Adolescents living with HIV are disproportionally affected by depression, which worsens antiretroviral therapy adherence, increases viral load, and doubles the risk of mortality. Because most ...adolescents living with HIV live in low- and middle-income countries, few receive depression treatment due to a lack of mental health services and specialists in low-resource settings. Chatbot technology, used increasingly in health service delivery, is a promising approach for delivering low-intensity depression care to adolescents living with HIV in resource-constrained settings.
The goal of this study is to develop and pilot-test for the feasibility and acceptability of a prototype, optimized conversational agent (chatbot) to provide mental health education, self-help skills, and care linkage for adolescents living with HIV.
Chatbot development comprises 3 phases conducted over 2 years. In the first phase (year 1), formative research will be conducted to understand the views, opinions, and preferences of up to 48 youths aged 10-19 years (6 focus groups of up to 8 adolescents living with HIV per group), their caregivers (5 in-depth interviews), and HIV program personnel (5 in-depth interviews) regarding depression among adolescents living with HIV. We will also investigate the perceived acceptability of a mental health chatbot, including barriers and facilitators to accessing and using a chatbot for depression care by adolescents living with HIV. In the second phase (year 1), we will iteratively program a chatbot using the SmartBot360 software with successive versions (0.1, 0.2, and 0.3), meeting regularly with a Youth Advisory Board comprised of adolescents living with HIV who will guide and inform the chatbot development and content to arrive at a prototype version (version 1.0) for pilot-testing. In the third phase (year 2), we will pilot-test the prototype chatbot among 50 adolescents living with HIV naïve to its development. Participants will interact with the chatbot for up to 2 weeks, and data will be collected on the acceptability of the chatbot-delivered depression education and self-help strategies, depression knowledge changes, and intention to seek care linkage.
The study was awarded in April 2022, received institutional review board approval in November 2022, received funding in December 2022, and commenced recruitment in March 2023. By the completion of study phases 1 and 2, we expect our chatbot to incorporate key needs and preferences gathered from focus groups and interviews to develop the chatbot. By the completion of study phase 3, we will have assessed the feasibility and acceptability of the prototype chatbot. Study phase 3 began in April 2024. Final results are expected by January 2025 and published thereafter.
The study will produce a prototype mental health chatbot developed with and for adolescents living with HIV that will be ready for efficacy testing in a subsequent, larger study.
DERR1-10.2196/55559.
Abstract Objective We analyzed the interferon-α (IFN-α), IFN-β, and proinflammatory responses induced by Toll-like receptor (TLR) ligands in peripheral blood mononuclear cells (PBMCs) from obese ...subjects and their association with suppressor of cytokine signaling-1 (SOCS1) and SOCS3 expression. Methods The IFN responses were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay in PBMCs stimulated with TLR-3 and TLR-7 ligands from 30 non-obese (body mass index ≤25 kg/m2 ) and 30 obese (body mass index ≥30 kg/m2 ) volunteers. The mRNA expression of nuclear factor-κB, SOCS1, and SOCS3 also was evaluated by qRT-PCR. Proinflammatory cytokine responses were measured by enzyme-linked immunosorbent assay. Results Obese subjects showed a decreased ability to produce IFN-α and IFN-β in response to TLR ligands; this response was associated with increased basal levels of SOCS3 but not SOCS1. However, after stimulation, the expression of SOCS3 and SOCS1 mRNA was significantly lower in PBMCs from obese compared with non-obese subjects. The PBMCs from obese subjects also showed higher basal levels of interleukin-6 and a decreased response of proinflammatory cytokines interleukin-6 and interleukin-1β after stimulation with the TLR-3 ligand compared with PBMCs from non-obese participants. Conclusion These data suggest that obesity is related to impaired IFN-α and IFN-β responses and increased SOCS3 basal mRNA expression and that a signaling pathway by TLR-3 may be involved. These results could explain, at least in part, the inadequate response of obese people against viral infections, such as influenza.
We aimed to evaluate whether traditional risk scores short-term, 'psoriasis-modified' (multiplied by 1.5) and lifetime were able to capture high cardiovascular disease (CVD) risk as defined by the ...presence of atherosclerotic plaques in coronary, femoral, or carotid arteries in psoriasis.
