Role of Sodium-Glucose Cotransporter 2 Inhibitors for Management of Diabetes Mellitus in Renal Transplant Recipients and Management Strategies for Posttransplant Hypertension.

BACKGROUND: Diabetes mellitus and hypertension are the leading causes of cardiovascular disease in the renal transplant recipients. This review looks at the potential role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and reviews the management strategies for hypertension in this population. SUMMARY: Large-scale clinical trials are needed to study the potential cardiorenal benefits and risks of complications in renal transplant recipients. Future clinical trials are also needed to define optimal blood pressure treatment goals and therapies and how they influence graft and patient survival. KEY MESSAGES: Multiple recent prospective randomized clinical trials have shown the benefits of using SGLT2is to improve the cardiorenal outcomes in patients with chronic kidney disease with or without diabetes mellitus. Renal transplant recipients were not included in these trials due to concerns about genitourinary complications; hence, the role of these agents in this population is unclear. A number of small studies have highlighted the safety of using these agents in renal transplant recipients. Posttransplant hypertension is a complex problem requiring individualized management. Recent guidelines recommend using a calcium channel blocker or angiotensin receptor blocker as the first-line antihypertensive agents in adult renal transplant recipients.

PIEZO1 mutation: a rare aetiology for fetal ascites.

We present a case of isolated fetal ascites diagnosed at 20 weeks' gestation. No aetiology was identified on extensive prenatal workup, including prenatal microarray. The patient terminated the pregnancy at 23 weeks' gestation. Exome sequencing was performed on the products of conception, which ended up giving insight into a possible cause for the ascites. Two heterozygous missense variants of uncertain significance were identified in the PIEZO1 gene. The paternal variant has been linked to dehydrated hereditary stomatocytosis. The father of the baby suffers from haemolytic anaemia, splenomegaly and has had jaundice throughout his life. His brother and father have similar conditions. We suspect that at least one of the gene variants identified in our exome sequencing may be responsible for the illness that runs in this family, including the fetus with isolated ascites.

Nitric oxide mediated transcriptional modulation enhances plant adaptive responses to arsenic stress.

Arsenic (As) contamination in rice leads to yield decline and causes carcinogenic risk to human health. Although the role of nitric oxide (NO) in reducing As toxicity is known, NO-mediated genetic modulation in the plant during arsenic toxicity has not yet been established. We analyzed the key components of NO metabolism and the correlations between NO interaction and arsenic stress using rice as a relevant model plant. Illumina sequencing was used to investigate the NO-mediated genome-wide temporal transcriptomic modulation in rice root upon AsIII exposure during 12 days (d) of the growth period. Sodium nitroprusside (SNP) was used as NO donor. SNP supplementation resulted in marked decrease in ROS, cell death and As accumulation during AsIII stress. NO was found to modulate metal transporters particularly NIP, NRAMP, ABC and iron transporters, stress related genes such as CytP450, GSTs, GRXs, TFs, amino acid, hormone(s), signaling and secondary metabolism genes involved in As detoxification. We detected NO-mediated change in jasmonic acid (JA) content during AsIII stress. The study infers that NO reduces AsIII toxicity through modulating regulatory networks involved in As detoxification and JA biosynthesis.

A protective role for nitric oxide and salicylic acid for arsenite phytotoxicity in rice (Oryza sativa L.).

Nitric oxide (NO) and salicylic acid (SA) are important signaling molecules in plant system. In the present study both NO and SA showed a protective role against arsenite (AsIII) stress in rice plants when supplied exogenously. The application of NO and SA alleviated the negative impact of AsIII on plant growth. Nitric oxide supplementation to AsIII treated plants greatly decreased arsenic (As) accumulation in the roots as well as shoots/roots translocation factor. Arsenite exposure in plants decreased the endogenous levels of NO and SA. Exogenous supplementation of SA not only enhanced endogenous level of SA but also the level of NO through enhanced nitrate reductase (NR) activity, whether AsIII was present or not. Exogenously supplied NO decreased the NR activity and level of endogenous NO. Arsenic accumulation was positively correlated with the expression level of OsLsi1, a transporter responsible for AsIII uptake. The endogenous level of NO and SA were positively correlated to each other either when AsIII was present or not. This close relationship indicates that NO and SA work in harmony to modulate the signaling response in AsIII stressed plants.

Selenate mitigates arsenite toxicity in rice (Oryza sativa L.) by reducing arsenic uptake and ameliorates amino acid content and thiol metabolism.

