Use of Dichlorodimethylsilane to Produce Polydimethylsiloxane as a Substitute for Vitreous Humour: Characteristics and In Vitro Toxicity.

Polydimethylsiloxane (PDMS) is a substitute for vitreous humour in vitreoretinal surgery and is usually produced from octamethylcyclotetrasiloxane (D4). In Indonesia, both commercial PDMS and D4 are limited and expensive. Dichlorodimethylsilane (DCMS) can be an alternative to produce PDMS. DCMS is cheaper and easier to obtain than D4. However, more extra effort is needed in order to produce PDMS from DCMS. Therefore, this study aimed to produce PDMS from DCMS by varying the ratio of DCMS precursor to dichloromethane (DCM) solvent at ratios of 1:1 and 1:4 through the hydrolysis-condensation method under neutral conditions. The PDMS produced had medium- (2.06 Pa·s) and high viscosity (3.59 Pa·s), with densities ranging from 0.96 to 0.99 g/mL. The refractive index was 1.4034-1.4036 and surface tension was 21 × 10-3 N/m, while they were able to transmit ~100% visible light, which were similar values to the commercial PDMS characteristics. PDMS samples were characterized using IR and NMR spectroscopy, which confirmed they were of PDMS type. The most optimum DCMS:DCM ratio was 1:1 due to the medium-viscosity PDMS type that could be produced. The in vitro HET-CAM toxicity test showed that samples were non-irritant, similar to PDMS produced from D4. PDMS from DCMS was non-toxic and ready to be used as a vitreous humuor substitution.

The soluble suppression of tumorigenicity 2 as a biomarker of early cardiac remodeling in bradycardia patients receiving permanent pacemaker therapy.

Aim: This study aims to evaluate: the difference of soluble suppression of tumorigenicity 2 (sST2) level, a biomarker for cardiac remodeling and echocardiography parameters value prior to and 1 month after implantation; and the association between pacemaker parameters and pacemaker mode along with delta sST2 levels. Materials & methods: This prospective cohort study enrolled all symptomatic bradycardia patients aged >18 years with preserved ejection fraction who underwent permanent pacemaker (PPM) implantation. Results: A total of 49 patients were included in this study. The sST2 level (ng/ml) were significantly different between prior and 1 month following PPM implantation (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Conclusion: The early cardiac remodeling has occurred within 1 month after PPM implantation as indicated by increasing delta sST2 level.

It is widely known that pacing induced cardiomyopathy, which results from the utilization of a permanent pacemaker (PPM) within a long-term duration, will increase the risk of mortality and morbidity. Hence, early detection of the cardiac remodeling process is warranted in order to prevent this course. In this study, the soluble suppression of tumorigenicity 2 level (ng/ml), known as an indicator of cardiac remodeling, was significantly higher in 1 month following PPM implantation compared with the baseline (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Thus, it denotes that early cardiac remodeling might occur earlier than expected, within 1 month following PPM implantation.

MitoTEMPOL modulates mitophagy and histopathology of Wistar rat liver after streptozotocin injection.

Objectives: This study aims to explore the effect of mitoTEMPOL on histopathology, lipid droplet, and mitophagy gene expression of Wistar rat's liver after injection of streptozotocin (STZ). Materials and Methods: Twenty male Wistar rats were divided into 4 groups: Control (n=5); 100 mg/kg BW/day mitoTEMPOL orally (n=5); 50 mg/kg BW STZ intraperitoneal injection (n=5); and mitoTEMPOL+STZ (n=5). STZ was given a single dose, while mitoTEMPOL was given for 5 weeks after 1 week of STZ injection. Histopathological appearance, lipid droplets, mitophagy, and autophagy gene expression were examined after the mitoTEMPOL treatment. Results: We found metabolic zone shifting that might be correlated with the liver activity of fatty acid oxidation in the STZ group, a decrease of lipid droplets in mitoTEMPOL and mitoTEMPOL + STZ compared with Control and STZ groups were found in this study. We also found significant changes in PINK1, Parkin, BNIP3, Mfn1, and LC3 gene expression, but no difference in Opa1, Fis1, Drp1, and p62 gene expression, suggesting a change of mitochondrial fusion rather than mitochondrial fission correlated with mitophagy. Conclusion: All this concluded that mitoTEMPOL could act as a modulator of mitophagy and metabolic function of the liver, thus amplifying its crucial role in preventing mitochondrial damage in the liver in the early onset of diabetes mellitus.

