NOS3 gene intron 4 a/b polymorphism is associated with ESRD in autosomal dominant polycystic kidney disease patients / O polimorfismo intron 4 a/b do gene NOS3 está associado à DRET em pacientes com doença renal policística autossômica dominante

Abstract Introduction: Endothelial nitric oxide synthase (eNOS) genes have been implicated in renal hemodynamics as potent regulators of vascular tone and blood pressure. It has been linked to a reduction in plasma nitric oxide levels. Several studies have recently been conducted to investigate the role of NOS3 gene polymorphisms and end-stage renal disease (ESRD). However, the results are still unclear and the mechanisms are not fully defined. As a result, we conducted a meta-analysis to examine the relationship between NOS3 gene polymorphism and ESRD in autosomal polycystic kidney disease (ADPKD) patients. Methods: To assess the relationship between NOS3 gene polymorphism and ESRD, relevant studies published between September 2002 and December 2020 were retrieved from the PubMed (Medline), EMBASE, Google Scholar, and Web of Science databases. The pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using a fixed-effect model. To assess the heterogeneity of studies, we used Cochrane's Q test and the Higgins and Thompson I2 statistics. Results: Our meta-analysis of 13 studies showed that the presence of the two NOS3 gene polymorphisms significantly increased ESRD risk in ADPKD patients with 4a/b gene polymorphism (aa+ab vs. bb: OR=1.95, 95% CI=1.24-3.09, p=0.004). In addition, no significant association was found between the NOS3 894G>T (Glu298Asp) polymorphism and the risk of ESRD in ADPKD patients (GT+TT vs. GG: OR=1.21, 95% CI=0.93-1.58, p=0.157). There was no evidence of publication bias. Conclusions: The findings of the current meta-analysis suggest that NOS3 intron 4a/b polymorphism plays a vital role in the increasing risk of ESRD in ADPKD patients.

Resumo Introdução: Genes da óxido nítrico sintase endotelial (eNOS) têm sido implicados na hemodinâmica renal como potentes reguladores do tônus vascular e pressão arterial. Tem sido vinculado a uma redução nos níveis plasmáticos de óxido nítrico. Realizou-se recentemente vários estudos para investigar o papel de polimorfismos do gene NOS3 e doença renal em estágio terminal (DRET). Entretanto, os resultados ainda não são claros e os mecanismos não estão totalmente definidos. Como resultado, realizamos meta-análise para examinar a relação entre polimorfismo do gene NOS3 e DRET em pacientes com doença renal policística autossômica dominante (DRPAD). Métodos: Para avaliar a relação entre polimorfismo do gene NOS3 e DRET, recuperou-se estudos relevantes publicados entre Setembro-2002 e Dezembro-2020 dos bancos de dados PubMed (Medline), EMBASE, Google Scholar, Web of Science. Calculamos odds ratio (OR) e intervalo de confiança (IC) de 95% utilizando modelo de efeitos fixos. Para avaliar a heterogeneidade dos estudos, utilizamos teste Q de Cochrane e estatísticas I2 de Higgins e Thompson. Resultados: Nossa meta-análise de 13 estudos mostrou que a presença dos dois polimorfismos do gene NOS3 aumentou significativamente o risco de DRET em pacientes com DRPAD com polimorfismo do gene 4a/b (aa+ab vs. bb: OR=1,95; IC 95%=1,24-3,09; p=0,004). Ademais, não encontramos associação significativa entre polimorfismo 894G>T NOS3 (Glu298Asp) e risco de DRET em pacientes com DRPAD (GT+TT vs. GG: OR=1,21; IC 95%=0,93-1,58; p=0,157). Não houve evidência de viés de publicação. Conclusões: Achados da meta-análise atual sugerem que o polimorfismo intron 4a/b do NOS3 desempenha papel vital no aumento do risco de DRET em pacientes com DRPAD.

Clinical and Genetic Spectrum of Inborn Errors of Immunity in a Tertiary Care Center in Southern India

Objectives To study the incidence, clinical manifestations, and genetic spectrum of primary immunodefciency diseases (PID)/inborn errors of immunity (IEI) in a tertiary care hospital in Southern India. Methods A retrospective analysis of all patients with a clinical suspicion of PID/IEI seen at a tertiary care hospital was performed. All patients had at least one or more warning signs of PID. Serum immunoglobulin levels and other targeted investigations were performed as warranted by the clinical presentation. All families with suspected PID were counseled and ofered genetic testing. Results A total of 225 children were evaluated for PID during the study period of 6 y. Fifty-six of them did not meet the European Society of Immunodefciencies (ESID) criteria (working defnition of clinical diagnosis) and were excluded. An IEI was found in 30/49 (61.2%) patients. The most frequent reason for referral was recurrent/unusual or serious infections (28%), or cytopenia (16%). Group IV diseases of immune dysregulation was the most common category (19%), followed by group III predominant antibody defciencies in 23/163 (14%), as per the International Union of Immunological Societies (IUIS) classifcation. Conclusions This study highlights the heterogeneity of the present cohort, the underuse of genetic tests, and eforts to provide optimal care for children with possible IEI in this center.

