Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients.

The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.

Eruptive Xanthomas.

This case report describes numerous dome-shaped, firm, yellow papules that were present symmetrically on the back, shoulder, arm, thigh, and knees.

HDL-C, longitudinal change and risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: High-density lipoprotein cholesterol (HDL-C) concentration and variability are both important factors of cardiovascular disease (CVD) and mortality. We aimed to explore the associations of HDL-C and longitudinal change in HDL-C with risk of mortality. METHODS AND RESULTS: We recruited a total of 69,163 participants aged ≥40 years and had medical examination records of HDL-C during 2010-2014 from the Yinzhou District, Ningbo, China. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. We observed a non-linear association of HDL-C with risks of non-accidental and CVD mortality. Compared with the moderate concentration group (1.4-1.6 mmol/L), HDL-C <1 mmol/L was associated with a higher risk of non-accidental mortality (HR: 1.13 (95% CI: 1.01-1.27)) and both HDL-C <1 mmol/L and ≥2 mmol/L were associated with a higher risk of CVD mortality (HRs: 1.23 (95% CI: 1.01-1.50) and 1.37 (95% CI: 1.03-1.82), respectively). Compared with the stable group ([-0.1, +0.1 mmol/L]), a large decrease ([-0.5, -0.3 mmol/L]) and very large decrease (<-0.5 mmol/L) in HDL-C were associated with a higher risk of non-accidental mortality (HRs: 1.40 (95% CI: 1.21-1.63) and 1.78 (95% CI: 1.44-2.20), respectively). Similar results were observed for CVD mortality and cancer mortality. CONCLUSION: Extremely low or high HDL-C and a large decrease or very large decrease in HDL-C were associated with a higher risk of cause-specific mortality. Monitoring of HDL-C may have utility in identifying individuals at higher risk of mortality.

Low LDL-C levels are associated with risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data. METHODS: We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100-130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80-3.53), CVD (HR = 1.84, 95% CI: 1.28-2.61), ischemic stroke (HR = 2.29, 95% CI:1.32-3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57-7.85), and cancer (HR = 2.12, 95% CI: 1.04-4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1. CONCLUSIONS: Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.

Effect of COVID-19 on hospital visits in Ningbo, China: an interrupted time-series analysis.

OBJECTIVE: Unprecedented rigorous public health measures were implemented during the coronavirus disease 2019 (COVID-19) epidemic, but it is still unclear how the intervention influenced hospital visits for different types of diseases. We aimed to evaluate the impact of the intervention on hospital visits in Yinzhou District, Ningbo, Zhejiang province, China. METHODS: We conducted an interrupted time-series analysis from 1 January 2017 to 6 September 2020 based on the Yinzhou Health Information System in Ningbo, Zhejiang province. The beginning of the intervention was on 23 January 2020, and thus, there were 160 weeks before the intervention and 32 weeks after the implementation of the intervention. Level changes between expected and observed hospital visits in the post-intervention period were estimated using quasi-Poisson regression models. RESULTS: Compared with the expected level, there was an estimated decrease of -22.60% (95% confidence interval (CI): -27.53%, -17.36%) in the observed total hospital visits following the intervention. Observed hospital visits for diseases of the respiratory system were found to be decreased dramatically (-62.25%; 95% CI: -65.62%, -58.60%). However, observed hospital visits for certain diseases were estimated to be increased, including diseases of the nervous system (+11.17%; 95% CI: +3.21%, +19.74%); diseases of pregnancy, childbirth and the puerperium (+27.01%; 95% CI: +17.89%, +36.85%); certain conditions originating in the perinatal period (+45.05%; 95% CI: +30.24%, +61.56%); and congenital malformation deformations and chromosomal abnormalities (+35.50%; 95% CI: +21.24%, +51.45%). CONCLUSIONS: Our findings provided scientific evidence that cause-specific hospital visits evolve differently following the intervention during the COVID-19 epidemic.

The Great Imitator: Atypical Cutaneous Manifestations of Primary Syphilitic Chancre.

Objective To analyze the reasons of misdiagnosis of primary syphilitic chancre and strengthen the understanding of atypical features of this disease. Methods A case series of twenty-seven challenging primary syphilis patients who were not immediately recognized as chancre was included in our study. The clinical data including the patients' age, sex, skin lesions, HIV status, syphilis serologic test results, treatment, and follow-up results were collected. Hematoxylin-eosin and immunohistochemistry staining of skin biopsy sections were reviewed. Results Four female cases with extragenital chancres presenting as erythema or erosive skin lesions on the nipple were misdiagnosed as Paget's disease or eczema. The disorder of missed or misdiagnosed male cases manifested as syphilitic balanitis or multiple chancres on the penis root and adjacent pubis rather than coronal sulcus or frenum. Patients with nonreactive nontreponemal tests at initial presentation were also easily missed or misdiagnosed. Conclusion Primary syphilis presenting as multiple lesions rather than a single chancre, at atypical locations, or with a nonreactive nontreponemal test result, tends to be missed or misdiagnosed.

Effect of syphilis infection on HIV acquisition: a systematic review and meta-analysis.

OBJECTIVES: Co-infection of syphilis and HIV remains hard to manage and its morbidity shows a rising tendency. Syphilis has been associated with increased risk of HIV acquisition in high-risk groups, especially in men who have sex with men (MSM). This systematic review and meta-analysis estimates the effect of syphilis infection on subsequent HIV acquisition, and assesses its difference between MSM and other high-risk populations. METHODS: Five electronic databases were searched for literature published to 21 September 2019 without language restrictions. Longitudinal studies that enrolled key populations to compare the incidence of HIV with and without syphilis exposure were included. We used a random-effects model to estimate the effect of syphilis infection on HIV acquisition among high-risk populations, which include MSM, sex workers, serodiscordant couples, people who inject drugs and attendees of STD clinics. RESULTS: A total of 17 cohorts and 5 case-control studies involving 65 232 participants were included. HIV incidence showed a two-time increase after syphilis exposure, compared with a control group (relative risk (RR) 2.67 (95% CI 2.05 to 3.47); p<0.05 for prevalence; RR 3.21 (95% CI 2.26 to 4.57); p=0.419 for incidence). No significant differences were observed between MSM and other high-risk groups in syphilis infection prevalence (RR 2.60 (95% CI 1.78 to 3.80); p<0.05 vs RR, 2.98 (95% CI 2.15 to 4.14); p<0.05; ratio of relative risk 0.76 (95% CI 0.49 to 1.17)). CONCLUSIONS: Syphilis infection increases the risk of HIV acquisition in high-risk populations. There is no evidence to suggest MSM are at greater risk than other high-risk populations. Prompt diagnosis, timely treatment, preventive interventions against syphilis infection would be a worthwhile investment for reducing HIV incidence. Strategies to combat stigma and discrimination targeted at MSM are pragmatically needed.

Parabrachial nucleus circuit governs neuropathic pain-like behavior.

The lateral parabrachial nucleus (LPBN) is known to relay noxious information to the amygdala for processing affective responses. However, it is unclear whether the LPBN actively processes neuropathic pain characterized by persistent hyperalgesia with aversive emotional responses. Here we report that neuropathic pain-like hypersensitivity induced by common peroneal nerve (CPN) ligation increases nociceptive stimulation-induced responses in glutamatergic LPBN neurons. Optogenetic activation of GABAergic LPBN neurons does not affect basal nociception, but alleviates neuropathic pain-like behavior. Optogenetic activation of glutamatergic or inhibition of GABAergic LPBN neurons induces neuropathic pain-like behavior in naïve mice. Inhibition of glutamatergic LPBN neurons alleviates both basal nociception and neuropathic pain-like hypersensitivity. Repetitive pharmacogenetic activation of glutamatergic or GABAergic LPBN neurons respectively mimics or prevents the development of CPN ligation-induced neuropathic pain-like hypersensitivity. These findings indicate that a delicate balance between excitatory and inhibitory LPBN neuronal activity governs the development and maintenance of neuropathic pain.

Impact of Individual and Combined Lifestyle Factors on Mortality in China: A Cohort Study.