We used two prospectives obseravational cohorts. European cohort: femoral and carotid atherosclerotic plaques were evaluated by ultrasound in 73 psoriasis patients. Lifetime CVD risk (LTCVR) was evaluated with QRISK-LT; short-term CVD risk was evaluated with SCORE and psoriasis-modified SCORE. American cohort: 165 patients underwent coronary computed tomography angiography to assess presence of coronary plaques. LTCVR was evaluated with atherosclerotic cardiovascular disease (ASCVD-LT) lifetime; short-term CVD risk was evaluated with ASCVD and psoriasis-modified ASCVD. European cohort: subclinical atherosclerosis was present in 51% of patients. QRISK-LT identified 64% of patients with atherosclerosis missing a high proportion (35%) with atheroma plaque (P < 0.05). The percentage of patients with atherosclerosis identified by QRISK-LT was significantly higher than those detected by SCORE (0%) and modified SCORE (10%). American cohort: subclinical atherosclerosis was present in 54% of patients. ASCVD-LT captured 54% of patients with coronary plaques missing a high proportion (46%) with coronary plaque (P < 0.05). The percentage of patients with atheroma plaques detected with ASCVD and modified ASCVD were only 20% and 45%, respectively.
Application of lifetime, short-term and 'psoriasis-modified' risk scores did not accurately capture psoriasis patients at high CVD risk.
Adaptive immunity is crucial in controlling
infection in the intestinal mucosa, and some dietary lipids may improve mucosal immune function. The aim of this study was to evaluate conjugated linoleic ...acid (CLA) on the Th17/Treg response and secretory IgA production in a model of giardiasis infection.
C3H/HeN male mice were infected with 5×10
trophozoites (GS/M-83-H7, ATCC collection). Mice were assigned randomly to experimental and control groups. CLA was administered to the experimental group and phosphate-buffered saline (PBS) was given to the control group. Parasite load kinetics was determined. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate IgA and cytokines. Nuclear transcription factors and cytokines were measured by RT-qPCR, and histology of small bowel cells was evaluated.
CLA administration reduced the parasite load (
0.05) and increased early
-specific secretory IgA production. CLA also increased the expression of interleukin-10, transforming growth factor (TGF)-β, and inducible nitric oxide synthase (iNOS) (
0.05), while infection elevated the expression of Foxp3, with a peak at 40 days post-infection (
0.05). There were no pathological changes in the colonic mucosa due to infection or treatment. Thus, CLA stimulated mucosal immunity and enhanced the humoral response against
, not only for early infection control but also to promote regulatory cytokine production at 40 dpi, restoring the intestinal balance after parasite elimination.
Our findings reveal novel anti-parasitic effects through the immune-modulatory activity of CLA against the intestinal parasite
.
Objectives: Semicircular lipoatrophy (SL) is an emerging occupational pathology. Its etiology is poorly understood. We intend to establish the probable risk factors and estimate the relative risk. ...Methods: A case-control study was performed. Our company had 55 diagnosed cases. As controls, we used the 3 closest healthy coworkers to each case. We calculated the chi square, odds ratio and logistic regression for different exposures, during the 3 years from September 2007 to August 2010. Results: There was 100% participation for the cases and 70.9% for the controls (ratio 1:2.1 case-control). The only risk variables found were female gender (p<0.02) and exposure to leaning on the edge of a table (p<0.01). In addition, a breakdown by sex objectifiles a much stronger association with leaning on the edge of a table in women (p<0.01) than men (p 0.67). Conclusions: Female gender and leaning on the edge of a table (repeated microtrauma), especially in women, are risk factors for development of SL. Other variables seem to be confounding factors associated with female gender. There were no SL cases showing statistically significant relations with history of cancer or autoimmune diseases. There was also no significance with regard to wearing jeans. There is therefore a new risk for office staff in addition to the more traditional disorders (musculoskeletal, ocular, and psychosocial). Further studies are necessary to evaluate what we consider an underdiagnosed condition, since there is a large percentage of people that are potentially exposed and we found very little information in the literature on the matter.
Chronic kidney disease (CKD) patients are at high-risk for severe Covid-19. The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of ...SARS-CoV-2 vaccines in CKD patients. Safety and immediate humoral response results are reported here.
Four cohorts of patients were included: kidney transplant (KT) recipients, haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analyzed.
1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (p<0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated to KT (OR 20.56, p = 0.001) and to BNT162b2 vaccine (OR 6.03, p = 0.023).
The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%; suggesting that KT patients require persistent isolation measures and booster doses of a Covid-19 vaccine. Potential differences between Covid-19 vaccines should be explored in prospective controlled studies.
Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The ...aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D 25(OH) vitamin D levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p=0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p=0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p=0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p=0.65). In subanalysis, patients with GA+AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p=0.03). No increased risk was observed in GT+TT genotypes of CYP27B1 rs10877012 (p=0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA+AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.
