Miracle-dz/UniFAR-FTUs huggingface dataset:
Paediatric Urinary Tract Infection: A Hospital Based Experience.

INTRODUCTION Paediatric Urinary Tract Infection (UTI) is one of the commonly encountered entities by paediatricians. Studies have shown easy vulnerability of paediatric urinary tract in any acute febrile illness and a miss in diagnosis could have long term consequences like renal scaring with its adverse effects. Bearing these evidence based preludes in view we designed our study to know the prevalence of UTI in Kashmir province. AIM Aim of the present study was to know the prevalence of UTI in febrile children and to know the sensitivity of different imaging modalities like Renal and Urinary Bladder Ultrasonography (RUS), Voiding Cystourethrography (VCUG) and Dimercaptosuccinic Acid (DMSA) scan in diagnosing UTI. MATERIALS AND METHODS A total of 304 patients, between 2 months to 10 years, with axillary temperature of ≥ 100.4oF (38oC), who did not have a definite source for their fever and who were not on antibiotics were included in the study. Detailed history and through clinical examination was done to rule out any potential or definite focus of infection as per the predesigned proforma. Routine urine examination with culture and sensitivity, followed by RUS and VCUG was done in all patients where routine urine examination was suggestive of UTI. DMSA was done in only culture proven cases after 6 months to document the renal scarring. RESULTS Out of 304 children, 140 were males and 164 were females, UTI was present in 40 patients who had fever without any apparent cause giving a prevalence of 13.2%. Escherichia coli (E. coli) were the commonest isolated organism, followed by Klebsiella and Citrobacter species. Renal and Urinary Bladder Ultrasonography (RUS) detected Vesicoureteral Reflux (VUR) in 25% (10/40) while VCUG showed VUR in 55% (22/40) giving a RUS sensitivity of 45% for detecting VUR. DMSA done only after 6 months in UTI diagnosed patients showed a renal scarring in 25% (10/40) patients. CONCLUSION Missing a febrile paediatric UTI, can prove a future catastrophe if not timely diagnosed and treated.
Nuclear Protein Quality Is Regulated by the Ubiquitin-Proteasome System through the Activity of Ubc4 and San1 in Fission Yeast*

Eukaryotic cells monitor and maintain protein quality through a set of protein quality control (PQC) systems whose role is to minimize the harmful effects of the accumulation of aberrant proteins. Although these PQC systems have been extensively studied in the cytoplasm, nuclear PQC systems are not well understood. The present work shows the existence of a nuclear PQC system mediated by the ubiquitin-proteasome system in the fission yeast Schizosaccharomyces pombe. Asf1-30, a mutant form of the histone chaperone Asf1, was used as a model substrate for the study of the nuclear PQC. A temperature-sensitive Asf1-30 protein localized to the nucleus was selectively degraded by the ubiquitin-proteasome system. The Asf1-30 mutant protein was highly ubiquitinated at higher temperatures, and it remained stable in an mts2-1 mutant, which lacks proteasome activity. The E2 enzyme Ubc4 was identified among 11 candidate proteins as the ubiquitin-conjugating enzyme in this system, and San1 was selected among 100 candidates as the ubiquitin ligase (E3) targeting Asf1-30 for degradation. San1, but not other nuclear E3s, showed specificity for the mutant nuclear Asf1-30, but did not show activity against wild-type Asf1. These data clearly showed that the aberrant nuclear protein was degraded by a defined set of E1-E2-E3 enzymes through the ubiquitin-proteasome system. The data also show, for the first time, the presence of a nuclear PQC system in fission yeast.
Baseline Stage, Severity, and Effort Effects Differentiate Stable Smokers from Maintainers and Relapsers

This cross-sectional study (N = 4,144) compared three longitudinal dynatypes (Maintainers, Relapsers, and Stable Smokers) of smokers on baseline demographics, stage, addiction severity, and transtheoretical model effort effect variables. There were significant small-to-medium-sized differences between the Stable Smokers and the other two groups on stage, severity, and effort effect variables in both treatment and control groups. There were few significant, very small differences on baseline effort variables between Maintainers and Relapsers in the control, but not the treatment group. The ability to identify Stable Smokers at baseline could permit enhanced tailored treatments that could improve population cessation rates.
Production, Secretion, and Stability of Human Secreted Alkaline Phosphatase in Tobacco NT1 Cell Suspension Cultures

