Occurrence and distribution of heavy metals in water and soil sediments of Vellore District, Tamil Nadu, India.

The occurrence of heavy metals (HMs) in water and soil sediments represents a serious environmental concern. This study revealed the presence and distribution of HMs in water and soil sediments of various places in Vellore District, Tamil Nadu, India. Twenty-one sites were selected along the study area, and inductively coupled plasma-optical emission spectrometry (ICP-OES) was used to analyze the concentration of the heavy metals. The dominance of various HMs in the soil sediment sample follows the order strontium (Sr) > Manganese (Mn) > Barium (Ba) > Zinc (Zn) > Nickel (Ni) and Sr > Mn > Zn > Boron (B) > , respectively. It was found that the concentration of HMs in water and soil sediments in Ambur market and Mottukollai area was significantly higher than the recommended limits. Thus, the results showed that the presence of HMs in water and soil sediments could be threatened pollution factors unsafe for irrigation, drinking, and other human activities.

Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study.

Background: Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, clinically presenting with common symptoms of fever, dry cough, and breathlessness within 14 days of exposure. Its severity ranges from mild to severe, latter manifesting into severe acute respiratory syndrome. As a part of multidisciplinary team, physiotherapy along with medical management was administered to patients with COVID-19 in an acute care setup. This retrospective study aims to explore various patient characteristics and will aid in identifying the impairments associated with the disease, giving a direction to the physiotherapy community in planning future management strategy to improve quality of life. Patients and methods: The present study is a unicentric study wherein prospective analysis of retrospective data of patients referred for physiotherapy from May 13 to July 31, 2020, was performed. (i) Characteristics of patients, (ii) associated comorbidities, (iii) hospital course since the time of admission to discharge, (iv) mode of oxygen delivery, (v) pre- and post-physiotherapy treatment values of oxygen saturation and heart rate, and (vi) physiotherapy treatment were recorded. The archived data were analyzed using the commercially available SPSS software version 24. Wilcoxon's matched pair test was used to compare pre- and post-treatment oxygen saturation and heart rate, and McNemar's test was used to compare mode of oxygen delivery and pre- and post-physiotherapy treatment. Results: Descriptive analysis of data showed a better outcome in terms of grade of dyspnea and rate of discharge on day 14 of physiotherapy treatment. Hence, a comparative analysis of day 1 and day 14 was performed for mode of oxygen delivery, oxygen saturation, and heart rate. A statistically significant improvement was observed in the heart rate (p = 0.001) and oxygen delivery (p = 0.000). However, no significant difference in the level of oxygen saturation was found (p = 0.6433). Conclusion: Physiotherapy treatment in conjunction with medical treatment can be effectively administered in patients with COVID-19 in acute care setup taking into consideration the health status and the hemodynamic stability of the patients. It emphasizes the role of physiotherapy in the alleviation of symptoms, facilitating early weaning and recovery enabling early discharge from the hospital. How to cite this article: Verma CV, Arora RD, Mistry HM, Kubal SV, Kolwankar NS, Patil PC, et al. Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study. Indian J Crit Care Med 2021;25(3):317-321.

A Small Cysteine-Rich Protein from the Asian Soybean Rust Fungus, Phakopsora pachyrhizi, Suppresses Plant Immunity.

The Asian soybean rust fungus, Phakopsora pachyrhizi, is an obligate biotrophic pathogen causing severe soybean disease epidemics. Molecular mechanisms by which P. pachyrhizi and other rust fungi interact with their host plants are poorly understood. The genomes of all rust fungi encode many small, secreted cysteine-rich proteins (SSCRP). While these proteins are thought to function within the host, their roles are completely unknown. Here, we present the characterization of P. pachyrhizi effector candidate 23 (PpEC23), a SSCRP that we show to suppress plant immunity. Furthermore, we show that PpEC23 interacts with soybean transcription factor GmSPL12l and that soybean plants in which GmSPL12l is silenced have constitutively active immunity, thereby identifying GmSPL12l as a negative regulator of soybean defenses. Collectively, our data present evidence for a virulence function of a rust SSCRP and suggest that PpEC23 is able to suppress soybean immune responses and physically interact with soybean transcription factor GmSPL12l, a negative immune regulator.

The E3 Ligase TaSAP5 Alters Drought Stress Responses by Promoting the Degradation of DRIP Proteins.

In Arabidopsis (Arabidopsis thaliana) plants growing under normal conditions, DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN2A (DREB2A) is present at low levels because it is ubiquitinated and destabilized by DREB2A INTERACTING PROTEIN1 (DRIP1) and DRIP2 through 26S proteasome-mediated proteolysis. Drought stress counteracts the ubiquitination and proteolysis of DREB2A, thus allowing the accumulation of sufficient amounts of DREB2A protein to activate downstream gene expression. The mechanisms leading to drought stress-mediated DREB2A accumulation are still unclear. Here, we report that the wheat (Triticum aestivum) TaSAP5 protein, which contains an A20/AN1 domain, acts as an E3 ubiquitin ligase to mediate DRIP degradation and thus increase DREB2A protein levels. Drought induces TaSAP5 expression in wheat, and TaSAP5 overexpression in Arabidopsis and wheat seedlings increased their drought tolerance, as measured by survival rate and grain yield under severe drought stress. TaSAP5 can interact with and ubiquitinate TaDRIP, as well as AtDRIP1 and AtDRIP2, leading to their subsequent degradation through the 26S proteasome pathway. Consistent with this, TaSAP5 overexpression enhances DRIP degradation and increases the levels of DREB2A protein and its downstream targets. These results suggest that TaSAP5 acts to link drought with DREB2A accumulation and illustrate the molecular mechanisms involved in this process.

Biocatalysis for synthesis of pharmaceuticals.

Chirality is a key factor in the safety and efficacy of many drug products and thus the production of single enantiomers of drug intermediates and drugs has become important and state of the art in the pharmaceutical industry. There has been an increasing awareness of the enormous potential of microorganisms and enzymes (biocatalysts) for the transformation of synthetic chemicals with high chemo-, regio- and enatioselectivities providing products in high yields and purity. In this article, biocatalytic processes are described for the synthesis of key chiral intermediates for development pharmaceuticals.

Twenty-Four Syndrome: An Untold Presentation of Pontine Hemorrhage.

Pontine hemorrhages are relatively uncommon. Various atypical manifestations of pontine stroke like eight-and-a-half syndrome, fifteen-and-a-half syndrome, and sixteen syndrome have been described in the past. We came across a case of pontine bleed that presented with bilateral facial palsy, bilateral horizontal gaze palsy, and contralateral sensorineural hearing loss accounting to the hitherto not described "twenty-four syndrome" with Horner's syndrome and left hemiparesis.

Energy production through organic fraction of municipal solid waste-A multiple regression modeling approach.

In the 21st century, people migrated from rural to urban areas for several reasons. As a result, the populations of Indian cities are increasing day by day. On one hand, the country is developing in the field of science and technology and on the other hand, it is encountering a serious problem called 'Environmental degradation'. Due to increase in population, the generation of solid waste is also increased and is being disposed in open dumps and landfills which lead to air and land pollution. This study is attempted to generate energy out of organic solid waste by the bio- fermentation process. The study was conducted for a period of 7 months at Erode, Tamilnadu and the reading on various parameters like Hydraulic retention time, organic loading rate, sludge loading rate, influent pH, effluent pH, inlet volatile acids, out let volatile fatty acids, inlet VSS/TS ratio, outlet VSS/TS ratio, influent COD, effluent COD and % of COD removal are recorded for every 10 days. The aim of the present study is to develop a model through multiple linear regression analysis with COD as dependent variable and various parameters like HRT, OLR, SLR, influent, effluent, VSS/TS ratio, influent COD, effluent COD, etc as independent variables and to analyze the impact of these parameters on COD. The results of the model developed through step-wise regression method revealed that only four parameters Influent COD, effluent COD, VSS/TS and Influent/pH were main influencers of COD removal. The parameters influent COD and VSS/TS have positive impact on COD removal and the parameters effluent COD and Influent/pH have negative impact. The parameter Influent COD has the highest order of impact, followed by effluent COD, VSS/TS and influent pH. The other parameters HRT, OLR, SLR, INLET VFA and OUTLET VFA were not significantly contributing to the removal of COD. The implementation of the process suggested through this study might bring in dual benefit to the community, viz treatment of solid waste and creation of energy.

Jasminum grandiflorum oral gel as an add-on to standard of care in radiation induced grade 2 oral mucositis - an open label pilot clinical trial.

