Is Exposure to Social Media Advertising and Promotion Associated with E-cigarette Use? Evidence from Indonesia

Background: E-cigarette use is a growing public health concern globally, including in Indonesia. Objective: Our study aimed to assess whether exposure to advertising and promotion in social media is associated with e-cigarette use in Indonesia, an upper-middle-income country. Methods: We conducted mixed-method research including quantitative and qualitative methods. For the quantitative methods, we did an online survey in the five largest cities in the country with 1,239 participants during September-October 2020. For the qualitative method, we conducted an in-person focused group discussion during November 2020 (while complying to the COVID-19 protocols). Results: We found high rates of e-cigarette ever use (29%) and current use (13%) among study participants. There was high exposure to e-cigarette advertising and promotion in social media, with a majority of participants (84%) reported ever seeing e-cigarette adverts or promotions on Facebook, Instagram, YouTube, and others. Both high rates of e-cigarette use and exposure to social media advertising are associated. Participants reported ever seeing adverts and promotions were 2.91 times and 2.82 times more likely ever to use and currently use e-cigarettes, respectively, after controlling for socioeconomic factors, region, and cigarette smoking status. Conclusion: Exposure to social media advertising and promotion is associated with e-cigarette use in Indonesia.     

Comparison of Polymerase Chain Reaction–Restriction Fragment Length Polymorphism,Immunohistochemistry, and DNA Sequencing for the Detection of IDH1 Mutations in Gliomas

Background: IDH1 mutation shows diagnostic, prognostic, and predictive value in gliomas. Direct Sanger sequencing is considered the gold standard to detect IDH1 mutation. However, this technology is not available in most neuropathological centers in developing countries such as Indonesia. Immunohistochemistry (IHC) and polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) have also been used to detect IDH1 mutation. This study aimed to compare DNA sequencing, IHC, and PCR–RFLP in detecting IDH1 mutations in gliomas. Methods: Research subjects were recruited from Dr. Sardjito Hospital. Genomic DNA was extracted from fresh or formalin-fixed paraffin-embedded samples of tumor tissue. DNA sequencing, PCR–RFLP and IHC were performed to detect IDH1 mutation. Sensitivity, specificity, and accuracy of PCR–RFLP and IHC were calculated by comparing them to DNA sequencing as the gold standard. Results: Among 61 recruited patients, 13 (21.3%) of them carried a mutation in codon 132 of the IDH1 gene, as shown by DNA sequencing. PCR–RFLP and DNA sequencing have a concordance value of 100%. Meanwhile, the concordance value between IDH1 R132H IHC and DNA sequencing was 96.7%. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy for PCR–RFLP were all 100%. On the other hand, the sensitivity, specificity, and accuracy of IHC were 92.3%, 97.9%, and 96.7%, respectively. Conclusion: This study showed that both PCR–RFLP and IHC have high accuracy in detecting IDH1 mutation. We recommend a combination of PCR–RFLP and IHC to detect IDH1 mutation in resource-limited settings.     

Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers

Cell transplantation is a promising therapy for a myriad of debilitating diseases; however, current delivery protocols using direct injection result in poor cell viability. We demonstrate that during the actual cell injection process, mechanical membrane disruption results in significant acute loss of viability at clinically relevant injection rates. As a strategy to protect cells from these damaging forces, we hypothesize that cell encapsulation within hydrogels of specific mechanical properties will significantly improve viability. We use a controlled in vitro model of cell injection to demonstrate success of this acute protection strategy for a wide range of cell types including human umbilical vein endothelial cells (HUVEC), human adipose stem cells, rat mesenchymal stem cells, and mouse neural progenitor cells. Specifically, alginate hydrogels with plateau storage moduli (G') ranging from 0.33 to 58.1 Pa were studied. A compliant crosslinked alginate hydrogel (G'=29.6 Pa) yielded the highest HUVEC viability, 88.9% ± 5.0%, while Newtonian solutions (i.e., buffer only) resulted in 58.7% ± 8.1% viability. Either increasing or decreasing the hydrogel storage modulus reduced this protective effect. Further, cells within noncrosslinked alginate solutions had viabilities lower than media alone, demonstrating that the protective effects are specifically a result of mechanical gelation and not the biochemistry of alginate. Experimental and theoretical data suggest that extensional flow at the entrance of the syringe needle is the main cause of acute cell death. These results provide mechanistic insight into the role of mechanical forces during cell delivery and support the use of protective hydrogels in future clinical stem cell injection studies.     

Phylogeny and In Silico Structure Analysis of Major Capsid Protein (L1) Human Papillomavirus 45 from Indonesian Isolates

Background: Human papillomavirus (HPV)-45 genotype circulates in high percentage in Bandung area - Indonesia, after HPV-16 and HPV-18. The aim of this study was to analyse variations of major capsid (L1) HPV-45 and its phylogeny. Furthermore in silico protein structure and epitope prediction was explored. Methods: L1 gene of HPV-45 was amplified, sequenced and aligned. Phylogenetic tree had been built and compared with a complete L1 HPV-45 sequence. Structure and epitope prediction of L1 protein were then developed in silico. Results: Of 5 L1 HPV-45 sequences collected, we have detected one variant of sub lineage A2 which was considered as a new variant, and two variants of B2. Superimposition of structure of these two variants with reference showed very similar structure. Furthermore, seven amino acid substitutions were found within these L1 variants of which two substitutions might change the polarity of corresponding amino acid I329T and S383G. The S383G occurred in surface loop (HI-Loop) of new L1 HPV-45 variant. Conclusion: Similar structure of Indonesian variants indicates that amino acids variations do not affect the L1 structure. However, one substitution with altered amino acid polarity found within the area of surface loop suggests a potential impact in antibody recognition and neutralization.     

Surgical Release of the First Extensor Compartment for Refractory de Quervain's Tenosynovitis: Surgical Findings and Functional Evaluation Using DASH Scores

Background

Few studies have evaluated surgical outcomes in patients with refractory de Quervain''s disease using validated outcome measures. We assessed the clinical outcomes of dorsal release of the first extensor compartment for the treatment of de Quervain''s disease using the disabilities of the arm, shoulder and hand (DASH) score.

Methods

From October 2003 to May 2009, we retrospectively evaluated 33 patients (3 men and 30 women) who underwent surgical treatment for de Quervain''s disease. All patients had a positive Finkelstein test and localized tenderness over the first dorsal compartment. All operations were performed under local anesthesia. A 2-cm-long transverse skin incision was made over the first extensor compartment and the dorsal retinaculum covering the extensor pollicis brevis was incised longitudinally. Preoperative and postoperative clinical evaluation included the use of DASH score, Finkelstein test, and visual analogue scale (VAS) score.

Results

In 18 patients (55%), the extensor pollicis brevis tendon compartment was separated from the abductor pollicis longus compartment. Eight patients had intracompartmental ganglia in the extensor pollicis brevis subcompartment. All patients except one had negative sign on Finkelstein test at the last follow-up. The average VAS score decreased from 7.42 preoperatively to 1.33 postoperatively (p < 0.05), and DASH score was improved from 53.2 to 3.45 (p < 0.05). There were no postoperative complications such as subluxation of the tendon of the first dorsal compartment or injury to the sensory branch of the radial nerve.

Conclusions

Intracompartment ganglia and the separate septum of extensor pollicis brevis are often related to de Quervain''s disease. The release of the first extensor compartment for refractory de Quervain''s disease resulted in good clinical outcomes with minimal morbidity.     

Characteristics of drugs safety signals that predict safety related product information update

Purpose

Investigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016.

Methods

A comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI.

Results

Multivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources (adjusted odds ratio [OR] 7.8 95% CI [1.5, 40.1]); mechanistic plausibility of the drug‐event association (adjusted OR 3.9 95% CI [1.9, 8.0]); seriousness of the event (adjusted OR 4.2 95% CI [1.3, 13.9]); and age of drugs ≤5 years (adjusted OR 3.9 95% CI [1.2, 12.7]) were associated with the decision to change the PI (P < 0.05).

Conclusions

This study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates.     

Fatal outbreak of human toxoplasmosis along the Maroni River: epidemiological, clinical, and parasitological aspects.

BACKGROUND: Well-documented outbreaks of human toxoplasmosis infection are infrequently reported. Here, we describe a community outbreak of multivisceral toxoplasmosis that occurred in Patam, a Surinamese village near the French Guianan border. METHODS: From the end of December 2003 through the middle of January 2004, 5 adult patients in Patam, including 2 pregnant women, were initially hospitalized for multivisceral toxoplasmosis. A French-Surinamese epidemiological investigation was conducted in the village; inquiries and clinical examinations were performed, and blood and environmental samples were obtained. For all serologically confirmed cases of toxoplasmosis, molecular analysis and mouse inoculations were performed for diagnosis and genetic characterization of Toxoplasma gondii. RESULTS: The hospitalized patients, who did not have any immunodeficiencies, presented with an infectious disease with multivisceral involvement. Serological examination confirmed acute toxoplasmosis. One adult died, and a neonate and a fetus with congenital toxoplasmosis also died. During the investigation, 4 additional acute cases of toxoplasmosis were diagnosed among the 33 villagers. Only 3 inhabitants had serological evidence of previous T. gondii infection. In total, we reported 11 cases of toxoplasmosis: 8 multivisceral cases in immunocompetent adults, resulting in 1 death; 2 cases of lethal congenital toxoplasmosis in a neonate and a fetus; and 1 symptomatic case in a child. Molecular analysis demonstrated that identical isolates of only 1 atypical strain were responsible for at least 5 of the 11 cases of toxoplasmosis in the outbreak. No epidemiological sources could be linked to this severe community-wide outbreak of toxoplasmosis. CONCLUSION: This report is in agreement with the particular features of toxoplasmosis involving atypical strains that were recently described in French Guiana.     

exSSSRs (extracellular S100 soil sensor receptors)-Fc fusion proteins work as prominent decoys to S100A8/A9-induced lung tropic cancer metastasis

Within the “seed and soil” theory of organ tropic cancer metastasis is a growing compilation of evidence that S100A8/A9 functions as a soil signal that attracts cancer cells to certain organs, which prove beneficial to their growth. S100A8/A9-sensing receptors including Toll-like receptor 4 (TLR4), advanced glycation end products (RAGE), and also important receptors we recently succeeded in identifying (EMMPRIN, NPTNβ, MCAM, and ALCAM) have the potential to become promising therapeutic targets. In our study, we prepared extracellular regions of these novel molecules and fused them to human IgG2-Fc to extend half-life expectancy, and we evaluated the anti-metastatic effects of the purified decoy proteins on metastatic cancer cells. The purified proteins markedly suppressed S100A8/A9-mediated lung tropic cancer metastasis. We hence expect that our novel biologics may become a prominent medicine to prevent cancer metastasis in clinical settings through cutting the linkage between “seed and soil”.