Tobacco NT1 cell suspension cultures secreting active human secreted alkaline phosphatase (SEAP) were generated for the first time as a model system to study recombinant protein production, secretion, and stability in plant cell cultures. The SEAP gene encodes a secreted form of the human placental alkaline phosphatase (PLAP). During batch culture, the highest level of active SEAP in the culture medium (0.4 U/mL, corresponding to approximately 27 mg/L) was observed at the end of the exponential growth phase. Although the level of active SEAP decreased during the stationary phase, the activity loss did not appear to be due to SEAP degradation (based on Western blots) but due to SEAP denaturation. The protein‐stabilizing agents polyvinylpirrolidone (PVP) and bacitracin were added extracellularly to test for their ability to reduce the loss of SEAP activity during the stationary phase. Bacitracin (100 mg/L) was the most effective treatment at sustaining activity levels for up to 17 days post‐subculture. Commercially available human placental alkaline phosphatase (PLAP) was used to probe the mechanism of SEAP deactivation. Experiments with PLAP in sterile and conditioned medium corroborated the denaturation of SEAP by factors generated by cell growth and not due to simple proteolysis. We also show for the first time that the factors promoting activity loss are heat labile at 95 °C but not at 70 °C, and they are not inactivated after a 5 day incubation period under normal culture conditions (27 °C). In addition, there were no significant changes in pH or redox potential when comparing sterile and cell‐free conditioned medium during PLAP incubation, indicating that these factors were unimportant.
In Vitro Evaluation of Ertapenem (MK-0826), a Long-Acting Carbapenem, Tested Against Selected Resistant Strains

Abstract Ertapenem (MK-0826) is a novel, long-acting parenteral carbapenem. The purpose of this In Vitro study was to test ertapenem's activity against a collection of multiply-resistant strains of Gram-positive and -negative bacteria isolated from locations worldwide, and to examine its bactericidal activity and ability to act in a synergistic manner in combination with other antimicrobial agents. Ertapenem was active against a variety of Gram-negative pathogens, with particular potency noted for Escherichia coli and Klebsiella pneumoniae (MIC90s <0.015-0.5 μg/mL) including extended spectrum β-lactamase producing strains. Less ertapenem activity was seen against Pseudomonas aeruginosa, especially ceftazidime-resistant strains (MIC50 16 μg/mL). Except for enterococci, ertapenem was active against most Gram-positive species, including β-haemolytic streptococci (MIC90 0.03 μg/mL; 100% susceptible), viridans group streptococci (MIC90 2 μg/mL; 98.1% susceptible), and penicillin-susceptible Streptococcus pneumoniae (MIC90 <0.015 μg/mL; 100% susceptible). Ertapenem was also very potent against Haemophilus influenzae (MIC90 0.25 μg/mL; 100% susceptible). Bactericidal action was observed versus staphylo-cocci, E. coli, and K. pneumoniae, and at least an additive effect was detected against the majority of the strains tested when ertapenem was combined with ciprofloxacin or gentamicin. These results from testing 902 organisms indicate that ertapenem appears to be a promising broad-spectrum carbapenem with a possible role against some emerging resistant species.
Spectrum of ocular firework injuries in children: A 5-year retrospective study during a festive season in Southern India

Purpose: Ocular trauma is a major cause of acquired monocular blindness in children. Firework injuries account for 20% of ocular trauma. The purpose of our study was to document the profile of ocular firework injuries in children during the festive season of Diwali and to determine the prevalence of unilateral blindness in them. Materials and Methods: A retrospective chart analysis of ocular firework injury in children during the festival of Diwali from 2009 to 2013, conducted in a tertiary care eye center in Tamil Nadu, Southern India. Children below 18 years of age with ocular firework injuries who presented to the emergency department for 3 consecutive days - the day of Diwali, 1 day before, and 1 day after Diwali - were included in this study. Results: Eighty-four children presented with firework-related ocular injuries during the study period. Male to female ratio was 4:1 with mean age 9.48 ± 4 years. Forty-four percentage required hospitalization. The prevalence of unilateral blindness in children due to fireworks was found to be 8% (95% confidence interval - 2–13%). Conclusion: Vision 2020 gives high priority to avoidable blindness, especially in children. In our study, for every 12 children who presented with firecracker injury, one resulted in unilateral blindness. This is an avoidable cause of blindness. Awareness needs to be created, and changes in policy regarding sales and handling of firecrackers including mandatory use of protective eyewear should be considered.
Meibomian Gland Alteration in Patients with Primary Chronic Dacryocystitis: An In vivo Confocal Microscopy Study

