Discussion of HIV and Other Sexually Transmitted Infections with Sex Partners of Nigerian Men who have Sex with Men and Transgender Women: Implications for Interventions to Promote Safer Sex Practices.

BACKGROUND: Discussion of HIV and other sexually transmitted infections (STIs) among sex partners facilitates risk reduction. We evaluated HIV/STI-related communications, including broad assessment of any self-reported discussion of the topic and specific discussion of each partners' HIV status, among a historically marginalized and presently criminalized community of sexual and gender minorities (SGM) in Nigeria. METHODS: From 2013-2018, we enrolled SGM aged 18+ in Lagos or 16+ in Abuja who reported anal sex with men. At enrollment and 3-, 9-, and 15-month follow-up visits, participants were asked about their sexual behaviors and communications with main sexual partners (MSP) and casual sexual partners (CSP). Questions included "have you talked with your [MSP/CSP] about sexually transmitted infections and HIV?" Multivariable robust Poisson regression with generalized estimating equations was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV/STI-related communications with some or all of each type of sexual partner. RESULTS: Among 2795 SGM enrolled with median age 23 years (interquartile range 20-27), questions about HIV/STI-related communications with MSP were answered by 2436 (87.2%) and with CSP by 2398 (85.9%). Communication with MSP was reported by 68.1% (1659/2436), of whom 897 (54.1%) discussed their own HIV status and 925 (55.8%) discussed their partner's status. Communication with CSP was reported by 43.9% (1052/2398), of whom 389 (37.0%) discussed their own HIV status and 385 (36.6%) discussed their partner's status. Among participants with both MSP and CSP, HIV/STI-related communication with MSP was more common among participants with higher than secondary education (aRR 1.40 [95%CI 1.24-1.58)], who were divorced/separated/widowed (aRR 1.19 [95% CI 1.06-1.33]), who discussed their HIV status with CSP (aRR 1.18 [95%CI 1.10-1.25]), discussed CSP's HIV status (aRR 1.20 [95%CI 1.13-1.27]), and used a condom at last sex with CSP (aRR 1.16 [95%CI 1.08-1.25]). HIV/STI-related communication with CSP was more common among participants with higher than secondary education (aRR 1.36 [95%CI 1.12-1.66]); who were divorced/separated/widowed (aRR 1.38 [95%CI 1.13-1.69]), who discussed their HIV status with MSP (aRR 1.47 [95%CI 1.27-1.69]), who discussed CSP's HIV status (aRR 1.22 [95%CI 1.06-1.40]) and used a condom at last sex with CSP (aRR 1.22 (95%CI 1.08-1.38]). CONCLUSION: HIV/STI-related communications with main and casual sex partners were both associated with safer sex with CSP. HIV prevention and treatment programs for SGM should promote open communications in sexual relationships and consider deployment of modern strategies to facilitate disclosure, especially in settings with criminalizing legislation.

Genetic diagnosis of a rare COL7A1 variant causing dystrophic epidermolysis bullosa pruriginosa through whole­exome sequencing.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of inherited DEB. In the present study, whole-exome sequencing was conducted on 12 individuals from the same affected family and a rare heterozygous variation was identified in the collagen type VII, α1 (COL7A1) gene, namely c.6859G>A (p.Gly2287Arg). Subsequently, this heterozygous variant was confirmed using Sanger sequencing of individual plasma cell-free DNA (cfDNA) and it was demonstrated for the first time, to the best of our knowledge, that COL7A1 exons can be amplified from plasma cfDNA. Within the large pedigree examined, 14 out of 18 individuals carried the variant, 3 carried the wild type, and one exceptional case, III-9, showed no disease symptoms despite carrying the disease variant. A general association between genotype and phenotype was established. Of note, the mutation landscape indicated that this G2287R variant is primarily reported in Asian countries. In silico structure prediction suggested that the residue resulting from the mutation may affect collagen protein stability. In conclusion, the present study provides evidence for the involvement of the COL7A1 G2287R gene variant in the development of DEB-Pr and highlights the potential utility of cfDNA in genetic disease diagnosis.

