Determination of degradation/reaction rate for surface water quality of recycled water using Lake2K model for large-scale water recycling.

The depletion of groundwater resources in the water-stressed regions has led to the overuse of surface water reservoirs. Recharging groundwater by rejuvenating dried surface reservoirs using recycled water is a new sustainable solution. To ensure the prevention of groundwater contamination and associated health risks (as recycled water is used), it is crucial to assess the surface reservoir water quality. The study for the first time suggests the Lake2K model, a one-dimensional mechanistic mass-balance model, to simulate the changes in water quality in a series of man-made surface water reservoirs where recycled water flows under an indirect groundwater recharge scheme (soil aquifer treatment system). The model was developed, calibrated, and validated using field observations to estimate degradation/reaction rate constants for various water quality parameters. The observed average degradation/reaction rate constants for parameters including ammonia-N, nitrate-N, total nitrogen, total organic carbon, and organic phosphorous were 0.043 day-1, 0.04 day-1, 0.043 day-1, 0.055 day-1, and 0.056 day-1, respectively, which were found to be relatively high compared to existing literature, indicating a greater degradation of these parameters in warmer climates. The results showed that the water quality improved significantly as the water progressed through the reservoirs, aligning with field observations. Additionally, the simulated seasonal variations revealed that the maximum growth rate of phytoplankton occurred during July, August, and September for each reservoir, while the nutrient pool (nitrate-N and orthophosphates) experienced the greatest depletion during this growth period. These findings shed light on the dynamics of surface water quality in regions facing water scarcity and contribute to the development of sustainable groundwater management strategies.

The Administration of Levodopa in a Patient With Parkinson's Disease Using a Novel Maxillofacial Route: A First-in-Human Report.

Parkinson's disease is characterized by the loss of nigrostriatal dopaminergic neurons in the brain. Dopamine cannot be administered systemically because it does not cross the blood-brain barrier. Oral levodopa remains the gold standard to date. Currently, for patients who show a poor response to oral levodopa and for those who cannot take it orally, the alternate routes available are inhalation and continuous administration via intestinal and subcutaneous routes. In this report, a novel maxillofacial route was used for the first time in the world to administer levodopa to a Parkinson's patient. Furthermore, the efficacy of maxillofacial administration was compared with the oral route of administration.

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.

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.

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina.

Protein drugs are used for treating many diseases of the eye and the brain. The formidable blood neural barriers prevent the delivery of these drugs into the eye and the brain. Hence, there is a need for a protein drug delivery system to deliver large proteins across blood-neural barriers. Low half-life, poor penetration of epithelial barriers, low stability, and immunogenicity limit the use of non-invasive systemic routes for delivering proteins. In this pre-clinical study, the efficacy of a new maxillofacial route for administering protein drugs using a novel drug delivery system is compared with systemic administration through intra-peritoneal injection and ocular administration through topical eye drops and subconjunctival and intravitreal injections. Bevacizumab and retinoschisin proteins were administered using the maxillofacial technique along with systemic and ocular routes in wild-type male C57BL/6J mice. Liquid chromatography with tandem mass spectrometry and western blot was used to detect bevacizumab in tissue samples. Furthermore, immunohistochemistry was performed to detect the presence and localization of bevacizumab and retinoschisin in the retina and brain. The maxillofacial route of delivery could target the brain including regions involved in the visual pathway and optic nerve. The maxillofacial technique and intravitreal injection were effective in delivering the drugs into the retina. A new concept based on the glymphatic pathway, cerebrospinal fluid drug distribution, and the crossover of ipsilateral optic nerve fibers at optic chiasma is proposed to explain the presence of the drug in contralateral eye following maxillofacial administration and intravitreal injection.

Therapeutic compounds from medicinal plant endophytes: molecular and metabolic adaptations.

