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A 31-year-old primigravida, with spontaneous singleton pregnancy, presented in 21 weeks of gestation with abdominal pain. Abdominal ultrasound (USS) and Magnetic Resonance Imaging (MRI) showed a 12 × 14cm large complex lesion arising from the right ovary suspicious for an ovarian malignancy. The radiological staging demonstrated no further metastatic disease; however, it also revealed a 6 cm lesion in the contralateral ovary, consistent with a dermoid cyst. After tumour board discussion the patient underwent a mid-line laparotomy with right oophorectomy, cytology, and peritoneal and omental staging, under oral tocolysis with indomethacin. The left presumed ovarian dermoid was left in situ to avoid additional surgical and obstetrical morbidity. Histology confirmed a grade 3 immature teratoma with primitive neuroepithelium focally present on the capsular surface and atypical cells in the cytology amounting to a stage 1 C2 disease at least. Due to high-risk disease, she was offered adjuvant treatment. The patient received one cycle of intravenous paclitaxel, etoposide, and cisplatin chemotherapy, in an adjuvant setting. She underwent an elective caesarean section at 36 weeks, with the safe delivery of a healthy baby girl. After 6 weeks of her delivery, she received three further cycles of etoposide, and cisplatin to complete her course of adjuvant chemotherapy. Three months after the last chemotherapy cycle, she underwent a laparoscopic removal of the left ovarian dermoid that had increased in size to 8 cm. Final histology revealed no immature elements. To this point, 2 years after initial diagnosis, both mother and child are healthy with no long-term complications. The patient has resumed her normal menstrual cycle and being in remission, she wishes soon to try for a second child. To our knowledge, this is the only reported case of ovarian immature teratoma in pregnancy treated successfully with surgery and adjuvant iv paclitaxel, etoposide, and cisplatin chemotherapy regime.

Placental Site Trophoblastic Tumor (PSTT) is a rare malignancy that often presents with extensive disease and can be resistant to traditional treatments. We present the case of a woman with stage IV PSTT who was initially managed with neoadjuvant chemotherapy followed by tumor debulking. Adjuvant therapy was guided by further pathologic analysis that revealed high levels of staining for PD-L1 as well as the presence of tumor infiltrating lymphocytes (TILs). Subsequently, the patient was treated with traditional chemotherapy with the EP/EMA regimen with the addition of pembrolizumab. The patient’s treatment course was complicated by the development of pulmonary arteriovenous malformations, autoimmune thyroiditis thought to be secondary to immunotherapy, and significant tinnitus secondary to platinum agents. Currently the patient is in follow up and remains in a complete remission.

NH 2 -functionalized metal-organic frameworks (NH 2 -functionalized MOFs) can abate organic pollutants, predominantly favored by their chemical, mechanical, and thermal stabilities. The present review stated the chemistry of identifying NH 2 -functionalization and its role in enhancing the properties of bare MOFs. The integration of the amine group bestows several advantages: 1.) enabling band structure modification, 2.) establishing strong metal-NH 2 bonds, 3.) preserving MOF structures from reactive oxygen species, and 4.) shielding MOF structures against pH alterations. Consequently, the NH 2 -functionalized MOFs are promising materials for the photodegradation of organic contaminants. The following section illustrates the two approaches (pre-synthetic and post-synthetic) for NH 2 -functionalized MOFs. Nevertheless, specific intrinsic limitations, entailing a high recombination rate of charge carriers and inadequate optical adsorption, restrain the applicability of NH 2 -functionalized MOFs. Accordingly, the succeeding segment presents strategies to elevate the photocatalytic activities of NH 2 -functionalized MOFs via heterojunction fabrication. The importance of the NH 2 -functionalized MOFs-based heterojunction has been evaluated in terms of the effect on the enhancement of charge separation, optical adsorption, and redox ability of charge carriers. Subsequently, the potential application for organic pollutant degradation via NH 2 -functionalized MOFs-based heterojunctions has been scrutinized, wherein the organic pollutants. Eventually, the review concluded with challenges and potential opportunities in engaging and burgeoning domains of the NH 2 -functionalized MOFs-based heterojunctions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Over the years, bioaccumulation of hazardous chemicals in the food chain has become a critical issue, resulting in numerous health risks. Environmental mitigation aims to clean up contaminated sites and eliminate hazardous materials from the air, water, or soil to restore the site to its original and safe condition. Pesticides constitute one of the most dangerous environmental pollutants which are generally used to increase crop production. Addressing the removal or treatment of pesticides has become pivotal in mitigating environmental threats. Diverse remediation methods are employed to protect the environment and public health. Graphene-based materials have emerged as promising candidates with exceptional properties, including excellent adsorption capacity due to their high surface area, strong hydrophilicity, and tunable properties. Owing to these properties, they have been attracting major research attention in the field of design and fabrication of materials for the mitigation of pesticides from the environment such as from contaminated food, water and other samples. Various physical, chemical and biological extraction techniques are adopted to remove pesticides. This review article provides an insight into the potential role of graphene-based materials in the environmental remediation of pesticides. We have focused on the removal of Organophosphates, Organochlorines, Carbamates and Pyrethroids present in water, fruit, vegetable and other samples, highlighting the urgent need for environmental remediation. While graphene-based materials hold potential for pesticide remediation, addressing challenges in scalable production, assessing long-term sustainability, and mitigating potential environmental impacts are critical steps for successful large-scale applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Obesity has become a worldwide public health issue. Many obese patients concomitantly suffer with heart failure with reduced ejection fraction. There have been reports of improvement in left ventricular systolic function following significant weight loss after bariatric surgery. We sought to investigate this phenomenon within our institution. This was a retrospective single-center analysis of patients conducted between 2010 and 2019. The study included patients with morbid obesity (body mass index >35 kg/m 2 and an obesity-related comorbid condition, or a body mass index >40 kg/m 2 ) and left ventricular systolic dysfunction. Analysis was performed based on systolic function recovery after bariatric surgery and advanced heart failure therapy. Of the 190 patients identified, 57 patients had a left ventricular ejection fraction of <40%. Twenty-two patients underwent bariatric surgery, of which at least 54.5% had systolic function recovery. Patients who had systolic function recovery after bariatric surgery were significantly older (51.58 years ± 10.48 vs 32.3 years ± 5.03, P = 0.001). Older age and female sex were predictors of systolic function recovery. In patients with obesity and heart failure with reduced ejection fraction, weight loss following bariatric surgery was shown to be correlated with significant improvement in left ventricular systolic function., (Copyright © 2022. Published by Elsevier Inc.)

