Background
Higher rates of hepatitis C virus (HCV) reinfection after viral clearance have been well described among HIV‐positive men who have sex with men (MSM) in Europe. The epidemiology of HCV ...reinfection, however, has rarely been investigated among HIV‐positive patients in Asia‐Pacific region.
Methods
We retrospectively identified HIV‐positive patients with recent HCV infection who had cleared their primary infection, either spontaneously or via treatment, between January 2011 and May 2018. All included patients were observed until 31 March 2019. HCV reinfection was defined as recurrent HCV viraemia after achieving viral clearance with anti‐HCV treatment or after spontaneous clearance.
Results
During the study period, 219 HIV‐positive patients (90.4% MSM) were diagnosed with recent HCV infection. Viral clearance with successful treatment was achieved in 108 patients (49.3%) and spontaneous clearance occurred in 20 (9.1%); of them, 18 (14.1%) acquired HCV reinfections, resulting in an incidence rate of 8.2 per 100 person‐years of follow‐up (95% CI 5.2‐13.1). With the adjusted Cox proportional hazards model, we found a higher reinfection risk in patients with syphilis (adjusted hazard ratio 10.3, 95% CI 1.4‐77.8, P = .023) compared to those without syphilis. HCV RNA testing, if performed only following syphilis and elevated aminotransferases, might miss 44.4% and 33.3% of HCV reinfections, respectively.
Conclusions
Similar to the findings in Europe, we observed a high incidence of HCV reinfection among HIV‐positive Taiwanese with recent HCV infection, which was significantly associated with syphilis. To identify HCV reinfections, annual HCV RNA testing should be instituted instead of testing driven by symptoms, syphilis or elevated aminotransferases.
The menopausal transition is often accompanied with distressing manifestations, such as vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) ...have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of n-3 PUFAs supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic literature search of randomized controlled trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 identified studies, nine studies met the inclusion criteria and were incorporated into this systematic review. Notably, four studies detected potential benefits of n-3 PUFAs in improving hot flashes and night sweats. On the contrary, sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales, such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, we found inconclusive evidence of n-3 PUFA’s impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of n-3 PUFAs in improving vasomotor symptoms, sleep quality, and depression. Further well-designed randomized clinical trials with larger participant groups are crucial to validate and generalize these results. Review Registration: PROSPERO registration no: CRD42023421922.
Semaphorins (SEMAs) are axon guidance factors that participate in axonal connections and nerve system development. However, the functional roles of SEMAs in tumorigenesis are still largely uncovered. ...By using in silico data analysis, we found that SEMA6C was downregulated in pancreatic cancer, and its reduction was correlated with worse survival rates. RNA sequencing revealed that cell cycle-related genes, especially cyclin D1, were significantly altered after blockage of SEMA6C by neutralizing antibodies or ectopic expressions of SEMA6C. Mechanistic investigation demonstrated that SEMA6C acts as a tumor suppressor in pancreatic cancer by inhibiting the AKT/GSK3 signaling axis, resulting in a decrease in cyclin D1 expression and cellular proliferation. The enhancement of cyclin D1 expression and cyclin-dependent kinase activation in SEMA6C-low cancer created a druggable target of CDK4/6 inhibitors. We also elucidated the mechanism underlying SEMA6C downregulation in pancreatic cancer and demonstrated a novel regulatory role of miR-124-3p in suppressing SEMA6C. This study provides new insights of SEMA6C-mediated anti-cancer action and suggests the treatment of SEMA6C-downregulated cancer by CDK4/6 inhibitors.
Indium-gallium-zinc oxide (IGZO) photodetectors have been mostly studied in the ultraviolet region and rarely in the X-ray region. This study fabricates IGZO X-ray detectors on glass substrates using ...different post-deposition annealing (PDA) times. The photo-to-dark current ratio increases significantly from 2.6 to 392.3 after PDA because of a considerable reduction of the deep-level states. There are fewer residual electrons in the conduction band and recombination centers in the middle of the bandgap are eliminated. An IGZO X-ray detector with optimal PDA time has a sensitivity of <inline-formula> <tex-math notation="LaTeX">8.5\times 10^{-{3}}\,\,\mu \text{C} </tex-math></inline-formula>/(mGy<inline-formula> <tex-math notation="LaTeX">\cdot </tex-math></inline-formula>cm<inline-formula> <tex-math notation="LaTeX">^{{2}}{)} </tex-math></inline-formula> and a rise/decay time of 5.1/12.2 s with a bias of 10 V at a dose rate of 100 mGy/s. This result shows that IGZO is eminently suited to applications for X-ray detection.
