Molecular therapies for viral hepatitis

Current treatment modalities available for hepatitis B virus (HBV) or hepatitis C virus (HCV) infections are not efficient. The enormous disease burden caused by these two infections makes the development of novel therapies critical. For HCV, the development of an effective vaccine is urgent in view of the escalating number of infected individuals. Molecular therapies for HBV and HCV infection can be directed at reducing viral load by interfering with the life cycle of the viruses or at generating immune response against viral epitopes. The antiviral approaches consist of the delivery or expression of antisense RNAs, ribozymes or dominant negative proteins. Viral biology can be interrupted by attacking various potential targets within the two viruses. DNA-based vaccination strategies are being explored for both prevention and treatment of these diseases. Both non-viral and recombinant viral vectors are being developed for safe, effective and long-term gene transfer to the liver. Although no "ideal" vector is available at this time, the ingenuity of numerous investigators is leading to the improvement of the vector systems, promising successful application of gene therapy to the prevention and treatment of viral hepatitis in the foreseeable future.     

Method for rapid identification and differentiation of the species of the Mycobacterium chelonae complex based on 16S-23S rRNA gene internal transcribed spacer PCR-restriction analysis

Members of the Mycobacterium chelonae complex (MCC), including M. immunogenum, M. chelonae, and M. abscessus, have been associated with nosocomial infections and occupational hypersensitivity pneumonitis due to metalworking fluid (MWF) exposures. In order to minimize these health hazards, an effective and rapid assay for detection of MCC species and differentiation of MCC species from other species of rapidly growing mycobacteria (RGM) and from one another is warranted. Here we report such a method, based on the variable 16S-23S rRNA gene internal transcribed spacer (ITS) region. Mycobacterium genus-specific primers derived from highly conserved sequences in the ITS region and the flanking 16S rRNA gene were used. Specificity of the primers was verified using the MCC member species, 11 non-MCC RGM species, 3 slow-growing mycobacterial (SGM) species (two strains each), and 19 field isolates, including 18 MCC isolates (from in-use MWF) and one non-MCC isolate (from reverse osmosis water). The ITS amplicon size of M. immunogenum varied from those of M. chelonae and M. abscessus. Sequencing of the approximately 250-bp-long ITS amplicons of the three MCC member species showed differences in 24 to 34 bases, thereby yielding variable deduced restriction maps. ITS PCR-restriction analysis using the in silico-selected restriction enzyme MaeII or HphI differentiated the three MCC members from one another and from other RGM and SGM species without sequencing. The enzyme MaeII discriminated all three member species; however, HphI could only differentiate M. immunogenum from M. chelonae and M. abscessus. Use of an optimized rapid DNA template preparation step based on direct cell lysis in the PCR tube added to the simplicity and adaptability of the developed assay.     

Primary carcinoma of the frontal sinus

A case of Primary Carcinoma of the Frontal Sinus.     

Soft tissue aneurysmal bone cyst of left hemithorax with review of literature

Soft tissue aneurysmal bone cysts (STABCs) are extremely rare extraosseous counterpart of aneurysmal bone cyst (ABC), with close resemblance to histo-morphologic characteristics of ABC. Here we would like to report a 13-year-old female patient, who presented with a large mass, occupying the entire left hemithorax. Patient underwent resection of the thoracic mass. On histopathological examination, it was found to be a soft tissue ABC. It is a very rare tumor and until date 28 cases have been reported in English literature, to the best of our knowledge. On review of the literature, we found this to be the first case of STABC reported in thoracic cavity. The objective of this case presentation is to provide information regarding clinical presentation, radiological and pathological features, and course of management for this rare disease. Soft tissue ABCs are a new class of tumors, so more extensive research is required to establish standard guidelines for their diagnosis and management, to yield better prognosis.     

