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Objectives To create a mouse model pertaining to mesh-elicited suburethral functional and histological changes after vaginal distention, and to examine the possible mechanism behind these complications. Methods We divided 48 virgin female C57BL/6 mice into four groups: vaginal distention alone, vaginal distention followed by prolene mesh implantation, vaginal distention followed by sham mesh implantation and untreated control. Each group was divided into two subgroups for conscious cystometrogram, leak-point pressure testing and harvesting of suburethral tissue 4 or 10 days after vaginal distention. The suburethral tissues underwent immunohistochemistry and western blot analysis of nerve growth factor, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2. Urodynamic results were compared among groups using one way ANOVA, with Tukey's multiple comparisons post-test for pair wise comparisons. Results Leak-point pressure in the vaginal distention and vaginal distention + sham mesh groups were significantly lower than in the control and vaginal distention + mesh groups at day 4. Leak-point pressure in the vaginal distention + mesh group were significantly higher than in the other three groups at both day 4 and 10. Immunohistochemistry and western blotting showed increased matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 levels in the vaginal distention + mesh group at day 4 and 10. Furthermore, nerve growth factor expression was increased in the same area and same group at 10 days. Conclusions Increased suburethral tissue matrix metalloproteinase and nerve growth factor expression might be related to tissue remodeling after prolene mesh implantation for stress urinary incontinence. [ABSTRACT FROM AUTHOR]

Sarcopenia is defined as the loss of skeletal muscle mass and muscle function. It is common in patients with malignancies and often associated with adverse clinical outcomes. The presence of sarcopenia in patients with cancer is determined by body composition, and recently, radiologic technology for the accurate estimation of body composition is under development. Artificial intelligence- (AI-) assisted image measurement facilitates the detection of sarcopenia in clinical practice. Sarcopenia is a prognostic factor for patients with cancer, and confirming its presence helps to recognize those patients at the greatest risk, which provides a guide for designing individualized cancer treatments. In this review, we examine the recent literature (2017-2021) on AI-assisted image assessment of body composition and sarcopenia, seeking to synthesize current information on the mechanism and the importance of sarcopenia, its diagnostic image markers, and the interventions for sarcopenia in the medical care of patients with cancer. We concluded that AI-assisted image analysis is a reliable automatic technique for segmentation of abdominal adipose tissue. It has the potential to improve diagnosis of sarcopenia and facilitates identification of oncology patients at the greatest risk, supporting individualized prevention planning and treatment evaluation. The capability of AI approaches in analyzing series of big data and extracting features beyond manual skills would no doubt progressively provide impactful information and greatly refine the standard for assessing sarcopenia risk in patients with cancer. [ABSTRACT FROM AUTHOR]

Abstract: Dehydroepiandrosterone sulphate is one of the most important neurosteroids. In the present paper, we studied the effect of dehydroepiandrosterone sulphate on persistent sodium currents and its mechanism and functional consequence with whole-cell patch clamp recording method combined with a pharmacological approach in the rat medial prefrontal cortex slices. The results showed that dehydroepiandrosterone sulphate inhibited the amplitude of persistent sodium currents and the inhibitory effect was significant at 0.1 μM, reached maximum at 1 μM and decreased with the increase in the concentrations of above 1 μM. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was canceled by the Gi protein inhibitor and the protein kinase C inhibitor, but not by the protein kinase A inhibitor. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was also canceled by the sigma-1 receptor blockers and the sigma-1 receptor agonist could mimic the effect of dehydroepiandrosterone sulphate. Dehydroepiandrosterone sulphate had no significant influence on neuronal excitability but could significantly inhibit chemical inhibition of mitochondria-evoked increase in persistent sodium currents. These results suggest that dehydroepiandrosterone sulphate inhibits persistent sodium currents via the activation of sigma-1 receptors–Gi protein–protein kinase C-coupled signaling pathway, and the main functional consequence of this effect of DHEAS is presumably to protect neurons under ischemia. [Copyright &y& Elsevier]

• A significant weight gain occurs after switching from non-integrase inhibitor-based antiretroviral therapy to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF). • Weight gain is correlated with later clinic visit, baseline weight, diabetes mellitus, and age. • The switch to E/C/F/TAF is associated with dyslipidemia and an increase in HbA1c level. To evaluate the evolution of weight and lipid profiles before and after switch to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) among virally suppressed HIV-positive patients. Patients switching to E/C/F/TAF between March and July 2018 were included. Weight, lipid profile (triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), and glycated hemoglobin (HbA1c) levels at 48 weeks before and after the switch were analyzed using generalized estimating equations in order to identify the associated factors. A total of 693 patients were included, and a weight gain was noted after the switch at weeks 12 (mean +0.63 kg), 24 (+1.25), 36 (+1.58), and 48 (+1.75) (all p < 0.0001). The weight change after the switch was significantly greater than that observed within the preceding 48-week period before the switch (+1.75 kg vs +0.54, p < 0.0001) and was correlated with switch to E/C/F/TAF (coefficient 0.29), later clinic visit (0.15), baseline weight (0.99), diabetes mellitus (coefficient −0.96), and age (−0.02) (all p < 0.01). At week 48, significant increases were observed for TG (mean +62.93 mg/dl), TC (+22.30), LDL-C (+9.70), HDL-C (+3.65) (all p < 0.01), and HbA1c (+0.08%) (p < 0.05), but not TC/HDL-C ratio (+0.12, p = 0.38). Virally suppressed HIV-positive patients gained a moderate amount of weight and had significant increases in lipid levels after switching to E/C/F/TAF. [ABSTRACT FROM AUTHOR]

• More than 50% of people living with human immunodeficiency virus (PLWH) in Taiwan had at least one non-communicable disease. • The prevalence of polypharmacy was 18.7%, and this increased with age. • The prevalence of potential drug–drug interactions was 16.5%, which was lower than noted previously. • Older PLW; those with polypharmacy; and those who are taking booster-containing antiretroviral therapy, medications in the alimentary tract and metabolism category, or anti-neoplastic and immunomodulating agents were at higher risk of drug–drug interactions. To investigate the prevalence of polypharmacy and potential drug–drug interactions (DDIs), and the factors associated with DDIs among people living with human immunodeficiency virus (HIV; PLWH) in the modern era of antiretroviral therapy (ART). This cross-sectional study included PLWH who had been on ART for ≥3 months at two designated HIV hospitals in Taiwan. All ART and non-ART prescriptions were collected from the NHI-MediCloud System and screened for DDIs using the University of Liverpool HIV drug interactions database. A case–control analysis was conducted to investigate the factors associated with DDIs. In total, 1007 PLWH were included in this study from June 2021 to August 2022. The median age was 40 (interquartile range 33–49) years, and 96.2% were taking integrase strand transfer inhibitor (INSTI)-based ART. The proportions of PLWH with at least one non-communicable disease and polypharmacy were 50.0% and 18.7%, respectively. Seven (0.7%) PLWH had red-flagged DDIs, and 159 (15.8%) had amber-flagged DDIs. In multi-variable models, the prevalence of DDIs was associated with older age [adjusted odds ratio (aOR) per 1-year increase 1.022), number of co-medications (aOR 1.097), use of boosted INSTI-based ART (vs unboosted INSTI, aOR 8.653), and concomitant medications in the alimentary tract and metabolism category (aOR 11.058) and anti-neoplastic and immunomodulating agents (aOR 14.733). In the INSTI era, the prevalence of potential DDIs is lower than noted previously, but remains substantial. Clinicians should monitor DDIs routinely, especially in older PLWH, those taking a higher number of co-medications, and those who are taking booster-containing ART or medications from specific categories. [ABSTRACT FROM AUTHOR]

