Converting Short-Acting Insulin into Thermo-Stable Longer-Acting Insulin Using Multi-Layer Detachable Microneedles.

The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40 °C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186 °C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59 %. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration.

Being overweight and obese increases suicide risk, the severity of depression, and the inflammatory response in adolescents with major depressive disorders.

Background: There is a bidirectional relationship between obesity and depression. We investigated whether the coexistence of obesity and depression increases the risk of having severe depression and a high suicide risk in adolescents with major depressive disorder (MDD). Additionally, we explored the potential mechanisms linking the coexistence of obesity and depression to worse outcomes in these patients. Methods: The odds of high suicide risk and severe depression were compared among MDD patients based on different body mass index (BMI) groups. Complete blood count (CBC) parameters, inflammatory ratios (neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], and platelet-lymphocyte ratio [PLR]), and cytokine levels (IFN-γ, IL-1ß, IL-6, IL-8, MCP-1, TNF-α, and TGF-ß1) were evaluated across BMI groups. Additionally, Pearson correlation coefficients (r) were assessed to understand the relationships between the 8Q and 9Q scores, CBC parameters, inflammatory ratios, cytokine levels, and BMI. Results: A total of 135 antidepressant-naive adolescents with MDD were included. Overweight and obese MDD patients had higher odds of having high suicide risk and severe depression than lean individuals. Furthermore, they exhibited significantly higher white blood cell (WBC), and neutrophil counts. The NLR tended to be higher in obese MDD patients than in leans. Overweight and obese MDD patients had elevated levels of interleukin (IL)-1ß and IL-6 compared to lean individuals, while TGF-ß1 levels appeared to decline as body weight increased. BMI showed weak positive correlations with 8Q score, WBC count, neutrophil count, monocyte count, platelet count, neutrophil percentage, and NLR, and a weak negative correlation with lymphocyte percentage. The 8Q score displayed weak positive correlations with BMI, neutrophil percentage, monocyte percentages, NLR, and MLR, and a weak negative correlation with lymphocyte percentage. Conclusion: The findings suggest that coexistence of overweight or obesity with depression heightened inflammatory responses, leading to worse outcomes and increased suicide risk in adolescents MDD patients.

Hybrid and herd immunity 6 months after SARS-CoV-2 exposure among individuals from a community treatment program.

The death rate from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in 2022 was lower than the death rate in 2021, when the infection rate increased. Hybrid immunity provided by a combination of vaccination and infection, including asymptomatic infection, may confer effective protection against death. We explored the combined effect of asymptomatic infection and hybrid immunity by studying T-cell and antibody responses against SARS-CoV-2 among individuals treated in home health care services 6 months after SARS-CoV-2 exposure. Asymptomatic SARS-CoV-2 infection was demonstrated in 24.4% of close contacts. The levels of immunity were not different between patients and close contacts. Anti-RBD IgG against SARS-CoV-2 increased in a dose-dependent manner with the number of vaccine doses. Interestingly, the T-cell response decreased soon after a booster dose of vaccine. Asymptomatic SARS-CoV-2 infection could not enhance immunity against SARS-CoV-2 among vaccinated close contacts. Full vaccination was crucial to provide hybrid immunity. However, when designing vaccine strategies, T-cell exhaustion after multiple vaccinations should be considered.

Implementation of diabetes care and educational program via telemedicine in patients with COVID-19 in home isolation in Thailand: A real-worldexperience.

BACKGROUND: The coronavirus disease (COVID-19) outbreak in Bangkok led to a shortage of hospital capacity, and a home isolation system was set up. We described the process of diabetes self-management education and support (DSMES) and glycemic management via telemedicine, along with outcomes in home-isolated patients with COVID-19 infection. METHODS: A retrospective chart review of glucose values, insulin and corticosteroids use, and outcomes was performed. RESULTS: A volunteer group of 21 endocrinologists and 21 diabetes educators/nurses formed the consultation team. Patients with diabetes or at high-risk of diabetes and receiving corticosteroids were referred by primary volunteer physicians. Glucometers and related supplies, and insulin were donated, and delivered via same-day delivery services. A chat group of an individual patient/their caregiver, diabetes educator, endocrinologist, and primary physician was formed (majority via LINE® platform) to assess the patient's clinical status and need. Real-time virtual DSMES sessions were performed and treatments were adjusted via smartphone application or telephone. There were 119 patients (1,398 service days), mean (SD) age 62.0 (13.6) years, 85.7% had a history of type 2 diabetes, and 84.0% received corticosteroids. Insulin was used in 88 patients; 69 of whom were insulin-naïve. During the first 10 days, there were 2,454 glucose values. The mean glucose level on day 1 was 280.6 (122.3) mg/dL, and declined to 167.7 (43.4) mg/dL on day 10. Hypoglycemia occurred in 1.4% of the values. A majority of patients (79.5%) recovered at home. CONCLUSION: Diabetes care and DSMES delivered via telemedicine to patients on home isolation during COVID-19 pandemic was safe and effective.

Pneumomediastinum as initial presentation of paralytic rabies: a case report.

BACKGROUND: Rabies is readily diagnosed when it presents as the classic furious form. Paralytic and atypical forms can pose significant problems in diagnosis. Catastrophic incidents included 7 organ transplant recipients who died of rabies recently in United States and Germany. Although rabies remains top in the lists of differential diagnosis of encephalitis in rabies endemic area, its complication may divert physicians from making a relevant management. We encountered an unusual case of paralytic rabies who presented with spontaneous pneumomediastinum. CASE PRESENTATION: A young male presented with fever and dysphagia. There was a history of fluctuating consciousness and aerophobia but they were absent or could not be demonstrated at the time of admission. He exhibited subcutaneous chest wall emphysema and was found to have pneumomediastinum which resulted in surgical intervention. He developed paralysis followed by seizures during postoperative period. Diagnosis was confirmed by demonstration of rabies RNA in saliva during the preterminal phase and by the autopsy. Over 200 hospital staff subsequently received rabies postexposure prophylaxis. CONCLUSION: Spontaneous pneumomediastinum can be a rare complication of rabies. It may lead clinicians to perform inappropriate treatment, particularly when phobic spasms are not present and agitation is not prominent. High level of awareness of rabies in any patient with confusion albeit subtle or with any obscure neurological presentations such as difficulty swallowing with no identifiable causes must be borne in mind.