The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy

IntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer.MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review.ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001).ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.

Detection of COVID-19 in smartphone-based breathing recordings: A pre-screening deep learning tool

This study was sought to investigate the feasibility of using smartphone-based breathing sounds within a deep learning framework to discriminate between COVID-19, including asymptomatic, and healthy subjects. A total of 480 breathing sounds (240 shallow and 240 deep) were obtained from a publicly available database named Coswara. These sounds were recorded by 120 COVID-19 and 120 healthy subjects via a smartphone microphone through a website application. A deep learning framework was proposed herein that relies on hand-crafted features extracted from the original recordings and from the mel-frequency cepstral coefficients (MFCC) as well as deep-activated features learned by a combination of convolutional neural network and bi-directional long short-term memory units (CNN-BiLSTM). The statistical analysis of patient profiles has shown a significant difference (p-value: 0.041) for ischemic heart disease between COVID-19 and healthy subjects. The Analysis of the normal distribution of the combined MFCC values showed that COVID-19 subjects tended to have a distribution that is skewed more towards the right side of the zero mean (shallow: 0.59±1.74, deep: 0.65±4.35, p-value: <0.001). In addition, the proposed deep learning approach had an overall discrimination accuracy of 94.58% and 92.08% using shallow and deep recordings, respectively. Furthermore, it detected COVID-19 subjects successfully with a maximum sensitivity of 94.21%, specificity of 94.96%, and area under the receiver operating characteristic (AUROC) curves of 0.90. Among the 120 COVID-19 participants, asymptomatic subjects (18 subjects) were successfully detected with 100.00% accuracy using shallow recordings and 88.89% using deep recordings. This study paves the way towards utilizing smartphone-based breathing sounds for the purpose of COVID-19 detection. The observations found in this study were promising to suggest deep learning and smartphone-based breathing sounds as an effective pre-screening tool for COVID-19 alongside the current reverse-transcription polymerase chain reaction (RT-PCR) assay. It can be considered as an early, rapid, easily distributed, time-efficient, and almost no-cost diagnosis technique complying with social distancing restrictions during COVID-19 pandemic.

Full title: COVID-19 disease progression according to initial symptoms. A telemedicine cohort study.

Objective COVID-19 progression to severe or critical illness may be related to initial clinical presentation. Main objective was to identify initial symptoms related to highest risk of disease progression, in mild or moderate suspected or confirmed COVID-19 patients or in asymptomatic subjects in contact with a recently diagnosed patient. Design and methods Historic cohort study of Mexican patients with suspected or confirmed mild or moderate COVID-19 or asymptomatic subjects in recent contact with positive patients. They sought medical attention in Centro Medico ABC or claimed for remote attention, and daily telemedicine follow up until recovery or illness progression, from April 17th to October 08th 2020. Data excerpted for analysis were sex, age, body mass index, comorbidities, and signs, and symptoms presented in first day of disease manifestations and during follow up. We used logistic regression to identify initial symptoms associated with progression disease and through a conjunctive consolidation analysis a symptom index was created. Results 120 of 1635 patients (7.2%) had clinical progression disease. By logistic regression we found as initial symptoms related to progression: fever OR 3 (1.89-4.77, p<0.001), cough OR 2.34 (1.56-3.52, p<0.001), myalgias or arthralgias OR 1.69 (1.09-2.63, p=0.018), and fatigue OR 1.65 (1.08-2.53, p=0.019). Conjunctive consolidation was processed with the previous symptoms, and a 3 groups score resulted C-19PAIS Index: 1) Fever with cough or fever with fatigue, with a probability of progression disease of 29% (31/106 patients), 2) Fever or cough or fatigue or cough with fatigue, 10.7% (66/615 patients) and 3) No fever, no cough, no fatigue, 2% (23/914). Conclusions Initial symptoms predict clinical progression in COVID-19 patients.