Comparative evaluation of diode laser and simvastatin gel in pulpotomy of primary molars A randomized clinical trial

Background: Pulpotomy is a vital pulp therapy performed in carious pulp exposures in teeth in which the inflamed coronal pulp is removed and medicament is placed to conserve the vital root pulps. Recently, simvastatin which is a cholesterol-lowering drug has been found to be associated with the pulp regenerative potential. Aim: The aim of this parallel two-arm randomized control trial was to evaluate and compare the clinical and radiographic efficacy of diode laser (DL) and simvastatin gel (SG) in pulpotomy of carious primary molars. Methods: Hundred primary molars (in 98 children, 65 males, 33 females with age 4–8 years) requiring pulpotomy were randomized into the DL or SG group. Pulpotomy was performed as per the standardized protocol; thereafter, all teeth were restored with resin modified glass ionomer cement followed by stainless steel crowns. Follow-up evaluations were done at 3 and 12 months using clinical and radiographic criteria. Statistical analysis was done using Chi-square test at a significance level of 0.05. Results: At 12 months, out of 92 teeth available for clinical and radiographic evaluation by blinded evaluators, DL group showed clinical and radiographic success rates of 76.1% and 52.1%, while SG group showed 80.4% and 65.2% success rates, respectively. There was no statistically significant difference between the efficacy of two techniques clinically (P = 0.49) or radiographically (P = 0.30). Conclusions: Both SG and DL had similar efficacy for primary tooth pulpotomy, clinically and radiographically after 12 months. Considering its ease of application and low-cost, SG can be recommended as a potential pulpotomy medicament in primary molars.

Deciphering the interaction of benzoxaborole inhibitor AN2690 with connective polypeptide 1 (CP1) editing domain of Leishmania donovani leucyl-tRNA synthetase

Leucyl-tRNA synthetases (LRS) catalyze the linkage of leucine with tRNALeu. A large insertion CP1 domain(Connective Polypeptide 1) in LRS is responsible for post-transfer editing of mis-charged aminoacyl-tRNAs.Here, we characterized the CP1 domain of Leishmania donovani, a protozoan parasite, and its role in editingactivity and interaction with broad spectrum anti-fungal, AN2690. The deletion mutant of LRS, devoid of CP1domain (LRS-CP1D) was constructed, followed by determination of its role in editing and aminoacylation.Binding of AN2690 and different amino acids with CP1 deletion mutant and full length LRS was evaluatedusing isothermal titration calorimetry (ITC) and molecular dynamics simulations. The recombinant LRS-CP1Dprotein did not catalyze the aminoacylation and the editing reaction when compared to full-length LRS. Thus,indicating that CP1 domain was imperative for both aminoacylation and editing activities of LRS. Bindingstudies with different amino acids indicated selectivity of isoleucine by CP1 domain over other amino acids.These studies also indicated high affinity of AN2690 with the editing domain. Molecular docking studiesindicated that AN2690-CP1 domain complex was stabilized by hydrogen bonding and hydrophobic interactions resulting in high binding affinity between the two. Our data suggests CP1 is crucial for the function of L.donovani LRS.

Broad ligament term pregnancy in an unscarred uterus: misdiagnosis and the challenges