Abstract Purpose: To evaluate meibomian gland (MG) alterations in patients with primary chronic dacryocystitis (PCD) by in vivo confocal microscopy (IVCM), and to correlate the finding with clinical presentation. Methods: Twenty-eight eyes with the diagnosis of PCD and their contralateral unaffected eyes were studied and compared with 27 normal controls. All subjects completed an Ocular Surface Disease Index questionnaire (OSDI) and underwent slit-lamp biomicroscopy examination, tear break-up time (BUT) measurements, fluorescein staining, Schirmer test I, and an IVCM examination of the MG. IVCM parameters, including the MG acinar unit density (MGAUD), periglandular inflammatory cell density (ICD), MG acinar unit longest diameter (MGALD), and MG acinar unit shortest diameter (MGASD) and their correlation with clinical data were analyzed. Results: The mean MG expressibility scores, BUT values, and staining scores were significantly worse in eyes with PCD compared with the contralateral clinically unaffected eyes and controls (p < 0.05). A significant decrease in MGAUD was observed in PCD eyes compared with the controls and the contralateral clinically unaffected eyes. Conversely, the mean ICD and MGASD values were significantly higher in the PCD eyes. There were no significant differences in mean MGALD value between the PCD eyes and the contralateral clinically unaffected eyes. In addition, there were significant changes in the IVCM parameters in the contralateral unaffected eyes compared with the controls, including MGAUD, ICD, MGALD, and MGASD. All IVCM parameters showed a strong, significant correlation with MG dropout grades, MG expressibility, fluorescein staining scores, and OSDI values (all p < 0.05). Conclusions: Patients with unilateral PCD demonstrated significant changes in MG as compared with the contralateral clinically unaffected eyes and controls. The MG function should be closely observed in these patients.
Cerebral cortical dysfunction in chronic obstructive pulmonary disease: role of transcranial magnetic stimulation.

SETTING Chest and Neurology Departments, Assiut and Al-Azhar University Hospitals, Egypt. OBJECTIVES To study a large population with respect to previous preliminary data, using transcranial magnetic stimulation (TMS) as a prognostic method for evaluation of cerebral cortical functions during acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). DESIGN In a case-control study, 41 patients with AE-COPD and 30 healthy controls were included. For all, TMS was used to assess corticospinal pathway function and cortical excitability. RESULTS Patients demonstrated increased motor threshold (resting and active), central motor conduction time and increased cortical silent period. Significant correlation was identified between TMS parameters and pulmonary function tests (forced vital capacity, forced expiratory volume 1%, forced expiratory volume in one second) and arterial blood gases (pH, paO(2) and HCO(3)), serum chloride and potassium. CONCLUSION These results indicate that the motor cortex is less excitable during AE-COPD. This is attributed to reduction of cortical excitability due to chronic hypoxaemia. Therefore, early detection of cerebral changes might be in accordance with the importance of early O(2) therapy in reducing morbidity and mechanical ventilation dependency in COPD. This opens discussion for future early therapeutic use of GABAergic and glutaminergic modulating drugs with oxygen to protect the brains of COPD patients.
2,3,7,8-Tetrachlorodibenzo-p-Dioxin Decreases Estradiol Production Without Altering the Enzyme Activity of Cytochrome P450 Aromatase of Human Luteinized Granulosa Cells In Vitro1