Hepatitis A virus (HAV) and hepatitis E virus (HEV) share the similar fecal‐oral transmission route. During an outbreak of sexually transmitted acute hepatitis A among men who have sex with men (MSM) ...worldwide between 2015 and 2017, we investigated the possibility of sexual transmission and related morbidity of HEV infection among human immunodeficiency virus (HIV)‐positive patients. From March 1, 2015 to August 31, 2017, anti‐HEV immunoglobulin G was retrospectively determined among 3,293 HIV‐positive patients, who were mainly MSM (87.6%) with a median CD4 count of 575 cells/μL. Prevalence and incidence of HEV infection were 3.7% (123 of 3,293) and 4.35 per 1,000 person‐years of follow‐up (PYFU), respectively, which were significantly lower compared with those of HAV infection (31.1% 996 of 3,204 and 12.61 per 1,000 PYFU, respectively). The number of patients with HEV infection did not increase with the hepatitis A epidemic. The factor associated with prevalent HEV infection was older age (per 1‐year increase, adjusted odds ratio, 1.07; 95% confidence interval, 1.05‐1.09), but neither sexual orientation nor acquisition of sexually transmitted infections was related to prevalent or incident HEV infection. Among 23 patients with incident HEV infection, 22 patients had viremia caused by HEV genotype 4. No patients had prolonged HEV viremia or clinical symptoms, and only a mild elevation of serum aminotransferase, ranging from 34 to 77 IU/L, was noted. Although 4 patients had hepatitis for a prolonged duration of between 8 and 17 months, no abdominal imaging revealed liver fibrosis or cirrhosis. Conclusion: HEV endemicity remained low among HIV‐positive patients in Taiwan during the outbreak of acute hepatitis A. Our data suggest that sexual transmission of HEV with significant morbidity of HEV infection, if any, is rare in this population.
•The need for enhanced and better-tolerated approaches for effective migraine prevention remains strong.•Neuroinflammatory pathways with nutraceutical intervention may be promising targets for ...migraine.•High-dose EPA could be a promising prophylactic option for managing episodic migraine.•Patients receiving high-dose EPA showed significant improvements in psychological symptoms associated with episodic migraine.•The EPA treatment demonstrated a lack of major adverse events, underscoring its safety for use in patients with episodic migrain.
Omega-3 polyunsaturated fatty acids (PUFAs) may benefit migraine improvement, though prior studies are inconclusive. This study evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy individuals with EM participated in a 12-week randomized, double-blind, placebo-controlled trial from March 2020 and May 2022. They were randomly assigned to either the EPA (N = 35, 2 g fish oil with 1.8 g of EPA as a stand-alone treatment daily), or the placebo group (N = 35, 2 g soybean oil daily). Migraine frequency and headache severity were assessed using the monthly migraine days, visual analog scale (VAS), Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Pittsburgh Sleep Quality Index (PSQI) in comparison to baseline measurements. The EPA group significantly outperformed the placebo in reducing monthly migraine days (−4.4 ± 5.1 days vs. − 0.6 ± 3.5 days, p = 0.001), days using acute headache medication (−1.3 ± 3.0 days vs. 0.1 ± 2.3 days, p = 0.035), improving scores for headache severity (ΔVAS score: −1.3 ± 2.4 vs. 0.0 ± 2.2, p = 0.030), disability (ΔMIDAS score: −13.1 ± 16.2 vs. 2.6 ± 20.2, p = 0.001), anxiety and depression (ΔHADS score: −3.9 ± 9.4 vs. 1.1 ± 9.1, p = 0.025), and quality of life (ΔMSQ score: −11.4 ± 19.0 vs. 3.1 ± 24.6, p = 0.007). Notably, female particularly benefited from EPA, underscoring its potential in migraine management. In conclusion, high-dose EPA has significantly reduced migraine frequency and severity, improved psychological symptoms and quality of life in EM patients, and shown no major adverse events, suggesting its potential as a prophylactic for EM.
Understanding the risk behaviors associated with sexually-transmitted hepatitis C virus (HCV) infection among men who have sex with men (MSM) may inform the public health policies and interventions ...aiming to achieve HCV microelimination.