Arsenic (As) is a toxic element with the potential to cause health effects in humans. Besides rice is a source of both amino acids (AAs) and mineral nutrients, it is undesired source of As for billions of people consuming rice as the staple food. Selenium (Se) is an essential metalloid, which can regulate As toxicity by strengthening antioxidant potential. The present study was designed to investigate As(III) stress mitigating effect of Se(VI) in rice. The level of As, thiolic ligands and AAs was analyzed in rice seedlings after exposure to As(III)/Se(VI) alone and As(III)+Se(VI) treatments. Selenate supplementation (As(III) 25µM+Se(VI) 25µM) decreased total As accumulation in both root and shoot (179 & 144%) as compared to As(III) alone treatment. The As(III)+Se(VI) treatment also induced the levels of non-protein thiols (NPTs), glutathione (GSH) and phytochelatins (PCs) as compared to As(III) alone treatment and also modulated the activity of enzymes of thiol metabolism. The content of amino acids (AAs) was significantly altered with Se(VI) supplementation. Importantly, essential amino acids (EAAs) were enhanced in As(III)+Se(VI) treatment as compared to As(III) alone treatment. In contrast, stress related non-essential amino acids (NEAAs) like GABA, Glu, Gly, Pro and Cys showed enhanced levels in As(III) alone treatment. In conclusion, rice supplemented with Se(VI) tolerated As toxicity with reduced As accumulation and increased the nutrition quality by increasing EAAs.

Reduced arsenic accumulation in rice (Oryza sativa L.) shoot involves sulfur mediated improved thiol metabolism, antioxidant system and altered arsenic transporters.

Arsenic (As) contamination in rice is at alarming level as majority of rice growing regions are As contaminated such as South East Asia. Restricting the As in aerial parts of rice plant may be an effective strategy to reduce As contamination in food chain. Sulfur (S), an essential element for plant growth and development, plays a crucial role in diminishing heavy metal toxicity. Current study is designed to investigate the role of S to mitigate As toxicity in rice under different S regimes. High S (5 mM) treatment resulted in enhanced root As accumulation as well as prevented its entry in to shoot. Results of thiol metabolism indicate that As was complexed in plant roots through enhanced synthesis of phytochelatins. High S treatment also reduced the expression of OsLsi1 and OsLsi2, the potent transporters of As in rice. High S treatment enhanced the activities of antioxidant enzymes and mitigated the As induced oxidative stress. Thus from present study it is evident that proper supply of S nutrition may be helpful in prevention of As accumulation in aerial parts of plant as well as As induced toxicity.

Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves.

Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

Sulfur mediated reduction of arsenic toxicity involves efficient thiol metabolism and the antioxidant defense system in rice.

Arsenic (As) contamination is a global issue, with South Asia and South East Asia being worst affected. Rice is major crop in these regions and can potentially pose serious health risks due to its known As accumulation potential. Sulfur (S) is an essential macronutrient and a vital element to combat As toxicity. The aim of this study was to investigate the role of S with regards to As toxicity in rice under different S regimes. To achieve this aim, plants were stressed with AsIII and AsV under three different S conditions (low sulfur (0.5mM), normal sulfur (3.5mM) and high sulfur (5.0mM)). High S treatment resulted in increased root As accumulation, likely due to As complexation through enhanced synthesis of thiolic ligands, such as non-protein thiols and phytochelatins, which restricted As translocation to the shoots. Enzymes of S assimilatory pathways and downstream thiolic metabolites were up-regulated with increased S supplementation; however, to maintain optimum concentrations of S, transcript levels of sulfate transporters were down-regulated at high S concentration. Oxidative stress generated due to As was counterbalanced in the high S treatment by reducing hydrogen peroxide concentration and enhancing antioxidant enzyme activities. The high S concentration resulted in reduced transcript levels of Lsi2 (a known transporter of As). This reduction in Lsi2 expression level is a probable reason for low shoot As accumulation, which has potential implications in reducing the risk of As in the food chain.

Co-application of selenite and phosphate reduces arsenite uptake in hydroponically grown rice seedlings: toxicity and defence mechanism.

The study empirically evaluates the abatement of As(III) uptake in rice seedlings (7d), in presence of Se and phosphate (P) under hydroponic condition. Positive correlation between As(III) translocation to the shoots of As(III) and P treated seedlings, shows P dependent As(III) translocation in rice. Whereas, presence of both P (5 and 10µgml(-1)) and (0.75µgml(-1)) of Se significantly reduces the As(III) uptake in rice seedlings. Application of Se alone also reduces As(III) uptake both in shoots and roots significantly, however, the seedlings suffers from lipid peroxidation. Among all the studied treatments, lower rates of P (5µgml(-1)) and Se (0.75µgml(-1)) when co-applied, significantly reduced As(III) translocation to the shoots without inflicting much toxicity in the seedlings which is manifested as significant increase in biomass with lower thio-barbituric reactive substances (TBARS). Also, significantly lower TBARS in seedlings receiving As(4)+Se(0.75) and higher TBARS in As(4)+Se(1.5), demonstrates that Se applied at lower rates (0.75µgml(-1)), lowers As induced toxicity. Higher SOD, APX and guaiacol peroxidase (POD) activities in As(4)+P(5)+Se(0.75) compared to that of As(4)+P(5) and As(4)+Se(0.75), supports that lower rate of P and Se provides tolerance towards As induced stress. The nitrogen metabolism in As(4)+P+Se treated seedlings is affected adversely at higher rates of Se and P application. Overall study concluded that application of lower rates of P (5µgml(-1)) and Se (0.75µgml(-1)) provides maximum amelioration of As(III) toxicity in rice seedlings.

