Less is more: Validating a single method for comprehensive rh-insulin analysis.

The objective of this current study is to establish a single method for potency and related proteins analysis of human insulin formulations using reverse-phase high performance liquid (RP-HPLC) chromatography technique which was validated and verified for the potency analysis in insulin formulations. Chromatographic separation was achieved using an octadecylsilane (C-18) stationary phase and a mobile phase composed of 55% (v/v) buffer (0.2 M sodium sulfate in water, {pH 2.3}) and 45% (v/v) acetonitrile. Detection was performed by UV detector at 214 nm with a flow rate of 1 ml/min and an injection volume of 20 µL, at 40°C. Currently there are separate methods available in Indian Pharmacopoeia for analysis of Potency and Related proteins in human insulin. We have validated a single method where quantitation of potency and related proteins can be performed in the same run. The method validation exhibited linearity over the concentration range of 0.08-4.5 mg/ml (r2=0.999) with limit of detection of 0.094 mg/ml The accuracy of the method was 99-102.8%. Thus, it is proposed that both potency and related proteins in insulin formulations can be precisely evaluated using a single run thus saving the time and cost for quality analysis of insulin preparations both at manufacturing and regulatory laboratories which in turn will increase the market availability of such standard quality insulin preparations for public health use.

Aggrephagy-related gene signature correlates with survival and tumor-associated macrophages in glioma: Insights from single-cell and bulk RNA sequencing.

BACKGROUND: Aggrephagy is a lysosome-dependent process that degrades misfolded protein condensates to maintain cancer cell homeostasis. Despite its importance in cellular protein quality control, the role of aggrephagy in glioma remains poorly understood. OBJECTIVE: To investigate the expression of aggrephagy-related genes (ARGs) in glioma and in different cell types of gliomas and to develop an ARGs-based prognostic signature to predict the prognosis, tumor microenvironment, and immunotherapy response of gliomas. METHODS: ARGs were identified by searching the Reactome database. We developed the ARGs-based prognostic signature (ARPS) using data from the Cancer Genome Atlas (TCGA, n = 669) by Lasso-Cox regression. We validated the robustness of the signature in clinical subgroups and CGGA cohorts (n = 970). Gene set enrichment analysis (GSEA) was used to identify the pathways enriched in ARPS subgroups. The correlations between ARGs and macrophages were also investigated at single cell level. RESULTS: A total of 44 ARGs showed heterogeneous expression among different cell types of gliomas. Five ARGs (HSF1, DYNC1H1, DYNLL2, TUBB6, TUBA1C) were identified to develop ARPS, an independent prognostic factor. GSEA showed gene sets of patients with high-ARPS were mostly enriched in cell cycle, DNA replication, and immune-related pathways. High-ARPS subgroup had higher immune cell infiltration states, particularly macrophages, Treg cells, and neutrophils. APRS had positive association with tumor mutation burden (TMB) and immunotherapy response predictors. At the single cell level, we found ARGs correlated with macrophage development and identified ARGs-mediated macrophage subtypes with distinct communication characteristics with tumor cells. VIM+ macrophages were identified as pro-inflammatory and had higher interactions with malignant cells. CONCLUSION: We identified a novel signature based on ARGs for predicting glioma prognosis, tumor microenvironment, and immunotherapy response. We highlight the ARGs-mediated macrophages in glioma exhibit classical features.

Efficacy of Transdermal Ketoprofen Patch in Comparison to Transdermal Diclofenac Patch in Postoperative Analgesia for Orthodontic Extractions: A Randomized Split-Mouth Study.

Introduction Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed analgesics for controlling post-exodontia pain, administered by various routes. The transdermal route possesses the advantages of providing sustained release of the drug, being non-invasive, bypassing first-pass metabolism, and eliminating gastrointestinal adverse effects. This study compared the analgesic efficacy of diclofenac 200 mg and ketoprofen 30 mg transdermal patches for post-orthodontic exodontia pain. Materials and methods Thirty patients who underwent orthodontic bilateral maxillary and/or mandibular premolar extractions under local anaesthesia were included in the study. Each patient received single transdermal diclofenac 200 mg patch and single transdermal ketoprofen 30 mg patch on the outer, ipsilateral upper arm immediately post-extraction in the two appointments in random order. The pain score was recorded every second hourly for the first 24 hours postoperatively using a visual analog scale (VAS). The requirement of rescue analgesics at various time points and the total number of rescue analgesics taken in the first 24 hours postoperatively were noted. Any allergic reaction to the transdermal patches was also recorded. Results The analgesic efficacy of the two transdermal patches at any given time point in 24 hours by Mann-Whitney U test showed no statistically significant (p<0.05) difference. An overall intragroup statistically significant difference (p<0.05), by Wilcoxon matched pairs test, was found by comparison of VAS pain scores at different time points to that at 0-2 hours after application of transdermal ketoprofen and diclofenac patches, respectively. The mean maximum pain intensity was slightly lower for ketoprofen (2.33) than diclofenac (2.60) transdermal patch. Patients consumed the rescue analgesic within the first 12 hours postoperatively, with the mean value of the total number of rescue analgesics taken with ketoprofen transdermal patch (0.23) slightly lower than diclofenac transdermal patch (0.27) application. Conclusion Ketoprofen and diclofenac transdermal patches provide similar analgesia post orthodontic extraction. The patients required rescue analgesics only during the initial hours of the postoperative follow-up period.

Characteristics and result reporting of registered COVID-19 clinical trials of Chinese and Indian traditional medicine: A comparative analysis.

Objective: To assess the main characteristics and result reporting of registered COVID-19 interventional trials of traditional Chinese medicine and traditional Indian medicine. Materials and methods: We assessed design quality and result reporting of COVID-19 trials of traditional Chinese medicine (TCM) and traditional Indian medicine (TIM) registered before 10 February 2021, respectively, on Chinese Clinical Trial Registry (ChiCTR) and Clinical Trial Registry-India (CTRI). Comparison groups included registered COVID-19 trials of conventional medicine conducted in China (WMC), India (WMI), and in other countries (WMO). Cox regression analysis was used to assess the association between time from trial onset to result reporting and trial characteristics. Results: The proportion of COVID-19 trials investigating traditional medicine was 33.7% (130/386) among trials registered on ChiCTR, and 58.6% (266/454) on CTRI. Planned sample sizes were mostly small in all COVID-19 trials (median 100, IQR: 50-200). The proportion of trials that were randomized was 75.4 and 64.8%, respectively, for the TCM and TIM trials. Blinding measures were used in 6.2% of the TCM trials, and 23.6% of the TIM trials. Cox regression analysis revealed that planned COVID-19 clinical trials of traditional medicine were less likely to have results reported than trials of conventional medicine (hazard ratio 0.713, 95% confidence interval: 0.541-0.939; p = 0.0162). Conclusion: There were considerable between-country and within-country differences in design quality, target sample size, trial participants, and reporting of trial results. Registered COVID-19 clinical trials of traditional medicine were less likely to report results than trials of conventional medicine.

Detection and removal of poly and perfluoroalkyl polluting substances for sustainable environment.

PFAs (poly and perfluoroalkyl compounds) are hazardous and bioaccumulative chemicals that do not readily biodegrade or neutralize under normal environmental conditions. They have various industrial, commercial, domestic and defence applications. According to the Organization for Economic Co-operation and Development, there are around 4700 PFAs registered to date. They are present in every stream of life, and they are often emerging and are even difficult to be detected by the standard chemical methods. This review aims to focus on the sources of various PFAs and the toxicities they impose on the environment and especially on humankind. Drinking water, food packaging, industrial areas and commercial household products are the primary PFAs sources. Some of the well-known treatment methods for remediation of PFAs presented in the literature are activated carbon, filtration, reverse osmosis, nano filtration, oxidation processes etc. The crucial stage of handling the PFAs occurs in determining and analysing the type of PFA and its remedy. This paper provides a state-of-the-art review of determination & tools, and techniques for remediation of PFAs in the environment. Improving new treatment methodologies that are economical and sustainable are essential for excluding the PFAs from the environment.