A broad ligament pregnancy is a rare condition, but full term broad ligamnet pregnancy especially in an unscarred uterus is extremely rare. It is often misdiagnosed and usually finally diagnosed during surgery. Here is case of full term broad ligament pregnancy, which remained undiagnosed throughout her pregnancy, unfortunately had IUFD. Patient was referred to our hospital in view of failure of induction with increased BP records. No ultrasound was available on admission. On clinical assessment it appeared as transverse lie with IUFD. So cesarean was decided as a mode of delivery. Emergency ultrasound could just confirm IUFD with pelvic mass? Fibroid (actually deviated uterus). On laparotomy the broad ligament pseudosac had occupied entire abdomen. After delivery of baby, anatomy was found completely distorted. Highly vascular omental adhesions on fundus with difficulty in placental removal. Placenta could be traced reaching abdomen posteriorly. The first clinical impression was suspicion of placenta percreta. Uterus appeared non salvageable and hysterectomy was decided. Placenta was found lying in abdomen, adhered to bowel, omentum and fundus of uterus. The final diagnosis of broad ligament pregnancy could be made after the cut section of the uterus and anatomic evaluation. Patient required blood transfusions preoperatively .She remained stable and discharged on postoperative day nine. This case holds importance because may be outcome was different if it was a booked and investigated pregnancy. May be baby and uterus were salvageable with better outcome.

Role of sildenafil citrate therapy in pregnant women with foetal growth restriction and oligohydrominos from Northern India

Background: No specific treatment is available for severe early-onset IUGR. To best of my knowledge, very few studies have assessed the potential benefit of Sildenafil therapy targeted to improve perinatal outcomes in pregnancies complicated by severe early-onset IUGR in Indian pregnant women.Methods: The present hospital based prospective study was carried out on one hundred ANC pregnant women with early and late fetal growth restriction and oligohydrominos at Pannadhai Mahila Chikatsalya, Rabindra Nath Tagore (RNT) Medical College, Udaipur, during Jan to Dec 2017. Sildenafil citrate 25 mg three times in a day was  administered until delivery. Study subjects were subjected to fetal Doppler and ultrasound twice a week after the Sildenafil administration.Results: After sildenafil therapy, out of total 45 cases of IUGR alone, 39 cases (86.66 %) had improvement. Out of 35 cases of oligohydramnios alone, 28 cases (80 %) had improvement.  Out of 20 cases having both IUGR and Oligohydramnios 16 had improvement (80 %) and only 4 cases did not show any improvement. Among gestation age 27-30 weeks group at the time of admission, there were total 10 cases out of which 5 (50 %) had early premature delivery (32-34 weeks), 3 (30 %) had late premature delivery (34-37 weeks) and 2 cases (2 %) had term delivery i.e. between 37-39 weeks after giving sildenafil treatment.Conclusions: The findings of the present study indicate that sildenafil citrate may offer a potential therapeutic strategy to improve outcomes in pregnant women facing foetal growth restriction and oligohydrominos.

An Unusual Occurrence Of Two Palatal Canals In Maxillary First Molar - A Case Report.

The endodontist should have a detailed and thorough knowledge of root canal anatomy to effectively perform endodontic treatment, negligence to which might lead to endodontic failures. Maxillary first molars show considerable variation in root canal anatomy with respect to number of roots and number of canals. Literature states that canal variations can reach up to 33% in maxillary first molars. There is an overall low prevalence (<2%) of anatomic variations in the palatal canal of maxillary molars among different populations. This case report deals with one such palatal canal variations in maxillary first molar with 4 canals: 2 separate palatal canals, mesiobuccal and distobuccal canal and its management.. Clinician awareness on careful assessment of extra palatal canal in maxillary molar teeth using conventional radiograph has been reinforced in this case report to achieve long term success in endodontic treatment.

Study of Malaria Parasite with Special Reference to Liver Function Test of the Patient Attending at TMU Hospital Moradabad (U.P)

Background: Malaria is an important infectious vector borne disease caused by a Plasmodium species. Liver involvement in severe Plasmodium falciparum infection is commonly a significant cause of morbidity and mortality among humans. Objective: In this study, we show the correlation of malaria positive cases with liver derangement. Methods: The present study had been conducted in Teerthankar Mahaveer Medical college Hospital and Research Center, Moradabad, U.P. from February 2014 to January 2015  on both IPD & OPD patients .Results: The present study included  200 clinically suspected cases of Malaria with derange Liver function. 67.5% patients show increased level of Total and indirect bilirubin followed by 45% of patient shows increased level of direct bilirubin. 27.5% patient’s shows increased level SGPT followed by 40% of SGOT. Conclusions: Deranged liver functions are commonly seen as a complication of severe malarial infection.

Evaluation of matrix metalloproteinase and cysteine cathepsin activity in dentin hybrid layer by gelatin zymography.

Aim: The aim of this study was to comparatively assess the gelatinolytic activity of matrix metalloproteinases(MMPs) and Cysteine Cathepsins (CCs) in the adhesive interface using etch and rinse adhesive at different time intervals using zymographic technique. Methodology: Twenty freshly extracted non-carious human third molars were used in this study. Occlusal surfaces were ground flat and 1mm thick horizontal dentin slabs were obtained from each tooth using a diamond disc. The dentin surface was polished with 600-grit silicon-carbide paper. Five out of 20 samples were directly pulverized. In the remaining fifteen samples, the dentin was etched and adhesive was applied and light cured according to the manufacturer’s instructions. A 1mm thick flowable composite was build up and light cured. Bonded specimens were cut vertically into 3 to 4 dentin slabs by means of diamond disc to expose the adhesive/ dentin interfaces. These were then ground down to 500 μm thick resin-dentin interface using a hard tissue microtome. These sections were then pulverised into powder. Following this, every five samples were subjected to zymographic analysis after 1 day, 7 days and 21 days. Results: Zymograms showed clear, thicker bands on all three isoforms in the etched samples compared to control samples at 1st and 7th day intervals and became inactive at 21st day for all three isoforms. MMP 9 activity was relatively higher when compared to CCs and MMP 2. Conclusion: Etch and rinse adhesive activated MMPs and CCs within the hybrid layer that remained active till 7th day and no gelatinolytic activity was found on 21st day and MMPs are more active compared to CCs and MMP-2.

To study the Prevalence and Antibiotic Sensitivity Pattern of Isolated Bacteria from the Blood, Urine, CSF and Pus Samples in a Tertiary Care Teaching Hospital

Introduction: The worldwide escalation in both community- and hospital-acquired antimicrobial-resistant bacteria is threatening the ability to effectively treat patients, emphasizing the need for continued surveillance, more appropriate antimicrobial prescription, prudent infection control, and new treatment alternatives. Objective: To study the prevalence of bacteria from the different samples (Blood, Urine, CSF, PUS) and to examine the antibiotic sensitivity pattern of isolated organisms. Methods: Around n=150 samples of Urine, Blood, CSF and Pus sample were collected from the patient attending Teerthanker Mahaveer medical Hospital college and Research Centre. Results: Out of 150 clinical samples, highest number of isolates were gram-positive, Staphylococcus aureus n=47 (31.33%) followed by E. Coli n=37(24.66%), Klebseilla n=33(22.00%), Pseudomonas n=11(07.33%). S. aureus was highly sensitive to Gentamycin (88.09%) and least sensitive to Co-trimoxazole (14.28%). Tobramycin & Linezolid were 95.23% sensitive followed by Amikacin (90.47%), Meropenem (90.47%), Levofloxacin (88.09%). Conclusion: In our study Staphylococcus aureus to be most common isolates followed by Escherichia coli, Klebseilla, Pseudomonas, Citrobacter, Proteus.

Amniotic Fluid Embolism.

Amniotic Fluid Embolism (AFE) is a potentially fatal rare obstetric complication. In this paper, the death of a 30-year old apparently healthy parturient due to AFE is reported. She underwent Lower Segment Caesarean Section (LSCS) under spinal anaesthesia but after about half an hour of the operative procedure, she developed features of Acute Respiratory Distress Syndrome (ARDS) and shock, and died within five hours of the onset of the symptoms. The sudden death of an apparently healthy parturient may lead to medical negligence claims by the relatives. In developing countries, it still remains a post-mortem diagnosis and in the present case, histopathological examination findings helped in coming to a conclusive opinion of AFE.

Social Exclusion of Students with Visual Impairments at a Tertiary Institution in KwaZulu-Natal

Objectives: People with visual impairment experience exclusion and marginalisation from family; mainstream school; the community and university. The experience of social exclusion is multistructural; multidimensional and complex. This article is based on a study that aimed to describe the social exclusion of students with visual impairment at a tertiary institution where the authors are employed.Design: The study was qualitative. It used an exploratory design to provide compelling data on the insider perspectives of students.Setting and subjects: Fifteen students participated in the study; of whom nine were men and six women. Eleven students were partially sighted and four were blind. All the subjects were from the university where the authors are employed.Results: The study established that participants' exclusion from access to opportunities and development left them psychologically; socially; financially and emotionally scarred.Conclusion: The study established that visual impairment and poverty were related and that women experienced oppression on two counts. The first was because of their disabled status and the second was oppression by other female students at the university. Recommendations are for changes within families; schools; communities and universities

