Seeking graduation in medical colleges outside India: Is it a 'win-win' or 'lose-lose' situation for the stakeholders and the nation?

The future of Indian students who return as 'foreign medical graduates' (FMG) after training in certain countries is often uncertain. We collected data from newspapers, government resources and agencies involved in handling this issue. We analysed the current status of medical education in India, the Commonwealth of Independent States (CIS) and some neighbouring countries. Of approximately 1.4 million (14 lakh) students taking the National Eligibility cum Entrance Test (NEET), about 5.8% get admission in medical colleges. There are about 554 medical colleges in India with 82 550 MBBS seats, 51.9% seats belong to the government quota. Parents who send their children to a foreign country to do medicine spend ₹1.5 million (15 lakh) tò4 million (40 lakh) against an estimated annual income of ₹1.2 million (12 lakh) and the child spends 4-6 years in a foreign country. Of 38 150 FMGs who took the examinations conducted by the National Board of Examinations from 2015 to 2018, 18.9% passed the FMG examination mandatory for registration to practise medicine in India. The National Medical Commission is trying to solve this issue by removing the age bar for entry to MBBS and recommending lowering of fees for MBBS in government quota. Seeking graduation in medical colleges outside India may not be advisable for those from the middle/ low-income group of India.

Measurements of an ablator-gas atomic mix in indirectly driven implosions at the National Ignition Facility.

We present the first results from an experimental campaign to measure the atomic ablator-gas mix in the deceleration phase of gas-filled capsule implosions on the National Ignition Facility. Plastic capsules containing CD layers were filled with tritium gas; as the reactants are initially separated, DT fusion yield provides a direct measure of the atomic mix of ablator into the hot spot gas. Capsules were imploded with x rays generated in hohlraums with peak radiation temperatures of ∼294 eV. While the TT fusion reaction probes conditions in the central part (core) of the implosion hot spot, the DT reaction probes a mixed region on the outer part of the hot spot near the ablator-hot-spot interface. Experimental data were used to develop and validate the atomic-mix model used in two-dimensional simulations.

Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation.

Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen-reactive Tregs (arTregs) are more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short-term cultures using good manufacturing practice-compliant reagents. This process uses CD40L-activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100- to 1600-fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen-expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model.

Behavioral rehabilitation of the eye closure reflex in senescent rats using a real-time biosignal acquisition system.

In this paper the replacement of a lost learning function of rats through a computer-based real-time recording and feedback system is shown. In an experiment two recording electrodes and one stimulation electrode were implanted in an anesthetized rat. During a classical-conditioning paradigm, which includes tone and airpuff stimulation, biosignals were recorded and the stimulation events detected. A computational model of the cerebellum acquired the association between the stimuli and gave feedback to the brain of the rat using deep brain stimulation in order to close the eyelid of the rat. The study shows that replacement of a lost brain function using a direct bidirectional interface to the brain is realizable and can inspire future research for brain rehabilitation.

Islands as nanometric probes of strain distribution in heterogeneous surfaces.

Many of the surface phenomena are driven by elastic energy and elastic interactions. Despite the fact that there are many microscopic techniques with nm and atomic resolution, an established technique to study the distribution of strain on the surface is still lacking. We present a study on the Gd(0001)/W(110) system, in which undulations in the Gd layer are detected by STM. This creates a heterogeneous surface with reduced strains, due to relaxation, on the crests of the waved surface and elevated strains in the troughs. An additional part of the strain is released through Stransky-Krastanov growth of Gd islands. Utilizing a strain-relief model, we show that the island size and shape reflect the strain variations on the surface. Strain maps were calculated, using the island as nanoprobes, with good correlation to the surface topography.

Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder.

