Myroides: A Rare but Hard-to-crack Villain in a Critical Care Setup

How to cite this article: Mahendran AJ, Agrawal S, Rastogi N, et al. Myroides: A Rare but Hard-to-crack Villain in a Critical Care Setup. Indian J Crit Care Med 2021;25(6):735–736.     

Improving mental health care for people with an intellectual disability in Singapore: bridging the health-social care divide

Intellectual disability is known to be associated with a high incidence of psychiatric co-morbidity and problem behaviours. However, there are many challenges in trying to meet the mental health needs of people with an intellectual disability, and these are often not adequately addressed in Singapore's current healthcare system. This article outlines the present service provisions for this area in the country and details the importance of, as well as difficulties in the integration of health and social care measures in service development and delivery.     

Development of a histone deacetylase 6 inhibitor and its biological effects

Development of isoform-selective histone deacetylase (HDAC) inhibitors is important in elucidating the function of individual HDAC enzymes and their potential as therapeutic agents. Among the eleven zinc-dependent HDACs in humans, HDAC6 is structurally and functionally unique. Here, we show that a hydroxamic acid-based small-molecule N-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB) selectively inhibits HDAC6 catalytic activity in vivo and in vitro. HPOB causes growth inhibition of normal and transformed cells but does not induce cell death. HPOB enhances the effectiveness of DNA-damaging anticancer drugs in transformed cells but not normal cells. HPOB does not block the ubiquitin-binding activity of HDAC6. The HDAC6-selective inhibitor HPOB has therapeutic potential in combination therapy to enhance the potency of anticancer drugs.Histone deacetylase 6 (HDAC6) is unique among the eleven zinc-dependent HDACs in humans. HDAC6 is located in the cytoplasm, and it has two catalytic domains and an ubiquitin-binding domain at the C-terminal region (1–3). This study focused on the development of a HDAC6-selective inhibitor and its biological effects. The substrates of HDAC6 include nonhistone proteins such as α-tubulin, peroxiredoxin (PRX), cortactin, and heat shock protein 90 (Hsp90) but not histones (4–7). HDAC6 plays a key role in the regulation of microtubule dynamics including cell migration and cell–cell interactions. The reversible acetylation of Hsp90, a substrate of HDAC6, modulates its chaperone activity and, accordingly, the stability of survival and antiapoptotic factors, including epidermal growth factor receptor (EGFR), protein kinase AKT, proto-oncogene C-RAF, survivin, and other factors. HDAC6, through its ubiquitin-binding activity and interaction with other partner proteins, plays a role in the degradation of misfolded proteins by binding polyubiquitinated proteins and delivering them to the dynein and motor proteins for transport into aggresomes which are degraded by lysosomes (8–10). Thus, HDAC6 has multiple biological functions through deacetylase-dependent and -independent mechanisms modulating many cellular pathways relevant to normal and tumor cell growth, migration, and death. HDAC6 is an attractive target for potential cancer treatment.There are several previous reports on the development of HDAC6-selective inhibitors (11–15). The most extensively studied is tubacin (16, 17). Tubacin has non–drug-like qualities, high lipophilicity, and difficult synthesis and has proved to be more useful as a research tool rather than as a potential drug (18). We and others (12–15, 19) have developed HDAC6-selective inhibitors whose pharmacokinetics, toxicity, and efficacy make them potentially more useful than tubacin as therapeutic agents. ACY-1215, 2-(Diphenylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide, a HDAC6-selective inhibitor, is currently being evaluated in clinical trials (http://clinicaltrials.gov).HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), consist of three structural domains: a metal-binding domain, a linker domain, and a surface domain (20). The catalytic pocket of HDAC1 is deeper and narrower than the catalytic pocket of HDAC6 (14). To develop HDAC6-selective inhibitors, we synthesized small molecules with bulkier and shorter linker domains than the pan-HDAC inhibitor SAHA (20, 21). A hydroxamic acid-based small-molecule N-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB) was synthesized that selectively inhibits HDAC6. We report the effects of this HDAC6-selective inhibitor on normal and transformed cells. Further, we found that selective inhibition of HDAC6 increases the effectiveness of anticancer agents, etoposide, doxorubicin, and SAHA in inducing cell death of transformed cells but not normal cells.     

Quality of life after postoperative endophthalmitis

Purpose: The aim of this study is to determine if postoperative endophthalmitis adversely affects quality of life after cataract surgery. Methods: We compared quality of life in patients who developed endophthalmitis after cataract surgery between 1 January and 31 December 2003 with those who had uncomplicated surgery. The National Eye Institute VFQ‐25 (VFQ‐25) and EuroQol EQ‐5D (EQ‐5D) questionnaires and time trade‐off utility scores were used to compare self‐perceived general health and vision‐related quality of life between groups. Linear regression was used to model differences between groups after adjusting for age, gender and visual acuity in the better eye. Results: Nineteen postoperative endophthalmitis cases were compared with 30 who had uncomplicated cataract surgery. Following surgery the mean composite VFQ‐25 score was 13.5% (95% confidence interval [CI]: 6.0–26.4, P < 0.01) lower in endophthalmitis cases. Endophthalmitis patients reported significantly lower (P < 0.05) general vision, near vision, peripheral vision, mental health and role difficulties subscales scores after adjusting for age, sex and visual acuity. No significant differences were found in other subscales. Mean time trade‐off utility and all EQ‐5D scores were similar except for mobility (95% CI: 0.04–0.68, P < 0.05). Conclusions: Endophthalmitis after cataract surgery negatively impacts on self‐perceived vision‐related quality of life, resulting in poorer psychological well‐being and ability to maintain a role in daily life.