Background: Depression is prevalent among people living with HIV/AIDS (PLWHA), but there are few longitudinal studies investigating the prevalence of depression among HIV respondents in Taiwan. Objectives: This study examined the trend in the prevalence of depression and its main predictors among PLWHA in Taiwan. Methods: This study analyzed the 2-million random-sample data set of the Taiwanese longitudinal health research database using data from 2000 to 2011and applied the Internal Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes for the detection of HIV infection and depression. Chi-square tests and logistic regression analyses were conducted to determine predictive factors for depression. Results: A total of 769 PLWHA who met the criterion of HIV infection were extracted from the database. Of these respondents, 20.03% had a diagnosis of depression after their HIV-positive diagnosis. The annual prevalence of depression among the study respondents increased significantly from 1.95% in 2000 to 6.93% in 2011 according to time trend analysis (χ2 = 6.428, df =11, p =.03). Multivariate, logistic regression analysis indicated a history of drug abuse was the main predictor of a diagnosis of depression. Discussion: The increasing trend in the prevalence of depression revealed an urgent need for the development of care programs for PLWHA with depression. Such programs should take into consideration a history of drug abuse as a strong risk factor for the development of depression. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: We hypothesized that transobturator tape (TOT) is safe and efficacious for the treatment of urodynamic stress incontinence in the long term. Methods: We conducted a prospective study of patients with confirmed urodynamic stress incontinence (USI) who underwent a Monarc TOT procedure in a tertiary center between February 2006 and March 2009 without other concurrent surgical procedures. Urodynamics were conducted at 1 and 3 years postoperatively. Subjective evaluation included Incontinence Impact Questionnaire (IIQ-7), Urinary Distress Inventory Questionnaire (UDI-6), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Objective cure was defined as no urinary leakage demonstrable on provocative filling cystometry and/ or 1-h pad test of <2 g. Subjective cure was based on a negative response to question 3 in UDI-6. Paired-samples t test, chi-square, and Fisher exact tests were applied; p < 0.05 was considered significant. The log-rank tests were used to compare event-free survival. Results: Sixty patients were enrolled, and 56 were evaluated at 5 years postoperatively. The majority were middle aged, postmenopausal, and overweight. Mean operating time was 31.1 ± 8.9 min, intraoperative complications were minor, and median period of follow-up was 80.3 ± 9.6 months. At 5 years of follow-up, objective and subjective cure rates were 89.3 % and 87.5 %, respectively. No mesh-related complications were seen. One patient needed a repeat midurethral sling procedure, and one patient each had bladder and bowel cancer. Conclusion: Monarc TOT was safe and retained its high cure rate in the short- and long-term treatment of stress urinary incontinence. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: To study the outcomes following repeat midurethral sling (MUS) surgery in patients with persistent or recurrent stress urinary incontinence after failure of primary MUS surgery and risk factors for surgical failure. Methods: The medical records of 24 patients who underwent repeat MUS surgery at a single tertiary center from January 2004 to February 2014 were reviewed. The types of MUS used for the repeat surgey were transobturator, retropubic and single incision slings. Objective cure was defined as no demonstrable involuntary leakage of urine during increased abdominal pressure in the absence of a detrusor contraction observed during filling cystometry, and subjective cure was defined as a negative response to Urogenital Distress Inventory six (UDI-6) question 3 during follow-up between 6 months and 1 year postoperatively. The change in the inclination angle between the urethra and pubic axis was measured with introital ultrasonography and the cotton swab test performed. Results: The objective and subjective cure rates were 79.2 % and 75 %, respectively. There were no differences in demographics between the patients with failure of surgery and those with successful surgery. Significant independent risk factors for failure of repeat MUS surgery were a change in cotton swab angle at rest and straining of <30° (OR 4.6, 95 % CI 2.5 - 7.9°), a change in inclination angle of <30° (OR 4.6, 95 % CI 2.5 - 7.9°), intrinsic sphincter deficiency (OR 3.4, 95 % CI 1.8 - 6.1) and a mean urethral closure pressure of <60 cm HO (OR 2.9, 95 % CI 1.5 - 4.5). In one patient the bladder was perforated. Conclusions: Repeat MUS surgery is safe and has a good short-term success rate, both objectively and subjectively, with independent risk factors for failure related to bladder neck hypomobility and poor urethral function. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The objective of this study was to identify the predictors for persistent urodynamic stress incontinence (P-USI) in women following extensive pelvic reconstructive surgery (PRS) with and without midurethral sling (MUS). Mmethods: A total of 1,017 women who underwent pelvic organ prolapse (POP) surgery from January 2005 to December 2013 in our institutions were analyzed. We included 349 USI women who had extensive PRS for POP stage III or more of whom 209 underwent concomitant MUS. Results: Of the women who underwent extensive PRS without MUS, 64.3 % (90/140) developed P-USI compared to only 10.5 % (22/209) of those who had concomitant MUS. Those with concomitant MUS and PRS alone were at higher risk of developing P-USI if they had overt USI [odds ratio (OR) 2.2, 95 % confidence interval (CI) 1.3-4.0, p = 0.014 and OR 4.7, 95 % CI 2.0-11.3, p < 0.001, respectively], maximum urethral closure pressure (MUCP) of < 60 cm HO (OR 5.0, 95 % CI 3.0-8.1, p < 0.001 and OR 5.3, 95 % CI 2.7-10.4, p < 0.001, respectively), and functional urethral length (FUL) of < 2 cm (OR 5.4, 95 % CI 2.7-8.8, p < 0.001 and OR 3.9, 95 % CI 2.4-6.9, p < 0.001, respectively). Parity ≥ 6 (OR 3.9, 95 % CI 1.7-5.2, p < 0.001) and Prolift T (OR 3.1, 95 % CI 1.9-4, p < 0.001) posed a higher risk of P-USI in those with concomitant surgery. Perigee and Avaulta A seemed to be protective against P-USI in those without MUS. Conclusions: Overt USI with advanced POP together with low MUCP and FUL values have a higher risk of developing P-USI. Therefore, counseling these women is worthwhile while considering the type of mesh used. [ABSTRACT FROM AUTHOR]

Introduction: To clinically and sonographically evaluate the influence of anterior vaginal mesh (AVM) surgery with concomitant mid-urethral sling surgery (MUS) for stress urinary incontinence (SUI). Materials and Methods: Women with severe symptomatic pelvic organ prolapse (POP) stage III or IV with concomitant SUI were divided into two groups: Group I had transobturator tape (TOT) and AVM surgery and Group II underwent TOT without AVM surgery. Clinical outcome was assessed pre-operatively and 1 year post-operatively, while ultrasound evaluations were performed after one year. Objective cure was defined as no urinary leakage demonstrable on provocative filling cystometry. Subjective SUI cure was a negative response to Urogenital Distress Inventory Six (UDI-6) (question 3). Results: A total of 97 women were recruited, 57 in Group I and 40 in Group II. Three women had symptomatic prolapse in Group I and 5 in Group II. There were no differences in the ultrasound and clinical outcomes between women who had mid-urethral slings with and without AVM. Successful SUI outcome was reported in 85 women. Urethral kinking was demonstrable in 50% of successful cases, but none with failed outcomes. Subanalysis among those with successful SUI outcome (n = 85) and failure (n = 12) revealed the tape, bladder neck and mesh mobility was significantly higher (P < 0.001) among those with SUI success. Conclusions: Among women who had MUS, there were no differences in the ultrasound and clinical outcome between those who had AVM or otherwise. [ABSTRACT FROM AUTHOR]

