Human rickettsial infections in India - A review.

Rickettsial infections are emerging and/or re-emerging disease that poses a serious global threat to humans and animals. Transmission to humans and animals is through the bite of the ectoparasites including ticks, fleas and chigger mites. Most of the rickettsial diseases are endemic in India, but underdiagnosed. This review is aimed at analyzing the prevalence of rickettsiosis in India and the advancement of rickettsial diagnosis. We have conducted a systematic review on the prevalence of rickettsial disease in India ranging from 1.3% to 46.6% for spotted fever, 2.4% to 77.8% for scrub typhus and 1% to 46.4% for Q fever, based on the literature published with the evidence of isolation, serological, and molecular diagnostics. Search engines Medline/PubMed, Science Direct, ProQuest, and EBSCO were used to retrieve the articles from electronic databases by using appropriate keywords to track the emergence of these rickettsial diseases in India for the period of 1865 to till date. We retrieved 153 published rickettsial articles on hospital-based studies from India that were purely made on the basis of prevalence and the laboratory parameters viz., Weil-Felix test (WF) and Rapid Immunochromatographic tests (RICT) with reference to the gold standard IFA and ELISA. More epidemiological studies are required for epidemic typhus to know the exact prevalence status of this louse-borne rickettsiosis in India. Currently, there is no confirmed specific inflammatory marker for rickettsial diseases. Moreover, serological cross-reactivity is an important aspect, and it should be investigated in endemic areas, there is also a need to include molecular diagnostic techniques for further confirmation in healthcare settings.

CP110 and CEP135 localize near the proximal and distal centrioles of cattle and human spermatozoa.

Centrosomes play an important role in the microtubule organization of a cell. The sperm's specialized centrosome consists of the canonical barrel-shaped proximal centriole, the funnel-shaped distal centriole, and the pericentriolar material known as striated columns (or segmented columns). Here, we examined the localization of the centriole proteins CEP135 and CP110 in cattle and human spermatozoa. In canonical centrioles, CP110 is a centriole tip protein that controls cilia formation, while CEP135 is a structural protein essential for constructing the centriole. In contrast, we found antibodies recognizing CEP135 and CP110 label near the proximal and distal centrioles at the expected location of the striated columns and capitulum in cattle and humans in an antibody and species-specific way. These findings provide a pathway to understanding the unique functions of spermatozoan centrosome.

IL-33 mediates Pseudomonas induced airway fibrogenesis and is associated with CLAD.

BACKGROUND: Long term outcomes of lung transplantation are impacted by the occurrence of chronic lung allograft dysfunction (CLAD). Recent evidence suggests a role for the lung microbiome in the occurrence of CLAD, but the exact mechanisms are not well defined. We hypothesize that the lung microbiome inhibits epithelial autophagic clearance of pro-fibrotic proteins in an IL-33 dependent manner, thereby augmenting fibrogenesis and risk for CLAD. METHODS: Autopsy derived CLAD and non-CLAD lungs were collected. IL-33, P62 and LC3 immunofluorescence was performed and assessed using confocal microscopy. Pseudomonas aeruginosa (PsA), Streptococcus Pneumoniae (SP), Prevotella Melaninogenica (PM), recombinant IL-33 or PsA-lipopolysaccharide was co-cultured with primary human bronchial epithelial cells (PBEC) and lung fibroblasts in the presence or absence of IL-33 blockade. Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate IL-33 expression, autophagy, cytokines and fibroblast differentiation markers. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of Beclin-1. RESULTS: Human CLAD lungs demonstrated markedly increased expression of IL-33 and reduced basal autophagy compared to non-CLAD lungs. Exposure of co-cultured PBECs to PsA, SP induced IL-33, and inhibited PBEC autophagy, while PM elicited no significant response. Further, PsA exposure increased myofibroblast differentiation and collagen formation. IL-33 blockade in these co-cultures recovered Beclin-1, cellular autophagy and attenuated myofibroblast activation in a Beclin-1 dependent manner. CONCLUSION: CLAD is associated with increased airway IL-33 expression and reduced basal autophagy. PsA induces a fibrogenic response by inhibiting airway epithelial autophagy in an IL-33 dependent manner.

Postoperative management of children after lung transplantation.

Pediatric lung transplantation is a highly specialized treatment option at a select few hospitals caring for children. Advancements in surgical and medical approaches in the care of these children have improved their care with only minimal improvement in outcomes which remain the lowest of all solid organ transplants. A crucial time period in the management of these children is in the perioperative period after performance of the lung transplant. Supporting allograft function, preventing infection, maintaining fluid balance, achieving pain control, and providing optimal respiratory support are all key factors required for this highly complex pediatric patient population. We review commonly encountered complications that these patients often experience and provide strategies for management.

Four Cases of Multisystem Inflammatory Syndrome in Adults Associated with SARS-COV-2 Infection - An Overview of Clinical Features, Diagnosis and Treatment.

The varied spectrum of presentation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is intriguing. Multisystem inflammatory syndrome in children (MIS-C) is a well described and documented condition that is associated with the active or recent COVID-19 infection. A similar presentation in adults is termed as Multisystem inflammatory syndrome in Adults (MIS-A). With only very limited cases reported from the west, MIS-A is considered a rare and serious complication of COVID-19. However, it is not as uncommon as we think. Many cases go undiagnosed for lack of COVID -19 like symptoms and unawareness among treating clinicians about this newer clinical entity. Further, antibody testing and inflammatory markers are not easily available in many of the Indian hospitals especially in rural India where the second wave had been intense, thereby making it difficult for the diagnosis of MIS-A. Also, there is no clear treatment guideline for MIS-A unlike MIS-C where the treatment protocol is well laid out. Awareness about MIS-A among treating clinicians can thus help in further evaluation and increased identification of the syndrome at the early stages thereby helping in the early institution of treatment. Our tertiary COVID care hospital in South India which has handled about 5200 cases of COVID-19 is been able to identify 04 cases of MIS-A proving that this clinical entity is not as rare as it is thought but lacks reporting and prompt identification. Here we describe 04 cases of MIS-A and strive to bring in the various aspects of it, including the clinical presentation, laboratory markers, diagnostic criteria and treatment considerations in this post second wave of the COVID-19 pandemic in India.

Effectiveness of Medical Nutritional Therapy in the Management of Type 2 Diabetes Mellitus.

AIM: To assess the effect of medical nutritional therapy (MNT) provided by dieticians on medical and clinical outcomes for adults with Type 2 Diabetes Mellitus. OBJECTIVE: To compare effectiveness of MNT administered monthly to MNT administered once in 03 months. METHOD: The study was conducted at the Department of Endocrinology in a tertiary care hospital. 98 men and women of the age group above 18 years were recruited in the study. 49 consenting individuals were randomly assigned to each of the 02 groups namely Group A and Group B. Group A consisted of 02 visits with dietician (including the initial visit) in the first month and thereafter every monthly. Group B consisted of initial visit with the dietician and there after every 03 monthly. An additional 49 adults with type 2 Diabetes mellitus at one site who had no facility for a contact with dietician were included as a comparison group.Medical outcome measures including fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and serum lipid levels were compared and analysed. Clinical outcomes included Body weight, Height and Body mass index (BMI).Data was collected at the entry to the study and at 03 and 06 months interval. RESULT: In our study, the baseline fasting plasma glucose (FPG), HbA1C, total cholesterol and BMI was more or less similar in all 3 groups. There was a sustained decrease in all the four parameters in Group A which received the maximum nutritional therapy over a period of 06 months (A mean decrease of FPG 15.2 mg/dL, HbA1C 0.59%, total cholesterol 19.6 mg/dL, BMI 0.5 kg/m2 from baseline at 03 months and a mean decrease of FPG 33.4 mg/dL, HbA1C 1.24%, total cholesterol 40.8 mg/dL, BMI 1.1 kg/m2 from baseline at 06 months was seen). However, in Group B which received intermitted nutritional therapy, the decrease in these parameters were observed initially but over a period of 06 months, they increased to more or less near the baseline value months (A mean decrease of FPG 12.9 mg/dL, HbA1C 0.73%, total cholesterol 16.1 mg/dL, BMI 0.5 kg/m2 from baseline at 03 months but a mean increase of FPG 3.2 mg/dL and a mean decrease of HbA1C 0.24%, total cholesterol of 4.3 mg/dL and BMI 0.15 kg/m2 from baseline at 06 months was seen). In Group C which had no means of access to nutritional therapy, there was a subtle decrease in FPG and gradual increase in HbA1C, total cholesterol and BMI at 03 months but all four parameters increased significantly higher than the baseline value at the end of 06 months months (A mean decrease of FPG 6.2 mg/dL and mean increase of HbA1C 0.31%, total cholesterol 16.0 mg/dL, BMI 0.3 kg/m2 from baseline at 03 months and a mean increase of FPG 5.9 mg/dL, HbA1C 0.73%, total cholesterol 31.1 mg/dL, BMI 0.81 kg/m2 from baseline at 06 months was seen). CONCLUSION: Our study has clearly indicated that medical nutritional therapy is of great importance in the holistic management of Type 2 Diabetes mellitus in adults. MNT has got the advantage of not only maintaining a strict glycemic control (in terms of FPG and HbA1C reduction) but also in the lowering of cholesterol and BMI which are the main contributors to cardiovascular (CVD) events among people with type 2 Diabetes mellitus. Also, people who were given frequent MNT had a clear advantage over those who received intermittent MNT in terms of all the measured parameters.

Molecular modelling of coat protein of the Groundnut bud necrosis tospovirus and its binding with Squalene as an antiviral agent: In vitro and in silico docking investigations.

Bud blight disease caused by groundnut bud necrosis virus (GBNV) is a serious constraint in the cultivation of agricultural crops such as legumes, tomato, chilies, potato, cotton etc. Owing to the significant damage caused by GBNV, an attempt was made to identify suitable organic antiviral agents through molecular modelling of the nucleocapsid Coat Protein of GBNV; molecular docking and molecular dynamics that disclosed the interaction of the ligands viz., Squalene and Ganoderic acid-A with coat protein of GBNV. Invitro inhibitory effect of Squalene and Ganoderic acid-A was examined in comparison with different concentrations, against GBNV in cowpea plants under glasshouse condition. The different concentrations of Squalene (50, 100, 150, 250 and 500 ppm) tested in vitro resulted in reduction of lesion numbers (1.69 cm2) as well as reduced virus titre in co-inoculation spray. The present study suggests the antiviral activity of Squalene by effectively fitting into binding site of coat protein of GBNV with favourable hydrophilic as well as strong hydrophobic interactions thereby challenging and blocking the binding of viral replication RNA with coat protein and propagation. The present organic antiviral molecules will be helpful in development of suitable eco-friendly formulations to mitigate GBNV infection disease in plants.

Antiviral activity of basidiomycetous fungi against Groundnut bud necrosis virus in tomato.

Tomato is an important vegetable crop which is severely affected by Groundnut bud necrosis virus (GBNV). Until now effective antiviral agents have not been reported for the management of necrosis disease caused by GBNV. Therefore, a study was undertaken to manage the necrosis disease caused by GBNV using culture filtrate of basidiomycetous fungi viz., Coprinopsiscinerea, Ganoderma lucidum and Lentinula edodes. In vitro studies were conducted in the indicator host cowpea and primary host tomato in glasshouse under insect proof condition; co-inoculation spraying of culture filtrate of Ganoderma lucidum at 0.1% concentration reduced the lesion numbers and inhibited the virus population build-up when compared to inoculated control in the indicator host cowpea upto 77.83%. DAC-ELISA test was performed to quantify the virus titre, indicated reduced virus titre in co- inoculation spray of culture filtrate of G. lucidum treated cowpea with OD value 0.17 ± 0.01 at 405 nm and in tomato plants 0.14 ± 0.01 respectively. The viral copy numbers were quantified by qPCR. About 2.0 × 101 viral copy numbers were observed in tomato plants treated with G. lucidum (co-inoculation) which was lesser than untreated inoculated control plants (2.4 × 108). In order to identify the antiviral properties of G. lucidum, GCMS analysis was carried out and we found the triterpenoid compound Squalene. This is the first study to analyse and confirm the antiviral activity of G. lucidum against a plant virus.

Bioprospecting of seaweeds (Ulva lactuca and Stoechospermum marginatum): The compound characterization and functional applications in medicine-a comparative study.

Seaweeds are considered to be one of the richest bio-reserves, comprising of numerous bioactive compounds with versatile properties and multiple activities. The present study examined the antibacterial activity of two types of seaweeds, Ulva lactuca (green) and Stoechospermum marginatum (brown) collected from Oman Coastal region against five multidrug-resistant bacteria. The aqueous extracts of the seaweeds showed better antibacterial activity compared to methanol extracts. The results of the antibacterial assay revealed the excellent inhibitory effects of U.lactuca with the maximum activity against E.coli(8 mm) followed by K.pneumonia(4 mm) and S.typhi(2 mm). S.marginatum formed a clear zone of inhibition only against E.coli(3 mm).The major phytochemical constituents identified in both the types of seaweeds were Alkaloids, Terpenoids, Saponins, Flavonoids, and Steroids. Fourier transform infrared spectroscopy (FTIR) results confirmed the presence of alcoholic/phenolic groups, and amide groups in the seaweed extracts. Gas chromatography-mass spectrometry (GC-MS) results evidenced the presence of bioactive compounds such as 5-Octadecenal, 1-Tricosanol, Neophytadiene, Lactaropallidin, Phytol, Fenretinide, Lucenin, Vincadifformine in U.lactuca. Additionally, U.lactuca displayed better antioxidant activity (33.05%) in the DPPH free radical scavenging activity test compared to the S.marginatum (21.51%). Thus, the green seaweed U.lactuca could be considered as a potential source of natural antioxidant and antibacterial agents for food and pharmaceutical products.

Exit-Site Infection: A Comparison of Classification Systems.

In general, in peritoneal dialysis (PD) practice in hospitals, Twardowski and Prowant's exit-site classification system is used, while the International Society for Peritoneal Dialysis (ISPD) exit-site scoring system is practical to use in community visits with less experienced healthcare personnel. Nevertheless, when exit-site scoring is 3 points under the ISPD exit-site score system and it falls in the category of equivocal under the Twardowski and Prowant's exit-site classification, the physician should be vigilant about the possibility of developing peritonitis, and hence, patients need to be kept under periodic monitoring.

A distinct seed-transmissible strain of tomato leaf curl New Delhi virus infecting Chayote in India.

