Kelainan Peak Expiratory Flow Rate Dibandingkan dengan Keluhan Sistim Pernapasan – studi pada 75 anggota pasukan kuning, Surabaya

Telah dilakukan kajian untuk membandingkan hasil pemeriksaan faal paru Peak Expiratory Flow Rate (PEFR) dalam mendeteksi kelainan paru obstruktif dengan anamnesis adanya keluhan batuk, pengeluaran dahak, sesak nafas dan nafas berbunyi. Sebagai subyek penelitian adalah anggota pasukan kuning Kotamadya Surabaya yang bertugas di jalan raya sebanyak 75 orang. Dipilih anggota pasukan kuning karena dalam melaksanakan tugas sehari-hari diduga mendapat pemaparan polusi debu dan gas buang kendaraan bermotor. Hasil yang didapat adalah proporsi kelainan PEFR secara keseluruhan sebesar 42,67%, di antara yang mengeluh keluhan batuk sebesar 24,00%, di antara yang mengeluarkan dahak sebesar 14,67%, di antara yang sesak nafas sebesar 22,67% dan di antara yang nafasnya berbunyi sebesar 10,67%. Ternyata didapatkan hubungan antara kelainan faal paru PEFR dengan adanya keluhan batuk (p = 0,0216), dengan keluhan pengeluaran dahak (p = 0,0005), dengan keluhan sesak nafas (p = 0,018) dan dengan keluhan nafas berbunyi (p = 0,0000). Subyek dengan kelainan faal paru PEFR tanpa keluhan berkisar antara 30,67 –36% dari seluruh subyek yang diperiksa

Understanding community health worker employment preferences in Malang district, Indonesia using a discrete choice experiment

BACKGROUND: Community health workers (CHWs) play a critical role in supporting health systems, and in improving accessibility to primary healthcare. In many settings CHW programmes do not have formalised employment models and face issues of high attrition and poor performance. This study aims to determine the employment preferences of CHWs in Malang district, Indonesia, to inform policy interventions. METHODS: A discrete choice experiment was conducted with 471 CHWs across 28 villages. Attributes relevant to CHW employment were identified through a multistage process including literature review, focus group discussions and expert consultation. Respondents’ choices were analysed with a mixed multinomial logit model and latent class analyses. RESULTS: Five attributes were identified: (1) supervision; (2) training; (3) monthly financial benefit; (4) recognition; and (5) employment structure. The most important influence on choice of job was a low monthly financial benefit (US$~2) (β=0.53, 95$~20) was most unappealing to respondents (β=−0.13, 95% CI=−0.23 to −0.03). Latent class analysis identified two groups of CHWs who differed in their willingness to accept either job presented and preferences over specific attributes. Preferences diverged based on respondent characteristics including experience, hours’ worked per week and income. CONCLUSION: CHWs in Malang district, Indonesia, favour a small monthly financial benefit which likely reflects the unique cultural values underpinning the programme and a desire for remuneration that is commensurate with the limited number of hours worked. CHWs also desire enhanced methods of performance feedback and greater structure around training and their rights and responsibilities. Fulfilling these conditions may become increasingly important should CHWs work longer hours

Understanding COVID-19 vaccine hesitancy: A cross-sectional study in Malang District, Indonesia

Introduction: Vaccine hesitancy could undermine efforts to reduce incidence of coronavirus disease 2019 (COVID-19). Understanding COVID-19 vaccine hesitancy is crucial to tailoring strategies to increase vaccination acceptance. This study aims to investigate the prevalence of and the reasons for COVID-19 vaccine hesitancy in Malang District, Indonesia. Methods: Data come from a cross-sectional study among individuals aged 17-85 years old (N = 3,014). Multivariate ordered logistic regression was used to identify factors associated with postponing or refusing COVID-19 vaccines. The Oxford COVID-19 vaccine hesitancy scale was used to measure vaccine hesitancy. A wide range of reasons for hesitancy, including coronavirus vaccine confidence and complacency, vaccination knowledge, trust and attitude in health workers and health providers, coronavirus conspiracy, anger reaction and need for chaos, populist views, lifestyle, and religious influence, was examined. Results and discussion: The results show that 60.2% of the respondents were hesitant to receive the COVID-19 vaccine. Low confidence and complacency beliefs about the vaccine (OR = 1.229, 95% CI = 1.195–1.264) and more general sources of mistrust within the community, particularly regarding health providers (OR = 1.064, 95% CI = 1.026–1.102) and vaccine developers (OR = 1.054, 95% CI = 1.027–1.082), are associated with higher levels of COVID-19 vaccine hesitancy. Vaccine hesitancy is also associated with anger reactions (OR = 1.019, 95% CI = 0.998–1.040), need for chaos (OR = 1.044, 95% CI = 1.022–1.067), and populist views (OR = 1.028, 95% CI = 1.00–1.056). The findings were adjusted for socio-demographic factors, including age, sex, education, marital status, working status, type of family, household income, religious beliefs, and residency. The results suggest the need for an effective health promotion program to improve community knowledge of the COVID-19 vaccine, while effective strategies to tackle “infodemics” are needed to address hesitancy during a new vaccine introduction program

