Cooling and heating of the fluid in the cylindrical volume

Experimental studies of the non-stationary heat exchange in the system «environment I – body II» have been carried out. It is established that in the body II, which consists of the fluid and thin-walled metal envelope, the characteristic features of the regular thermal mode occur, i.e., cooling (heating) rate of the body II- m = const; heat transfer coefficient between the water (environment I) and body II is practically stable α1 = const; uneven temperatures distribution coefficient in the body II ψ = const. This new notion of the heat transfer regularities in the body II is planned to apply for further development of the experimental-calculation method for the forecasting of the heat exchange intensity in the compound fluid media with limited information regarding thermophysical and rheological properties.

Tablet Disintegration and Dispersion under In Vivo-like Hydrodynamic Conditions

Disintegration and dispersion are functional properties of tablets relevant for the desired API release. The standard disintegration test (SDT) described in different pharmacopoeias provides only limited information on these complex processes. It is considered not to be comparable to the biorelevant conditions due to the frequent occurrence of high hydrodynamic forces, among other reasons. In this study, 3D tomographic laser-induced fluorescence imaging (3D Tomo-LIF) is applied to analyse tablet disintegration and dispersion. Disintegration time (DT) and time-resolved particle size distribution in close proximity to the tablet are determined in a continuously operated flow channel, adjustable to very low fluid velocities. A case study on tablets of different porosity, which are composed of pharmaceutical polymers labelled with a fluorescent dye, a filler, and disintegrants, is presented to demonstrate the functionality and precision of the novel method. DT results from 3D Tomo-LIF are compared with results from the SDT, confirming the analytical limitations of the pharmacopoeial disintegration test. Results from the 3D Tomo-LIF method proved a strong impact of fluid velocity on disintegration and dispersion. Generally, shorter DTs were determined when cross-linked sodium carboxymethly cellulose (NaCMCXL) was used as disintegrant compared to polyvinyl polypyrrolidone (PVPP). Tablets containing Kollidon VA64 were found to disintegrate by surface erosion. The novel method provides an in-depth understanding of the functional behaviour of the tablet material, composition and structural properties under in vivo-like hydrodynamic forces regarding disintegration and the temporal progress of dispersion. We consider the 3D Tomo-LIF in vitro method to be of improved biorelevance in terms of hydrodynamic conditions in the human stomach.

Coronary Artery Disease and Cancer: Treatment and Prognosis Regarding Gender Differences

Cardiovascular disease and cancer remain the leading causes of hospitalization and mortality in high-income countries. Survival after myocardial infarction has improved but there is still a difference in clinical outcome, mortality, and developing heart failure to the disadvantage of women with myocardial infarction. Most major cardiology trials and registries have excluded patients with cancer. As a result, there is only very limited information on the effects of coronary artery disease in cancer patients. In particular, the outcomes in women with cancer and coronary artery disease and its management remain empiric. We reviewed studies of over 27 million patients with coronary artery disease and cancer. Our review focused on the most important types of cancer (breast, colon, lung, prostate) and hematological malignancies with particular attention to sex-specific differences in treatment and prognosis.

Local immune response of Canarian Majorera goats infected with Teladorsagia circumcincta

