Development of pulmonary hypertension in patients with end stage renal disease

INTRODUCTION Cardiovascular disease is the leading cause of morbidity and mortality in dialysis patients, accounting for 50%of deaths. Pulmonary hypertension (PHT) comprises a group of clinical and pathophysiological entities with similar features but a variety of underlying causes. There are several etiologies for PHT. Pulmonary hypertension (PHT) can be the result of heart, lung or systemic disorders. Regardless of the etiology, morbidity and mortality from long-standing PHT exceed that expected from the causative condition. PHT was frequently found in patients with chronic renal failure (CRF). Review of literature showed that in one study, PHT was found in 40% of patients with end stage renal disease (ESRD) on chronic hemodialysis therapy via arterio venous access. Adekunle et al. stated that PHT is an independent predictor of mortality in ESRD patients. PHT involves vasoconstriction and obliteration of the lumen of small vessels in the lungs by plexiform lesions resulting in increased resistance to flow. Proposed mechanisms for the formation of the plexiform lesion included regulation of endothelial growth and angiogenic response to local triggers. Hormonal and metabolic derangement associated with ESRD might lead to pulmonary arterial vasoconstriction and an increase of the pulmonary vascular resistance. Pulmonary artery pressure (PAP) may be further increased by high cardiac output resulting from the arterio venousaccess itself and also worsened by commonly occurring anemia and fluid overload. Subclinical left ventriculardysfunction also occurs in patients with ESRD, and is evidenced as abnormal myocardial diastolic rather than systolic dysfunction. Local vascular tone and function of pulmonary vessels are regulated by the balance between vasodilators, such as nitric oxide, and vasoconstrictors, such as thromboxane. Patients with CRF show an endothelial dysfunction related to defective nitric oxide activity, which is not corrected by hemodialysis (HD). Increased brain natriuretic hormone is associated with age, left ventricular hypertrophy, renal failure, and PHT. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a byproduct of brain natriuretic peptide (BNP) that has been shown to be of prognostic value in PHT. AIM : In this study, we aim to find the prevalence of PHT in patients with ESRD and compare the incidence of PHT between those on hemodialysis and those on conservative management. We also compare the biochemical data of the patients with and without PHT to find out any possible associations. METHODOLOGY : Study Method : The study was conducted on patients attending the in-patient/out-patient department of nephrology in PSG hospital. All patients with a diagnosis of ESRD where taken up for the study after the application of the inclusion and exclusion criteria and after obtaining consent. These patients were divided into two groups – those who receive dialysis and those on conservative management. The biochemical data collected were the average of the last six readings .ECG, CXR and echocardiography to assess PHT were done to those patients who were selected to be included in the study. Study Place : The study was conducted in PSG Hospitals, Coimbatore. Study Population : Patients diagnosed with end stage renal disease presenting to PSG hospitals during a time period of 6 months were included in the study after the application of inclusion and exclusion criteria. Study Period : The study was conducted during the time period of April 2010 to October 2010. All patients with a diagnosis of ESRD attending the Nephrology department who gave consent to be included in the study were included during this time period. Total of 73 patients were studied. Inclusion Criteria : ESRD patients on HD or conservative management were selected. ESRD due to all etiologies and patients of all age groups were selected. Exclusion Criteria : COPD, Parenchymal Lung Disease, Chest Wall Disease, Previous history of PHT, Previous pulmonary embolism, Smoker ( >5 pack years), Collagen Vascular Disease, LV EF <50%, Significant mitral/aortic valve disease. HD patients were being treated with standard bicarbonate dialysis for 4 hours, 3 times a week. Subjects gave their informed consent and the study protocol was approved by the institute’s Committee on Human Research. RESULTS : PHT is more common among those on hemodialysis than those who are on conservative management. The cause of a higher PAP in group 1 may be related to the process of HD or the hemodynamic changes caused by AVF. The process of HD itself may be a contributing factor for elevated PAP, but the exact cause is not known and vasoconstrictors such as endothelin may be involved. Microbubble emboli are another cause. In addition, HD causes recurrent episodes of hypoxemia due to partial blockage of the pulmonary capillary bed by white cells or silicone microemboli. Recurrent hypoxemia is associated with elevation of PAP. CONCLUSION : This study shows that PHT is very common in ESRD patients. a. 31.5% of total patients (73) with ESRD had PHT, b. 35% of 37 patients on HD had PHT, c. 28% of 36 patients on conservative management had PHT. Also, PHT is much more common in ESRD patients receiving HD than those on conservative management. Since pulmonary arterial hypertension usually presents at a very late stage, early diagnosis is a key to proper management and a better outcome. Estimation and follow-up of PAP using doppler echocardiography may be indicated in all patients with ESRD undergoing HD via an arteriovenous access

Analysis of development of Index Left Ventricular Systolic Dysfunction after revascularization in Acute ST Elevation Myocardial Infarction.

Introduction : Myocardial infarction is the most cause of heart failure. The incidence of heart failure after MI has been reported as high as 23% in various studies. Characteristics of patients in India who develop heart failure after a myocardial infarction are less well studied. Though presence of higher incidence of reduced LV function with delay in revascularization time is established, rates of reduced LV function after different modes of revascularization and correlation with coronary artery lesion is not well established. Aim and Objectives : To study the incidence of left ventricular dysfunction after the initial episode of myocardial infarction and to determine the difference in rates of development of LV dysfunction depending on time to perform revascularization and based on mode of revascularization and to correlate the development of LV dysfunction with the coronary artery lesion as determined by coronary angiogram. Methodology : 93 patients admitted in PSG Hospital from 1st March 2013 to 31st December 2013 with a diagnosis of Acute ST Elevation Myocardial Infarction and undergoing reperfusion therapy with either streptokinase or by percutaneous coronary intervention were included. Window period and door to needle/door to balloon time are recorded. Left ventricular ejection fraction, as determined by volumetric method, is measured within first 24 hours and on day 5 by a single person to avoid interpersonal variation. Development of heart failure based on Framingham criteria is noted. Use of diuretics is noted. Coronary artery lesion by coronary angiogram is noted. Results : Out of 93 patients included in the study, 32 underwent primary PCI and 61 underwent thrombolysis. Patients with longer reperfusion time showed a significant reduction in LV ejection fraction. Patients retaining a normal ejection fraction when reperfusion times are between 0-3, 3-6, 6-12 and more than 12 were 70%, 59%, 32% and 0 respectively. Patients who underwent primary PCI had more chance of a preserved LVEF compared to those who underwent thrombolysis (82% Vs 44%. p=0.013). Patients with anterior wall STEMI had less number of patients with normal LVEF when reperfusion times were between 3 to 6 hours (41% Vs 93%. p=0.001) compared to non-anterior wall STEMI patients. No significant associations were found between age, presence of diabetes and the number of vessels involved to LVEF. Conclusion : Longer reperfusion times are associated with significant reduction in LVEF. Primary PCI leads to better outcome in patients presenting between 3-6 hours when compared with thrombolysis. AW STEMI patients develop significant reduction in LVEF at 3-6 hours compared to non-AW STEMI patients

Variable Chaplygin Gas: Constraints from CMBR and SNe Ia

We constrain the parameters of the variable Chaplygin gas model, using the location of peaks of the CMBR spectrum and SNe Ia ``gold '' data set. Equation of state of the model is $P=-A(a)/\rho$, where $A(a)=A_0 a^{-n}$ is a positive function of the cosmological scale factor $a$, $A_0$ and $n$ being constants. The variable Chaplygin gas interpolates from dust-dominated era to quintessence dominated era. The model is found to be compatible with current type Ia Supernovae data and location of first peak if the values of $\Omega_m$ and $n$ lie in the interval $[0.017,~0.117]$ and $[-1.3,~2.6]$ respectively.Comment: 9 pages,4 figure

Draft genome sequence of Sclerospora graminicola, the pearl millet downy mildew pathogen:Genome sequence of pearl millet downy mildew pathogen

Sclerospora graminicola pathogen is one of the most important biotic production constraints of pearl millet worldwide. We report a de novo whole genome assembly and analysis of pathotype 1. The draft genome assembly contained 299,901,251 bp with 65,404 genes. Pearl millet [Pennisetum glaucum (L.) R. Br.], is an important crop of the semi-arid and arid regions of the world. It is capable of growing in harsh and marginal environments with highest degree of tolerance to drought and heat among cereals (1). Downy mildew is the most devastating disease of pearl millet caused by Sclerospora graminicola (sacc. Schroet), particularly on genetically uniform hybrids. Estimated annual grain yield loss due to downy mildew is approximately 10?80 % (2-7). Pathotype 1 has been reported to be the highly virulent pathotype of Sclerospora graminicola in India (8). We report a de novo whole genome assembly and analysis of Sclerospora graminicola pathotype 1 from India. A susceptible pearl millet genotype Tift 23D2B1P1-P5 was used for obtaining single-zoospore isolates from the original oosporic sample. The library for whole genome sequencing was prepared according to the instructions by NEB ultra DNA library kit for Illumina (New England Biolabs, USA). The libraries were normalised, pooled and sequenced on Illumina HiSeq 2500 (Illumina Inc., San Diego, CA, USA) platform at 2 x100 bp length. Mate pair (MP) libraries were prepared using the Nextera mate pair library preparation kit (Illumina Inc., USA). 1 ?g of Genomic DNA was subject to tagmentation and was followed by strand displacement. Size selection tagmented/strand displaced DNA was carried out using AmpureXP beads. The libraries were validated using an Agilent Bioanalyser using DNA HS chip. The libraries were normalised, pooled and sequenced on Illumina MiSeq (Illumina Inc., USA) platform at 2 x300 bp length. The whole genome sequencing was performed by sequencing of 7.38 Gb with 73,889,924 paired end reads from paired end library, and 1.15 Gb with 3,851,788 reads from mate pair library generated from Illumina HiSeq2500 and Illumina MiSeq, respectively. The sequences were assembled using various assemblers like ABySS, MaSuRCA, Velvet, SOAPdenovo2, and ALLPATHS-LG. The assembly generated by MaSuRCA (9) algorithm was observed superior over other algorithms and hence used for scaffolding using SSPACE. Assembled draft genome sequence of S. graminicola pathotype 1 was 299,901,251 bp long, with a 47.2 % GC content consisting of 26,786 scaffolds with N50 of 17,909 bp with longest scaffold size of 238,843 bp. The overall coverage was 40X. The draft genome sequence was used for gene prediction using AUGUSTUS. The completeness of the assembly was investigated using CEGMA and revealed 92.74% proteins completely present and 95.56% proteins partially present, while BUSCO fungal dataset indicated 64.9% complete, 12.4% fragmented, 22.7% missing out of 290 BUSCO groups. A total of 52,285 predicted genes were annotated using BLASTX and 38,120 genes were observed with significant BLASTX match. Repetitive element analysis in the assembly revealed 8,196 simple repeats, 1,058 low complexity repeats and 5,562 dinucleotide to hexanucleotide microsatellite repeats.publishersversionPeer reviewe

HIV-1 Promotes Intake of Leishmania Parasites by Enhancing Phosphatidylserine-Mediated, CD91/LRP-1-Dependent Phagocytosis in Human Macrophages

Over the past decade, the number of reported human immunodeficiency virus type-1 (HIV-1)/Leishmania co-infections has risen dramatically, particularly in regions where both diseases are endemic. Although it is known that HIV-1 infection leads to an increase in susceptibility to Leishmania infection and leishmaniasis relapse, little remains known on how HIV-1 contributes to Leishmania parasitaemia. Both pathogens infect human macrophages, and the intracellular growth of Leishmania is increased by HIV-1 in co-infected cultures. We now report that uninfected bystander cells, not macrophages productively infected with HIV-1, account for enhanced phagocytosis and higher multiplication of Leishmania parasites. This effect can be driven by HIV-1 Tat protein and transforming growth factor-beta (TGF-β). Furthermore, we show for the first time that HIV-1 infection increases surface expression of phosphatidylserine receptor CD91/LRP-1 on human macrophages, thereby leading to a Leishmania uptake by uninfected bystander cells in HIV-1-infected macrophage populations. The more important internalization of parasites is due to interactions between the scavenger receptor CD91/LRP-1 and phosphatidylserine residues exposed at the surface of Leishmania. We determined also that enhanced CD91/LRP-1 surface expression occurs rapidly following HIV-1 infection, and is triggered by the activation of extracellular TGF-β. Thus, these results establish an intricate link between HIV-1 infection, Tat, surface CD91/LRP-1, TGF-β, and enhanced Leishmania phosphatidylserine-mediated phagocytosis

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Personalized Denture…Let’s make a difference!! -A clinical case report on characterized denture.

Despite the fact that solutions to functional and comfort problems are often available, successfully restoring the&nbsp;appearance of an edentulous patient remains a challenge. Esthetics pertains to the sense of the beautiful or the science&nbsp;which deduces from nature and taste the rules and principles of art. Esthetics has always exerted a profound influence in&nbsp;history. Because it has always been a prime concern of individuals, having the effect of exciting emotions of approval ordisapproval. This case report differentiate a method of restoring esthetics for a 54 year-old male patient with completely&nbsp;edentulous maxillary and mandibular arches. Patient was treated with removable maxillary and mandibular conventional&nbsp;complete denture and characterized removable maxillary and mandibular complete denture. The results were significant&nbsp;with use of characterized denture compared to conventional denture were improvements in facial esthetics and more rapid&nbsp;social integration of this patient

Study of antinociceptive activity of SSRI (fluoxetine and escitalopram) and atypical antidepressants (venlafaxine and mirtazepine) and their interaction with morphine and naloxone in mice

Objective : to study the probable site of antinociceptive action of SSRI (fluoxetine, escitalopram) and atypical antidepressants (mirtazapine, venlafaxine) and their interaction with morphine and naloxone. Materials and Methods : the study was conducted on albino mice (25-35 grams) of either sex. Different doses of morphine (0.5 and 1 mg/kg), fluoxetine (2, 5 and 10 mg/kg), venlafaxine (30, 40 and 50 mg/kg), mirtazapine (3, 5 and 7 mg/kg) and escitalopram (2.5, 5 and 10 mg/kg) were administered subcutaneously to obtain their subanalgesic doses using tail flick analgesiometer. Tail flick latencies were obtained at 15, 30, 60 and 120 min. after drug administration. Naloxone (1 mg/kg) was administered 10 minutes prior to test drug for testing antagonism. Observations : fluoxetine (5 and 10 mg/kg), mirtazapine (5 and 7 mg/kg) and venlafaxine (40 and 50 mg/kg) were found to have antinociceptive activity but not at lower doses. Escitalopram failed to show any antinociceptive activity at any of the doses used. The antinociceptive effect of all the drugs was antagonized by naloxone (1 mg/kg). Further, subanalgesic doses of fluoxetine, mirtazapine and venlafaxine showed analgesic activity with suboptimal dose of morphine (0.5 mg/kg). Result and conclusion : fluoxetine, mirtazapine and venlafaxine have antinociceptive activity whereas escitalopram doesn′t; their site of action seems to be the same as that of opioid analgesics (′mue′ receptors). However, other pathways (cholinergic, histaminic, noradrenergic, GABAergic) may be involved in mediation of their analgesic activity, deserving further elucidation. Results apparently show that these drugs may be useful in the management of pain as monotherapy or in combination with other opioids

Interforaminal hemorrhage during anterior mandibular implant placement: An overview

Implant surgery in mandibular anterior region may turn from an easy minor surgery into a complicated one for the surgeon, due to inadequate knowledge of the anatomy of the surgical area and/or ignorance toward the required surgical protocol. Hence, the purpose of this article is to present an overview on the: (a) Incidence of massive bleeding and its consequences after implant placement in mandibular anterior region. (b) Its etiology, the precautionary measures to be taken to avoid such an incidence in clinical practice and management of such a hemorrhage if at all happens. An inclusion criterion for selection of article was defined, and an electronic Medline search through different database using different keywords and manual search in journals and books was executed. Relevant articles were selected based upon inclusion criteria to form the valid protocols for implant surgery in the anterior mandible. Further, from the selected articles, 21 articles describing case reports were summarized separately in a table to alert the dental surgeons about the morbidity they could come across while operating in this region. If all the required adequate measures for diagnosis and treatment planning are taken and appropriate surgical protocol is followed, mandibular anterior region is no doubt a preferable area for implant placement