During the last few decades, endophytes have attracted increased attention due to their ability to produce a plethora of bioactive secondary metabolites. These compounds not only help the endophytes to outcompete other plant-associated microbes or pathogens through quorum sensing, but also enable them to surmount the plant immune system. However, only a very few studies have described the interlink between various biochemical and molecular factors of host-microbe interactions involved in the production of these pharmacological metabolites. The peculiar mechanisms by which endophytes modulate plant physiology and metabolism through elicitors, as well as how they use transitional compounds of primary and secondary metabolism as nutrients and precursors for the synthesis of new compounds or enhancing existing metabolites, are still less understood. This study thus attempts to address the aspects of synthesis of such metabolites used in therapeutics by the endophytes in the light of their ecological significance, adaptation, and intercommunity interactions. Our study explores how endophytes adapt to the specific host environment, especially in medicinal plants that produce metabolites with pharmacological potential and simultaneously modulate host gene expression for the biosynthesis of these metabolites. We also discuss the differential interactions of fungal and bacterial endophytes with their hosts.

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.

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.

Collateral implications of carbon and metal pollution on carbon dioxide emission at land-water interface of the Ganga River.

Atmospheric CO2 source and sink is among the most debated issues that have puzzled climate change geochemist for decades. Here, we tested whether heavy metal pollutants in river sediments favor preservation of organic matter through shielding microbial degradation. We measured CO2 emission and extracellular enzyme activities at land-water interface (LWI) of 7 sites along a 285 km main stem of the Ganga River and 60 locations up- and downstream of two contrasting point sources discharging urban (Assi drain; Asdr) and industrial (Ramnagar drain; Rmdr) wastewaters to the river. We found the lowest CO2 flux at Rmdr mouth characterized by the highest concentrations of Cu, Cr, Zn, Pb, Ni, and Cd. The fluxes were relatively higher at locations up- and downstream Rmdr. Substrate induced respiration (SIR), protease, FDAase, and ß-D-glucosidase all showed a similar trend, but phenol oxidase and alkaline phosphatase showed opposite trend at the main river stem and Asdr. Sites rich in terrestrially derived organic matter have high phenol oxidase activity with low CO2 emission. The CO2 emission in the main river stem showed curvilinear relationships with total heavy metals (∑THM; R2 = 0.68; p < 0.001) and TOC (R2 = 0.65; p < 0.001). The dynamic fit model of main stem data showed that the ∑THM above 337.4 µg g-1 were able to significantly decrease the activities of protease, FDAase, and ß-D-glucosidase. The study has implications for understanding C-cycling in human-impacted river sediments where metal pollution shields microbial degradation consequently carbon and nutrient release and merits attention towards river management decisions.

SARS-CoV-2: The Road Less Traveled-From the Respiratory Mucosa to the Brain.

Neurological manifestations have been reported in COVID-19; however, the route used by SARS-CoV-2 to enter the brain is still under debate. Recent studies have focused on the olfactory route. SARS-CoV-2 viral proteins were also detected in the glossopharyngeal and vagal nerves originating from the lower brainstem and in isolated cells of the brainstem. Our proof of concept in vivo real-time imaging study of mice using an indocyanine green dye indicated that the neurovascular component of the connective tissue of the respiratory mucosa can also provide an alternate route to the brain.

Cytokine Storm in COVID19: A Neural Hypothesis.

Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.

Pulmonary Edema in COVID19-A Neural Hypothesis.

In COVID-19, lung manifestations present as a slowly evolving pneumonia with insidious early onset interstitial pulmonary edema that undergoes acute exacerbation in the late stages and microvascular thrombosis. Currently, these manifestations are considered to be only consequences of pulmonary SARS-CoV-2 virus infection. We are proposing a new hypothesis that neurogenic insult may also play a major role in the pathogenesis of these manifestations. SARS-CoV-2 mediated inflammation of the nucleus tractus solitarius (NTS) may play a role in the acute exacerbation of pulmonary edema and microvascular clotting in COVID-19 patients.

Happy Hypoxemia in COVID-19-A Neural Hypothesis.

Many COVID-19 patients are presenting with atypical clinical features. Happy hypoxemia with almost normal breathing, anosmia in the absence of rhinitis or nasal obstruction, and ageusia are some of the reported atypical clinical findings. Based on the clinical manifestations of the disease, we are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of the nucleus tractus solitarius may be the reason for happy hypoxemia in COVID-19 patients.

Rhinomaxillary mucormycosis presenting as palatal ulcer: A case report with comprehensive pathophysiology.