Chayote (Sechium edule (Jacq. Sw.) is a single seeded cucurbitaceous vegetable crop mainly grown for its fruit. During 2015-2016, mosaic and leaf distortion type of symptoms were observed in chayote plants in hilly regions of Tamil Nadu. The disease incidence was 50. 3-100% and yield loss was about 69.9% in Dindigul district. The infected chayote plants showed yellow spots, yellow mosaic, leaf curling, puckering, and enations. The fruits of infected plants were malformed and were not marketable. The begomovirus causing the disease was identified as a variant of tomato leaf curl New Delhi virus. The chayote isolates of ToLCNDV share only 91 to 92% identity with other ToLCNDV isolates, deserving to be designated as distinct strain. The phylogenetic analysis on the basis of DNA A component nucleotides clearly indicated common origin of chayote, ridge gourd, ash gourd isolates of India along with Spanish isolates of ToLCNDV. This was contrasting to diverse origin of ToLCNDV isolates from other countries. The virus was sap transmissible to selected cucurbitaceous hosts. The whitefly population (Asia-I) reared in the glass house transmitted the virus to bottle gourd with 4 h of acquisition access period (AAP) and 24 h of inoculation feeding period (IFP). Heavy infestation of greenhouse whiteflies, Trialeurodes vaporariorum on infected chayote plant in Kodaikanal paved way to investigations on its role in vector transmission of ToLCNDV. The field population of T. vaporariorum was found to be viruliferous in PCR using virus specific primers. The greenhouse whitefly efficiently transmitted the virus with 4 h of AAP and 24 h IFP. Seed-borne nature of ToLCNDV was confirmed in PCR by using Roja's and ToLCNDV specific primers in different parts of the fruit viz., pericarp, mesocarp, seed coat, endosperm and embryo. This is the first report of seed transmissible nature of ToLCNDV, its implication in transboundary movement of the virus across several countries is discussed.

Cephalic Arch Stenosis: Location of Stenosis in Indian Hemodialysis Patients.

The cephalic vein is formed over the "anatomical snuff box" and joins the axillary vein just below the clavicular level. The definition of cephalic arch is varied. In the radiology literature, it is defined as the central perpendicular portion of the cephalic vein as it traverses the deltopectoral groove and joins the axillary vein. The possible etiologies of cephalic arch stenosis are numerous. This study aimed to identify patients with cephalic arch stenosis and to discern the domain site of stenosis. This is a retrospective case series of patients who had an arteriovenous fistula with dysfunction of access and ipsilateral upper-limb edema. The clinical features of the access dysfunction were strong pulse due to increased pressure, weak thrill due to poor proximal flow, high static pressure, or decreased dialysis efficiency. All these 25 patients underwent computed tomography (CT) angiogram. The CT angiographic findings revealed cephalic arch stenosis and stenosis in 13 patients (52%). domain IV was slightly more affected than other domains of cephalic arch.

Association of Amelogenesis Imperfecta and Bartter's Syndrome.

Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.

In vitro and in vivo anticancer activity of 2-acetyl-benzylamine isolated from Adhatoda vasica L. leaves.

One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0.40 and 0.39mM at 24h when compared to other tested cells, respectively. Apoptosis was confirmed by annexin V-FITC/PI kit using flow cytometry and confocal microscope in MOLM-14 and NB-4 cells. In addition, 2-acetyl-benzylamine induced cell cycle arrest at G2/M phase in MOLM-14 cells and G0/G1 phase in NB-4 cells. Apoptosis mechanism was confirmed by RT-PCR and Western blot analysis. Treatment with 2-acetyl-benzylamine decreased the Bcl-2 activity and increased the Bax expression; cytochrome c was released and caspases-3 was activated in MOLM-14 and NB-4 cells. Besides, 2-acetyl-benzylamine inhibited the expression of JAK2/STAT3 in MOLM-14 and NB-4 cells. In vivo administration of 2-acetyl-benzylamine inhibited the growth of MOLM-14 cells in xenograft mice model. Molecular docking study has been performed to investigate the binding mode and to estimate the binding energy of 2-acetyl-benzylamine with the active site of JAK-2, AKT1, FLT3 and Bcl-2. The above findings proved that 2-acetyl-benzylamine could be developed as a potential therapeutic agent against cancer.

Toxic Epidermal Necrolysis and Acute Kidney Injury due to Glyphosate Ingestion.

The literature, particularly from India, is scarce on the renal effects of glyphosate poisoning. Glyphosate causes toxicity not only after its ingestion but also after dermal exposure by inhalation route and on eye exposure. We present a patient report of glyphosate consumption which resulted in toxic epidermal necrolysis - the first report after glyphosate consumption and acute kidney injury.