Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin resistance, inflammation, and blood pressure determine vascular dysfunction in CKD.

BACKGROUND Conventional cardiovascular risk equations underestimate the risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD), implying a role for novel risk factors. Our aim was to compare vascular function and arterial compliance, known markers of CVD, between patients with CKD and healthy controls and examine their association with traditional and novel CVD risk factors. METHODS Vascular function was determined by using high-resolution ultrasonography to measure brachial artery endothelial-dependent flow-mediated dilatation (FMD) and endothelial-independent glyceryl trinitrate (GTN)-mediated dilatation. Arterial compliance was measured by using pulse contour analysis to generate large-artery (C1) and small-artery (C2) compliance. We also examined the relationship between vascular function, arterial compliance and blood pressure, lipid and lipoprotein levels, insulin resistance, inflammation, oxidative stress, and calcium and phosphate levels in 105 patients with CKD and 40 healthy controls. RESULTS Vascular function and arterial compliance were significantly impaired in patients with CKD compared with healthy controls: mean FMD, 3.8% +/- 0.3% (SE) versus 5.7% +/- 0.6%; GTN-mediated dilatation, 15.7% +/- 0.9% versus 19.6% +/- 1.0%; C1, geometric mean, 12.1 mL/mm Hg; 95% confidence interval (CI), 11.2 to 13.1 versus 15.1 mL/mm Hg; 95% CI, 13.7 to 16.5; and C2, 3.8 mL/mm Hg; 95% CI, 3.4 to 4.3 versus 5.0 mL/mm Hg; 95% CI, 4.2 to 6.0; all P < 0.05. Patients with CKD had greater waist-hip ratios, systolic blood pressures (SBPs), pulse pressures, triglyceride levels, oxidized low-density lipoprotein levels, high-sensitivity interleukin 6 levels, and Homeostasis Model Assessment (HOMA) scores (all P < 0.05) and lower high-density lipoprotein levels (P < 0.001). In patients with CKD, HOMA score and SBP were associated negatively with FMD (model R(2) = 0.28; P < 0.001), and SBP and waist-hip ratio were associated negatively with GTN-mediated dilatation (model R(2) = 0.25; P < 0.001). Pulse pressure was associated negatively with C1 (R(2) = 0.37; P < 0.001), and pulse pressure and high-sensitivity interleukin 6 level were associated negatively with C2 (model R(2) = 0.36; P < 0.001). CONCLUSION Insulin resistance, inflammation, systolic hypertension, and increased pulse pressure, but not dyslipidemia, were associated with vascular dysfunction and may be targets for future interventional strategies to reduce CVD risk in patients with CKD.
Real ileal protein and amino acid digestibilities in feedstuffs for growing pigs as determined with the 15N-isotope dilution technique.

Twelve gilts, with an average initial BW of 38 kg, were fitted with a simple T-cannula at the distal ileum and two catheters in the external jugular veins. The animals were fed 700 g of one of the experimental diets, twice daily at 0800 and 2000. Diets 1 and 2 were cornstarch-based diets formulated to contain 16% CP from soybean meal and canola meal, respectively. Diets 3 and 4 contained 93.9% wheat and barley, respectively. Chromic oxide was included to determine nutrient digestibilities. Following recovery from surgery, 15N-leucine was infused continuously via a jugular catheter for 9 d at a rate of 40 mg.kg BW-1.d-1. Blood samples were taken at every feeding. Ileal digesta were collected for 24 h on d 7 and 9 of the infusion period. Assuming that the 15N-enrichment excess in the trichloroacetic acid-soluble fraction of the blood was similar to that in endogenous N, the contribution of endogenous to total N in ileal digesta was calculated. The amount of endogenous protein (N x 6.25) recovered in digesta collected from the distal ileum were 25.5, 30.5, 27.4 and 27.7 g/kg DM intake for the pigs fed diets 1, 2, 3 and 4, respectively. In the same order for the diets, the real ileal protein digestibilities were 97.5, 84.1, 99.0 and 94.2%, respectively. In addition, the real ileal amino acid digestibilities were calculated. The recoveries of endogenous protein in ileal digesta and the real ileal protein and amino acid digestibilities were higher than those determined by feeding protein-free diets for determining the recovery of endogenous protein and amino acids in ileal digesta.
Psychological distress in women with uterovaginal agenesis (Mayer-Rokitansky-Kuster-Hauser Syndrome, MRKH).

BACKGROUND Uterovaginal agenesis (Mayer-Rokitansky-Küster-Hauser Syndrome; MRKH) is a congenital nonformation of the vagina and the uterus, but with normal ovaries. OBJECTIVE The authors investigated the psychological impact of this disorder, about which very little is known. METHOD A group of 66 women with MRKH were compared with 31 control-group women on a range of self-rating scales assessing psychological distress and self-esteem. RESULTS Women with MRKH had significantly more pathological scores on some of the scales and subscales, such as phobic anxiety and psychoticism (interpersonal alienation), with a similar trend for subscales measuring depression and anxiety. CONCLUSION MRKH has a lasting negative impact on affected women's level of psychological distress and self-esteem.
In the puerperium, primiparae exhibit higher levels of anxiety and serum peptidase activity and greater immune responses than multiparae.

BACKGROUND Delivery is accompanied by increases in anxiety levels that are significantly related to an activation of the inflammatory response system (IRS), as indicated by increases in the serum concentrations of interleukin-6 and the interleukin-1 receptor antagonist (IL-1RA) and increases in the activity of prolyl endopeptidase (PEP), a cytosolic endopeptidase that cleaves peptide bonds on the carboxyl side of proline in behaviorally active neuropeptides involved in anxiety. Primiparae may show an immune responsivity differing from that in multiparae. The aims of this study were to examine whether there are differences in anxiety levels, the IRS, and serum PEP values between primiparae and multiparae before and after delivery. METHOD We administered the Spielberger State-Trait Anxiety Inventory (STAI) to and assessed serum IL-1RA and soluble CD8 (sCD8) concentrations and serum PEP activity in 48 primiparae and 48 multiparae at the end of term and 1 and 3 days after delivery. Data were gathered in 1996 and 1997. RESULTS We found that in primiparae (p =.001), but not in multiparae (p =.6), there was a significant increase in the STAI score 3 days after delivery and that primiparae had significantly higher STAI scores than multiparae 3 days after delivery (p =.01). Primiparae showed significantly higher serum IL-1RA levels than multiparae 1 (p =.003) and 3 (p =.02) days after delivery, but not before delivery. Primiparae also had lower serum sCD8 and higher serum PEP activity than multiparae before and after delivery. CONCLUSIONS The results suggest that primiparae suffer greater anxiety and have a different neuroimmune responsivity than multiparae and that the increased anxiety levels in primiparae may be related to changes in the IRS and serum PEP activity.
Gene Transfer into Neurons from Hippocampal Slices: Comparison of Recombinant Semliki Forest Virus, Adenovirus, Adeno-Associated Virus, Lentivirus, and Measles Virus

Viral vectors are useful for transferring genes into neurons. Here, we characterized recombinant Semliki Forest virus (SFV), adenovirus type 5 (Ad5), adeno-associated virus type 2 (AAV), lentivirus, and measles virus (MV) by their expression of green fluorescent protein (GFP) in rat hippocampal slice cultures. SFV infected more neurons (>90% of all GFP-positive cells) than AAV, lentivirus, and MV (71, 69, and 62%, respectively), whereas no infected neurons were identified with Ad5. AAV-mediated GFP expression was neuron-specific when the platelet-derived growth factor beta-chain promoter rather than cytomegalovirus promoter was used. Transgene expression occurred rapidly but transiently for SFV, increased slowly but remained stable with AAV and lentivirus, and was fast with MV. Resting membrane potential and conductance, action potentials, firing accommodation, and H-current appeared normal in infected CA1 pyramidal cells. Thus, SFV is useful for short-term and AAV and lentivirus for long-term transduction of hippocampal slices, while MV constitutes a novel vector.
Docetaxel in 253 previously treated patients with progressive locally advanced or metastatic breast cancer: results of a compassionate use program in The Netherlands

The aims of this study were to evaluate the efficacy and safety of docetaxel (Taxotere®) in patients with progressive locally advanced or metastatic breast cancer, previously treated with at least one chemotherapy regimen, and the effect of the number of previous chemotherapy lines on response rate, progression-free survival and overall survival. Two-hundred and fifty-three patients from 10 hospitals in The Netherlands received docetaxel as part of a compassionate use program. The majority had received prior anthracycline-containing chemotherapy (84.2%). The recommended starting dose was 100 mg/m2 i.v. every 3 weeks. All patients received corticosteroid premedication. Two-hundred and thirty patients were evaluable for response. The overall response rates (ORR) to docetaxel when used as second-, third- or fourth-line treatment were, respectively, 40.2, 26.0 and 34.6% (p value 0.30). The median progression-free survival for this population was 4.9 months and the median overall survival of the whole group was 8.5 months, and both were not related to the number of previous chemotherapy regimens (p value, respectively, 0.71 and 0.16). The toxicity of docetaxel was manageable and neutropenia was the most frequently noted toxicity. This study confirms that docetaxel is an active cytotoxic agent in pretreated patients with progressive locally advanced or metastatic breast cancer and is still active when used as third- or fourth-line treatment.
Pre-infection transcript levels of FAM26F in peripheral blood mononuclear cells inform about overall plasma viral load in acute and post-acute phase after simian immunodeficiency virus infection

CD8+ cells from simian immunodeficiency virus (SIV)-infected long-term non-progressors and some uninfected macaques can suppress viral replication in vitro without killing the infected cells. The aim of this study was to identify factors responsible for non-cytolytic viral suppression by transcriptional profiling and to investigate their potential impact on SIV replication. Results of microarray experiments and further validation with cells from infected and uninfected macaques revealed that FAM26F RNA levels distinguished CD8+ cells of controllers and non-controllers (P=0.001). However, FAM26F was also expressed in CD4+ T-cells and B-cells. FAM26F expression increased in lymphocytes after in vitro IFN-γ treatment on average 40-fold, and ex vivo FAM26F RNA levels in peripheral blood mononuclear cells correlated with plasma IFN-γ but not with IFN-α. Baseline FAM26F expression appeared to be stable for months, albeit the individual expression levels varied up to tenfold. Investigating its role in SIV-infection revealed that FAM26F was upregulated after infection (P<0.0008), but did not directly correlate with viral load in contrast to MX1 and CXCL10. However, pre-infection levels of FAM26F correlated inversely with overall plasma viral load (AUC) during the acute and post-acute phases of infection (e.g. AUC weeks post infection 0–8; no AIDS vaccine: P<0.0001, Spearman rank correlation coefficient (rs)=−0.89, n=16; immunized with an AIDS vaccine: P=0.033, rs=−0.43; n=25). FAM26F transcript levels prior to infection can provide information about the pace and strength of the antiviral immune response during the early stage of infection. FAM26F expression represented, in our experiments, one of the earliest prognostic markers, and could supplement major histocompatibility complex (MHC)-typing to predict disease progression before SIV-infection.
Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups.

The incidence of deep venous thrombosis (DVT) and the efficacy of prophylactic measures were prospectively evaluated in all patients admitted to a level I trauma center during 1991. Patients with Injury Severity Scores (ISS) > 9 who survived a minimum of 48 hours (n = 395) were monitored using venous Doppler and ultrasound studies during hospitalization (total, 1308 studies). Two hundred eighty-one patients (71%) were randomly assigned to low-dose heparin or sequential compression devices. There were 18 cases of lower extremity DVT (4.6%) and four cases (1.0%) of pulmonary emboli (PE), three of which were fatal. Eight patients (2.9%) on prophylaxis and 10 (8.8%) without prophylaxis developed DVT (p < 0.02 by Chi-square). There were two PEs in each group. Fourteen of these 18 patients sustained blunt trauma and included seven spinal fractures or subluxations (four paraplegic) and four severe head injuries. This represented 14.0% of 50 patients admitted with spinal injuries and 4.3% of 92 patients with severe head injuries. Compared with those with no neurologic injury (7 of 253 or 2.7%), the risk of DVT is significantly higher in the spinal injury patients (p < 0.001, Chi-square) and twice as high as in the head injury group, although not statistically significant (p = 0.4, Chi-square). Three of the four patients with penetrating trauma and DVT had venous injuries. We conclude that DVT prophylaxis can significantly reduce the incidence of DVT in trauma patients with ISS > 9. Patients with severe neurologic injuries (particularly spinal cord) are at high risk for DVT and PE and may be considered for a prophylactic Greenfield filter.
The Objective Measurement of Brace-Use Adherence in the Treatment of Idiopathic Clubfoot.

BACKGROUND A successful outcome for the treatment of idiopathic clubfoot is believed to require adequate adherence to brace use. Previous studies have relied on parental reporting of brace application. We used temperature sensors to determine the adherence to the bracing protocol, the accuracy of parent-reported use, and differences in adherence between patients who experienced relapse of deformity and those who did not. METHODS Using wireless sensors attached to brace sandals, we monitored brace wear over a 3-month period in this cross-sectional study involving 48 patients in 4 age-based groups: 6 to 12 months (Group 1), >1 to 2 years (Group 2), >2 to 3 years (Group 3), and >3 to 4 years (Group 4). Parents were blinded to the purpose of the sensors. The mean number of hours of daily brace use as measured by the sensors was compared with the physician-recommended hours and parent-reported hours of brace use. RESULTS Sensors were retrieved from 44 of 48 patients. Overall, the median brace use recorded by the sensors was 62% (range, 5% to 125%) of that recommended by the physician, and 77% (range, 6% to 213%) of that reported by the parents. For Groups 1 to 3, the difference between the physician-recommended and measured number of hours of daily brace use was significant (p ≤ 0.002), and the difference between the parent-reported and measured number of hours of daily brace use was also significant (p ≤ 0.013). Eight (18%) of the 44 patients who completed the study experienced relapse during the period of monitoring; most importantly, the mean number of hours of brace wear for these patients, 5 hours per day (median, 4; and standard deviation [SD], 3 hours per day) was significantly lower than the 8 hours per day for those who did not experience relapse (median, 9; and SD, 5 hours per day) (p = 0.045). CONCLUSIONS The present study objectively quantified the number of daily hours of post-corrective brace wear for patients with clubfoot in varying age groups and provides an estimate of the number of hours required to avoid relapse. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Crystal structure of the MID-PIWI lobe of a eukaryotic Argonaute protein