Background Due to increased anthelmintic resistance, alternative methods to drugs are necessary to control gastrointestinal nematodes (GINs). Some of the most promising alternatives are based on the immune response of the host, such as the selection of genetically resistant breeds or the use of vaccines against these parasites. Given the limited information available on the immune response against GINs in goats, this study investigated the local immune response of goat kids of an indigenous Canary Islands breed (Majorera breed) experimentally infected with Teladorsagia circumcincta, one of the most pathogenic and prevalent GIN species. Methods For this purpose, the relationship between different parasitological (number of mature and immature worms, worm length, and number of intrauterine eggs) and immunological parameters at the local level (related to both the humoral and cellular immune response) was analyzed at early (1 week post-infection [wpi]) and late (8 wpi) stages of infection. Results Primary infection of goat kids with T. circumcincta infective larvae (L3) generated a complex immune response that could be defined as Th2 type, characterized by increased infiltration in abomasal tissues of several effector cells as well as a progressive presence of specific antibodies against parasitic antigens in the gastric mucus. Cellular responses were evidenced from 1 wpi onward, showing an increase in antigen-presenting cells and various lymphocyte subsets in the gastric mucosa. Conclusions The complexity of the host response was evidenced by statistically significant changes in the number of all these subpopulations (MHCII+, CD4+, CD8+, γδ+, CD45R+, IgA+, and IgG+), as well as in the evolution of the relative cytokine gene expression. From a functional point of view, negative associations were observed between the number of most of the immune cells (CD4, IgA, IgG, and CD45R cells) and parameters that could be related to the fecundity of worms, a phenomenon that was especially evident when the number of IgG and CD45R cells or the specific IgA levels of the gastric mucus were compared with parasitological parameters such as the female worm length or fecal egg counts at 8 wpi. Graphical Abstract

Reduced and highly diverse peripheral HIV-1 reservoir in virally suppressed patients infected with non-B HIV-1 strains in Uganda

Background Our understanding of the peripheral human immunodeficiency virus type 1 (HIV-1) reservoir is strongly biased towards subtype B HIV-1 strains, with only limited information available from patients infected with non-B HIV-1 subtypes, which are the predominant viruses seen in low- and middle-income countries (LMIC) in Africa and Asia. Results In this study, blood samples were obtained from well-suppressed ART-experienced HIV-1 patients monitored in Uganda (n = 62) or the U.S. (n = 50), with plasma HIV-1 loads < 50 copies/ml and CD4+ T-cell counts > 300 cells/ml. The peripheral HIV-1 reservoir, i.e., cell-associated HIV-1 RNA and proviral DNA, was characterized using our novel deep sequencing-based EDITS assay. Ugandan patients were slightly younger (median age 43 vs 49 years) and had slightly lower CD4+ counts (508 vs 772 cells/ml) than U.S. individuals. All Ugandan patients were infected with non-B HIV-1 subtypes (31% A1, 64% D, or 5% C), while all U.S. individuals were infected with subtype B viruses. Unexpectedly, we observed a significantly larger peripheral inducible HIV-1 reservoir in U.S. patients compared to Ugandan individuals (48 vs. 11 cell equivalents/million cells, p < 0.0001). This divergence in reservoir size was verified measuring proviral DNA (206 vs. 88 cell equivalents/million cells, p < 0.0001). However, the peripheral HIV-1 reservoir was more diverse in Ugandan than in U.S. individuals (8.6 vs. 4.7 p-distance, p < 0.0001). Conclusions The smaller, but more diverse, peripheral HIV-1 reservoir in Ugandan patients might be associated with viral (e.g., non-B subtype with higher cytopathicity) and/or host (e.g., higher incidence of co-infections or co-morbidities leading to less clonal expansion) factors. This highlights the need to understand reservoir dynamics in diverse populations as part of ongoing efforts to find a functional cure for HIV-1 infection in LMICs.

A digital self-care intervention for Ugandan patients with heart failure and their clinicians: User-centred design and usability study

Background: The prevalence of heart failure (HF) is increasing in Uganda. Ugandan patients with HF report receiving limited information about their illness, disease management, or empowerment to engage in self-care behaviors. Interventions targeted at improving HF self-care have been shown to improve patient quality of life and to reduce hospitalizations in high-income countries. However, such interventions remain underutilized in resource-limited settings like Uganda. Objective: To develop a digital health intervention that enables improved self-care amongst HF patients in Uganda. Methods: We implemented a user-centred design process to develop a self-care intervention entitled Medly Uganda. The ideation phase comprised a systematic scoping review and preliminary data collection amongst HF patients and clinicians in Uganda. An iterative design process was then used to advance an initial prototype into a fully-functional digital health intervention. The evaluation phase involved usability testing of the developed intervention amongst Ugandan patients with HF and their clinicians. Results: Medly Uganda is a digital health intervention that is fully integrated within a government-operated mobile health platform. The system allows patients to report daily HF symptoms, receive tailored treatment advice, and connect with a clinician when showing signs of decompensation. Medly Uganda harnesses Unstructured Supplementary Service Data technology that is already widely used in Uganda for mobile phone-based financial transactions. Usability testing showed the system to be accepted by patients, caregivers, and clinicians. Conclusions: Medly Uganda is a fully-functional and well-accepted digital health intervention that enables Ugandan HF patients to better care for themselves. Moving forward, we expect the system to help decongest cardiac clinics and improve self-care efficacy amongst HF patients in Uganda.