Merging tumor targeting and molecular-genetic imaging into an integrated platform is limited by lack of strategies to enable systemic yet ligand-directed delivery and imaging of specific transgenes. ...Many eukaryotic viruses serve for transgene delivery but require elimination of native tropism for mammalian cells; in contrast, prokaryotic viruses can be adapted to bind to mammalian receptors but are otherwise poor vehicles. Here we introduce a system containing
cis-elements from adeno-associated virus (AAV) and single-stranded bacteriophage. Our AAV/phage (AAVP) prototype targets an integrin. We show that AAVP provides superior tumor transduction over phage and that incorporation of inverted terminal repeats is associated with improved fate of the delivered transgene. Moreover, we show that the temporal dynamics and spatial heterogeneity of gene expression mediated by targeted AAVP can be monitored by positron emission tomography. This new class of targeted hybrid viral particles will enable a wide range of applications in biology and medicine.
This paper provides a new methodological approach to analyse secular patterns of flooding (magnitude and frequency) from sedimentary evidence (palaeofloods), taking into account changes in channel ...geometry, and their links to historical environmental changes and the inherent social and demographic evolution within the catchment. A case study analysis was focused in Rambla de la Viuda (drainage area of 1500 km2) whose stream flow is related to extreme rainfalls. A 500 years sedimentary archive was reconstructed from eight stratigraphic profiles comprising continuous sequences of slackwater flood deposits interbedded with episodic colluvial and edaphic horizons. Discharge estimates associated to sedimentary flood evidences were obtained from one-dimensional hydraulic modelling. The stratigraphic units were sampled to characterise their geochemical and paleobotanical (phytoliths) contents. Palaeoflood chronology was obtained from radiocarbon and luminescence (OSL) dating, supported by documentary data (written historical documents). A high frequency and high magnitude palaeoflood period took place during the 15th-middle 16th century, which seem to correlate in time with general wetter conditions. Three short-term environment stability conditions (land use and climatic) also made possible the development of three paleosols. The lowest flood magnitude and discharges in the sedimentary record was found between the mid-17th to mid-18th centuries, under prevailing drier environmental conditions. Episodic high magnitude flooding took place at late 18th century, correlating in time with palaeovegetation and geochemical evidences of important changes on land use (deforestation and grazing). Poorer developed soils were found at upper stratigraphic sequences (19th century) characterised by thick units of colluvium deposits, usually culminating sequences of short-lived continuous slackwater flood units. Despite of the potential human influence (land-use) on soil hydrology, the long-term behaviour of high magnitude floods (>1000 m3 s-1) has been stationary over the last 500 years.
•Multidisciplinary approach in the study of hydrological extreme events: palaeohydrology analysis, historical archives, bioliths analysis.•Analysis of secular patterns of flooding (magnitude and frequency) from sedimentary evidence taking into account changes in channel geometry.•New data on hydroclimatic phases in Iberian Mediterranean basins since 15th century.•Provides an enlarged hydrological record to apply on dam safety analysis in the area.
Despite the clinical success of the programmed death ligand 1 (PD-L1) blocking therapy in cancer treatment, only a subset of patients exhibits durable responses, therefore further exploration of ...other immunotherapeutic alternatives are needed. This paper reported the development of the PKPD-L1Vac vaccine, a new protein vaccine candidate that uses aluminum phosphate as an adjuvant and as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal portion of the LpdA protein from N. meningitides (PKPD-L1). The PKPD-L1 antigen has different physical and biological characteristics than those found in the natural molecule and in others PD-L1 vaccine candidates. The quimeric protein has a reduced binding capacity to the PD-1 and CD80 receptors to decrease their pro-tumoral activity. Besides, the distinctive feature of the PKPD-L1 polypeptide to be structurally aggregated could be desirable for its immunogenic properties. PKPD-L1Vac elicited anti-PD-L1-specific IgG antibodies and T lymphocyte-mediated immunity in mice and non-human primates. The vaccine administration demonstrated antitumor activity on CT-26 and B16–F10 primary tumor models in mice. Moreover, the immunization with PKPD-L1Vac increased the tumor-infiltrating lymphocytes and decreased the proportion of CD3+CD8+PD1+high anergic T cells in CT-26 tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. In summary, the PKPD-L1Vac vaccine exhibits very promising preclinical results and deserves to move forward to a phase I clinical trial.
•PKPD-L1Vac uses as an antigen the extracellular domain of human PD-L1 fused to a portion of the LpdA protein from N. meningitides.•PKPD-L1 antigen has a reduced binding capacity to their receptors to decrease their potential pro-tumoral activity.•PKPD-L1Vac elicited anti-PDL1-specific IgG antibodies and T lymphocyte-mediated immunity in mice and non-human primates.•PKPD-L1Vac administration demonstrated antitumor activity on CT-26 and B16–F10 primary tumor models in mice.
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