Objective To investigate whether placebo effects can experimentally be separated into the response to three components-assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship-and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components.

The CRISPR-Cas12a RNA-guided complexes have tremendous potential for nucleic acid detection but are limited to the picomolar detection limit without an amplification step. Here, we develop a platform with engineered crRNAs and optimized conditions that enabled us to detect various clinically relevant nucleic acid targets with higher sensitivity, achieving a limit of detection in the femtomolar range without any target pre-amplification step. By extending the 3′- or 5′-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discover a self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA and with significant improvement in specificity for target recognition. Particularly, the 7-mer DNA extension to crRNA is determined to be universal and spacer-independent for enhancing the sensitivity and specificity of LbCas12a-mediated nucleic acid detection. We perform a detailed characterization of our engineered ENHANCE system with various crRNA modifications, target types, reporters, and divalent cations. With isothermal amplification of SARS-CoV-2 RNA using RT-LAMP, the modified crRNAs are incorporated in a paper-based lateral flow assay that can detect the target with up to 23-fold higher sensitivity within 40–60 min.

ObjectivesWe assessed health-related quality of life (HRQOL), its associated factors, and examined measurement properties of the EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) in HIV/AIDS patients.MethodsA cross-sectional multi-site survey was conducted in 1016 patients (age: 35.4 ± 7.0 years; 63.8% male) in three epicenters of Vietnam. Internal consistency reliability, convergent validity, and discriminative validity of the EQ-5D-5L and a visual analogue scale (VAS) were evaluated. Tobit censored regression models were used to identify predictors of HRQOL in HIV/AIDS patients.ResultsThe mean EQ-5D-5L single index and VAS were 0.65 (95% Confidence Interval (CI) = 0.63; 0.67) and 70.3 (95% CI = 69.2; 71.5). Cronbach’s alpha of five dimensions was 0.85. EQ-5D-5L has a good convergent validity with VAS (0.73). It discriminated patients at different HIV/AIDS stages, duration of ART, and CD4 cell count. Predictors of poorer HRQOL included being female, lower education level, unemployment, alcohol and drug use, CD4<200 cells/mL, and advanced HIV/AIDS stages.ConclusionThe EQ-5D-5L has good measurement properties in HIV/AIDS patients and holds potentials for monitoring ART outcomes. Integration of HRQOL measurement using EQ-5D-5L in HIV/AIDS clinical practice could be helpful for economic evaluation of HIV/AIDS interventions.

There are consistent observations that depletion of intracellular glycogen stores in muscle is associated with reduced muscle performance (Bergstr om et al. 1967;Galbo et al. 1979;Voellestad et al. 1988;Fitts, 1994;Chin & Allen, 1997), but the cellular mechanisms responsible for the glycogen depletion-related impairment of muscle function are not understood (Fitts 1994;Chin & Allen, 1997). So far, all studies on the role of glycogen in muscle have involved the depletion of the muscle glycogen pool by inducing a state of muscle fatigue. Therefore, from these studies it is not possible to draw unequivocal conclusions concerning the nature of the relationship between glycogen content and muscle contractility because in addition to glycogen depletion, many other factors, known to affect excitation-contraction (E-C) coupling (Stephenson et al. 1998), would have been altered in the myoplasm of the fatigued muscle fibres. Further advances can be made if the relationship between glycogen and muscle contractility is investigated in single fibres containing different concentrations of glycogen under conditions where the ionic composition of the myoplasmic environment is kept constant and similar to that in a rested muscle. The mechanically skinned single muscle fibre preparation is particularly well suited for such a task

Health-related quality of life (HRQL) is a good indicator to monitor and evaluate healthcare services for adults with HIV/AIDS. This study described HRQL of adults with HIV and its determinants, and compared it with HRQL for the general population. A cross-sectional study with a national multistage sampling of households with and without HIV-positive people was conducted in 2008. Six provinces were purposively selected to represent areas of the country and progressions of HIV epidemics. Households were sampled with probability-proportional-to-size, following the selection of rural and urban districts. A total of 820 HIV-positive and HIV-negative adults (mean age: 32.5; 38.7% female) were interviewed. Among 400 HIV-positive people, 52.3% had a history of injecting drugs, and 56.3% were at AIDS stage and receiving antiretroviral treatment (ART). HRQL was measured using the EuroQOL five-dimension questionnaire (EQ-5D). Multiple regression models were purposefully constructed to examine the determinants of HRQL. The EQ-5D index and visual analog scale (VAS) score in less advanced HIV people (0.90, 69.3) and AIDS patients (0.88, 65.2) were significantly lower than those of the general population (0.96, 81.6) (p<0.001). The frequency of reported problems across EQ-5D dimensions in the HIV population (2.4-30.9%) was significantly higher than in the general population (0.7-12.1%). Compared to ART patients, those at earlier HIV stages reported having problems at similar proportions across four HRQL dimensions, except pain/discomfort, where ART patients had a significantly higher proportion. Injecting drug users taking ART perceived lower HRQL score than non-injecting drug users. Multiple regression determined that joblessness (p<0.01) and inaccessibility to health services (p<0.05) were associated with lower HRQL. In addition, involvements in self-help groups significantly improved HRQL among HIV-positive participants (p<0.05). The findings highlight the need to improve the health service referral system and enhance psychological and social supports for patients in early stages of HIV infection in Vietnam.