Revisiting exercise-induced premature ventricular complexes as a prognostic factor for mortality in asymptomatic patients: A systematic review and meta-analysis.

Background: Recent investigations suggest that premature ventricular complexes (PVCs) during an exercise test are associated with an elevated risk of mortality in asymptomatic individuals. However, given the small number of studies included, the association between these two entities in the asymptomatic population remains obscure. Our aim was to evaluate this matter. Methods: A comprehensive literature search was conducted utilizing several online databases up to April 2022. The study comprised cohort studies examining the relationship between exercise-induced premature ventricular complexes (EI-PVCs) and all-cause mortality (ACM) as well as cardiovascular mortality (CVM) in asymptomatic populations. To provide diagnostic values across the statistically significant parameters, we additionally calculated sensitivity, specificity, and area under the curve (AUC). Results: A total of 13 studies consisting of 82,161 patients with a mean age of 49.3 years were included. EI-PVCs were linked to an increased risk of ACM (risk ratio (RR) = 1.30 (95% confidence interval (CI) = 1.18-1.42); p < 0.001; I 2 = 59.6%, p-heterogeneity < 0.001) and CVM (RR = 1.67 (95% CI = 1.40-1.99); p < 0.001; I 2 = 7.5%, p-heterogeneity = 0.373). Subgroup analysis based on the frequency of PVCs revealed that frequent PVCs were similarly related to a higher risk of ACM and CVM, but not infrequent PVCs. Moreover, diagnostic test accuracy meta-analysis showed that recovery phase EI-PVCs have a higher overall specificity than exercise phase EI-PVCs regarding our outcomes of interest. Conclusion: EI-PVCs are correlated with a higher risk of ACM and CVM. When compared to the exercise phase, the specificity of PVCs generated during the recovery period in predicting interest outcomes is higher. As a result, we propose that the exercise ECG be utilized on a regular basis in middle-aged asymptomatic individuals to measure the frequency of PVCs and stratify the risk of mortality. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=328852], identifier [CRD42022328852].

Electrocardiographic Markers Indicating Right Ventricular Outflow Tract Conduction Delay as a Predictor of Major Arrhythmic Events in Patients With Brugada Syndrome: A Systematic Review and Meta-Analysis.

Introduction: Risk stratification in Brugada Syndrome (BrS) patients is still challenging due to the heterogeneity of clinical presentation; thus, some additional risk markers are needed. Several studies investigating the association between RVOT conduction delay sign on electrocardiography (ECG) and major arrhythmic events (MAE) in BrS patients showed inconclusive results. This meta-analysis aims to evaluate the association between RVOT conduction delay signs presented by aVR sign and large S wave in lead I, and MAE in BrS patients. Methods: The literature search was performed using several online databases from the inception to March 16th, 2022. We included studies consisting of two main components, including ECG markers of RVOT conduction delay (aVR sign and large S wave in lead I) and MAE related to BrS (syncope/VT/VF/SCD/aborted SCD/appropriate ICD shocks). Results: Meta-analysis of eleven cohort studies with a total of 2,575 participants showed RVOT conduction delay sign was significantly associated with MAE in BrS patients [RR = 1.87 (1.35, 2.58); p < 0.001; I 2= 52%, P heterogeneity = 0.02]. Subgroup analysis showed that aVR sign [RR = 2.00 (1.42, 2.83); p < 0.001; I 2= 0%, P heterogeneity = 0.40] and large S wave in lead I [RR = 1.74 (1.11, 2.71); p = 0.01; I 2= 60%, P heterogeneity = 0.01] were significantly associated with MAE. Summary receiver operating characteristics analysis revealed the aVR sign [AUC: 0.77 (0.73-0.80)] and large S wave in lead I [AUC: 0.69 (0.65-0.73)] were a good predictor of MAE in BrS patients. Conclusion: RVOT conduction delay sign, presented by aVR sign and large S wave in the lead I, is significantly associated with an increased risk of MAE in BrS patients. Hence, we propose that these parameters may be useful as an additional risk stratification tool to predict MAE in BrS patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022321090.

Pharmacological Treatment Options for Coronavirus Disease-19 in Renal Patients.

