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Rebecca Ingenhoff,1,2 Nicole Robertson,3 Richard Munana,4,5 Benjamin E Bodnar,6 Ivan Weswa,5 Isaac Sekitoleko,7,8 Julia Gaal,1 Bruce J Kirenga,9 Robert Kalyesubula,5,10,11 Felix Knauf,1,11 Trishul Siddharthan12 1Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany; 2Charité Center for Global Health, Charité - Universitätsmedizin Berlin, Berlin, Germany; 3University of Kentucky College of Medicine, Lexington, KY, USA; 4School of Public Health, Makerere University College of Health Sciences, Makerere University, Kampala, Uganda; 5African Community Center for Social Sustainability, Nakaseke, Uganda; 6Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 7MRC/UVRI and LSHTM Uganda Research Unit, Kampala, Uganda; 8London School of Hygiene and Tropical Medicine, London, UK; 9Makerere University Lung Institute, Kampala, Uganda; 10Department of Physiology, Department of Internal Medicine, Makerere University College of Health Sciences, Kampala, Uganda; 11Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; 12Department of Pulmonary, Critical Care and Sleep Medicine, University of Miami, Coral Gables, FL, USACorrespondence: Rebecca Ingenhoff, Email Rebecca.ingenhoff@charite.deBackground: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The burden of COPD is expected to increase in low- and middle-income countries (LMICs). COPD screening and diagnostics tools are often inaccessible in rural settings of LMICs. To contribute to the growing body of evidence on the effectiveness of Community Health Worker (CHW) interventions, this study aims to understand the facilitators and barriers of implementing a CHW-led COPD screening and referral program in rural Uganda.Methods: This qualitative study was conducted from September to October 2022 to explore Community Members, CHWs, and Healthcare Providers (HCPs) perceptions on the challenges of CHW-delivered COPD programming in Nakaseke, rural Uganda. In total, we held eight individual in-depth interviews with CHWs, ten in-depth interviews with HCPs and six focus group discussions with 34 Community Members. Research assistants audio-recorded and transcribed interviews verbatim. The implementation outcomes framework guided the thematic analysis.Results: Implementation acceptability was constrained by a lack of COPD awareness, a lack of perceived utility in COPD screening as well as stigma around the diagnostic process. Limited spirometry adoption was also attributed to Community Member accessibility and willingness to participate in the COPD diagnostic referral process. The high patient volume and the complex, time-consuming diagnostic and referral process hindered successful implementation. To enhance program sustainability, all participants suggested increasing CHW support, medication access, decentralizing COPD care and upscaling follow-up of Community Members by CHWs.Conclusion: CHW-led interventions remain a potentially critical tool to alleviate barriers to treatment and self-management in settings where access to care is limited. While community-based interventions can create sustainable infrastructure to improve health outcomes, formative assessments of the potential barriers prior to intervention are required. Evidence-based, localized approaches and sustained funding are imperative to achieve this.Keywords: community health workers, task shifting, screening and referral, chronic obstructive pulmonary disease, Uganda

Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system of the mammalian kidney. The principal aim of the present study was to determine if Ksp-cadherin played a critical role in the development and maintenance of the adult mammalian kidney by generating and evaluating a mouse line deficient in Ksp-cadherin. Ksp-null mutant animals were viable and fertile, and kidneys from both neonates and adults showed no evidence of structural abnormalities. Immunolocalization and Western blot analyses of Na+ -K+ -ATPase and E-cadherin indicated that Ksp-cadherin is not essential for either the genesis or maintenance of the polarized tubular epithelial phenotype. Moreover, E-cadherin expression was not altered to compensate for Ksp-cadherin loss. Plasma electrolytes, total CO2, blood urea nitrogen, and creatinine levels were also unaffected by Ksp-cadherin deficiency. However, a subtle but significant developmental delay in the ability to maximally concentrate urine was detected in Ksp-null mice. Expression analysis of the principal proteins involved in the generation of the corticomedullary osmotic gradient and the resultant movement of water identified misexpression of aquaporin-2 in the inner medullary collecting duct as the possible cause for the inability of young adult Ksp-cadherin-deficient animals to maximally concentrate their urine. In conclusion, Ksp-cadherin is not required for normal kidney development, but its absence leads to a developmental delay in maximal urinary concentrating ability. [ABSTRACT FROM AUTHOR]

The bar extrusion process is characterised by extruding a billet through a forming die with a punch. Compared to conventional bar extrusion other tool concepts are required for semi-solid extrusion processes because forming has to take place in the semi-solid state, followed by a solidification step []. Under variations of the main process parameters like press velocity, extrusion channel length and die as well as the press channel geometry semi-solid extrusions are performed. The bars are characterised by a limited length due to insufficient solidification in the extrusion channel. Analyses concerning chemical composition, pore formation, microstructure and mechanical properties discover properties independent of the chosen process parameters. The chemical composition is constant over the bar length. It differs between globulites and eutectic. In the homogeneous microstructure few pores can be found. The determination of the mechanical properties shows a wide range of values because of the pores included in the bars. [ABSTRACT FROM AUTHOR]

This paper shows the possibility of producing demonstrating components by combining the forming operation with a simultaneous insertion of additional components. With this technology it is possible to shorten conventional process chains and to create a new generation of components. As base materials two different steel alloys are used, the low melting cold forming tool steel X210CrW12 and the bearing steel 100Cr6. As insert materials steel alloys as well as copper based alloys are considered. Consequently, the main challenges for this technology are the embedding of the inserts into the semi-solid matrix without destroying the geometry due to deforming or remelting. To characterise the produced components concerning their microstructure development and resulting material properties optical and mechanical testings were carried out. As result it could be shown that the die filling and the embedding of the inserts were feasible. The development of the microstructure of the solidified material was influenced by the geometrical conditions which also cause differences in the mechanical properties. Furthermore, there could be shown design restrictions which have to be considered in future to avoid the damaging of the inserted components. [ABSTRACT FROM AUTHOR]

Abstract Background Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy. To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features. Methods In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons. Results A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA). Conclusions Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features.