The mitochondrial thiolase ACAT1 regulates monocyte/macrophage type I interferon via epigenetic control.

Lipid-derived acetyl-CoA is shown to be the major carbon source for histone acetylation. However, there is no direct evidence demonstrating lipid metabolic pathway contribututions to this process. Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes the final step of ß-oxidation, the aerobic process catabolizing fatty acids (FA) into acetyl-CoA. To investigate this in the context of immunometabolism, we generated macrophage cell line lacking ACAT1. 13C-carbon tracing combined with mass spectrometry confirmed incorporation of FA-derived carbons into histone H3 and this incorporation was reduced in ACAT1 KO macrophage cells. RNA-seq identified a subset of genes downregulated in ACAT1 KO cells including STAT1/2 and interferon stimulated genes (ISGs). CHIP analysis demonstrated reduced acetyl-H3 binding to STAT1 promoter/enhancer regions. Increasing histone acetylation rescued STAT1/2 expression in ACAT1 KO cells. Concomitantly, ligand triggered IFNß release was blunted in ACAT1 KO cells and rescued by reconstitution of ACAT1. Furthermore, ACAT1 promotes FA-mediated histone acetylation in an acetylcarnitine shuttle-dependent manner. In patients with obesity, levels of ACAT1 and histone acetylation are abnormally elevated. Thus, our study identified a novel link between ACAT1 mediated FA metabolism and epigenetic modification on STAT1/2 that uncovers a regulatory role of lipid metabolism in innate immune signaling and opens novel avenues for interventions in human diseases such as obesity.

PD-1 negatively tunes macrophage immune activation by turning off JNK and STAT1 signaling: Exploited by Leishmania for its intra-macrophage survival.

The anti-inflammatory role of the programmed death-1 receptor (PD-1) is well appreciated. However, the mechanism of how PD-1 signaling inhibits the pro-inflammatory cytokine responses in macrophages, which is further exploited by Leishmania to foster their intracellular survival, was unknown. We found that among three major MAP kinases regulating immune activation, PD-1 signaling decreased only JNK phosphorylation without perturbing p38 and ERK. Inflammatory transcription factor STAT1 was also inhibited by PD-1. Association studies documented that SHP, the downstream phosphatase of PD-1, is directly responsible for the decreased phosphorylation of JNK and STAT1. JNK and STAT1 deactivation led to Elk-1/c-Fos inhibition, which significantly decreased IL-12 and TNF-α levels. Further investigation revealed c-Fos deactivation ultimately rendered transcription factor AP1 inactive and facilitating parasite-favorable anti-inflammatory environment.

Impacts of the COVID-19 pandemic on landfilling and recycling in the city of Fargo, North Dakota, USA.

The COVID-19 pandemic impacted different aspects of human lifestyle, including waste generation and management. The landfilled and recycled waste volume from the City of Fargo's annual solid waste report between 2019 and 2021 was critically analyzed to understand these impacts. The analysis showed a 4.5% increase in the residential waste volume in 2020 compared to 2019 and 2021, suggesting a pandemic-induced lockdown effect. The monthly residential waste volume was approximately 5-15% greater during the mandatory quarantine period (April - November 2020) than in 2019 and 2021. Commercial waste volume decreased by 12% during 2020 and then sharply increased in 2021 as commercial facilities reopened. The total recycling volume increased slightly by 2.5% in 2020 compared to 2019 and 2021. Cardboard recycling showed a 5.8% increase in 2020 from 2019 and a 13% increase in 2021 compared to 2020. This was presumably caused by the reliance on online shopping during the pandemic and becoming habituated to online shopping. The COVID-19 pandemic did not significantly impact other classes of recycled waste volumes. In summary, COVID-19 affected landfilling and recycling in different capacities in the City of Fargo. The data will contribute to the global understanding of the impact of COVID-19 on solid waste management practices.Implications: The COVID-19 pandemic impacted waste generation and management. In Fargo, USA, the monthly residential waste volume increased by up to 15% during the mandatory quarantine period in 2020 compared to the same period in 2019 and 2021. Conversely, the monthly commercial waste volume decreased during the mandatory quarantine period in 2020. The commercial waste volume increased in 2021 as commercial activities became normal. The cardboard recycling increased significantly because people became used to online shopping during the lockdown, and the practice continues. The findings will contribute to the global understanding of the impact of COVID-19 on solid waste management practices.

Urinary Neutrophil Gelatinase Associated Lipocalin: A Novel Biomarker Determining Steroid Responsiveness in Nephrotic Syndrome.

BACKGROUND: Urinary Neutrophil Gelatinase Associated Lipocalin (uNGAL) has been demonstrated to be a powerful marker of progression in chronic kidney disease. The present study was done to find out the ability of uNGAL as a biomarker to differentiate steroid-sensitive nephrotic syndrome (SSNS), steroid-dependent nephrotic syndrome (SDNS), and steroid-resistant nephrotic syndrome (SRNS) from each other. METHOD: The cross-sectional study included 45 patients with Idiopathic Nephrotic Syndrome (INS) (15 each of SSNS, SDNS, and SRNS). uNGAL was measured by ELISA. Demographic profile of patients with INS, lab parameters including Serum albumin, cholesterol, urinary albumin, creatinine, etc., were estimated using standard laboratory methods. Various statistical methods were used to assay the usefulness of NGAL as a diagnostic marker. RESULTS: Among the three groups, the median value of uNGAL was 8.68 ng/ml in SSNS, higher in SDNS (32.8 ng/ml), and highest in the SRNS group (50 ng/ml). The receiver operating curve (ROC) was generated for uNGAL to differentiate between SDNS and SSNS. Cut-off 13.26 ng/ml had a sensitivity of 86.7% and specificity of 97.4%, PPV 92.9%, and NPV 87.5 % with an area under the curve (AUC) of 0.958. Another ROC was generated for uNGAL to differentiate between SRNS and SDNS, and cut-off 40.02 ng/ml had a sensitivity of 80% and specificity of 86.7% with an AUC of 0.907. A similar result was observed when ROC was generated to differentiate SRNS from SSNS and SDNS combined. CONCLUSION: uNGAL can distinguish between SSNS, SDNS, and SRNS.

Improvement of Hand Hygiene Compliance Using the Plan-Do-Study-Act Method: Quality Improvement Project From a Tertiary Care Institute in Bihar, India.

Background Hospital-acquired infections (HAIs) are the most severe complications of intensive care stay, especially in pediatric patients. Proper hand hygiene (HH) is the cheapest, simplest, but often neglected method to prevent HAIs. The World Health Organization (WHO) has formulated and promoted a standardized recommendation for HH. Both the WHO and the Centers for Disease Control and Prevention (CDC) recommend the use of soap and water for handwashing whenever there is visible dirt on the hands. In all other situations, an alcohol-based hand rub is an effective alternative. The quality improvement (QI) methodology has been widely followed in many countries to improve basic and advanced healthcare systems. The QI strategy follows the plan-do-study-act (PDSA) method. Methodology This quasi-experimental (pre- and post-intervention), prospective, QI study was conducted at the neonatal intensive care unit and pediatric intensive care unit of the pediatrics department in a tertiary care hospital in Bihar, India. A QI team was formed. The study was divided into four phases. WHO charts for assessing HH compliance were used for observation and data collection. The EQUATOR Checklist (Squire Checklist) was used to accurately report the QI work. Epi Info™ (version 7.2.5) was used for statistical analysis. The chi-square test was used to measure the statistical difference between pre- and post-intervention HH compliance (proportions). Results In the pre-intervention phase, a total of 106 HH opportunities were observed. The HH compliance at this stage was 40.6%. The QI team conducted several meetings, and a root cause analysis was performed with the help of the Fishbone diagram. It was decided to target three probable causes, namely, (a) less awareness, (b) inconvenient locations of hand rub dispensers, and (c) forgetfulness. The QI team decided to run three PDSA cycles. In the last phase, 212 HH opportunities were observed with a compliance percentage of 69.8%. There was a significant improvement when data of pre- and post-intervention HH compliance were compared in all categories of healthcare workers (HCWs), except doctors, where the improvement was not statistically significant. When the cumulative data of all subtypes of HCWs were analyzed, there was a significant improvement (p < 0.0001). Run charts and box plots were used for the easy depiction of the results. Conclusions Adopting proper HH methods remains the most effective way of preventing nosocomial infections, especially in intensive care units. We used the WHO model of HH in our study. The pre-intervention HH compliance was 40.6%. QI methodology using root cause analysis and implementation of three PDSA cycles were used to increase the HH compliance percentage. Post-intervention HH compliance increased to 69.8% and the effect was sustained. The study highlights the usefulness of the QI methodology in bringing small but important changes in clinical practice for better patient care.

Bilateral Neck of Femur Fracture in a Child With Underlying Vitamin D Deficiency: A Case Report on Management and 10-Year Follow-Up.