There is an urgent need to detect depression using a non-intrusive approach that is reliable and accurate. In this paper, a simple and efficient unimodal depression detection approach based on speech is proposed, which is non-invasive, cost-effective and computationally inexpensive. A set of spectral, temporal and spectro-temporal features is derived from the speech signal of healthy and depressed subjects. To select a minimal subset of the relevant and non-redundant speech features to detect depression, a two-phase approach based on the nature-inspired wrapper-based feature selection Quantum-based Whale Optimization Algorithm (QWOA) is proposed. Experiments are performed on the publicly available Distress Analysis Interview Corpus Wizard-of-Oz (DAICWOZ) dataset and compared with three established univariate filtering techniques for feature selection and four well-known evolutionary algorithms. The proposed model outperforms all the univariate filter feature selection techniques and the evolutionary algorithms. It has low computational complexity in comparison to traditional wrapper-based evolutionary methods. The performance of the proposed approach is superior in comparison to existing unimodal and multimodal automated depression detection models. The combination of spectral, temporal and spectro-temporal speech features gave the best result with the LDA classifier. The performance achieved with the proposed approach, in terms of F1-score for the depressed class and the non-depressed class and error is 0.846, 0.932 and 0.094 respectively. Statistical tests demonstrate that the acoustic features selected using the proposed approach are non-redundant and discriminatory. Statistical tests also establish that the performance of the proposed approach is significantly better than that of the traditional wrapper-based evolutionary methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Curcumin has shown remarkable therapeutic utilization for various medical conditions. Still, its limited chemical stability and rapid hydrolysis capped its applications to a certain extent. Approaches have been made in the past to surpass these shortcomings by encapsulating the drug in surfactant-based micelles or liposomes and so far, natural surfactants have been used to do this bidding. Through this report, we are presenting curcumin entrapped inside synthetic metal-based liposomal assembly (metallosomes) based on hybrid-surfactants known as metallosurfactants (MS). Three metallosomes i.e. metallosomes (a), (b), and (c) were synthesized with increasing cholesterol (Chl) ratio w.r.t MS (MS:Chl 1:0, 1:0.5, and 1:1). Firstly, the membrane properties of the metallosomes were studied in the absence of the drug. The studies confirmed the direct influence of Chl concentration on the membrane properties and the metallosomes were found to be more hydrophobic, rigid, homogenous, stable, and less fluid with Chl incorporation. These studies were proven beneficial when drug-loaded metallosomes were studied and metallosomes (c), with the highest Chl content, emerged as the maximum drug loader due to their most hydrophobic nature. However, the drug was released at the slowest rate for this metallosomal system due to its less fluid and more rigid nature. On the other hand, these metallosomes were more efficient for shielding entrapped drug from acidic and alkaline environs as lesser drug degradation was observed in the experiments compared to the free curcumin. These metallosomes also exhibited efficient interactional behavior with bacterial (MRSA) DNA., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Epoxide functional group is a part of several natural as well as synthetic compounds. Irrespective of the role of epoxide group in drug efficacy and the use of epoxide compounds as tool molecules, uncertainty prevails over concerns associated with the reactivity of this functional group. Herein, we compile information about epoxide-based medicinal compounds and biochemical probes and look into the related advantages and challenges of the epoxide functional group. As a whole, this study is focussed on analyzing the strategies which have been adopted for the successful development of epoxide-based compounds within drug discovery programs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Keeping in view the involvement of inflammation in the pathogenesis of several diseases including cancer, diabetes, neurodegenerative disorders and rheumatoid arthritis, herein, we review the processes for the initiation of inflammation and the treatment measures. While focusing on the cyclooxygenase mediated arachidonic acid metabolic pathways, biochemistry of inflammatory prostaglandins is discussed. The data corresponding to efficacy, pharmacokinetic profile and the side effects of the available natural and synthetic anti-inflammatory drugs is reviewed. Moreover, the given information for the drug-based design of new anti-inflammatory agents may help in the development of more potent and safe molecules., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In advanced biomedical diagnosis, various supramolecular assemblies based on inorganic-organic hybrids have found great interest as functional materials. These assemblies describe a new field of metallovesicles where the introduction of metal ions enables the chemical manipulation of assemblies in terms of their structural stability, redox activity, and pH stability. Additionally, they mimic the elaborative architecture of natural liposomal assemblies and exhibit hierarchical morphologies, and promise novel functions. With the constant developments in this field, various supramolecular assemblies such as MCsomes, Polymersomes, and Metallosomes, etc. came into existence. These hybrid assemblies have been utilized for several applications such as drug delivery, MRI contrasting, DNA delivery, and catalytic activity. The key advantage of these assemblies is their ability to deliver therapeutics to specific locations due to their biomimetic properties and release their contents at the desired time. Hence, they provide a valuable platform for the treatment of a variety of diseases. Through the present article, we intend to provide insights into the latest developments made in this field. This modularity underscores the tremendous promise of supramolecular assemblies as an emerging interdisciplinary research branch at the interface of chemistry and biological sciences., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: A large proportion of infants in low- and middle-income countries are stunted. These infants are often fed complementary foods that are low-quality, primarily in terms of protein and micronutrients., Objectives: We aimed to test 2 milk-cereal mixes supplemented with modest and high amounts of protein during 6-12 mo of age, compared with no supplementation, for their effect on length-for-age z score (LAZ) at 12 mo of age., Methods: Eligible infants (6 mo plus ≤29 d) were randomly assigned to either of the 2 interventions (modest- and high-protein) or a no supplement group. The milk-cereal mixes provided ∼125 kcal, 30%-45% energy from fats, and 80%-100% RDA of multiple micronutrients (MMN). The modest-protein group received 2.5 g protein [protein energy ratio (PER): 8%; 0.75 g from milk source] and the high-protein group received 5.6 g protein (PER: 18%, 1.68 g from milk source). One packet was given daily for 180 d. Counseling on continued breastfeeding and optimal infant-care practices was provided to all., Results: We enrolled 1548 infants (high-protein: n = 512; modest-protein: n = 519; and no supplement: n = 517). Compared with the no supplement group, there was an improvement in LAZ [adjusted mean difference (MD): 0.08; 95% CI: 0.01, 0.15], weight-for-age z score (MD: 0.12; 95% CI: 0.06, 0.19), weight-for-length z score (MD: 0.11; 95% CI: 0.02, 0.19), and midupper arm circumference z score (MD: 0.10; 95% CI: 0.02, 0.18) in the high-protein group at 12 mo of age. No significant differences for these anthropometric indicators were noted between the modest-protein and no supplement groups or between the high- and modest-protein groups., Conclusions: Cereal mixes with higher amounts of milk-based protein and MMN may lead to improvement in linear growth and other anthropometric indexes in infants, compared with no supplementation.This trial was registered at ctri.nic.in as CTRI/2018/04/012932., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Immunotherapy is implemented as an important treatment strategy in various malignancies. In cancer, immunotherapy is employed for successful killing of tumor cells with high specificity and greater efficacy, with minimum side effects. Despite various available strategies, cellular immunotherapy including innate (NK cells, macrophages, dendritic cells) and adaptive (B cells and T cells) immune cells plays a critical role in tumor microenvironment. Since past few years, many drugs targeting immune checkpoint proteins including CTLA-4 and PD-1/PD-L1 have been investigated as immunotherapy approach against cancer but complete effectiveness still remains a question, as diverse mechanisms involved in tumorigenesis may result in the development of cancer cell resistance. Number of evidences have highlighted the significant role of non-coding RNAs (ncRNAs) in regulating multiple stages of cancer initiation, progression & immunity. ncRNAs comprises 98% human transcriptome and are basically considered as dark genome. Among ncRNAs, miRNAs and lncRNAs have been extensively studied in regulating diverse processes of cancer tumorigenesis. Upregulation of oncogenic and downregulation of tumor suppressive miRNAs/lncRNAs has been reported to facilitate the cancer progression and invasiveness. This chapter summarizes how an interplay between ncRNAs and immune cells in cancer pathogenesis can be therapeutically targeted to improve current treatment regimen. Strategies should be employed to improve the efficacy and reduce off-target effects of ncRNA based immunotherapy. Henceforth, combination of ncRNAs and available immunotherapy can be argued to enhance the efficacy of existing immunotherapeutic approaches against cancer to improve patient's survival., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Staphylococcus aureus is a common cause of skin infections, food poisoning and severe life-threatening infections. Methicillin-Resistant Staphylococcus aureus (MRSA) is known to cause chronic nosocomial infections by virtue of its multidrug resistance and biofilm formation mechanisms. The antimicrobial resistance owned by S. aureus is primarily due to efflux pumps and formation of microbial biofilms. These drug resistant, sessile and densely packed microbial communities possess various mechanisms including quorum sensing and drug efflux. Quorum sensing is a cooperative physiological process which is used by bacterial cells for social interaction and signal transduction in biofilm formation whereas efflux of drugs is derived by efflux pumps. Apart from their significant role in multidrug resistance, efflux pumps also contribute to transporting cell signalling molecules and due to their occurrence; we face the frightening possibility that we will enter the pre-antibiotic era soon. Compounds that modulate efflux pumps are also known as efflux pump inhibitors (EPI's) that act in a synergistic manner and potentiate the antibiotics efficacy which has been considered as a promising approach to encounter bacterial resistance. EPIs inhibit the mechanism of drug efflux s as well as transport of quorum sensing signalling molecules which are the supreme contributors of miscellaneous virulence factors. This review presents an accomplishments of the recent investigations allied to efflux pump inhibitors against S. aureus and also focus on related correspondence between quorum sensing system and efflux pump inhibitors in terms of S. aureus and MRSA biofilms that may open a new avenue for controlling MRSA infections., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Breast tumors enriched with breast cancer stem cells (BCSCs), play a crucial role in metastasis and tumor relapse. Hence, targeting BCSCs may lead to efficacious breast cancer therapy. BCSCs have a unique expression of stemness markers, including Nanog, POU5F1, SOX2, and CD44, which play a vital role in cancer stem cell properties. However, the regulation of microRNAs (miRNAs)-mediated cancer stem cell marker expressions is largely unclear., Methods: MIENTURNET was used to predict miRNA-target interactions. miR-TV, UALCAN and GEPIA databases were used to analyze the expression of miR-145-5p and SOX2. Survival analysis was obtained by cBioportal, KM plotter and Breast Cancer Gene-Expression Miner. RNAComposer was used to perform miRNA-mRNA duplex prediction. In vitro mRNA and miRNA analysis was performed by qRT-PCR., Results: It was observed that miR-145-5p was the common miRNA targeting stemness markers. miR-145-5p expression was found to be lower in breast cancer patients compared to healthy subjects. Based on survival analysis, low expression of miR-145-5p and high expression of SOX2 led to a poor overall survival rate in breast cancer patients. Pathway enrichment analysis indicated that SOX2 was highly enriched with transcription factors. Moreover, SOX2 expression level was also upregulated in axillary metastatic lymph nodules. Further, in vitro ectopic expression of miR-145-5p by its mimic downregulated the SOX2 expression compared to the control mimic. Overall, SOX2 was a direct target for miR-145-5p as per the binding and minimal-free energy., Conclusions: In this study, miR-145-5p targeting SOX2 was identified as a potential predictive biomarker for breast cancer stemness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Gestational trophoblastic disease (GTD) is subclassified into hydatidiform mole (HM), gestational trophoblastic tumours (GTT) and non-neoplastic trophoblastic lesions. HM, partial and complete, originate from villous trophoblast and are considered as preneoplastic conditions. The risk for the development of persistent GTD, mostly as invasive HM, ranges from 0.5% to 20%, which depends on the type of molar pregnancy. The risk of development of trophoblastic tumour after PHM is <0.5% and 2%-3% after CHM. GTT represent a spectrum of neoplasms that originates from the intermediate, largely extravillous, trophoblast and these include choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), epithelioid trophoblastic tumour (ETT) and mixed trophoblastic tumour. Among tumour like conditions, exaggerated placental site reaction (EPSR) and placental site nodule (PSN) (s)/plaque (s) are included. The morphological appearances of HM can be mimicked by abnormal (non-molar) villous lesions, and similarly, GTT can be mimicked both by non-malignant tumour-like conditions and non-gestational tumours with trophoblastic differentiation, which add to the diagnostic dilemma of these rare conditions. GTT have a favourable prognosis and better response to specific chemotherapeutic regimens when compared with non-gestational malignant genital tract neoplasms. The correct diagnosis and classification of these rare conditions are therefore important. This article focusses on the morphological appearances, immunocytochemistry as an aid in the diagnosis and the changes in current WHO classification of GTDs (WHO 2020)., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

