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Abstract Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX3CR1+ and CSF1R+ source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally.

Soil is one of the largest carbon reservoirs sequestering more carbon than vegetation and atmosphere. Due to the enormous potential of soil to sequester atmospheric CO2, it becomes a feasible option to alleviate the current and impending effects of changing climate. Soil is a vulnerable resource globally because it is highly susceptible to global environmental problems such as land degradation, biodiversity loss, and climate change. Therefore, protecting and monitoring worldwide soil carbon pools is a complicated challenge. Soil organic carbon (SOC) is a vital factor affecting soil health since it is a major component of SOM and contributes to food production. This review attempts to summarize the information on carbon sequestration, storage, and carbon pools in the major terrestrial ecosystems and underpin soil carbon responses under climate change and mitigation strategies. Topography, pedogenic, and climatic factors mainly affect carbon input and stabilization. Humid conditions and low temperature favor high soil organic carbon content. Whereas warmer and drier regions have low SOC stocks. Tropical peatlands and mangrove ecosystems have the highest SOC stock. The soil of drylands stores 95% of the global Soil Inorganic Carbon (SIC) stock. Grasslands include rangelands, shrublands, pasturelands, and croplands. They hold about 1/5th of the world’s total soil carbon stocks.

Abstract Nanophthalmos is characterised by shorter posterior and anterior segments of the eye, with a predisposition towards high hyperopia and primary angle-closure glaucoma. Variants in TMEM98 have been associated with autosomal dominant nanophthalmos in multiple kindreds, but definitive evidence for causation has been limited. Here we used CRISPR/Cas9 mutagenesis to recreate the human nanophthalmos-associated TMEM98 p.(Ala193Pro) variant in mice. The p.(Ala193Pro) variant was associated with ocular phenotypes in both mice and humans, with dominant inheritance in humans and recessive inheritance in mice. Unlike their human counterparts, p.(Ala193Pro) homozygous mutant mice had normal axial length, normal intraocular pressure, and structurally normal scleral collagen. However, in both homozygous mice and heterozygous humans, the p.(Ala193Pro) variant was associated with discrete white spots throughout the retinal fundus, with corresponding retinal folds on histology. This direct comparison of a TMEM98 variant in mouse and human suggests that certain nanophthalmos-associated phenotypes are not only a consequence of a smaller eye, but that TMEM98 may itself play a primary role in retinal and scleral structure and integrity.

Abstract There have been reports of deep vein thrombosis and supraventricular tachycardia following the Moderna vaccination. The timing of SVT and DVT just after vaccination in our case series could suggest possible temporal relationships to the vaccination. But further studies are needed to establish such evidence.

Abstract Rivers are the lifeline of every living being, be it humans or animals. Clean water is essential for everyone. However, increased urbanization and rapid industrialization have led to rising pollution level in rivers. COVID-19 on the contrary has changed the entire ecosystem. Limited industrial activities, reduced people movement during COVID times has led to improvement in environment, be it atmosphere or hydrosphere. Present work aims to study the impact of COVID-19 on water quality index of river Yamuna as it traverses from Himalayan segment to Upper segment. Five sites are chosen between a stretch of 60+ km, and samples are collected during monsoon and post-monsoon seasons. Physico-chemical parameters (pH, Turbidity, Sulphate, Phosphate, Fluoride, Chloride, Total Hardness, Calcium, Magnesium, Dissolved Oxygen, BOD, COD, Alkalinity), water quality index and Pearson correlation coefficient were calculated for all chosen sites. Since the study was initiated during COVID, initial results show the impact of reduced industrial and urban activities in improving the overall water quality.

Objective An ambulance is a medically equipped vehicle which is used in case of any medical emergency for the transport of patients to treatment facilities. The ambulances help in the transportation of thousands of patients per year, and such patients may carry infectious microorganisms which pose a major threat to the treatment of such patients. In this study, we analyzed the extent of bacterial contamination in our ambulance vehicles and measured the degree of antimicrobial resistance among isolated pathogens. Material and Method This study included five ambulances of our tertiary care hospital and different random sites were swabbed in each vehicle. These were selected based on their well-known high frequency of contact by emergency personnel and patients. Swabs were inserted into sterile test tubes containing normal saline and immediately transferred to our microbiology laboratory to identify bacterial contaminants utilizing standard microbiological procedures. Result A total of 198 swab samples were collected from all the five ambulances, out of which 170 (85.8%) swabs were sterile and 28 (14.2%) swabs yielded potentially pathogenic bacterial isolates. The highest contamination rate with pathogenic bacteria was detected in the oxygen flow meter knob (60%), suction machine tubing (60%), and stethoscope (40%). Staphylococcus aureus (32%) was the most frequently detected microorganism. Conclusion Our study showed low prevalence of bacterial contamination in ambulances because of good infection control policy of our hospital, however, some areas still need improvement and require proper standard operating procedures of disinfection policies of these emergency vehicles.

Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric cataract genes in 33 affected individuals with a family history (cases with previously known or published mutations were excluded) using the Ion Torrent Personal Genome Machine. Variants were prioritized for validation if they were predicted to alter the protein sequence and were absent or rare with minor allele frequency 60% of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.

Abstract Background Cataract is a major cause of severe visual impairment in childhood. The purpose of this study was to determine the genetic cause of syndromic congenital cataract in an Australian mother and son. Method Fifty-one genes associated with congenital cataract were sequenced in the proband using a custom Ampliseq library on the Ion Torrent Personal Genome Machine (PGM). Reads were aligned against the human genome (hg19) and variants were annotated. Variants were prioritised for validation by Sanger sequencing if they were novel, rare or previously reported to be associated with paediatric cataract and were predicted to be protein changing. Variants were assessed for segregation with the phenotype in the affected mother. Result A novel likely pathogenic variant was identified in the transactivation domain of the MAF gene (c.176C > G, p.(Pro59Arg)) in the proband and his affected mother., but was absent in 326 unrelated controls and absent from public variant databases. Conclusion The MAF variant is the likely cause of the congenital cataract, Asperger syndrome, seizures, hearing loss and facial characteristics in the proband, providinga diagnosis of Aymé-Gripp syndrome for the family.

Fuchs endothelial corneal dystrophy (FECD) is one of the most common reasons for corneal transplantation, and is known to cluster in families. Here, the authors discover new genetic loci associated with FECD with sex-specific effects and implications for disease mechanism.

Pseudomonas monteilii (P. monteilii) is a gram negative, rod shaped, nonsporing, motile, non-fermenting bacterium belonging to family Pseudomonadaceae. It is a known environmental contaminant, has been seen as an emerging opportunistic pathogen and is closely related to Pseudomonas putida. We isolated this organism from a young immunocompetent patient with meningoencephalitis, who despite of treatment had a fatal outcome.

Fuchs' endothelial corneal dystrophy (FECD) is a progressive, vision impairing disease. Common single nucleotide polymorphisms (SNPs) and a trinucleotide repeat polymorphism, thymine-guanine-cytosine (TGC), in the TCF4 gene have been associated with the risk of FECD in some populations. We previously reported association of SNPs in TCF4 with FECD risk in the Australian population. The aim of this study was to determine whether TGC repeat polymorphism in TCF4 is associated with FECD in the Australian population. In 189 unrelated Australian cases with advanced late-onset FECD and 183 matched controls, the TGC repeat polymorphism located in intron 3 of TCF4 was genotyped using a short tandem repeat (STR) assay. The repeat length was verified by direct sequencing in selected homozygous carriers. We found significant association between the expanded TGC repeat (≥ 40 repeats) in TCF4 and advanced FECD (P = 2.58 × 10-22; OR = 15.66 (95% CI: 7.79-31.49)). Genotypic analysis showed that 51% of cases (97) compared to 5% of controls (9) were heterozygous or homozygous for the expanded repeat allele. Furthermore, the repeat expansion showed stronger association than the most significantly associated SNP, rs613872, in TCF4, with the disease in the Australian cohort. This and haplotype analysis of both the polymorphisms suggest that considering both the polymorphisms together rather than either of the two alone would better predict susceptibility to FECD in the Australian population. This is the first study to report association of the TGC trinucleotide repeat expansion in TCF4 with advanced FECD in the Australian population.

PURPOSE:To identify biological processes associated with POAG and its subtypes, high-tension (HTG) and normal-tension glaucoma (NTG), by analyzing rare potentially damaging genetic variants. METHODS:A total of 122 and 65 unrelated HTG and NTG participants, respectively, with early onset advanced POAG, 103 non-glaucoma controls and 993 unscreened ethnicity-matched controls were included in this study. Study participants without myocilin disease-causing variants and non-glaucoma controls were subjected to whole exome sequencing on an Illumina HiSeq2000. Exomes of participants were sequenced on an Illumina HiSeq2000. Qualifying variants were rare in the general population (MAF < 0.001) and potentially functionally damaging (nonsense, frameshift, splice or predicted pathogenic using SIFT or Polyphen2 software). Genes showing enrichment of qualifying variants in cases were selected for pathway and network analysis using InnateDB. RESULTS:POAG cases showed enrichment of rare variants in camera-type eye development genes (p = 1.40×10-7, corrected p = 3.28×10-4). Implicated eye development genes were related to neuronal or retinal development. HTG cases were significantly enriched for key regulators in the unfolded protein response (UPR) (p = 7.72×10-5, corrected p = 0.013). The UPR is known to be involved in myocilin-related glaucoma; our results suggest the UPR has a role in non-myocilin causes of HTG. NTG cases showed enrichment in ion channel transport processes (p = 1.05×10-4, corrected p = 0.027) including calcium, chloride and phospholipid transporters involved in plasma membrane homeostasis. Network analysis also revealed enrichment of the MHC Class I antigen presentation pathway in HTG, and the EGFR1 and cell-cycle pathways in both HTG and NTG. CONCLUSION:This study suggests that mutations in eye development genes are enriched in POAG. HTG can result from aberrant responses to protein misfolding which may be amenable to molecular chaperone therapy. NTG is associated with impaired plasma membrane homeostasis increasing susceptibility to apoptosis.

Introduction: Helicobacter pylori (H.pylori) infection is very common worldwide. A reliable diagnosis is crucial for better treatment of the patients. However, there is no single diagnostic method that can meet the criteria in identification of H.pylori. Aim: To detect H.pylori from endoscopic biopsies in dyspeptic patients and to compare the sensitivity and specificity of different diagnostic methods for H. pylori infection. Materials and Methods: This observational and crosssectional study was conducted in the Department of Microbiology and Medicine, Himalayan Institute of Medical Sciences (HIMS), Swami Ram Nagar, Dehradun, over a period of 12 months. Biopsies of gastric antrum from 100 patients with dyspepsia were studied for the detection of H.pylori by various methods like bacterial culture, Rapid Urease Test (RUT) and Christensen‘s Tube Urease (CTU) test. Stool samples from all the patients were also screened for H.pylori stool antigen (HpSA) test. Bacterial culture was considered as gold standard in this study and other diagnostic tests were compared with the gold standard. Results: Out of 100 patients H.pylori was detected by bacterial culture, RUT, CTU and HpSA in 34%, 61%, 53% and 28% cases respectively. Sensitivity of RUT, CTU and HpSA were 100%, 91% and 73.5% respectively and specificity of RUT, CTU and HpSA were 59%, 66.7% and 95.3% respectively. Thus, RUT was the most sensitive (100%) and HpSA (95.3%) was the most specific test, when culture was being considered as gold standard. Conclusion: RUT is best considered as a screening test and not as the gold standard for H. pylori. The HpSA test is also rapid, simple and non-invasive test with acceptable results that can be used for monitoring.

Introduction: Acute undifferentiated febrile illness (AUFI) is a common clinical entity in most of the hospitals. The fever can be potentially fatal if the aetiology is not recognized and appropriately treated early. Aim: To describe the aetiology of fever among patients in a tertiary care hospital in Northern India. Materials and Methods: A one-year retro-prospective, observational study was conducted in adults (age>18years) presenting with undifferentiated febrile illness (of duration 5-14 days). Diagnosis was confirmed by suitable laboratory tests after exhaustive clinical examination. Results: A total of 2547 patients with AUFI were evaluated. Of these, 1663 (65.3%) were males and 884 (34.7%) were females. Dengue (37.54%); enteric fever (16.5%); scrub typhus (14.42%); bacterial sepsis (10.3%); malaria (6.8%); hepatitis A (1.9%); hepatitis E (1.4%); leptospirosis (0.14%); were the main infections while no specific diagnosis could be delineated in 11%. Mixed infections were noted in 48 (1.9%) patients. Conclusion: A good clinical acumen supported by the basic investigations can help diagnose the cause of fever with reasonable certainty.

Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.

It has recently been shown that there are highly significant associations for common single nucleotide polymorphisms (SNPs) near the CDKN2B-AS1 gene region at the 9p21 locus with primary open angle glaucoma (POAG), a leading cause of irreversible blindness. This gene region houses the CDKN2B/p15(INK4B) , CDKN2A/p16(INK4A) and p14ARF (rat equivalent, p19(ARF) ) tumour suppressor genes and is adjacent to the S-methyl-5'-thioadenosine phosphorylase (MTAP) gene. In order to understand the ocular function of these genes and, therefore, how they may be involved in the pathogenesis of POAG, we studied the distribution patterns of each of their products within human and rat ocular tissues. MTAP mRNA was detected in the rat retina and optic nerve and its protein product was localised to the corneal epithelium, trabecular meshwork and retinal glial cells in both human and rat eyes. There was a very low level of p16(INK4A) mRNA present within the rat retina and slightly more in the optic nerve, although no protein product could be detected in either rat or human eyes with any of the antibodies tested. P19(ARF) mRNA was likewise only present at very low levels in rat retina and slightly higher levels in the optic nerve. However, no unambiguous evidence was found to indicate expression of specific P19(ARF)/p14(ARF) proteins in either rat or human eyes, respectively. In contrast, p15(INK4B) mRNA was detected in much higher amounts in both retina and optic nerve compared with the other genes under analysis. Moreover, p15(INK4B) protein was clearly localised to the retinal inner nuclear and ganglion cell layers and the corneal epithelium and trabecular meshwork in rat and human eyes. The presented data provide the basis for future studies that can explore the roles that these gene products may play in the pathogenesis of glaucoma and other models of optic nerve damage.

Congenital cataract is the most common cause of treatable visual impairment in children worldwide. Mutations in many different genes lead to congenital cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have been found to cause congenital cataract in six different families. Although these findings have established EPHA2 as a causative gene, the total contribution of mutations in this gene to congenital cataract is unknown. In this study, for the first time, a population-based approach was used to investigate the frequency of disease causing mutations in the EPHA2 gene in inherited cataract cases in South-Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel changes were assessed for segregation with the disease within the family and in unrelated controls. Microsatellite marker analysis was performed to establish any relationship between families carrying the same mutation. We report a novel congenital cataract causing mutation c.1751C>T in the EPHA2 gene and the previously reported splice mutation c.2826-9G>A in two new families. Additionally, we report a rare variant rs139787163 potentially associated with increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of inherited cataract cases in South-Eastern Australia. Interestingly, the identified rare variant provides a link between congenital and age-related cataract.

There have been reports of deep vein thrombosis and supraventricular tachycardia following the Moderna vaccination. The timing of SVT and DVT just after vaccination in our case series could suggest possible temporal relationships to the vaccination. But further studies are needed to establish such evidence. [ABSTRACT FROM AUTHOR]