Patients with chronic kidney disease (CKD), including dialysis and transplant patients, are at greater risk of contracting SARS-CoV-2 due to kidney dysfunction and preexisting comorbidities. To date, a specific guideline on managing these high-risk patients infected with COVID-19 has not been established. As the current management of COVID-19 comprises mainly experimental drugs, the authors aim to provide information on dosing adjustments at different stages of kidney dysfunction and notable renal side effects. We performed a nonsystematical review of currently available COVID-19 drugs exploring several different clinical trial databases and search browsers. Several antivirals and monoclonal antibodies used in COVID-19 treatment require dosage adjustments in kidney dysfunction. In a global pandemic setting, nephrologists need to consider the appropriate dosage according to the renal function and closely monitor the side effects of different drug combinations to obtain the optimum therapeutic effect while avoiding further renal damage. Further studies are required to determine the safety and efficacy of these drugs in renal patients.

The Influence of Right Ventricular Pacing Location, Pacing Burden and Paced QRS Duration to Subclinical Left Ventricular Systolic Dysfunction as Shown by Global Longitudinal Strain Echocardiography.

BACKGROUND: Prolonged pacing of the right ventricle (RV) is associated with left ventricular (LV) systolic dysfunction. Several studies have shown that the RV pacing location, pacing burden (percentage), and paced QRS duration may affect LV systolic function. Subclinical LV dysfunction may occur early after implantation of a permanent pacemaker (PPM). Therefore, this study aims to detect early subclinical LV systolic dysfunction measured by global longitudinal strain (GLS) using speckle tracking echocardiography (STE) at one month after PPM implantation. METHODS: A single-center, prospective cohort study was conducted, and all patients indicated for PPM implantation with preserved LV systolic function were included. Data of RV pacing location (RV apical vs right ventricular outflow tract (RVOT), pacing burden (percentage) (≤40% vs >40%), and paced QRS duration (≤150 ms and >150 ms) were obtained. The change of GLS was also measured before and one month after PPM implantation (delta GLS). RESULTS: 37 patients were enrolled in this study, which demonstrated significant difference between GLS before (-20.30 SD 3.38) and after (-16.93 SD 3.47) PPM implantation (p=<0.001). There were no significant difference in delta GLS either between patients with RV pacing location on RV apical vs RVOT ((2.30 (0.00-10.50) vs 2.95(0.10-8.30), p=0.648) or between patient with paced QRS duration ≤150ms vs >150ms ((1.70 (0.30-8.30) vs 3.45 (0.0-10.5)), p=0.266). Meanwhile, there was a significant difference of delta GLS between patients with pacing burden ≤40% vs >40% (Mean 1.92 SD 1.37 vs 3.98 SD 3.04), p=0.007). Further analysis found that pacing burden only affected the delta GLS in group with apical RV pacing (≤40% (1.58 SD 0.59) vs > 40% (4.67 SD 3.47), p = 0.008) and did not affect the delta GLS in group with RVOT pacing (≤40% (2.32 SD 1.98) vs > 40% (3.29 SD 2.48), p = 0.446). CONCLUSION: The pacing parameter, particularly pacing burden > 40% may induce the subclinical LV systolic dysfunction after one month of pacemaker implantation as shown by decline of GLS,  especially when the RV pacing location was placed on apical.

The estimated healthcare cost of diabetic retinopathy in Indonesia and its projection for 2025.

PURPOSE: To estimate the total healthcare cost associated with diabetic retinopathy (DR) in type 2 diabetes in Indonesia and its projection for 2025. METHODS: A prevalence-based cost-of-illness model was constructed from previous population-based DR study. Projection for 2025 was derived from estimated diabetes population in 2025. Direct treatment costs of DR were estimated from the perspective of healthcare. Patient perspective costs were obtained from thorough interview including only transportation cost and lost of working days related to treatment. We developed four cost-of-illness models according to DR severity level, DR without necessary treatment, needing laser treatment, laser +intravitreal (IVT) injection and laser + IVT +vitrectomy. All costs were estimated in 2017 US$. RESULTS: The healthcare costs of DR in Indonesia were estimated to be $2.4 billion in 2017 and $8.9 billion in 2025. The total cost in 2017 consisted of the cost for no DR and mild-moderate non-proliferative DR (NPDR) requiring eye screening ($25.9 million), severe NPDR or proliferative DR (PDR) requiring laser treatment ($0.25 billion), severe NPDR or PDR requiring both laser and IVT injection ($1.75 billion) and advance level of PDR requiring vitrectomy ($0.44 billion). CONCLUSIONS: The estimated healthcare cost of DR in Indonesia in 2017 was considerably high, nearly 2% of the 2017 national state budget, and projected to increase significantly to more than threefold in 2025. The highest cost may incur for DR requiring both laser and IVT injection. Therefore, public health intervention to delay or prevent severe DR may substantially reduce the healthcare cost of DR in Indonesia.