Background: A human chorionic gonadotropin (hCG) cut-off of ≤300 IU/l for starting actinomycin D (ActD) in post-molar gestational trophoblastic neoplasia (GTN) patients developing methotrexate resistance (MTX-R) reduced the number of women needing toxic multi-agent chemotherapy (etoposide, MTX and ActD alternating weekly with cyclophosphamide and vincristine; EMA/CO) without affecting survival. Here we assess whether an increased hCG cut-off of ≤1000 IU/l spares more women EMA/CO., Patients and Methods: All post-molar GTN patients treated with first-line methotrexate and folinic acid (MTX/FA) were identified in a national cohort between 2009 and 2016. Data collected included age, FIGO score, the hCG levels at MTX-R, and treatment outcomes., Results: In total, 609 GTN patients commenced treatment with MTX/FA achieving a complete response in 57% (348/609). Resistance developed in 25.1% (153/609) at an hCG ≤ 1000 IU/l and switching to ActD achieved remission in 92.8% without any major toxicity with the remaining 7.2% remitting on EMA/CO. Comparative analysis of patients switching at an hCG <100 versus 100-300 versus 300-1000 IU/l revealed a significant fall in the cure rate with second-line ActD from 97% (93/96) to 87% (34/39) to 78% (14/18), respectively, P = 0.009. However, by increasing the hCG cut-off from ≤300 to ≤1000 IU/l, 14 patients were spared EMA/CO chemotherapy. Moreover, in the present series, all post-molar GTN remain in remission., Conclusion: This study demonstrates that increasing the hCG cut-off from ≤300 to ≤1000 IU/l for choosing patients for ActD following MTX-R spares more women with GTN from the greater toxicity of EMA/CO without compromising 100% survival outcomes., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Identification and repurposing of therapeutic and preventive strategies against COVID-19 are rapidly undergoing. Several medicinal plants from the Himalayan region have been traditionally used to treat various human disorders. Thus, in our current study, we intended to explore the potential ability of Himalayan medicinal plant (HMP) bioactives against COVID-19 using computational investigations., Methods: Molecular docking was performed against six crucial targets involved in the replication and transmission of SARS-CoV-2. About forty-two HMP bioactives were analyzed against these targets for their binding energy, molecular interactions, inhibition constant, and biological pathway enrichment analysis. Pharmacological properties and potential biological functions of HMP bioactives were predicted using the ADMETlab and PASS webserver respectively., Results: Our current investigation has demonstrated that the bioactives of HMPs potentially act against COVID-19. Docking results showed that several HMP bioactives had a superior binding affinity with SARS-CoV-2 essential targets like 3CL pro , PLpro, RdRp, helicase, spike protein, and human ACE2. Based on the binding energies, several bioactives were selected and analyzed for pathway enrichment studies. We have found that selected HMP bioactives may have a role in regulating immune and apoptotic pathways. Furthermore, these selected HMP bioactives have shown lower toxicity with pleiotropic biological activities, including anti-viral activities in predicting activity spectra for substances., Conclusions: Current study results can explore the possibility of HMPs as therapeutic agents against COVID-19., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In lower-middle-income settings, growth faltering in the first 6 mo of life occurs despite exclusive breastfeeding., Objective: The aim was to test the efficacy of an approach to improve the dietary adequacy of mothers during lactation and thus improve the growth of their infants., Methods: Eligible mother-infant dyads (infants ≤7 d of age) were randomly assigned to either intervention or control groups. Mothers in the intervention group received snacks that were to be consumed daily, which provided 600 kcal of energy-with 25-30% of energy derived from fats (150-180 kcal) and 13% of energy from protein (80 kcal). Micronutrients were supplemented as daily tablets. We provided counseling on breastfeeding and infant-care practices to mothers in both groups. The primary outcome was attained infant length-for-age z scores (LAZ) at 6 mo of age. Secondary outcomes included exclusive breastfeeding proportion reported by the mother, maternal BMI and midupper arm circumference (MUAC), hemoglobin concentrations in mothers and infants, and the proportion of anemic infants at 6 mo of age., Results: We enrolled 816 mother-infant dyads. The intervention did not achieve a significant effect on LAZ at 6 mo (adjusted mean difference: 0.09; 95% CI: -0.03, 0.20). Exclusive breastfeeding at 5 mo was higher (45.1% vs. 34.5%; RR: 1.31; 95% CI: 1.04, 1.64) in the intervention group compared with the controls. There were no significant effects on mean hemoglobin concentration or the proportion of anemic infants at 6 mo of age compared with the control group. We noted significant effects on maternal nutritional status (BMI, MUAC, hemoglobin concentration, and proportion anemic)., Conclusions: Postnatal supplementation of 600 kcal energy, 20 g protein, and multiple micronutrients daily to lactating mothers did not affect infant LAZ at age 6 mo. Such supplementation may improve maternal nutritional status. This trial was registered at Clinical Trials Registry-India as CTRI/2018/04/013095., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

We applied a cobalt-porphyrin modified DNA as electrochemical marker, which was attached to nanoparticles, to detect specific DNA sequences. We compare the performance of gold and silver NPs in oligonucleotide sensors to determine if a change in metal will lead to either higher sensitivity or different selectivity, based on the redox behaviour of silver vs. gold. Surprisingly, we find that using either gold or silver NPs yields very similar overall performance. The electrochemical measurements of both types of sensors show the same redox behaviour which is dominated by the cobalt porphyrin, indicating that the electron pathway does not include the NP, but there is direct electron transfer between the porphyrin and the electrode. Both sensors show a linear response in the range of 5 × 10 -17 -1 × 10 -16 M; the limit of detection (LOD) is 3.8 × 10 -18 M for the AuNP sensor, and 5.0 × 10 -18 M for the AgNP sensor, respectively, which corresponds to the detection of about 20-50 DNA molecules in the analyte. Overall, the silver system results in a better DNA economy and using cheaper starting materials for the NPs, thus shows better cost-effectivness and could be more suitable for the mass-production of highly sensitive DNA sensors., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: In vascular and cardiac surgery, the ability to maintain haemostasis and seal haemorrhagic tissues is key. Fibrin and thrombin based sealants were introduced as a means to prevent or halt bleeding during surgery. Whether fibrin and thrombin sealants affect surgical outcomes is poorly established. A systematic review and meta-analysis was performed to examine the impact of fibrin or thrombin sealants on patient outcomes in vascular and cardiac surgery., Data Sources: Cochrane CENTRAL, Embase, and MEDLINE, as well as trial registries, conference abstracts, and reference lists of included articles were searched from inception to December 2019., Review Methods: Studies comparing the use of fibrin or thrombin sealant with either an active (other haemostatic methods) or standard surgical haemostatic control in vascular and cardiac surgery were searched for. The Cochrane risk of bias tool and the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) were used to assess the risk of bias of the included randomised and non-randomised studies; quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two reviewers screened studies, assessed risk of bias, and extracted data independently and in duplicate. Data from included trials were pooled using a random effects model., Results: Twenty-one studies (n = 7 622 patients) were included: 13 randomised controlled trials (RCTs), five retrospective, and three prospective cohort studies. Meta-analysis of the RCTs showed a statistically significant decrease in the volume of blood lost (mean difference 120.7 mL, in favour of sealant use [95% confidence interval {CI} -150.6 - -90.7; p < .001], moderate quality). Time to haemostasis was also shown to be reduced in patients receiving sealant (mean difference -2.5 minutes [95% CI -4.0 - -1.1; p < .001], low quality). Post-operative blood transfusions, re-operation due to bleeding, and 30 day mortality were not significantly different for either RCTs or observational data., Conclusion: The use of fibrin and thrombin sealants confers a statistically significant but clinically small reduction in blood loss and time to haemostasis; it does not reduce blood transfusion. These Results may support selective rather than routine use of fibrin and thrombin sealants in vascular and cardiac surgery., Competing Interests: Conflicts of interest None., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Behavioural counselling via internet- or mobile-based digital platforms is recommended for hypertension; however, outcome heterogeneity is problematic in trials of this digital intervention. Our objective was to assess how therapeutic outcome was optimized in digital trials for hypertension, according to key features of the intervention design and protocol., Methods: We identified randomized controlled digital trials for systolic blood pressure (SBP) reduction in taskforce guideline and policy statements, systematic reviews, and meta-analyses published since 2010, by searching the EMBASE, Cochrane Library, psycINFO, and PubMed databases. This search was updated to January 2019. Trials included patients with elevated cardiovascular risk or cardiovascular disease. We classified digital trials by the number of components of the intervention, and whether the protocol was organized by an explicit model of behavioural change or counselling. The influence of these features was evaluated for treatment efficacy and heterogeneity of SBP outcomes., Results: Seventeen trials met inclusion criteria: pooled n = 5780, 33% female, 93% taking antihypertensive medications. SBP reduction was -7.3 mm Hg for digital counselling (95% confidence interval: -7.0 to -7.5) vs -3.6 mm Hg for control (95% confidence interval: -3.4 to -3.9), P < 0.0001, with high-moderate heterogeneity (I 2  = 67%). Trials with multiple behavioural intervention components and an organized theoretical framework of behaviour change or counselling demonstrated optimal SBP reduction with low-moderate heterogeneity (I 2  = 49%)., Conclusions: Digital health interventions optimize the efficacy of medical therapy for SBP reduction. There is opportunity to promote a disruptive change in clinical science that accompanies technological developments in digital health promotion., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study focuses on degradation and mineralization of a third generation cephalosporin antibiotic ceftriaxone (CTA) in UVA- and UVC-induced persulfate (PS) system combined with heterogeneous (α-FeO(OH) and Fe 3 O 4 ) activators. The CTA oxidation efficiency was investigated in buffered solution (pH 7.4) to stimulate the inhibitory properties of environmental and processed water matrices. Irrespective of the studied UV-induced persulfate system, the mineralization was less effective than CTA degradation. In turn, UVC-induced systems proved to be more effective than UVA-induced processes for decomposition of the target compound and removal of TOC. Accordingly, 2-h oxidation in UVA-induced systems resulted in partial decomposition and negligible mineralization of CTA. While the application of UVC-activated persulfate processes resulted in complete CTA degradation during the first 15 min of oxidation with the most efficient k obs of 0.53 min -1 and 38.3% TOC removal obtained in the UVC/PS system at [PS] 0  = 500 μM. Groundwater (GW) trials results clearly indicated the inhibitory effect of the GW composition on the effectiveness of CTA degradation in the studied UV-induced PS-based systems, while the potential treatment efficacy in GW proved predictable based on the results obtained in the buffered UW trials. Adjusting the pH to 3 considerably improved the removal of TOC and the use of PS in both of the water matrices studied. The results of radicals scavenging experiments indicated that both SO 4 - and HO contributed to the CTA decomposition efficacy in the UV-induced persulfate systems, but the former was the predominant radical in all studied processes. The findings of the study strongly suggest that the UV-induced PS systems are promising treatment technologies for the abatement of cephalosporin antibiotics pollution in natural aqueous matrices., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Highly crystalline polyethylene glycol (PEG) coated Tb 3+ doped ZnS nanoparticles have been synthesized and successfully used for norfloxacin sensing. The crystallographic and morphological analyses of PEG coated Tb 3+ doped ZnS nanoparticles were performed by X-ray diffraction and Transmission electron microscopy, respectively. The confirmation of Tb 3+ doping in ZnS host matrix was done by emission spectroscopy and energy dispersive X-ray spectroscopy. Further, the interaction of norfloxacin with PEG coated Tb 3+ doped ZnS nanomaterials was confirmed by optical analysis: spectrophotometrically and spectrofluorimetrically. Norfloxacin sensing was measured by luminescence intensity which increased with increase in concentration of norfloxacin in range from 2.0 × 10 -9 -8.0 × 10 -7  mol L -1 , with its correlation coefficient 0.9991. The detection limit of proposed method was 0.05 × 10 -9  mol L -1 . The developed luminescence method was successfully applied for the determination of norfloxacin using PEG coated Tb 3+ doped ZnS nanoparticles in urine and pharmaceutical samples., (Copyright © 2019. Published by Elsevier B.V.)

Background: Worldwide introduction of the International Fedaration of Gynaecology and Obstetrics (FIGO) 2000 scoring system has provided an effective means to stratify patients with gestational trophoblastic neoplasia to single- or multi-agent chemotherapy. However, the system is quite elaborate with an extensive set of risk factors. In this study, we re-evaluate all prognostic risk factors involved in the FIGO 2000 scoring system and examine if simplification is feasible., Patients and Methods: Between January 2003 and December 2012, 813 patients diagnosed with gestational trophoblastic neoplasia were identified at the Trophoblastic Disease Centre in London and scored using the FIGO 2000. Multivariable analysis and stepwise logistic regression were carried out to evaluate whether the FIGO 2000 scoring system could be simplified., Results: Of the eight FIGO risk factors only pre-treatment serum human chorionic gonadotropin (hCG) levels exceeding 10 000 IU/l (OR = 5.0; 95% CI 2.5-10.4) and 100 000 IU/l (OR = 14.3; 95% CI 4.7-44.1), interval exceeding 7 months since antecedent pregnancy (OR = 4.1; 95% CI 1.0-16.2), and tumor size of over 5 cm (OR = 2.2; 95% CI 1.3-3.6) were identified as independently predictive for single-agent resistance. In addition, increased risk was apparent for antecedent term pregnancy (OR = 3.4; 95% CI 0.9-12.7) and the presence of five or more metastases (OR = 3.5; 95% CI 0.4-30.4), but patient numbers in these categories were relatively small. Stepwise logistic regression identified a simplified risk scoring model comprising age, pretreatment serum hCG, number of metastases, antecedent pregnancy, and interval but omitting tumor size, previous failed chemotherapy, and site of metastases. With this model only 1 out 725 patients was classified different from the FIGO 2000 system., Conclusion: Our simplified alternative using only five of the FIGO prognostic factors appears to be an accurate system for discriminating patients requiring single as opposed to multi-agent chemotherapy. Further work is urgently needed to validate these findings., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A simple and easily synthesized colorimetric and fluorescent chemosensor 1, based on aromatic OH and imine moieties as a binding and anthracene as signaling unit, has been synthesized in a one-step procedure. The chemosensor 1 is developed as a dual chemosensor for detection of Hg 2+ and Al 3+ ions in CH 3 OH, which exhibited a color change from light yellow to dark yellow with Hg 2+ ions, enabling 1 a suitable "bare eye" indicator for Hg 2+ ions. On the other hand, fluorescent enhancement with blue shift along with brilliant cyan fluorescence was observed upon binding with Al 3+ ions. A possible sensing mechanism has been proposed by means of Job's plot and 1 H NMR titration., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The incidence of atrial fibrillation (AF) among patients undergoing left ventricular assist device (LVAD) implantation is high. However, the impact of AF on clinical outcomes has not been clarified. We reviewed our 9-year experience of continuous flow (CF) LVADs to determine the impact of preoperative AF on stroke, device thrombosis, and survival., Methods: Between March 2006 and May 2015, 231 patients underwent implantation of 240 CF LVADs, 127 (52.9%) as bridge to transplantation and 113 (47.1%) as destination therapy. Effect of AF on postoperative outcomes was assessed by using Kaplan-Meier survival and Cox proportional hazard regression., Results: There were 78 patients (32.5%) with preoperative AF with a mean age of 55.7 ± 11.4 years. A similar incidence of stroke was found in patients with and without AF, 12.8% versus 16.0%, respectively (p = 0.803). Survival was similar, with 1-, 6-, 12-, and 24-month survivals of 96.2%, 91.7%, 84.5%, and 69.2%, respectively, for AF patients, versus 93.1%, 85.0%, 79.4%, and 74.1%, respectively, for non-AF patients (p = 0.424). Preoperative AF was not a significant independent predictor of survival with the use of Cox proportional hazard regression (hazard ratio 1.08, 95% confidence interval: 0.66 to 1.76)., Conclusions: Preoperative AF was associated with a similar incidence of postoperative stroke, device thrombosis, and survival. On the basis of these data, it seems unnecessary to perform a left atrial appendage ligation or to alter postoperative anticoagulation in patients with AF undergoing LVAD implantation., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection., Competing Interests: Authors have no conflict of interests to declare.