BACKGROUND: Radiation-induced oral mucositis is one of the most critical dose-limiting toxicities associated with radiation therapy for oral cancer which can result in treatment interruption and compromise the quality of the life of cancer patients. Jati (Jasminum grandiflorum) is used in Ayurveda to treat oral conditions like stomatitis and mouth ulcers. OBJECTIVE: To test the feasibility of Jati oral gel as an add on therapy in grade 2 radiation-induced oral mucositis. MATERIALS AND METHODS: A prospective, open-label, non-randomised pilot trial was conducted on 20 patients with grade 2 radiation-induced oral mucositis at a tertiary cancer hospital. The control group received sodium bicarbonate mouthwash 4-5 times daily as the standard of care, while the intervention arm also received Jati oral gel twice daily. We used the ImageJ software for objective assessment and the Visual Analogue Scale for subjective pain assessment. The study was continued for 15 days or until the mucositis progressed to grade 3 or resolved to grade 1. RESULT: There was a significant reduction in the mean pain score and mean area of mucositis in the intervention group compared to the control group. CONCLUSION: Jati oral gel is a suitable medicament as an add-on therapy in managing grade 2 radiation-induced oral mucositis.

Myopathies of endocrine origin: A review for physicians.

Myopathies are a common manifestation of endocrine disorders. Endocrine myopathies are often overlooked while considering differential diagnoses in patients with musculoskeletal symptoms. The hindrance to mobility and the musculoskeletal discomfort owing to these myopathies are important causes of disability and depreciated quality of life in these patients. Endocrine myopathies occur due to the effects of endogenous or iatrogenic hormonal imbalance on skeletal muscle protein and glucose metabolism, disrupting the excitation-contraction coupling. Abnormalities of the pituitary, thyroid, parathyroid, adrenal, and gonadal hormones have all been associated with myopathies and musculoskeletal symptoms. Endocrine myopathies can either be the complication of a secondary endocrine disorder or a presenting symptom of a missed underlying disorder. Therefore, an underlying endocrine abnormality must always be excluded in all patients with musculoskeletal symptoms. This review presents a compilation of various endocrine myopathies, their etiopathogenesis, clinical presentation, diagnostic modalities, and treatment protocols.

Fruit waste-derived cellulose-polyaniline composite for adsorption-coupled reduction of chromium oxyanions.

Hexavalent chromium oxyanions, known as potentially toxic micropollutants, exist in the effluents and discharges of metallurgical, electroplating, refractory, chemical, and tanning industries. The exposure of chromium-contaminated water causes severe health hazards. The present work outlines a facile approach to grow polyaniline (PANI) on fruit-waste-derived cellulose (CEL) via oxidative polymerization of aniline; followed by chemical processing with NH4OH to obtain CEL-PANI-EB composites for adsorptive separation-coupled reduction of highly toxic hexavalent chromium oxyanions. The spectroscopic analyses of the CEL-PANI-EB composite before and after adsorption of Cr(VI) oxyanions revealed hydrogen bonding, electrostatic, and complexation as major interactive pathways. The adsorbed hexavalent chromium oxyanions are reduced into Cr(III) species by oxidation of PANI-based benzenoid amine into quinoid imine in the CEL-PANI-EB composite. The adsorption of Cr(VI) oxyanions by the CEL-PANI-EB composite showed negligible effects of other anionic co-pollutants, like NO3- and SO42-. The CEL-PANI-EB composite adsorbed Cr(VI) oxyanions with a removal capacity of 469 mg g-1, based on the Langmuir adsorption isotherm model. The hydroxyl functionalities in cellulose and amine/imine functionalities in PANI facilitate the electrostatic attraction between the CEL-PANI-EB and Cr(VI) oxyanions in an acidic environment beside the hydrogen linkages. The adsorbed Cr(VI) oxyanions are reduced to Cr(III)-based species by the benzenoid amines of PANI, as revealed from the XPS analyses. The CEL-PANI-EB composite showed excellent recyclability and maintained 83.4% adsorption efficiency after seven runs of chromium adsorption-desorption. The current findings reveal the potential of CEL-PANI-EB composites for the adsorptive removal of Cr(VI) oxyanions and their conversion into a lesser toxic form, making them promising materials for wastewater treatment applications.

A candidate male-fertility female-fertility gene tagged by the soybean endogenous transposon, Tgm9.

In soybean, the W4 gene encoding dihydroflavonol-4-reductase controls anthocyanin pigment biosynthesis in flowers. The mutant allele, w4-m, is characterized by variegated flowers and was evolved from the insertion of an endogenous transposable element, Tgm9, in intron II of the W4 gene. In the w4-m mutant line, reversion of the unstable allele from variegated to normal purple flower in revertants would indicate Tgm9's excision accompanied by its insertion into a second locus. We identified a male-sterile, female-sterile mutant from such germinal revertant bearing purple flowers. The objectives of our investigation were to map the sterility locus, identify candidate genes for the male-fertile, female-fertile phenotype, and then determine if sterility is associated with the insertion of Tgm9 in the sterility locus. We used bulked segregant analysis to map the locus to molecular linkage group J (chromosome 16). Fine mapping enabled us to flank the locus to a 62-kb region that contains only five predicted genes. One of the genes in that region, Glyma16g07850.1, codes for a helicase. A rice homolog of this gene has been shown to control crossing over and fertility phenotype. Thus, Glyma16g07850.1 is most likely the gene regulating the male and female fertility phenotype in soybean. DNA blot analysis of the segregating individuals for Tgm9 showed perfect association between sterility and the presence of the transposon. Most likely, the sterility mutation was caused by the insertion of Tgm9. The transposable element should facilitate identification of the male- and female-fertility gene. Characterization of the fertility gene will provide vital molecular insight on the reproductive biology of soybean and other plants.

Investigation of the Fusarium virguliforme fvtox1 mutants revealed that the FvTox1 toxin is involved in foliar sudden death syndrome development in soybean.

The soil borne fungus, Fusarium virguliforme, causes sudden death syndrome (SDS) in soybean, which is a serious foliar and root rot disease. The pathogen has never been isolated from the diseased foliar tissues; phytotoxins produced by the pathogen are believed to cause foliar SDS symptoms. One of these toxins, a 13.5-kDa acidic protein named FvTox1, has been hypothesized to interfere with photosynthesis in infected soybean plants and cause foliar SDS. The objective of this study is to determine if FvTox1 is involved in foliar SDS development. We created and studied five independent knockout fvtox1 mutants to study the function of FvTox1. We conducted Agrobacterium tumefaciens-mediated transformation to accomplish homologous recombination of FvTox1 with a hygromycin B resistance gene, hph, to generate the fvtox1 mutants. Approximately 40 hygromycin-resistant transformants were obtained from 10(6) conidial spores of the F. virguliforme Mont-1 isolate when the spores were co-cultivated with the A. tumefaciens EHA105 but not with LBA4044 strain carrying a recombinant binary plasmid, in which the hph gene encoding hygromycin resistance was flanked by 5'- and 3'-end FvTox1 sequences. We observed homologous recombination-mediated integration of hph into the FvTox1 locus among five independent fvtox1 mutants. In stem-cutting assays using cut soybean seedlings fed with cell-free F. virguliforme culture filtrates, the knockout fvtox1 mutants caused chlorophyll losses and foliar SDS symptoms, which were over twofold less than those caused by the virulent F. virguliforme Mont-1 isolate. Similarly, in root inoculation assays, more than a twofold reduction in foliar SDS development and chlorophyll losses was observed among the seedlings infected with the fvtox1 mutants as compared to the seedlings infected with the wild-type Mont-1 isolate. These results suggest that FvTox1 is a major virulence factor involved in foliar SDS development in soybean. It is expected that interference of the function of this toxin in transgenic soybean plants will lead to generation of SDS-resistant soybean cultivars.

Markov modulated Poisson process models incorporating covariates for rainfall intensity.

Time series of rainfall bucket tip times at the Beaufort Park station, Bracknell, in the UK are modelled by a class of Markov modulated Poisson processes (MMPP) which may be thought of as a generalization of the Poisson process. Our main focus in this paper is to investigate the effects of including covariate information into the MMPP model framework on statistical properties. In particular, we look at three types of time-varying covariates namely temperature, sea level pressure, and relative humidity that are thought to be affecting the rainfall arrival process. Maximum likelihood estimation is used to obtain the parameter estimates, and likelihood ratio tests are employed in model comparison. Simulated data from the fitted model are used to make statistical inferences about the accumulated rainfall in the discrete time interval. Variability of the daily Poisson arrival rates is studied.

Water, sanitation, and hygiene implications of large-scale recycling of treated municipal wastewater in semi-arid regions.

