Molecular characterisation of Amblyomma integrum circulating in southern India.

Amblyomma integrum is a large gooseberry sized longirostrate tick (when fully repleted) found in India and Sri Lanka. In Kerala (India), this tick is commonly found in the forest and its fringe areas frequently infesting deer and hence it is locally known as "maan chellu / maanunny" (deer tick). In the present study, molecular characterisation and phylogenetic analysis of A. integrum collected from the area grazed by the sambar deer (Rusa unicolor) of Kerala, south India was performed using three molecular markers viz., the mitochondrial cytochrome c oxidase subunit 1 (COI), mitochondrial 16S ribosomal RNA, and nuclear 18S ribosomal RNA genes. Cytochrome c oxidase subunit 1 (COI) gene showed better resolving ability for elucidating the evolutionary relationship of A. integrum and identified two distinct clades, viz., A and B. The Tamil Nadu isolates of south India and Marayoor isolate 1 (from Idukki district of Kerala bordering with Tamil Nadu) belonged to clade A. Majority of Wayanad isolates from Kerala, occupied clade B. The intraspecific genetic distance among the A. integrum species ranged from 0.00 to 13.34%. Between clades A and B, the genetic distance observed was 11.49%. The clade B isolates were genetically close to A. geoemydae (GD: 1.22%). Morphological variations between the clades included darker exoskeletal coloration in clade A and distinct differences in the shape of basis capitulum. Further analysis using Assemble Species by Automatic Partitioning (ASAP) and Generalized Mixed Yule Coalescent (GMYC) provided additional insights. Assemble Species by Automatic Partitioning (ASAP) identified 26 Molecular Operational Taxonomic Units (MOTUs) at a threshold distance of 5.38%, supporting the species partition of A. integrum clade B. Generalized Mixed Yule Coalescent (GMYC) analysis retained the same species complex (A. integrum-geoemydae Complex) inferred from the ASAP analyses. It could be inferred from the present study that the A. integrum clades A and B could be two different putative pseudocryptic species.

Evaluation of Lung Glucose Uptake with Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/CT in Patients with Pulmonary Arterial Hypertension and Pulmonary Hypertension Due to Left Heart Disease.

Aim: Previous studies have demonstrated increased glucose uptake by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in lung parenchyma in animal models or small pulmonary arterial hypertension (PAH) cohorts. However, it is not well known whether increased FDG uptake in the lung is a unique phenomenon in PAH or whether elevated pulmonary artery pressure (PAP) induces FDG uptake. Methods and results: Nineteen patients with PAH, 8 patients with pulmonary hypertension due to left heart disease (PH-LHD), and 14 age matched control subjects were included. All PH patients underwent right heart catheterization and FDG-PET. The mean standard uptake value (SUV g/mL) of FDG in each lung was obtained and average values of both lungs were calculated as mean lung FDG SUV. The correlation between hemodynamics and mean lung FDG SUV was also analyzed in PH patients. Mean PAP (mPAP) was not significantly different between PAH and PH-LHD (45±11 vs 43±5 mmHg, p=0.51). PAH patients demonstrated significantly increased mean lung FDG SUV compared with PH-LHD and controls (PAH: 0.76±0.26 vs PH-LHD: 0.51±0.12 vs controls: 0.53±0.16, p=0.0025). The mean lung FDG SUV did not correlate with mPAP either in PAH or PH-LHD. Conclusion: PAH is associated with increased lung FDG uptake indicating increased glucose utilization in the lung. This may represent metabolic shift to glycolysis and/or active inflammation in the remodeled pulmonary vasculature, and is observed to a greater extent in PAH than in patients with PH secondary to LHD and control subjects without PH.

The Predictive Score for Patients Hospitalized With COVID-19 in Resource-Limited Settings.