Background: Continuous-flow left ventricular assist devices (LVADs) have become the standard of care for patients with advanced heart failure. The goal of this study was to review our 9-year institutional experience., Methods: From March 2006 through May 2015, 231 patients underwent implantation of 240 CF LVADs, HeartMate II LVAD (Thoratec Corp., Pleasanton, CA; n = 205) or HVAD (HeartWare Inc., Framingham, MA; n = 35). Of these, 127 devices (52.9%) were implanted as bridge to transplantation (BTT) and 113 (47.1%) as destination therapy (DT)., Results: Mean age was 51.2 ± 11.9 years for BTT patients and 58.2 ± 11.4 years for DT patients (p < 0.001). There was a higher incidence of preoperative diabetes, renal insufficiency, peripheral vascular disease, and previous cardiac operation in DT patients (p < 0.05). Survival was higher for BTT patients, with 1-, 6-, 12-, and 24-month survivals of 91.0%, 90.0%, 88.5%, and 72.1%, respectively, versus 85.3%, 81.1%, 75.6%, and 59.0%, respectively, for DT patients (p = 0.038). Gastrointestinal bleeding was the most common complication (29.6%), followed by right ventricular failure (22.5%) and stroke (15.0%), with a similar incidence for BTT and DT patients. Preoperative liver biopsy (hazard ratio [HR] 2.27, p = 0.036), mechanical support (HR 1.82, p = 0.025), aspartate transaminase (HR 1.07, p = 0.001), and alanine aminotransferase (HR 0.95, p = 0.024) were severe independent predictors of survival in multivariate analysis., Conclusions: These data indicate excellent survival for BTT and DT patients on long-term LVAD support. However, for LVAD therapy to become a plausible alternative to heart transplantation, we need to further decrease the incidence of postoperative complications., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Silver ion-exchanged nanocrystalline zeolite (Ag-Nano-ZSM-5) and silver ion-exchanged conventional zeolite (Ag-ZSM-5) were synthesized. Zeolites were incubated in simulated body fluid at 310K for different time periods to grow hydroxyapatite in their matrixes. Significant large amount of hydroxyapatite was grown in Ag-Nano-ZSM-5 matrix after incubation in simulated body fluid when compared to Ag-ZSM-5. The resultant material was characterized using X-ray diffraction, N2-adsorption, scanning/transmission electron microscopy, energy dispersive X-ray, and inductively coupled plasma analysis. Mechanical properties such as compressive modulus, compressive strength, and strain at failure of the parent materials were evaluated. Biocompatibility assays suggested that Ag-Nano-ZSM-5 and hydroxyapatite grown in Ag-Nano-ZSM-5 were compatible and did not impose any toxicity to RAW 264.7 cells macrophase and Caco2 cells suggesting considerable potential for biomedical applications such as bone implants., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ionic liquids (ILs) coated Fe3O4 based inorganic-organic hybrid materials (represented as Fe3O4/ILs) were synthesized. ILs such as methylimidazolium chloride ([Hmim][Cl]) and 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]) were investigated. For comparative study, quaternary ammonium salts such as choline chloride, cetyltrimethylammonium bromide [C16H33N(CH3)3][Br], and trimethylstearylammonium chloride [C18H37N(CH3)3][Cl] were also investigated. Materials were characterized by X-ray diffraction, nitrogen sorption, Fourier transform infrared and scanning/transmission electron microscopy. Electrochemical sensors based on Fe3O4/ILs modified glassy carbon electrodes were fabricated for the simultaneous determination of all four DNA bases. The electrochemical behavior of DNA bases was investigated in detail. Various reaction parameters such as effect of scan rate, number of electrons involved in the rate determining step, electron transfer coefficient, surface adsorbed concentration, and the electrode reaction standard rate constant were investigated. Catalytic activity obtained at various Fe3O4/ILs modified electrodes was explained using DFT calculation. The analytical performance of the sensor was demonstrated in the simultaneous determination of guanine, adenine, thymine, and cytosine in calf thymus DNA sample., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In this paper, we report the synthesis of silver nanoparticle-decorated reduced graphene oxide composite (AgNPs/rGO) by heating the mixture of graphene oxide and silver nitrate aqueous solution in the presence of sodium hydroxide. This material was characterized by means of X-ray diffraction, UV-vis spectroscopy, and transmission electron microscopy. AgNPs/rGO based electrochemical sensor was fabricated for the simultaneous determination of ascorbic acid, dopamine, uric acid, and tryptophan. Electrochemical studies were carried out by using cyclic voltammetry, linear sweep voltammetry, and chronoamperometry. AgNPs/rGO modified electrode exhibited excellent electrocatalytic activity, stability, sensitivity, and selectivity with well-separated oxidation peaks toward ascorbic acid, dopamine, uric acid, and tryptophan in the simultaneous determination of their quaternary mixture. The analytical performance of this material as a chemical sensor was demonstrated for the determination of ascorbic acid and dopamine in commercial pharmaceutical samples such as vitamin C tablets and dopamine injections, respectively. The applicability of this sensor was also extended in the determination of uric acid in human urine samples., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Parachute tricuspid valve is a rare anomaly usually reported in small children. This report describes transthoracic and trans-oesophageal echocardiographic (TEE) features of parachute mitral valve in an adult patient., (Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Objective: To examine the association with renal damage in patients with posterior urethral valves (PUV) of two renin-angiotensin system gene polymorphisms: angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin type 2 receptor (AT2R A1332G), PATIENTS AND METHODS: In 120 patients with PUV, after stabilization, transurethral fulguration or a Blocksom vesicostomy was performed. Records were reviewed for age at diagnosis, biochemical renal function at diagnosis, results of urine cultures, voiding cystourethrograms, radiologic, sonographic and nuclear medicine scan findings, and follow-up data. ACE I/D genotypes were determined by the polymerase chain reaction using allele specific primers., Results: The frequency of the ACE DD genotype was significantly higher in patients with chronic kidney disease (P=0.02) and renal scarring (P=0.05). These genotypes were also associated with a statistically higher incidence of vesicoureteral reflux, diurnal incontinence, proteinuria and hypertension. A significantly higher frequency of the AT2R GG genotype was found in PUV patients as compared to healthy unrelated control subjects (P=0.001), and in PUV patients with scarring (P=0.02)., Conclusion: The ACE DD and AT2R GG genotypes are associated with chronic kidney disease and scarring in PUV patients. The GG genotype incidence is higher among PUV patients compared to the control population, and further studies in this area may help understanding of the genetic basis of PUV., (Copyright © 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Takotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient left ventricular regional wall motion abnormalities (with peculiar apical ballooning appearance), chest pain or dyspnea, electrocardiographic changes and minor elevations of cardiac enzyme level in the absence of coronary artery disease. We present 3 cases of a transient cardiomyopathy, noted in young women with associated emotional, physical or pharmacologic triggering events, that are distinct in that they all manifested initially with acute pulmonary edema with systolic akinesis involving different LV segments with rapid recovery. It is a reversible cardiac condition that should be differentiated from ischemic and peripartum cardiomyopathy.

