Lyonia ovalifolia (Angeri) poisoning: A case report

Lyonia ovalifolia (angeri) is a deciduous tree whose shoot and leaves are toxic. Its chemical constituents include grayanane diterpenoids, lyoniol A, and other toxic compounds. Young children might consume it intentionally or unintentionally, with subsequent adverse health outcomes and even mortality depending on the amount ingested. We present a case of an adolescent girl who developed poisoning on ingestion of angeri leaves.     

The silent epidemic: Death by suicide among physicians

Suicidal deaths among physicians have been on a steady rise in the past few decades, despite being a part of the healthcare system, training for early identification and easy access to treatment services. While there is no doubt that this warrants concern at individual, institutional, and community levels, physician suicide remains an under-researched topic. We examine the correlates of suicidal deaths among physicians along with risks and protective factors conferred to physicians as a population and emphasize the need for preventive and risk-reduction initiatives that are specifically tailored for physicians and the healthcare provider community.     

Benzenesulfonamides with trisubstituted triazole motif as selective carbonic anhydrase I,II, IV,and IX inhibitors

Twenty novel 1,2,3-triazole benzenesulfonamides featuring nitrile 8a–g , carbothioamide 9a–f , and N′-hydroxycarboximidamide 10a–g functionalities were designed and synthesized to improve potency and selectivity as carbonic anhydrase inhibitors (CAIs). The synthesized 1,2,3-triazole compounds were tested in vitro as CAIs against four physiologically and pharmacologically relevant isoforms of human carbonic anhydrase (hCA I, II, IV, and IX). Compounds 8a–g , 9a–f , and 10a–g displayed variable inhibition constants ranging from 8.1 nM to 3.22 μM for hCA I, 4.7 nM to 0.50 μM for hCA II, 15.0 nM to 3.7 μM for hCA IV, and 29.6 nM to 0.27 μM for hCA IX. As per the inhibition data profile, compounds 9a–e exhibited strong efficacy for hCA IV, whereas the inhibition was found to be somewhat diminished in the case of hCA IX by nearly all the compounds. A computational protocol based on docking and MM-GBSA was conducted to reveal the plausible interactions of the targeted sulfonamides within the hCA II and IX binding sites. The outcomes of appending various functionalities at the C-4 position of the 1,2,3-triazole motif over the inhibition potential and selectivity of the designed sulfonamides were examined with a potential for the discovery of new isoform selective CAIs. The CAI and SAR data established the significance of the synthesized 1,2,3-triazoles as building blocks for developing CAI drugs.     

Ataxia due to vitamin E deficiency: A case report and updated review

Ataxia with vitamin E deficiency (AVED) is a rare cause of hereditary ataxia in developing countries with unknown prevalence. AVED is an autosomal‐recessive disorder, which is characterized by ataxia, areflexia, and proprioceptive and vibratory sensory loss. The disease is characterized clinically by symptoms with often resembling to those of Friedreich ataxia (FRDA). Vitamin E supplementation improves symptoms and prevents the progression of the disease. In this case report, we reviewed the recently updated findings in AVED in regard to the management and present a case of AVED in a 16‐year‐old boy, who was initially misdiagnosed as FRDA, prior to the genetic test.     

Dynamic assessment of oropharynx with ultrasonography as a screening tool for obstructive sleep apnea

Ultrasonography is an easily available and portable tool to assess the dynamic changes in the upper airway and surrounding soft tissue. This study aimed to evaluate the utility of oropharynx ultrasonography as a screening tool for obstructive sleep apnea (OSA). The study sequentially enrolled overweight individuals (body mass index >25 kg/m²) and subjected them to OSA screening tools (Berlin questionnaire, Epworth Sleepiness Scale and STOP-Bang scores), ultrasonography of the oropharynx followed by overnight polysomnography. A total of 30 healthy individuals were also recruited as controls. Detailed dynamic and static ultrasonography measurements of the oropharynx and surrounding tissue were done. The diagnostic ability of various ultrasonography parameters to detect OSA was determined using receiver operating characteristic curve analysis. A total of 63 subjects were enrolled, with 33 in the OSA group and 30 in non-OSA overweight group. All baseline characteristics were similar in the two groups. Except for the dynamic measurements of oropharynx (Retropalatal% change-inspiration, retropalatal% change-Muller manoeuvre, retroglossal% change-inspiration, and retroglossal% change-Muller manoeuvre) all other parameters were similar in the OSA and non-OSA overweight subjects. The area under the receiver operating characteristic curve was highest for retropalatal% change-inspiration: 0.989, followed by retropalatal% change-Muller manoeuvre: 0.988. Both were also significant predictors of OSA with odds ratios of 0.338 (p = 0.003; 95% confidence interval [CI] 0.164–0.696) and 0.346 (p = 0.018; 95% CI 0.143–0.837), respectively. Ultrasonography provides a near complete picture of the dynamic changes and collapsibility of the oropharynx and can be an effective tool in screening for OSA.     

Heterozygous gain of function variants in a critical region of RNF13 cause congenital microcephaly,epileptic encephalopathy,blindness, and failure to thrive

Missense variants in the RNF13 gene have been previously known to cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive through a gain-of-function disease mechanism. Here, we identify a nonsense variant, expected to result in protein truncation, in a similarly affected patient. We show that this nonsense variant, residing in the terminal exon, is likely to escape nonsense-mediated decay while removing a critical region for protein function, thus resulting in a gain-of-function effect. We review the literature and disease databases and identify several other affected individuals with overlapping phenotypes carrying distinct truncating variants in the terminal exon upstream of the putative critical region. Furthermore, we analyze truncating variants from the general population, namely, the Genome Aggregation Database (gnomAD), and provide additional evidence supporting our hypothesis, and ruling out haploinsufficiency as an alternative disease mechanism. In summary, our case report, literature review, and analysis of disease and population databases strongly support the hypothesis that heterozygous gain-of-function variants in a critical region of RNF13 cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive.