Engineered Wnt7a ligands rescue blood-brain barrier and cognitive deficits in a COVID-19 mouse model.

Respiratory infection with SARS-CoV-2 causes systemic vascular inflammation and cognitive impairment. We sought to identify the underlying mechanisms mediating cerebrovascular dysfunction and inflammation following mild respiratory SARS-CoV-2 infection. To this end, we performed unbiased transcriptional analysis to identify brain endothelial cell signalling pathways dysregulated by mouse adapted SARS-CoV-2 MA10 in aged immunocompetent C57Bl/6 mice in vivo. This analysis revealed significant suppression of Wnt/ß-catenin signalling, a critical regulator of blood-brain barrier (BBB) integrity. We therefore hypothesized that enhancing cerebrovascular Wnt/ß-catenin activity would offer protection against BBB permeability, neuroinflammation, and neurological signs in acute infection. Indeed, we found that delivery of cerebrovascular-targeted, engineered Wnt7a ligands protected BBB integrity, reduced T-cell infiltration of the brain, and reduced microglial activation in SARS-CoV-2 infection. Importantly, this strategy also mitigated SARS-CoV-2 induced deficits in the novel object recognition assay for learning and memory and the pole descent task for bradykinesia. These observations suggest that enhancement of Wnt/ß-catenin signalling or its downstream effectors could be potential interventional strategies for restoring cognitive health following viral infections.

Assessment of Biomedical Waste Generation in Dialysis Units: A Prospective Observational Study-Is it Time for "Green Dialysis"?

Introduction: Chronic kidney disease and as a consequence end-stage kidney disease (EKSD) is increasing globally. More and more people across the world are requiring hemodialysis (HD). The HD procedure produces a large quantity of biomedical waste. In addition, HD consumes a large quantity of water. In this study, we estimated the waste generated from our government-funded HD unit. Materials and methods: It is a prospective study that was carried out in the dialysis unit in the nephrology department over a period of 1 year. The daily dialysis waste generated by the unit was measured using a spring balance. The proportion of plastic and nonplastic waste was determined. The quantity of biomedical waste generated per person in 1 year was calculated. Water input to the dialysis unit was noted. Water consumption per dialysis was calculated. Liquid chemical waste consumed was determined. Electricity consumed by the unit was measured by the electricity meter. The cost of waste disposal was calculated. The cost of electricity consumption and water consumption was also calculated. Results: The approximate weight of waste disposables generated in one dialysis was 0.75 kg. Approximately each person generates 1.29 kg of waste per dialysis. Each dialysis required 125 L of reverse osmosis (RO) water and to generate 125 L of RO water 250 L of raw water was used. This happens as 125 L of water are rejected during the generation of 125 L of RO water. Thus, the net water consumption for each dialysis was 250 L. Chemical waste generated per dialysis includes 90 mL citric acid per dialysis and 130 mL bleach. Each dialysis consumes 3 kWh (three units) of electricity. The cost of electricity for each dialysis was 25.5 INR and the cost of water was 25 INR per dialysis. The cost of waste disposal for each dialysis bed was 6 INR. Discussion: Each dialysis patient produced 1.29 kg of waste per dialysis which was like other studies. Unlike other studies, the waste was not being reprocessed or recycled. Conclusion: Hemodialysis produces substantial biomedical waste. Proper waste disposal techniques and policies to promote reduction, reuse, and recycling will go a long way toward promoting green dialysis and reducing environmental as well as economic burdens. How to cite this article: Sahay M, Sahay RK, Seshadri B, et al. Assessment of Biomedical Waste Generation in Dialysis Units: A Prospective Observational Study-Is it Time for "Green Dialysis"? J Assoc Physicians India 2023;71(10):49-52.

Chemogenetic control of GABAergic activity within the interpeduncular nucleus reveals dissociable behavioral components of the nicotine withdrawal phenotype.

Chronic exposure to nicotine results in the development of a dependent state such that a withdrawal syndrome is elicited upon cessation of nicotine. The habenulo-interpeduncular (Hb-IPN) circuit contains a high concentration of nAChRs and has been identified as a main circuit involved in nicotine withdrawal. Here we investigated the contribution of two distinct subpopulations of IPN GABAergic neurons to nicotine withdrawal behaviors. Using a chemogenetic approach to specifically target Amigo1-expressing or Epyc-expressing neurons within the IPN, we found that activity of the Amigo1 and not the Epyc subpopulation of GABAergic neurons is critical for anxiety-like behaviors both in naïve mice and in those undergoing nicotine withdrawal. Moreover, data revealed that stimulation of Amigo1 neurons in nicotine-naïve mice elicits opposite effects on affective and somatic signs of withdrawal. Taken together, these results suggest that somatic and affective behaviors constitute dissociable components of the nicotine withdrawal phenotype and are likely supported by distinct subpopulations of neurons within the IPN.

Synthesis of new benzimidazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates with efficient DNA-binding affinity and potent cytotoxicity.

The synthesis of new benzimidazole linked pyrrolobenzodiazepine conjugates is described. Some of these conjugates show significant DNA-binding affinity and, a representative compound 4c shows promising in vitro cytotoxicity against a number of human cancer cell lines.

Phosphonate-linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates: synthesis, DNA-binding affinity and cytotoxicity.

Pyrrolobenzodiazepine-diethylphosphonate conjugates have been designed and synthesized that link through two different types of spacers that are simple alkane chain and also a piperazine moiety side-armed with the alkane chains. These pyrrolobenzodiazepine conjugates have exhibited remarkable DNA-binding affinity and improved solubility in water, a representative compound 7d showing promising in vitro cytotoxicity.

Comparative analysis of speciation and bioaccessibility of arsenic in rice grains and complementary medicines.

In many countries, rice grains and complementary medicines are important sources of arsenic (As) consumption. The objective of this study was to compare the speciation and bioaccessibility of As in selected rice grains and complementary medicines. A number of rice grain samples, and a range of herbal and ayurvedic medicines were analyzed for total As, speciation of As using sequential fractionation and extended x-ray absorption fine structure (EXAFS) techniques, and bioaccessibility of As using an in vitro extraction test. The daily intake of As through the uptake of these As sources was compared with the safety guidelines for As. The results demonstrated higher levels of As in ayurvedic medicines compared to herbal medicines and rice grains. The sequential fractionation showed the dominance of organic-bound As species in rice grains and herbal medicines, however, inorganic-bound As species dominated the ayurvedic medicines. This implies that As is derived from plant uptake in herbal medicines and rice grains, and from inorganic mineral input in ayurvedic medicines. Arsenic bioaccessibility was higher in ayurvedic than herbal medicines and rice grains, suggesting that inorganic As added as a mineral therapeutic input is more bioaccessible than organic As species derived from plant uptake. This study also showed a positive relationship between soluble As fractions and bioaccessibility indicating that solubility is an important factor controlling bioaccessibility. The daily intake values for As as estimated by total As content are likely to exceed the safe threshold level in rice grains that are enriched with As.

Potential value of phosphate compounds in enhancing immobilization and reducing bioavailability of mixed heavy metal contaminants in shooting range soil.