Predicting response of immunotherapy and targeted therapy and prognosis characteristics for renal clear cell carcinoma based on m1A methylation regulators.

In recent years, RNA methylation modification has been found to be related to a variety of tumor mechanisms, such as rectal cancer. Clear cell renal cell carcinoma (ccRCC) is most common in renal cell carcinoma. In this study, we get the RNA profiles of ccRCC patients from ArrayExpress and TCGA databases. The prognosis model of ccRCC was developed by the least absolute shrinkage and selection operator (LASSO) regression analysis, and the samples were stratified into low-high risk groups. In addition, our prognostic model was validated through the receiver operating characteristic curve (ROC). "pRRophetic" package screened five potential small molecule drugs. Protein interaction networks explore tumor driving factors and drug targeting factors. Finally, polymerase chain reaction (PCR) was used to verify the expression of the model in the ccRCC cell line. The mRNA matrix in ArrayExpress and TCGA databases was used to establish a prognostic model for ccRCC through LASSO regression analysis. Kaplan Meier analysis showed that the overall survival rate (OS) of the high-risk group was poor. ROC verifies the reliability of our model. Functional enrichment analysis showed that there was a obviously difference in immune status between the high-low risk groups. "pRRophetic" package screened five potential small molecule drugs (A.443654, A.770041, ABT.888, AG.014699, AMG.706). Protein interaction network shows that epidermal growth factor receptor [EGRF] and estrogen receptor 1 [ESR1] are tumor drivers and drug targeting factors. To further analyze the differential expression and pathway correlation of the prognosis risk model species. Finally, polymerase chain reaction (PCR) showed the expression of YTHN6-Methyladenosine RNA Binding Protein 1[YTHDF1], TRNA Methyltransferase 61B [TRMT61B], TRNA Methyltransferase 10C [TRMT10C] and AlkB Homolog 1[ALKBH1] in ccRCC cell lines. To sum up, the prognosis risk model we created not only has good predictive value, but also can provide guidance for accurately predicting the prognosis of ccRCC.

Randomized, Placebo-Controlled, Multicenter Clinical Study on the Efficacy and Safety of Lidocaine Patches in Chinese Patients with Postherpetic Neuralgia.

INTRODUCTION: To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). METHODS: Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. RESULTS: Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. CONCLUSIONS: Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

Effects of Coconut Oil and Palm Oil on Growth, Rumen Microbiota, and Fatty Acid Profile of Suckling Calves.

This study aimed to evaluate the effects of coconut oil and palm oil in milk replacer (MR) on the growth performance, blood lipids, rumen fermentation, rumen microbiota, and fatty acid profile of hepatic and muscle of suckling calves. Thirty-six Holstein male calves were randomly assigned to three treatments. Three milk replacers containing different fat sources were as follows: control group (CON, milk fat), coconut oil group (CCO, coconut oil powder as fat), and palm oil group (PLO, palm oil powder as fat). Calves were weighed and blood sampled at 14, 28, 42, and 56 days old, respectively, and the feed intake and fecal score were recorded daily. Fat sources in milk replacers had no effects on body weight, ADG, DMI, fecal score, or days of abnormal fecal in suckling calves among the three groups, while the PLO group tended to decrease starter intake compared with the other groups. Serum concentrations of TC, HDL-C, LDL-C, and VLDL-C in the CCO group increased compared with those of the CON group. Palm oil also decreased the serum GLU concentration of calves but had no effects on serum lipids compared with milk fat. Coconut oil or palm oil had no effects on rumen fermentation, rumen chyme enzyme activity, rumen bacterial community richness and diversity, and dominant phyla and genera when compared with milk fat. However, compared with the CON group, the CCO group increased the proportion of MCFAs and n-6 PUFAs, and decreased the proportion of UFAs and MUFAs in liver tissue, while the PLO group increased the proportion of PUFAs and decreased the proportion of n-3 PUFAs in liver tissue. In addition, compared with the CON group, the CCO group increased the proportion of MCFAs, and decreased the proportion of UFAs and n-3 PUFAs in longissimus dorsi, while the PLO group increased the proportion of PUFAs and decreased the proportion of n-3 PUFAs in longissimus dorsi. In conclusion, compared with milk fat, coconut oil or palm oil in MR had no effects on growth performance, rumen fermentation, and rumen microflora but significantly increased serum lipids concentration and changed some proportions of MCFAs and PUFAs in liver and longissimus dorsi in suckling calves. These results indicate that coconut oil or palm oil as the sole fat source for MRs has no adverse effect on calf rumen fermentation and rumen microbiota but has a detrimental effect on n-3 PUFAs deposition in the liver and longissimus dorsi muscle.

Food and Water Insecurity in Sexual and Gender Minority Groups Living With HIV in Lagos, Nigeria.

BACKGROUND: Food and water insecurity are associated with poor health outcomes that may be exacerbated by social marginalization and barriers to health care experienced by sexual and gender minorities (SGM) in resource-limited settings. We explored factors associated with food and water insecurity in SGM with HIV. SETTING: A longitudinal study of 357 men who have sex with men, transgender women, and other gender-identifying people in Lagos, Nigeria. METHODS: Laboratory testing, interviews, food and water assessments, and anthropometry were performed quarterly. Robust Poisson regression with generalized estimating equations was used to evaluate factors potentially associated with food and water insecurity. RESULTS: From 2014 to 2018, 357 SGM with HIV completed either the food or water assessments. At baseline, participants identified as cisgender men who have sex with men 265 (74.2%), transgender women 63 (17.7%), or as nonbinary/other gender 29 (8.1%). Food insecurity and water insecurity were reported by 63/344(18.3%) and 113/357(31.7%), respectively, at any visit. Food and water insecurity each decreased with ongoing study participation. Food insecurity was associated with nonpartnered relationship status, CD4 count <500 cells/mm 3 , and lack of access to piped water. Water insecurity was associated with age 25 years or older, living with a man, transactional sex, and food insecurity. CONCLUSIONS: Food and water insecurity were common among SGM in Nigeria and decreased with continued study participation, suggesting amenability to intervention when SGM are successfully engaged in care. Targeted interventions to support food and water security may improve HIV-related outcomes, such as CD4 count.

Associations of gender identity with sexual behaviours, social stigma and sexually transmitted infections among adults who have sex with men in Abuja and Lagos, Nigeria.

INTRODUCTION: Sexual and gender minority populations are disproportionately affected by the global syndemic of HIV and other sexually transmitted infections (STIs). We hypothesized that transgender women (TGW) and non-binary individuals in Nigeria have more STIs than cis-gender men who have sex with men (cis-MSM), and that experiences of stigma and sexual practices differ between these three groups. METHODS: From 2013 to 2020, TRUST/RV368 enrolled adults assigned male sex at birth who reported anal sex with men in Abuja and Lagos, Nigeria. Participants were tested for STIs and completed questionnaires about sexual behaviours and social stigma every 3 months. Participants were categorized as cis-MSM, TGW or non-binary/other based on self-reported gender identity. Gender group comparisons were made of HIV, gonorrhoea and chlamydia prevalence and incidence; stigma indicators; and condom use during anal sex. RESULTS: Among 2795 participants, there were 2260 (80.8%) cis-MSM, 284 (10.2%) TGW and 251 (9.0%) non-binary/other individuals with median age of 23 years (interquartile range 20-27). HIV prevalence among cis-MSM, TGW and non-binary/other participants was 40.8%, 51.5% and 47.6%, respectively (p = 0.002). HIV incidence was 8.7 cases per 100 person-years (PY) (95% confidence interval [CI] 6.9-10.8), 13.1 cases/100 PY (95% CI 6.5-23.4) and 17.6 cases/100 PY (95% CI 9.8-29.0, p = 0.025), respectively. Anorectal gonorrhoea incidence was lower in cis-MSM than TGW (22.2 [95% CI 19.6-25.0] vs. 35.9 [95% CI 27.3-46.3]). TGW were more likely than cis-MSM to report being affected by stigma, including assault (47.2% vs. 32.3%), fear of walking around (32.4% vs. 19.2%) and healthcare avoidance (25.0% vs. 19.1%; all p < 0.05). TGW were more likely to report always using condoms than non-binary/other individuals (35.3% vs. 26.2%, p = 0.041) during receptive anal sex. CONCLUSIONS: Sexual and gender minorities in Nigeria have heterogeneous sexual behaviours and experiences of social stigma that may influence the vulnerability to HIV and other STIs. There is a need for tailored interventions that acknowledge and are informed by gender. Further research is needed, particularly among understudied non-binary individuals, to better understand disparities and inform tailored interventions to improve outcomes among these communities.

Effects of Anemoside B4 on Diarrhea Incidence, Serum Indices, and Fecal Microbial of Suckling Calves.

The study was conducted to evaluate the effects of Anemoside B4 on diarrhea incidence, serum indices, and fecal microbial of suckling calves. Sixty newborn Chinese Holstein calves with similar body weight (43.7 ± 3.9 kg) were randomly divided into four groups with 15 calves each, fed the diet which was supplied 0 (CON), 15 (A1), 30 (A2), and 45 (A3) mg/day of Anemoside B4, respectively. The trial period is 56 days. The blood and fecal samples were collected at 28 and 56 days of age. Results show that during the whole trial period, the diarrhea incidence in Group A1, A2, and A3 was significantly lower than that in Group CON (p < 0.05). Compared with the Group CON, Anemoside B4 supplementation significantly decreased the contents of serum D-lactic acid and diamine oxidase at 28-day-old (p < 0.05). At 56-day-old, the content of serum D-lactic acid in Group A3 tended to be higher (0.05 < p < 0.01), and the content of serum diamine oxidase in Group A3 increased significantly, in comparison with Group CON (p < 0.05). Group A3 increased the level of Chao1 and Simpson indices at 28-day-old (0.05 < p < 0.01), and Chao1, Observed_species, Shannon, and Simpson indices at 56-day-old (p < 0.05), in comparison to Group CON. Compared with Group CON, 45 mg / day Anemoside B4 supplementation significantly increased the contents of Bacteroidota (at the phylum level), Prevotella (at the genus level) at 28-day-old (p < 0.05), and the content of Sutterella (at the genus level) at 56-day-old (p < 0.05), promoted the processes of energy metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins (p < 0.05). A positive correlation was observed between Prevotella and metabolism of cofactors and vitamins, energy metabolism, and glycan biosynthesis and metabolism. A positive correlation was observed between Sutterella and energy metabolism. In conclusion, Anemoside B4 could effectively alleviate calf diarrhea, protect the integrity of intestinal mucosa, and change the structure of intestinal microbiota, indicating the potential value of Anemoside B4 in regulating intestinal microbiota and the prevention of intestinal diseases.

Comparison of Growth Performance, Immunity, Antioxidant Capacity, and Liver Transcriptome of Calves between Whole Milk and Plant Protein-Based Milk Replacer under the Same Energy and Protein Levels.

High-cost milk proteins necessitate cheaper, effective milk replacer alternatives, such as plant proteins. To examine plant protein-based milk replacer's impact on growth performance, serum immune and antioxidant indicators, and liver transcriptome profiles in suckling calves. We assigned 28 newborn Holstein calves (41.60 ± 3.67 kg of body weight at birth) to milk (M) or milk replacer (MR) and starter diets pre-weaning (0-70 d of age) but with the same starter diet post-weaning (71-98 d of age). During the pre-weaning period, compared with the M group, MR group had significantly lower body weight, withers height, heart girth, average daily gain, feed efficiency, serum immunoglobulin (Ig) M concentration, superoxide dismutase concentration, and total antioxidant capacity; whereas they had significantly higher serum aspartate aminotransferase concentration. During the post-weaning period, MR group presented significantly higher average daily gain, alanine transaminase, aspartate aminotransferase, and malonaldehyde concentrations; whereas they had significantly lower serum IgA and IgM concentrations than the M group. Transcriptome analysis revealed 1, 120 and 293 differentially expressed genes (DEGs; MR vs. M group) in the calves from pre- and post-weaning periods, respectively. The DEGs related to xenobiotic and lipid metabolism and those related to energy metabolism, immune function, and mineral metabolism were up- and downregulated, respectively, during the pre-weaning period; during the post-weaning period, the DEGs related to osteoclast differentiation and metabolic pathways showed difference. In this study, compared with M group, MR group had the same growth performance during the overall experimental period; however, MR affected the hepatic metabolism, immune, and antioxidant function of calves. These observations can facilitate future studies on milk replacers.

Interleukin-17A Inhibitor Secukinumab Treatment in HIV-Positive Psoriasis Patient: A Case Report.

Psoriasis is an immune-mediated chronic inflammatory dermatosis influenced by hereditary and environmental factors. Human immunodeficiency virus (HIV) infection affects the immune system and exacerbates psoriatic lesions. We report the case of a 33-year-old male patient diagnosed with psoriasis vulgaris, psoriatic arthritis and HIV infection. Acitretin capsules, etanercept and high-active antiretroviral therapy (HAART) were effective. Two months after etanercept was discontinued, his condition worsened. After switching to secukinumab combined with HAART, the symptoms of psoriatic arthritis resolved rapidly after four weeks, with a Disease Activity Index for Psoriatic Arthritis score of 0. The time to achieve psoriasis area and severity index 40, 75, 90, and 100 were 2, 4, 8, and 29 weeks. The treatment was maintained for 1 year with no adverse reactions. Regarding the stable CD4+ T lymphocyte count and the viral load, administering anti-IL-17 monoclonal antibodies is an effective treatment option for psoriasis patients.

First Case of Subcutaneous Mycoses Caused by Dirkmeia churashimaensis and a Literature Review of Human Ustilaginales Infections.

Objective: Dirkmeia churashimaensis, belonging to Ustilaginales fungi, has never been reported as clinical pathogenic until very recently. In this study, we report an unusual subcutaneous infection with Dirkmeia churashimaensis and reviewed all human Ustilaginales infections. The aim is to better understand their epidemiology, infection type, risk factors, and the sensitivity to antifungal agents. Methods: An 80-year-old female farmer developed extensive plaques and nodules on her left arm within 2 years. Pathological and microbiological examinations identified a new pathological agent, Dirkmeia churashimaensis, as the cause of this infection. The patient was successfully cured by oral itraconazole. We reviewed a total of 31 cases of Ustilaginales cases, among of which only three were skin infections. Results: Local barrier damage (i.e., surgery, trauma, and basic dermatosis) and systemic immunodeficiency (i.e., preterm and low birthweight, Crohn's disease, malignant cancer, and chemotherapy) are risk factors for Ustilaginales infection. The D1/D2 and ITS regions are the frequently used loci for identifying the pathogens together with phenotype. Most patients could survive due to antifungal treatment, whereas seven patients died. Amphotericin B, posaconazole, itraconazole, and voriconazole showed good activity against these reported strains, whereas fluconazole, 5-flucytosine, and echinocandins usually showed low susceptibility. Itraconazole had good efficiency for subcutaneous infections. Conclusions: The present case study and literature review reveal that Ustilaginales can be opportunistic pathogenic normally in immunocompromised and barrier damage people. A proper identification of fungi can be crucial for clinical treatment, and more data of antifungal are needed for choice of medication against this kind of infections.

Magnetized Micropillar-Enabled Wearable Sensors for Touchless and Intelligent Information Communication.

The wearable sensors have recently attracted considerable attentions as communication interfaces through the information perception, decoding, and conveying process. However, it is still challenging to obtain a sensor that can convert detectable signals into multiple outputs for convenient, efficient, cryptic, and high-capacity information transmission. Herein, we present a capacitive sensor of magnetic field based on a tilted flexible micromagnet array (t-FMA) as the proposed interaction interface. With the bidirectional bending capability of t-FMA actuated by magnetic torque, the sensor can recognize both the magnitude and orientation of magnetic field in real time with non-overlapping capacitance signals. The optimized sensor exhibits the high sensitivity of over 1.3 T-1 and detection limit down to 1 mT with excellent durability. As a proof of concept, the sensor has been successfully demonstrated for convenient, efficient, and programmable interaction systems, e.g., touchless Morse code and Braille communication. The distinguishable recognition of the magnetic field orientation and magnitude further enables the sensor unit as a high-capacity transmitter for cryptic information interaction (e.g., encoded ID recognition) and multi-control instruction outputting. We believe that the proposed magnetic field sensor can open up a potential avenue for future applications including information communication, virtual reality device, and interactive robotics.

A study on fungal defensin against multidrug-resistant Clostridium perfringens and its treatment on infected poultry.

In the present study, we aimed to investigate the antibacterial activity and mechanisms of plectasin-derived peptide NZ2114 in vitro and its therapeutic effects in vivo on broilers challenged with Clostridium perfringens. In vitro assay showed that NZ2114 had potent (minimal inhibitory concentration, 0.91 µM) and rapid antibacterial activity (99.9% reduction within 2 h), and the dual antibacterial mechanisms (including interfering with the cell membrane and intracellular DNA) against C. perfringens CVCC 2030. In vivo study, NZ2114 tended to increase linearly and quadratically the average daily gain as NZ2114 level increased and was the highest at 20 mg/L. NZ2114 at 10 ~ 40 mg/L dramatically reduced jejunal lesion score. Besides, the levels of IL-6, TNF-α, and IL-1ß tended to downregulate linearly and quadratically as the NZ2114 level increased and were all the lowest at the dose of 20 mg/L. NZ2114 significantly upregulated those levels of IgA, IgG, IgM, and sIgA with a linear and quadratic dose effect, with the highest IgA, IgG, IgM, and sIgA at 20 mg/L. Finally, NZ2114 tended to linearly and quadratically increase the numerical value of crypt depth, with the lowest value at 40 mg/L. Lincomycin only dramatically reduced the jejunal lesion score and increased the numerical value of crypt depth. These results indicate that NZ2114 has the potential as a new alternative to antibiotics for the treatment of C. perfringens-induced necrotic enteritis infection.Key points• NZ2114 could kill C. perfringens by dual antibacterial mechanisms• Broiler necrotic enteritis model induced by C. perfringens was established• NZ2114 treatment could ameliorate C. perfringens-induced necrotic enteritis.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

Factors Associated With Condom Failure in a Longitudinal Cohort of Men Who Have Sex With Men and Transgender Women in Abuja and Lagos, Nigeria.

BACKGROUND: Effective condom use is a critical intervention to limit the spread of HIV and other sexually transmitted infections, particularly among individuals in high-risk networks who practice anal sex. We characterized condom failures in cisgender men who have sex with men and transgender women in Nigeria. SETTING: The TRUST/RV368 cohort provided condoms, compatible lubricants, and safer sex education to men who have sex with men and transgender women at community-engaged health centers in Abuja and Lagos, Nigeria. METHODS: Participants completed structured interview questions about condom usage and failure every 3-6 months. Robust Poisson regression models with generalized estimating equations were used to estimate relative risks and 95% confidence intervals for prespecified factors potentially associated with condom failure in the previous month. RESULTS: From September 2013 to September 2019, 2221 of 2737 participants (81.1%) reported condom use for anal sex with a male partner in the last month, and 305 (13.7%) reported condom failure during this time. Multivariate analyses demonstrated an increased risk of condom failure at postenrollment visits, as well as in participants who reported frequent Internet use, 2 or more casual sexual partners, and 2-4 main sexual partners. Those who cohabited with a woman had reduced risk. CONCLUSIONS: Condom failure was common in this population despite freely available condoms, compatible lubrication, and education. Increased risk of condom failure over time could reflect message fatigue a ceiling for effective condom use, or new uptake of condoms by inexperienced users.