Mucormycosis is an emerging fungal infection which has exceptionally high mortality rates in immunocompromised patients and remains a life-threatening infection in uncontrolled diabetics. The reported cases in literature may be less in number due to its frequent misdiagnosis. Imaging techniques in the early stages are usually nondiagnostic and cytological smears are not very reliable, thus, the gold standard for definitive diagnosis remains with the histopathological examination. A thorough understanding of the pathogenesis and host fungus interaction aids in the histopathological evaluation and clinical management. Despite of surgical and medical management, the overall mortality rate remains high in persistently immunocompromised individuals. We present a case report of a 58-year-old female patient with rhinomaxillary mucormycosis with a history of uncontrolled diabetes.

Effect of Biohythane Production from Distillery Spent Wash with Addition of Landfill Leachate and Sewage Wastewater.

Rapid development of the industrial and domestic sectors has led to the rise of several energy and environmental issues. In accordance with sustainable development and waste minimization issues, biohydrogen production along with biomethane production via two-stage fermentation process using microorganisms from renewable sources has received considerable attention. In the present study, biohythane production with simultaneous wastewater treatment was studied in a two-stage (Biohydrogen and Biomethane) fermentation process under anaerobic conditions. Optimization of high organic content (COD) distillery spent wash effluent (DSPW) with dilution using sewage wastewater was carried out. Addition of leachate as a nutrient source was also studied for effective biohythane production. The experimental results showed that the maximum biohythane production at optimized concentration (substrate concentration of 60 g/L with 30% of leachate as a nutrient source) was 67 mmol/L bio-H2 and with bio-CH4 production of 42 mmol/L. Graphical Abstract.

Heavy Metal Pollution in the Ganga River Enhances Carbon Storage Relative to Flux.

This study evaluated the relationships between metal pollution and carbon production at six sites along a 285 km length of the Ganga River. Metal contaminated sites did show a significant reduction in microbial biomass, substrate induced respiration, fluorescein diacetate hydrolytic assay (FDAase) and ß-D-glucosidase. Concordantly, despite a high concentration of total organic carbon at these sites, CO2 emission at the land-water interface remained low. We found a strong positive correlation between CO2 emission and TOC (r = 0.92; p < 0.001). However, this relationship weakens when the sum of total heavy metal (∑THM) exceed 400 µg g-1. Also, CO2 emission did show a positive correlation (r = 0.85; p < 0.001) with FDAase. The study shows that metal accumulation in riverbed sediment could potentially lead to better carbon sequestration on account of reduced microbial/enzyme activities. This carries significance for riverine carbon budget and modeling.

Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that regulates gene expression through poly(ADP)-ribosylation, resulting in the loosening of chromatin structure. PARP-1 enzymatic activity has been shown to be necessary for the expression of several genes required for memory formation and consolidation. Previously, we showed that nucleolar PARP-1 is significantly decreased in hippocampal pyramidal cells in Alzheimer's disease (AD). We proposed that the displacement of PARP-1 from the nucleolus results in downregulation of new rRNA expression and ribosome biogenesis, leading to cognitive impairment. To further investigate the relationship between nucleolar PARP-1 and memory impairment, we examined PARP-1 expression in the hippocampi of individuals with mild cognitive impairment (MCI) compared to control and AD cases. We used immunohistochemical techniques to examine the nucleolar distribution of PARP-1 in the Cornu Ammonis (CA region) of the hippocampus. PARP-1 positive cells were then scored for the presence or absence of PARP-1 in the nucleolus. We found a significant decrease of PARP-1 staining in the nucleolar compartment of hippocampal pyramidal cells in MCI compared with Control and AD. When the four CA (CA1-4) regions were considered separately, only the CA1 region showed significant differences in nucleolar PARP-1 with Control > AD > MCI cases. Categorization of nucleolar PARP-1 into "distinct" and "diffuse" groups suggest that most of the changes occur within the distinct group. In addition, measurements of the nucleolar diameter of nucleolar PARP-1 positive cells in CA2 and CA4 showed Control > MCI. Thus, MCI cases had a lower percentage of PARP-1 nucleolar positive cells in CA1 and smaller nucleolar diameters in CA2 and CA4, compared to Control. Our data suggest that disruption of nucleolar form and function is an early and important step in the progression of cognitive impairment.

Metal Contamination in Seven Tributaries of the Ganga River and Assessment of Human Health Risk from Fish Consumption.