Immune checkpoint inhibitor therapy-associated graft intolerance syndrome in a failed kidney transplant recipient

Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies against inhibitory receptors on T cells resulting in anticancer activity. In kidney transplant (KT) recipients, ICPI use has been associated with acute allograft rejection. In failed allografts, however, the effects of ICPIs are unknown. We present a case of a 66-year-old man with a history of diabetes, renal cell cancer, left native nephrectomy, and end-stage kidney disease. He received a deceased donor KT which failed after 6 years due to biopsy-proven recurrent diabetic nephrosclerosis. He was started on hemodialysis and his immunosuppression was gradually weaned off. A year later, he was diagnosed with renal cell cancer in his right native kidney requiring nephrectomy. He later developed metastasis and was started on combination ICPIs. He developed hematuria, allograft pain, and malaise consistent with graft intolerance syndrome 28 days after starting ICPIs. Urine culture and cystoscopy were normal. A computed tomography scan of his abdomen revealed an enlarged allograft with patchy enhancement. After a multidisciplinary discussion, he underwent transplant nephrectomy. Histopathology showed chronic active T cell–mediated rejection. As ICPI use becomes prevalent, practitioners need to be aware of its potential complications among KT recipients both with functioning and failed allografts.     

Factors Influencing the Sex Ratio at Birth in India: A New Analysis based on Births Occurring between 2005 and 2016

Previous research on sex ratio at birth (SRB) in India has largely relied on macro‐analysis of census data that do not contain the breadth of factors needed to explain patterns in SRB. Additionally, no previous research has examined the differentiation of factors associated with SRB across birth orders, a key determinant in societies affected by son preference. This study aims to fill these gaps using micro‐data related to 553,461 births occurring between 2005 and 2016 collected as part of the 2015–2016 National Family Health Survey. Analyses used multivariable logistic regressions stratified by birth order to examine associations with SRB at the national level. The SRB at birth order 1 was outside the biological normal limit, and generally increased with birth order. First births in households with wealth in the middle and richest quintiles, with mothers who desired a higher ideal number of sons than daughters, and in lower fertility communities had a higher probability of being male. Most SRB correlates were visible at birth orders 3 or higher. Programs and policies designed to address India's male‐skewed SRB must consider the diverse factors that influence SRB, particularly for higher order births.     

Mobile methadone dispensing in Delhi,India: implementation research

ObjectiveTo assess the implementation of a mobile dispensing service to improve opioid users’ access to methadone maintenance therapy.MethodsIn March 2019, we started mobile methadone dispensing in an urban underprivileged locality in Delhi, India. The doctor was available only at the main community drug treatment clinic for clinical services, while the nurse dispensed methadone from a converted ambulance. We involved patients in identifying community leaders for sensitization and in deciding the location and timings for dispensing. We conducted a retrospective chart review of the programme data collected during delivery of clinical services. We compared the numbers of patients registered for methadone therapy and their retention and adherence to therapy in the 12-month periods before and after implementation of the mobile service.FindingsThe number of patients registered for therapy at the clinic increased from 167 in the year before implementation to 671 in the year after. A significantly higher proportion of patients were retained in therapy at 3, 6 and 9 months after enrolment; 9-month retention rates were 19% (32/167 patients) and 45% (44/97 patients) in the year before and after implementation, respectively. There was no significant difference in patients’ adherence to therapy between the two periods. Challenges included providing suitable dispensing hours for patients in employment and concerns of local community near to the dispensing sites.ConclusionIt is feasible to dispense methadone by a mobile team in an urban setting, with better retention rates in therapy compared with dispensing through a stationary clinic.     

Clinical presentation,viral kinetics,and management of human monkeypox cases from New Delhi,India 2022

We describe the clinical and demographic characteristics, virological follow-up, and management of five confirmed monkeypox cases from New Delhi, India without any international travel history. The viral load kinetics and viral clearance were estimated in oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), EDTA blood, serum, urine, and various lesion specimens on every fourth day of follow-up ranging from 5 to 24 post onset day (POD) of illness. All five cases presented with mild to moderate-grade intermittent fever, myalgia, and lesions on the genitals, groins, lower limb, trunk, and upper limb. Four cases had non-tender firm lymphadenopathy. No secondary complications or sexually transmitted infections were recorded in these cases except for the presence of viral hepatitis B infection marker hepatitis B virus surface antigen (HBsAg) in one case. All the cases were mild and had a good recovery. A higher viral load was detected in lesion fluid (POD 9), followed by lesion roof (POD 9), urine (POD 5), lesion base (POD 5), and OPS/NPS (POD 5). The monkeypox virus (MPXV) DNA was detected in clinical samples from 5th to 24th POD. These monkeypox cases without international travel history suggest the underdiagnosed monkeypox infection in the community. This emphasizes the need for active surveillance of MPXV in the high-risk population such as men having sex with men and female sex workers.