Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

O treinamento da musculatura inspiratória é ineficiente em pacientes graves submetidos à ventilação mecânica

PURPOSE: Invasive mechanical ventilation is associated with complications, and its abbreviation is desirable. The imbalance between increased workload, decreased inspiratory muscle strength and endurance is an important determinant of ventilator dependence. Low endurance may be present due to respiratory muscle atrophy, critical illness, or steroid use. Specific inspiratory muscle training may increase or preserve endurance. The objective of the study was to test the hypothesis that inspiratory muscle training from the beginning of mechanical ventilation would abbreviate the weaning duration and decrease reintubation rate. As a secondary objective, we described the evolution of inspiratory muscle strength with and without inspiratory muscle training. METHODS: Prospective, randomized clinical trial in an adult clinical-surgical intensive care unit. Twelve patients trained the inspiratory muscles twice a day, and 13 patients did not (control). Training was performed adjusting the sensitivity of the ventilator based on the maximal inspiratory pressure. Patients underwent daily surveillance of the maximal inspiratory pressure. RESULTS: The weaning duration (31 ± 22 hr, control and 23 ± 11 hr, training group; P = .24) and reintubation rate (5 control and 3 training group; P = .39) were not statistically different. The maximal inspiratory pressure of the control group showed a trend toward a modest increase. In contrast, the training group showed a small decrease (P = .34). CONCLUSIONS: In acute critically ill patients, inspiratory muscle training from the beginning of mechanical ventilation neither abbreviated the weaning duration, nor decreased the reintubation rate. Inspiratory muscle strength tended to stay constant, along the mechanical ventilation, with or without this specific inspiratory muscle training.OBJETIVO: A ventilação mecânica invasiva é associada a complicações, portanto sua abreviação é desejada. O desbalanço entre o aumento da carga sobre os músculos inspiratórios, a diminuição da força e a resistência muscular é determinante na dependência da ventilação. A baixa resistência muscular pode ser causada por atrofia muscular, pela doença grave ou pelo uso de corticoesteróides. O treinamento da musculatura inspiratória pode aumentar ou preservar a resistência. O objetivo principal do estudo foi testar a hipótese que o treinamento da musculatura inspiratória desde o início da ventilação iria abreviar o desmame da ventilação e diminuir a taxa de reintubação. Como objetivo secundário descrevemos a evolução da pressão inspiratória máxima com e sem treinamento da musculatura inspiratória. MÉTODOS: Estudo prospectivo e aleatorizado em unidade de tratamento intensivo Clínico-Cirúrgica. Doze pacientes treinaram a musculatura inspiratória duas vezes ao dia e treze não treinaram (controle). O treinamento foi realizado ajustando a sensibilidade do ventilador, baseando-se na pressão inspiratória máxima. Os pacientes tiveram sua pressão inspiratória máxima verificada diariamente. RESULTADOS: A duração do desmame (31 ± 22 controle e 23 ± 11 horas grupo treinamento; p=0.24) não foi estatisticamente diferente. A pressão inspiratória máxima do grupo controle teve leve tendência ao aumento, enquanto o grupo treinamento teve leve tendência à diminuição. CONCLUSÃO: Em pacientes graves, o treinamento da musculatura inspiratória desde o início da ventilação mecânica não abreviou o desmame, nem diminuiu a reintubação. A pressão inspiratória máxima tendeu a manter-se constante ao longo da ventilação mecânica, com ou sem o treinamento inspiratório aplicado