Treatment with specific and pan-plasma membrane calcium ATPase (PMCA) inhibitors reduces malaria parasite growth in vitro and in vivo

BACKGROUND: Rapid emergence of Plasmodium resistance to anti-malarial drug mainstays has driven a continual effort to discover novel drugs that target different biochemical pathway (s) during infection. Plasma membrane Calcium + 2 ATPase (PMCA4), a novel plasma membrane protein that regulates Calcium levels in various cells, namely red blood cell (RBC), endothelial cell and platelets, represents a new biochemical pathway that may interfere with susceptibility to malaria and/or severe malaria. METHODS: This study identified several pharmacological inhibitors of PMCA4, namely ATA and Resveratrol, and tested for their anti-malarial activities in vitro and in vivo using the Plasmodium falciparum 3D7 strain, the Plasmodium berghei ANKA strain, and Plasmodium yoelii 17XL strain as model. RESULTS: In vitro propagation of P. falciparum 3D7 strain in the presence of a wide concentration range of the inhibitors revealed that the parasite growth was inhibited in a dose-dependent manner, with IC(50)s at 634 and 0.231 µM, respectively. RESULTS: The results confirmed that both compounds exhibit moderate to potent anti-malarial activities with the strongest parasite growth inhibition shown by resveratrol at 0.231 µM. In vivo models using P. berghei ANKA for experimental cerebral malaria and P. yoelii 17XL for the effect on parasite growth, showed that the highest dose of ATA, 30 mg/kg BW, increased survival of the mice. Likewise, resveratrol inhibited the parasite growth following 4 days intraperitoneal injection at the dose of 100 mg/kg BW. CONCLUSION: The findings indicate that the PMCA4 of the human host may be a potential target for novel anti-malarials, either as single drug or in combination with the currently available effective anti-malarials

Functionalised peptide hydrogel for the delivery of cardiac progenitor cells.

Heart failure (HF) remains one of the leading causes of death worldwide; most commonly developing after myocardial infarction (MI). Since adult cardiomyocytes characteristically do not proliferate, cells lost during MI are not replaced. As a result, the heart has a limited regenerative capacity. There is, therefore, a need to develop novel cell-based therapies to promote the regeneration of the heart after MI. The delivery and retention of cells at the injury site remains a significant challenge. In this context, we explored the potential of using an injectable, RGDSP-functionalised self-assembling peptide - FEFEFKFK - hydrogel as scaffold for the delivery and retention of rat cardiac progenitor cells (CPCs) into the heart. Our results show that culturing CPCs in vitro within the hydrogel for one-week promoted their spontaneous differentiation towards adult cardiac phenotypes. Injection of the hydrogel on its own, or loaded with CPCs, into the rat after injury resulted in a significant reduction in myocardial damage and left ventricular dilation

Identification of key small non-coding MicroRNAs controlling pacemaker mechanisms in the human sinus node

BACKGROUND: The sinus node (SN) is the primary pacemaker of the heart. SN myocytes possess distinctive action potential morphology with spontaneous diastolic depolarization because of a unique expression of ion channels and Ca2+-handling proteins. MicroRNAs (miRs) inhibit gene expression. The role of miRs in controlling the expression of genes responsible for human SN pacemaking and conduction has not been explored. The aim of this study was to determine miR expression profile of the human SN as compared with that of non-pacemaker atrial muscle. METHODS AND RESULTS: SN and atrial muscle biopsies were obtained from donor or post-mortem hearts (n=10), histology/ immunolabeling were used to characterize the tissues, TaqMan Human MicroRNA Arrays were used to measure 754 miRs, Ingenuity Pathway Analysis was used to identify miRs controlling SN pacemaker gene expression. Eighteen miRs were significantly more and 48 significantly less abundant in the SN than atrial muscle. The most interesting miR was miR-486-3p predicted to inhibit expression of pacemaking channels: HCN1 (hyperpolarization-activated cyclic nucleotide-gated 1), HCN4, voltage-gated calcium channel (Cav )1.3, and Cav 3.1. A luciferase reporter gene assay confirmed that miR-486-3p can control HCN4 expression via its 3′ untranslated region. In ex vivo SN preparations, transfection with miR-486-3p reduced the beating rate by ≈35±5% (P<0.05) and HCN4 expression (P<0.05). CONCLUSIONS: The human SN possesses a unique pattern of expression of miRs predicted to target functionally important genes. miR-486-3p has an important role in SN pacemaker activity by targeting HCN4, making it a potential target for therapeutic treatment of SN disease such as sinus tachycardia.</p

The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria

From Springer Nature via Jisc Publications RouterHistory: received 2021-03-03, accepted 2021-06-24, registration 2021-06-24, pub-electronic 2021-07-02, online 2021-07-02, collection 2021-12Publication status: PublishedFunder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/P015816/1Abstract: Background: Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell. Methods: In this study the course of three different Plasmodium spp. infections were examined in mice with systemic knockout of Pmca4 expression. Results: Ablation of PMCA4 reduced the size of RBCs and their haemoglobin content but did not affect RBC maturation and reticulocyte count. Surprisingly, knockout of PMCA4 did not significantly alter peripheral parasite burdens or the dynamics of blood stage Plasmodium chabaudi infection or reticulocyte-restricted Plasmodium yoelii infection. Interestingly, although ablation of PMCA4 did not affect peripheral parasite levels during Plasmodium berghei infection, it did promote slight protection against experimental cerebral malaria, associated with a minor reduction in antigen-experienced T cell accumulation in the brain. Conclusions: The finding suggests that PMCA4 may play a minor role in the development of severe malarial complications, but that this appears independent of direct effects on parasite invasion, growth or survival within RBCs

Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion

Aims Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway. PMCA4 activity is inhibited by the small molecule aurintricarboxylic acid (ATA). We hypothesize that inhibition of PMCA4 with ATA might enhance VEGF-induced angiogenesis. Methods and results We show that inhibition of PMCA4 with ATA in endothelial cells triggers a marked increase in VEGF-activated calcineurin/NFAT signalling that translates into a strong increase in endothelial cell motility and blood vessel formation. ATA enhances VEGF-induced calcineurin signalling by disrupting the interaction between PMCA4 and calcineurin at the endothelial-cell membrane. ATA concentrations at the nanomolar range, that efficiently inhibit PMCA4, had no deleterious effect on endothelial-cell viability or zebrafish embryonic development. However, high ATA concentrations at the micromolar level impaired endothelial cell viability and tubular morphogenesis, and were associated with toxicity in zebrafish embryos. In mice undergoing experimentally-induced hindlimb ischaemia, ATA treatment significantly increased the reperfusion of post-ischaemic limbs. Conclusions Our study provides evidence for the therapeutic potential of targeting PMCA4 to improve VEGF-based pro-angiogenic interventions. This goal will require the development of refined, highly selective versions of ATA, or the identification of novel PMCA4 inhibitors

Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients

From Springer Nature via Jisc Publications RouterHistory: received 2021-03-02, accepted 2021-05-04, registration 2021-05-05, pub-electronic 2021-05-17, online 2021-05-17, collection 2021-12Publication status: PublishedFunder: Universitas Airlangga; doi: http://dx.doi.org/10.13039/501100008463; Grant(s): Mandate Reserach Grant COVID-19Abstract: Background: Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host’s response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. Results: We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. Conclusion: Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19

RNA extraction from self-assembling peptide hydrogels to allow qPCR analysis of encapsulated cells

Self-assembling peptide hydrogels offer a novel 3-dimensional platform for many applications in cell culture and tissue engineering but are not compatible with current methods of RNA isolation; owing to interactions between RNA and the biomaterial. This study investigates the use of two techniques based on two different basic extraction principles: solution-based extraction and direct solid-state binding of RNA respectively, to extract RNA from cells encapsulated in four β-sheet forming self-assembling peptide hydrogels with varying net positive charge. RNA-peptide fibril interactions, rather than RNA-peptide molecular complexing, were found to interfere with the extraction process resulting in low yields. A column-based approach relying on RNA-specific binding was shown to be more suited to extracting RNA with higher purity from these peptide hydrogels owing to its reliance on strong specific RNA binding interactions which compete directly with RNA-peptide fibril interactions. In order to reduce the amount of fibrils present and improve RNA yields a broad spectrum enzyme solution—pronase—was used to partially digest the hydrogels before RNA extraction. This pre-treatment was shown to significantly increase the yield of RNA extracted, allowing downstream RT-qPCR to be performed