Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperinsulinemia and waist circumference in childhood metabolic syndrome.

OBJECTIVE To determine the characteristics of obese children presenting at a tertiary care hospital and the frequency of metabolic syndrome (MS) in them using two paediatric definitions. STUDY DESIGN Cross-sectional study. PLACE AND DURATION OF STUDY The Endocrine Clinic of National Institute of Child Health, Karachi, from November 2005 till May 2008. METHODOLOGY A total of 262 obese children aged 4-16 years, with BMI greater than 95th percentile were included. Children having obesity due to syndromes, medications causing weight gain, chronic illness and developmental disability were excluded. Blood pressure, waist circumference, fasting triglycerides, HDL, insulin and glucose levels were obtained. Obesity was defined as BMI > 95th percentile for age and gender according to the UK growth reference charts. The prevalence of metabolic syndrome was estimated using to the De Ferrantis and Lambert definitions. RESULTS The frequency of MS varied between 16% and 52% depending on whether insulin levels were included in the definition. There was a significant positive correlation(r) when the metabolic parameters were correlated with waist circumference and insulin levels, except HDL which was negatively correlated. All the metabolic parameters like waist circumference, triglycerides, high density lipoprotein cholesterol and systolic blood pressure increased considerably across the insulin quartile (p < 0.05). The most noteworthy anthropometric and metabolic abnormality were the waist circumference (46.5%) and insulin levels (58%) respectively. CONCLUSION There was a marked difference in the frequency of metabolic syndrome according to the definition used. The waist circumference and hyperinsulinemia are significant correlates of MS in obese children. There is a need for establishing normal insulin ranges according to age, gender and pubertal status. The clinical examination and investigations ought to include waist circumference and insulin levels together as a part of the definition of MS, for early detection and intervention of childhood obesity.
Brain Imaging Modality before Systemic Thrombolysis for Ischemic Stroke within Three Hours

Objective: In Japan, MRI-based thrombolysis after CT screening is the most common imaging strategy prior to intravenous thrombolysis (IVT) with tissue plasminogen activator (tPA) within 3 h after ischemic stroke. A choice of MRI with MR angiography (MRA) provides a higher diagnostic accuracy, but may delay an initiation of thrombolysis. Methods: In our neuro-unit, brain CT is the first screening image for suspected stroke. We retrospectively examined a delay to thrombolysis, imaging modality, diagnostic accuracy, and clinical outcomes at 3 months by the modified Rankin Scale in patients receiving IVT within 3 h. Results: Among 67 patients receiving IVT with tPA, brain imaging prior to IVT was solely CT in 10 (15%) patients and CT + MRI/MRA in 57 (85%) patients. Final diagnosis of brain ischemia was 100%. Patients receiving CT + MRI had significantly shorter pre-hospital delay (mean 54 vs. 83 min; p = 0.012), but longer door-to-needle time (mean 90 vs. 57 min; p = 0.019) than those receiving CT only. Finally, time from onset to thrombolysis was not different between the two groups and clinical outcomes were also comparable. The earlier patients arrived, the longer door-to-needle times were (p < 0.001). Conclusions: The imaging strategy of initial CT screening with optional MRI/MRA scans prior to IVT was feasible. However, it resulted in an additional 30 min in-hospital delay of tPA administration, which may affect clinical outcomes.
Large Store-operated Calcium Selective Currents Due to Co-expression of Orai1 or Orai2 with the Intracellular Calcium Sensor, Stim1*

The molecular nature of store-operated Ca2+-selective channels has remained an enigma, due largely to the continued inability to convincingly demonstrate Ca2+-selective store-operated currents resulting from exogenous expression of known genes. Recent findings have implicated two proteins, Stim1 and Orai1, as having essential roles in store-operated Ca2+ entry across the plasma membrane. However, transient overexpression of these proteins on their own results in little or no increase in store-operated entry. Here we demonstrate dramatic synergism between these two mediators; co-transfection of HEK293 cells with Stim1 and Orai1 results in an approximate 20-fold increase in store-operated Ca2+ entry and Ca2+-selective current. This demonstrates that these two proteins are limiting for both the signaling and permeation mechanisms for Ca2+-selective store-operated Ca2+ entry. There are three mammalian homologs of Orai1, and in expression experiments they all produced or augmented store-operated Ca2+ entry with efficacies in the order Orai1 > Orai2 > Orai3. Stim1 apparently initiates the signaling process by acting as a Ca2+ sensor in the endoplasmic reticulum. This results in rearrangement of Stim1 within the cell and migration toward the plasma membrane to regulate in some manner Orai1 located in the plasma membrane. However, we demonstrate that Stim1 does not incorporate in the surface membrane, and thus likely regulates or interacts with Orai1 at sites of close apposition between the plasma membrane and an intracellular Stim1-containing organelle.
Chronology of optic nerve head and retinal responses to elevated intraocular pressure.