HIV status disclosure by Nigerian men who have sex with men and transgender women living with HIV: a cross-sectional analysis at enrollment into an observational cohort.

BACKGROUND: Men who have sex with men (MSM) and transgender women (TGW) are disproportionately impacted by HIV and may face barriers to HIV status disclosure with negative ramifications for HIV prevention and care. We evaluated HIV status disclosure to sexual partners, HIV treatment outcomes, and stigma patterns of MSM and TGW in Abuja and Lagos, Nigeria. METHODS: Previously-diagnosed MSM and TGW living with HIV who enrolled in the TRUST/RV368 cohort from March 2013 to August 2018 were asked, "Have you told your (male/female) sexual partners (MSP/FSP) that you are living with HIV?" In separate analyses, robust Poisson regression models were used to estimate risk ratios (RRs) and 95% confidence intervals (95% CIs) for characteristics associated with HIV status disclosure to MSP and FSP. Self-reported stigma indicators were compared between groups. RESULTS: Of 493 participants living with HIV, 153 (31.0%) had disclosed their HIV status to some or all MSP since being diagnosed. Among 222 with FSP, 34 (15.3%) had disclosed to some or all FSP. Factors independently associated with disclosure to MSP included living in Lagos (RR 1.58 [95% CI 1.14-2.20]) and having viral load < 50 copies/mL (RR 1.67 [95% CI 1.24-2.25]). Disclosure to FSP was more common among participants who were working in entertainment industries (RR 6.25 [95% CI 1.06-36.84]) or as drivers/laborers (RR 6.66 [95% CI 1.10-40.36], as compared to unemployed) and also among those married/cohabiting (RR 3.95 [95% CI 1.97-7.91], as compared to single) and prescribed ART (RR 2.27 [95% CI 1.07-4.83]). No differences in self-reported stigma indicators were observed by disclosure status to MSP but disclosure to FSP was associated with a lower likelihood of ever having been assaulted (26.5% versus 45.2%, p = 0.042). CONCLUSIONS: HIV status disclosure to sexual partners was uncommon among Nigerian MSM and TGW living with HIV but was associated with improved HIV care outcomes. Disclosure was not associated with substantially increased experiences of stigma. Strategies to encourage HIV status disclosure may improve HIV management outcomes in these highly-marginalized populations with a high burden of HIV infection.

The Limiting Sequence and Appropriate Amino Acid Ratio of Lysine, Methionine, and Threonine for Seven- to Nine-Month-Old Holstein Heifers Fed Corn-Soybean M-Based Diet.

An "Amino acid (AA) partial deletion method" was used in this experiment to study the limiting sequences and appropriate ratio of lysine (Lys), methionine (Met), and threonine (Thr) in the diets of 7- to 9-month-old Holstein heifers. The experiment was conducted for three months with 72 Holstein heifers (age = 22 ± 0.5 weeks old; BW = 200 ± 9.0 kg; mean ± standard deviation). Following an initial two weeks adaptation period, heifers were allocated to one of four treatments: a theoretically balanced amino acid diet (positive control [PC]; 1.00% Lys, 0.33% Met, and 0.72% Thr), a 30% Lys deleted diet (partially deleted Lys [PD-Lys]; 0.66% Lys, 0.33% Met, and 0.72% Thr), a 30% Met deleted diet (partially deleted Met, [PD-Met]; 1.00% Lys, 0.22% Met, and 0.72% Thr), and a 30% Thr deleted diet (partially deleted Thr [PD-Thr]; 1.00% Lys, 0.33% Met, and 0.45% Thr). Experimental animals were fed a corn-soybean meal-based concentrate and alfalfa hay. In addition, the animals were provided with supplemental Lys, Met, and Thr (ruminal bypass). The results found no differences in the growth performance and nitrogen retention between PD-Thr treatment and PC treatment (p > 0.05). The average daily gain (p = 0.0013) and feed conversion efficiency (p = 0.0057) of eight- to ninr-month-old heifers were lower in both PD-Lys and PD-Met treatment than those in PC treatment. According to growth performance, Lys was the first limiting AA, followed by Met and Thr. Moreover, nine-month-old Holstein heifers in PD-Lys treatment and PD-Met treatment had higher levels of serum urea nitrogen (p = 0.0021), urea nitrogen (p = 0.0011) and total excreted N (p = 0.0324) than those in PC treatment, which showed that nitrogen retention significantly decreased (p = 0.0048) as dietary Lys and Met levels decreased. The limiting sequence based on nitrogen retention was the same as that based on growth performance. The appropriate ratio of Lys, Met, and Thr in the diet based on nitrogen retention was 100:32:57. In summary, the limiting sequence and appropriate amino acid ratio of Lys, Met, and Thr for seven- to nine-month-old Holstein heifers fed a corn-soybean meal-based diet were Lys > Met > Thr and 100:32:57, respectively.

Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study.

BACKGROUND: Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy. METHODS: For this prospective cohort study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy at 20 centres in nine countries. Patients were followed up for 10 years. We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinically meaningful mobility and upper limb milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to stand from supine of 5 s or longer and 10 s or longer, and loss of stand from supine, four-stair climb, ambulation, full overhead reach, hand-to-mouth function, and hand function. Risk of death was also assessed. This study is registered with ClinicalTrials.gov, number NCT00468832. FINDINGS: 440 patients were enrolled during two recruitment periods (2006-09 and 2012-16). Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated (log-rank p<0·0001). Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1-4·4 years and upper limb milestones by 2·8-8·0 years compared with treatment for less than 1 month. Deflazacort was associated with increased median age at loss of three milestones by 2·1-2·7 years in comparison with prednisone or prednisolone (log-rank p<0·012). 45 patients died during the 10-year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related causes in patients with known duration of glucocorticoids usage. 28 (9%) deaths occurred in 311 patients treated with glucocorticoids for 1 year or longer compared with 11 (19%) deaths in 58 patients with no history of glucocorticoid use (odds ratio 0·47, 95% CI 0·22-1·00; p=0·0501). INTERPRETATION: In patients with Duchenne muscular dystrophy, glucocorticoid treatment is associated with reduced risk of losing clinically meaningful mobility and upper limb disease progression milestones across the lifespan as well as reduced risk of death. FUNDING: US Department of Education/National Institute on Disability and Rehabilitation Research; US Department of Defense; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases; and Parent Project Muscular Dystrophy.

Pretreatment behavior and subsequent medication effects in childhood absence epilepsy.

OBJECTIVE: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE). METHODS: The Child Behavior Checklist (CBCL) was administered at baseline, week 16-20, and month 12 visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure. RESULTS: A total of 382 participants at baseline, 310 participants at the week 16-20 visit, and 168 participants at the month 12 visit had CBCL data. At baseline, 8% (95% confidence interval [CI] 6%-11%) of children with CAE had elevated total problems scores (mean 52.9 ± 10.91). At week 16-20, participants taking valproic acid had significantly higher total problems (51.7 [98.3% CI 48.6-54.7]), externalizing problems (51.4 [98.3% CI 48.5-54.3]), attention problems (57.8 [98.3% CI 55.6-60.0]), and attention-deficit/hyperactivity problems (55.8 [98.3% CI 54.1-57.6]) scores compared to participants taking ethosuximide (46.5 [98.3% CI 43.4-49.6]; 45.8 [98.3% CI 42.9-48.7]; 54.6 [98.3% CI 52.4-56.9]; 53.0 [98.3% CI 51.3-54.8]). Lack of seizure freedom and elevated week 16-20 Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month 12, participants taking valproic acid had significantly higher attention problems scores (57.9 [98.3% CI 55.6-60.3]) compared to participants taking ethosuximide (54.5 [95% CI 52.1-56.9]). CONCLUSIONS: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE. CLINICALTRIALSGOV IDENTIFIER: NCT00088452. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine.

Pretreatment seizure semiology in childhood absence epilepsy.

OBJECTIVE: To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. METHODS: For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit. RESULTS: Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern. CONCLUSIONS: Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome.