Organ- and Cell-Selective Delivery of mRNA In Vivo Using Guanidinylated Serinol Charge-Altering Releasable Transporters.

Selective RNA delivery is required for the broad implementation of RNA clinical applications, including prophylactic and therapeutic vaccinations, immunotherapies for cancer, and genome editing. Current polyanion delivery relies heavily on cationic amines, while cationic guanidinium systems have received limited attention due in part to their strong polyanion association, which impedes intracellular polyanion release. Here, we disclose a general solution to this problem in which cationic guanidinium groups are used to form stable RNA complexes upon formulation but at physiological pH undergo a novel charge-neutralization process, resulting in RNA release. This new delivery system consists of guanidinylated serinol moieties incorporated into a charge-altering releasable transporter (GSer-CARTs). Significantly, systematic variations in structure and formulation resulted in GSer-CARTs that exhibit highly selective mRNA delivery to the lung (∼97%) and spleen (∼98%) without targeting ligands. Illustrative of their breadth and translational potential, GSer-CARTs deliver circRNA, providing the basis for a cancer vaccination strategy, which in a murine model resulted in antigen-specific immune responses and effective suppression of established tumors.

Novel orexin receptor agonists based on arene- or pyridine-fused 1,3-dihydro-2H-imidazole-2-imines.

A structurally novel class of benzo- or pyrido-fused 1,3-dihydro-2H-imidazole-2-imines was designed and evaluated in an inositol phosphate accumulation assay for Gq signaling to measure agonistic activation of the orexin receptor type 2 (OX2R). These compounds were synthesized in 4-9 steps overall from readily available starting materials. Analogs that contain a stereogenic methyl or cyclopropyl substituent at the benzylic center, and a correctly configured alkyl ether, alkoxyalkyl ether, cyanoalkyl ether, or α-hydroxyacetamido substituted homobenzylic sidechain were identified as the most potent activators of OX2R coupled Gq signaling. Our results also indicate that agonistic activity was stereospecific at both the benzylic and homobenzylic stereogenic centra. We identified methoxyethoxy-substituted pyrido-fused dihydroimidazolimine analog 63c containing a stereogenic benzylic methyl group was the most potent agonist, registering a respectable EC50 of 339 nM and a maximal response (Emax) of 96 % in this assay. In vivo pharmacokinetic analysis indicated good brain exposure for several analogs. Our combined results provide important information towards a structurally novel class of orexin receptor agonists distinct from current chemotypes.

Cadmium toxicity: its' uptake and retaliation by plant defence system and ja signaling.

Cadmium (Cd+2) renders multifarious environmental stresses and highly toxic to nearly all living organisms including plants. Cd causes toxicity by unnecessary augmentation of ROS that targets essential molecules and fundamental processes in plants. In response, plants outfitted a repertory of mechanisms to offset Cd toxicity. The main elements of these are Cd chelation, sequestration into vacuoles, and adjustment of Cd uptake by transporters and escalation of antioxidative mechanism. Signal molecules like phytohormones and reactive oxygen species (ROS) activate the MAPK cascade, the activation of the antioxidant system andsynergistic crosstalk between different signal molecules in order to regulate plant responses to Cd toxicity. Transcription factors like WRKY, MYB, bHLH, bZIP, ERF, NAC etc., located downstream of MAPK, and are key factors in regulating Cd toxicity responses in plants. Apart from this, MAPK and Ca2+signaling also have a salient involvement in rectifying Cd stress in plants. This review highlighted the mechanism of Cd uptake, translocation, detoxification and the key role of defense system, MAPKs, Ca2+ signals and jasmonic acid in retaliating Cd toxicity via synchronous management of various other regulators and signaling components involved under stress condition.

Association of Diabetic Peripheral Neuropathy with Micronutrients.