• Incidence of low-level viraemia (LLV) was similar between bictegravir- and dolutegravir-based ART. • Among PLWH receiving second-generation INSTIs, LLV was not associated with subsequent virologic failure (VF). • In patients who developed VF, there were no emergent resistance-associated mutations. Real-world experience with low-level viraemia (LLV) and its impact remain less reported among people living with HIV (PLWH) who receive antiretroviral therapy (ART) containing second-generation integrase strand transferase inhibitors, including dolutegravir and bictegravir. This retrospective cohort study included virally suppressed PLWH who achieved plasma HIV-RNA viral load (PVL) <50 copies/mL for ≥6 months and were switched to either dolutegravir- or bictegravir-based ART. Incidence rates of developing LLV events (PVL, 50–200 copies/mL) and virologic failure (VF) (PVL ≥1000 copies/mL) were compared between the dolutegravir and bictegravir cohorts. A total of 623 and 862 PLWH switched to dolutegravir-based and bictegravir-based ART, respectively, were included. The incidence rate of developing LLV was 6.2 per 100 person-years of follow-up (PYFU) in the bictegravir cohort and 3.8 per 100 PYFU in the dolutegravir cohort [incidence rate ratio (IRR) = 1.63, 95% confidence interval (CI), 0.90–2.95; P = 0.08], while rates of VF were 0.69 per 100 PYFU and 0.95 per 100 PYFU, respectively, in the bictegravir and dolutegravir cohorts (IRR = 0.72, 95% CI 0.12–3.39; P = 0.34). Presence of LLV events was not associated with subsequent VF in multivariate analysis. Secondary analysis also demonstrated that resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (NRTIs) before switch were not associated with adverse virologic outcomes in either cohort. In conclusion, among virally suppressed PLWH, the incidences of developing LLV or VF were similar after switch to dolutegravir- or bictegravir-based ART. Pre-existing RAMs to NRTIs or LLV events were not associated with subsequent VF. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The aim of this study was to look for possible predictors preoperatively for the development of de novo stress urinary incontinence (SUI) in urodynamically continent women who underwent pelvic reconstructive surgery (PRS). Materials and methods: Medical records of 637 continent women who underwent PRS for severe prolapse from January 2005 to December 2013 in our institutions were included in this study. We excluded women who had urodynamic stress incontinence (UDI) either occult or overt, detrusor overactivity, neurogenic bladder-voiding dysfunction, and previous anti-incontinent surgery. Primary outcome measure was the development of de novo SUI at 6 months to 1 year post operation. Results: Of women in this study, 11 % developed postoperative de novo SUI at 6 months to 1 year of follow-up. Women older than 66 years were 2.86 times [95 % confidence interval (CI) 1.01-2.53, p = 0.14], diabetes mellitus (DM) 2.18 times (95 % CI 1.63-4.21, p = 0.002), certain type of transvaginal mesh procedure 3.5 times (95 % CI, p < 0.001), maximum urethral closure pressure (MUCP) < 60 mmH0 4.65 times (95 % CI, 2.87-8.64, p < 0.001), and functional urethral length (FUL) < 2 cm 3.48 times (95 % CI, 2.13-5.83, p < 0.001) at greater risk of developing de novo SUI. Conclusions: Continent women with advanced pelvic organ prolapse (POP) > 66 years, with DM or low MUCP and FUL values during preoperative urodynamic evaluation have higher risk of developing de novo SUI; therefore, we suggest counselling such women for concomitant PRS and anti-incontinent surgery. [ABSTRACT FROM AUTHOR]

A short and efficient synthesis of (+)-subersic acid in 6 steps with an overall yield of 8.6% from (−)-Sclareol was presented using Mitsunobu reaction and Claisen rearrangement as critical steps. This elegant protocol gave a convenient access to gram scales of (+)-subersic acid, which could be a precursor for its structural analogues and for further bioactivity researches. [ABSTRACT FROM AUTHOR]

Aim To evaluate and compare the long-term outcome of sacrospinous ligament fixation ( SSF) in combination with various other compartment defect native tissue repairs with hysterectomy or hysteropexy. Methods Medical records of 159 patients who underwent surgery for pelvic organ prolapse ( POP) between April 2004 and August 2008 were reviewed retrospectively. Patients were assessed at baseline and at 5-year postoperative follow-up. SSF, anterior ( AC) and posterior colporrhaphy ( PC), both with and without hysterectomy, were performed. Primary outcome was objective cure (POP quantification system [POP-Q] ≤1) and subjective cure (negative response to questions 2 and 3 on Pelvic Organ Prolapse Distress Inventory 6 [ POPDI-6]). Subanalysis was done on patients who had uterus preserved compared with those with vaginal hysterectomy. Results Postoperative data were available for 146 patients: 120 in the hysterectomy group and 26 in the hysteropexy group. Mean age, parity, postmenopausal status and mean operating time in the hysterectomy group were significantly higher than in the hysteropexy group. At median follow-up of 86 months, objective cure at overall compartments for all patients was 67.8%, and for subjective cure, this was 64.4%. There was no difference in the adjusted odds ratio for objective and subjective cure rates in both groups, but the hysterectomy group had a significantly lower mean total POPDI-6 score. Conclusion SSF plus AC and PC have a low reoperation rate despite a moderate success rate at 7-year follow-up. There was no difference in the adjusted objective, subjective success rates and sexual function between sacrospinous hysteropexy and hysterectomy. The hysterectomy group, however, had fewer bothersome prolapse symptoms. [ABSTRACT FROM AUTHOR]