OBJECTIVE: This is a study estimating diagnostic accuracy of CSF asialotransferrin to transferrin ratio measurement in eIF2B related disorders by using clinical evaluation and EIF2B mutation analysis as the reference standard. eIF2B-related disorder is a relatively common leukodystrophy with broad phenotypic variation that is caused by mutations in any of the five EIF2B genes. There is a need for a simple and clinically valid screening tool for physicians evaluating patients with an unclassified leukodystrophy. METHODS: CSF two-dimensional gel (2DG) electrophoresis analyses to measure asialotransferrin to transferrin ratios were performed in 60 subjects including 6 patients with documented EIF2B gene mutations, patients with other types of leukodystrophy, and patients with no leukodystrophy. RESULTS: All six patients with mutation proven eIF2B-related disease showed low to nearly undetectable amounts of asialotransferrin in their CSF when compared to 54 unaffected controls by CSF 2DG analyses in this study. eIF2B-like patients, with clinically similar presentations but no mutations in EIF2B1-5, were distinguished from patients with mutations in EIF2B1-5 by this biomarker. Patients with mutations in EIF2B1-5 had asialotransferrin/transferrin ratio levels significantly different from the group as a whole (p < 0.001). Using 8% asialotransferrin/transferrin ratio as a cutoff, this biomarker has a 100% sensitivity (95% CI = 52-100%) and 94% specificity (95% CI = 84-99%). CONCLUSION: Decreased asialotransferrin/transferrin ratio in the CSF of patients with eIF2B-related disorder is highly sensitive and specific. This rapid (<48 hours) and inexpensive diagnostic tool for eIF2B-related disorders has the potential to identify patients with likely eIF2B-related disorder for mutation analysis.

IL18 and IL18R1 polymorphisms, lung CT and fibrosis: A longitudinal study in coal miners.

It has been suggested that interleukin (IL)-18 plays a role in the development of inflammatory and fibrosing lung diseases. Associations of polymorphisms in the genes coding for IL-18 (IL18 /G-656T, C-607A, G-137C, T113G, C127T) and its receptor (IL18R1 /C-69T) with coal workers' pneumoconiosis (CWP) were studied in 200 miners who were examined in 1990, 1994 and 1999. Coal-dust exposure was assessed according to job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-yr change in CT score and CWP incidence and prevalence. CT score in 1990 was a good predictor of radiographic grade in 1999 and, therefore, an appropriate subclinical quantitative trait. The IL18 -137C allele was associated with lower CT score in 1990 and 1994 (1.24 versus 1.69 and 1.57 versus 2.46, respectively), slower progression of CT score between 1990 and 1994 and lower pneumoconiosis prevalence in 1999 relative to the G allele (0.33 versus 0.77 and 8.2 versus 19.6%, respectively). Smoking- or dust-adjustment, and stratification on IL18R1 genotype and adjustment for haplotype effects did not change the conclusions. In conclusion, the results of the present study suggest a role for IL18 in reducing the development of this fibrosing lung disease.

Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders.

OBJECTIVE: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. METHODS: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. RESULTS: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. CONCLUSIONS: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.

Sharing of the home base: a social test in rats.

The open field provides abundant opportunities for a pair of rats to express social interactions. Rats demonstrate social proximity while exploring the open field and also during simultaneous occupancy of a home base (HB). The HB is defined as a place in the field for which rats show a long-term preference, both in terms of occupancy and as a starting and ending point of exploratory excursions. In the present study, the social proximity of pairs of rats treated with phencyclidine (PCP; 2 mg/kg) or saline (Sal), and rats treated with clozapine (CLZ; 1.3 mg/kg) alone or in combination with PCP (CLZ-PCP), was videotaped and analysed algorithmically. PCP was tested for its disruptive effects on social interactions, and CLZ was tested for its ability to reverse some forms of the disruptive effects of PCP. The results showed that PCP reduced the rate of pairs establishing a common HB and shortened social HB occupancy, but had no effect on episodes of social exploration in the field. These findings demonstrate that the antisocial effect of PCP cannot be generalized across the entire spectrum of behavioural states in the open field. CLZ further decreased rather than increased social HB occupancy. This effect was derived from the reduction in rate of pairs establishing a common HB.

Effect of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners: a model of gene-environment interaction. Tumour necrosis factor and lymphotoxin alpha.

INTRODUCTION: Interaction between genetic background and oxidative environmental stimuli in the pathogenesis of human lung disease has been largely unexplored. METHODS: A prospective epidemiological study was undertaken in 253 coal miners. Intermediate quantitative phenotypes of response to oxidant exposure, including erythrocyte glutathione peroxidase (GSH-Px) and catalase activities, were studied. Oxidant exposures studied were smoking habits and cumulative dust exposure assessed by job history and ambient measures. Disease phenotypes included subclinical computed tomography score at the first survey and x ray profusion grades twice, five years apart, to assess established coal workers' pneumoconiosis (CWP). Miners were genotyped for common functional polymorphisms in the gene for tumour necrosis factor alpha (TNF) and lymphotoxin alpha (LTA), two proinflammatory cytokines that have been implicated in the pathogenesis of chronic lung diseases. RESULTS: Regarding gene-environment interaction on intermediate phenotypes, results showed interaction of a promoter polymorphism at the -308 position in TNF with occupational exposure on erythrocyte GSH-Px activity with a significant association in those with high exposure (p=0.003), whereas no association was observed among those with low exposure (interaction p=0.06). Regarding gene intermediate phenotype interaction on clinical outcome, results showed an association of CWP prevalence with an NcoI polymorphism in LTA in those with low catalase activity (p=0.05), whereas no association was observed in those with high activity (interaction p=0.03). No other significant association was observed. CONCLUSION: The results suggest that interactions of genetic background with environmental exposure and intermediate response phenotypes are important components in the pathogenesis of CWP.

Social attraction between rats in open field: long-term consequences of kindled seizures.

Kindling of the amygdaloid complex in rats results in an enhanced emotionality frequently expressed by an elevated anxiety and defensive attitude toward other animals. Defensive attitude may have important consequences in social context and if tested in a large space it may eventually lead to social withdrawal. To test this hypothesis, rats were subjected to daily kindling sessions and their behavior was compared to implanted-sham and intact rats. Blood was collected after selected kindling trials for assessment of corticosterone response. Behavioral tests started 1 month after the last kindling trial and consisted of two open field sessions. A solitary rat was tested in the 1st session and pair of rats was tested simultaneously in the second session. Results showed that kindling changed the balance between exploration and occupation of a home base (HB) in the open field, in favor of higher preference of the home base occupancy. These results were apparent only during the social session leading to the conclusion that rats preferred to stay in the home base to maximize the proximity to a partner rat. This was supported by the observation that by increasing the occupancy of the HB, the kindled rats accomplished the longest concurrent presence with the partner rat in the common HB. We discuss the level of inter-rats aggression as a factor defining whether the anxious kindled rats will respond with increased or decreased social attraction in the open field test.

Two-stage theory of conditioning: involvement of the cerebellum and the amygdala.

Classical conditioning is thought to proceed through two successive stages: fast rate emotional conditioning followed by slower motor conditioning. To verify the involvement of the amygdala and the cerebellum in these two stages of learning, rats were subjected to paired tone-airpuff (CS-US) trials. Lick suppression to CS was used as an index of conditioned emotional response (emotional CRs) and head movement was used as an index of motor CRs. The results showed that the fast acquisition of emotional CRs was dependent on the integrity of the amygdala and the slow acquisition of motor CRs was dependent on the integrity of the cerebellar interpositus nucleus. Cerebellar lesions had no effect on the acquisition of the emotional CRs but prevented the extinction of the emotional CRs seen in intact rats after massive conditioning. These findings suggest that the amygdala and the cerebellum provide the neuronal substrates of the fast and slow conditioning systems, respectively, and that conditioning-related cerebellar output interacts with the amygdala-based emotional conditioning.

Involvement of the amygdala in classical conditioning of eyeblink response in the rat.

The two-factor theory postulates that classical conditioning proceeds through two stages, which support successive acquisition of emotional and motor responses. Emotional conditioning is thought to facilitate the subsequent acquisition of the motor response. This form of interaction between the two stages of learning can be investigated while considering the central role of the amygdala and the cerebellum in emotional and motor conditioning, respectively. Rats with bilateral lesions of the amygdala or the cerebellar interpositus or intact rats were subjected to a fear conditioning session followed by four eyeblink conditioning sessions. Another group of intact rats was subjected to eyeblink conditioning only. The CS in the fear conditioning session was a 73 dB tone, paired with a 100 dB noise-US. The same CS was paired with a periorbital electroshock-US during eyeblink conditioning. Results showed that fear preconditioning facilitated the subsequent eyeblink conditioning among the intact groups. Amygdaloid lesions abolished this facilitatory effect of fear conditioning. These findings demonstrate that amygdala-mediated emotional conditioning facilitates the subsequent acquisition of cerebellum-mediated motor responses.