INTRODUCTION: Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress. Mitochondrial dysfunction and inflammation of blood vessels are associated with a greater need for micronutrients in diabetic patients. These micronutrients may have an association with the complications in diabetics. The purpose of this study was to show the association of diabetic peripheral neuropathy (DPN) with levels of micronutrients such as copper (Cu), zinc (Zn), magnesium (Mg), and vitamin B12 (Vit B12). MATERIALS AND METHODS: This cross-sectional study was conducted in the Department of Medicine, Lala Lajpat Rai Memorial Medical College, Meerut. A total of 130 randomly selected cases of confirmed type-2 diabetic patients were included in this study. DPN cases were identified using the Michigan neuropathy screening instrument. Out of 130 diabetic patients, 28 patients were found to have diabetic neuropathy. The level of various micronutrients was assessed and correlated with the development of DPN. RESULTS: The association of DPN with Zn (p-value of 0.02) and Vit B12 (p-value of 0.008) was found to be significant, whereas Cu (p-value of 0.57) and Mg (p-value of 0.24) were found to be insignificant.

Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice.

The sleep disorder narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic male orexin/tTA; TetO-DTA mice. TAK-925 (1-10 mg/kg, s.c.) and ARN-776 (1-10 mg/kg, i.p.) were injected 15 min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc ) and activity were recorded by telemetry; recordings for the first 6 h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the second hour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6 h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterised by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the second hour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity, and Tsc , suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HCRTR2 agonists.

Measurement of unmet healthcare needs to assess progress on universal health coverage - exploring a novel approach based on household surveys.

BACKGROUND: Universal Health Coverage (UHC) aims to ensure universal access to quality healthcare according to health needs. The extent to which population health needs are met should be a key measure for progress on UHC. The indicators in use for measuring access mostly relate to physical accessibility or insurance coverage. Or, utilization of services is taken as indirect measure for access but it is assessed against only the perceived healthcare needs. The unperceived needs do not get taken into account. The present study was aimed at demonstrating an approach for measuring the unmet healthcare needs using household survey data as an additional measure of UHC. METHODS: A household survey was conducted in Chhattisgarh state of India, covering a multi-stage sample of 3153 individuals. Healthcare need was measured in terms of perceived needs which would be self-reported and unperceived needs where clinical measurement supplemented the interview response. Estimation of unperceived healthcare needs was limited to three tracer conditions- hypertension, diabetes and depression. Multivariate analysis was conducted to find the determinants of the various measures of the perceived and unperceived needs. RESULTS: Of the surveyed individuals, 10.47% reported perceived healthcare needs for acute ailments in the last 15 days. 10.62% individuals self-reported suffering from chronic conditions. 12.75% of those with acute ailment and 18.40% with chronic ailments received no treatment, while 27.83% and 9.07% respectively received treatment from unqualified providers. On an average, patients with chronic ailments received only half the medication doses required annually. The latent need was very high for chronic ailments. 47.42% of individuals above 30 years age never had blood pressure measured. 95% of those identified with likelihood of depression had not sought any healthcare and they did not know they could be suffering from depression. CONCLUSION: To assess progress on UHC more meaningfully, better methods are needed to measure unmet healthcare needs, taking into account both the perceived and unperceived needs, as well as incomplete care and inappropriate care. Appropriately designed household surveys offer a significant potential to allow its periodic measurement. Their limitations in measuring the 'inappropriate care' may necessitate supplementation with qualitative methods.

Evaluation of C4b as an adjunct marker in symptomatic RT-PCR negative Covid-19 cases.

Introduction: Detecting low viral load has been a challenge in this pandemic, which has led to its escalated transmission. Complement activation has been implicated in pathogenesis of Covid-19 infection. Thus, evaluation of complement activation in suspected Covid-19 infection may help to detect infection and limit false negative cases thus limiting transmission of infection. We speculate that measuring C4b, produced from an activated complement system due to the presence of Covid-19 may help in its detection, even when the viral titers are low. Methods: Plasma C4b levels of symptomatic RT-PCR positive patients (cases, n = 40); symptomatic RT-PCR negative patients (n = 35) and asymptomatic RT-PCR negative controls (n = 40) were evaluated. Plasma C5b-9, IL-6, D-dimer and C1-Inhibitor (C1-INH) were also measured in cases and controls. ELISA kits were used for all measurements. Statistical analyses were carried out using Stata, version 12 (Stata Corp., Texas, USA). Results: C4b levels were found to be significantly increased in RT-PCR positive patients as compared to asymptomatic RT-PCR negative controls. RT-PCR negative but symptomatic patients still showed increased C4b levels. The significantly higher levels of C4b in cases with a cut-off value of ≥ 116 ng/ml with optimum sensitivity and specificity of 80% and 52% respectively is indicative of its possible use as an adjunct marker. Increased levels of D-dimer, IL6, along with decreased levels of C1-INH were found in cases compared to controls. Whereas, C5b-9 levels were not significantly raised in cases. Conclusions: The results of our study suggests that plasma C4b may help to detect infection in false negative cases of RT-PCR that escape detection owing to low viral load. However, to confirm it a large-scale study is needed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01033-z.

Molecular basis of differential adventitious rooting competence in poplar genotypes.

Recalcitrant adventitious root (AR) development is a major hurdle in propagating commercially important woody plants. Although significant progress has been made to identify genes involved in subsequent steps of AR development, the molecular basis of differences in apparent recalcitrance to form AR between easy-to-root and difficult-to-root genotypes remains unknown. To address this, we generated cambium tissue-specific transcriptomic data from stem cuttings of hybrid aspen, T89 (difficult-to-root) and hybrid poplar OP42 (easy-to-root), and used transgenic approaches to verify the role of several transcription factors in the control of adventitious rooting. Increased peroxidase activity was positively correlated with better rooting. We found differentially expressed genes encoding reactive oxygen species scavenging proteins to be enriched in OP42 compared with T89. A greater number of differentially expressed transcription factors in cambium cells of OP42 compared with T89 was revealed by a more intense transcriptional reprograming in the former. PtMYC2, a potential negative regulator, was less expressed in OP42 compared with T89. Using transgenic approaches, we demonstrated that PttARF17.1 and PttMYC2.1 negatively regulate adventitious rooting. Our results provide insights into the molecular basis of genotypic differences in AR and implicate differential expression of the master regulator MYC2 as a critical player in this process.

Trimethylene Methane Dianion Equivalent for the Asymmetric Consecutive Allylation of Aldehydes: Applications to Prins-Driven Macrocyclizations for the Synthesis of Bryostatin 1 and Analogues.

We report a one-step (one-flask) generation and reaction of a bifunctional allylating reagent, a trimethylene methane dianion equivalent, that provides a route for the asymmetric 2-(trimethylsilylmethyl) allylation of aldehydes. The product of the first aldehyde allylation process is then set to engage in a second separate aldehyde allylation, providing an improved Prins macrocyclization strategy both for the scalable synthesis of bryostatin 1 and for the total synthesis of a new potent bryostatin analogue.

Shaping the root system architecture in plants for adaptation to drought stress.

Root system architecture plays an important role in plant adaptation to drought stress. The root system architecture (RSA) consists of several structural features, which includes number and length of main and lateral roots along with the density and length of root hairs. These features exhibit plasticity under water-limited environments and could be critical to developing crops with efficient root systems for adaptation under drought. Recent advances in the omics approaches have significantly improved our understanding of the regulatory mechanisms of RSA remodeling under drought and the identification of genes and other regulatory elements. Plant response to drought stress at physiological, morphological, biochemical, and molecular levels in root cells is regulated by various phytohormones and their crosstalk. Stress-induced reactive oxygen species play a significant role in regulating root growth and development under drought stress. Several transcription factors responsible for the regulation of RSA under drought have proven to be beneficial for developing drought tolerant crops. Molecular breeding programs for developing drought-tolerant crops have been greatly benefitted by the availability of quantitative trait loci (QTLs) associated with the RSA regulation. In the present review, we have discussed the role of various QTLs, signaling components, transcription factors, microRNAs and crosstalk among various phytohormones in shaping RSA and present future research directions to better understand various factors involved in RSA remodeling for adaptation to drought stress. We believe that the information provided herein may be helpful in devising strategies to develop crops with better RSA for efficient uptake and utilization of water and nutrients under drought conditions.