HIV-positive MSM who had one of the following conditions were enrolled to undergo face-to-face questionnaire interviews to collect information on their sexual practices in the past 12 months: (1) elevation of aminotransferases in the past 6 months; (2) acquisition of sexually transmitted infections in the past 6 months; and (3) previous HCV infections. Plasma HCV RNA were tested at enrolment and every 3 months during follow-up. Baseline characteristics and risky behaviors were compared to identify factors associated with HCV viremia between HCV-viremic MSM and HCV-aviremic MSM in multivariate analysis.
Among 781 MSM with a median age of 36 years, 57 (7.3%) had HCV viremia and 724 (92.7%) no HCV viremia during follow-up. A high proportion (38.9%) of the participants reported having used recreational drugs in the past 12 months, with 34.4% of them having slamming, but only 4.8% reported having shared their injection equipment. In multivariate analysis, use of recreational drugs (adjusted odds ratio aOR, 2.14; 95% CI, 1.16–3.96), having participated in group sex (aOR, 2.35; 95% CI 1.24–4.40) and having had condomless receptive anal intercourse (aOR, 1.97; 95% CI 1.07–3.62) were significantly associated with HCV viremia.
Among high-risk HIV-positive MSM, use of recreational drugs and risky sexual contacts were associated with HCV viremia, suggesting the mucosal contacts as the major route of HCV transmission.
Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting ...arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12 ). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 μM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.
To evaluate the perioperative outcome of laparoendoscopic two-site myomectomy (LETS-M).
The medical records of 204 women receiving LETS-M in a tertiary referral center, including 183 surgeries ...performed by the experienced surgeon and 21 surgeries performed by 3 well-supervised trainees were retrospectively reviewed.
The age of the participants was 39.3 ± 6.4 years. The mean diameter of the largest myoma and the mean number of myomas were 8.5 ± 2.2 cm and 1.7 ± 1.1, respectively. Thirty-one (15%) operations removed more than 2 myomas larger than 5 cm in diameter. The mean weight of the myomas was 281.1 ± 183.1 g. The operation time was 97.6 ± 40.2 min, and the intraoperative blood loss was 99.3 ± 115.2 mL. There were 3 (1%) cases of excessive blood loss (more than 500 mL) and 2 (1%) of postoperative hematoma. The only significant difference between the experienced surgeon and trainees was the operation time (92.3 ± 32.2 min vs. 141.2 ± 54 min, p < .001), while the myoma number, myoma diameter, myoma weight, and intraoperative blood loss were not significantly different. The operation time did not differ among different myoma locations. In multivariate analysis, virginity, myoma number, more than 2 large myomas, and myoma size were independent variables for longer operation times. No patient experienced any major complications.
LETS-M using conventional laparoscopic equipment is a minimally invasive surgical method that is safe, effective, and easy to learn for managing uterine myoma. It is useful to achieve a favorable perioperative outcome with acceptable operation time.
The nephrotoxicity of sofosbuvir (SOF) on human immunodeficiency virus and hepatitis C virus (HIV/HCV)‐coinfected patients receiving antiretroviral therapy (ART) remains controversial. We ...prospectively compared the estimated glomerular filtration rate (eGFR) changes in 167 patients receiving SOF‐based direct‐acting antivirals (DAAs) who also received tenofovir disoproxil fumarate (TFV)‐based (n = 116) and TFV‐free ART (n = 51). The eGFR was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation, and the eGFR changes between ART regimens were compared by the generalized estimated equation. During DAA treatment, participants on TFV‐based ART had a higher eGFR decline than those on TFV‐free ART (slope coefficient difference: −0.82 ml/min/1.73 m2/month 95% CI: −1.21 to −0.43; p < 0.001), whereas the eGFR changes did not differ between groups (slope coefficient difference: 0.13 ml/min/1.73 m2/month 95% CI: −0.32 to 0.58; p = 0.42) after discontinuing DAAs. Participants on TFV TDF‐based ART had a higher eGFR decline than those on TFV alafenamide fumarate (TAF)‐based ART (slope coefficient difference: −0.31 ml/min/1.73 m2/month 95% CI: −0.50 to −0.12; p = 0.01). After discontinuing DAAs, the eGFR changes did not differ between groups (slope coefficient difference: 0.06 ml/min/1.73 m2/month 95% CI: −0.98 to 1.10; p = 0.91). In conclusion, HIV/HCV‐coinfected patients on TFV‐based ART had a slight eGFR decline compared to those on TFV‐free ART during SOF‐based DAA therapy. A similar trend between TDF‐based and TAF‐based ART was also observed. Because the differences of eGFR changes are limited, the physicians should not discourage the use of SOF‐based DAAs in HIV‐positive patients on TFV‐based ART.
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