Optimal diagnostic tool for surveillance of oesophageal varices during COVID-19 pandemic.

AIM: To study the diagnostic accuracy and utility of triphasic abdominal computed tomography (CT) in the diagnosis and grading of oesophageal varices (OVs) as an alternative to endoscopy during the COVID-19 pandemic. MATERIALS AND METHODS: A prospective analysis was undertaken of retrospective data from cirrhotic patients who underwent oesophago-gastro-duodenoscopy (OGD) and a triphasic abdominal CT from January to December 2019. Endoscopists and radiologists provided their respective independent assessment of OV grading after being blinded to the clinical details. Performance of CT grading of OVs was compared with the reference standard endoscopic grading using weighted kappa (k). Non-invasive scores such, as aspartate transaminase (AST)-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) Index, platelet: spleen (PS) ratio were correlated between the two techniques. RESULTS: OV grading between endoscopists and radiologists showed 81.73% agreement (85 out of 104 patients) in the comparative analysis of 104 cirrhotic patients, of which no varices (57.1%, n=4), small (85.1%, n=23), medium (72.2%%, n=26), and large varices (94.1%, n=32) with a weighted k score of 0.88 (95% confidence interval 0.82-0.94). Overall, the sensitivity of CT in the diagnosis of no, small, medium, and large OVs was 66.6%, 79.3%, 89.6%, and 94.1%, respectively, with an area under the receiver operating curve (AUROC) score of 0.775, 0.887, 0.839, and 0.914. Performance of APRI, FIB-4, and PS ratio correlated well with the severity of OVs with no difference between OGD and CT grading. CONCLUSION: Triphasic abdominal CT can be an invaluable tool in the diagnosis and grading of OVs during the COVID-19 pandemic.

High frequency of occupied attB regions in Norwegian Staphylococcus aureus isolates supports a two-step MRSA screening algorithm.

Rapid nucleic acid amplification tests for methicillin-resistant Staphylococcus aureus (MRSA) diagnostics commonly target the mec resistance gene, genes specific for S. aureus, and the integration site for the SCCmec resistance cassette, orfX. Due to poor specificity when these target genes are used individually, additional culture is required to verify positive results. The combination of these targets is useful, but the optimal algorithm may depend on the presence of the genetic markers in S. aureus isolates, as well as the prevalence of MRSA in a population. The aim of the present study was to identify a rapid, low-cost, and functional screening algorithm in order to reduce the response time for MRSA diagnostics. An in-house orfX-SCCmec polymerase chain reaction (PCR) assay was established and evaluated. The results were compared with an existing mec/nuc PCR assay and traditional culture. Methicillin-sensitive S. aureus (MSSA) that tested false-positive in the orfX-SCCmec PCR assay were further investigated with full genome sequencing using the Ion PGM™ System to verify results and causality. Based on these data, a two-step screening algorithm with initial mec/nuc PCR followed by orfX-SCCmec PCR on positive samples was suggested and tested on 1443 patient samples. 22.5 % of MSSA isolates tested false-positive with the orfX-SCCmec PCR. Full genome sequencing of these isolates identified genetic variation in the attB region of S. aureus, including empty cassette variants and non-mec SCC. The suggested two-step MRSA screening algorithm allowed us to report MRSA results for 95.6 % of all samples and 99 % of MRSA-negative samples after one day.

Disability and quality of life among elderly persons with mental illness.

The present study was undertaken to understand the level of disability and quality of life of elderly persons with chronic and persistent mental illnesses and to compare it with those who were elderly but well with no illness. For the purpose 200 elderly persons with mental illness (PMI), attending psychiatric services were included in the study. A comparison group of 103 well elderly persons was drawn from the same study area as control group (CG). They were assessed using WHO-DAS and WHOQOL-BREF. Results revealed that PMI experienced higher disability compared to the CG. Deficits in the domain of moving around, getting along with people, engaging in life activities and participation in society contributed most to the high level of disability in the PMI group. PMI from rural area had higher disability compared to the urban group. As for QOL, elderly PMI had a poor quality of life compared to the CG. Quality of life was found to be negatively associated with level of disability. Higher the level of disability, lower was the quality of life. The authors opine that persons with chronic mental illness continue to experience psychiatric disability in old age and this cannot be attributed to normal aging. Level of disability has a negative impact on their quality of life.

Stigma of mental illness: An interventional study to reduce its impact in the community.

BACKGROUND: Research literature has documented the nature of stigma associated with mental illness (MI) and its consequences in all spheres of life of ill persons and their families. It is also suggested that there is a need to develop intervention strategies to reduce stigma. However, very little is reported about these initiatives in the Indian context. AIM: To understand the nature of stigma associated with MI in a rural and semi-urban community in India and to develop an intervention package and study its impact. MATERIALS AND METHODS: The study adopted a pre- and post-experimental/action research design with a random sample of community members including persons with chronic MI and their caregivers from rural and semi-urban areas. A semi structured interview schedule was used to assess the nature of stigma. An intervention package, developed on the basis of initial findings, was administered, and two post assessments were carried out. RESULTS: Stigmatized attitude related to various aspects of MI were endorsed by the respondents. Caregivers had less stigmatizing attitude than the members of the community. Postintervention assessments (PIAs) revealed significant changes in attitudes towards some aspects of MI and this improved attitude was sustained during the second PIA, that is, after 3 months of intervention. CONCLUSION: People in the rural and semi-urban community have stigmatizing attitude toward MI. Intervention package focusing on the relevant aspect of MI can be used for reducing stigma of MI.

Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta).

BACKGROUND & OBJECTIVES: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 µg)] and combination rabies vaccine [CRV (100 µg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. METHODS: As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. RESULTS: In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28 th day. INTERPRETATION & CONCLUSIONS: The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.

Efficacy of psychosocial rehabilitation program: The RFS experience.

BACKGROUND: People with severe and persistent mental illness need help in most aspects of their lives, as the disability associated with these diseases can be debilitating. Psychosocial rehabilitation interventions aim to help them relearn skills that would reduce disabilities so that they can be reintegrated into society. OBJECTIVE: To study the efficacy of the rehabilitation program at the Richmond Fellowship Society (RFS) 'ASHA' half-way home. SUBJECTS: Fifty-four clients diagnosed with either schizophrenia or affective disorder who stayed at the half-way home for more than 6 months. MATERIALS AND METHODS: A retrospective evaluative approach was followed. An evaluation checklist was developed for the purpose and this was used to assess the level of functioning of the clients. A paired sample t-test was used to score changes in client progress between admission and discharge. RESULTS: Significant improvement ( P≤.05 level) was noticed on all the parameters from baseline to discharge. CONCLUSION: The psychosocial rehabilitation program at the RFS half-way home has a beneficial effect.

Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.

The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.

Family support group in psychosocial rehabilitation.

BACKGROUND: Support groups for families of persons with mental illness are emerging as significant components in psychosocial rehabilitation programmes. AIM: To ascertain the expectations of family members who attend family support group meetings and to find out the efficacy of such programmes. METHODS: The data were collected from support group members using a semi-structured interview schedule. The study sample (n=20) was drawn from family members who attended the support group meetings regularly for a minimum period of 6 months. Data analysis was done using percentile. RESULTS: Analysis of the data revealed that members attending the support group meetings expected to get more information about the illness, develop skills to cope with problems at home and learn skills to deal with the ill person. An important finding of the study was that the members developed a 'feeling of togetherness' as a result of being a member of a group with common aims. CONCLUSION: Participation in a support group meeting positively affects key variables in the participant's adaptation to mental illness in a relative.

Coacervate microspheres as carriers of recombinant adenoviruses.

The therapeutic utility of recombinant adenoviruses (rAds) is limited in part by difficulties in directing the viruses to specific sites and by the requirement for bolus administration, both of which limit the efficiency of target tissue infection. As a first step toward overcoming these limitations, rAds were encapsulated in coacervate microspheres comprised of gelatin and alginate followed by stabilization with calcium ions. Ultrastructural evaluation showed that the microspheres formed in this manner were 0.8-10 microM in diameter, with viruses evenly distributed. The microspheres achieved a sustained release of adenovirus with a nominal loss of bioactivity. The pattern of release and the total amount of virus released was modified by changes in microsphere formulation. Administration of the adenovirus-containing microspheres to human tumor nodules engrafted in mice showed that the viral transgene was transferred to the tumor cells. It is concluded that coacervate microspheres can be used to encapsulate bioactive rAd and release it in a time-dependent manner.