Background and aims The second wave of coronavirus disease 2019 (COVID-19) has been devastating in India and many developing countries. The mortality reported has been 40% higher than in the first wave, overwhelming the nation's health infrastructure. Despite a better understanding of the disease and established treatment protocols including steroids and heparin, the second wave was disastrous. Subsequent waves have the potential to further cripple healthcare deliveries, also affecting non-COVID-19 care across many developing economies. It is then important to identify and triage high-risk patients to best use the limited resources. Routine tests such as neutrophil and monocyte counts have been identified but have not been successfully validated uniformly, and their utility is still being understood in COVID-19. Various predictive models that are available require online resources and calculators and additionally await validation across all populations. These, although useful, might not be available or accessible across all institutions. It is then important to identify easy-to-use scores that utilize tests done routinely. In identifying with this goal, we did a retrospective review of the institutional database to identify potential predictors of intensive care unit (ICU) admission and mortality in patients hospitalized during the second wave who accessed healthcare at our academic setup. Results Three predictors of mortality and four predictors of ICU admission were identified. Absolute neutrophil count was a common predictor of both ICU admission and mortality but with two separate cut points. An absolute neutrophil count of >4,200 predicted need for ICU admission (odds ratio (OR): 3.1 (95% confidence interval (CI): 2.0, 4.8)), and >7,200 predicted mortality (adjusted OR: 4.2 (95% CI: 1.9, 9.4)). We observed that a blood urea level greater than 45 was predictive of needing ICU care (adjusted OR: 8.0 (95% CI: 3.7, 17.6)). In our dataset, serum ferritin of >500 was predictive of ICU admission (adjusted OR: 2.7 (95% CI: 1.2, 5.9)). We noted a right shift of partial pressure (p50 is the oxygen tension at which hemoglobin is 50% saturated) (p50c) in SARS-CoV-2 as a predictor of ICU care (OR: 2.6 (95% CI: 1.7, 3.9)) when partial pressure is >26.5. In our analysis, a serum protein of less than 7 g/dL (OR: 2.8 (95% CI: 1.7, 4.4)) was a predictive variable for ICU admission. An LDH value of >675 was predictive of severity with a need for ICU admission (OR: 9.2 (95% CI: 5.4, 15.5)) in our series. We then assigned a score to each of the predictive variables based on the adjusted odds ratio. Conclusion We identified a set of easy-to-use predictive variables and scores to recognize the subset of patients hospitalized with COVID-19 with the highest risk of death or clinical worsening requiring ICU care.

COVID-19 Vaccines Portray the Bright Side of Human Creativity, But It Means Nothing until They Prove Their Worth: A Study on Seroconversion after the first Dose of Covishield Vaccine in Central Kerala.

Background: COVID-19 vaccines, we believe, have come to rescue us from the clutches of the dreaded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With rapid ongoing mutations, it is difficult to predict the effectiveness of seroconversion following vaccination. This study aims to find out the proportion of people with seroconversion following first dose of Covishield vaccine. Methods: Randomly selected health-care workers were followed up for SARS-CoV-2 immunoglobulin G (IgG) antibodies between 28 and 42 days after receiving their first vaccine dose. The VITROS SARS-CoV-2 IgG test (Ortho-Clinical Diagnostics, USA) with 100% specificity and > 90% sensitivity was used to assess seroconversion. Results: The first dose of vaccine induced seroconversion in 91.7% of beneficiaries. Nearly one-third (30.2%) of them had high antibody titers, and it showed a significant association with female gender (9.6 ± 5.5 vs. 7.6 ± 5.6) and younger age (P = 0.008). In addition, those with previous COVID infection showed a more robust immune response when compared to others (P = 0.001). Conclusion: Seroconversion rate of more than 90% offers a promising hope toward successful pandemic control. In the current scenario, the inability to attain the targeted coverage due to an upsurge in vaccine hesitancy, compounded with only lower proportion of seroconversion in elderly, faster rollout of the vaccines without any age limit, will help achieve the herd threshold more rapidly.

Primary peritoneal carcinoma and ovarian carcinoma - a ten-year comparative analysis.

