Role of informal healthcare providers in tuberculosis care in low- and middle-income countries: A systematic scoping review.

Achieving targets set in the End TB Strategy is still a distant goal for many Low- and Middle-Income Countries (LMICs). The importance of strengthening public-private partnership by engaging all identified providers in Tuberculosis (TB) care has long been advocated in global TB policies and strategies. However, Informal Healthcare Providers (IPs) are not yet prioritised and engaged in National Tuberculosis Programs (NTPs) globally. There exists a substantial body of evidence that confirms an important contribution of IPs in TB care. A systematic understanding of their role is necessary to ascertain their potential in improving TB care in LMICs. The purpose of this review is to scope the role of IPs in TB care. The scoping review was guided by a framework developed by the Joanna Briggs Institute. An electronic search of literature was conducted in MEDLINE, EMBASE, SCOPUS, Global Health, CINAHL, and Web of Science. Of a total 5234 records identified and retrieved, 92 full-text articles were screened, of which 13 were included in the final review. An increasing trend was observed in publication over time, with most published between 2010-2019. In 60% of the articles, NTPs were mentioned as a collaborator in the study. For detection and diagnosis, IPs were primarily involved in identifying and referring patients. Administering DOT (Directly Observed Treatment) to the patient was the major task assigned to IPs for treatment and support. There is a paucity of evidence on prevention, as only one study involved IPs to perform this role. Traditional health providers were the most commonly featured, but there was not much variation in the role by provider type. All studies reported a positive role of IPs in improving TB care outcomes. This review demonstrates that IPs can be successfully engaged in various roles in TB care with appropriate support and training. Their contribution can support countries to achieve their national and global targets if prioritized in National TB Programs

Population genomic analysis of mango (Mangifera indica) suggests a complex history of domestication

Trust Humans have domesticated diverse species from across the plant kingdom, yet much of our foundational knowledge of domestication has come from studies investigating relatively few of the most important annual food crops. Here, we examine the impacts of domestication on genetic diversity in a tropical perennial fruit species, mango (Mangifera indica). We used restriction site associated DNA sequencing to generate genomic single nucleotide polymorphism (SNP) data from 106 mango cultivars from seven geographical regions along with 52 samples of closely related species and unidentified cultivars to identify centers of mango genetic diversity and examine how post-domestication dispersal shaped the geographical distribution of diversity. We identify two gene pools of cultivated mango, representing Indian and Southeast Asian germplasm. We found no significant genetic bottleneck associated with the introduction of mango into new regions of the world. By contrast, we show that mango populations in introduced regions have elevated levels of diversity. Our results suggest that mango has a more complex history of domestication than previously supposed, perhaps including multiple domestication events, hybridization and regional selection. Our work has direct implications for mango breeding and genebank management, and also builds on recent efforts to understand how woody perennial crops respond to domestication

Multifrequency Strategies for the Identification of Gamma-Ray Sources

More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd

Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al

Respiratory-gated (4D) contrast-enhanced FDG PET-CT for radiotherapy planning of lower oesophageal carcinoma: Feasibility and impact on planning target volume

Background: To assess the feasibility and potential impact on target delineation of respiratory-gated (4D) contrast-enhanced 18 Fluorine fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT), in the treatment planning position, for a prospective cohort of patients with lower third oesophageal cancer. Methods: Fifteen patients were recruited into the study. Imaging included 4D PET-CT, 3D PET-CT, endoscopic ultrasound and planning 4D CT. Target volume delineation was performed on 4D CT, 4D CT with co-registered 3D PET and 4D PET-CT. Planning target volumes (PTV) generated with 4D CT (PTV 4DCT), 4D CT co-registered with 3D PET-CT (PTV 3DPET4DCT) and 4D PET-CT (PTV 4DPETCT ) were compared with multiple positional metrics. Results: Mean PTV 4DCT , PTV 3DPET4DCT and PTV 4DPETCT were 582.4 ± 275.1 cm 3 , 472.5 ± 193.1 cm 3 and 480.6 ± 236.9 cm 3 respectively (no significant difference). Median DICE similarity coefficients comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.85 (range 0.65-0.9), 0.85 (range 0.69-0.9) and 0.88 (range 0.79-0.9) respectively. The median sensitivity index for overlap comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.78 (range 0.65-0.9), 0.79 (range 0.65-0.9) and 0.89 (range 0.68-0.94) respectively. Conclusions: Planning 4D PET-CT is feasible with careful patient selection. PTV generated using 4D CT, 3D PET-CT and 4D PET-CT were of similar volume, however, overlap analysis demonstrated that approximately 20% of PTV 3DPETCT and PTV 4DPETCT are not included in PTV 4DCT , leading to under-coverage of target volume and a potential geometric miss. Additionally, differences between PTV 3DPET4DCT and PTV 4DPETCT suggest a potential benefit for 4D PET-CT. Trial registration: ClinicalTrials.gov Identifier - NCT02285660(Registered 21/10/2014)

Reliability of the Marlowe-Crowne social desirability scale in Ethiopia, Kenya, Mozambique, and Uganda

<p>Abstract</p> <p>Background</p> <p>Studies of HIV often use self-reported surveys to measure sexual knowledge, attitudes, and practices. However, the self-reported data are vulnerable to social desirability (SD), a propensity of individuals to report favorable responses. The Marlowe-Crowne Social Desirability Scale (MC-SDS) was developed as a measure of the effect of social desirability, but it has not been adapted for or used in Africa. This study aimed to apply the MC-SDS nested in an HIV behavioral intervention program and to measure its reliability in four African countries.</p> <p>Methods</p> <p>The MC-SDS was adapted based on consultations with local stakeholders and pilot tested in Ethiopia, Kenya, Mozambique, and Uganda. Trained interviewers administered the modified 28-item MC-SDS survey to 455 men and women (ages 15-24 years). The scores for the social desirability scales were calculated for all participants. An analysis of the internal consistency of responses was conducted using the Cronbach's α coefficient. Acceptable internal consistency was defined as an α coefficient of ≥ 0.70.</p> <p>Results</p> <p>Mean social desirability scores ranged from a low of 15.7 in Kenya to a high of 20.6 in Mozambique. The mean score was 17.5 for Uganda and 20.6 for Mozambique. The Cronbach's α coefficients were 0.63 in Kenya, 0.66 in Mozambique, 0.70 in Uganda, and 0.80 in Ethiopia.</p> <p>Conclusions</p> <p>The MC-SDS can be effectively adapted and implemented in sub-Saharan Africa. The reliability of responses in these settings suggest that the MC-SDS could be a useful tool for capturing potential SD in surveys of HIV related risk behaviors.</p

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions