Towards a Sustainable Happiness Model for UAE: Lessons from Latin America

Traditionally studies on Happiness have been using income as a proxy for wellbeing and quality of life using GDP to measure progress of nations. We need to understand here that while income is an objective measure, Happiness is a subjective measure. One of the key criticisms leveled against GDP is that it does not take into account sustainability. Sometimes growth may be there but not achieved through sustainable thereby risking the future. On the flip side economic growth itself may not be sustainable in some cases. So can we depend on economic factors alone to be happy? In the past decade or so more and more countries are looking at the “Beyond GDP “agenda. in 2011 the OECD developed a framework for measuring wellbeing that can reflect and support development of measurement frameworks on a national level. there are a sizeable number of Latin American countries scoring consistently high on the Happiness index despite a number of socio economic issues. The recently published World Happiness report (2018) suggests that this is not a mere coincidence. It is based on the fact that Happiness in Latin America has social foundations. UAE lists in the top 20 countries with a happiness index of 6.774. (Source: World Happiness ranking 2015-17).This is the first ever attempt to superimpose the Latin American happiness model on the UAE local community to arrive at a sustainable happiness model for them. &nbsp

Identification of copper metabolism as a KRAS-specific vulnerability in colorectal cancer

KRAS est parmi les gènes les plus fréquemment mutés dans les cancers humains, tel que ~ 45% des cancers colorectaux (CCR). Malgré les efforts déployés pour réduire son potentiel oncogénique, KRAS muté est fréquemment associé à la résistance aux médicaments et est extrêmement difficile à cibler sur le plan thérapeutique. Les protéines à la surface cellulaire sont souvent dérégulées dans les cancers et sont des cibles thérapeutiques attrayantes en raison de leur accessibilité aux anticorps. Nous avons séquençé les ARNm de cellules épithéliales intestinales exprimant KRAS muté et observé que ces dernières présentaient des changements importants dans les gènes codant pour des protéines de surface cellulaire. Par conséquent, notre objectif était d'identifier de nouvelles cibles thérapeutiques exprimées à la surface de cellules transformées par l’oncogène KRAS. En utilisant une approche de pointe en protéomique de surface cellulaire, nous avons identifié plusieurs protéines différentiellement exprimées dans les cellules avec KRAS muté par rapport à leurs homologues de type sauvage. Nous avons ensuite effectué un crible CRISPR/Cas9 basé sur les protéines de surface cellulaire, qui a révélé que la perte de la protéine Atp7a affectait de manière différentielle les cellules épithéliales intestinales, en fonction de leur statut KRAS. De façon intéressante, nous avons constaté que ATP7A était régulé à la hausse dans les cellules avec KRAS muté par rapport à leurs homologues de type sauvage. ATP7A a un double rôle dans les cellules; alors qu'il est essentiel pour la maturation des enzymes dépendantes du cuivre (Cu), ATP7A protège les cellules d'une toxicité excessive induite par le Cu (cuproptose). Chez l'homme, les mutations dans ATP7A entraînent des troubles caractérisés par des déficiences systémiques dans le transport et les niveaux de Cu. Chez les animaux et dans les modèles de culture cellulaire, tel que les cellules épithéliales intestinales, les niveaux intracellulaires de Cu sont directement corrélés avec l'abondance post-transcriptionnelle d'ATP7A. Dans le même ordre d'idées, nous avons observé que les cellules de CCR avec KRAS muté avaient relativement plus de Cu intracellulaire, et la surexpression d'ATP7A protégeait les cellules KRAS muté de la cuproptose, par rapport à leurs homologues de type sauvage. Nous avons également observé que la croissance in vivo des xénogreffes KRAS mutées était réduite lorsque les souris étaient nourries avec un régime pauvre en Cu. Le Cu est utilisé par plusieurs enzymes qui régulent des fonctions cellulaires critiques, notamment la respiration mitochondriale, la motilité cellulaire et la prolifération. Nous montrons que les cellules mutantes KRAS étaient plus sensibles au chélateur de Cu, ammonium tetrathiomolybdate (TTM), par rapport aux cellules de type sauvage. De plus, les cellules avec KRAS muté traitées avec le TTM ont présenté des activités réduites de MEK1/2 dépendant du Cu et de l'enzyme de la chaîne de transport d'électrons mitochondriale, cytochrome c oxidase (CCO). Nous avons été surpris de constater que le transporteur de Cu de haute affinité, CTR1, est régulé à la baisse dans les cellules avec KRAS muté, et avons donc émis l'hypothèse que les cellules KRAS mutées doivent absorber le Cu par d'autres moyens. Ainsi, nous avons constaté que la macropinocytose agit comme une voie non canonique d'approvisionnement en Cu dans les cellules avec KRAS muté. Le traitement de cellules in vivo avec l'inhibiteur de la macropinocytose, EIPA, a inhibé l'expression d'ATP7A et diminué le Cu biodisponible dans les xénogreffes KRAS mutées. En conclusion, nos résultats montrent que les cellules avec KRAS muté augmentent les niveaux de Cu et d'ATP7A pour soutenir la tumorigenèse en augmentant l'activité cuproenzymatique et diminuant la cuproptose. Cette étude est pertinente pour le cancer, car les tissus tumoraux contiennent fréquemment des niveaux de Cu plus élevés que les tissus normaux. Des études récentes ont mis en évidence un potentiel de repositionnement du chélateur de Cu TTM, qui est disponible en clinique et utilisé pour traiter les troubles du Cu. Nos résultats démontrent que la biodisponibilité du Cu pourrait être exploitée pour traiter le CCR avec KRAS muté avec de tels inhibiteurs. Les travaux futurs comprennent l'identification de stratégies combinatoires qui peuvent être améliorer les effets anti-cancéreux de la chélation du Cu.KRAS is amongst the most frequently mutated genes driving human cancers, including ~ 45% of colorectal cancers (CRC). Despite intense efforts to curb its oncogenic potential, mutant KRAS is frequently associated with drug resistance and is extremely challenging to target therapeutically. Cell-surface proteins are often spatially dysregulated in cancers and are attractive therapeutic targets due to their easy accessibility. We performed RNA sequencing of mutant KRAS-expressing intestinal epithelial cells and observed that cells undergoing transformation exhibited dramatic changes in cell surface-coding genes. Therefore, our goal was to identify novel druggable targets expressed at the cell surface of mutant KRAS-transformed cells. Using a cutting-edge cell surface proteomics approach, we identified several differentially expressed proteins at the surface of KRAS-mutant cells compared to wild-type counterparts. We then performed a cell surface based CRISPR/Cas9 screen, which revealed that loss of the copper exporter Atp7a differentially affected the fitness of intestinal epithelial cells, depending on their KRAS status. Interestingly, we found that ATP7A was upregulated in KRAS-mutant cells compared to wild-type counterparts. ATP7A has a dual role in cells; while it is essential for maturation of copper (Cu)-dependent enzymes, ATP7A protects cells from excess Cu-induced toxicity (cuproptosis). In humans, ATP7A mutations result in disorders characterized by systemic deficiencies in Cu transport and levels. In animals and in tissue culture models, including intestinal epithelial cells, intracellular Cu levels are directly correlated with the post-transcriptional abundance of ATP7A. In line with this, we observed that KRAS-mutant CRC cells and tissues had relatively more intracellular Cu, and ATP7A-overexpression protected KRAS-mutant cells from cuproptosis, compared to wild-type counterparts. We also observed that in vivo growth of KRAS-mutant xenografts was reduced when mice were fed a Cu-deficient diet. Cu is utilized by several enzymes that regulate critical cellular functions including mitochondrial respiration, cell motility and proliferation. We show that KRAS-mutant cells were more sensitive to the Cu chelating drug ammonium tetrathiomolybdate (TTM), compared to wild-type cells. Moreover, TTM-treated KRAS-mutant cells displayed reduced activities of Cu-dependent MEK1/2 and mitochondrial electron transport chain enzyme, cytochrome c oxidase (CCO). We were surprised to find that the high-affinity CTR1 importer is downregulated in KRAS-mutant cells, and so we hypothesized that KRAS cells must uptake Cu through alternate means. In accordance with this, we found that macropinocytosis acts as a non-canonical Cu-supply route in KRAS-mutant cells. In vivo, treating cells with the macropinocytosis inhibitor EIPA, inhibited the expression of ATP7A and decreased bioavailable Cu in KRAS xenografts. In conclusion, our results show that KRAS-mutant cells increase Cu and ATP7A levels, likely to support tumorigenesis by elevating cuproenzymatic activity and parallelly dealing with cuproptosis. This study is relevant to cancer as tumor tissues and patients contain higher Cu levels than normal controls. Recent studies have highlighted a potential for repurposing the clinically available copper chelator TTM, which is used to treat Cu disorders. Our results demonstrate that copper bioavailability could be exploited to treat KRAS-mutated CRC with such inhibitors. Future work includes identification of combinatorial strategies that may be synthetic lethal to copper chelation

Development of a methodology to delineate hurricane evacuation zones

The main focus of this study is to exhibit a simple and easily implemented process to identify hurricane evacuation zones. The proposed study presents a new methodology to delineate hurricane evacuation zones. The new methodology helps in easier identification of zones, thereby making the task of evacuation officials easier. Hurricane evacuation zones were identified based on the elevation of the points comprising the study area. An area layer was created based on the storm surge models run, and were overlaid with zip code boundary layer and land use data available. Elevation point file data was superimposed on the study area layer to find out the mean elevation and standard deviation values of elevation, which help in identifying the adjacent zones which are similar in elevation. These zones are grouped together and the process of joining zones is continued until the zones are sufficiently reduced. The entire process was carried out in TransCAD, a Transportation/GIS software package. This task involves an iterative process which would be extremely tedious to perform manually. Hence, the process was automated by writing a customized add-in program to TransCAD. The study also included the application of this methodology to the New Orleans metropolitan area, it being an ideal test case for implementing the methodology that was developed. The results portray New Orleans area being ideally and conveniently divided into hurricane evacuation zones based on their elevations, zip code and storm surge data. The GIS program developed during this study provides a framework, which may be built upon and shared with other researchers in the future

To evaluate the expression of Podoplanin Marker in oral squamous cel l carcinoma

Oral squamous cell carcinoma (ORCC) is one of the most prevalent cancer in India, especially in males. Podoplanin is a transmembrane glycoprotein that is expressed mostly in lymphatic endothelium and also in various normal tissues. The podoplanin expression was found to be higher in different squamous cell carcinoma (SCC) including oral squamous cell carcinoma (OSCC). Therefore, evaluation of the podoplanin expression in oral squamous cells would be helpful for the diagnosis of early OSCC. Monoclonal antibody D2-40 has been used to identify podoplanin expression in tissue samples with primary oral cancer. Delay in diagnosis is one of the major causes for low survival rate in oral cancer patients. Therefore, novel diagnostic methods of oral cancer need to be developed for early diagnosis and therapy. A better understanding of mechanisms leading to OSCC is required to enhance more efficient diagnostic and therapeutic methods for oral cancer. The present study was comprised of 20 patients, diagnosed with oral squamous cell carcinoma (OSCC) and we also used 5 normal tissue (alveolar mucosa) samples as controls. The samples and clinical data were collected from Department of Oral Pathology and Microbiology at Madha Dental College and Hospital, Tamil Nadu, India. Immunohistochemical (IHC) staining method were used to detect the expression of podoplanin within the cell. Primary antibody used in this study was mouse monoclonal antibody (clone D2-40) and immunohistochemical staining was done by using the PolyExcel HRP/DAB Detection System. The association between podoplanin expression and other relevant factors were analyzed using appropriate statistical tools with the help of IBM SPSS software 24.0. Our present study evaluated the podoplanin expression in 20 OSCC cases, of which 12 cases (60%) showed podoplanin expression. Eight OSCC cases (40%) showed no detectable podoplanin expression (scored as 0), 6 cases (30%) showed podoplanin expression between 31-50% (scored as 3), 5 cases (25%) showed podoplanin expression between 51-80% (scored as 4), and only 1 case (5%) showed expression between 11-30% (scored as 1). We also observed grade-IV OSCC (poorly differentiated) exhibiting significantly higher levels of podoplanin expression, as compared to moderately (grade-II) or well differentiated (grade-I) OSCC (P=0.004). Higher podoplanin expression was found in buccal mucosa (46.1%) as compared to alveolar mucosa (24.3%) and we also found higher podoplanin expression in tobacco-betel quid chewers (56.7%), smokers (42.9%) and alcohol consumers (53.9%) as compared to non-consumers. However, only alcohol consumptions showed statistically significant correlation with podoplanin expressions (P=0.044). Our study concludes that the expression of podoplanin could be used as a molecular biomarker for early detection of oral squamous cell carcinoma (OSCC). More studies containing a larger sample size are required to validate the clinical perspective of podoplanin as a molecular biomarker for OSCC risk assessment. Present study opens up the new way to analyze the expression of podoplanin from biopsied tissues to evaluate the status of OSCC. Further investigations on the association between the podoplanin expression and habit-related factors in a larger sample size are needed. In recent times, different anti-podoplanin based therapeutic agents, like CasMab anti-podoplanin, have been tested to improve the prognosis of cancer patients

Comparative Difficulties with Non-Scientific General Vocabulary and Scientific/Medical Terminology in English as a Second Language (ESL) Medical Students

Objectives: Medical education requires student comprehension of both technical (scientific/medical) and non-technical (general) vocabulary. Our experience with “English as a second language” (ESL) Arab students suggested they often have problems comprehending scientific statements because of weaknesses in their understanding of non-scientific vocabulary. This study aimed to determine whether ESL students have difficulties with general vocabulary that could hinder their understanding of scientific/medical texts. Methods: A survey containing English text was given to ESL students in the premedical years of an English-medium medical school in an Arabic country. The survey consisted of sample questions from the Medical College Admission Test (USA). Students were instructed to identify all unknown words in the text. Results: ESL students commenced premedical studies with substantial deficiencies in English vocabulary. Students from English-medium secondary schools had a selective deficiency in scientific/medical terminology which disappeared with time. Students from Arabic-medium secondary schools had equal difficulty with general and scientific/medical vocabulary. Deficiencies in both areas diminished with time but remained even after three years of English-medium higher education. Conclusion: Typically, when teaching technical subjects to ESL students, attention is focused on subject-unique vocabulary and associated modifiers. This study highlights that ESL students also face difficulties with the general vocabulary used to construct statements employing technical words. Such students would benefit from increases in general vocabulary knowledge

Transient Pseudohypoaldosteronism due to Urinary Tract Infection in Infancy: A Report of 4 Cases

Hyponatremia with hyperkalemia in infancy is an uncommon but life-threatening occurrence. In the first weeks of life, this scenario is often associated with aldosterone deficiency due to salt-wasting congenital adrenal hyperplasia. However, alternative diagnoses involving inadequate mineralocorticoid secretion or action must be considered, particularly for infants one month of age or older. We report four infants who presented with profound hyponatremia accompanied by urinary tract infection, ultimately leading to the diagnosis of transient pseudohypoaldosteronism. Our cases provide support for the idea that the renal tubular resistance to aldosterone is due to urinary tract infection itself rather than to underlying urinary tract anomalies typically found in these infants. Awareness of this condition is important so that serum aldosterone, urine sodium, and urine cultures may be obtained immediately in any infant presenting with hyponatremia and hyperkalemia in whom a diagnosis of congenital adrenal hyperplasia was not found. Adequate replacement with intravenous saline and antibiotic therapy is sufficient to correct sodium levels over 24–48 hours

A Critical Study On Global Recession - 2008 And Its Impact On India

In recent years, the Indian Economy experienced a pronounced slow down in economic activity. In many ways, the slow down looked like a typical recession driven by a fall in aggregate supply. Seven notable shocks explain this event. They are ● Increase in excess demand ● Increase Money supply ● Fall in the real GDP ● Fall in the composition of agriculture to GDP ● Increase in unemployment rate ● Lower capital inflow ● Unfavorable BoT The responsiveness of fiscal and monetary policy quickly to this events and their impact in rectifying the problems is analyzed in this paper

TRINITY OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS-2: ORIGIN, GENOTYPE, PHENOTYPE, AND IMMUNE RESPONSE IN CORONAVIRUS DISEASE-2019

The coronavirus disease-2019 (COVID-19) outbreak by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or a novel coronavirus (2019-CoV) has prompted global health concerns. A pandemic resulted from the disease’s transmission through many routes. In this pandemic, the interaction between coronavirus and the host immune system, particularly the innate immune system, is becoming more prominent. Against viruses and pathogens, innate immunity serves as a first line of defense. Our understanding of pathogenesis will benefit from a better grasp of the mechanisms of immune evasion techniques. The origin, classification, structure, and method of transmission of SARS-CoV-2 were summarized in this paper. We have discussed the importance of important communications. In this review, we have discussed the function of important components of the innate immune system in COVID-19 infection, as well as how the virus evades innate immunity through multiple tactics and contributes to a wide range of clinical symptoms and outcomes

Mechanisms and Prospects of Ischemic Tolerance Induced by Cerebral Preconditioning

In the brain, brief episodes of ischemia induce tolerance against a subsequent severe episode of ischemia. This phenomenon of endogenous neuroprotection is known as preconditioning-induced ischemic tolerance. The purpose of this review is to summarize the current state of knowledge about mechanisms and potential applications of cerebral preconditioning and ischemic tolerance. Articles related to the terms ischemic preconditioning and ischemic tolerance were systematically searched via MEDLINE/PubMed, and articles published in English related to the nervous system were selected and analyzed. The past two decades have provided interesting insights into the molecular mechanisms of this neuroprotective phenomenon. Although both rapid and delayed types of tolerance have been documented in experimental settings, the delayed type has been found to be more prominent in the case of neuronal ischemic tolerance. Many intracellular signaling pathways have been implicated regarding ischemic preconditioning. Most of these are associated with membrane receptors, kinase cascades, and transcription factors. Moreover, ischemic tolerance can be induced by exposing animals or cells to diverse types of endogenous and exogenous stimuli that are not necessarily hypoxic or ischemic in nature. These cross-tolerances raise the hope that, in the future, it will be possible to pharmacologically activate or mimic ischemic tolerance in the human brain. Another promising approach is remote preconditioning in which preconditioning of one organ or system leads to the protection of a different (remote) organ that is difficult to target, such as the brain. The preconditioning strategy and related interventions can confer neuroprotection in experimental ischemia, and, thus, have promise for practical applications in cases of vascular neurosurgery and endo-vascular therapy