Shooting range soils contain mixed heavy metal contaminants including lead (Pb), cadmium (Cd), and zinc (Zn). Phosphate (P) compounds have been used to immobilize these metals, particularly Pb, thereby reducing their bioavailability. However, research on immobilization of Pb's co-contaminants showed the relative importance of soluble and insoluble P compounds, which is critical in evaluating the overall success of in situ stabilization practice in the sustainable remediation of mixed heavy metal contaminated soils. Soluble synthetic P fertilizer (diammonium phosphate; DAP) and reactive (Sechura; SPR) and unreactive (Christmas Island; CPR) natural phosphate rocks (PR) were tested for Cd, Pb and Zn immobilization and later their mobility and bioavailability in a shooting range soil. The addition of P compounds resulted in the immobilization of Cd, Pb and Zn by 1.56-76.2%, 3.21-83.56%, and 2.31-74.6%, respectively. The reactive SPR significantly reduced Cd, Pb and Zn leaching while soluble DAP increased their leachate concentrations. The SPR reduced the bioaccumulation of Cd, Pb and Zn in earthworms by 7.13-23.4% and 14.3-54.6% in comparison with earthworms in the DAP and control treatment, respectively. Bioaccessible Cd, Pb and Zn concentrations as determined using a simplified bioaccessibility extraction test showed higher long-term stability of P-immobilized Pb and Zn than Cd. The differential effect of P-induced immobilization between P compounds and metals is due to the variation in the solubility characteristics of P compounds and nature of metal phosphate compounds formed. Therefore, Pb and Zn immobilization by P compounds is an effective long-term remediation strategy for mixed heavy metal contaminated soils.

Speciation and bioavailability of lead in complementary medicines.

Complementary medicines have associated risks which include toxic heavy metal(loid) and pesticide contamination. The objective of this study was to examine the speciation and bioavailability of lead (Pb) in selected complementary medicines. Six herbal and six ayurvedic medicines were analysed for: (i) total heavy metal(loid) contents including arsenic (As), cadmium (Cd), Pb and mercury (Hg); (ii) speciation of Pb using sequential fractionation and extended x-ray absorption fine structure (EXAFS) techniques; and (iii) bioavailability of Pb using a physiologically-based in vitro extraction test (PBET). The daily intake of Pb through the uptake of these medicines was compared with the safety guidelines for Pb. The results indicated that generally ayurvedic medicines contained higher levels of heavy metal(loid)s than herbal medicines with the amount of Pb much higher than the other metal(loid)s. Sequential fractionation indicated that while organic-bound Pb species dominated the herbal medicines, inorganic-bound Pb species dominated the ayurvedic medicines. EXAFS data indicated the presence of various Pb species in ayurvedic medicines. This implies that Pb is derived from plant uptake and inorganic mineral input in herbal and ayurvedic medicines, respectively. Bioavailability of Pb was higher in ayurvedic than herbal medicines, indicating that Pb added as a mineral therapeutic input is more bioavailable than that derived from plant uptake. There was a positive relationship between soluble Pb fraction and bioavailability indicating that solubility is an important factor controlling bioavailability. The daily intake values for Pb as estimated by total and bioavailable metal(loid) contents are likely to exceed the safe threshold level in certain ayurvedic medicines. This research demonstrated that Pb toxicity is likely to result from the regular intake of these medicines which requires further investigation.

Landfills as a biorefinery to produce biomass and capture biogas.

While landfilling provides a simple and economic means of waste disposal, it causes environmental impacts including leachate generation and greenhouse gas (GHG) emissions. With the introduction of gas recovery systems, landfills provide a potential source of methane (CH4) as a fuel source. Increasingly revegetation is practiced on traditionally managed landfill sites to mitigate environmental degradation, which also provides a source of biomass for energy production. Combustion of landfill gas for energy production contributes to GHG emission reduction mainly by preventing the release of CH4 into the atmosphere. Biomass from landfill sites can be converted to bioenergy through various processes including pyrolysis, liquefaction and gasification. This review provides a comprehensive overview on the role of landfills as a biorefinery site by focusing on the potential volumes of CH4 and biomass produced from landfills, the various methods of biomass energy conversion, and the opportunities and limitations of energy capture from landfills.

A comparison of the gum pads of Afro-Caribbean and Caucasian British subjects at birth.

The gum pads of 34 subjects of Afro-Caribbean origin are compared with those of an equal number of Caucasian British subjects, matched for sex and birth weight. Some differences of size, form, and relationship are described, and are considered large enough to merit further investigation on a larger sample.