BACKGROUND: Primary peritoneal carcinoma (PPC) at presentation often masquerades as epithelial ovarian carcinoma (OC) but behaves different with respect to treatment response, recurrence patterns and has inferior outcomes. The objective of this study is to compare the clinicopathological features and survival outcomes of PPC and OC. METHODS: Prospectively maintained database of patients presenting to the gynecologic oncology department at a tertiary hospital was reviewed between 1st January 2010 and 31st December 2020. A comparative analysis of high-grade serous stage III/IV PPC and OC was done. Demographics, treatment details, complications and survival outcomes were collected from electronic medical records. RESULTS: 151 OC and 69 PPC patients were included. A higher proportion of women with PPC had reduced performance status prior to hysterectomy with salpingo-oophorectomy, a shorter symptom to treatment interval, and large volume ascites. A significantly lower number of women with PPC (4.3 vs. 46.1%; P < 0.001) underwent primary cytoreduction, had a lower median surgical complexity score (3 vs. 4; P < 0.001) but higher recurrence rates (66.7 vs. 47.0%; P = 0.041) as compared to the patients with OC. The median progression-free survival (PFS) was 18 (15-20) months in PPC and 23 (17-28) months in OC patients (log-rank P = 0.034), while the median overall survival (OS) was similar (44 vs. 48 months; log-rank P = 0.696). The presence of extraperitoneal disease and interval cytoreduction was associated with shorter PFS. Suboptimal cytoreduction and delay in adjuvant chemotherapy beyond 6 weeks post-surgery was associated with reduced OS. CONCLUSION: PPC is an aggressive disease with lower PFS compared to OC. Commonly presenting with large volume carcinomatosis, it is not amenable for primary cytoreduction, making the usage of neoadjuvant chemotherapy a common practice and pragmatic approach.

Detection of Newcastle disease virus and assessment of associated relative risk in backyard and commercial poultry in Kerala, India.

BACKGROUND: Newcastle disease (ND) is an economically important viral disease affecting the poultry industry. In Kerala, a state in South India, incidences of ND in commercial and backyard poultry have been reported. But a systematic statewide study on the prevalence of the disease has not been carried out. OBJECTIVES: A cross-sectional survey was performed to detect the presence of Newcastle disease virus (NDV) in suspect cases and among apparently healthy commercial flocks and backyard poultry, in the state and to identify risk factors for NDV infection. METHODS: Real-time reverse transcription-PCR (RT-PCR) was used to detect the M gene of NDV in choanal swabs and tissue samples collected from live and dead birds, respectively and the results were statistically analysed. RESULTS: The predominant clinical signs of the examined birds included mild respiratory signs, huddling together and greenish diarrhoea. Nervous signs in the form of torticollis were noticed in birds in some of the affected flocks. On necropsy, many birds had haemorrhages in the proventriculus and caecal tonsils which were suggestive of ND. Of the 2079 samples tested, 167 (8.0%) were positive for the NDV M-gene by RT-PCR. Among 893 samples collected from diseased flocks, 129 (14.5%), were positive for M gene with pairwise relative risk (RR) of 15.6 as compared to apparently healthy flocks where 6 out of 650 (0.9%) samples were positive. All positive samples were from poultry; none of the ducks, pigeons, turkey and wild birds were positive. Commercial broilers were at higher risk of infection than commercial layers (RR: 4.5) and backyard poultry (RR: 4.9). Similarly, birds reared under intensive housing conditions were at a higher risk of being infected as compared to those reared under semi-intensive (RR: 6.7) or backyard housing (RR: 2.1). Multivariable analysis indicated that significantly higher risk of infection exists during migratory season and during ND outbreaks occurring nearby. Further, lower risk was observed with flock vaccination and backyard or semi-intensive housing when compared to intensive housing. When the M gene positive samples were tested by RT-PCR to determine whether the detected NDV were mesogenic/velogenic, 7 (4.2%) were positive. CONCLUSIONS: In Kerala, NDV is endemic in poultry with birds reared commercially under intensive rearing systems being affected the most. The outcome of this study also provides a link between epidemiologic knowledge and the development of successful disease control measures. Statistical analysis suggests that wild bird migration season and presence of migratory birds influences the prevalence of the virus in the State. Further studies are needed to genotype and sub-genotype the detected viruses and to generate baseline data on the prevalence of NDV strains, design better detection strategies, and determine patterns of NDV transmission across domestic poultry and wild bird populations in Kerala.

Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection.

Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulates apoptosis and promotes Mtb clearance in vitro. We performed histone acetylation quantitative trait locus (haQTL) analysis on the dataset and identified 69 candidate causal variants for immune phenotypes among granulocyte haQTLs and 83 among monocyte haQTLs. Our study provides proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.

Sweet Memories or Not? A Comparative Study on Cognitive Impairment in Diabetes Mellitus.

INTRODUCTION: Type 2 Diabetes Mellitus is a modern-day epidemic and dementia has been declared as a global challenge. It is, therefore, worthwhile to investigate the effect that Diabetes has on cognition. Although effective screening is routinely carried out for various complications of Diabetes, its effect on Higher Mental Functions is often overlooked. METHODOLOGY: A cross-sectional analytical study to assess Cognitive Impairment was carried out on 800 participants, 400 diabetics and 400 non-diabetics attending a tertiary care center. The Addenbrooke's Cognitive Examination- III was used, which is a validated, highly sensitive tool having a maximum score of 100. Patients with a score < /= 82 were considered to have impaired Cognition. Statistical analysis was done using SPSSv.21. Suitable statistical tests like Mann-Whitney U, t-test, ROC curve and Logistic regression analysis were done. RESULTS: Cognitive Impairment was present in 63.8% of the diabetics when compared to only 10.8% in the non-diabetics, with an Odds Ratio-8.78 (CI-4.47-17.22). The total ACE score in diabetics [median-82 (IQR-4), mean rank-270.06] was less compared to the non-diabetic patients [median- 85 (IQR-3), mean rank-530.94] (U = 27822, p-0.001). Attention, Memory, Language, and Visuospatial domains were significantly lower in the diabetics compared to the non-diabetics. However, the fluency domain was not affected. Hypertension and the presence of macrovascular diseases were significantly associated with Cognitive Impairment (p < 0.005). Those with Cognitive dysfunction also had higher mean RBS values and longer duration of Diabetes (p-0.001). The cut-off value for RBS (to distinguish people with and without Cognitive Impairment) from ROC curve was 142.5 (AUC = 0.834, Youden's Index-0.586, p-0.001) and for duration of Diabetes was 7.5 years (AUC = 0.847, Youden's Index-0.529, p-0.001). CONCLUSION: This paper highlights that Cognitive Impairment exists in a very high proportion of diabetic patients in Kerala. So, it is important that we do an early assessment of cognitive function in diabetes patients and manage them prudently. Early interventions may prove to be beneficial in the long run, considering the burden of diabetes and cognitive dysfunction associated with the disease.

Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Together let us confront it: An outbreak investigation of hepatitis B in Pathanamthitta district, Kerala.

INTRODUCTION: Hepatitis B is a potentially life-threatening liver infection caused by the Hepatitis B virus (HBV). The established routes of transmission are from mother to infant, sexual contact, and exposure to blood or body fluids. Though HBV is preventable by vaccine and robust infection control practices, outbreaks of HBV infection do occur in India. However, the state of Kerala with its health parameters, one among the best in the country, cannot afford to have continuing outbreaks. An unusual increase in the reported cases of Hepatitis B in a rural area of Pathanamthitta district of Kerala, called for an outbreak investigation. AIMS: To describe the epidemiological features, to determine the risk factors associated with HBV transmission, and to suggest measures to prevent future transmission. METHODS: A community-based case-control study (1:2) was undertaken. A total of 162 participants (54 cases and 108 age, gender, and neighborhood matched controls) took part in the study. Focus group discussions were conducted with subject experts to develop an interview schedule assessing 40 risk factors. It was further reviewed by the University of Sydney. Data was collected by trained Junior Health Inspectors and Junior Public Health Nurses of the Primary Health Centers. Data was analyzed using SPSS v. 20. Proportions were compared by Univariate analysis, sub-group analysis, and logistic regression. Population Attributable Risk (PAR) was also calculated. RESULTS AND CONCLUSION: More than 90% of the infections were IgM anti-HBc positive, suggesting a recent infection. Interventions during hospitalization [OR: 7.98 (95% CI - 2.17--29.4)], family history of Hepatitis B [OR. 4.14 (95%CI - 1.73--9.9)], and laboratory investigations [OR: 3.99 (1.72--9.31)] were found to be significant risk factors. PAR was highest for laboratory interventions (32%). Vaccinating household contacts and strict enforcement of infection control practices could substantially reduce the burden of this fatal disease.