Background The Food and Drug Administration has recently highlighted an increase in reported complications associated with the use of transvaginal mesh. Aims To describe the clinical outcomes, presentation, timing and management of mesh exposure/extrusion Materials and Methods Retrospective study from December 2006 to March 2012. A total of 40 women had vaginal mesh exposure/extrusion secondary to prior transvaginal mesh ( TVM) surgery. Descriptive statistics were used for demographics and pre-operative data. Paired-samples t-test was applied for comparison of pre- and postoperation. A P value of <0.05 was considered statistically significant. Results The mesh exposure/extrusion rate was noted to be 2.64% (17/642). Vaginal bleeding in 29 of 40 (72.5%) and hispareunia in 12 of 13 (92.3%) were identified as the most common symptoms for mesh exposure/extrusion. The onset of complications occurred in two peaks: between 3 and 4 months and after 1-year of follow-up. Initial conservative treatment was given for 12.5% (5/40) of women, while 87.5% (35/40) had undergone repair for mesh exposure/extrusion (21 outpatient and 14 inpatient cases). Among those who had conservative treatment, 80% (4/5) had persistent mesh exposure. Conclusion Persistent or new-onset abnormal vaginal bleeding and hispareunia after TVM surgery should be considered as 'red flag' symptoms for mesh exposure/extrusion. Frequent follow-up from the first 3-4 months up to 1 year postoperative may identify complications. Utilisation of mesh excision or trimming as the initial means of treatment may yield a better outcome. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the incidence of de novo stress urinary incontinence (SUI) and sonographic features of implanted transvaginal mesh in continent women treated with Elevate anterior/apical [single-incision mesh (SIM-A)] or Perigee [transvaginal mesh with sacrospinous fixation (TVM + SSF)] in extensive pelvic organ reconstruction surgery. Methods: This prospective observational study was done from May 2010 to January 2013. Patients were recruited from two tertiary centers, and the Elevate and Perigee systems were compared. Patients who had overt or occult SUI, previous prolapse or mesh insertion were excluded. Result: Fifty-seven patients in the SIM-A group and sixty-one in the TVM + SSF group were analysed. All completed a minimum of 1-year follow-up. Groups were demographically and statistically similar. There was a significantly high incidence of de novo SUI postoperatively in the SIM-A group. The objective and subjective cure rate of pelvic organ prolapse (POP) were comparable between groups, with incidence of mesh erosion in the SIM-A group and three in the TVM + SSF group. Sonographic evaluation showed significant increase in mesh length in the SIM-A group. Conclusion: Elevate a offered lower incidence of mesh erosion and comparable results on anatomical POP correction; however, incidence of de novo SUI was high. There is an apparent lengthening of implanted Elevate® mesh sonographically. [ABSTRACT FROM AUTHOR]

Background: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations., Methods: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected., Results: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m 2 increase), but was not associated with HIV serostatus., Conclusion: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus., Competing Interests: Declaration of competing interest CCH has received honoraria for speaking at educational events or consulting from Gilead Sciences, and research funding from Gilead Sciences. HYS has received research funding from Gilead Sciences. The remaining authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH)., Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months., Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm 3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine)., Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

Background: Cingulin (CGN) is a pivotal cytoskeletal adaptor protein located at tight junctions. This study investigates the link between CGN mutation and increased cancer susceptibility through genetic and mechanistic analyses and proposes a potential targeted therapeutic approach., Methods: In a high-cancer-density family without known pathogenic variants, we performed tumor-targeted and germline whole-genome sequencing to identify novel cancer-associated variants. Subsequently, these variants were validated in a 222 cancer patient cohort, and CGN c.3560C > T was identified as a potential cancer-risk allele. Both wild-type (WT) (c.3560C > C) and variant (c.3560C > T) were transfected into cancer cell lines and incorporated into orthotopic xenograft mice model for evaluating their effects on cancer progression. Western blot, immunofluorescence analysis, migration and invasion assays, two-dimensional gel electrophoresis with mass spectrometry, immunoprecipitation assays, and siRNA applications were used to explore the biological consequence of CGN c.3560C > T., Results: In cancer cell lines and orthotopic animal models, CGN c.3560C > T enhanced tumor progression with reduced sensitivity to oxaliplatin compared to the CGN WT. The variant induced downregulation of epithelial marker, upregulation of mesenchymal marker and transcription factor, which converged to initiate epithelial-mesenchymal transition (EMT). Proteomic analysis was conducted to investigate the elements driving EMT in CGN c.3560C > T. This exploration unveiled overexpression of IQGAP1 induced by the variant, contrasting the levels observed in CGN WT. Immunoprecipitation assay confirmed a direct interaction between CGN and IQGAP1. IQGAP1 functions as a regulator of multiple GTPases, particularly the Rho family. This overexpressed IQGAP1 was consistently associated with the activation of Rac1, as evidenced by the analysis of the cancer cell line and clinical sample harboring CGN c.3560C > T. Notably, activated Rac1 was suppressed following the downregulation of IQGAP1 by siRNA. Treatment with NSC23766, a selective inhibitor for Rac1-GEF interaction, resulted in the inactivation of Rac1. This intervention mitigated the EMT program in cancer cells carrying CGN c.3560C > T. Consistently, xenograft tumors with WT CGN showed no sensitivity to NSC23766 treatment, but NSC23766 demonstrated the capacity to attenuate tumor growth harboring c.3560C > T., Conclusions: CGN c.3560C > T leads to IQGAP1 overexpression, subsequently triggering Rac1-dependent EMT. Targeting activated Rac1 is a strategy to impede the advancement of cancers carrying this specific variant., (© 2024. The Author(s).)

Lactoferrin (LF) stands as one of the extensively investigated iron-binding glycoproteins within milk, exhibiting diverse biological functionalities. The global demand for LF has experienced consistent growth. Biotechnological strategies aimed at enhancing LF productivity through microbial expression systems offer substantial cost-effective advantages and exhibit fewer constraints compared to traditional animal bioreactor technologies. This study devised a novel recombinant plasmid, wherein the AOX1 promoter was replaced with a glucose-inducible G1 promoter (P G1 ) to govern the expression of recombinant porcine LF (rpLF) in Pichia pastoris GS115. High-copy-number P G1 -rpLF yeast clones were meticulously selected, and subsequent induction with 0.05 g/L glucose demonstrated robust secretion of rpLF. Scaling up production transpired in a 5 L fermenter, yielding an estimated rpLF productivity of approximately 2.8 g/L by the conclusion of glycerol-fed fermentation. A three-step purification process involving tangential-flow ultrafiltration yielded approximately 6.55 g of rpLF crude (approximately 85% purity). Notably, exceptional purity of rpLF was achieved through sequential heparin and size-exclusion column purification. Comparatively, the present glucose-inducible system outperformed our previous methanol-induced system, which yielded a level of 87 mg/L of extracellular rpLF secretion. Furthermore, yeast-produced rpLF demonstrated affinity for ferric ions (Fe 3+ ) and exhibited growth inhibition against various pathogenic microbes ( E. coli , S. aureus , and C. albicans ) and human cancer cells (A549, MDA-MB-231, and Hep3B), similar to commercial bovine LF (bLF). Intriguingly, the hydrolysate of rpLF (rpLFH) manifested heightened antimicrobial and anticancer effects compared to its intact form. In conclusion, this study presents an efficient glucose-inducible yeast expression system for large-scale production and purification of active rpLF protein with the potential for veterinary or medical applications.

From June 2022 to April 2023, 1629 HIV-positive participants were assessed for the risk of atherosclerotic cardiovascular disease (ASCVD). The 10-year ASCVD risk of <5 %, 5 % to <7.5 %, ≥7.5 % to <20 % and ≥20 % were 59.9 %, 14.4 %, 20.7 % and 5.0 %, respectively; 440 (27.0 %) participants met the criteria for statin therapy, but only 171 (38.8 %) were prescribed statins., (Copyright © 2024. Published by Elsevier B.V.)

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities., Competing Interests: The authors declare no competing interests.

Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets ( p < 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal-fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE.