Electrospun Cellulosic Membranes toward Efficient Chiral Resolutions via Enantioselective Permeation.

Cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC), known as one of the most versatile chiral selectors packed in columns for chiral chromatography, is electrospun for the first time. The electrospun nanofibers with a mean diameter of 329 nm form a self-standing nonwoven textile with a specific surface area of 5.6 m2/g. The textile is sandwiched between commercially available polytetrafluoroethylene membrane filters as a support material to fabricate a CDMPC membrane system for the chiral resolution of a racemic mixture, (R,S)-1-(1-naphthyl)ethanol. A vacuum filtration of the racemic mixture through the membrane system using a mixed solvent of n-hexane/2-propanol = 9/1 (v/v) enriches the S-enantiomer in the filtrate due to an enantioselective sorption of the R-enantiomer. The sorption capacity can be regenerated repeatedly via extractions of the adsorbed enantiomers from the membrane system after the filtrations. By repeating the vacuum filtration-extraction process for 15 cycles, the enantiomeric excess (e.e.) of the S-isomer in the filtrate increases up to 32.9%.

Essential and Expendable: Migrant Domestic Workers and the COVID-19 Pandemic.

In this article, we examine the effects of the COVID-19 pandemic on the labor conditions of domestic workers in the epicenter of the United States. We focus our analysis on the symbolic categorization of domestic work as "essential labor." While domestic workers are lauded as heroes in public discourse, we argue that this symbolic recognition does not extend to material remuneration. Instead, we find that labor conditions better fit their categorization as expendable essential workers, meaning those whose essential labor is magnified during the pandemic but whose work remains materially undervalued. Data used in this article draw from observations of more than 30 hours of virtual town hall meetings on the pandemic hosted by migrant domestic worker advocacy groups in Los Angeles and New York.

Permanent superhydrophilic surface modification in microporous polydimethylsiloxane sponge for multi-functional applications.

Polydimethylsiloxane (PDMS) is one of the most preferred material in microfluidic device/biomedical applications because of its unique properties. However, improvement in surface wettability of PDMS is highly desired for microfluidic and biomedical applications as its surface is inherently hydrophobic in nature that restricts flow of aqueous fluid or adherence of biomolecules onto its surface. In spite of several surface modification techniques, prompt recurrence of hydrophobic properties is quite typical in PDMS. Here, we demonstrate a facile and a permanent conversion of a hydrophobic PDMS sponge onto a superhydrophilic state. PDMS sponge was prepared using an eco-friendly sugar leaching method and modified by an ultra-thin coating of polyacrylic acid (PAA). The resultant PDMS-PAA hybrid sponge was found to have highly stable and sustained superhydrophilic property for more than 18 months with water absorption efficiency as high as 89%. Valuable applications like, portable pressure pump in a microfluidic device and as a bioactive matrix for microbial cell immobilization for biodegradation of distillery industry effluent treatment has been demonstrated using these surface modified PDMS sponges.

Multiple skin cancers in a single patient: Multiple pigmented Bowen's disease, giant basal cell carcinoma, squamous cell carcinoma.

Basal cell carcinoma (BCC) and squamous cell carcinoma are the most common type of nonmelanoma skin cancers (NMSCs). Bowen's disease (BD), a premalignant condition, has a marginal potential (3-5%) to progress to invasive carcinoma. We report here a rarest of a rare case of multiple pigmented BD with overlying squamous cell cancer along with a giant neglected BCC on the scalp of a 76-year-old man. The occurrence of multiple BD and NMSC in a single patient compelled us to explore the following hypothesis: (1) The multiple precancerous and cancerous lesions can be due to common etiopathogenesis. Chronic ultraviolet exposure, immunosupresssion, human papillomavirus infection, dietary factors, and environmental factors including arsenic exposure were probed in to. (2) There is evolution of precancerous lesions into a different type of cancers in different time frame. (3) The new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.