Advocacy, Politics, & Philanthropy

Over the course of our history, Atlantic has made some big bets designed to help solve major social issues. Needless to say, our 11-year, $70 million initiative to reform America's immigration system certainly ranks among the biggest of such bets. Among the factors leading to our decision to take on this challenging work was our deep concern that millions of immigrants to the United States have been without access to basic rights accorded by law or common practice to the majority of Americans. As a result of a broken immigration system, far too many individuals and families have been left vulnerable to a wide range of discrimination and abuse in the workplace, in housing and in healthcare settings, among others. Undocumented immigrants increasingly face growing social marginalization and hostility from those whose ancestors arrived on our shores in earlier times. At the time we started this work, as far back as 2004, we also firmly believed there was a willingness at the federal level and in the United States Congress to find a workable solution

Lamins, laminopathies and disease mechanisms: possible role for proteasomal degradation of key regulatory proteins

Lamins are major structural proteins of the nucleus and are essential for nuclear integrity and organization of nuclear functions. Mutations in the human lamin genes lead to highly degenerative genetic diseases that affect a number of different tissues such as muscle, adipose or neuronal tissues, or cause premature ageing syndromes. New findings on the role of lamins in cellular signalling pathways, as well as in ubiquitin-mediated proteasomal degradation, have given important insights into possible mechanisms of pathogenesis

Paternally inherited trisomy at D21S11 and mutation at DXS10135 microsatellite marker in a case of fetus paternity establishment

AbstractThe case of establishment of paternity of an aborted fetus was examined with 15 autosomal STR markers. The genotype of the fetus was X at amelogenin marker and showed inheritance of both the alleles of father at D21S11 marker, thus displaying unusual tri-allelic pattern. The cases where mutation in any of biparental autosomal STR markers is observed, the use of additional STR marker system is recommended. On testing all the three samples with 12 X-STR markers, all the maternal and paternal alleles were accounted in the female fetus except at DXS10135 marker. The genotypes of mother, fetus and father at DXS10135 were 20, 22; 20, 20 and 21, which confirmed mutation of the paternal allele in the female fetus. The paternal allele contracted from 21 to 20. The allele peak heights of D21S11 and DXS10135 markers were also examined to rule out the possibility of any false allele. The probability of paternity was 0.99999999, which confirmed the paternity of the fetus. This paper presents unusual occurrence of mutation observed with two multiplex STR systems, with AmpflSTR identifier plus Kit (Applied Biosystems, Foster City, CA) and Investigator Argus X-12 multiplex kit (Qiagen, Germany), thus suggesting forensic DNA experts on high alert while interpreting the DNA test results

Ketamine but not glycine potentiates antidepressant like action of citalopram in mice exposed to chronic mild stress

Background: The present study was designed to investigate the effect of citalopram, ketamine, glycine and their combinations on animal models of depression. Methods: Swiss Albino male mice were subjected to chronic mild stress for 6 weeks for inducing depression, and randomly divided into different groups: citalopram (5 and 10 mg/kg), ketamine (17.5 and 35 mg/kg), glycine (50 and 100 mg/kg), ketamine (17.5 mg/kg) + citalopram (5 mg/kg) and ketamine (17.5 mg/kg) + glycine (50 mg/kg). Two behavioural tests were utilized for the assessment of depression, namely tail suspension test (TST) and forced swim test (FST). Immobility time was recorded for 6 min, before and after administration of drug. Results: Citalopram (10 mg/kg) administration caused significant decrease in the immobility time in TST model only but not in FST. Citalopram (5 mg/kg) and ketamine (17.5 mg/kg) caused insignificant decrease in immobility time in both the models. Moreover, ketamine in combination with Citalopram significantly reduced the immobility time in both the models. Glycine at a dose of 100 mg/kg (but not 50 mg/kg) significantly increased the immobility time in both the models as compared to control group. Further, ketamine when administered with glycine caused increase in the immobility time on both the paradigms, though insignificant. Conclusions: Ketamine demonstrated antidepressant like action in both TST and FST models. Moreover, it potentiated the antidepressant effect of citalopram that might be due to the role of NMDA receptors

Genetic analysis of yield and heat stress related traits in wheat (Triticum aestivum L. em. Thell) using microsatellite markers

Microsatellite markers were used for genetic analysis of terminal heat tolerance in F2 (PBW373 × WH1081) population of wheat (Triticum aestivum L. em. Thell). Two parents were evaluated in field under normal sown and late sown conditions. For genotyping DNA from both parents PBW373 and WH1081 was amplified using 200 SSRs. Only 22 SSRs produced polymorphic bands, of size between 100 to 300 bp and an average of 1.45 alleles. The single marker analysis identified 19 markers indicating the putative QTLs for yield, its components and heat stress related physiological traits. The number of markers on these 16 linkage groups varied from one to four. On A genome 13 QTLs on B genome 5 QTLs and on D genome 9 QTLs were identified, respectively. The A, B and D genomes had 1360.3 cM, 272.4 cM and 919.5 cM of linkage coverage with average interval distances of 104.63 cM, 54.48 cM and 102.16 cM/Marker. A total of nine QTLs were resolved following composite interval mapping, one QTL was detected at a LOD score equal to threshold value of 2.5 while eight at LOD scores above the threshold value. All the nine QTLs were shown to be on definitive location on chromosome 3A (QDh.CCSHAU-3A, QDa.CCSHAU-3A and QPm.CCSHAU-3A), chromosome (QBm.CCSHAU-5A, QCtd.CCSHAU-5A and QCl.fl.CCSHAU-5A), chromosome6A (QPh.CCSHAU-6A) and chromosome3B (QTgw.CCSHAU and QMts.CCSHAU-3B). Use of these markers save times, resources and energy that are needed not only for raising large segregating populations for sveral generations, but also for estimating the parameters used for selection

Lamin A/C haploinsufficiency modulates the differentiation potential of mouse embryonic stem cells

Background: Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a spectrum of genetic diseases that affect specific tissues. Most available mouse models for laminopathies recapitulate disease symptoms for muscle diseases and progerias. However, loss of human lamin A/C also has highly deleterious effects on fetal development. Hence it is important to understand the impact of lamin A/C expression levels on embryonic differentiation pathways. Methodology and Principal Findings: We have investigated the differentiation potential of mouse embryonic stem cells containing reduced levels of lamin A/C by detailed lineage analysis of embryoid bodies derived from these cells by in vitro culture. We initially carried out a targeted disruption of one allele of the mouse lamin A/C gene (Lmna). Undifferentiated wild-type and Lmna+/− embryonic stem cells showed similar expression of pluripotency markers and cell cycle profiles. Upon spontaneous differentiation into embryoid bodies, markers for visceral endoderm such as α-fetoprotein were highly upregulated in haploinsufficient cells. However, neuronal markers such as β-III tubulin and nestin were downregulated. Furthermore, we observed a reduction in the commitment of Lmna+/− cells into the myogenic lineage, but no discernible effects on cardiac, adipocyte or osteocyte lineages. In the next series of experiments, we derived embryonic stem cell clones expressing lamin A/C short hairpin RNA and examined their differentiation potential. These cells expressed pluripotency markers and, upon differentiation, the expression of lineage-specific markers was altered as observed with Lmna+/− embryonic stem cells. Conclusions: We have observed significant effects on embryonic stem cell differentiation to visceral endoderm, neuronal and myogenic lineages upon depletion of lamin A/C. Hence our results implicate lamin A/C level as an important determinant of lineage-specific differentiation during embryonic development

An Update on JE Vaccine Development and Use

Japanese encephalitis (JE) is an emerging and re- emerging arboviral infection of global significance. Its causative agent Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia, Southeast Asia and Pacific. Nearly 3 billion people living in JE endemic areas account for 10000- 15000 deaths annually. The disease has high fatality rate (~30%) and nearly 50% survivors develop permanent neuropsychiatric sequelae. There is no specific treatment for JE. Vaccination is the only effective strategy available for prevention and control of JE. The wider availability and inclusion of JE vaccination in the national immunization programme in many of the affected countries have resulted in better prospects for control of JE. This review is an update on vaccines currently available, their development, recommended immunization schedule for them as well as the upcoming challenges related with cross- protectivity against hetrologous genotypes

How do specialist trainee doctors acquire skills to practice patient-centred care? A qualitative exploration

Objectives: The importance of patient centred care (PCC) has been increasingly recognised. However, there is limited work exploring what doctors actually understand by PCC, and how they perceive they acquire PCC skills in the workplace. The objectives of our study were to explore (1) what UK doctors, in specialist training, perceive to be the essential components of PCC, and (2) if/how they acquire these skills; (3) any facilitators/barriers for engaging in PCC; and (4) views on their PCC training. Design: Qualitative study using in-depth individual semi-structured interviews with UK specialist trainees. Interview transcripts were thematically analysed.Setting and Participants: Thirty-one specialist trainee doctors, with at least 4 years postgraduate experience, were interviewed. Participants worked in various medical specialities within the Medical Directorate of an acute hospital in the East Midlands of England (UK). Results: Interview data were transcribed verbatim and categorised into three main themes. The first theme was ‘Understanding PCC’ where the doctors gave varied perspectives on what they understood by PCC. Although many were able to highlight key components of PCC there were also some accounts which demonstrated a lack of understanding. The second theme was ‘Learning PCC skills: A work in progress’. Learning to be patient-centred was perceived to be an on-going process. Within this, trainee doctors reported ‘on-the-job’ learning as the main means of acquiring PCC skills, but they also saw a place for formal training (e.g., educational sessions focussing on PCC, clinical scenarios/role play). ‘Delivering PCC: Beyond the physician’ referred to the many influences the doctors reported in learning and delivering PCC including patients, the organisation and colleagues. Observing consultants taking a patient-centred approach was cited as an important learning tool. Conclusions: Our findings may assist clinical educators in understanding how trainee doctors perceive PCC, and the factors that influence their learning; thereby, helping them shape PCC skills training

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study

Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country’s largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks