficiency on CKD in diet-induced obese mice, four groups of male C57BL/6 mice were fed either a normal-fat diet (NF) with folate (NF+f); NF without folate (NF-f); high-fat high-fructose diet (HFF) with folate (HFF+f); or HFF without folate (HFF-f) for 12 months during the study. The results showed that HFF increased not only body weight, fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and blood pressure, but also cytokines levels, such as interleukin (IL)-2, interferon (IFN)-γ, IL-17A/F, IL-6, monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-ß1. The indicators of kidney failure including urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), renal type I and IV collagen deposits and leptin content, and serum creatinine were also increased by HFF. Folate-deficient diets further elevated serum TC, LDL-cholesterol, IL-6, tumor necrosis factor (TNF)-α, MCP-1, TGF-ß1, and leptin, but decreased IL-10 level, and thus exacerbated renal fibrosis. To investigate the possible mechanisms of folate deficiency on renal injury, phosphorylation of pro-fibrosis signaling molecules, including signal transducer and activator of transcription (STAT)3 and small mothers against decapentaplegic (Smad)2/3, were assayed. Both HFF and folate deficiency significantly increased the phosphorylation of STAT3 and Smad2/3, suggesting synergistic effects of HFF-f on chronic renal inflammation and fibrosis. In conclusion, the results demonstrated that folate deficiency might aggravate inflammatory status and enhance renal fibrosis.

Temporal Machine Learning Analysis of Prior Mammograms for Breast Cancer Risk Prediction.

The identification of women at risk for sporadic breast cancer remains a clinical challenge. We hypothesize that the temporal analysis of annual screening mammograms, using a long short-term memory (LSTM) network, could accurately identify women at risk of future breast cancer. Women with an imaging abnormality, which had been biopsy-confirmed to be cancer or benign, who also had antecedent imaging available were included in this case-control study. Sequences of antecedent mammograms were retrospectively collected under HIPAA-approved guidelines. Radiomic and deep-learning-based features were extracted on regions of interest placed posterior to the nipple in antecedent images. These features were input to LSTM recurrent networks to classify whether the future lesion would be malignant or benign. Classification performance was assessed using all available antecedent time-points and using a single antecedent time-point in the task of lesion classification. Classifiers incorporating multiple time-points with LSTM, based either on deep-learning-extracted features or on radiomic features, tended to perform statistically better than chance, whereas those using only a single time-point failed to show improved performance compared to chance, as judged by area under the receiver operating characteristic curves (AUC: 0.63 ± 0.05, 0.65 ± 0.05, 0.52 ± 0.06 and 0.54 ± 0.06, respectively). Lastly, similar classification performance was observed when using features extracted from the affected versus the contralateral breast in predicting future unilateral malignancy (AUC: 0.63 ± 0.05 vs. 0.59 ± 0.06 for deep-learning-extracted features; 0.65 ± 0.05 vs. 0.62 ± 0.06 for radiomic features). The results of this study suggest that the incorporation of temporal information into radiomic analyses may improve the overall classification performance through LSTM, as demonstrated by the improved discrimination of future lesions as malignant or benign. Further, our data suggest that a potential field effect, changes in the breast extending beyond the lesion itself, is present in both the affected and contralateral breasts in antecedent imaging, and, thus, the evaluation of either breast might inform on the future risk of breast cancer.

Inter-observer and intra-observer reliability between manual segmentation and semi-automated segmentation for carotid vessel wall volume measurements on three-dimensional ultrasonography.

PURPOSE: Carotid vessel wall volume (VWV) measurement on three-dimensional ultrasonography (3DUS) outperforms conventional two-dimensional ultrasonography for carotid atherosclerosis evaluation. Although time-saving semi-automated algorithms have been introduced, their clinical availability remains limited due to a lack of validation, particularly an extensive reliability analysis. This study compared inter-observer and intra-observer reliability between manual segmentation and semi-automated segmentation for carotid VWV measurements on 3DUS. METHODS: Thirty-one 3DUS volume datasets were prospectively acquired from 20 healthy subjects, aged >18 years, without previous stroke, transient ischemic attack, or cardiovascular disease. Five observers segmented all volume datasets both manually and semi-automatically. The process was repeated five times. Reliability was expressed by the intraclass correlation coefficient, supplemented by the coefficient of variation. RESULTS: Carotid VWV measurements using the common carotid artery (CCA) were more reliable than those using the internal carotid artery (ICA) or external carotid artery (ECA) for both manual and semiautomated segmentation (manual segmentation, CCA: inter-observer, 0.935; intra-observer, 0.934 to 0.966; ICA: inter-observer, 0.784; intra-observer, 0.756 to 0.878; ECA: inter-observer, 0.732; intraobserver, 0.919 to 0.962; semi-automated segmentation, CCA: inter-observer, 0.986; intra-observer, 0.954 to 0.993; ICA: inter-observer, 0.977; intra-observer, 0.958 to 0.978; ECA: inter-observer, 0.966; intra-observer, 0.884 to 0.937). Total carotid VWV measurements by manual (inter-observer, 0.922; intra-observer, 0.927 to 0.961) and semi-automated segmentation (inter-observer, 0.987; intra-observer, 0.968 to 0.989) were highly reliable. Semi-automated segmentation showed higher reliability than manual segmentation for both individual and total carotid VWV measurements. CONCLUSION: 3DUS carotid VWV measurements of the CCA are more reliable than measurements of the ICA and ECA. Total carotid VWV measurements are highly reliable. Semi-automated segmentation has higher reliability than manual segmentation.

