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Background: Fiji faces a growing burden of diseases and a significant emigration of health workers, heightening the role of community health workers (CHWs) in healthcare delivery. Effective training is crucial for CHWs to enhance their capacity and service quality. This study evaluates CHW training in Fiji, aiming to identify areas for improvement., Methods: A qualitative study was conducted, encompassing a review of national policies on CHW training, six focus group discussions, and interviews with CHWs and their supervisors across Fijian subdivisions. This study was collaboratively designed with Fiji's Ministry of Health and Medical Services (MOHMS). Data was transcribed, coded, and thematically analysed using the Community Health Workers Assessment and Improvement Matrix (CHW-AIM)., Findings: While CHW training policies in Fiji are well-established, discrepancies exist between the policy and its implementation. Challenges include inconsistent training for new recruits, limited resources, and variability in training content and frequency of training across divisions, especially concerning noncommunicable disease (NCD) training., Interpretation: To enhance the CHW training program in Fiji, a restructuring and standardisation of both pre-service and in-service training is necessary, tailored to the needs of each division. Investment in ongoing capacity building, alongside the development and revision of training guidelines, particularly for managing NCD complications in the community, is crucial. Implementing these changes will enable CHWs in Fiji to be better equipped for providing essential community-based care., (© 2024. The Author(s).)

The Mango I and II RNA aptamers have been widely used in vivo and in vitro as genetically encodable fluorogenic markers that undergo large increases in fluorescence upon binding to their ligand, TO1-Biotin. However, while studying nucleic acid sequences, it is often desirable to have trans -acting probes that induce fluorescence upon binding to a target sequence. Here, we rationally design three types of light-up RNA Mango Beacons based on a minimized Mango core that induces fluorescence upon binding to a target RNA strand. Our first design is bimolecular in nature and uses a DNA inhibition strand to prevent folding of the Mango aptamer core until binding to a target RNA. Our second design is unimolecular in nature, and features hybridization arms flanking the core that inhibit G-quadruplex folding until refolding is triggered by binding to a target RNA strand. Our third design builds upon this structure, and incorporates a self-inhibiting domain into one of the flanking arms that deliberately binds to, and precludes folding of, the aptamer core until a target is bound. This design separates G-quadruplex folding inhibition and RNA target hybridization into separate modules, enabling a more universal unimolecular beacon design. All three Mango Beacons feature high contrasts and low costs when compared to conventional molecular beacons, with excellent potential for in vitro and in vivo applications., (© 2024 Abdolahzadeh et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Within biofilms, gradients of electron acceptors such as oxygen stimulate the formation of physiological subpopulations. This heterogeneity can enable cross-feeding and promote drug resilience, features of the multicellular lifestyle that make biofilm-based infections difficult to treat. The pathogenic bacterium Pseudomonas aeruginosa produces pigments called phenazines that can support metabolic activity in hypoxic/anoxic biofilm subzones, but these compounds also include methylated derivatives that are toxic to their producer under some conditions. In this study, we uncover roles for the global regulators RpoS and Hfq/Crc in controlling the beneficial and detrimental effects of methylated phenazines in biofilms. Our results indicate that RpoS controls phenazine methylation by modulating activity of the carbon catabolite repression pathway, in which the Hfq/Crc complex inhibits translation of the phenazine methyltransferase PhzM. We find that RpoS indirectly inhibits expression of CrcZ, a small RNA that binds to and sequesters Hfq/Crc, specifically in the oxic subzone of P. aeruginosa biofilms. Deletion of rpoS or crc therefore leads to overproduction of methylated phenazines, which we show leads to increased metabolic activity-an apparent beneficial effect-in hypoxic/anoxic subpopulations within biofilms. However, we also find that under specific conditions, biofilms lacking RpoS and/or Crc show increased sensitivity to phenazines indicating that the increased metabolic activity in these mutants comes at a cost. Together, these results suggest that complex regulation of PhzM allows P. aeruginosa to simultaneously exploit the benefits and limit the toxic effects of methylated phenazines.

Background: Following reports of new scientific research there are frequently discussions in the media about the effectiveness of antidepressants., Aim: To find out whether recently published meta-analyses about the effectiveness of antidepressants have consequences for clinical practice., Method: Two recent meta-analyses which investigated the effectiveness of antidepressants are discussed. results The two studies were conducted along similar lines using similar methods. Both meta-analyses concluded that antidepressants are effective in the more serious type of depressive disorders. They are less effective in mild depressive disorders., Conclusion: On the basis of these two meta-analyses it was concluded that antidepressants should be prescribed solely for patients with severe depressive disorders.

Objective: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively., Methods: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors., Results: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively)., Conclusion: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

The lungs play an important role in the metabolism of vasoactive substances including endogenous amines. The role of pulmonary clearance of circulating norepinephrine has not been well defined in the young lamb (7-8 d of age). Using radiolabeled tracer norepinephrine in acutely instrumented lambs, we determined the in vivo pulmonary clearance and spillover rate of norepinephrine under baseline and hypoxic conditions. The fractional extraction of norepinephrine, the percent removed on a single pass through the pulmonary circulation, was 23 +/- 2%. The corresponding pulmonary clearance rate was 61 +/- 10 mL/kg/min and the net pulmonary norepinephrine removal rate was 0.41 +/- 0.14 nmol/kg/min. This clearance represented over 70% of whole body norepinephrine clearance. The spillover of synaptic norepinephrine was 0.22 +/- 0.13 nmol/kg/min. During hypoxia, animals showed significant increases in pulmonary artery pressure and resistance. Fractional extraction and norepinephrine decreased to 16 +/- 3%, p less than 0.005. Pulmonary clearance decreased to 31 +/- 7 mL/kg/min, and net pulmonary norepinephrine removal rate decreased to 0.27 +/- 0.07 nmol/kg/min. These results demonstrate that pulmonary clearance plays a significant role in norepinephrine clearance in 1-wk-old lambs. Alteration of norepinephrine clearance during physiologic states such as hypoxia may be important in the pathophysiology of altered pulmonary vascular resistance in newborn animals.

At birth, there is a marked increase in circulating plasma catecholamine concentrations. This increase is critical to many of the physiologic adjustments to postnatal life. Because the levels observed are higher than those seen in most other physiologic conditions in adults, previous investigators have suggested that the newborn is less sensitive to adrenergic stimulation or that desensitization to adrenergic stimulation occurs rapidly. To investigate this question, we designed experiments to measure myocardial beta-adrenergic receptor density and sensitivity before and after exposure to the catecholamine surge at birth in term newborn sheep. We also measured the status of sympathetic innervation, reflected by myocardial norepinephrine content. At birth, plasma catecholamines increased 4- to 6-fold with associated increases in heart rate, blood pressure, and cardiac output. Myocardial beta-adrenergic receptor at birth (135 fmol/mg protein) did not change significantly by 6 h of life (157 fmol/mg protein). Myocardial adenyl cyclase activity, reflecting receptor sensitivity, and myocardial sympathetic innervation also did not change. These results suggest that, despite exposure to sustained adrenergic stimulation, myocardial adrenergic effector mechanisms do not change in the newborn sheep at birth.

The effect of hypoxia on plasma met-enkephalin and catecholamine levels was studied in chronically catheterized fetal sheep. Maternal and fetal hypoxia was maintained for 20 min. We found hypoxia significantly increased the plasma levels of large mol wt met-enkephalin containing peptides from 1755 +/- 229 pg/mL during baseline to 4408 +/- 1426 pg/mL by 15 minutes of hypoxia. The levels of the met-enkephalin pentapeptide were unchanged during hypoxia from a baseline value of 168 +/- 56 pg/mL. Norepinephrine and epinephrine levels increased 5- and 10-fold, respectively, by 15 min of hypoxia. These observations suggest cosecretion of the large mol wt met-enkephalin peptides with catecholamines during stress in developing animals.