Model-Driven Chatbot Development

Esta versión del artículo ha sido aceptada para su publicación, después de la revisión por pares (cuando corresponda) y está sujeta a los términos de uso de AM de Springer Nature, pero no es la Versión de Registro y no refleja mejoras posteriores a la aceptación, ni ninguna corrección. La versión del registro está disponible en línea en: https://doi.org/10.1007/978-3-030-62522-1_15Chatbots are software services accessed via conversation in natural language. They are increasingly used to help in all kinds of procedures like booking flights, querying visa information or assigning tasks to developers. They can be embedded in webs and social networks, and be used from mobile devices without installing dedicated apps. While many frameworks and platforms have emerged for their development, identifying the most appropriate one for building a particular chatbot requires a high investment of time. Moreover, some of them are closed – resulting in customer lock-in – or require deep technical knowledge. To tackle these issues, we propose a model-driven engineering approach to chatbot development. It comprises a neutral meta-model and a domainspecific language (DSL) for chatbot description; code generators and parsers for several chatbot platforms; and a platform recommender. Our approach supports forward and reverse engineering, and model-based analysis. We demonstrate its feasibility presenting a prototype tool and an evaluation based on migrating third party Dialogflow bots to RasaWork funded by the Spanish Ministry of Science (RTI2018095255-B-I00) and the R&D programme of Madrid (P2018/TCS-4314

TREATMENT OF CHRONIC NONRESPONSIVE PATIENTS WITH A NONFORCE TECHNIQUE

ABSTRACT Objective: To investigate how chronic pain patients respond to treatment with Bio-Energetic Synchronization Technique (BEST). Methods: Twenty-four adult patients with chronic pain-related conditions that failed to respond to previous chiropractic care were recruited. Subjects were given baseline assessments including pain Visual Analog Scale, Profile of Mood States, and the Global Well-being Scale. The 5-week treatment program consisted of an initial 3-day session with BEST therapy, followed by a single treatment session for the following 4 weeks. Patients were reevaluated at the end of the 3-day session and at weekly intervals throughout the course of care. At the end of week 5, patients were asked to assess their degree of satisfaction with the treatment. Results: Patients had 3 main categories of pain: headache (n = 8, mean duration 15 years), neck pain (n = 18, mean duration 11 years), and low back pain (n = 17, mean duration 10 years). Global Well-Being Scale scores significantly improved at the end of the 3-day session ( P N .05) but not subsequently. The Profile of Mood States reflected favorable changes in all areas. Significant improvement in vigor ( P N .003) and fatigue ( P N .006) existed at the end of 5 weeks ( P b .01). The reduction of pain was significant at both the end of the 3-day session and at follow-up ( P = .0003). A statistically significant decrease in depression ( P = .004) was noted after 3 days, and a substantial although not significant ( P = .06) decrease in depression existed at the end of 1 month. Eighty-two percent reported satisfaction with BEST (47% reported being bextremely satisfiedQ and 35% bsatisfiedQ). Conclusion: In this group of chronic pain patients, improvement in patient outcome measures was seen after 5 weeks of therapy. These patients also responded with a high degree of satisfaction with care. (J Manipulative Physiol Ther 2005;28:259-264

Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses

<p>Abstract</p> <p>Background</p> <p>Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries.</p> <p>Methods</p> <p>The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without <it>a priori </it>surface classifications, were applied to our data.</p> <p>Results</p> <p>The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that <it>a priori </it>caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h²= 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns.</p> <p>Conclusions</p> <p>This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.</p

BARCRAWL and BARTAB: software tools for the design and implementation of barcoded primers for highly multiplexed DNA sequencing

<p>Abstract</p> <p>Background</p> <p>Advances in automated DNA sequencing technology have greatly increased the scale of genomic and metagenomic studies. An increasingly popular means of increasing project throughput is by multiplexing samples during the sequencing phase. This can be achieved by covalently linking short, unique "barcode" DNA segments to genomic DNA samples, for instance through incorporation of barcode sequences in PCR primers. Although several strategies have been described to insure that barcode sequences are unique and robust to sequencing errors, these have not been integrated into the overall primer design process, thus potentially introducing bias into PCR amplification and/or sequencing steps.</p> <p>Results</p> <p><it>Barcrawl </it>is a software program that facilitates the design of barcoded primers, for multiplexed high-throughput sequencing. The program <it>bartab </it>can be used to deconvolute DNA sequence datasets produced by the use of multiple barcoded primers. This paper describes the functions implemented by <it>barcrawl </it>and <it>bartab </it>and presents a proof-of-concept case study of both programs in which barcoded rRNA primers were designed and validated by high-throughput sequencing.</p> <p>Conclusion</p> <p><it>Barcrawl </it>and <it>bartab </it>can benefit researchers who are engaged in metagenomic projects that employ multiplexed specimen processing. The source code is released under the GNU general public license and can be accessed at <url>http://www.phyloware.com</url>.</p

Understanding Urban Demand for Wild Meat in Vietnam: Implications for Conservation Actions

Vietnam is a significant consumer of wildlife, particularly wild meat, in urban restaurant settings. To meet this demand, poaching of wildlife is widespread, threatening regional and international biodiversity. Previous interventions to tackle illegal and potentially unsustainable consumption of wild meat in Vietnam have generally focused on limiting supply. While critical, they have been impeded by a lack of resources, the presence of increasingly organised criminal networks and corruption. Attention is, therefore, turning to the consumer, but a paucity of research investigating consumer demand for wild meat will impede the creation of effective consumer-centred interventions. Here we used a mixed-methods research approach comprising a hypothetical choice modelling survey and qualitative interviews to explore the drivers of wild meat consumption and consumer preferences among residents of Ho Chi Minh City, Vietnam. Our findings indicate that demand for wild meat is heterogeneous and highly context specific. Wild-sourced, rare, and expensive wild meat-types are eaten by those situated towards the top of the societal hierarchy to convey wealth and status and are commonly consumed in lucrative business contexts. Cheaper, legal and farmed substitutes for wild-sourced meats are also consumed, but typically in more casual consumption or social drinking settings. We explore the implications of our results for current conservation interventions in Vietnam that attempt to tackle illegal and potentially unsustainable trade in and consumption of wild meat and detail how our research informs future consumer-centric conservation actions

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality

A survey of training and practice patterns of massage therapists in two US states

BACKGROUND: Despite the growing popularity of therapeutic massage in the US, little is known about the training or practice characteristics of massage therapists. The objective of this study was to describe these characteristics. METHODS: As part of a study of random samples of complementary and alternative medicine (CAM) practitioners, we interviewed 226 massage therapists licensed in Connecticut and Washington state by telephone in 1998 and 1999 (85% of those contacted) and then asked a sample of them to record information on 20 consecutive visits to their practices (total of 2005 consecutive visits). RESULTS: Most massage therapists were women (85%), white (95%), and had completed some continuing education training (79% in Connecticut and 52% in Washington). They treated a limited number of conditions, most commonly musculoskeletal (59% and 63%) (especially back, neck, and shoulder problems), wellness care (20% and 19%), and psychological complaints (9% and 6%) (especially anxiety and depression). Practitioners commonly used one or more assessment techniques (67% and 74%) and gave a massage emphasizing Swedish (81% and 77%), deep tissue (63% and 65%), and trigger/pressure point techniques (52% and 46%). Self-care recommendations, including increasing water intake, body awareness, and specific forms of movement, were made as part of more than 80% of visits. Although most patients self-referred to massage, more than one-quarter were receiving concomitant care for the same problem from a physician. Massage therapists rarely communicated with these physicians. CONCLUSION: This study provides new information about licensed massage therapists that should be useful to physicians and other healthcare providers interested in learning about massage therapy in order to advise their patients about this popular CAM therapy

Change and Aging Senescence as an adaptation

Understanding why we age is a long-lived open problem in evolutionary biology. Aging is prejudicial to the individual and evolutionary forces should prevent it, but many species show signs of senescence as individuals age. Here, I will propose a model for aging based on assumptions that are compatible with evolutionary theory: i) competition is between individuals; ii) there is some degree of locality, so quite often competition will between parents and their progeny; iii) optimal conditions are not stationary, mutation helps each species to keep competitive. When conditions change, a senescent species can drive immortal competitors to extinction. This counter-intuitive result arises from the pruning caused by the death of elder individuals. When there is change and mutation, each generation is slightly better adapted to the new conditions, but some older individuals survive by random chance. Senescence can eliminate those from the genetic pool. Even though individual selection forces always win over group selection ones, it is not exactly the individual that is selected, but its lineage. While senescence damages the individuals and has an evolutionary cost, it has a benefit of its own. It allows each lineage to adapt faster to changing conditions. We age because the world changes.Comment: 19 pages, 4 figure