Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objectives: The purpose of this study was to develop a valid and reliable instrument for assessing patients’ behavior toward the risk of hypoglycemia through self-assessment. Insufficient education and supervision of type 2 diabetes mellitus (DM) outpatients by healthcare providers is a significant concern, affecting their behavior during the treatment process. Additionally, inappropriate behavior typically increases the risk of hypoglycemia. To mitigate this risk, several studies have recommended evaluating patients’ behavior, necessitating the development of a new instrument. Methods: The study procedures were conducted in 3 stages: instrument development (face and content validity, stage I), construct validity and reliability test (stage II), and criterion validity (stage III). Stage I involved 5 healthcare practitioners, including internal medicine doctors, nurses, dietitians, and pharmacists in hospitals and community health centers. Stage II included 20 respondents using a 1-shot test method. Stage III involved 237 type 2 DM outpatients at Central General Hospital (RSUP) in Jakarta, employing a cross-sectional design and consecutive sampling. Results: The results indicated that the developed instrument was valid and reliable, comprising 9 domains (29 questions). These domains included behavior toward blood glucose monitoring, diet, physical activity, medication, assistance from healthcare providers, hypoglycemia management, self-care, family support, and insulin use. Furthermore, poor behavior was found to increase the risk of hypoglycemia by 2.36 times. Conclusions Based on these results, the developed instrument could be effectively used to evaluate behavior toward hypoglycemia among type 2 DM outpatients, confirming its validity and reliability.

Objective: Osteoarthritis (OA), particularly knee OA, affects 24% of adults and is a significant cause of disability. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used but have many adverse effects. Antioxidant and anti-iflammatory properties of Curcuma longa might decrease pain thus improving joint function. Methods: This systematic review and meta-analysis evaluated randomized controlled trials (RCTs) on Curcuma longa efficacy for knee OA. We reported mean differences (MD) with 95% confidence interval (CI) for continuous outcomes and evaluated Visual Analog Scale (VAS) for pain and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score over 4 to 6 weeks for treatment effects. Results: Ten RCTs with 786 patients were included. Curcuma longa significantly improved VAS for pain than placebo (MD:18.25, 95% CI: 7.79 to 28.72, p=0.0006). It was not inferior to NSAIDs in WOMAC total score improvement (MD: –11.99, 95% CI: –39.21 to 15.23, p=0.39). Both dosages (<1,000 and ≥1,000 mg/day) of Curcuma longa demonstrated similar improvement in VAS for pain compared to placebo (MD: 27.02, 95% CI: 1.45 to 52.60, p=0.04; MD: 21.48, 95% CI: 1.78 to 41.18, p=0.03). Conclusion Curcuma longa benefits knee OA pain and function, being more effective than placebo and comparable to NSAIDs.Despite positive results, limitation and heterogeneity of the studies necessitates further research to explore optimal dosages and administration methods of Curcuma longa as therapeutic option for knee OA.

Quetiapine-induced hypokalemic periodic paralysis (QIHPP) is a rare condition. Herein, we present the case of a 31-year-old pregnant Malay woman diagnosed with bipolar II disorder and QIHPP. She presented to the casualty department with a 2-day history of bilateral lower limb weakness and numbness. Her renal function tests showed moderate hypokalemia (2.5 mmol/L), whereas other investigations were normal. Quetiapine was suspected to be the cause, prompting a psychiatric referral to manage her acute condition. Balancing the risks of untreated QIHPP against the potential relapse of bipolar symptoms from quetiapine discontinuation or dosage reduction poses a significant treatment challenge for pregnant women with QIHPP. Finally, we reduced the quetiapine dosage after careful consideration, leading to the normalization of potassium levels and symptom resolution. Therefore, clinicians should be aware of this side effect when initiating or continuing quetiapine treatment in women of childbearing age or pregnant women with psychiatric disorders. It is crucial to monitor serum electrolytes, especially potassium, following quetiapine administration and warn patients about its potential side effects.

Quetiapine-induced hypokalemic periodic paralysis (QIHPP) is a rare condition. Herein, we present the case of a 31-year-old pregnant Malay woman diagnosed with bipolar II disorder and QIHPP. She presented to the casualty department with a 2-day history of bilateral lower limb weakness and numbness. Her renal function tests showed moderate hypokalemia (2.5 mmol/L), whereas other investigations were normal. Quetiapine was suspected to be the cause, prompting a psychiatric referral to manage her acute condition. Balancing the risks of untreated QIHPP against the potential relapse of bipolar symptoms from quetiapine discontinuation or dosage reduction poses a significant treatment challenge for pregnant women with QIHPP. Finally, we reduced the quetiapine dosage after careful consideration, leading to the normalization of potassium levels and symptom resolution. Therefore, clinicians should be aware of this side effect when initiating or continuing quetiapine treatment in women of childbearing age or pregnant women with psychiatric disorders. It is crucial to monitor serum electrolytes, especially potassium, following quetiapine administration and warn patients about its potential side effects.

This report describes an approach to recover SARS-CoV-2 RNA from rapid antigen test kit (RTK-antigen) cassettes for whole-genome sequencing (WGS). RNA samples were recovered from 33 RTK-antigen cassettes for WGS, with 18 samples achieving more than 80% genome coverage. This work provides a proof-of-concept that positive RTK-antigen cassettes can be safely transported, stored and subjected to WGS, enabling swift identification of circulating variants.

Purpose: To describe the clinical presentation, ocular complications, treatment, and visual outcomes in a series of 17 patients from New Zealand with neuroretinitis secondary to Bartonella henselae. Methods: Retrospective cross-sectional single-center study from 2001 to 2024. Data was extracted from a clinical database of all patients treated for B. henselae over the past 23 years. Statistical analysis was performed using IBM SPSS Statistics ver. 26.0. Results: Seventeen patients (19 eyes) were included with 11 (65%) being female. The mean age at presentation was 28.3 ± 12.3 years (range, 13–60 years). The mean presenting visual acuity (Early Treatment Diabetic Retinopathy Study testing) was 50 ± 23 (range, 4–90). The mean final visual acuity was 78 ± 12 (range, 45–90). Eleven patients (65%) had cats or kittens at home, with only one (6%) recounting a history of being scratched. Eight patients (47%) demonstrated the characteristic macular star at presentation, with all eventually developing macular star within a mean of 6 days. Four patients (24%) had macular oedema, three (18%) had vasculitis, two (12%) had uveitis, two (12%) had disc granuloma, and one (6%) had multifocal chorioretinitis. Six patients (35%) were treated with rifampicin and doxycycline, one (6%) with rifampicin and azithromycin, two (12%) with doxycycline only, two (12%) with co-trimoxazole monotherapy, and one patient (6%), who was breast-feeding, was treated with erythromycin. Four patients (24%) did not have receive any treatment. Conclusions The characteristic macular star is not always manifest at initial presentation for patients with neuroretinitis secondary to B. henselae, nor is there always a preceding history of cat exposure. Not all patients require treatment to have a good visual outcome, and the immune status of the patient is important.