Objective: The COVID-19 pandemic has had an enormous impact on society and the medical environment in Taiwan in 2022. As pregnant women with COVID-19 are at higher risk for multiple complications, Taiwan needs a COVID-19 specialized maternity unit to improve the quality of maternal and neonatal care., Materials and Methods: We share our experience with specialized maternity unit for pregnant women with COVID-19 at the National Cheng Kung University Hospital, where we can have careful evaluation, safe birth, and comprehensive postpartum care., Results: Our COVID-19 specialized maternity unit enrolled 253 pregnant women with COVID-19, 90 (35.6%) pregnant women were admitted to the specialized maternity unit, and 71 (28.1%) pregnant women gave birth during hospitalization in two months. All pregnant women recovery well and real-time polymerase chain reaction tests on all infants were negative for COVID-19., Conclusion: A specialized maternity unit can provide pregnant women with a safe birth environment, immediate maternity care, and high medical quality. It can also help health workers in non-specialized maternity units deal with COVID-19-related psychological stress. Therefore, setting up one specialized maternity unit in the city during the pandemic should be guardedly considered., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Background: MicroRNAs are a group of small non-coding RNAs that are involved in development and diseases such as cancer. Previously, we demonstrated that miR-335 is crucial for preventing collagen type XI alpha 1 (COL11A1)-mediated epithelial ovarian cancer (EOC) progression and chemoresistance. Here, we examined the role of miR-509-3p in EOC., Methods: The patients with EOC who underwent primary cytoreductive surgery and postoperative platinum-based chemotherapy were recruited. Their clinic-pathologic characteristics were collected, and disease-related survivals were determined. The COL11A1 and miR-509-3p mRNA expression levels of 161 ovarian tumors were determined by real-time reverse transcription-polymerase chain reaction. Additionally, miR-509-3p hypermethylation was evaluated by sequencing in these tumors. The A2780CP70 and OVCAR-8 cells transfected with miR-509-3p mimic, while the A2780 and OVCAR-3 cells transfected with miR-509-3p inhibitor. The A2780CP70 cells transfected with a small interference RNA of COL11A1, and the A2780 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis, luciferase, and chromatin immunoprecipitation assays were performed in this study., Results: Low miR-509-3p levels were correlated with disease progression, a poor survival, and high COL11A1 expression levels. In vivo studies reinforced these findings and indicated that the occurrence of invasive EOC cell phenotypes and resistance to cisplatin are decreased by miR-509-3p. The miR-509-3p promoter region (p278) is important for miR-509-3p transcription regulation via methylation. The miR-509-3p hypermethylation frequency was significantly higher in EOC tumors with a low miR-509-3p expression than in those with a high miR-509-3p expression. The patients with miR-509-3p hypermethylation had a significantly shorter overall survival (OS) than those without miR-509-3p hypermethylation. Mechanistic studies further indicated that miR-509-3p transcription was downregulated by COL11A1 through a DNA methyltransferase 1 (DNMT1) stability increase. Moreover, miR-509-3p targets small ubiquitin-like modifier (SUMO)-3 to regulate EOC cell growth, invasiveness, and chemosensitivity., Conclusion: The miR-509-3p/DNMT1/SUMO-3 axis may be an ovarian cancer treatment target., (© 2023. The Author(s).)

Background: While some evidence has suggested the benefits of co-formulated bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in improving the quality of life of people living with HIV (PLWH), patient-reported outcome studies that focus on Asian population remain scarce. We aimed to determine the changes in HIV-related symptom burden in virally-suppressed PLWH switching to B/F/TAF in a real-world setting., Methods: PLWH on stable antiretroviral therapy (ART) for ≥6 months with plasma HIV RNA <200 copies/mL who decided to switch to B/F/TAF were eligible for the study. Participants' experience with 20 symptoms were assessed using HIV Symptom Index at baseline and weeks 24 and 48. Responses were dichotomized in two ways: 1) present vs. not present; and 2) bothersome vs. not bothersome, and compared across time points., Results: Six hundred and thirty participants (prior regimen, 94.4% integrase inhibitor-based) who completed week 48 visit were included in the analysis. Forty-eight weeks after switching to B/F/TAF, six symptoms were significantly less prevalent, and seven symptoms were significantly less bothersome. Improvement was more pronounced in participants whose prior regimen was elvitegravir-based versus dolutegravir-based. Logistic regression results showed that prior dolutegravir-based ART and pre-existing diabetes independently predicted improvement in diarrhea/loose bowels and muscle aches/joint pain, respectively. Despite the overall improvement, some symptoms persisted in a substantial proportion of participants., Conclusions: Virally-suppressed PLWH might benefit from a regimen switch to B/F/TAF to reduce the prevalence and level of bother of HIV-related symptoms. Nevertheless, additional multidisciplinary interventions are warranted to further alleviate the symptom burden of PLWH., Competing Interests: Declaration of competing interest CCH declares that he has received honoraria for speaking at educational events or consulting from Gilead Sciences and ViiV Healthcare, and research funding from Gilead Sciences, Merck, and ViiV Healthcare by participating in clinical trials. HYS declares that she has received research funding from Gilead Sciences. The remaining authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Lung cancer continues to be the leading cause of cancer death in the United States. Despite recent advances, the five-year survival rate for lung cancer compared to other cancers still remains fairly low. The discovery of molecular targets for lung cancer is key to the development of new approaches and therapies. Electrically silent voltage-gated potassium channel (KvS) subfamilies, which are unable to form functional homotetramers, are implicated in cell-cycle progression, cell proliferation and tumorigenesis. Here, we analyzed the expression of KvS subfamilies in human lung tumors and identified that potassium voltage-gated channel subfamily F member 1 (KCNF1) was up-regulated in non-small cell lung cancer (NSCLC). Silencing of KCNF1 in NSCLC cell lines reduced cell proliferation and tumor progression in mouse xenografts, re-established the integrity of the basement membrane, and enhanced cisplatin sensitivity. KCNF1 was predominately localized in the nucleoplasm and likely mediated its functions in an ion-independent manner. We identified integrin β4 subunit (ITGB4) as a downstream target for KCNF1. Our findings suggest that KCNF1 promotes lung cancer by enhancing ITGB4 signaling and implicate KCNF1 as a novel therapeutic target for lung cancer., (© 2022. The Author(s).)

As long-lived apex predators, Indo-Pacific humpback dolphins ( Sousa chinensis ) are key indicators of marine coastal environmental health. Skin marks can be observed on dorsal body surfaces that are visible during mark-recapture studies that rely on photo-identification (photo-ID) methods. Skin mark prevalence may be an indicator of environmental or anthropogenic stressors in the ecosystem, which may lead to individual and/or population-level health concerns. The prevalence of marks of anthropogenic origin was assessed in the Critically Endangered S. chinensis taiwanensis population along the coasts of central Taiwan. Fifty, twenty-eight, and thirty-four individuals were identified in 2018, 2019, and 2021, respectively. At least one category of injuries was observed in 47 of 57 distinctive individuals (82%), and adults showed a higher prevalence of deep injuries than the other coloration stages. At least one category of skin lesion was observed in 33 of 57 distinctive individuals (58%), and high prevalence of skin lesions was found in mature individuals. Given the difficulty in taking direct observations, skin mark prevalence is proposed as a proxy for estimating habitat health and anthropogenic stressors upon S. chinensis taiwanensis . The moderate-to-high prevalence of skin marks in this study was designated as a warning of risks. This study provides important updated information for the assessment of the health and survival of this population. More effective management measures are urgently needed to reverse the observed population decline.

Objective: Desmoid fibromatosis (DF) is a rare, locally aggressive soft tissue tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) play a critical role in the diagnosis of DF and in developing treatment plans. Currently, observation is the primary therapeutic option for a biopsy-confirmed DF. Here, we present a case of a DF that was misdiagnosed as uterine fibroid before surgery., Case Report: A 36-year-old woman presented with urinary frequency and a palpable lower abdominal mass, which was suspected as uterine fibroid based on sonography and CT. During surgery, an abdominal wall mass was found to be densely adherent to the bladder. Permanent pathology revealed that the tumor was desmoid-type fibromatosis., Conclusion: Desmoid tumors often occur in the abdomen, abdominal wall, extremities, head, and neck. Abdominal wall DF involving the rectus abdominis muscles is most commonly observed. Conversely, desmoid tumors involving the bladder are less described. The review of similar cases reported since 1985 showed that partial cystectomy was primarily performed for complete resection., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH., Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis., Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm 3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm 3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89)., Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm 3 and DM had consistently lower serological responses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Between March and October, 2018, 1248 people living with HIV completed questionnaire interviews for cancer screening, of whom 46.9% (n = 585) completed free-of-charge cancer screening. Time constraint (50.1%) was the most common reason provided for refusal to participate in cancer screening. None of the participants were diagnosed with any of the four cancers., (Copyright © 2021. Published by Elsevier B.V.)

Background/purpose: Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak., Methods: We conducted a retrospective case-control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors., Results: From a total of 15,305 MSM client visits during 2006-2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6-7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006-2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps < 0.05)., Conclusion: Non-opioid recreational drugs use is associated with incident HIV infection in this prolonged HIV outbreak. There is an urgent need to formulate an effective public health response to mitigate the risk., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

One new compound, crocusatin M (1), and three new glycosidic compounds, crocusatins N-P (2-4), along with nine known compounds were isolated from the dried stigmas of Crocus sativus. The structures of new compounds were elucidated on the basis of spectroscopic analysis, and the absolute configurations of 1, 2, and 3 were unambiguously assigned by the comparison of experimental and calculated ECD data. This is the first report of the isolation of 4 with the HMG moiety from the genus Crocus. Compounds 1 and 4 exhibited weak anti-inflammatory activities on inhibiting lipopolysaccharide (LPS)-induced NO production., (© 2021. The Japanese Society of Pharmacognosy.)

The tumor microenvironment is a well-recognized framework in which immune cells present in the tumor microenvironment promote or inhibit cancer formation and development. A crown-like structure (CLS) has been reported as a dying or dead adipocyte surrounded by a 'crown' of macrophages within adipose tissue, which is a histologic hallmark of the inflammatory process in this tissue. CLSs have also been found to be related to formation, progression and prognosis of some types of cancer. However, the presence of CLSs in the omentum of advanced-stage high-grade serous ovarian carcinoma (HGSOC) has not been thoroughly investigated. By using CD68, a pan-macrophage marker, and CD163, an M2-like polarization macrophage marker, immunohistochemistry (IHC) was performed to identify tumor-associated macrophages (TAMs) and CLSs. This retrospective study analyzed 116 patients with advanced-stage HGSOC who received complete treatment and had available clinical data from July 2008 through December 2016 at National Cheng Kung University Hospital (NCKUH) (Tainan, Taiwan). Based on multivariate Cox regression analysis, patients with omental CD68 + CLSs had poor OS (median survival: 24 vs. 38 months, p = 0.001, hazard ratio (HR): 2.26, 95% confidence interval (CI): 1.41-3.61); patients with omental CD163 + CLSs also had poor OS (median survival: 22 vs. 36 months, HR: 2.14, 95%CI: 1.33-3.44, p = 0.002). Additionally, patients with omental CD68 + or CD163 + CLSs showed poor PFS (median survival: 11 vs. 15 months, HR: 2.28, 95%CI: 1.43-3.64, p = 0.001; median survival: 11 vs. 15 months, HR: 2.17, 95%CI: 1.35-3.47, respectively, p = 0.001). Conversely, the density of CD68 + or CD163 + TAMs in ovarian tumors was not associated with patient prognosis in advanced-stage HGSOC in our cohort. In conclusion, we, for the first time, demonstrate that the presence of omental CLSs is associated with poor prognosis in advanced-stage HGSOC.

Ovarian cancer has a unique tumor microenvironment (TME) that enables cancer-associated fibroblasts (CAFs) to interact with cellular and matrix constituents and influence tumor development and migration into the peritoneal cavity. Collagen type XI alpha 1 (COL11A1) is overexpressed in CAFs; therefore this study examines its role during CAF activation in epithelial ovarian cancer (EOC). Coculturing human ovarian fibroblasts (HOFs) with high COL11A1-expressing EOC cells or exposure to the conditioned medium of these cells prompted the expression of COL11A1 and CAF phenotypes. Conversely, coculturing HOFs with low COL11A1-expressing EOC cells or COL11A1-knockdown abrogated COL11A1 overexpression and secretion, in addition to CAF activation. Increased p-SP1 expression attributed to COL11A1-mediated extracellular signal-regulated kinase activation (ERK) induced p65 translocation into the nucleus and augmented its binding to the insulin-like growth factor binding protein 2 (IGFBP2) promoter, ultimately inducing TGF-β3 activation. The CAF-cancer cell crosstalk triggered interleukin-6 release, which in turn promoted EOC cell proliferation and invasiveness. These in vitro results were confirmed by in vivo findings in a mouse model, showing that COL11A1 overexpression in EOC cells promoted tumor formation and CAF activation, which was inhibited by TGF-β3 antibody. Human tumors with high TGF-β3 levels showed elevated expression of COL11A1 and IGFBP2, which was associated with poor survival. Our findings suggest the possibility that anti-TGF-β3 treatment strategy may be effective in targeting CAFs in COL11A1-positive ovarian tumors.