Argonaute proteins (AGOs) are essential effectors in RNA-mediated gene silencing pathways. They are characterized by a bilobal architecture, in which one lobe contains the N-terminal and PAZ domains and the other contains the MID and PIWI domains. Here, we present the first crystal structure of the MID-PIWI lobe from a eukaryotic AGO, the Neurospora crassa QDE-2 protein. Compared to prokaryotic AGOs, the domain orientation is conserved, indicating a conserved mode of nucleic acid binding. The PIWI domain shows an adaptable surface loop next to a eukaryote-specific α-helical insertion, which are both likely to contact the PAZ domain in a conformation-dependent manner to sense the functional state of the protein. The MID-PIWI interface is hydrophilic and buries residues that were previously thought to participate directly in the allosteric regulation of guide RNA binding. The interface includes the binding pocket for the guide RNA 5′ end, and residues from both domains contribute to binding. Accordingly, micro-RNA (miRNA) binding is particularly sensitive to alteration in the MID-PIWI interface in Drosophila melanogaster AGO1 in vivo. The structure of the QDE-2 MID-PIWI lobe provides molecular and mechanistic insight into eukaryotic AGOs and has significant implications for understanding the role of these proteins in silencing.
Comparative study of various grading systems in oral squamous cell carcinoma and their value in predicting lymph node metastasis.

BACKGROUND Regional lymph node (LN) metastasis is the single most prognostic factor for oral squamous cell carcinoma (OSCC). An analysis of the prognostic factors is important for predicting prognosis and reducing the mortality in these patients. OBJECTIVES (1) To compare the value of various grading systems in predicting LN metastasis. (2) To evaluate histopathological parameters, which could help in predicting LN metastasis. MATERIALS AND METHODS A total of 20 excisional biopsies of OSCCs, were graded according to the four grading systems that is, Broder's, Jakobsson's, Anneroth and Hansen's, and Brynes. We also evaluated various histopathological parameters, which could help in predicting LN metastasis. RESULTS Grading at the invasive front was most prognostic of LN metastasis. Tumors with total malignancy score ≥8 showed higher incidence of metastases. CONCLUSION The histopathological parameters that could help in predicting lymph node metastases (LNM) are keratinization, nuclear pleomorphism (NP), and the pattern of invasion (POI) when assessed at the invasive front. When the whole tumor was considered, histopathological parameters like NP and POI were significant in predicting LNM.
Factors affecting peri-implant bone resorption in four Implant supported mandibular full-arch restorations: a 3-year prospective study.

BACKGROUND Peri-implant marginal bone-level (MBL) alteration represents one of the parameters included in the criteria for determining implant health. OBJECTIVE Factors affecting peri-implant MBL alteration for 4-implant-supported fixed mandibular prostheses (4-ISFMP) were assessed. MATERIAL & METHODS A 3-year prospective, cohort study was conducted on 44 mandibularly edentulous patients treated with 4-ISFMP. Peri-implant MBL alteration was evaluated radiographically at the 12-, 24- and 36-month follow-ups considering to patient-related risk factors [age, gender, diabetes mellitus, smoking, cardiovascular disease (CVD), rheumatic disorders (RD)] and implant/prosthesis-related features (implant location, keratinized gingiva, denture cantilever length, prosthesis supporting zone, opposing dentition) as well as to peri-implant biological parameters (plaque-, bleeding-, calculus index). RESULTS 148/176 implants (37 patients, drop-out: 15%) were followed for 3 years showing significant (p < 0.001) annual differences of MBL alterations over time. The univariate analysis demonstrated differences of MBL alterations for smokers (p = 0.014), for patients with CVD (p = 0.001) and RD (p = 0.011). In the 3-year multivariate analysis, MBL alteration was influenced by time (p < 0.001) and showed relationship with risk factors as smoking (p < 0.002; OR = 18.965), CVD (p < 0.021; OR = 5.172), RD (p < 0.006; OR = 50.171) and plaque-index (p = 0.034; OR = 3.252). CONCLUSIONS Although peri-implant MBL alteration increased annually, significant odds ratios, were found for patients-related risk factors identifying them potentiating the alterations.
Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms.

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.