DXA-Derived Indices in the Characterisation of Sarcopenia

Sarcopenia is linked with increased risk of falls, osteoporosis and mortality. No consensus exists about a gold standard “dual-energy X-ray absorptiometry (DXA) index for muscle mass determination” in sarcopenia diagnosis. Thus, many indices exist, but data on sarcopenia diagnosis agreement are scarce. Regarding sarcopenia diagnosis reliability, the impact of influencing factors on sarcopenia prevalence, diagnosis agreement and reliability are almost completely missing. For nine DXA-derived muscle mass indices, we aimed to evaluate sarcopenia prevalence, diagnosis agreement and diagnosis reliability, and investigate the effects of underlying parameters, presence or type of adjustment and cut-off values on all three outcomes. The indices were analysed in the BioPersMed cohort (58 ± 9 years), including 1022 asymptomatic subjects at moderate cardiovascular risk. DXA data from 792 baselines and 684 follow-up measurements (for diagnosis agreement and reliability determination) were available. Depending on the index and cut-off values, sarcopenia prevalence varied from 0.6 to 36.3%. Height-adjusted parameters, independent of underlying parameters, showed a relatively high level of diagnosis agreement, whereas unadjusted and adjusted indices showed low diagnosis agreement. The adjustment type defines which individuals are recognised as sarcopenic in terms of BMI and sex. The investigated indices showed comparable diagnosis reliability in follow-up examinations

Innovative Approaches to Assess Intermediate Cardiovascular Risk Subjects: A Review From Clinical to Metabolomics Strategies

Current risk stratification strategies for coronary artery disease (CAD) have low predictive value in asymptomatic subjects classified as intermediate cardiovascular risk. This is relevant because not all coronary events occur in individuals with traditional multiple risk factors. Most importantly, the first manifestation of the disease may be either sudden cardiac death or acute coronary syndrome, after rupture and thrombosis of an unstable non-obstructive atherosclerotic plaque, which was previously silent. The inaccurate stratification using the current models may ultimately subject the individual to excessive or insufficient preventive therapies. A breakthrough in the comprehension of the molecular mechanisms governing the atherosclerosis pathology has driven many researches toward the necessity for a better risk stratification. In this Review, we discuss how metabolomics screening integrated with traditional risk assessments becomes a powerful approach to improve non-invasive CAD subclinical diagnostics. In addition, this Review highlights the findings of metabolomics studies performed by two relevant analytical platforms in current use–mass spectrometry (MS) hyphenated to separation techniques and nuclear magnetic resonance spectroscopy (NMR) –and evaluates critically the challenges for further clinical implementation of metabolomics data. We also discuss the modern understanding of the pathophysiology of atherosclerosis and the limitations of traditional analytical methods. Our aim is to show how discriminant metabolites originated from metabolomics approaches may become promising candidate molecules to aid intermediate risk patient stratification for cardiovascular events and how these tools could successfully meet the demands to translate cardiovascular metabolic biomarkers into clinical settings.

Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects

CD4+ CCR6+ T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6+ T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are no existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin, Candida albicans, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.

Assessment of Cognitive Symptoms in Brain Bank-Registered Control Subjects: Feasibility and Utility of a Telephone-Based Screening

Background: For neuroscience research, the study of brain tissue of neurologically unimpaired subjects is crucial to interpret findings in neurodegenerative diseases. Sub-optimal neurological follow-up and the presence of neuropathological lesions in supposedly asymptomatic subjects casts doubt as to whether these subjects present an undetected underlying neurodegenerative disease or are resilient to neurodegeneration. Objective: We aimed to assess whether the control donors registered in the Neurological Tissue Bank-Hospital Clínic-IDIBAPS (NTB-HCI) are still free of cognitive symptoms at follow-up and to evaluate the feasibility and utility of a telephone-based screening. Methods: All control subjects older than 65 years registered at the NTB-HCI database were selected for the study. After a structured telephone interview, those subjects already diagnosed with a neurological disease were excluded. Then, a cognitive screening was performed, including the telephone version of the Mini-Mental State Examination (t-MMSE) and the eight-item interview (AD-8) to the subject and to one informant. Results: In total, 73.8% of the registered donors collaborated in the study. Only 21.4% had at least one of the three cognitive screening tools impaired, and 2.7% had a profile highly suggestive of cognitive impairment. AD-8i correlated moderately with t-MMSE. Conclusion: Telephone-based neurologic screening in control donors is feasible and was within the normal range in most of the subjects in our cohort. Albeit, the involvement of neurologists and periodic neurological screenings are desirable in a control subjects brain donor program, AD8-i could be used to screen the control’s neurological status in the absence of accurate clinical data at the time of the death.