Background: Pharmacogenetic studies have shown that slow and intermediate metabolizers of efavirenz (EFV) gained less weight compared with extensive metabolizers. It is hypothesized that increased EFV exposure suppresses weight gain. We investigated the effect of EFV mid-dose plasma concentration (C12) on long-term weight change among virologically suppressed people living with HIV (PLWH)., Methods: Participants in a prospective EFV pharmacokinetic study were included if they had been taking EFV-containing combination antiretroviral therapy for more than 240 weeks and had 3 or more weight measurements. The weight changes and time to ≥5% of weight gain over 192 weeks were compared between PLWH with higher and those with lower EFV C12 (using mean population C12 as the cutoff). EFV C12 and CYP2B6 516G>T polymorphism were examined in generalized estimating equations and in a Cox proportional hazards model for associations with weight gain, after adjustments for age, sex, companion antiretroviral agent, CD4 lymphocyte count, and plasma HIV RNA., Results: One hundred eighteen PLWH were included. PLWH with higher EFV C12 had less mean weight gain compared with those with lower C12 after 192 weeks (-0.09 vs +1.58 kg, P = 0.033). PLWH with higher C12 were less likely to gain ≥5% weight in Kaplan-Meier analysis (P = 0.0003). In both generalized estimating equations and Cox proportional hazards models, a higher EFV C12 was associated with less weight gain, while CYP2B6 516G>T was not, after adjustments made for confounding factors., Conclusions: Our findings support that increased EFV exposure was associated with less weight gain., Competing Interests: C.-C.H. received research support from Gilead Sciences, Merck, and ViiV, speaker honoraria from Gilead Sciences and ViiV, and served on advisory boards for Gilead Sciences and ViiV. The remaining authors have no funding or conflicts of interest to disclose. This does not potentially influence what is written in the submitted work., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background/purpose: Early initiation of antiretroviral therapy (ART) reduces the risks for serious infections and mortality. We aimed to assess the outcomes of initiating ART among HIV-positive Taiwanese according to the CD4 cut-off values by the WHO recommendations., Methods: We reviewed medical records of patients with newly diagnosed HIV infection between 2004 and 2015 and 3 groups of patients were defined according to the timing of ART initiation based on CD4 count recommended by WHO: Group 1 between 2004 and 2009; Group 2 between 2010 and 2012; and Group 3 between 2013 and 2015. The primary outcome was all-cause mortality. All patients were followed until 2 years after the last patient was included in each group., Results: Of 2022 patients included, the mortality rate was 18.28, 14.01, and 9.10 deaths per 1000 person-years of follow-up (PYFU) in Groups 1, 2, and 3, respectively. In multivariable Cox regression analysis, factors associated with mortality were age (per 1-year increase, adjusted hazard ratio [AHR], 1.06; 95% CI, 1.05-1.08), presence of AIDS-defining disease at HIV diagnosis (AHR, 4.81; 95% CI, 2.99-7.74), solid-organ malignancy (AHR, 3.10; 95% CI, 1.86-5.18), and initiation of ART (AHR, 0.09; 95% CI, 0.05-0.16). By competing risk regression model for non-AIDS-related death, the AHR for Group 3 versus Group 1 was 0.27 (95% CI, 0.09-0.80)., Conclusions: While continued efforts are needed to improve early diagnosis and linkage to care, initiation of cART improved survival among HIV-positive patients in Taiwan according to the increasing CD4 cut-off values that were recommended by the WHO., (Copyright © 2019. Published by Elsevier B.V.)

Ganjiang Lingzhu Decoction is one of the first 100 classical prescriptions published by China in 2018. According to the published literature, it was found that there is no review on the history, evolution and research progress of this prescription. In order to reflect the history, modifications, quality control and clinical applications, this paper focuses on the origination, evolution, current development and modern studies of Ganjiang Lingzhu Decoction, in the hope of providing a reference for the heritage and innovation of other classical prescriptions.

Background: Cardiovascular disease (CVD) is an emerging cause of morbidity and mortality among HIV-positive patients receiving successful combination antiretroviral therapy, but their CVD risk has been rarely investigated in Asia-Pacific region. We aimed to assess the CVD risk of HIV-positive Taiwanese outpatients., Methods: We did cross-sectional questionnaire interviews to collect information of HIV-positive Taiwanese patients aged 40-79 at the HIV clinics of a medical center from 1 March to 31 August, 2017. The Framingham Risk Score (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) risk score and Data-Collection on Adverse effects of Anti-HIV Drugs (D:A:D) risk score were used to estimate their CVD risk., Results: Of the screened 1251 patients, 1006 (80.4%) with complete data to assess their CVD risk were included for analyses. The prevalence of patients aged 40-75 and with a high CVD risk was 30.6% by FRS, 3.7% by D:A:D (R) risk score, and 22.2% by ASCVD risk score. In multiple logistic regression, older age, current smoking, higher systolic blood pressure, and higher triglyceride and fasting glucose levels were independently associated with the ASCVD risk score ≥7.5%. If current smokers aged 55-59 had stopped smoking, the proportions of them with a 10-year CVD risk of ≥10% by FRS and ≥7.5% by ASCVD risk score would have decreased by 35.3% and 20.0%, respectively., Conclusions: Higher CVD risk estimates among HIV-positive Taiwanese aged 40-75 were associated with an older age, current smoking, higher systolic blood pressure, hypertriglyceridemia, and hyperglycemia. Smoking cessation could potentially lead to significant decreases of CVD risk., (Copyright © 2019. Published by Elsevier B.V.)

Background: HIV-positive patients are at high risk of suicide behaviors. Because most previous studies have investigated suicide behaviors among HIV-positive patients during their first six months of diagnosis only, there is a current lack of understanding of suicide behaviors among this group., Purpose: This study aimed at HIV-positive patients who had been diagnosed between six months and one year ago and examined their suicide ideation and suicide attempt profiles and the associated factors of suicide., Methods: This study adopted a cross-sectional design. A total of 114 HIV-positive patients were interviewed in the HIV clinics of a medical center in Taipei City. Information collections included demographic and HIV-related data and measurements of suicide ideation, suicide attempt, depression, body image, meaning in life, and social support. Independent samples t tests, chi square tests, and logistic regressions were conducted to examine the associated factors and predictors of suicide ideation and suicide attempt., Results: Slightly over one-quarter (27.2 %) of the participants reported suicide ideation and 14.0% reported attempting suicide in recent one week prior the study interview. Duration since being diagnosed HIV-positive, level of education, and history of depression were each associated with suicide ideation, while only history of depression was associated with suicide attempt. Having a higher level of education and having a higher level of social (family) support were both predictors of lower risk of suicide ideation, while having a higher level of depression predicted a greater risk of suicide attempt., Conclusions / Implications for Practice: This study found high prevalences of suicide ideation and attempting suicide among HIV-positive patients during the six month to one year period after diagnosis. Moreover, the prevalence was similar to that among HIV-positive patients during the first six months of diagnosis. Suicide prevention should be a focus of care plans provided to HIV-positive patients during their first year after diagnosis. These results may be provided as a reference for developing suicide-prevention strategies for HIV-positive patients. Routine screening for depression, guiding families to increase their provision of social support, and giving assistance to individuals with higher levels of depression contribute to the effective prevention of suicide among HIV-positive patients.

Van der Waals heterobilayers of transition metal dichalcogenides with spin-valley coupling of carriers in different layers have emerged as a new platform for exploring spin/valleytronic applications. The interlayer coupling was predicted to exhibit subtle changes with the interlayer atomic registry. Manually stacked heterobilayers, however, are incommensurate with the inevitable interlayer twist and/or lattice mismatch, where the properties associated with atomic registry are difficult to access by optical means. Here, we unveil the distinct polarization properties of valley-specific interlayer excitons using epitaxially grown, commensurate WSe 2 /MoSe 2 heterobilayers with well-defined (AA and AB) atomic registry. We observe circularly polarized photoluminescence from interlayer excitons, but with a helicity opposite to the optical excitation. The negative circular polarization arises from the quantum interference imposed by interlayer atomic registry, giving rise to distinct polarization selection rules for interlayer excitons. Using selective excitation schemes, we demonstrate the optical addressability for interlayer excitons with different valley configurations and polarization helicities.

