Predicting Future of Senior Housing Markets amid COVID-19 Pandemic in India Using Dependency Models

The COVID-19 pandemic has contributed to a very high percentage of senior deaths in India. Senior citizens constitute about 10% of total population while 73% of deaths during COVID-19 pandemic in India have been of people with co-morbidities such as diabetes, hypertension, heart and respiratory diseases. Amidst this pandemic, the senior housing market is poised for exponential growth despite a low market share as well as slow sales. To inquire as to which factors influence the seniors for not buying into exclusive senior housing communities and whether the decision varies among ages as well as genders; a questionnaire survey was conducted pre-COVID-19 using sales leads of 143 senior respondents from five cities; Delhi, Lavasa, Chennai, Pune and Ahmedabad. These data were tested using binary probit regression models for age and gender. The survey required the respondents to rate decision factors which included; amenities, location, social isolation, wealth, family, urban connect, new relationships, inheritance and moral values - on Likert scale of 1 to 9. The tested model for gender shows that males are dependent on factors of location of the project and fear isolation as compared to females. Males also rated new acquaintances as a discouraging factor as compared to females. The age model shows that older seniors (aged 66-75) do not wish to move to an exclusive senior citizen homes due to factors of distance, fear of social isolation and attachment to urban elements as compared to younger seniors (aged 55-65). An attempt is made to use the results arising from these models to predict the future of senior housing market post-COVID-19 pandemic in India. By integrating new factors such as social distancing, personal hygiene and recreational activities, the existing models can be used to forecast post-COVID-19 senior housing markets in India

Predicting Future of Senior Housing Markets amid COVID-19 Pandemic in India Using Dependency Models

The COVID-19 pandemic has contributed to a very high percentage of senior deaths in India. Senior citizens constitute about 10% of total population while 73% of deaths during COVID-19 pandemic in India have been of people with co-morbidities such as diabetes, hypertension, heart and respiratory diseases. Amidst this pandemic, the senior housing market is poised for exponential growth despite a low market share as well as slow sales. To inquire as to which factors influence the seniors for not buying into exclusive senior housing communities and whether the decision varies among ages as well as genders; a questionnaire survey was conducted pre-COVID-19 using sales leads of 143 senior respondents from five cities; Delhi, Lavasa, Chennai, Pune and Ahmedabad. These data were tested using binary probit regression models for age and gender. The survey required the respondents to rate decision factors which included; amenities, location, social isolation, wealth, family, urban connect, new relationships, inheritance and moral values - on Likert scale of 1 to 9. The tested model for gender shows that males are dependent on factors of location of the project and fear isolation as compared to females. Males also rated new acquaintances as a discouraging factor as compared to females. The age model shows that older seniors (aged 66-75) do not wish to move to an exclusive senior citizen homes due to factors of distance, fear of social isolation and attachment to urban elements as compared to younger seniors (aged 55-65). An attempt is made to use the results arising from these models to predict the future of senior housing market post-COVID-19 pandemic in India. By integrating new factors such as social distancing, personal hygiene and recreational activities, the existing models can be used to forecast post-COVID-19 senior housing markets in India

Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition

Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. We have performed structural and kinetic studies on hPL kinase with several potential inhibitors, including ginkgotoxin and theophylline. The structural studies show ginkgotoxin and theophylline bound at the substrate site, and are involved in similar protein interactions as the natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin is also observed bound at the active site. This work provides insights into the molecular basis of hPL kinase inhibition and may provide a working hypothesis to quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors. Such adverse effects may be prevented by administration of an appropriate form of vitamin B6, or provide clues of how to modify these drugs to help reduce their hPL kinase inhibitory effects

Neural Net Classification Combined With Movement Analysis to Evaluate Setaria viridis as a Model System for Time of Day of Anther Appearance