Phytonadione therapy in a multiple-drug overdose involving warfarin.

We cared for a patient who ingested an unknown amount of acetaminophen with zopiclone and warfarin. The only liver function test that was abnormal was an increased international normalized ratio (INR), which remained elevated despite treatment with subcutaneous phytonadione and a prolonged infusion of N-acetylcysteine. An interaction between acetaminophen and warfarin may have decreased the hepatic metabolism of warfarin. The patient received numerous antibiotics that may have contributed to the increased INR. The prolonged elevation of INR also may have been due to infrequent administration of phytonadione.

The expression of the calcium binding protein calretinin in the rat striatum: effects of dopamine depletion and L-DOPA treatment.

The activity of the striatum is regulated by glutamate and dopamine neurotransmission. Consequent to striatal dopamine depletion the corticostriatal excitatory input is increased, which in turn can raise intracellular calcium levels. We investigated changes in the neuronal expression of the calcium binding protein calretinin related to dopamine depletion and l-DOPA administration. Immunohistochemical methods were used to assess calretinin in the striatum of rats with unilateral lesions of the nigrostriatal system. In these animals we observed a loss of the patchy distribution of calretinin fibers. Moreover, after dopaminergic depletion we detected two new, not previously described, calretinin cell types, the presence of which could be related to morphological changes induced by loss of a dopaminergic input. We also found an increase in the number of calretinin-labeled cells in the striatum ipsilateral to the lesion compared to the contralateral striatum or to the striatum of normal rats. This increase was mostly evident at 3 weeks postlesion and tended to decrease toward normal levels at 6, 10, and 18 weeks postlesion. In unlesioned animals, l-DOPA administration did not induce changes in the expression of calretinin. In unilaterally lesioned animals, l-DOPA reversed the increase in the number of calretinin-positive cells induced by the lesion. However, chronic l-DOPA administration was less effective than acute l-DOPA in reversing the effect of the lesion. The present data suggests that striatal calretinin neurons are sensitive to dopamine depletion. Increased expression of calretinin in striatal cells may be consequent to enhanced striatal excitatory input.

Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team.

OBJECTIVES: To compare the impact of three different nucleoside reverse transcriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (ddI) monotherapy, and ZDV plus ddI combination therapy, on central nervous system (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: Serial neurologic examinations, neurocognitive tests, and brain growth assessments (head circumference measurements and head computed tomography or magnetic resonance imaging studies) were performed in 831 infants and children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Trials Group study 152 conducted between 1991 and 1995 enrolled antiretroviral therapy-naive children. Subjects were stratified by age (3 to <30 months of age or 30 months to 18 years of age) and randomized in equal proportions to the three treatment groups. RESULTS: Combination ZDV and ddI therapy was superior to either ZDV or ddI monotherapy for most of the CNS outcomes evaluated. Treatment differences were observed within both age strata. ZDV monotherapy showed a modest statistically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection against CNS deterioration no clear difference was observed between the two monotherapy arms. CONCLUSIONS: Combination therapy with ZDV and ddI was more effective than either of the two monotherapies against CNS manifestations of human immunodeficiency virus disease. The results of this study did not indicate a long-term beneficial effect for ZDV monotherapy compared with ddI monotherapy.

Effects of prenatal exposure to gamma rays on circling and activity behavior in prepubertal and postpubertal rats.