Access to water, sanitation, and hygiene (WaSH) is crucial for national development, as it improves human health and fulfills a fundamental need. This study examines the impact of a large-scale groundwater (GW) recharge scheme using secondary treated wastewater (STW) on WaSH characteristics and identifies the major determinants of improved WaSH charecteristics in drought-hit regions of Kolar district, southern India. The study quantifies improved WaSH practices by comparing WaSH characteristics between impacted areas (influenced by STW) and non-impacted areas (not influenced by STW) of Kolar, using household survey data. Pearson's chi-square and student's t-test are used to verify differences between WaSH characteristics. Furthermore, a composite WaSH score is formulated, and a hierarchical stepwise multiple linear regression model is constructed to identify major determinants of improved WaSH scores. The results show that impacted areas have better WaSH characteristics, including daily water supply by gram panchayat, enhanced toilet uses among all family members, bathing patterns, cloth washing practices, toilet cleaning patterns, and water consumption per capita per day. The maximum and minimum WaSH scores of impacted areas were 17.50 and 6.50, respectively, while those of non-impacted areas were 14 and 4.5. This study finds that improved water availability, quality, and security due to daily water supply at the household level are the major determinants of improved WaSH practices. These results can inform policymakers in designing sanitation and hygiene improvement policies that integrate water recycling projects in drought-hit areas.

Socio-economic impact assessment of large-scale recycling of treated municipal wastewater for indirect groundwater recharge.

Reusing treated wastewater is an emerging solution to address freshwater scarcity, and surface water contamination faced worldwide. A unique large-scale wastewater recycling project was implemented to replenish groundwater by filling secondary treated wastewater (STW) into existing irrigation tanks in severely drought-hit areas of the Kolar districts of Southern India. This study quantifies the socio-economic impacts of this large-scale indirect groundwater recharge scheme. The changes in areas receiving STW i.e., impacted areas and those areas which did not receive STW i.e., non-impacted areas was studied. Also, pre and post recycling changes were quantified in the Kolar district. The results show that surface water quality meets India's most stringent treated wastewater discharge standards prescribed by the Hon'ble National Green Tribunal. Due to these recycling efforts, significant improvements in groundwater level and quality were found. It was observed that there was a noticeable difference in agricultural cropping areas, seasons, patterns, and production between impacted and non-impacted areas. Post-recycling, farmers tended to cultivate cash and water-intensive crops over less water-intensive crops. During the post-recycling period, livestock and milk production also increased, and in impacted areas, it was significantly higher. Post-recycling, fish production increased and land prices per hectare increased by 118 % in impacted areas. The farmer's net income under flowers and vegetable farming increased by 202 % and 150 % respectively in impacted areas compared to non-impacted areas. Furthermore, this project contributes to a circular economy transition in the water sector, which has economic, environmental, social, and cultural benefits. A key recommendation from the outcomes of the study is to draft and implement a policy that encourages the reuse of recycled water for groundwater recharge which in turn will improve the agro-economic system and food security.

Investigating the effects of irrigation with indirectly recharged groundwater using recycled water on soil and crops in semi-arid areas.

The utilization of direct wastewater for irrigation poses many environmental problems such as soil quality deterioration due to the accumulation of salts, heavy metals, micro-pollutants, and health risks due to undesirable microorganisms. This hampers its agricultural reuse in arid and semi-arid regions. To address these concerns, the present study introduces a recent approach that involves using indirectly recharged groundwater (GW) with secondary treated municipal wastewater (STW) for irrigation through a Soil Aquifer Treatment-based system (SAT). This method aims to mitigate freshwater scarcity in semi-arid regions. The study assessed GW levels, physicochemical properties, and microbial diversity of GW, and soil in both impacted (receiving recycled water) and non-impacted (not receiving recycled water) areas, before recycling (2015-2018) and after recycling (2019-2022) period of the project. The results indicated a significant increase of 68-70% in GW levels of the studied boreholes in the impacted areas. Additionally, the quality of indirectly recharged GW in the impacted areas improved notably in terms of electrical conductivity (EC), hardness, total dissolved solids (TDS), sodium adsorption ratio (SAR), along with certain cations and anions (hard water to soft water). No significant difference was observed in soil properties and microbial diversity of the impacted areas, except for EC and SAR, which were reduced by 50% and 39%, respectively, after the project commenced. The study also monitored specific microbial species, including total coliforms, Escherichia coli (as indicator organisms), Shigella, and Klebsiella in some of the harvested crops (beetroot, tomato, and spinach). However, none of the analysed crops exhibited the presence of the studied microorganisms. Overall, the study concludes that indirectly recharged GW using STW is a better sustainable and safe irrigation alternative compared to direct wastewater use or extracted hard GW from deep aquifers.

Assessing groundwater recharge rates, water quality changes, and agricultural impacts of large-scale water recycling.

The over-exploitation and insufficient replenishment of groundwater (GW) have resulted in a pressing need to conserve freshwater and reuse of treated wastewater. To address this issue, the Government of Karnataka launched a large-scale recycling (440 million liters/day) scheme to indirectly recharge GW using secondary treated municipal wastewater (STW) in drought-prone areas of Kolar district in southern India. This recycling employs soil aquifer treatment (SAT) technology, which involves filling surface run-off tanks with STW that intentionally infiltrate and recharge aquifers. This study quantifies the impact of STW recycling on GW recharge rates, levels, and quality in the crystalline aquifers of peninsular India. The study area is characterized by hard rock aquifers with fractured gneiss, granites, schists, and highly fractured weathered rocks. The agricultural impacts of the improved GW table are also quantified by comparing areas receiving STW to those not receiving it, and changes before and after STW recycling were measured. The AMBHAS_1D model was used to estimate the recharge rates and showed a tenfold increase in daily recharge rates, resulting in a significant increase in the GW levels. The results indicate that the surface water in the rejuvenated tanks meets the country's stringent water discharge standards for STW. The GW levels of the studied boreholes increased by 58-73 %, and the GW quality improved significantly, turning hard water into soft water. Land use land cover studies confirmed an increase in the number of water bodies, trees, and cultivated land. The availability of GW significantly improved agricultural productivity (11-42 %), milk productivity (33 %), and fish productivity (341 %). The study's outcomes are expected to serve as a role model for the rest of Indian metro cities and demonstrate the potential of reusing STW to achieve a circular economy and a water-resilient system.

Sleep Disturbances among Caregivers of Home-Isolated and Hospitalized COVID-19 Patients: A Multi-National Cross-Sectional Study.

Background: Since the coronavirus (COVID-19) pandemic began, several studies were published on the possible prevention and treatment of the disease caused by severe acute respiratory syndrome coronavirus (SARSCoV-2), and its complications. However, one aspect that was overlooked is the impact on the mental health of the caregivers of COVID-19 patients. The current study endeavors to investigate sleep quality disturbances in the caregivers of COVID-19 patients in different countries. Material and Methods: This cross-sectional multi-center study was performed between August 1, 2021, and August 30, 2022, across 11 countries. A total of 2411 responses meeting the inclusion criteria (being a family member or caregiver involved in patient care) were collected. The sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI) 12. Total scores ranged from 0 to 21. A ≥5 indicated poor sleep quality with 89.6% sensitivity and 86.5% specificity. Results: A total of 2411 responses meeting the inclusion criteria showed that mean PSQI scores (P = 0.3604) were higher in caregivers of hospitalized patients than in patients isolated at home. Approximately 62.4% of caregivers reported sleep quality problems while caring for their patients. Conclusion: The results showed that the majority of caregivers of patients with COVID-19 reported disturbances in sleep quality and impaired sleep was more common among caregivers of hospitalized patients, perhaps because hospitalization is associated with a more severe course of the disease. There is a pressing need to take measures to improve the mental health of these caregivers. There should be treatment programs set up to reverse sleep disturbances in this population sufficiently.

Rescue of calcineurin Aα(-/-) mice reveals a novel role for the α isoform in the salivary gland.

Calcineurin is an important signal transduction mediator in T cells, neurons, the heart, and kidneys. Recent evidence points to unique actions of the two main isoforms of the catalytic subunit. Although the ß isoform is required for T-cell development, α is important in the brain and kidney. In addition, mice lacking α but not ß suffer from failure to thrive and early mortality. The purpose of this study was to identify the cause of postnatal death of calcineurin α null (CnAα(-/-)) mice and to determine the mechanism of α activity that contributes to the phenotype. CnAα(-/-) mice and wild-type littermate controls were fed a modified diet and then salivary gland function and histology were examined. In vitro studies were performed to identify the mechanism of α action. Data show that calcineurin is required for normal submandibular gland function and secretion of digestive enzymes. Loss of α does not impair nuclear factor of activated T-cell activity or expression but results in impaired protein trafficking downstream of the inositol trisphosphate receptor. These findings show a novel function of calcineurin in digestion and protein trafficking. Significantly, these data also provide a mechanism to rescue to adulthood a valuable animal model of calcineurin inhibitor-mediated neuronal and renal toxicities.