INTRODUCTION: Although numerous studies have suggested that lifestyle-related factors are associated with chronic diseases and preventable deaths, limited evidence is available for the Chinese population. METHODS: This study established a prospective cohort of >360,000 residents on the basis of the Yinzhou Health Information System in China during 2004-2017 and calculated the combined effects of lifestyle-related factors, including BMI, smoking, alcohol consumption, and physical activity, using a points system. A Cox regression model estimated the combined effects of lifestyle-related factors on total mortality, and a competing risk model estimated the combined effects on cancer and cardiovascular disease mortality. All data analyses were conducted in 2018‒2019. RESULTS: During 3,755,879 person-years of follow-up, 11,791 deaths were identified, including 4,983 from cancer and 3,143 from cardiovascular disease. Having a standard BMI, never smoking, never drinking, and engaging in physical activity more than 4 times per week had protective effects on total mortality. Overall, the risk of total and cause-specific mortality increased with the increment of risk score. Compared with subjects in the lowest quartile, the risk of total and cause-specific mortality peaked among individuals in the fourth quartile (total mortality: hazard ratio=1.87, 95% CI=1.77, 1.98; cancer mortality: hazard ratio=2.05, 95% CI=1.87, 2.25; cardiovascular disease mortality: hazard ratio=1.51, 95% CI=1.35, 1.68). Sensitivity analyses excluding individuals with follow-up <3 years did not materially change the results. CONCLUSIONS: The combined effects of lifestyle-related factors, including BMI, smoking, alcohol drinking, and physical activity, are associated with total, cancer, and cardiovascular disease mortality among the Chinese population.

Regression-based normative data for social health scale for the elderly (short version) in eastern China.

BACKGROUNDS: Social Health Scale for the Elderly short version (SHSE-S) is a psychometrically sound instrument that comprehensively assesses the social health status of older adults in China. The aim of the present study was to establish continuous normative data of SHSE-S. METHODS: We conducted a multicenter cross-sectional study among 31 communities in eastern China. Older adults aged 60 years and above were invited to participate in the study. Each participant was interviewed in-person to finish a structured questionnaire. The SHES-S score was calculated and standardized for each participant. We split the sample into generation and validation datasets and compared the distribution of SHSE-S score between two datasets. Multivariable linear regression was used to assess the SHSE-S score and demographic variables. Regression-based norms were built using a four-step process. RESULTS: A total of 6089 participants (51.2% females) aged 60 years old and above (mean age = 71.3, SD = 8.0) were enrolled as the normative sample. No significant difference was found between the distribution of SHSE-S standardized score in the generation (N = 2392) and validation (N = 3697) datasets. Multivariable linear regression showed that females, higher education levels were positive indicators while aging, living alone, divorced or never married, multimorbidity were negative factors. The regression-based norm which taking demographic factors into account was established and a user-friendly worksheet was also provided to facilitate the scoring and norming of the SHSE-S. CONCLUSIONS: The population-based regression norm of SHSE-S can be a useful tool for assessing the social health status of the Chinese elderly population.

Association between visit-to-visit variability of HbA1c and cognitive decline: a pooled analysis of two prospective population-based cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate the association between visit-to-visit variability in HbA1c and cognitive function decline in the elderly population. METHODS: We performed a pooled analysis of two prospective population-based cohorts (the Health Retirement Study [HRS] and the English Longitudinal Study of Ageing [ELSA]). Cognitive function, including memory and executive function, were assessed at baseline and every 2 years, while HbA1c levels were assessed at baseline and every 4 years. Visit-to-visit variability (VVV) in HbA1c was calculated using the CV, SD and variation independent of the mean (VIM) during the follow-up period. Linear mixed models were used to evaluate the association between HbA1c variability and cognitive function decline with adjustment for demographics, mean HbA1c, education, smoking, alcohol consumption, BMI, baseline hypertension, baseline diabetes status and HDL-cholesterol. RESULTS: The study enrolled 6237 participants (58.23% women, mean age 63.38 ± 8.62 years) with at least three measurements of HbA1c. The median follow-up duration was 10.56 ± 1.86 years. In the overall sample, compared with the lowest quartile of HbA1c variability, participants in the highest quartile of HbA1c variability had a significantly worse memory decline rate (-0.094 SD/year, 95% CI -0.185, -0.003) and executive function decline rate (-0.083 SD/year, 95% CI -0.125, -0.041), irrespective of mean HbA1c values over time. Among individuals without diabetes, each 1-SD increment in HbA1c CV was associated with a significantly higher rate of memory z score decline (-0.029, 95% CI -0.052, -0.005) and executive function z score decline (-0.049, 95% CI -0.079, -0.018) in the fully adjusted model. CONCLUSIONS/INTERPRETATION: We observed a significant association between long-term HbA1c variability and cognitive decline among the non-diabetic population in this study. The effect of maintaining steady glucose control on the rate of cognitive decline merits further investigation.