PURPOSE To determine the chronology of optic nerve head and retinal responses to elevated intraocular pressure (IOP). METHODS After 1 to 39 days of unilaterally elevated IOP, experimental and fellow rat eyes were examined for morphology and immunohistochemical labeling alterations and for ganglion cell DNA fragmentation. RESULTS Mean IOP for the experimental eyes was 36 +/- 8 mm Hg, an approximately 15-mm Hg elevation above normal values. By 7 days of pressure elevation above 40 mm Hg, endogenous immunostaining for brain-derived neurotrophic factor and neurotrophin 4/5 was absent from the nerve head and superior retina, whereas normal labeling was present in the inferior retina and distal optic nerve of these same eyes. These changes were preceded by a loss of gap junctional connexin43 labeling and astrocytic proliferation in the nerve head and by increased retinal ganglion cell layer apoptosis in the retina. Nerve head depletion of neurotrophins coincided with evidence of axonal degeneration, loss of astrocytic glial fibrillary acidic protein staining, and spread of collagen VI vascular immunolabeling. After longer durations at these same pressures, neurotrophin labeling returned to nerve head glia and scattered retinal ganglion cells. CONCLUSIONS Optic nerve head and retinal responses, including the depletion of endogenous neurotrophins, are readily identified in the rat eye after experimental IOP elevation. However, the apparent chronology of these responses suggests that the withdrawal of neurotrophic support was not the only determinant of retinal ganglion cell apoptosis and axonal degeneration in response to pressure.
Risk Factors for Death and Severe Sequelae in Malawian Children With Bacterial Meningitis, 1997–2010

Background: Acute bacterial meningitis (ABM) causes significant death and disability in children worldwide, with HIV recognized as an established risk factor for infection and negative outcomes. However, additional major risk factors for death and disability in pediatric ABM remain unclear. Methods: We conducted a retrospective analysis of case data from 3 departmental studies of ABM involving 1784 children <15 years old who attended Queen Elizabeth Central Hospital in Blantyre, Malawi during 1997 to 2010. Univariate and multivariate logistic regression models were used to estimate the effects of HIV seropositivity, impaired consciousness and causative organism on death and severe sequelae. Results: Impaired consciousness or coma at the time of admission was strongly associated with death (coma: odds ratio [OR] = 14.4, 95% confidence interval [CI]: 9.42, 22.1) and severe sequelae (Coma: OR = 3.27, 95% CI: 2.02, 5.29) in multivariate logistic regression models. HIV seropositivity was significantly associated with increased odds of death (OR = 1.65, 95% CI: 1.20, 2.26) but not with developing severe sequelae (OR = 0.88, 95% CI: 0.56, 1.38). After adjustment, infection with Salmonella spp. was associated with increased odds of death (OR = 2.11, 95% CI: 1.06, 4.08) and pneumococcal meningitis was associated with increased odds of severe sequelae (OR = 1.84, 95% CI: 1.03, 3.29). Conclusions: Impaired consciousness and HIV infection increased the odds of death from ABM in Malawian children. Use of pneumococcal conjugate vaccine could greatly reduce the burden of ABM in Malawi.
A liver X receptor and retinoid X receptor heterodimer mediates apolipoprotein E expression, secretion and cholesterol homeostasis in astrocytes

