Study protocol on Enhanced Primary Healthcare (EnPHC) interventions: a quasi-experimental controlled study on diabetes and hypertension management in primary healthcare clinics

Aim: This paper describes the study protocol, which aims to evaluate the effectiveness of a multifaceted intervention package called ‘Enhanced Primary Healthcare’ (EnPHC) on the process of care and intermediate clinical outcomes among patients with Type 2 diabetes mellitus (T2DM) and hypertension. Other outcome measures include patients’ experience and healthcare providers’ job satisfaction. Background: In 2014, almost two-thirds of Malaysia’s adult population aged 18 years or older had T2DM, hypertension or hypercholesterolaemia. An analysis of health system performance from 2016 to 2018 revealed that the control and management of diabetes and hypertension in Malaysia was suboptimal with almost half of the patients not diagnosed and just one-quarter of patients with diabetes appropriately treated. EnPHC framework aims to improve diagnosis and effective management of T2DM, hypertension or hypercholesterolaemia and their risk factors by increasing prevention, optimising management and improving surveillance of diagnosed patients. Methods: This is a quasi-experimental controlled study which involves 20 intervention and 20 control clinics in two different states in Malaysia, namely Johor and Selangor. The clinics in the two states were matched and randomly allocated to ‘intervention’ and ‘control’ arms. The EnPHC framework targets different levels from community to primary healthcare clinics and integrated referral networks. Data are collected via a retrospective chart review (RCR), patient exit survey, healthcare provider survey and an intervention checklist. The data collected are entered into tablet computers which have installed in them an offline survey application. Interrupted time series and difference-in-differences (DiD) analyses will be conducted to report outcomes

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (gt;99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMOdependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness

High-Resolution Atomic Force Microscopy Imaging of Nucleic Acids

Exploring the limits of spatial resolution has been a constant in the history of atomic force microscopy imaging. Since its invention in 1986, the AFM has beaten the barrier of resolution continuously, thanks to technical developments, miniaturization of tips, and implementation of new imaging modes. The double helix structure of DNA has been always at the horizon of resolution. Today, this milestone has been reached, not only imaging DNA but also its close relative double-stranded RNA. Here, we provide a comprehensive description of the methods employed and the steps required to image the helical periodicity of these two nucleic acids with the sample immersed in a buffer solution.Peer reviewe

Neonatal cataract: Aetiology, pathogenesis and management

We review the epidemiology, aetiology, pathogenetic mechanisms and clinical management of neonatal cataract. Visual development and the effects of visual deprivation in the infant with congenital cataract are discussed and related to the timing of surgery. Surgical techniques and the important operative and post-operative complications are discussed. We review post-operative management and compare the different techniques available for aphakic correction, and describe the VEP changes found in patients with monocular cataract