Brain angiogenesis inhibitor 1 (BAI1) is a transmembrane protein expressed on glial cells within the brain. Its expression is dramatically down-regulated in many glioblastomas, consistent with its functional ability to inhibit angiogenesis and tumor growth in vivo. We have shown that the soluble anti-angiogenic domain of BAI1 (termed Vstat120) requires CD36, a cell surface glycoprotein expressed on microvascular endothelial cells (MVECs), for it to elicit an anti-angiogenic response. We now report that Vstat120 binding to CD36 on MVECs activates a caspase-mediated pro-apoptotic pathway, and this effect is abrogated by histidine-rich glycoprotein (HRGP). HRGP is a circulating glycoprotein previously shown to function as a CD36 decoy to promote angiogenesis in the presence of thrombospondin-1 or -2. Data here show that Vstat120 specifically binds HRGP. Under favorable MVEC growth conditions this interaction allows chemotactic-directed migration as well as endothelial tube formation to persist in in vitro cellular systems, and increased tumor growth in vivo as demonstrated in both subcutaneous and orthotopic brain tumor models, concomitant with an increase in tumor vascularity. Finally, we show that HRGP expression is increased in human brain cancers, with the protein heavily localized to the basement membrane of the tumors. These data help define a novel angiogenic axis that could be exploited for the treatment of human cancers and other diseases where excess angiogenesis occurs.

The formation of 5-methyl-2'-deoxycytidine (5-MedC) following methylation of the C-5 position of cytosine in genomic DNA provides an epigenetic mechanism for the regulation of gene expression and cellular differentiation. We describe the development of a method using HPLC-ultraviolet (UV) detection for the accurate determination of 5-MedC in DNA. Genomic DNA was obtained from HeLa cells and rat liver tissue using an optimised anion-exchange column DNA extraction procedure incorporating a ribonuclease incubation step to remove any potential interference from RNA. Following extraction the DNA samples were enzymatically hydrolysed to 2'-deoxynucleosides using a combination of an endo-exonuclease plus 5'-exonuclease together with a 3'-nucleotidase. The hydrolysed DNA samples (10 microg on column) were analysed using narrow-bore reverse phase HPLC-UV detection. The level of 5-MedC in the DNA samples was expressed as a percentage of the level of 2'-deoxycytidine (dC) determined from calibration lines constructed using authentic standards for 5-MedC and dC. The percentage 5-MedC level determined for commercially available calf thymus DNA was 6.26%, for HeLa cell DNA was 3.02% and for rat liver DNA was 3.55%.

Aim: To evaluate the comparative efficacy and safety of extended-release (ER) and instant-release (IR) tolterodine preparations in a pediatric population with neural tube defects having cystometric abnormalities., Materials and Methods: Twenty-five patients with neural tube defects and a similar demographic profile underwent a routine hemogram, liver function tests, renal function tests, urine culture, X-ray lumbo-sacral spine, and renal and bladder ultrasound. Vesicoureteric reflux was diagnosed by micturating cystourethrogram under fluoroscopy. Dimercaptosuccinic acid renal scintigraphy was performed to study the presence or absence of renal scars. Patients were treated with tolterodine ER (Group I: 2mg once daily for 21 days) and tolterodine IR (Group II: 2mg twice daily for 21 day) in a cross-over study with a 10-day washout period between administrations. Evaluation was by subjective assessment, visual analog scale, urodynamic assessment and adverse drug reaction monitoring., Results: There was ultrasound evidence of hydroureteronephrosis in 20% of the patients. One patient out of 25 had impaired renal function and eight patients had renal scarring on dimercaptosuccinic acid scans. Both forms of the drug increased the maximum cystometric bladder capacity, decreased detrusor leak pressures and increased compliance compared to pre-therapy levels (P=0.0001). Visual analog scale showed a significant clinical improvement with both ER and IR tolterodine. A significant increase in maximum bladder capacity in the group receiving IR tolterodine as compared to the ER preparation was noted (P=0.0001). The decrease in detrusor leak pressures and improvement in compliance were not significantly different between the groups. No adverse effects of hyperpyrexia, flushing or intolerance to outdoor temperatures, or dryness of mouth were observed in either group. No patient suffered from constipation., Conclusion: ER tolterodine 2mg once daily is as effective and well tolerated in children with neurogenic bladder as IR tolterodine 2mg twice a day. The latter was found to be more effective in terms of urodynamic parameters. ER formulation of tolterodine is less expensive and has the advantage of single dosage.

Purpose: To investigate the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and other risk factors with renal scarring in patients with posterior urethral valves (PUV)., Materials and Methods: Forty consecutive patients from North-west India were treated for PUV in 1997-2004. The patients were divided into group 1 (no renal scarring, n=12) and group 2 (renal scars present, n=28) based on dimercato-succinic acid scans. ACE I/D polymorphism was determined by polymerase chain reaction in PUV patients and unrelated healthy controls (n=100)., Results: Mean age at presentation was 23.7+/-37.2 months and mean follow up was 4.8+/-1.5 years. Preoperative mean serum creatinine levels for group 1 (non-scarred) and group 2 (scarred) were 1.1+/-1.6 mg/dl and 1.7+/-1.6 mg/dl, respectively. One year after treatment, the serum creatinine levels had decreased to 0.6+/-0.1 mg/dl and 0.8+/-0.3 mg/dl in group 1 and group 2, respectively. ACE genotype distribution in children with PUV was no different from that of controls. The occurrence of D allele was significantly (p=0.04) higher in patients of group 2. Multivariate logistic regression analysis showed that D allele had a significant impact on renal scar formation, introducing a 4.6-fold risk (odds ratio 4.6, 95% confidence interval 1.03-20.38, p=0.04). A highly significant correlation between the occurrence of renal scarring and presence of breakthrough urinary tract infection (odds ratio=7.5, 95% confidence interval 1.60-35.07, p=0.006) and serum creatinine at follow up (odds ratio=0.6, 95% confidence interval 0.47-0.81, p=0.03) was observed. The mean values for glomerular filtration rate (GFR) after 1 year of treatment (p=0.006) and at follow up (p=0.027) were significantly different between the patients with II genotype and ID/DD genotype. Hypertension was observed in 13 patients and proteinuria in nine patients with no significant difference between the patients having II/I D/DD genotypes., Conclusion: The presence of D allele is associated with progression of renal scarring and reduced GFR in PUV patients.