Bilateral femoral neck fracture is a rare entity in the pediatric age group. These types of fractures occur mostly due to high-velocity trauma. We report the surgical outcome with approximately 10 years of follow-up in a 10-year-old child presenting with bilateral femoral neck fracture after trivial trauma and underlying nutritional vitamin D deficiency. A 10-year-old female child with bilateral neglected fracture neck of femur was managed with a primary valgus osteotomy done on the left side and closed reduction and screw fixation with fibular grafting done on the right side. Later on, as the right side fracture progressed to non-union, it was converted to valgus osteotomy fixed with an external fixator. The patient had a good functional outcome at 10 years of follow-up with no difficulty in her day-to-day activities. Pathological bilateral fracture neck of femur is rare in children and it is often mismanaged due to a delayed diagnosis. It can have potentially dangerous complications with a grave outcome affecting the rest of the life of the child. Hence it is important to know about such rare presentations so that they can be adequately addressed early on, thereby minimizing the risk of complications like non-union and avascular necrosis.

Non Cystic Fibrosis Bronchiectasis.

Bronchiectasis is a pathological abnormality of the airways in which there is permanent dilatation and thickening of the airways. Precise incidence/prevalence in India is not known. Recent data suggests that about 1 % young children admitted in a hospital with pneumonia may develop bronchiectasis. Due to significant burden of pneumonia in young children in developing countries including India, it may be a significant problem that is possibly under recognized. Causes of bronchiectasis depend on the burden of respiratory infections and availability of the investigations for identification of the underlying cause. Post infectious causes are common in countries where infections are more common; however, since these countries are usually resource constrained and therefore, are not able to appropriately diagnose the other causes, leading to more than real overrepresentation of infections as a cause. In countries with less of infectious illnesses and good diagnostic facilities, malformations of airways, immune deficiency disorders and primary ciliary dyskinesia are common causes of bronchiectasis. High resolution CT scan of chest confirms the diagnosis. Treatment is supportive care and consists of maintenance of nutrition, airway clearance and antibiotics for exacerbations. Medical treatment is successful in the majority.

Improvement in the yield and quality of kalmegh (Andrographis paniculata Nees) under the sustainable production system.

Andrographis paniculata Nees is an annual erect herb with wide medicinal and pharmacological applications due to the presence of andrographolide and other active chemical constituents. The large-scale cultivation of the kalmegh is not in practice. The aim of this study was to establish sustainable production systems of A. paniculata cv CIM-Megha with the application of different bioinoculants and chemical fertilisers. A. paniculata herb and andrographolide yield in the dried leaves was found to be highest (218% and 61.3%, respectively) in treatment T3 (NPK+Bacillus sp.) compared with T1 (control). The soil organic carbon, soil microbial respiration, soil enzymes activity and available nutrients improved significantly with combined application of bioinoculants and chemical fertilisers.

An ecologically-sustainable surface water withdrawal framework for cropland irrigation: a case study in Alabama.

Agricultural production in the state of Alabama, USA, is mostly rain-fed, because of which it is vulnerable to drought during growing season. Since Alabama receives a significant portion of its annual precipitation during winter months, the goal of this study was to evaluate the feasibility of water withdrawal from streams during winter months for irrigation in the growing season. The Soil and Water Assessment Tool (SWAT) was used to estimate the quantity of water that can be sustainably withdrawn from streams during winter high flow periods. The model was successfully calibrated and validated for surface runoff, base flow, and total stream flow. The stream flows generated by the model at several locations within the watershed were then used to examine how much water can be sustainably withdrawn from streams of various orders (first, second and third). Although there was a considerable year-to-year variability in the amount of water that can be withdrawn, a 16-year average showed that first, second, and third order streams can irrigate about 11.6, 10.3, and 10.6% of their drainage areas, respectively. The percentage of drainage area that can be irrigated was not a function of stream order.

Comparative study of skin grafting with and without surgical removal of granulation tissue in chronic burn wounds.

A prospective comparative study of skin grafting of chronic wounds with and without surgical removal of granulation tissue was done on 51 patients with an objective of finding a better method of skin grafting objectively in the chronic burns wounds. Comparative study was done on those patients who had wounds on both the sides of their body. Wounds present on the right side of the body labeled as Group A were skin grafted after removal of granulation tissue and wounds present on left side of the body labeled as Group B were skin grafted without removal of granulation tissue. There was no significant difference in the comparative bacteriology, graft uptake and cosmetic appearance of the grafts. We found no effect of bacteriology and chronicity of the wounds on the uptake of grafts in the two groups. Serum albumin levels <4 g% was found to be associated with statistically significant decreased graft uptake only in Group A wounds. It was further observed that Group A wounds were associated with more blood loss, less secure haemostasis, prolonged surgical duration and thus more cost of surgery as compared to Group B wounds.