Identification of Anticancer and Anti-inflammatory Drugs from Drug-target Interaction Descriptors by Machine Learning..

Background: Drug repositioning is an important subject in drug-disease research. In the past, most studies simply used drug descriptors as the feature vector to classify drugs or targets, or used qualitative data about drug-target or drug-disease to predict drug-target interactions. These data provide limited information for drug repositioning. Objective: Considering both drugs and targets and constructing quantitative drug-target interaction descriptors as a method of drug characteristics are of great significance to the study of drug repositioning. Methods: Taking anticancer and anti-inflammatory drugs as research objects, the interaction sites between drugs and targets were determined by molecular docking. Sixty-seven drug-target interaction descriptors were calculated to describe the drug-target interactions, and 22 important descriptors were screened for drug classification by SVM, LightGBM and MLP. Results: The accuracy of SVM, LightGBM and MLP reached 93.29%, 92.68% and 94.51%, their Matthews correlation coefficients reached 0.852, 0.840 and 0.882, and their areas under the ROC curve reached 0.977, 0.969 and 0.968, respectively. Conclusion: Using drug-target interaction descriptors to build machine learning models can obtain better results for drug classification. Number of atom pairs, force field, hydrophobic interactions and bSASA are the four types of key features for the classification of anticancer and anti-inflammatory drugs.

Demographic and Life History Characteristics of Black Bullheads Ameiurus melas in a North Temperate USA Lake

Black bullheads Ameiurus melas are an environmentally tolerant omnivorous fish species that are found throughout much of North America and parts of Europe. Despite their prevalence, black bullheads are an infrequently studied species making their biology, ecology, and life history poorly understood. Although limited information has been published on black bullheads, evidence suggests that bullheads can dominate the fish biomass and have profound influences on the fish community in some north temperate USA lakes. The goal of our study was to provide additional information on black bullhead population demographics, growth rates, life history characteristics, and seasonal diet preferences in a northern Wisconsin lake. Using common fish collection gears (fyke netting, electrofishing), fish aging protocols, fecundity assessments, and diet indices, our results suggested that black bullheads exhibited relatively fast growth rates, early ages at maturity, moderate fecundity, and a diverse omnivorous diet. Due to these demographic and life history characteristics, black bullheads have the potential to dominate fish community biomass in their native and introduced range. Results from our study may inform the management of black bullhead as native and invasive species.

Test-retest reliability of the HEXACO-100—And the value of multiple measurements for assessing reliability

Despite the widespread use of the HEXACO model as a descriptive taxonomy of personality traits, there remains limited information on the test-retest reliability of its commonly-used inventories. Studies typically report internal consistency estimates, such as alpha or omega, but there are good reasons to believe that these do not accurately assess reliability. We report 13-day test-retest correlations of the 100- and 60-item English HEXACO Personality Inventory-Revised (HEXACO-100 and HEXACO-60) domains, facets, and items. In order to test the validity of test-retest reliability, we then compare these estimates to correlations between self- and informant-reports (i.e., cross-rater agreement), a widely-used validity criterion. Median estimates of test-retest reliability were .88, .81, and .65 (N = 416) for domains, facets, and items, respectively. Facets’ and items’ test-retest reliabilities were highly correlated with their cross-rater agreement estimates, whereas internal consistencies were not. Overall, the HEXACO Personality Inventory-Revised demonstrates test-retest reliability similar to other contemporary measures. We recommend that short-term retest reliability should be routinely calculated to assess reliability.