We investigated the distribution of Zn, Cu, Ni, Pb, Cr, and Cd in water, sediment, and two dietary fish (an omnivore, Labeo rohita and a benthic carnivore, Clarias batrachus) and potential health risk to human consumers during summer low flow (2017-2018) at 28 sites across 7 tributary confluences of the Ganga River. We selected Devprayag, an upper reach site, as a reference for data comparison. We found significant spatial variations in the distribution of study metals and the concentrations remained higher in tributaries, confluences, and downstream cities. The pollution load index showed all sites except Devprayag in the polluted category. Ecological risk analysis indicated 1 site with very high risk, 7 with considerable risk, and 10 with moderate-risk category. The Zn did appear the most, and Cd the least accumulated metal in the fish. The metal accumulation was higher in C. batrachus. The levels of Cd, Cr, and Pb in the study fishes were higher compared with the international standards. The health risk analysis indicated safe levels for individual metals except for Cd where the target hazard quotient (THQ) did exceed 1 for C. batrachus at the Ramganga and Varuna confluences. When all metals were considered, the THQ was > 1 (> 2 for C. batrachus), indicating the full possibility of adverse health effects to human consumers. Our study highlights the importance of tributaries in creating a mosaic of metal-rich habitats in the Ganga River and food chain associated with a health risk to human consumers.

Pro- and anti-inflammatory effects of sulforaphane on placental cytokine production.

Placental inflammation increases the risk of adverse pregnancy outcomes and possibly neurodevelopmental disorders in the offspring. Previous research suggests it may be possible to modulate the placental immune response to bacteria to favor an anti-inflammatory phenotype with dietary factors. Sulforaphane (SFN) is a dietary supplement with known anti-inflammatory activities, however, its effects on placental cytokine production are unclear. Therefore, we evaluated the effects of SFN on biomarkers of inflammation and neurodevelopment under basal conditions and a setting of mild infection. Placental explant cultures were established and treated with up to 10 µM SFN in the presence and absence of 107 CFU/ml heat-killed E. coli. Concentrations of IL-1ß, TNF-α, IL-6, sgp130, HO-1 and BDNF in conditioned medium were quantified by immunoassay. SFN increased antioxidant HO-1 expression in the absence, but not the presence, of infection. SFN inhibited IL-1ß and IL-10, but tended to promote, TNF-α production by bacteria-stimulated cultures. IL-6 and BDNF were inhibited by SFN irrespective of co-treatment with E.coli. A negative regulator of IL-6 signaling, sgp130, was increased by SFN under basal conditions, but not in E. coli-stimulated cultures. These results suggest that SFN has mixed effects on the placenta inhibiting both pro-inflammatory (IL-1ß) and anti-inflammatory factors (IL-10) but promoting regulators of oxidative stress and inflammation (HO-1 and sgp130) in an infection-dependent manner.

Bio oil production from microalgae via hydrothermal liquefaction technology under subcritical water conditions.

The upsurge in the concerning issues like global warming, environmental pollution and depletion of fossil fuel resources led to the thrust on third generation biofuels. Algal research has gained a lot of importance in the recent years. Effective utilization of algal biomass in a single step is necessary as it can produce Bio-oil (BO), gases and in addition to a variety of valuable products, along with nutrient recovery. Hydrothermal liquefaction technology does not require the energy intensive drying steps and is an attractive approach for the conversion of algae to liquid fuels. This study investigates direct hydrothermal liquefaction (HTL) of microalgae (Algal biomass) to produce bio-oil using a high-pressure batch reactor under subcritical water conditions. Three different micro algae samples namely, Chlorella vulgaris, Botryococcus braunii and Scenedesmus quadricauda have been examined under hydrothermal liquefaction with different water concentrations (1:6, 1:7, 1:8, 1:9 & 1:10 ratio) at certain temperature range (200-320 °C), pressure (60 bars) and reaction time (30 min). Through liquefaction, the highest BO yield achieved with S. quadricauda was 18 wt% at 1:9 ratio. The chemical components of the obtained bio-oil were analyzed via gas chromatography and the results indicated that the algal BO was composed of furan, phenol, acid, and ester derivatives. Moreover, it was found that by increasing the temperatures, the BO yields increased. This was due to the polymerization reactions that converted the small biomass components into heavier molecules. FTIR spectra showed high percentage of Aliphatic, Phenolic, alcoholic, Carboxylic and Hydroxyl groups for solid residues.