Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of non‐enzymatic glycation by silk extracts from a Mexican land race and modern inbred lines of maize (Zea mays)

Non‐enzymatic glycation and the accumulation of advanced glycation end products (AGEs) are associated with various disease states, including complications of diabetes and aging. Secondary metabolites from several plant species are known to inhibit non‐enzymatic glycation and the formation of AGEs, including flavonoids found in the style (silk) of Zea mays (maize). Thirteen modern maize inbreds and one land race were tested for in vitro inhibition of non‐enzymatic glycation of bovine serum albumin. Many of the tested extracts exhibited inhibitory activity, in particular the newest inbreds, which were bred for resistance to gibberella ear rot (Fusarium graminearum) and common smut (Ustilago maydis). The most active maize genotype (CO441), displaying an IC50 of 9.5 µg/mL, was more effective than aminoguanidine, a known inhibitor of glycation. Zapalote chico, a land race with high maysin content, showed only moderate inhibitory activity compared with the modern maize genotypes. Antiglycation activity was highly correlated with the total phenolic content of silk extracts and mildly correlated with resistance to certain fungal infections. The results identify modern resistant and high phenolic maize inbreds as promising candidates for the development of natural AGE inhibitors for the prevention and treatment of diabetic complications and the degenerative effects of aging. Copyright © 2007 John Wiley & Sons, Ltd.
Dietary α-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice.

SCOPE Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. α-Mangostin (α-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary α-MG on murine experimental colitis and on the gut microbiota of healthy mice. METHODS AND RESULTS Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with α-MG (0.1%). α-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with α-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in α-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed α-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC. CONCLUSION α-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by α-MG. Our results suggest that the use of α-MG-containing supplements by patients with UC may have unintentional risk.
Regulation of adenovirus gene expression in human WI38 cells by an E1B-encoded tumor antigen

Adenovirus mutants carrying alterations in the gene encoding the E1B 19-kilodalton tumor antigen (19K protein) cause enhanced cytopathic effect (cyt phenotype) and the degradation of host-cell chromosomal DNA (deg phenotype) upon infection of human HeLa or KB cells. Furthermore, E1B 19K gene mutant viruses are defective for cellular transformation. We report that these mutant viruses possess a host-range phenotype for growth in human cells. In human HeLa cells the mutant viruses grew to the same levels as the wild-type virus, but they were severely defective for growth in KB cells. In human WI38 cells, the E1B 19K gene mutant viruses had a substantial growth advantage over the wild-type virus, yielding 500-fold-higher titers. Viral DNA synthesis was reduced 10- to 20-fold in WI38 cells infected with the wild-type virus relative to that synthesized by the E1B mutant viruses. Viral early and late protein synthesis was similarly reduced in wild type- relative to mutant-infected cells. These reduced levels of early gene expression in wild-type virus-infected cells were paralleled by comparably reduced levels of early cytoplasmic mRNA. The primary cause of this host-range phenotype appeared at the level of early gene transcription, since transcription of viral early genes in the mutant-infected cells was substantially greater than levels found in cells infected with the wild-type virus. These results implicate the E1B 19K tumor antigen in the regulation of adenovirus early gene expression. Specifically, the E1B 19K protein directly or indirectly exerts a negative effect on early gene transcription accounting for efficient gene expression from the E1B mutant viruses in WI38 cells. Based on these findings it is probable that the cyt and deg phenotypes observed in mutant-infected HeLa and KB cells are the result of the pleiotropic effect of this altered gene regulation.
Cortisol levels and mortality in severe sepsis

objective Serum cortisol levels rise in response to the stress of critical illness but the optimal range of serum cortisol in such settings is not clearly defined. The objectives of this study were to determine the range of serum cortisol levels in a group of medical intensive care unit patients with severe sepsis/septic shock using uniform criteria, and to correlate serum cortisol levels to mortality.
Retinoblastoma Family 2 is Required In Vivo for the Tissue-Specific Repression of dE2F2 target Genes

In higher eukaryotes, the Retinoblastoma and E2F families of proteins control the transcription of a large number of target genes. Here, we have mutated the second Drosophila Retinoblastoma family gene (Rbf2), and contrasted the in vivo molecular functions of RBF2 with dE2F2, the only E2F partner of RBF2. Previous studies failed to uncover a unique role for RBF2 in E2F regulation. Here we find that RBF2 functions in concert with dE2F2 in vivo to repress the expression of differentiation markers in ovaries and embryos where RBF2 is highly expressed. We have compared the profiles of transcripts that are mis-expressed in ovaries, embryos and S2 cells where RBF2 function has been ablated and find that RBF2 and dE2F2 control strikingly different transcriptional programs in each situation. In vivo promoter occupancy studies point to the redistribution of dE2F/RBF complexes to different promoters in different cell types as one mechanism governing the tissue-specific regulation of dE2F/RBF target genes. These results demonstrate that RBF2 has a unique function in repressing E2F-regulated differentiation markers and that dE2F2 and RBF2 are required to regulate different sets of target genes in different tissues.
Daily patterns of symptom reporting in families with adolescent children.

OBJECTIVES This study was designed to investigate how symptom reporting varies by time of day, day of the week, gender and generation. DESIGN Concurrent symptom reporting was assessed prospectively using a computer-assisted self-report method. METHODS A computer-assisted self-observation method was used to assess concurrent somatic complaints six times a day for 7 consecutive days. Parents and adolescents from 173 families (568 individuals) filled in questionnaires during a normal workweek. A generalized linear model approach for multi-level models was used to analyse the multiple daily observations. RESULTS Results show a curvilinear within-day pattern for the reporting of somatic complaints, such that complaints were reported most in the morning and evening and least in the middle of the day. On weekends, participants reported fewer complaints in the evening. Women reported more symptoms throughout the day. Adolescents show an earlier and more pronounced increase in symptom reporting towards the evening. In addition, a slight decline in symptom reporting over the observation period was observed. CONCLUSIONS Symptom reporting changes throughout the day, and is influenced by gender, generation and day of the week.
Desmoids and Genotype in Familial Adenomatous Polyposis

BACKGROUND: Desmoid disease can be a serious, life-threatening complication of familial adenomatous polyposis. The ability to predict patients at increased desmoid risk is important, but a convincing genotype-phenotype correlation for desmoid formation has not yet been described. PURPOSE: The aim of this study is to assess the relationship between desmoid disease and genotype in patients with familial adenomatous polyposis. DESIGN: This is a cohort study. PATIENTS: All patients with familial adenomatous polyposis and a documented pathogenic APC mutation in themselves or a first-degree relative were selected. MAIN OUTCOMES MEASURES: The comparison of genotype and the presence, stage, and site of desmoid disease are the primary end points of this study. RESULTS: Three hundred twenty-three patients from 219 families were identified. Mutations spanned the length of the gene, from codon 213 to codon 2051. Desmoid disease was diagnosed in 77 patients from 68 families. Desmoid disease was found in 14.9% of patients with a mutation 5′ of codon 400, 23.2% of patients with a mutation from codon 401 to 1400, and in 37.1% of those with a mutation 3′ of 1400. All patients with 5′ mutations had stage I or II abdominal desmoid disease, and all tumors were stable or shrinking. Twelve percent of patients who had desmoid disease with mutations between codons 400 and 1400 had stage III or IV desmoid disease, and 5 of 42 (12%) tumors were growing at the time of the study. There had been 2 desmoid-related deaths. Almost half (44%) of patients who had desmoid disease with mutations 3′ of codon 1400 had stage III or IV disease. Three of 14 tumors were growing (21%), and there were 4 desmoid-related deaths. LIMITATIONS: This study was conducted at a tertiary referral center, and there was no systematic surveillance for desmoids. CONCLUSION: Desmoid disease occurs in patients who have familial adenomatous polyposis with almost any APC mutation, although there is an increased propensity in those with a 3′ mutation. The incidence and severity of the desmoid disease are related to the site of the mutation.
The Effect of Facilitated Tucking (FT) During Venipuncture on Duration of Crying in Preterm Infants