Sero-prevalence of anti-Leptospira antibodies and associated risk factors in rural Rwanda: A cross-sectional study

Background Leptospirosis is a zoonotic disease transmitted through the urine of wild and domestic animals, and is responsible for over 50,000 deaths each year. In East Africa, prevalence varies greatly, from as low as 7% in Kenya to 37% in Somalia. Transmission epidemiology also varies around the world, with research in Nicaragua showing that rodents are the most clinically important, while studies in Egypt and Chile suggest that dogs may play a more important role. There are no published studies of leptospirosis in Rwanda. Methods & findings We performed a cross-sectional survey of asymptomatic adults recruited from five occupational categories. Serum samples were tested using ELISA and Microscopic Agglutination Test (MAT). We found that 40.1% (151/377) of asymptomatic adults had been exposed to Leptospira spp. Almost 36.3% of positive subjects reported contact with rats (137/377) which represent 90.7% among positive leptospira serology compared with 48.2% of negative subjects (182/377) which represent 80.5% among negative leptospira serology (OR 2.37, CI 1.25–4.49) and 1.7 fold on prevalence ratio and 2.37 of odd ratio. Furthermore, being a crop farmer was significantly associated with leptospirosis (OR 2.06, CI 1.29–3.28). We identified 6 asymptomatic subjects (1.6%) who met criteria for acute infection. Conclusions This study demonstrates a high prevalence of leptospiral antibodies infection among asymptomatic adults in rural Rwanda, particularly relative to neighboring countries. Although positive subjects were more likely to report rat contact, we found no independent association between rats and leptospirosis infection. Nonetheless, exposure was high among crop farmers, which is supportive of the hypothesis that rats together with domestic livestock might contribute to the transmission. Further studies are needed to understand infecting Leptospira servers and elucidate the transmission epidemiology in Rwanda and identify means of host transmitters.

Proteinuria is independently associated with carotid atherosclerosis: a multicentric study

Background and aims Atherosclerosis is a vital cause of cardiovascular diseases. The correlation between proteinuria and atherosclerosis, however, has not been confirmed. This study aimed to assess whether there is a relationship between proteinuria and atherosclerosis. Methods From January 2016 to September 2020, 13,545 asymptomatic subjects from four centres in southern China underwent dipstick proteinuria testing and carotid atherosclerosis examination. Data on demography and past medical history were collected, and laboratory examinations were performed. The samples consisted of 7405 subjects (4875 males and 2530 females), excluding subjects failing to reach predefined standards and containing enough information. A multivariate logistic regression model was used to adjust the influence of traditional risk factors for atherosclerosis on the results. Results Compared with proteinuria-negative subjects, proteinuria-positive subjects had a higher prevalence rate of carotid atherosclerosis. The differences were statistically significant (22.6% vs. 26.7%, χ2 = 10.03, p = 0.002). After adjusting for common risk factors for atherosclerosis, age, sex, BMI, blood lipids, blood pressure, renal function, hypertensive disease, diabetes mellitus and hyperlipidaemia, proteinuria was an independent risk factor for atherosclerosis (OR = 1.191, 95% CI 1.015–1.398, p = 0.033). The Hosmer–Lemeshow test was used to test the risk prediction model of atherosclerosis, and the results showed that the model has high goodness of fit and strong independent variable prediction ability. Conclusions Proteinuria is independently related to carotid atherosclerosis. With the increase in proteinuria level, the risk of carotid atherosclerotic plaque increases. For patients with positive proteinuria, further examination of atherosclerosis should not be ignored.