In many plant species, the time of day at which flowers open to permit pollination is tightly regulated. Proper time of flower opening, or Time of Day of Anther Appearance (TAA), may coordinate flowering opening with pollinator activity or may shift temperature sensitive developmental processes to cooler times of the day. The genetic mechanisms that regulate the timing of this process in cereal crops are unknown. To address this knowledge gap, it is necessary to establish a monocot model system that exhibits variation in TAA. Here, we examine the suitability of Setaria viridis, the model for C4 photosynthesis, for such a role. We developed an imaging system to monitor the temporal regulation of growth, flower opening time, and other physiological characteristics in Setaria. This system enabled us to compare Setaria varieties Ames 32254, Ames 32276, and PI 669942 variation in growth and daily flower opening time. We observed that TAA occurs primarily at night in these three Setaria accessions. However, significant variation between the accessions was observed for both the ratio of flowers that open in the day vs. night and the specific time of day where the rate is maximal. Characterizing this physiological variation is a requisite step toward uncovering the molecular mechanisms regulating TAA. Leveraging the regulation of TAA could provide researchers with a genetic tool to improve crop productivity in new environments

Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s

Antibody responses to variant surface antigens (VSAs) produced by the malaria parasite Plasmodium falciparum may contribute to age-related natural immunity to severe malaria. One VSA family, P. falciparum erythrocyte membrane protein-1 (PfEMP1), includes a subset of proteins that binds endothelial protein C receptor (EPCR) in human hosts and potentially disrupts the regulation of inflammatory responses, which may lead to the development of severe malaria. We probed peptide microarrays containing segments spanning five PfEMP1 EPCR-binding domain variants with sera from 10 Malian adults and 10 children to determine the differences between adult and pediatric immune responses. We defined serorecognized peptides and amino acid residues as those that elicited a significantly higher antibody response than malaria-naïve controls. We aimed to identify regions consistently serorecognized among adults but not among children across PfEMP1 variants, potentially indicating regions that drive the development of immunity to severe malaria. Adult sera consistently demonstrated broader and more intense serologic responses to constitutive PfEMP1 peptides than pediatric sera, including peptides in EPCR-binding domains. Both adults and children serorecognized a significantly higher proportion of EPCR-binding peptides than peptides that do not directly participate in receptor binding, indicating a preferential development of serologic responses at functional residues. Over the course of a single malaria transmission season, pediatric serological responses increased between the start and the peak of the season, but waned as the transmission season ended. IMPORTANCE Severe malaria and death related to malaria disproportionately affect sub-Saharan children under 5 years of age, commonly manifesting as cerebral malaria and/or severe malarial anemia. In contrast, adults in malaria-endemic regions tend to experience asymptomatic or mild disease. Our findings indicate that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues. Epitopes containing these residues may be promising targets for vaccines or therapeutics directed against severe malaria. Our approach provides insight into the development of natural immunity to a binding target linked to severe malaria by characterizing an "adult-like" response as recognizing a proportion of epitopes within the PfEMP1 protein, particularly regions that mediate EPCR binding. This "adult-like" response likely requires multiple years of malaria exposure, as increases in pediatric serologic response over a single malaria transmission season do not appear significant. </p

COVID-19 at War: The Joint Forces Operation in Ukraine

The ongoing pandemic disaster of coronavirus erupted with the first confirmed cases in Wuhan, China, in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) novel coronavirus, the disease referred to as coronavirus disease 2019, or COVID-19. The World Health Organization (WHO) confirmed the outbreak and determined it a global pandemic. The current pandemic has infected nearly 300 million people and killed over 3 million. The current COVID-19 pandemic is smashing every public health barrier, guardrail, and safety measure in underdeveloped and the most developed countries alike, with peaks and troughs across time. Greatly impacted are those regions experiencing conflict and war. Morbidity and mortality increase logarithmically for those communities at risk and that lack the ability to promote basic preventative measures. States around the globe struggle to unify responses, make gains on preparedness levels, identify and symptomatically treat positive cases, and labs across the globe frantically rollout various vaccines and effective surveillance and therapeutic mechanisms. The incidence and prevalence of COVID-19 may continue to increase globally as no unified disaster response is manifested and disinformation spreads. During this failure in response, virus variants are erupting at a dizzying pace. Ungoverned spaces where nonstate actors predominate and active war zones may become the next epicenter for COVID-19 fatality rates. As the incidence rates continue to rise, hospitals in North America and Europe exceed surge capacity, and immunity post infection struggles to be adequately described. The global threat in previously high-quality, robust infrastructure health-care systems in the most developed economies are failing the challenge posed by COVID-19; how will less-developed economies and those healthcare infrastructures that are destroyed by war and conflict fare until adequate vaccine penetrance in these communities or adequate treatment are established? Ukraine and other states in the Black Sea Region are under threat and are exposed to armed Russian aggression against territorial sovereignty daily. Ukraine, where Russia has been waging war since 2014, faces this specific dual threat: disaster response to violence and a deadly infectious disease. To best serve biosurveillance, aid in pandemic disaster response, and bolster health security in Europe, across the North Atlantic Treaty Alliance (NATO) and Black Sea regions, increased NATO integration, across Ukraine’s disaster response structures within the Ministries of Health, Defense, and Interior must be reinforced and expanded to mitigate the COVID-19 disaster