A new approach to endoscopic DCR.

AIM: To compare a composite technique of endoscopic dacrocystorhinostomy with the conventional technique. METHODS: A randomised prospective study was carried in the department of Otolaryngology Maulana Azad Medical College. Thirty patient selected for Endoscopic DCR were divided into two groups, one of which underwent conventional endoscopic DCR and the other group were treated with a newer technique using cautery, cold instrumentation and laser at different steps of endoscopic DCR. The patients were followed up for nine months. RESULTS/CONCLUSION: By using cautery, cold instrumentation and laser at different steps of endoscopic DCR we were able to achieve a success rate of around 94% with this composite technique as compared to 83.3% in conventional endoscopic DCR surgery.

Uma nova abordagem para a dacriocistorrinostomia endoscópica / A new approach to endoscopic DCR

OBJETIVO: Comparar uma técnica composta de dacriocistorrinotomia (DCR) endoscópica à técnica convencional. MÉTODO: Foi realizado um estudo prospectivo no Departamento de Otorrinolaringologia da Faculdade de Medicina Maulana Azad. Trinta pacientes selecionados para DCR endoscópica foram divididos em dois grupos, um submetido à DCR endoscópica convencional e outro tratado com uma técnica mais nova com o uso de cautere, instrumentação fria e laser em diferentes etapas da DCR endoscópica. Os pacientes foram seguidos por nove meses. RESULTADOS/CONCLUSÃO: Com o uso do cautere, instrumentação fria e laser em diferentes etapas da DCR endoscópica, fomos capazes de obter taxa de sucesso de cerca de 94% com a técnica composta em comparação a 83,3% da DCR endoscópica convencional.

AIM: To compare a composite technique of Endoscopic Dacrocystorhinostomy with the conventional technique. METHODS: A randomised prospective study was carried in the department of Otolaryngology Maulana Azad Medical College. Thirty patient selected for Endoscopic DCR were divided into two groups, one of which underwent conventional Endoscopic DCR and the other group were treated with a newer technique using cautery, cold instrumentation and laser at different steps of Endoscopic DCR. The patients were followed up for Nine months. RESULTS/CONCLUSION: By using cautery, cold instrumentation and laser at different steps of Endoscopic DCR we were able to achieve a success rate of around 94% with this composite technique as compared to 83.3% in conventional Endoscopic DCR surgery.

Bilateral first and second arch anomalies: a rare presentation.

Branchial sinuses are one of the most common congenital anomalies present. They are usually unilateral; bilateral cases are present but are rare. The presentation of bilateral branchial sinus anomalies along with bilateral first arch anomalies is very rare. Here, we present a case of bilateral first arch anomalies co-existing with bilateral second arch anomalies in a patient with no related family history and no associated syndrome.

Delayed postmastoidectomy bleed from anterior tympanic artery and its management using endovascular microcoils.

Bleeding during mastoidectomy usually occurs because of injury to the dura mater and/or sigmoid sinus, which, in most cases, can be controlled easily. The other important cause is damage to the internal carotid artery during its course in the middle ear. Bleeding from the external carotid artery or a branch of it is very rare and unknown. We hereby report an extremely rare and first case of delayed torrential bleeding after modified radical mastoidectomy, which was because of infective necrosis and subsequent blowout of the anterior tympanic branch of superficial temporal artery and its management using microcoils via an endovascular approach.

Primary tuberculosis of nose with intracranial extension: a rare presentation.

Tuberculosis continues to be a major public health problem. This disease has varying presenting features. We here present a case of primary tuberculosis of the nose with intracranial extension, a very rare presenting feature of tuberculosis.

The lifeline express--a mobile ear clinic for rural India.

The objectives of this study were to review the application and feasibility of providing screening, diagnosis, medical and surgical treatment for patients with ear discharge by setting a mobile hospital in rural India. The study was retrospective. The study involved collection of data from 1992 to 2005 from patients with ear diseases. The number of patients operated on for ear conditions and the distribution of free hearing aids were also recorded. Data regarding length of postoperative stay, complications and graft failure rates was collected from local medical centers and analyzed. Out of 304,321 patients, 4,426 were operated on for ear diseases, mostly ear perforations, grommet insertions and cholesteatoma surgeries. A total of 11,913 audiometric evaluations were done and 9,045 hearing aids were distributed. An overall success rate of 78.8% was achieved for achieving a dry ear and approximately 60% reported significant improvement in audiometric thresholds.