Folate Deficiency Increased Lipid Accumulation and Leptin Production of Adipocytes.

Imbalanced dietary habits are closely associated with poor micronutrients status and the development of obesity. Previous studies have shown that serum folate level is decreased in obese individuals. However, whether folate deficiency could result in adiposity is still unclear. The aim of this study was to investigate the effects of dietary folate on lipid accumulation and leptin production using both in vivo and in vitro studies. Male C57BL/6 mice were fed with a diet with (f1) or without (f0) folate in a high-fat (HF) diet containing high-sucrose (HFS-f1, HFS-f0) for 4.5-5 months in Experiment 1, or an HF diet (HF-f1, HF-f0) for 12 months in Experiment 2, or an HF diet containing high-fructose (HFF-f1, HFF-f0) for 12 months in Experiment 3, compared with the normal-fat (NF-f1, NF-f0) diet, respectively. The serum levels of folate and leptin, white adipose tissue (WAT), size of adipocytes, hepatic contents of triglyceride (TG), and cholesterol were measured. In vitro study, TG contents, proinflammatory cytokines, leptin, and expressions of hypoxia-inducible factor (HIF)-1α and lipogenesis-related genes of 3T3-L1 adipocytes cultured with (f1) or without (f0) folate were assayed. The results showed that folate deficiency together with a high-fat diet (HFS-f0, HF-f0, HFF-f0) had higher WAT mass, adipocyte size, serum leptin level, and hepatic TG compared to those of the folate-sufficient groups (HFS-f1, HF-f1, and HFF-f1). Folate deficiency with a high-fat high -sucrose or -fructose diet (HFS-f0, HFF-f0) significantly increased the body weight of the mice. Increased intracellular TG, leptin, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6 levels, and the expression of Hif1α and lipogenesis-related genes Cebpα, Cebpß, Acc1, Fasn, and Fabp4 were also detected in folate-deficient 3T3-L1 adipocytes. Our results suggested that folate deficiency increased lipid accumulation and leptin production of adipocytes, and thus, inadequate folate status might be one of the risk factors for adiposity.

Medication Adherence of Persons with Type 2 Diabetes in Malaysia: A Scoping Review and Meta-Analysis.

Objective: This is a scoping review of Malaysian scientific studies on medication adherence among persons with type 2 diabetes mellitus (T2DM). Methodology: We conducted a bibliographic search of PubMed, Scopus and Google Scholar using the following keywords: "medication adherence," "drug compliance," "DMTAC" and "Malaysia." The search covered all publications up to 31 December 2021. Eligible articles were original studies conducted in Malaysia that measured or quantified medication adherence among persons with T2DM. Results: We identified 64 eligible studies published between 2008 to 2021. Most studies included patients with T2DM in ambulatory facilities. Five studies were qualitative research. The quantitative research publications included clinical trials, and cross-sectional, validation, retrospective and prospective cohort studies. Thirty-eight studies used medication adherence scales. The Morisky Medication Adherence Scale (MMAS-8, used in 20 studies) and Malaysian Medication Adherence Scale (MALMAS, used in 6 studies) were the most commonly used tools. There were 6 validation studies with 4 medication adherence scales. A meta-analysis of 10 studies using MMAS-8 or MALMAS revealed that the pooled prevalence of low medication adherence is 34.2% (95% CI: 27.4 to 41.2, random effects model). Eighteen publications evaluated various aspects of the Diabetes Medication Therapy Adherence Clinics (DMTAC). Conclusion: This scoping review documented extensive research on medication adherence among persons with diabetes in Malaysia. The quantitative meta-analysis showed a pooled low medication adherence rate.