Background: Previous studies have shown that the durability of serological response is impaired in successfully vaccinated human immunodeficiency virus-1 (HIV-1) positive subjects after receiving 2 doses of inactivated hepatitis A virus (HAV) vaccine. We evaluated whether 3 doses compared with 2 doses of HAV vaccine could improve the long-term seroprotection for this susceptible group., Methods: Antibody persistence among HIV-positive men who have sex with men aged 18-40 years who had received 2 or 3 doses of HAV vaccine according to a 0-6- or a 0-1-6-month schedule was evaluated biannually for 5 consecutive years in this prospective, nonrandomized cohort study., Results: At the end of 5 years, seroprotection persisted in 79% (146/185) versus 76% (85/110) and 94% (146/155) versus 88% (84/95) of the 3- versus 2-dose primary responders by intention-to-treat and per-protocol analyses, respectively (P > .05). Throughout the 5 years, the geometric mean concentrations of anti-HAV immunoglobulin G (IgG) were significantly higher for the 3-dose than the 2-dose group. In the multivariable analysis, a 3-dose regimen compared with a 2-dose regimen (odds ratio = 3.36; 95% confidence interval = 1.14-9.93) was independently associated with sustained seroprotection., Conclusions: Three doses versus 2 doses of HAV vaccine improve the durability of immune responses in terms of higher concentrations of specific IgG, which take longer to decay to subthreshold levels., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Introduction and Hypothesis: The purpose of this study was to explore new preventable risk factors for mesh exposure., Methods: A retrospective review of 92 consecutive patients treated with transvaginal mesh (TVM) in the urogynecological unit of our university hospital. An analysis of perioperative predictors was conducted in patients after vaginal repairs using a type 1 mesh. Mesh complications were recorded according to International Urogynecological Association (IUGA) definitions. Mesh-exposure-free durations were calculated by using the Kaplan-Meier method and compared between different closure techniques using log-rank test. Hazard ratios (HR) of predictors for mesh exposure were estimated by univariate and multivariate analyses using Cox proportional hazards regression models., Results: The median surveillance interval was 24.1 months. Two late occurrences were found beyond 1 year post operation. No statistically significant correlation was observed between mesh exposure and concomitant hysterectomy. Exposure risks were significantly higher in patients with interrupted whole-layer closure in univariate analysis. In the multivariate analysis, hematoma [HR 5.42, 95 % confidence interval (CI) 1.26-23.35, P = 0.024), Prolift mesh (HR 5.52, 95 % CI 1.15-26.53, P = 0.033), and interrupted whole-layer closure (HR 7.02, 95 % CI 1.62-30.53, P = 0.009) were the strongest predictors of mesh exposure., Conclusion: Findings indicate the risks of mesh exposure and reoperation may be prevented by avoiding hematoma, large amount of mesh, or interrupted whole-layer closure in TVM surgeries. If these risk factors are prevented, hysterectomy may not be a relative contraindication for TVM use. We also provide evidence regarding mesh exposure and the necessity for more than 1 year of follow-up and preoperative counselling.

Objective: Voiding dysfunction following a midurethral sling procedure is still a relevant consequence that can affect patients' quality of life. Various invasive methods have been described to manage this problem. We hypothesize that we if we could diagnose the condition early using noninvasive tools, we would be able to offer appropriate effective management. We sought to study the effectiveness of attaching a tension-releasing suture on a single-incision sling (SIS) tape as a prophylactic measure for the treatment of immediate postoperative voiding dysfunctions, and secondarily, to evaluate the objective and subjective cure rates of the treatment for stress urinary incontinence., Materials and Methods: It is a prospective observational study. A tension-releasing suture was prepared by appending a polyglactin suture to one end of the MiniArc sling tip fiber, which could be used to manipulate the sling tip when postoperative voiding dysfunction was identified. Primary outcome measure was the number of patients requiring tension-releasing suture manipulation to treat postoperative voiding dysfunctions successfully., Results: Twelve of the 131 (9.2%) patients who underwent SIS procedure for urodynamic stress incontinence surgery required tension-releasing suture manipulation due to voiding dysfunction during the immediate postoperative period with a good outcome. Postoperative overall objective and subjective cure rates were 90.5% and 88.9% (126 available patients at 1-year follow up, mean 19.2 ± 8.0 months), respectively. The subanalysis of the objective and subjective cure rates of the group with tension-releasing suture manipulation were 91.7% (11/12) and 91.7% (11/12), and those of the group without tension-releasing suture manipulation were 90.4% (103/114) and 88.6% (101/114), respectively, at 1-year follow up., Conclusion: Tension-releasing suture is effective in the management of immediate postoperative voiding dysfunction in an SIS procedure. SIS operation has good short-term objective and subjective cure rates for female urodynamic stress incontinence., (Copyright © 2016. Published by Elsevier B.V.)

Background: Genotypic drug resistance testing for HIV-1 has been integrated into voluntary counselling and testing (VCT) programmes to investigate the trends of transmitted drug resistance (TDR), including integrase mutations, among individuals with recent or chronic HIV infections in Taiwan., Methods: Between 2006 and 2014, 745 of 21 886 subjects (3.4%) tested HIV positive in the VCT service. The BED assay was used to identify recent HIV infections. Genotypic resistance mutations were interpreted using the WHO 2009 list. Integrase resistance mutations were analysed using the Stanford HIV Drug Resistance Database., Results: Three-hundred-and-sixty (48.3%) patients were recently infected with HIV-1. Of 440 patients linked to HIV care with analysable reverse transcriptase and protease genes, 49 (11.1%) were infected with HIV-1 harbouring at least one resistance-associated mutation (RAM). The prevalence of TDR to NRTIs, NNRTIs and PIs was 4.1%, 6.4% and 2.3%, respectively. TDR prevalence did not change significantly during the study period. CD4 counts ≤500 cells/mm(3) and hepatitis B surface antigen positivity were independent factors associated with acquiring drug-resistant HIV. The prevalence of integrase mutations was 3.2%. Among the seven major integrase mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R and N155H), only one strain harbouring the Q148R mutation was detected. We found no statistically significant difference between patients with chronic infection and those with recent infection in the prevalence of drug-resistant mutations to any of the four classes of antiretroviral agents., Conclusions: The prevalence of TDR of HIV-1 strains to available antiretroviral agents is moderately high, but transmission of HIV-1 with drug-resistant mutations remains stable in Taiwan., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: The goal of the study was to compare the effects of isokinetic and isotonic strengthening program on the changes of muscle strength, functional capacity, life quality, and inflammatory cytokines in hemiparetic patients within 6 months of stroke attack., Methods: Thirty-one participants were randomly assigned into either isotonic training group or isokinetic training group. Both training programs were carried out 5 days a week for a total of 4 weeks. Outcome measures included the peak isometric torque of knees at 90° flexion, the peak torque of knees extension and flexion at angular velocities 60°/s and 120°/s, Short Form 36 (SF-36) Health Survey Questionnaire, Timed Up and Go test, and inflammatory cytokines including high sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α., Results: Seven patients were not able to complete the training program and were excluded from our study. The results from the remaining 24 patients showed that there were more peak torque, and SF-36 items significantly improved in the isokinetic training group compared with the isotonic group. The Timed Up and Go test and interleukin-6 were improved in both groups, but tumor necrosis factor-α was improved in only the isokinetic group. There were no significant differences between the improvements of the 2 groups except the isokinetic flexion torque at 60°/s and 120°/s., Conclusions: Early strengthening exercise is important for subacute stroke patients, and isokinetic program, if accessible, can bring more significant benefits for them., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)