Left ventricular volume: an optimal parameter to detect systolic dysfunction on prospectively triggered 64-multidetector row computed tomography: another step towards reducing radiation exposure

In this study, we define the correlation between LV volumes (both LV end-diastolic volume [LVEDV] and LV end-systolic volume [LVESV]) and ejection fraction (EF) on 64 slice multi-detector computed tomography (MDCT). We also determine the accuracy of all the LV volume (LVV) parameters to detect LV systolic dysfunction (LVSD) and investigate the feasibility of using LVV as a surrogate of LVSD on prospectively gated imaging to prevent the radiation exposure of retrospective imaging. 568 patients undergoing 64-detector MDCT were divided into 2 groups: Group 1—subjects without any heart disease and LVEF ≥ 50%; and Group 2—patients with coronary artery disease and LVEF < 50% (defined as LVSD). The LVV (LV cavity only) and Total LV volume (cavity + LV mass) at end-systole and end-diastole (LVESV, Total LVESV, LVEDV and Total LVEDV) were measured. The upper limit values (mean + 2 SD) of all LVV parameters in Group 1 were used as the reference criterion to diagnose LVSD in Group 2. An exponential correlation was found between LVEF and all the LVV parameters. The specificity to detect LVSD in Group 2 was >90% and the sensitivity was 88.9, 83.3, 61.3 and 74.9% by using LVESV, Total LVESV, LVEDV and Total LVEDV, respectively. Systolic and diastolic LV volumes had a high correlation with LVEF and a high accuracy to detect LVSD. Thus, on prospectively triggered imaging, ventricular volumes can predict patients with reduced LVEF, and appropriate referrals can be made

Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions

Most monogenic disorders have a primary clinical presentation. Inherited ISG15 deficiency, however, has manifested with two distinct presentations to date: susceptibility to mycobacterial disease and intracranial calcifications from hypomorphic interferon-II (IFN-II) production and excessive IFN-I response, respectively. Accordingly, these patients were managed for their infectious and neurologic complications. Herein, we describe five new patients with six novel ISG15 mutations presenting with skin lesions who were managed for dermatologic disease. Cellularly, we denote striking specificity to the IFN-I response, which was previously assumed to be universal. In peripheral blood, myeloid cells display the most robust IFN-I signatures. In the affected skin, IFN-I signaling is observed in the keratinocytes of the epidermis, endothelia, and the monocytes and macrophages of the dermis. These findings define the specific cells causing circulating and dermatologic inflammation and expand the clinical spectrum of ISG15 deficiency to dermatologic presentations as a third phenotype co-dominant to the infectious and neurologic manifestations.Fil: Martin Fernandez, Marta. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia SauditaFil: Bravo García Morato, María. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Gruber, Conor. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia SauditaFil: Murias Loza, Sara. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Malik, Muhammad Nasir Hayat. Twincore; Alemania. University Of Lahore; Países Bajos. Leibniz Universitat Hannover; Alemania. Helmholtz Gemeinschaft; AlemaniaFil: Alsohime, Fahad. King Saud University; Arabia SauditaFil: Alakeel, Abdullah. King Saud University; Arabia SauditaFil: Valdez, Rita. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Buta, Sofija. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Buda, Guadalupe. Bitgenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; ArgentinaFil: Marti, Marcelo Adrian. Bitgenia; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Larralde, Margarita. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Boisson, Bertrand. L'institut Des Maladies Génétiques Imagine; Francia. The Rockefeller University; Estados Unidos. Universite de Paris; FranciaFil: Feito Rodriguez, Marta. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Qiu, Xueer. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Chrabieh, Maya. L'institut Des Maladies Génétiques Imagine; FranciaFil: Al Ayed, Mohammed. Najran University; Arabia SauditaFil: Al Muhsen, Saleh. King Saud University; Arabia SauditaFil: Desai, Jigar V.. National Institutes of Health; Estados UnidosFil: Ferre, Elise M.N.. National Institutes of Health; Estados UnidosFil: Rosenzweig, Sergio D.. National Institutes of Health; Estados UnidosFil: Amador-Borrero, Blanca. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Bravo-Gallego, Luz Yadira. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Olmer, Ruth. Hannover Medical School; Alemania. German Center for Lung Research; AlemaniaFil: Merkert, Sylvia. Hannover Medical School; Alemania. German Center for Lung Research; AlemaniaFil: Bret, Montserrat. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Sood, Amika K.. University of North Carolina; Estados UnidosFil: Al-rabiaah, Abdulkarim. King Saud University; Arabia SauditaFil: Temsah, Mohamad Hani. King Saud University; Arabia SauditaFil: Halwani, Rabih. University of Sharjah; Emiratos Arabes UnidosFil: Hernandez, Michelle Marilyn. University of North Carolina; Estados UnidosFil: Pessler, Frank. Twincore; Alemania. Helmholtz Centre for Infection Research; AlemaniaFil: Casanova, Jean Laurent. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Howard Hughes Medical Institute; Estados Unidos. Universite de Paris; FranciaFil: Bustamante, Jacinta. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Universite de Paris; FranciaFil: Lionakis, Michail S.. National Institutes of Health; Estados UnidosFil: Bogunovic, Dusan. Icahn School Of Medicine At Mount Sinai; Estados Unido

Genome-Wide Compensatory Changes Accompany Drug- Selected Mutations in the Plasmodium falciparum crt Gene

Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the field and grow well in culture, which may reflect adaptive changes in the parasite genome to compensate for the mutations in PfCRT. Using three isogenic clones that have different drug resistance profiles corresponding to unique mutations in the pfcrt gene (106/1K76, 106/176I, and 106/76I-352K), we investigated changes in gene expression in these parasites grown with and without CQ. We also conducted hybridizations of genomic DNA to identify copy number (CN) changes in parasite genes. RNA transcript levels from 45 genes were significantly altered in one or both mutants relative to the parent line, 106/1K76. Most of the up-regulated genes are involved in invasion, cell growth and development, signal transduction, and transport activities. Of particular interest are genes encoding proteins involved in transport and/or regulation of cytoplasmic or compartmental pH such as the V-type H+ pumping pyrophosphatase 2 (PfVP2), Ca2+/H+ antiporter VCX1, a putative drug transporter and CN changes in pfmdr1. These changes may represent adaptations to altered functionality of PfCRT, a predicted member of drug/metabolite transporter superfamily found on the parasite food vacuole (FV) membrane. Further investigation of these genes may shed light on how the parasite compensates for functional changes accompanying drug resistance mutations in a gene coding for a membrane/drug transporter

Portrait of Candida albicans Adherence Regulators

Cell-substrate adherence is a fundamental property of microorganisms that enables them to exist in biofilms. Our study focuses on adherence of the fungal pathogen Candida albicans to one substrate, silicone, that is relevant to device-associated infection. We conducted a mutant screen with a quantitative flow-cell assay to identify thirty transcription factors that are required for adherence. We then combined nanoString gene expression profiling with functional analysis to elucidate relationships among these transcription factors, with two major goals: to extend our understanding of transcription factors previously known to govern adherence or biofilm formation, and to gain insight into the many transcription factors we identified that were relatively uncharacterized, particularly in the context of adherence or cell surface biogenesis. With regard to the first goal, we have discovered a role for biofilm regulator Bcr1 in adherence, and found that biofilm regulator Ace2 is a major functional target of chromatin remodeling factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a new connection between them. With regard to the second goal, our findings reveal existence of a large regulatory network that connects eleven adherence regulators, the zinc-response regulator Zap1, and approximately one quarter of the predicted cell surface protein genes in this organism. This limited yet sensitive glimpse of mutant gene expression changes had thus defined one of the broadest cell surface regulatory networks in C. albicans