Impact of antiretroviral therapy (ART) duration on ART adherence among men who have sex with men (MSM) living with HIV in Jinan of China.

BACKGROUND: Consistent and complete adherence is considered an essential requirement for patients on antiretroviral therapy (ART). This study aimed to evaluate the impact of ART duration on ART adherence, identify the trend of complete adherence, and compare the factors associated with ART adherence between short-term and long-term ART group among men who have sex with men (MSM) living with HIV in Jinan of China. METHODS: MSM living with HIV aged 18 or above and currently on ART were recruited from October to December 2020 using convenience sampling. Univariate and multivariable logistic regressions were used to evaluate the impact of ART duration on adherence and compare factors associated with ART adherence between subgroups. The Mann-Kendall test was used to identify the trend of complete adherence. RESULTS: A total of 585 participants were included in analysis, consisting of 352 on short-term ART (ART initiation ≤ 3 years) and 233 on long-term ART (ART initiation > 3 years). Significant difference of complete ART adherence between short-term and long-term ART group was detected (79.8% vs. 69.1%, P = 0.003). Multivariable analysis showed that men with longer ART duration were less likely to report complete ART adherence (AOR = 0.88, 95% CI 0.81-0.95). A descending trend of complete adherence was identified (Z = 1.787, P = 0.037). Alcohol use and lack of medication reminders were barriers to complete adherence for both of the subgroups. CONCLUSIONS: Sustained efforts to encourage maintaining adherence for a lifetime are necessary, especially for those on long-term ART. Future interventions should be tailored to subgroups with different ART duration and individuals with specific characteristics.

A Model to Study NMDA Receptors in Early Nervous System Development.

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play critical roles in neuronal development and nervous system function. Here, we developed a model to study NMDARs in early development in zebrafish, by generating CRISPR-mediated lesions in the NMDAR genes, grin1a and grin1b, which encode the obligatory GluN1 subunits. While receptors containing grin1a or grin1b show high Ca2+ permeability, like their mammalian counterpart, grin1a is expressed earlier and more broadly in development than grin1b Both grin1a-/- and grin1b-/- zebrafish are viable. Unlike in rodents, where the grin1 knockout is embryonic lethal, grin1 double-mutant fish (grin1a-/-; grin1b-/-), which lack all NMDAR-mediated synaptic transmission, survive until ∼10 d dpf (days post fertilization), providing a unique opportunity to explore NMDAR function during development and in generating behaviors. Many behavioral defects in the grin1 double-mutant larvae, including abnormal evoked responses to light and acoustic stimuli, prey-capture deficits, and a failure to habituate to acoustic stimuli, are replicated by short-term treatment with the NMDAR antagonist MK-801, suggesting that they arise from acute effects of compromised NMDAR-mediated transmission. Other defects, however, such as periods of hyperactivity and alterations in place preference, are not phenocopied by MK-801, suggesting a developmental origin. Together, we have developed a unique model to study NMDARs in the developing vertebrate nervous system.SIGNIFICANCE STATEMENT Rapid communication between cells in the nervous system depends on ion channels that are directly activated by chemical neurotransmitters. One such ligand-gated ion channel, the NMDAR, impacts nearly all forms of nervous system function. It has been challenging, however, to study the prolonged absence of NMDARs in vertebrates, and hence their role in nervous system development, due to experimental limitations. Here, we demonstrate that zebrafish lacking all NMDAR transmission are viable through early development and are capable of a wide range of stereotypic behaviors. As such, this zebrafish model provides a unique opportunity to study the role of NMDAR in the development of the early vertebrate nervous system.

Structure-Based Virtual Screening and Biological Evaluation of Peptide Inhibitors for Polo-Box Domain.

The polo-box domain of polo-like kinase 1 (PLK1-PBD) is proved to have crucial roles in cell proliferation. Designing PLK1-PBD inhibitors is challenging due to their poor cellular penetration. In this study, we applied a virtual screening workflow based on a combination of structure-based pharmacophore modeling with molecular docking screening techniques, so as to discover potent PLK1-PBD peptide inhibitors. The resulting 9 virtual screening peptides showed affinities for PLK1-PBD in a competitive binding assay. In particular, peptide 5 exhibited an approximately 100-fold increase in inhibitory activity (IC50 = 70 nM), as compared with the control poloboxtide. Moreover, cell cycle experiments indicated that peptide 5 effectively inhibited the expression of p-Cdc25C and cell cycle regulatory proteins by affecting the function of PLK1-PBD, thereby inducing mitotic arrest at the G2/M phase. Overall, peptide 5 can serve as a potent lead for further investigation as PLK1-PBD inhibitors.

Protocol to analyze 3D neurodegenerative vacuoles in Drosophila melanogaster.

Vacuole formation is a key hallmark of age-dependent neurodegeneration in the Drosophila brain. Here, we present a protocol to analyze 3D neurodegenerative vacuoles in the whole-mount Drosophila melanogaster brain. We describe steps for whole-brain dissection, staining, 3D imaging, and z-stack image processing using Fiji ImageJ. We then detail procedures for annotating and 3D-reconstructing neurodegenerative vacuoles with WEBKNOSSOS and Python, and performing statistical analysis in Python. This protocol enables measurement of parameters such as the number and volume of each vacuole. For complete details on the use and execution of this protocol, please refer to Elguero et al.1.

Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling.