Abstract This study was designed to examine the in vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on steroid production in human luteinizing granulosa cells (hLGC). TCDD (10 nM) or its solvent was added at the time of changing medium, directly to the cells, every 48 h for 8 days. To test the hypothesis that TCDD reduces estradiol (E2) synthesis by an effect on cytochrome P450 aromatase, aromatase protein and aromatase activity were evaluated. E2 decreased without changing either aromatase protein or its enzyme activity, suggesting that the target of toxicity of TCDD is upstream of aromatase in the steroidogenic pathway. When hLGC were incubated in the presence of labeled E2, no changes in the metabolism of E2 by treatment were observed. Since TCDD did not change progesterone or 17α-hydroxyprogesterone, the inhibition of E2 synthesis by TCDD would seem not to involve steps such as cholesterol transport. Furthermore, the TCDD effect on E2 concentration in these cells disappeared in the presence of excess androgens. We conclude that the inhibition of E2 secretion by TCDD involves intermediate steps, specifically, the provision of androgens for aromatization.
Calcium Interacts with Antifreeze Proteins and Chitinase from Cold-Acclimated Winter Rye1

During cold acclimation, winter rye (Secale cereale) plants accumulate pathogenesis-related proteins that are also antifreeze proteins (AFPs) because they adsorb onto ice and inhibit its growth. Although they promote winter survival in planta, these dual-function AFPs proteins lose activity when stored at subzero temperatures in vitro, so we examined their stability in solutions containing CaCl2, MgCl2, or NaCl. Antifreeze activity was unaffected by salts before freezing, but decreased after freezing and thawing in CaCl2 and was recovered by adding a chelator. Ca2+ enhanced chitinase activity 3- to 5-fold in unfrozen samples, although hydrolytic activity also decreased after freezing and thawing in CaCl2. Native PAGE, circular dichroism, and Trp fluorescence experiments showed that the AFPs partially unfold after freezing and thawing, but they fold more compactly or aggregate in CaCl2. Ruthenium red, which binds to Ca2+-binding sites, readily stained AFPs in the absence of Ca2+, but less stain was visible after freezing and thawing AFPs in CaCl2. We conclude that the structure of AFPs changes during freezing and thawing, creating new Ca2+-binding sites. Once Ca2+ binds to those sites, antifreeze activity, chitinase activity and ruthenium red binding are all inhibited. Because free Ca2+ concentrations are typically low in the apoplast, antifreeze activity is probably stable to freezing and thawing in planta. Ca2+ may regulate chitinase activity if concentrations are increased locally by release from pectin or interaction with Ca2+-binding proteins. Furthermore, antifreeze activity can be easily maintained in vitro by including a chelator during frozen storage.
Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 – Part II

ABSTRACT Introduction: TrkA/B/C receptor activation supports growth, survival, and differentiation of discrete neuronal populations during development, adult life, and ageing but also plays numerous roles in human disease onset and progression. Trk-specific inhibitors have therapeutic applications in cancer and pain and thus constitute a growing area of interest in oncology and neurology. There has been substantial growth in the number of structural classes of Trk inhibitors and the number of industrial entrants to the Trk inhibitor field over the past six years. Areas covered: In Part II of this two-part review, the discussion of recent patent literature covering Trk family inhibitors is continued from Part I and clinical research with Trk inhibitors is considered. Expert opinion: Trk has been molecularly targeted for over a decade resulting in the progressive evolution of structurally diversified Trk inhibitors arising from scaffold hopping and HTS efforts. Correspondingly, there have been a growing number of clinical investigations utilizing Trk inhibitors in recent years, with a particular focus on the treatment of NTRK-fusion positive cancers and chronic pain. The observed potential of Trk inhibitors to cause adverse CNS side effects however suggests the need for a more rigorous consideration of BBB permeation capabilities during drug development.
Development and Validation of the Teen Dating Aggression Measure Among Canadian Youth

Teen dating violence (TDV) victimization is a traumatic experience that can have adverse consequences for adolescents. Current measures that assess TDV do not fully distinguish between psychological and relational forms of aggression, nor do they capture aggressive acts that are common within adolescent relationships. The purpose of this study was to evaluate the psychometric properties of the Teen Dating Aggression Measure (TeDAM) using a sample of 730 Canadian adolescents (M = 15.88 years, SD = 1.23). The measure is an expansion of the Conflict in Adolescent Dating Relationships Inventory and includes items that describe other forms of violence such as coercion and control, along with more traditional indicators of dating violence (e.g., sexual aggression). Factor analyses yielded three factors, namely psychological aggression, sexual and physical aggression, and relational aggression, which were correlated with more frequent cannabis and alcohol use as well as rape myth acceptance. These results provide initial support for the utility of the TeDAM for assessing TDV with adolescents.
cAMP-responsive Element Modulator (CREM)α Protein Induces Interleukin 17A Expression and Mediates Epigenetic Alterations at the Interleukin-17A Gene Locus in Patients with Systemic Lupus Erythematosus*