Abstract Introduction Humans in the last trimester of gestation are assumed to be in a pain-free environment in the womb, but those neonates who are born preterm often spend weeks in the Neonatal intensive care unit (NICU) and undergo numerous painful procedures as part of their routine care. Materials and Methods In this semi-experimental study, 70 preterm infants born at average 32 to 36 weeks' Gestational age (GA), who needed routine blood collection, were allocated to two intervention (35 neonates) and control (35 neonates) groups. In experimental group a nurse held the infant in the side-lying, flexed fetal-type position during blood collection. The stopwatch was used to determine the duration of crying infants. The control group did not receive additional action for pain relief. Data were analyzed by using SPSS version 16 software. Results The mean age of infants was 34.45 ± 1.22 weeks. The results showed that the duration of crying after sampling in the two groups was statistically significant difference, this duration in control group was higher than the intervention group (P
Solution structure of human STARD1 protein and its interaction with fluorescently-labeled cholesterol analogues with different position of the NBD-group

Intracellular cholesterol transfer to mitochondria, a bottleneck of adrenal and gonadal steroidogenesis, relies on the functioning of the steroidogenic acute regulatory protein (StAR, STARD1), for which many disease-associated mutations have been described. Despite significant progress in the field, the exact mechanism of cholesterol binding and transfer by STARD1 remains debatable, and the solution conformation of STARD1 is insufficiently characterized, partially due to its poor solubility. Although cholesterol binding to STARD1 was widely studied by commercially available fluorescent NBD-analogues, the effect of the NBD group position on binding remained unexplored. Here, we analyzed in detail the hydrodynamic properties and solution conformation of STARD1 and its interaction with cholesterol-like steroids bearing 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group in different position, namely 22-NBD-cholesterol (22NC), 25-NBD-cholesterol (25NC), 20-((NBDamino)-pregn-5-en-3-ol (20NP) and 3-(NBDamino)-cholestane (3NC). The small-angle X-ray scattering (SAXS)-based modeling and docking simulations show that, apart from movements of the flexible Ω1-loop, STARD1 unlikely undergoes significant structural rearrangements proposed earlier as a gating mechanism for cholesterol binding. While being able to stoichiometrically bind 22NC and 20NP with high fluorescence yield and quantitative exhaustion of fluorescence of some protein tryptophans, STARD1 binds 25NC and 3NC with much lower affinity and poor fluorescence yield. In contrast to 3NC, binding of 20NP leads to STARD1 stabilization and increases the NBD fluorescence lifetime. Remarkably, in terms of fluorescence response, 20NP outperforms commonly used 22NC and is recommended for future studies. Our study benefits from state-of-the-art techniques and revisits the results of the STARD1 research over the last 20 years, revealing important novel information.
Outcome Analysis of End-to-End and End-to-Side Anastomoses in 131 Patients Undergoing Microsurgical Free Flap Reconstruction of the Lower Extremity

