Iodine-mediated C–N and N–N bond formation: a facile one-pot synthetic approach to 1,2,3-triazoles under metal-free and azide-free conditions

A novel strategy towards the synthesis of 1,4-disubstituted 1,2,3-triazoles via C–N and N–N bond formation has been demonstrated under transition metal-free and azide-free conditions. These 1,2,3-triazoles were obtained in a regioselective manner from commercially available anilines, aryl alkenes/aryl alkynes and N-tosylhydrazines using I₂ under O₂ atmosphere. Broad substrate scope, milder reaction conditions, good to moderate yields and clean protocol are the notable features of the method. Moreover, this protocol is amenable for the generation of a library of medicinally important key building blocks.

A novel strategy towards the synthesis of 1,4-disubstituted 1,2,3-triazoles via C–N and N–N bond formation has been demonstrated under transition metal-free and azide-free conditions.     

β-T594M epithelial sodium channel gene polymorphism and essential hypertension in individuals of Indo-Aryan ancestry in Northern India

Background

The T594M variant of the β-subunit of the sodium epithelial channel (ENaC) gene may contribute to hypertension in individuals of Indo-Aryan origin.

Methods

Present study was performed to assess the role of the ENaC gene variant as an independent risk factor for hypertension in subjects of Indo-Aryan ancestry. A total of 150 patients of recently detected essential hypertension and 150 matched controls were genotyped for the T594M polymorphism of the ENaC gene by PCR–RFLP method.

Results

β-T594M mutation was found to be non-polymorphic. There was major genotype call in both the groups i.e. cases and controls. Other phenotypic parameters like age, sex and body mass index were also similar among hypertensive patients and controls (P > 0.05). Hypertensive patients had significantly higher total cholesterol and triglycerides compared with controls (P < 0.0001).

Conclusion

These results do not suggest an important role for the T594M variant of the ENaC gene contributing to either the development or severity of hypertension in subjects of Indo-Aryan ancestry.     

Myocardial Infarction Type 2: Avoiding Pitfalls and Preventing Adverse Outcomes

Myocardial infarction type 2 (MI type 2) is an elevation of cardiac biomarkers in a physiologically stressful state leading to demand-supply mismatch of oxygen. This type of myocardial infarction is commonly seen in hospitalized patients. Since the introduction of clear definition, diagnostic criteria and International Classification of Disease (ICD) codes, the diagnosis has become increasingly common. There still remains plenty to learn about MI type 2 especially prevention and treatment strategies. Studies have shown that there is increased mortality and morbidity associated with MI type 2 when compared to MI type 1, and there may be benefit in having a multi-disciplinary approach including cardiology when treating such patients. Secondary prevention therapies may also play a role in decreasing adverse events from MI type 2. However, randomized control trials are insufficient, and results of studies are cautiously interpreted. In this article we have assessed the current evidence on MI type 2 and the gap in literature that will potentially be the focus of future analyses.     

Liver in the limelight in the corona (COVID-19) time

The novel coronavirus, severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2), is a topic of great interest currently in the medical field due to the significant morbidity and mortality associated with it. There is immense curiosity about this virus as knowledge about it is limited from pathogenesis, host related factors and the variable effect it has on different patient populations. Though it has claimed fame due to its ability to compromise the respiratory system, it possess the capability to infect other organs as well including the liver. It is important for clinicians to recognize that the virus can result in multi-organ dysfunction as well. Presentation with gastrointestinal symptoms and involvement of the liver can be subtle and can be misdiagnosed. Those with pre-existing liver disease may be more susceptible as well as those who are immunosuppressed or have other co-morbidities. This review article provides a brief overview of some of the information that is available so far with regards to how the liver is impacted by the coronavirus.     

The management of epilepsy in pregnancy

While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre-pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.     

Lithium decreased endothelium‐mediated,but not nonadrenergic noncholinergic,relaxation of guinea pig corpus cavernosum in vitro: a role for nitrergic system

Lithium causes erectile dysfunction in patients but its mechanism is yet unknown. The aim of our study was to verify the effect of acute lithium administration on the nonadrenergic noncholinergic (NANC)‐ and endothelium‐mediated relaxation of guinea pig isolated corpus cavernosum. Although lithium (0.5, 1, and 5 mm ) had no effect on the neurogenic relaxations, it significantly (P < 0.001) attenuated the relaxant responses to acetylcholine in a concentration‐dependent manner. Combination of low concentration of lithium (0.5 mm ) with either 0.1 or 1 μm l ‐NAME significantly (P < 0.001) reduced the endothelium‐mediated relaxation. Although the Nitric oxide (NO) precursor l ‐arginine at 1 mm did not alter the relaxant responses to acetylcholine in control strips, it improved the inhibition by lithium (1 mm ) of relaxant responses to acetylcholine. Sodium nitroprusside (SNP; 10 nm –1 mm ) produced similar concentration‐dependent relaxations in both groups. Our experiments indicated that lithium can result in impairment of the NO‐mediated endothelium‐dependent but not NANC relaxation of guinea pig corpus cavernosum.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

DNA testing for fragile X syndrome in schools for learning difficulties

Fragile X syndrome is the most common inherited cause of mental retardation. Early diagnosis is important not only for appropriate management of individuals but also to identify carriers who are unaware of their high risk of having an affected child. The disorder is associated with a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence within the gene at this locus designated FMR1. Clinical and molecular studies have been undertaken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern blot analysis of peripheral blood showed the characteristic abnormally large (CGG)n repeat sequence associated with fragile X syndrome in four of the 154 children. The findings were confirmed by cytogenetic observation of the fragile site and by further molecular studies. The families of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that there are still unrecognised cases of fragile X syndrome. Given the difficulty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.