Canadian Cardiovascular Society/Canadian Thoracic Society Position Statement on Pulmonary Hypertension.

The landscape of pulmonary hypertension (PH) has changed significantly since the last Canadian Cardiovascular Society/Canadian Thoracic Society position statement in 2005. Since then, advances in our understanding of the pathophysiology of PH and improvements in diagnostic and therapeutic options have transformed the care of patients with PH. Globally, PH has an estimated prevalence of 1%, increasing to 10% in those aged 65 years and older, most commonly due to left heart or lung disease. Although pulmonary arterial hypertension (PAH) is less common, the morbidity and mortality is significant and early diagnosis and treatment are essential. This document is targeted at clinicians and describes a framework for screening and diagnosis of PH, with recommendations for performance and interpretation of echocardiography, cardiac magnetic resonance imaging, and right heart catheterization. In addition, the current approach to PAH management in Canada including risk stratification and pharmacologic therapy aimed at achieving a low-risk profile is discussed. The rationale to avoid specific PAH therapy in patients with left heart disease and lung disease-related PH is emphasized, along with special considerations for the diagnosis and management of chronic thromboembolic PH. Future advancements in the identification of novel pathways and therapies, personalized approaches to direct therapy, as well as interventional approaches such as balloon pulmonary angioplasty for chronic thromboembolic PH promise to continue the rapid evolution of this field.

Incorporation of renal function in mortality risk assessment for pulmonary arterial hypertension.

BACKGROUND: Risk assessment is important for prognostication and individualized treatment decisions for patients with pulmonary arterial hypertension (PAH). The purpose was (1) to compare contemporary risk assessment tools and (2) to determine the prognostic significance of risk parameters of kidney function and whether they can further improve risk prediction for patients with PAH. METHODS: We identified a cohort of treatment-naive patients (n = 211) who received an incident diagnosis of PAH at the University of Ottawa Heart Institute. Using demographics, disease characteristics, and hemodynamic data at diagnosis, we categorized patients as low, intermediate, or high risk according to current European guidelines (European Society of Cardiology [ESC]) and registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL) risk scores. The primary end-point was transplant-free survival (TFS). RESULTS: Patients were predominantly women (64.6%) with World Health Organization function Class III symptoms (66.5%). The median TFS was 7.09 years. There was little agreement between ESC- and REVEAL-based risk estimates (weighted kappa = 0.21-0.34). Although both the ESC (log-rank, p = 0.0002) and REVEAL algorithms stratified TFS risk (p < 0.0001), the REVEAL score provided superior discrimination (C-statistic = 0.70 vs 0.59, p = 0.004). Renal function at diagnosis (p < 0.0001) and Δ renal function at 6 months (p < 0.0001) were identified as novel risk parameters and served to reclassify some patients in the intermediate-risk category to a lower or higher risk stratum (p < 0.0001). CONCLUSION: REVEAL-based strategies provide superior TFS risk discrimination to ESC/European Respiratory Society-based approaches. However, the classification of intermediate-risk patients varied significantly across tools. We demonstrate the importance of renal function, which further improved the stratification of risk in patients with PAH, particularly in patients who are considered intermediate risk.

ORAL HALOPERIDOL PREMEDICATION TO REDUCE CAPTURE STRESS PRIOR TO XYLAZINE-KETAMINE ANESTHESIA IN CAPTIVE SPOTTED DEER (AXIS AXIS).

A prospective clinical trial was performed to evaluate the efficacy of haloperidol premedication prior to xylazine-ketamine anesthesia with a goal of reducing capture stress in adult male captive spotted deer (Axis axis). On the morning of the study, deer were fed a banana either containing haloperidol tablets (1 mg/kg) (haloperidol group, n = 10) or without haloperidol (placebo group, n = 10). Six hours postadministration, xylazine (3 mg/kg) and ketamine (2 mg/kg) was administered intramuscularly via a dart. Rectal temperature, heart rate, respiratory rate, and SpO2 (percent hemoglobin saturation) were recorded at 5-min intervals. Blood gas analysis was performed at time 0 (venous blood) and 10 and 20 min (arterial blood) postinduction. Serum cortisol was determined from venous blood (35 min postinduction), following which yohimbine was administered at a dose of 0.15 mg/kg intramuscular and 0.15 mg/kg intravenous. Statistical analysis of repeated measures data was performed with a two-way analysis of variance. Paired data were analyzed with a Wilcoxon rank-sum test (categorical data) or a paired t-test (continuous data). Significance was set at P ≤ 0.05, and results were expressed as mean ± SEM. There was no significant difference in induction time or recovery time between treatment groups. Rectal temperature and heart rate were significantly lower in the haloperidol group. Both groups demonstrated acidosis with venous pH being significantly lower in the placebo group when compared to the haloperidol group. Serum cortisol and arterial plasma lactate were lower in the haloperidol group indicative of reduced stress and physical exertion. Haloperidol premedication proved to be beneficial in reducing capture stress, when administered prior to xylazine-ketamine anesthesia, in spotted deer.

Cardiovascular consequences of obstructive sleep apnea in women: a historical cohort study.

OBJECTIVE/BACKGROUND: Evidence on sex differences in the association between obstructive sleep apnea (OSA) and cardiovascular outcomes is limited and controversial. We conducted a historical cohort study to investigate this relationship. PATIENTS/METHODS: Clinical data on adults who underwent sleep study at a large urban academic hospital (Toronto, Canada) between 1994 and 2010 were linked to provincial health administrative data from 1991 to 2015. We fit Cox regressions to investigate the association between OSA severity and a cardiovascular composite outcome (all-cause mortality or hospitalization due to myocardial infarction, stroke, heart failure or atrial fibrillation), controlling for risk factors and stratifying by sex. RESULTS: A total of 10,149 subjects were included: median age of 49 years, 38% women. Over a median of 9.3 years, 1782 (18%) participants developed an outcome. The association between percentage of sleep time spent with oxygen saturation <90% and outcome was stronger for women (HR for IQR, 3 vs 0% = 1.30, 1.19-1.42) than for men (HR for IQR = 1.13, 1.06-1.21) (p for interaction = 0.01) in the adjusted model. Stratifying by sex, oxygen desaturations and heart rate in sleep were significant predictors in both men and women, while presence of daytime sleepiness, sleep efficiency and periodic leg movements in sleep were predictive in women but not in men. CONCLUSIONS: In a large clinical cohort with suspected OSA, the impact of OSA as measured by the degree of nocturnal oxygen desaturation on the composite outcome was found to be greater in women than in men. We also found a different predictive ability of OSA-related factors by sex.

Ticks and accompanying pathogens of domestic and wild animals of Kerala, South India.

The objective of the present study was to detect the chosen nucleotide DNA or RNA sequences of the pathogens in ticks of domestic and wild animals of Kerala, South India based on molecular techniques. Among 602 ticks collected, 413 were from bovines (cattle and buffalo), 26 from goats, 101 from dogs and 62 from wild animals. Amblyomma integrum, Am. gervaisi, Dermacentor auratus, Haemaphysalis bispinosa, Ha. intermedia, Ha. shimoga, Ha. spinigera, Rhipicephalus annulatus, Rh. microplus, Rh. haemaphysaloides and Rh. sanguineus s.l. were identified from various domestic and wild animals of Kerala. The cDNA synthesized from the RNA isolated from fully or partially engorged adult female/nymphal ticks was used as template for the specific polymerase chain reactions (PCR). Out of 602 ticks examined, nucleotide sequences of pathogens were detected in 28 ticks (4.65%). The nucleotide sequences of tick-borne pathogens like Theileria orientalis, Babesia vogeli, Hepatozoon canis, Anaplasma marginale, An. bovis, Rickettsia sp. closely related to Ri. raoultii, Ri. massiliae, Ri. africae and Ri. slovaca were detected. The identification of the previously unreported nucleotide sequences of rickettsial pathogens from India is of particular interest due to their zoonotic significance. The phylogenetic analysis of the major piroplasm surface protein (MPSP) gene of T. orientalis amplified from Rh. annulatus ticks revealed that they were genetically close to type 7, which belong to the highly pathogenic Ikeda group.

Whether Dirofilaria repens parasites from South India belong to zoonotic Candidatus Dirofilaria hongkongensis (Dirofilaria sp. hongkongensis)?

The canine and zoonotic dirofilarioses are arthropod-borne parasitic infections caused by nematodes of the genus Dirofilaria, infecting canines, felines and humans throughout the world. Dirofilaria repens was considered as the most common cause of human dirofilariosis in Kerala. In the present study, molecular characterization of Dirofilaria isolates causing dirofilariosis in humans, dogs and jackal from Kerala, South India was undertaken by performing sequence and phylogenetic analysis based on cytochrome oxidase subunit I (COI) gene. The live worms from swellings/ nodules in subconjunctiva or subcutaneous tissue or scrotum were recovered from humans (n = 3), dogs (n = 4) and one jackal. The PCRs targeting a repetitive fragment, 18S rRNA and COI genes yielded products of ~246 bp, ~875 bp and ~350 bp respectively in all the samples. The sequence analysis of 18S rRNA gene revealed the closest identity (98 to 99%) with an already published sequence of D. repens isolated from a human in Japan. However, based on the sequence and phylogenetic analysis of partial sequences of COI gene, the Dirofilaria infecting both animals (dogs, jackal) and humans native to Kerala, South India were identified as genetically conserved and closely related to Dirofilaria sp. hongkongensis. Hence, the results of the present study suggested the existence of Candidatus Dirofilaria hongkongensis (Dirofilaria sp. hongkongensis) in Kerala, South India causing zoonotic filariosis in canines and humans.

Ixodid Tick Vectors of Wild Mammals and Reptiles of Southern India.

BACKGROUND: We aimed to focus on the ixodid ticks parasitizing wild mammals and reptiles from Wayanad Wildlife Sanctuary, Western Ghat, southern India. METHODS: The taxonomic identification of ticks collected from wild mammals and reptiles was performed based on the morphology of adults. RESULTS: We revealed eight species of ticks including, Amblyomma integrum, Rhipicephalus (Boophilus) annulatus, Haemaphysalis (Kaiseriana) spinigera, H. (K.) shimoga, H. (K.) bispinosa, H. (Rhipistoma) indica, Rhipicephalus haemaphysaloides and R. sanguineus s.l. collected from nine species of wild mammals while four tick species Ablyomma kraneveldi, A. pattoni, A. gervaisi and A. javanense parasitizing on four species of reptiles. The highest host richness was shown by H. (K.) bispinosa and R. haemaphysaloides parasitizing six and five different host species, respectively. Reports of R. (B.) annulatus on sambar deer, A. javanense and A. kraneveldi on python as well as A. pattoni on Indian rat snake are the new host records from this region. CONCLUSION: Eight species of ticks parasitizing on nine species of wild mammals and four species of parasitizing on four species of reptiles were identified. The highest host richness was shown by H. (K.) bispinosa and R. haemaphysaloides. H. spinigera as the vector of KFD was also identified in this study.

Topical Delivery of Senicapoc Nanoliposomal Formulation for Ocular Surface Treatments.

Topical ophthalmologic treatments have been facing great challenges with main limitations of low drug bioavailability, due to highly integrative defense mechanisms of the eye. This study rationally devised strategies to increase drug bioavailability by increasing ocular surface residence time of drug-loaded nanoliposomes dispersed within thermo-sensitive hydrogels (Pluronic F-127). Alternatively, we utilized sub-conjunctival injections as a depot technique to localize nanoliposomes. Senicapoc was encapsulated and sustainably released from free nanoliposomes and hydrogels formulations in vitro. Residence time increased up to 12-fold (60 min) with 24% hydrogel formulations, as compared to 5 min for free liposomes, which was observed in the eyes of Sprague-Dawley rats using fluorescence measurements. Pharmacokinetic results obtained from flushed tears, also showed that the hydrogels had greater drug retention capabilities to that of topical viscous solutions for up to 60 min. Senicapoc also remained quantifiable within sub-conjunctival tissues for up to 24 h post-injection.