Abstract Background End-to-end and end-to-side anastomoses remain the most common techniques in microsurgical free flap reconstruction. Still, there is an ongoing effort to optimize established techniques and develop novel techniques. Numerous comparative studies have investigated flow dynamics and patency rates of microvascular anastomoses and their impact on flap survival. In contrast, few studies have investigated whether the type of anastomosis influences the outcome of microvascular free flap reconstruction of a lower extremity. Patients and Methods Retrospectively, we investigated the outcome of 131 consecutive free flaps for lower extremity reconstruction related to the anastomotic technique. Results No statistical significance between arterial or venous anastomoses were found regarding the anastomotic techniques (p = 0.5470). However, evaluated separately by vessel type, a trend toward statistical significance for anastomotic technique was observed in the arterial (p = 0.0690) and venous (p = 0.1700) vessels. No thromboses were found in arterial end-to-end anastomoses and venous end-to-side anastomoses. More venous (n = 18) than arterial thromboses (n = 9) occurred in primary anastomoses undergoing microsurgical free flap reconstruction (p = 0.0098). Flap survival rate was 97.37% in the end-to-end arterial group versus 86.36% in the end-to-side group. No thromboses were found in five arterial anastomoses using T-patch technique. Conclusion For lower extremities, there is a connate higher risk for venous thrombosis in anastomotic regions compared with arterial thrombosis. We observed divergent rates for thromboses between end-to-end and end-to-side anastomoses. However, if thrombotic events are explained by anastomotic technique and vessel type, the latter carries more importance.
RESPONSES OF NERVE-FREE VESSELS TO VASOACTIVE AMINES AND POLYPEPTIDES.

Contractile responses of helically cut strips of noninnervated human umbilical artery and vein were determined. Spontaneous, rhythmic contractions were exhibited by both preparations, but were greater in magnitude and duration in umbilical veins. Vasoconstriction elicited by sympathomimetic amines was variable, and generally of a low order. The response to norepinephrine was not potentiated by cocaine (10 µg/ml) but was blocked by Dibenamine (1.0–1.5 µg/ml). Umbilical vasoconstrictor response to tyramine (1.0–10.0 µg/ml) indicated the direct vasoconstrictor effect of this agent. The similar norepinephrine-to-tyramine sensitivity ratios of umbilical vessels and canine main pulmonary artery were interpreted as evidence against the indirect action of tyramine in vitro. Isoproterenol produced no vasodilation in umbilical vessels, suggesting the absence of s-adrenergic pathways. Oxytocin (>>0.1 mU/ml) was a highly effective umbilical vasoconstrictor. Native and synthetic oxytocin preparations were equiactive a.
Summertime sun protection used by adults for their children.

BACKGROUND Because an estimated 50% to 80% of the skin's lifetime sun damage is thought to occur in childhood and adolescence, it is during these critical periods that intense, intermittent sun exposure causing burning increases melanoma risk. METHODS A 1997 telephone survey of 503 households evaluated parental attitudes about their child having a tan, and ease of practicing sun protection, sun protection methods used, and sunburning on 5 successive summer weekends. RESULTS In a random sample of 1 child from each household, 13% of children sunburned during the past week or weekend, and 9% of their parents experienced a sunburn during the past weekend. Children's sunburn was significantly associated with sunburn in the adult respondent, increasing age of the child, having fair skin, being white, and using sunscreens. Duration and peak hours of sun exposure were associated for children and parents. Sunscreen with a sun protection factor of at least 15 was the predominant form of sun protection used. Sunscreen use in children was significantly associated with longer duration of sun exposure, sunny weather conditions, younger age, fair skin, a history of sunburns before this study, a family history of skin cancer, and a higher family income. Feeling that a tan appeared healthy was associated with male gender of the adult and increasing age of the child. Complimenting the child on the appearance of a tan was associated with male gender of the adult, older children, children with skin type reported as olive or dark, and lower educational levels. CONCLUSION Although there has been a promising initial effort to alert parents to the need to protect their children from sunburns, many view a tan as healthy and do not effectively implement sun protection behaviors for their children, which results in sunburns. Sun protection that prevents sunburning could be achieved by more children seeking shade, wearing protective clothing, limiting exposure during peak hours, and effectively using sunscreen.
Clericuzio type poikiloderma with neutropenia is distinct from Rothmund–Thomson syndrome

Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund–Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome. © 2004 Wiley‐Liss, Inc.
Special Interests or Citizens' Rights? “Senior Power,” Social Security, and Medicare

Conventional political analysts and mainstream media accounts attribute substantial political power to the elderly in the United States. This attribution of “senior power” is usually made in the context of the politics of Social Security and Medicare. This article contrasts the conventional construction of elderly political actors as a special interest with a more critical perspective that views Social Security and Medicare as citizens' rights. Critical examination of the welfare state's role in creating age as a potential political cleavage and the politics of Social Security and Medicare reveals that there is no undifferentiated politics of aging in the United States. Rather, age interacts with a variety of other statuses such as race/ethnicity, gender, and class to condition citizens' political mobilization. Welfare state policies—social insurance programs like Social Security and Medicare, means-tested programs like Medicaid and Supplemental Security Income, and targeted tax expenditures for private pensions and health insurance—differentially empower particular subgroups of elderly citizens and routinely disadvantage the most vulnerable elderly, including minority elders, women, and the oldest old.
Distinct Pools of Epithelial Sodium Channels Are Expressed at the Plasma Membrane*

The epithelial Na+ channel (ENaC) is assembled in the endoplasmic reticulum from three structurally related subunits (α, β, and γ). Channel maturation within the biosynthetic pathway involves cleavage of the α and γ subunits by furin and processing of N-linked glycans on α, β, and γ to complex type. Both mature and immature subunits have been observed at the surface of stably transfected Madin-Darby canine kidney cells. We have examined whether channel maturation is an all-or-none event or whether heterogeneous processing of channel subunits occurs within an individual channel complex. Using an immobilized lectin to isolate proteins with complex type N-glycans, we found that individual channel complexes with mature subunits lack immature subunits. Furthermore, terminal processing of N-glycans on ENaC subunits was not dependent on cleavage of ENaC subunits, and proteolysis of channel subunits was not dependent on prior processing of N-glycans. Our results suggest that processing of subunits within an individual channel complex is an all-or-none event such that channels present on the cell surface contain either all mature or all immature subunits. The presence of immature channel complexes at the plasma membrane provides epithelial cells with a reserve of poorly functional channels that can be activated by proteases in post-Golgi compartments.
Identification of gaps in the current knowledge on pulmonary hypertension in extremely preterm infants: A systematic review and meta‐analysis

BACKGROUND Pulmonary hypertension complicates the clinical course of extremely preterm infants and is associated with bronchopulmonary dysplasia (BPD). However, prevalence, risk factors, and outcome of pulmonary hypertension in these infants are insufficiently known. This systematic review and meta-analysis aims to provide an up-to-date overview of available data on prevalence, risk factors, and outcome of pulmonary hypertension and to identify current knowledge gaps. METHODS Medline, EMBASE, and the Cochrane Library databases were searched in July 2017. Two authors reviewed titles/abstracts and full-texts. Eligible studies reported prevalence, patient characteristics or mortality of infants with/without pulmonary hypertension. Studies were excluded if they did not include extremely preterm infants. Only similar study samples (selected infants with BPD or infants both with/without BPD) were compared in the meta-analyses. RESULTS Of 1829 unique articles identified, 25 were eligible for inclusion. Pulmonary hypertension was observed in infants with BPD (20%, 95% confidence interval [CI] 14, 25), but also in those without BPD (2%, 95% CI 0, 8). Infants with severe BPD were most at risk of pulmonary hypertension (risk ratio [RR] 2.7, 95% CI 1.7, 4.2). Infants with pulmonary hypertension were more at risk of mortality (RR 4.7, 95% CI 2.7, 8.3). CONCLUSIONS Pulmonary hypertension occurs in particularly in infants with severe BPD, and increases risk of mortality. Due to selected study populations, heterogeneous pulmonary hypertension-definitions and poorly reported timing of pulmonary hypertension assessments, however, data available in current reports are insufficient to allow accurate assessment of true prevalence, risk factors, and time-related outcome. Prospective studies, with standardised methodology and follow-up are needed to determine these factors.