In nervous system development, disease and injury, neurons undergo programmed cell death, leaving behind cell corpses that are removed by phagocytic glia. Altered glial phagocytosis has been implicated in several neurological diseases including Alzheimer's disease, Parkinson's disease, and traumatic brain injury. To untangle the links between glial phagocytosis and neurodegeneration, we investigated Drosophila mutants lacking the phagocytic receptor Draper. Loss of Draper leads to persistent neuronal cell corpses and age-dependent neurodegeneration. Here we investigate whether the phagocytic defects observed in draper mutants lead to chronic increased immune activation that promotes neurodegeneration. A major immune response in Drosophila is the activation of two NFκB signaling pathways that produce antimicrobial peptides, primarily in the fat body. We found that the antimicrobial peptide Attacin-A is highly upregulated in the fat body of aged draper mutants and that inhibition of the Immune deficiency (Imd) pathway in the glia and fat body of draper mutants led to reduced neurodegeneration, indicating that immune activation promotes neurodegeneration in draper mutants. Taken together, these findings indicate that phagocytic defects lead to neurodegeneration via increased immune signaling, both systemically and locally in the brain.

Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling.

In nervous system development, disease, and injury, neurons undergo programmed cell death, leaving behind cell corpses that are removed by phagocytic glia. Altered glial phagocytosis has been implicated in several neurological diseases including Alzheimer's disease. To untangle the links between glial phagocytosis and neurodegeneration, we investigated Drosophila mutants lacking the phagocytic receptor Draper. Loss of Draper leads to persistent neuronal cell corpses and age-dependent neurodegeneration. Here we investigate whether the phagocytic defects observed in draper mutants lead to chronic increased immune activation that promotes neurodegeneration. We found that the antimicrobial peptide Attacin-A is highly upregulated in the fat body of aged draper mutants and that the inhibition of the Immune deficiency (Imd) pathway in the glia and fat body of draper mutants led to reduced neurodegeneration. Taken together, these findings indicate that phagocytic defects lead to neurodegeneration via increased immune signaling, both systemically and locally in the brain.

Psychological impact of coronavirus disease (2019) (COVID-19) epidemic on medical staff in different posts in China: A multicenter study.

OBJECTIVE: An outbreak of coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and poses a big challenge to medical staff and general public. The aim is to investigate psychological impact of COVID-19 epidemic on medical staff in different working posts in China, and to explore the correlation between psychological disorder and the exposure to COVID-19. METHODS: A multicenter WeChat-based online survey was conducted among medical staff in China between 26 February and 3 March 2020. Medical staff deployed to Hubei province from other provinces and medical staffs in different posts outside Hubei were selected to represent diverse exposure intensities to the threat of COVID-19. Anxiety, depression, sleep quality, stress and resilience were evaluated using scales including GAD-7, PHQ-9, PSQI, PSS-14, and CD-RISC-10. Latent class analysis was performed to identify potential staff requiring psychological support. RESULTS: A total of 274 respondents were included, who serving at 4 posts as follows, staff backing Hubei province, isolation wards outside Hubei, fever clinic and infectious disease department, and other departments outside Hubei. The total scores of anxiety, depression, sleep quality and stress were statistically different among groups, meanwhile an increasing tendency of anxiety, depression and sleep quality scores with increasing risk of exposure to COVID-19 was found (p < 0.05). Subsequent post-hoc analysis indicated that the staff backing Hubei had higher scores of anxiety, depression, sleep quality and perceived stress (adjusted p < 0.05). The combined prevalence of anxiety, depression and insomnia of staff backing Hubei reached as high as 38%. Four-class latent class analysis showed 3 categories of population (69.4%) may need psychological support. CONCLUSIONS: High prevalence of anxiety, depression and insomnia exist in medical staff related to COVID-19. The higher the probability and intensity of exposure to COVID-19 patients, the greater the risk that medical staff will suffer from mental disorders, suggesting continuous and proper psychiatric intervention are needed.

[Epidemiological study of high risk human papillomavirus infection in 25 to 54 years old married women in Beijing.].

OBJECTIVE: To investigate high risk human papillomavirus (HR-HPV) prevalence among married women in Beijing and to study the high risk factors. METHODS: During March 2007 to September 2008, a total of 6185 married women sampled from 137 communities in 12 districts were screened by HR-HPV DNA test and cytological test. The interview was carried out with unified questionnaires. The database was set up and twice entered in EpiData 3.0. After checked up, the data were analyzed in SPSS 15.0. RESULTS: (1) The HR-HPV infection rate was 9.89%. The HR-HPV infection rate of the city zone, the suburb and the exurb were 9.34%, 10.51% and 9.51% (P > 0.05). The HR-HPV infection rate of the native and the outlander were 9.53%, 11.30% (P < 0.05). (2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups, which was the highest (11.21%) in 30 to 34 age group; then the rate was descended as the age raising, the rate of 50 to 54 age group was the lowest (7.78%). (3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month, possessing more than 1 sexual partner of her husband, outlander and high levels of education. (4) The prevalence of cervical intraepithelial neoplasia (CIN) in HR-HPV positive group was significantly higher than that in HR-HPV negative group (29.76% vs 3.32%, P < 0.01). CONCLUSIONS: (1) The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution. (2) The high risk population which should strengthen screening was the married bearing-age women with high level of family income, outlander, high levels of education and her husband possessing more than 1 sexual partner. (3) HR-HPV infection is the main risk factor for CIN and cervical cancer, while does not provide a causal relationship with them. The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.