Studying Drug Release through Polymeric Controlled Release Formulations in United States Pharmacopoeia 2 Apparatus Using Multiphysics Simulation and Experiments.

In vitro dissolution of oral drug formulations is often studied using the United States Pharmacopoeia (USP) apparatus. Although a well-stirred vessel or a perfect sink assumption is often employed in the modeling of in vitro dissolution in USP apparatus, such a limit is usually not realized in actual experimental conditions. The interplay of hydrodynamics in the vessel and the swelling and erosion of dosage forms often results in substantial deviations from the dissolution behavior obtained under perfect sink approximation. We develop a multiphysics model of drug release from controlled release tablets of polymeric excipients with active pharmaceutical ingredients (APIs). Simulations are performed in COMSOL for the USP 2 (paddle) apparatus and the effects of stirring speed, drug loading, erosion rate, and polymer swelling and erosion are analyzed in detail. We demonstrate that the drug release phenomena can be conveniently interpreted using the Weibull equation to fit the simulation results. This is further confirmed using drug release experiments performed on mechanically compressed tablets of naproxen sodium as the API with poly-methyl-methacrylate-co-methacrylic acid as the excipient. We show that the API-to-polymer ratio may be varied to obtain different regimes of controlled release.

Alleviating aluminum toxicity in plants: Implications of reactive oxygen species signaling and crosstalk with other signaling pathways.

Aluminum (Al) toxicity is a major limiting factor for plant growth and productivity in acidic soil. At pH lower than 5.0 (pH < 5.0), the soluble and toxic form of Al (Al3+ ions) enters root cells and inhibits root growth and uptake of water and nutrients. The organic acids malate, citrate, and oxalate are secreted by the roots and chelate Al3+ to form a non-toxic Al-OA complex, which decreases the entry of Al3+ into the root cells. When Al3+ enters, it leads to the production of reactive oxygen species (ROS) in cells, which are toxic and cause damage to biomolecules like lipids, carbohydrates, proteins, and nucleic acids. When ROS levels rise beyond the threshold, plants activate an antioxidant defense system that comprises of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione S-transferase (GST), ascorbic acid (ASA), phenolics and alkaloids etc., which protect plant cells from oxidative damage by scavenging and neutralizing ROS. Besides, ROS also play an important role in signal transduction and influence many molecular and cellular process like hormone signaling, gene expression, cell wall modification, cell cycle, programed cell death (PCD), and development. In the present review, the mechanisms of Al-induced ROS generation, ROS signaling, and crosstalk with other signaling pathways helping to combat Al toxicity have been summarized, which will help researchers to understand the intricacies of Al-induced plant response at cellular level and plan research for developing Al-toxicity tolerant crops for sustainable agriculture in acid soil-affected regions of the world.

Phytohormone signalling and cross-talk to alleviate aluminium toxicity in plants.

Aluminium (Al) is one of the most abundant metals in earth crust, which becomes toxic to the plants growing in acidic soil. Phytohormones like ethylene, auxin, cytokinin, abscisic acid, jasmonic acid and gibberellic acid are known to play important role in regulating Al toxicity tolerance in plants. Exogenous applications of auxin, cytokinin and abscisic acid have shown significant effect on Al-induced root growth inhibition. Moreover, ethylene and cytokinin act synergistically with auxin in responding against Al toxicity. A number of studies showed that phytohormones play vital roles in controlling root responses to Al toxicity by modulating reactive oxygen species (ROS) signalling, cell wall modifications, organic acid exudation from roots and expression of Al responsive genes and transcription factors. This review provides a summary of recent studies related to involvement of phytohormone signalling and cross-talk with other pathways in regulating response against Al toxicity in plants.

Comparing the average cost of outpatient care of public and for-profit private providers in India.

INTRODUCTION: Understanding the cost of care associated with different kinds of healthcare providers is necessary for informing the policy debates in mixed health-systems like India's. Existing studies reporting Out of Pocket Expenditure (OOPE) per episode of outpatient care in public and private providers in India do not provide a fair comparison because they have not taken into account the government subsidies received by public facilities. Public and private health insurance in India do not cover outpatient care and for-profit providers have to meet all their costs out of the payments they take from patients. METHODS: The average direct cost per acute episode of outpatient care was compared for public providers, for-profit formal providers and informal private providers in Chhattisgarh state of India. For public facilities, government subsidies for various inputs were taken into account. Resources used were apportioned using Activity Based Costing. Land provided free to public facilities was counted at market prices. The study used two datasets: a) household survey on outpatient utilisation and OOPE b) facility survey of public providers to find the input costs borne by government per outpatient-episode. RESULTS: The average cost per episode of outpatient care was Indian Rupees (INR) 400 for public providers, INR 586 for informal private providers and INR 2643 for formal for-profit providers and they managed 39.3, 37.9 and 22.9% of episodes respectively. The average cost for government and households put together was greater for using formal for-profit providers than the public providers. The disease profile of care handled by different types of providers was similar. Volume of patients and human-resources were key cost drivers in public facilities. Close to community providers involved less cost than others. CONCLUSIONS AND RECOMMENDATIONS: The findings have implications for the desired mix of public and private providers in India's health-system. Poor regulation of for-profit providers was an important structural cost driver. Purchasing outpatient care from private providers may not reduce average cost. Policies to strengthen public provisioning of curative primary care close to communities can help in reducing cost.

Identification and validation of reference genes for qRT-PCR based studies in horse gram (Macrotyloma uniflorum).

The quantitative real-time polymerase chain reaction (qRT-PCR) is the most sensitive and commonly used technique for gene expression studies in biological systems. However, the reliability of qRT-PCR results depends on the selection of reference gene(s) for data normalization. Horse gram (Macrotyloma uniflorum) is an important legume crop on which several molecular studies have been reported. However, the stability of reference genes has not been evaluated. In the present study, nine candidate reference genes were identified from horse gram RNA-seq data and evaluated in two horse gram genotypes, HPK4 and HPKM317 under six abiotic stresses viz. cold, drought, salinity, heat, abscisic acid and methyl viologen-induced oxidative stress. The results were evaluated using geNorm, Bestkeeper, Normfinder and delta-delta Ct methods and comprehensive ranking was assigned using RefFinder and RankAggreg software. The overall result showed that TCTP was one of the most stable genes in all samples and in genotype HPK4, while in HPKM317 profilin was most stably expressed. However, PSMA5 was identified as least stable in all the experimental conditions. Expression of target genes dehydrin and early response to dehydration 6 under drought stress was also validated using TCTP and profilin for data normalization, either alone or in combination, which confirmed their suitability for qRT-PCR data normalization. Thus, TCTP and profilin genes may be used for qRT-PCR data normalization for molecular and genomic studies in horse gram. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01104-0.

Equity and elderly health in India: reflections from 75th round National Sample Survey, 2017-18, amidst the COVID-19 pandemic.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak, called coronavirus disease - 2019 (COVID-19), has affected more than 200 countries across the globe with a higher fatality rate among the elderly population. Aim of the study is to highlight the vulnerability of the aged amidst the current COVID-19 pandemic, and in the light of the recent international evidence, suggests what government could do to mitigate their vulnerability. METHODS: Data from the recently released (November 2019) 75th Round National Sample Survey (NSS), which was conducted from July 2017 to June 2018, across 8077 rural villages and 6181 urban wards was used for this study. Data collected from 555,115 individuals (rural: 325,232; urban: 229,232) included 42,762 elderly individuals (60 years or above). Bivariate and multivariate analyses were used for the calculation. RESULTS: Of the total sample of elderly individuals, 27.7% reported suffering from an ailment in the last 15 days, whereas 8.5% had been hospitalized during the last 365 days. Among the elderly, hospitalization rate was higher in the urban areas (OR: 1.23), general social category (OR: 1.18), richest economic quintile (OR: 1.69), and among those living alone (OR: 2.40). Also, among the elderly, 64% of those in the scheduled tribe (social group) and 51% in the poorest economic quintile utilized public facilities for hospitalization. Cardiovascular ailments were the major cause for hospitalization (18.1%) and outpatient visit (32%) among the elderly. Ailments related to diabetes and hypertension constituted 55% of outpatient visit for the elderly. Only 18.9% of the elderly had health insurance though chances of facing catastrophic health expenditures were high among the elderly. 6.6% of elderly female and 1.6% male live alone, and 27.5% of age 80 years and above are immobile. 50% of male and 90% of female are financially dependent on others and more so in poorer economic quintiles. CONCLUSIONS: The vulnerability of India's elderly increases across economic levels, and other dimensions such as the place of residence, gender, social group (caste), marital status, living arrangements, surviving children, and economic dependence. The current COVID-19 pandemic poses a greater risk of social isolation among the elderly, which may cause detrimental health impact. TRIAL REGISTRATION: Not applicable since the study is based on secondary data.

Role of Phytochemicals in Cancer Prevention.

The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.

Comparative transcriptome and translatome analysis in contrasting rice genotypes reveals differential mRNA translation in salt-tolerant Pokkali under salt stress.

BACKGROUND: Soil salinity is one of the primary causes of yield decline in rice. Pokkali (Pok) is a highly salt-tolerant landrace, whereas IR29 is a salt-sensitive but widely cultivated genotype. Comparative analysis of these genotypes may offer a better understanding of the salinity tolerance mechanisms in rice. Although most stress-responsive genes are regulated at the transcriptional level, in many cases, changes at the transcriptional level are not always accompanied with the changes in protein abundance, which suggests that the transcriptome needs to be studied in conjunction with the proteome to link the phenotype of stress tolerance or sensitivity. Published reports have largely underscored the importance of transcriptional regulation during salt stress in these genotypes, but the regulation at the translational level has been rarely studied. Using RNA-Seq, we simultaneously analyzed the transcriptome and translatome from control and salt-exposed Pok and IR29 seedlings to unravel molecular insights into gene regulatory mechanisms that differ between these genotypes. RESULTS: Clear differences were evident at both transcriptional and translational levels between the two genotypes even under the control condition. In response to salt stress, 57 differentially expressed genes (DEGs) were commonly upregulated at both transcriptional and translational levels in both genotypes; the overall number of up/downregulated DEGs in IR29 was comparable at both transcriptional and translational levels, whereas in Pok, the number of upregulated DEGs was considerably higher at the translational level (544 DEGs) than at the transcriptional level (219 DEGs); in contrast, the number of downregulated DEGs (58) was significantly less at the translational level than at the transcriptional level (397 DEGs). These results imply that Pok stabilizes mRNAs and also efficiently loads mRNAs onto polysomes for translation during salt stress. CONCLUSION: Under salt stress, Pok is more efficient in maintaining cell wall integrity, detoxifying reactive oxygen species (ROS), translocating molecules and maintaining photosynthesis. The present study confirmed the known salt stress-associated genes and also identified a number of putative new salt-responsive genes. Most importantly, the study revealed that the translational regulation under salinity plays an important role in salt-tolerant Pok, but such regulation was less evident in the salt-sensitive IR29.

Effectiveness of government strategies for financial protection against costs of hospitalization Care in India.

BACKGROUND: In the past decade, India has seen the introduction of many 'publicly funded health insurance' schemes (PFHIs) that claim to cover approximately 300 million people and are essentially forms of purchasing care from both public and private providers to reduce out-of-pocket expenditure (OOPE) for hospitalization. METHODS: Data from a recent government-organized nationwide household survey, The National Sample Survey 71st Round, were used to analyse the effectiveness and equity of tax-funded public health services and PFHIs as distinct but overlapping approaches to financial protection for hospitalization across different socio-economic categories. Cross-tabulation analysis, multivariate logistic regression and propensity score matching were the main analytical methods used. RESULTS: Government hospitals provide access to 45.6% of all hospitalization needs. Although poorer quintiles use public hospitals more often, even in the poorest quintile, as many as 37.2% are utilizing private hospitals. The average OOPE that a household experiences for hospitalization in public hospitals is approximately only one-fifth of the OOPE for hospitalization in the private sector. PFHI schemes cover 12.8% of the population, and coverage is higher in upper quintiles and in urban areas. Hospitalization rates increase with PFHI coverage, and this occurs with both public and private providers. Propensity score matching shows that PFHI contributes to a marginal reduction (1%) in 'catastrophic health expenditure incidence at the 25% threshold' (CHE-25) for the bottom three quintiles. The reported coverage of PFHIs was greater in the upper income quintiles. Utilization of public services was greater in the poorer income quintiles and more marginalized social groups. CONCLUSIONS: Periodic surveys are essential to guide policy choices regarding the appropriate mix of strategies for financial protection in pluralistic systems. There is a need for caution regarding any shift in the role of governments from providing services to purchasing care, given the contexts and limitations of currently available PFHIs. Even with tax-funded public services, although the average OOPE is lower than the care purchased through PFHIs, there is still a modest level of CHE and impoverishment due to health care costs that persist. Both strategies need to be synergized for more effective financial protection.

Effect of Pneumoperitoneum and Patient Positioning on Intracranial Pressures during Laparoscopy: A Prospective Comparative Study.

STUDY OBJECTIVE: To evaluate the effect of pneumoperitoneum and head position during laparoscopic surgery on intracranial pressures (ICPs) using sonographic measurements of optic nerve sheath diameter (ONSD). DESIGN: Prospective observational study (Canadian Task Force classification II-1). SETTING: A tertiary-level hospital. PATIENTS: Sixty-one women aged 15 to 50 years with American Society of Anesthesiologists grade 1 risk and body mass index ≤ 29 kg/m2 were admitted to the hospital between November 2015 and October 2016 for elective laparoscopic surgery and were included in this study. INTERVENTION: Patients were placed in the Trendelenburg position with head down (group I; n = 33) and reverse Trendelenburg position with head up (group II; n = 28). MEASUREMENTS AND MAIN RESULTS: ONSD was measured via sonography at 4 time points: at baseline before pneumoperitoneum, after pneumoperitoneum, after patient was placed in respective position, and once pneumoperitoneum was released. Patient demographics were comparable in all respects. ICP as indicated by ONSD showed a significant increase after pneumoperitoneum (p = .0001 in group I and p = .0011 in group II). When patients were placed in either head position, ONSD showed a further increase in ICP. This increase was more pronounced in patients assuming the head-down Trendelenburg position compared with patients in reverse Trendelenburg (head-up) position. Baseline and preoperative ONSD measurements were not reached even after 5 minutes of desufflation. CONCLUSIONS: Pneumoperitoneum causes an increase in ICP. The patient position, either head up or head down as in gynecologic laparoscopic procedures, further worsens ICP. ONSD does not revert back to baseline until 5 minutes after desufflation.