Background: Expression levels of both IL-17A and transcription factor CREMα are increased in T cells from SLE patients. Results: In primary human T cells, CREMα binds to the proximal IL17A promoter and induces IL-17A expression by transcriptional activation and epigenetic modifications. Conclusion: CREMα promotes IL-17A expression. Significance: Suppression of CREMα expression should mitigate IL-17A-driven inflammatory responses. IL-17A is a proinflammatory cytokine that is produced by specialized T helper cells and contributes to the development of several autoimmune diseases such as systemic lupus erythematosus (SLE). Transcription factor cAMP-responsive element modulator (CREM)α displays increased expression levels in T cells from SLE patients and has been described to account for aberrant T cell function in SLE pathogenesis. In this report, we provide evidence that CREMα physically binds to a cAMP-responsive element, CRE (−111/−104), within the proximal human IL17A promoter and increases its activity. Chromatin immunoprecipitation assays reveal that activated naïve CD4+ T cells as well as T cells from SLE patients display increased CREMα binding to this site compared with T cells from healthy controls. The histone H3 modification pattern at the CRE site (−111/−104) and neighboring conserved noncoding sequences within the human IL17A gene locus suggests an accessible chromatin structure (H3K27 hypomethylation/H3K18 hyperacetylation) in activated naïve CD4+ T cells and SLE T cells. H3K27 hypomethylation is accompanied by decreased cytosine phosphate guanosine (CpG)-DNA methylation in these regions in SLE T cells. Decreased recruitment of histone deacetylase (HDAC)1 and DNA methyltransferase (DNMT)3a to the CRE site (−111/−104) probably accounts for the observed epigenetic alterations. Reporter studies confirmed that DNA methylation of the IL17A promoter indeed abrogates its inducibility. Our findings demonstrate an extended role for CREMα in the immunopathogenesis of SLE because it contributes to increased expression of IL-17A.
Tight junction proteins ZO-1, ZO-2, and occludin along isolated renal tubules.

BACKGROUND Tight junctions play a critical role in tubular function. In mammalian kidney, the transepithelial electrical resistance and the complexity of the tight junction increase from the proximal to the collecting tubule. The differential expression of three tight junction proteins, ZO-1, ZO-2, and occludin, along isolated rabbit renal tubules is examined in this article. METHODS Microdissected rabbit renal tubules were processed for immunofluorescence detection of ZO-1, ZO-2, and occludin. The quantitation of these proteins was done by Western blot determinations in Percoll isolated tubules. RESULTS ZO-1 stained cell boundaries independently of the identity of the tubule. However, the amount found in distal segments was significantly higher than that expressed in proximal regions. ZO-2 in the proximal region was found diffusely distributed in the cytoplasm, with faint staining at cell borders, while a clear signal at cell perimeters was detectable from the Henle's loop to collecting tubules. Nuclear staining of ZO-2 was found along the whole nephron. The presence of occludin at the proximal region was faint and discontinuous, while its expression in the more distant portions was conspicuous. The quantity of ZO-2 and occludin present at the distal region was significantly higher compared with the proximal segment. CONCLUSIONS The distribution of ZO-1, ZO-2, and occludin follows the increase in junction complexity encountered in renal tubules. The amount of the three proteins found in proximal and distal segments is significantly higher in the latter.
High-performance organic photovoltaic device using a new amorphous molecular material of bis(4-(N-(l-naphthyl)phenylamino) phenyl)fumaronitrile

An efficient organic photovoltaic devices (OPVs) have been realized by using a new amorphous absorption material, bis(4-(N-(l-naphthyl)phenylamino) phenyl)fumaronitrile (NPAFN). NPAFN exhibits a hole mobility of 0.07 cm2/Vs as determined by the thin-film transistor. The structure of double-heterojunction OPV, ITO/NPAFN/fulerene/bathocuproine/Al, shows high performance with open circuit voltage of 0.98 V, short current density of 3.72 mA/cm2, and power conversion efficiency of 1.72% under air-mass (AM) 1.5 G illumination at an light intensity of 100 mW/cm2.