Association between social health status and depressive symptoms among community-dwelling elderly adults in Zhejiang Province, China.

OBJECTIVE: Mental disorders of the elderly population in China deserve attention. Social health is significantly associated with depression. This study aimed to evaluate the rate of depressive symptoms and to test the relationships between social health and depressive symptoms among a large sample of community-dwelling elderly adults. METHODS: We conducted a cross-sectional study among community-dwelling adults aged 60 years or above in Zhejiang Province, China. Face-to-face interviews were used to complete a structured questionnaire for all participants. We used the Social Health Scale for the Elderly (SHSE) to evaluate social health status and used the short form of the Geriatric Depression Scale to evaluate depressive symptoms. Multivariate logistic regression was used to evaluate the association between social health status and depressive symptoms. RESULTS: Of the total of 3757 participants included, 1887 (50.23%) were female, and the mean±standard deviation (SD) age was (70.0±8.3) years. The rate of depressive symptoms was 25.92%. The social health score was higher in non-depressed participants than in depressed participants (raw score 50.7 vs. 48.3, P<0.001). Participants with "moderate" or "good" social health had a significantly lower risk of depressive symptoms than those with "poor" social health (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.46-0.66 for moderate social health; OR=0.45, 95% CI: 0.35-0.60 for good social health). The association between social health and depressive symptoms was consistent across several subgroups. CONCLUSIONS: Social health is significantly inversely associated with depressive symptoms. The SHSE may serve as an efficient screener to identify those elderly adults with social health deficits, but systematic assessment to guide intervention merits further investigation.

Intra-individual variability of total cholesterol is associated with cardiovascular disease mortality: A cohort study.

BACKGROUND AND AIMS: The relationship between serum total cholesterol (TC) and mortality remains inconsistent. Additionally, intra-individual variability of cholesterol has been of increasing interest as a new indicator for health outcomes. We aimed to examine the association between TC and its variability and risk of mortality. METHODS AND RESULTS: We performed a retrospective cohort study with 122,645 individuals aged over 40 years in Ningbo, China. The intra-individual variability was calculated using four metrics including standard deviation, coefficient variation, variation independent of mean and average successive variability. Hazard ratios and 95% confidence intervals were estimated for the associations of baseline and variability in TC with risk of mortality by Cox proportional hazards regression models. During 591,585.3 person-years of follow-up, 4563 deaths (including 1365 from cardiovascular disease, 788 from stroke and 1514 from cancer) occurred. A U-shaped association was observed for baseline TC level and risk of total, cardiovascular and cancer mortality, with lowest mortality at 5.46 mmol/L, 5.04 mmol/L and 5.51 mmol/L, respectively. As compared with subjects with TC variability in the lowest quartile, individuals in the highest quartile had 21% higher risk of all-cause mortality (HR = 1.21, 95% CI: 1.05 to 1.40), and 41% higher risk of CVD mortality (HR = 1.41, 95%CI: 1.10 to 1.81). CONCLUSION: Both too low and too high baseline TC level were associated with higher risk of total, cardiovascular disease and cancer mortality. Variability of TC could be a risk factor of total and CVD mortality, independent of mean TC level. Future studies are needed to confirm these findings.

Ultrafast Exciton Hopping Observed in Bare Semiconducting Carbon Nanotube Thin Films with Two-Dimensional White-Light Spectroscopy.

We observe ultrafast energy transfer between bare carbon nanotubes in a thin film using two-dimensional (2D) white-light spectroscopy. Using aqueous two-phase separation, semiconducting carbon nanotubes are purified from their metallic counterparts and condensed into a 10 nm thin film with no residual surfactant. Cross peak intensities put the time scale for energy transfer at <60 fs, and 2D anisotropy measurements determine that energy transfer is most efficient between parallel nanotubes, thus favoring directional energy flow. Lifetimes are about 300 fs. Thus, these results are in sharp contrast to thin films prepared from nanotubes that are wrapped by polymers, which exhibit picosecond energy transfer and randomize the direction of energy flow. Ultrafast energy flow and directionality are exciting properties for next-generation photovoltaics, photodetectors, and other devices.

Energy transfer pathways in semiconducting carbon nanotubes revealed using two-dimensional white-light spectroscopy.

Thin film networks of highly purified semiconducting carbon nanotubes (CNTs) are being explored for energy harvesting and optoelectronic devices because of their exceptional transport and optical properties. The nanotubes in these films are in close contact, which permits energy to flow through the films, although the pathways and mechanisms for energy transfer are largely unknown. Here we use a broadband continuum to collect femtosecond two-dimensional white-light spectra. The continuum spans 500 to 1,300 nm, resolving energy transfer between all combinations of bandgap (S1) and higher (S2) transitions. We observe ultrafast energy redistribution on the S2 states, non-Förster energy transfer on the S1 states and anti-correlated energy levels. The two-dimensional spectra reveal competing pathways for energy transfer, with S2 excitons taking routes depending on the bandgap separation, whereas S1 excitons relax independent of the bandgap. These observations provide a basis for understanding and ultimately controlling the photophysics of energy flow in CNT-based devices.

Evolution, kinetics, energetics, and environmental factors of graphene degradation on silicon dioxide.

Recent studies have qualitatively shown that the oxidative stability of monolayer graphene integrated on oxides is relatively poor. Here, the evolution, kinetics, and energetics of this degradation are quantified. Specifically, the deterioration of graphene on SiO2 is studied in grain interiors and at grain boundaries in ambient air, dry air and nitrogen between 473 and 673 K, using spatially and temporally resolved in situ Raman spectroscopy in addition to electron microscopy and charge transport measurements. The grain interiors of chemical vapor deposition (CVD) grown graphene monolayers oxidize with an activation energy of 0.63 ± 0.05 eV in ambient air (15,000 ppm H2O). This energy increases to 1.85 ± 0.17 eV in dry air, whereas degradation is immeasurable in nitrogen and for multilayers even in ambient air. Gasification at grain boundaries in a CVD monolayer proceeds at a rate of (1.08 ± 0.02) × 10(-1) nm s(-1) at 673 K with an activation energy E(A) = 1.14 ± 0.10 eV in ambient air. The more facile degradation of the monolayer grain interiors in ambient air indicates the role of the substrate in decreasing the stability against oxidation. The electrical transport mobility decays with an activation rate similar to that of grain interiors. These results can be used to quantitatively predict graphene oxidation and gasification on SiO2 in different environments and temperatures.

Polyfluorene-sorted, carbon nanotube array field-effect transistors with increased current density and high on/off ratio.

Challenges in eliminating metallic from semiconducting single-walled carbon nanotubes (SWCNTs) and in controlling their alignment have limited the development of high-performance SWCNT-based field-effect transistors (FETs). We recently pioneered an approach for depositing aligned arrays of ultra-high-purity semiconducting SWCNTs, isolated using polyfluorene derivatives, called dose-controlled floating evaporative self-assembly. Here, we tailor FETs fabricated from these arrays to achieve on-conductance (G(on)) per width and an on-off ratio (G(on)/G(off)) of 261 µS/µm and 2 × 10(5), respectively, for a channel length (L(ch)) of 240 nm and 116 µS/µm and 1 × 10(6), respectively, for an L(ch) of 1 µm. We demonstrate 1400× greater G(on)/G(off) than SWCNT FETs fabricated by other methods, at comparable G(on) per width of ∼250 µS/µm and 30-100× greater G(on) per width at comparable G(on)/G(off) of 10(5)-10(7). The average G(on) per tube reaches 5.7 ± 1.4 µS at a packing density of 35 tubes/µm for L(ch) in the range 160-240 nm, limited by contact resistance. These gains highlight the promise of using ultra-high-purity semiconducting SWCNTs with controlled alignment for next-generation semiconductor electronics.