Apolipoprotein E (apoE) is an important protein involved in lipoprotein clearance and cholesterol redistribution. ApoE is abundantly expressed in astrocytes in the brain and is closely linked to the pathogenesis of Alzheimer's disease (AD). We report here that small molecule ligands that activate either liver X receptors (LXR) or retinoid X receptor (RXR) lead to a dramatic increase in apoE mRNA and protein expression as well as secretion of apoE in a human astrocytoma cell line (CCF‐STTG1 cells). Examination of primary mouse astrocytes also revealed significant induction of apoE mRNA, and protein expression and secretion following incubation with LXR/RXR agonists. Moreover, treatment of mice with a specific synthetic LXR agonist T0901317 resulted in up‐regulation of apoE mRNA and protein in both hippocampus and cerebral cortex, indicating that apoE expression in brain can be up‐regulated by LXR agonists in vivo. Along with a dramatic induction of ABCA1 cholesterol transporter expression, these ligands effectively mediate cholesterol efflux in both CCF‐STTG1 cells and mouse astrocytes in the presence or absence of apolipoprotein AI (apoAI). Our studies provide strong evidence that small molecule LXR/RXR agonists can effectively mediate apoE synthesis and secretion as well as cholesterol homeostasis in astrocytes. LXR/RXR agonists may have significant impact on the pathogenesis of multiple neurological diseases, including AD.
Accelerated corpus callosum development in prematurity predicts improved outcome

To determine: (1) whether corpus callosum (CC) size and microstructure at 7 years of age or their change from infancy to 7 years differed between very preterm (VP) and full‐term (FT) children; (2) perinatal predictors of CC size and microstructure at 7 years; and (3) associations between CC measures at 7 years or trajectories from infancy to 7 years and neurodevelopmental outcomes.
A low phase noise 10-G bits/s clock and data recovery circuit with modified D latch for backplane applications using dual loop architecture

In this paper a clock and data recovery circuit (CDR) with modified D latch is designed meeting the standards of 10 Base-KR standard backplane. The designed circuit employs dual loop architecture in 0. 18μm UMC CMOS technology. The simulated results indicate a phase noise of voltage controlled oscillator (VCO) as -173.782dBC/HZ, VCO gain of 350MHz/V while consuming 85mW from 1.8V supply. LC oscillator is designed for achieving low jitter.
Interactions of apomyoglobin with membranes: Mechanisms and effects on heme uptake

The last step of the folding reaction of myoglobin is the incorporation of a prosthetic group. In cells, myoglobin is soluble, while heme resides in the mitochondrial membrane. We report here an exhaustive study of the interactions of apomyoglobin with lipid vesicles. We show that apomyoglobin interacts with large unilamellar vesicles under acidic conditions, and that this requires the presence of negatively charged phospholipids. The pH dependence of apomyoglobin interactions with membranes is a two‐step process, and involves a partially folded state stabilized at acidic pH. An evident role for the interaction of apomyoglobin with lipid bilayers would be to facilitate the uptake of heme from the outer mitochondrial membrane. However, heme binding to apomyoglobin is observed at neutral pH when the protein remains in solution, and slows down as the pH becomes more favorable to membrane interactions. The effective incorporation of soluble heme into apomyoglobin at neutral pH suggests that the interaction of apomyoglobin with membranes is not necessary for the heme uptake from the lipid bilayer. In vivo, however, the ability of apomyoglobin to interact with membrane may facilitate its localization in the vicinity of the mitochondrial membranes, and so may increase the yield of heme uptake. Moreover, the behavior of apomyoglobin in the presence of membranes shows striking similarities with that of other proteins with a globin fold. This suggests that the globin fold is well adapted for soluble proteins whose functions require interactions with membranes.
Chloroplast Biogenesis: Control of Plastid Development, Protein Import, Division and Inheritance

Abstract The chloroplast is a multi-copy cellular organelle that not only performs photosynthesis but also synthesizes amino acids, lipids and phytohormones. The plastid also responds to environmental stimuli such as gravitropism. Biogenesis of chloroplasts is initiated from proplastids in shoot meristems, and involves a series of important events. In the last decade, considerable progress has been made towards understanding various aspects of chloroplast biogenesis at the molecular level, via studies in model systems such as Arabidopsis. This review focuses on two important aspects of chloroplast biogenesis, synthesis/assembly and division/transmission. Chloroplasts originated through endosymbiosis from an ancestor of extant cyanobacteria, and thus contain their own genomes. DNA in chloroplasts is organized into complexes with proteins, and these are called nucleoids. The synthesis of chloroplast proteins is regulated at various steps. However, a majority of proteins are synthesized in the cytosol, and their proper import into chloroplast compartments is a prerequisite for chloroplast development. Fundamental aspects of plastid gene expression/regulation and chloroplast protein transport are described, together with recent proteome analyses of the organelle. Chloroplasts are not de novo synthesized, but instead are propagated from pre-existing plastids. In addition, plastids are transmitted from generation to generation with a unique mode of inheritance. Our current knowledge on the division machinery and the inheritance of plastids is described.
Fruit Flies Medicate Offspring After Seeing Parasites

Mother Knows Best Fruit flies feed on decomposing fruit, a food source rich in alcohol, and thus have evolved a high alcohol tolerance not shared by many other species. High levels of ingested alcohol protect fly larvae against parasitic wasp larvae. Kacsoh et al. (p. 947) show that this therapeutic use of alcohol to combat a parasite has an intergenerational component. When fly mothers were permitted to see parasitic wasps, they preferentially laid their eggs on substrates containing high alcohol levels as a way to medicate their offspring against potential infection. Flies deposit their eggs in protective, alcohol-rich environments when parasitic wasps are around. Hosts have numerous defenses against parasites, of which behavioral immune responses are an important but underappreciated component. Here we describe a behavioral immune response that Drosophila melanogaster uses against endoparasitoid wasps. We found that when flies see wasps, they switch to laying eggs in alcohol-laden food sources that protect hatched larvae from infection. This change in oviposition behavior, mediated by neuropeptide F, is retained long after wasps are removed. Flies respond to diverse female larval endoparasitoids but not to males or pupal endoparasitoids, showing that they maintain specific wasp search images. Furthermore, the response evolved multiple times across the genus Drosophila. Our data reveal a behavioral immune response based on anticipatory medication of offspring and outline a nonassociative memory paradigm based on innate parasite recognition by the host.
Effect of High-Salt Diet on Vascular Relaxation and Oxidative Stress in Mesenteric Resistance Arteries

This study tested the hypothesis that superoxide levels are elevated in isolated mesenteric resistance arteries (100–300 µm) from rats fed a short-term high-salt (HS) diet (4% NaCl for 3 days) compared to controls fed a low-salt (LS) diet (0.4% NaCl). Vascular relaxation induced by the superoxide dismutase mimetic tempol (4-hydroxytetramethylpiperidine-1-oxyl), the NADPH oxidase inhibitor apocynin and the xanthine/xanthine oxidase inhibitor oxypurinol was significantly larger in mesenteric arteries from animals fed HS diet compared to arteries from animals fed LS diet. Basal superoxide levels assessed via dihydroethidine (DHE) fluorescence were significantly elevated in arteries from rats fed HS diet, and were reduced by tempol, apocynin and oxypurinol, but not by L-NAME. Basal and methacholine-induced NO production (assessed by DAF-2T fluorescence) was significantly reduced in arteries from rats fed HS diet versus arteries from rats on LS diet. Impaired methacholine-induced NO release and vascular relaxation were restored by tempol and apocynin, but not by oxypurinol. These data suggest that the elevated production of superoxide by NADPH oxidase and xanthine/xanthine oxidase contribute to elevated basal superoxide levels, reduced NO release and impaired vascular relaxation in mesenteric resistance arteries of rats fed HS diet.
The diagnostic sensitivity of dynamic contrast-enhanced magnetic resonance imaging and breast-specific gamma imaging in women with calcified and non-calcified DCIS

Background Early detection of breast cancer reduces mortality. Therefore, diagnosis of ductal carcinoma in situ (DCIS) is important. Purpose To compare the sensitivities of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and breast-specific gamma imaging (BSGI) in pathologically proven calcified and non-calcified DCIS. Material and Methods Thirty-five patients with pathologically diagnosed DCIS from 1 June 2009 through 31 December 2011, underwent a protocol involving both breast MRI and BSGI. Each image was assessed by a separate dedicated breast radiologist. All lesions were divided into two groups; with or without microcalcifications on mammograms. In cases without microcalcifications, we recorded the mass, asymmetry, or negative findings on mammography. On MRI, the enhancement pattern was categorized as mass or non-mass-like enhancement. On BSGI, the uptake pattern was analyzed. The histopathological features of the lesions were obtained. Statistical analysis of the sensitivity of each modality was performed using McNemar’s test. Results Thirty-five women with a mean age of 48 years (range, 26–69 years) were enrolled in the study. The total sensitivities of MRI and BSGI in the 35 cases were 91.4% (32 of 35 DCIS) and 68.6% (24 of 35 DCIS), respectively. Eighteen cases with DCIS displayed microcalcifications on mammography, while 17 cases did not. Of these 17 cases without microcalcifications on mammography, 88.2% (15 of 17 DCIS) were detected by MRI and 52.9% (9 of 17 DCIS) by BSGI. Of 18 cases with microcalcifications on mammography, 94.4% (17 of 18 DCIS) were detected by MRI and 83.3% (15 of 19 DCIS) by BSGI. Conclusion MRI showed a higher sensitivity for the detection of calcified and non-calcified DCIS and is more helpful than BSGI in cases without microcalcifications on mammography.
HESSELMAN'S LAW, PROKOSCH'S LAW, AND MORAIC PRESERVATION IN THE GERMANIC QUANTITY SHIFT