Gilbert's syndrome

Gilbert's syndrome is a form of hereditary non-hemolytic jaundice transmitted by autosomal dominant pattern. Since there is low glucuronyl transferase activity in the liver there is a risk for anesthetic toxicity with a possibility of a catastrophic outcome. It is important for the anesthesiologists to understand the pathophysiology of the disease and the conditions leading to decreased glucuronyl transferase activity. We report a case of Gilbert's syndrome with hypertension, operated for cholelithiasis under thoracic epidural analgesia supplemented with transcutaneous electrical nerve stimulation in the postoperative period. Minimal administration of intravenous drugs, maintaining the organ perfusion and postoperative pain relief using epidural anesthesia offers a safe conduct of anesthesia which can be considered as an alternative to general anesthesia

Clinico-hematological profile of Pancytopenia in Manipur, India

To determine the etiology and clinical profile of pancytopenia in Manipur, India Prospective study Department of Pathology, Regional Institute of Medical Sciences [RIMS], Imphal, Manipur, a renowned referral hospital in north-east India Fifty cases of pancytopenia were examined in the department of Pathology, RIMS hospital, Imphal, Manipur,India, during a two year period from November 1999 to October 2001. Bone marrow aspiration and examination Correlation between pancytopenia and clinico-hematological diagnosis Hypoplastic anemia was the commonest cause of pancytopenia [22%] followed by megaloblastic anemia and myelodysplastic syndrome [18% each]. The other causes include subleukemic / aleukaemic leukemia [14%], iron deficiency anemia [8%], HIV infection [6%], congenital dyserythropoietic anemia [CDA, 4%], pyrexia of unknown origin [PUO] with hepatosplenomegaly [4%], congenital hepatic fibrosis [2%] and systemic lupus erythomatosus [SLE, 2%]. Rare causes of pancytopenia including iron deficiency anemia, HIV infection and CDA have to be kept in mind as possible disorders manifesting as pancytopenia

Occurrence of Cucumber mosaic virus on vanilla (Vanilla planifolia Andrews) in India.

Cucumber mosaic virus (CMV) causing mosaic, leaf distortion and stunting of vanilla (Vanilla planifolia Andrews) in India was characterized on the basis of biological and coat protein (CP) nucleotide sequence properties. In mechanical inoculation tests, the virus was found to infect members of Chenopodiaceae, Cucurbitaceae, Fabaceae and Solanaceae. Nicotiana benthamiana was found to be a suitable host for the propagation of CMV. The virus was purified from inoculated N. benthamiana plants and negatively stained purified preparations contained isometric particles of about 28 nm in diameter. The molecular weight of the viral coat protein subunits was found to be 25.0 kDa. Polyclonal antiserum was produced in New Zealand white rabbit, immunoglobulin G (IgG) was purified and conjugated with alkaline phosphatase enzyme. Double antibody sandwich-enzyme linked immunosorbent assay (DAS-ELISA) method was standardized for the detection of CMV infection in vanilla plants. CP gene of the virus was amplified using reverse transcriptase-polymerase chain reaction (RT-PCR), cloned and sequenced. Sequenced region contained a single open reading frame of 657 nucleotides potentially coding for 218 amino acids. Sequence analyses with other CMV isolates revealed the greatest identity with black pepper isolate of CMV (99%) and the phylogram clearly showed that CMV infecting vanilla belongs to subgroup IB. This is the first report of occurrence of CMV on V. planifolia from India.

Plasmodium falciparum: detection and strain identification of Indian isolates by polymerase chain reaction.

The polymerase chain reaction (PCR) was employed for detection and strain identification of P. falciparum in a comparative field study of Indian isolates. The primers were selected from highly conserved regions flanking the variable, tandemly repeated regions of highly polymorphic cell surface antigens, major merozoite surface antigen-1 (MSP-1), major surface antigen-2 (MSP-2), circumsporozoite surface antigen (CSP) and ring-infected erythrocyte surface antigen (RESA). Out of the 52 microscopically positive P. falciparum infected field samples, 47 samples were positive by PCR. Variation in the size of the amplified products was observed using MSP-1, MSP-2 specific primers respectively in different field isolates of P. falciparum, but CSP and RESA did not exhibit any variation in size of the amplified product. The multiplex PCR results demonstrated that amplified products from these surface antigens vary in size and there is a specific pattern for each strain and this could be utilized to identify a particular field isolate. One P. falciparum infected field sample detected by the above PCR method was found to be a mixed infection by two different strains. Five microscopically positive P. vivax infeced samples were also analyzed by PCR method using P. falciparum cell surface antigen (MSP-2) specific primers. PCR results showed one P. vivax infected sample was positive when P. falciparum specific primers were used, this could be due to inaccurate and reduced limit of detection of Plasmodial species by microscopic examination.