The study departs from the finding that postural asymmetries in low-weight female neonates are greatly increased following prenatal lesions inflicted by gamma irradiation at day 15. Given that amphetamine-induced rotation in adult rats could be predicted by their infantile axial asymmetry we expected a greater tendency for circling in rats exposed at day 15. To examine this prediction, Sprague-Dawley rats were exposed to a single dose of gamma radiation at 1.5 Gy with a dose-rate of 0.15 Gy/min. The dose was delivered on one of the embryonic days (E15, 17 or 19) throughout the whole body of pregnant dams. Sham prenatal exposure of controls consisted of placing pregnant rats in the same environment for 10 min. All rats were tested during the active part of the circadian cycle. At postnatal day 27 (P27) exposed pups did not differ in rates of either spontaneous or d-amphetamine-induced circling from the shams. At P57, in keeping with our prediction, E15 rats manifested enhanced rotation and higher net asymmetry. However, E17 also showed higher gyration tendency compared to their shams while exposed E19 rats did not differ from their shams. The role of intrinsic DAergic imbalance presumably sharpened by irradiation at E15 and of neocortical deficit inflicted at E15 and E17 are discussed.

Clinical features and treatment interventions for human immunodeficiency virus-associated neurologic disease in children.

HIV-1 infection in children and adolescents can cause progressive neurologic disease, affective brain growth, motor function, and neurodevelopment. In addition, myelopathies, neuropathies, myopathies, strokes, and psychiatric or behavioral manifestations can be a result of HIV-1 infection, OI, or toxicities of treatment interventions. CNS OI are important causes of morbidity and mortality, often mimicking the HIV-1 associated neurologic syndromes. Psychometric, clinical, neuroradiologic, and laboratory testing are valuable for diagnostic and treatment decisions. The cornerstone of treating HIV-1-associated neurologic disease is providing an effective regimen of antiretroviral drugs to reduce the viral burden. It is also necessary to provide rehabilitation, optimize nutrition, supply appropriate antimicrobial prophylaxis against OI, minimize pain, and treat neurobehavioral or psychiatric complications. Efforts at preventing HIV-1 infection are important for diminishing and allaying the growth of this international pandemic.

Reevaluation of the striatal role in the expression of turning behavior in the rat model of Parkinson's disease.

A traditional view holds the belief that the behavioral effects of l-dihydroxyphenilalanine (l-DOPA) in Parkinsonian patients are achieved through the action of the newly produced dopamine (DA) on striatal DA receptors. In contrast to this view, recent studies in the rat model of Parkinson's disease point to the substantia nigra pars reticulata as an important target for the behavioral effects of l-DOPA. In the present study, we tested the contribution of the substantia nigra vs. that of the striatum, in the expression of contralateral turning induced by l-DOPA in rats with unilateral dopaminergic depletion. Rats turned contralaterally to the lesion in response to either intrastriatal or systemic l-DOPA administration. Injections of lidocaine into the denervated striatum substantially decreased, and occasionally completely abolished, the contralateral turning after systemic l-DOPA. These findings indicate that activation of the DA depleted striatum is both sufficient and essential for the expression of behavioral response after systemic administration of l-DOPA. The contribution of the substantia nigra to this behavioral response seems to depend to a great extent on an active striatal outflow.

Dissociation between startle and prepulse inhibition in rats exposed to gamma radiation at day 15 of embryogeny.

The role of prenatal trauma in disordered sensory gating was explored in albino rats of the Sprague-Dawley strain. Pregnant rats were exposed to 1.5 Gy (0.15 Gy/min) of the whole-body gamma radiation on days 15, 17, or 19 of gestation. Controls were sham-exposed during 10 min in the same conditions. Exposed and control offsprings were evaluated for the auditory startle response (ASR) and its gating by either the habituation process or by the preceding weak sensory stimulus in the prepulse inhibition of startle (PPI) procedure. The tests were conducted when the animals reached 27 and 57 days of age. A noticeable hyperresponding and delayed habituation of startle were found in rats exposed at E15, with meager effects in rats exposed at E17 and E19. Maximal deficit was obtained on tests conducted on P57 but not on P27. However, in rats pretreated with amphetamine, dysfunctional startle was unmasked already on the P27 test. By contrast, PPI was insensitive to the damaging effect of prenatal irradiation at either period. This dissociation is reminiscent of one observed in patients with posttraumatic stress disorder (PTSD).