According to Hesselman's Law, lengthenings in closed syllables (CSL) precede lengthenings in open syllables (OSL). This paper surveys dialectal and philological evidence from North Germanic and Upper German in support of Hesselman's Law. The paper argues that CSL serves as a catalyst for OSL. After CSL, short vowels are always followed by long consonants and short consonants are always preceded by long vowels in stressed heavy syllables, a pattern consistent with crosslinguistic tendencies for V/C duration ratios. OSL occurs when language learners extend the pattern by lengthening short vowels followed by heterosyllabic short consonants. The Moraic Preservation Principle (MPP) accounts for the precedence of CSL over OSL despite the preference for bimoraic stressed syllables in Germanic known as Prokosch's Law. A generalization of the Moraic Conservation Principle proposed by Hayes (1989), the MPP states that lengthening processes preserve mora count. CSL does not violate MPP since it results in a bimoraic syllable remaining bimoraic. However, OSL constitutes a violation of MPP by adding to the mora count of the word.I would like to thank two anonymous JGL reviewers and Mark Louden for helpful comments and suggestions.
Trends in survival after childhood cancer in Denmark, 1943‐87: a population‐based study

Survival from cancer in childhood and adolescence was studied in a population‐based series of 8312 cases in children aged 0‐19 years notified to the Danish Cancer Registry during 1943‐87. During the first period (1943‐72), 5‐year survival rates from all malignant neoplasms increased from 23% (1943‐52) to 33% (1963‐72). The greatest improvement was seen during the period 1973‐87 when 5‐year survival rates reached 64% (1983‐87). Between 1973‐77 and 1983‐87, 5‐year survival rates increased from 32% to 62% for leukaemia, from 40% to 70% for acute lymphoblastic leukaemia, from 35% to 54% for non‐Hodgkin's lymphoma, from 50%) to 66% for central nervous system neoplasms and from 25% to 49% for bone tumours. An improvement in 5‐year survival rates from Wilms' tumour was seen between 1960 (19%) and 1980 (81 %). Up to 1972, the 5‐year survival rate from germ‐cell neoplasms was approximately 40%; among patients diagnosed in 1983‐87, 76% survived for 5‐years. Annual lethality decreased by 2.5% for all malignant neoplasms in 1943‐72 and by 4.4% in 1972‐87. Lethality was similar for boys and girls during the period 1943‐72, but was significantly lower for girls subsequently. A marked effect of age at diagnosis was seen in the early registration period, where lethality rate for the age group 0‐9 years was substantially higher compared with that in the age group 10‐19 years. This inequality persisted only for children less than 2 years of age at the time of diagnosis in the later period.
Pregnancy outcomes in women with chronic kidney disease: a systematic review.

BACKGROUND AND OBJECTIVES Pregnant women with chronic kidney disease (CKD) are at risk of adverse maternal and fetal outcomes. We conducted a systematic review of observational studies that described this risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched several databases from their date of inception through June 2010 for eligible articles published in any language. We included any study that reported maternal or fetal outcomes in at least five pregnant women in each group with or without CKD. We excluded pregnant women with a history of transplantation or maintenance dialysis. RESULTS We identified 13 studies. Adverse maternal events including gestational hypertension, pre-eclampsia, eclampsia, and maternal mortality were reported in 12 studies. There were 312 adverse maternal events among 2682 pregnancies in women with CKD (weighted average of 11.5%) compared with 500 events in 26,149 pregnancies in normal healthy women (weighted average of 2%). One or more adverse fetal outcomes such as premature births, intrauterine growth restriction, small for gestational age, neonatal mortality, stillbirths, and low birth weight were reported in nine of the included studies. Overall, the risk of developing an adverse fetal outcome was at least two times higher among women with CKD compared with those without. CONCLUSIONS This review summarizes current available evidence to guide physicians in their decision-making, advice, and care for pregnant women with CKD. Additional studies are needed to better characterize the risks.