The Yelandur study: a community-based approach to epilepsy in rural South India--epidemiological aspects.

Data on the epidemiology of epilepsy in a rural community in a developing country would be of value in planning a decentralized management of this malady in its early stages commensurate with available local resources. A detailed screening instrument covering various seizure types was used by trained paramedical workers in a door-to-door survey of a population of 64,963 in rural South India. The prevalence period was from 1 April 1990 to 31 March 1991. The crude prevalence rate per 1000 for active epilepsy was 4.38 for males, 3.40 for females and 3.91 for both. The minimum and maximum prevalence rates, the latter computed from a validation sample, were 3.91 and 4.63 for active epilepsy; 0.28 and 0.77 for inactive epilepsy and 4.19 and 5.41 for life-time prevalence. In addition, corresponding figures for hot-water epilepsy, a type of reflex epilepsy peculiar to this area, were 2.49 and 2.99 for active phase; 0.35 and 0.85 for inactive phase and 2.85 and 3.83 for life-time prevalence. The incidence rate for epilepsy was 49.3 per 100,000, the same as in developed countries. These data do not support the concept that the prevalence of epilepsy in developing countries is twice that in the developed world. However, the role of local/regional variations should be borne in mind before extrapolating the figures to an entire country.

A finite element model for predicting the distribution of drugs delivered intracranially to the brain.

Drug therapy to the central nervous system is complicated by the presence of the blood-brain barrier. The development of new drug delivery techniques to overcome this obstacle will be aided by a clear understanding of the transport processes in the brain. A rigorous theoretical framework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonance imaging has been used to track the transport of paramagnetic contrast markers in the brain. The information obtained by postprocessing spin-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and salient anatomic features and allows for two-dimensional transport of chemical species, including both diffusive and convective contributions. In addition, the effects of regional differences in tissue properties, ventricular boundary, and edema on the transport have been considered. The model has been used to predict transport of interleukin-2 in the brain and study the major determinants of transport, at both early and late times after drug delivery.

Utilization of tyrosine and tryptophan for protein synthesis by undernourished developing rat brain.

Incorporation of tracer doses of radiolabeled tryptophan and tyrosine into brain proteins was investigated in rats malnourished during gestation and lactation. Age and time dependent increases in the radioactivity was observed in the whole homogenate and in the TCA insoluble fraction. Protein malnourished rats showed increased incorporation of tryptophan and tyrosine. However the diet restricted (Pair-fed) animals showed increased incorporation of tyrosine only. The increased incorporation may probably be due to changes in the pool size of the amino acids and effective recycling of the amino acids. The enhanced utilization in protein synthesis may also probably offer a mechanism for conservation of these amino acids.

Free amino acid levels in undernourished developing rat brain.

Free amino acid levels in the brains of young ones born to mothers fed a 20% protein diet ad libitum (well nourished), 7.5% protein diet ad libitum (protein restricted) and a 20% protein diet in restricted amounts (pair-fed) were investigated during brain development in the present study. The dietary protein was obtained from a cereal-legume mixture. Protein restricted animals showed increases in the levels of taurine, glycine and glutamic acid and decreases in the concentrations of methionine, leucine, isoleucine, and GABA. The pair-fed animal showed increases only in glutamic acid and glycine and a decrease only in the levels of GABA. The significance of these observations is discussed.

Single daily dose chlorpromazine therapy in psychosis. An evaluation.

A double blind study was undertaken to compare the efficacy of a single bedtime dose of chlorpromazine (300 mg) with divided doses of the same drug (100 mg, thrice daily). Brief Psychiatric Rating Scale (BPRS) and Nurses' Observation Scale for Inpatient Evaluation (NOSIE) were administered to 80 acutely psychotic patients who took part in the study. Thirty-one patients in the experimental and 29 in the control group completed this 3-week trial. It was observed that there were no statistically significant differences between the two modes of treatment. Drowsiness was seen more often in the single bedtime schedule. Postural hypotension was observed in both patient groups. The implications of single night-time medication in psychotics is discussed.