Miracle-dz/UniFAR-FTUs huggingface dataset:
NSD1 duplication in Silver–Russell syndrome (SRS): molecular karyotyping in patients with SRS features

Silver–Russell syndrome (SRS) is a growth retardation syndrome characterized by intrauterine and postnatal growth retardation, relative macrocephaly and protruding forehead, body asymmetry and feeding difficulties. Nearly 50% of cases show a hypomethylation in 11p15.5, in 10% maternal uniparental disomy of chromosome 7 is present. A significant number of patients with SRS features also exhibit chromosomal aberrations. We analyzed 43 individuals referred for SRS genetic testing by molecular karyotyping. Pathogenic variants could be detected in five of them, including a NSD1 duplication in 5q35 and a 14q32 microdeletion. NSD1 deletions are detectable in overgrowth disorders (Sotos syndrome and Beckwith–Wiedemann syndrome), whereas NSD1 duplications are associated with growth retardation. The 14q32 deletion is typically associated with Temple syndrome (TS14), but the identification of a patient in our cohort reflects the clinical overlap between TS14 and SRS. As determination of molecular subtypes is the basis for a directed counseling and therapy, the identification of pathogenic variants in >10% of the total cohort of patients referred for SRS testing and in >16% of characteristic individuals with the characteristic SRS phenotype confirms the need to apply molecular karyotyping in this cohort.
Predictive value of pulmonary function testing during pulmonary exacerbations in cystic fibrosis

The optimal duration of therapy for acute exacerbations of cystic fibrosis (CF) has not been defined, and the utility of serial pulmonary function testing in predicting the duration of therapy has yet to be established. In a review of 90 pulmonary exacerbations of 39 patients with CF requiring hospitalization, we found that 72% of the patients recovered following 2 weeks of intravenous antibiotics and aggressive chest physiotherapy, and that 28% required an extended third week of therapy. Recovery was delayed in patients with more severe chronic pulmonary disease, but the rate of improvement was independent of the degree of pulmonary deterioration with the acute exacerbation. A 40% recovery of FEV, at 1 week was found to correlate significantly with the duration of hospitalization in the 90 patients. When prospectively applied to a second series of consecutively hospitalized patients with CF, 25/28 patients admitted for 2 weeks demonstrated > 40% improvement in FEV, at 1 week, as compared to 5/10 patients subsequently treated for ≤3 weeks (P = 0.030). The predictive values for 2‐ or 3‐week hospitalizations with 1‐week interval recovery of > 40% or > 40% in FEV, were 79% and 62%, respectively. These findings suggest that the response to intensive therapy in CF exacerbations is variable and that improvements in pulmonary function after 1 week of therapy may be used to predict the subsequent duration of therapy in the majority of CF patients with pulmonary exacerbations. Pediatr Pulmonol. 1993; 16:227–235. © 1993 Wiley‐Liss, Inc.
Pharmacodynamics and Pharmacokinetics of Irbesartan in Patients With Mild to Moderate Hypertension

Background: The pharmacodynamics (plasma angiotensin II [AII], plasma renin activity [PRA], renal function, blood pressure [BP], urinary excretion of major metabolites of pros tacyclin [PGI 2-M], and thromboxane A2 [TXA2-M]) and pharmacokinetics of irbesartan were assessed in hypertensive patients. Methods and Results: Twenty-four white patients with seated diastolic blood pressure 95 to 110 mmHg were randomized to double-blind irbesartan 300 mg or placebo once daily for 4 weeks, following a placebo lead-in. Irbesartan-treated patients had significantly greater 24- hour area under the curve values for mean change from baseline in AII and PRA versus pla cebo-treated patients on day B15 (AII [pg.h/mL]: 261 ± 515 vs 12 ± 51; PRA [(ng/mL/h). h]: 74 ± 162 vs -2 ± 14; P values < . 05). Irbesartan significantly lowered BP without clinically important changes in renal function. Irbesartan had no effect on 24-hour urinary TXA2-M excretion, but significantly increased 24-hour PGI2-M excretion versus placebo on day B29 (20.7 ± 23 pg/mg creatinine vs -2.3 ± 43 pg/mg creatinine; P < .05). Pharmacokinetics were comparable to those from previous studies. The hourly relationship between plasma irbesartan concentration and antihypertensive effect indicated a broad, clockwise hysteresis, with peak concentration occurring at 1.5 hours, whereas peak antihypertensive effect occurred at 4 hours. Conclusions: Irbesartan increases plasma AII and PRA and lowers BP consistent with AT1 receptor blockade, without clinically important effects on renal function.
Long-term outcomes of routine versus provisional T-stenting for de novo coronary bifurcation lesions: five-year results of the Bifurcations Bad Krozingen I study.

AIMS Previously, we reported that the nine-month angiographic result after treatment of coronary bifurcation lesions with provisional T-stenting was not significantly different from that with routine T-stenting. To compare long-term clinical outcomes of the two stenting strategies, we extended the follow-up of our study on bifurcation stenting. METHODS AND RESULTS One hundred and one patients with coronary bifurcation lesions had been randomly assigned to provisional T-stenting and 101 to routine T-stenting, using sirolimus-eluting stents. We performed complete five-year follow-up. The primary efficacy endpoint was the incidence of target lesion revascularisation (TLR), and the primary safety endpoint was the incidence of definite/probable stent thrombosis (ST). We also monitored death, myocardial infarction (MI) and MACE (composite of death, MI and TLR). The cumulative five-year incidence of TLR in the provisional T-stenting arm was not significantly different from that in the routine T-stenting arm (16.2% vs. 16.3%, p=0.97). The same was true for MACE (22.8% vs. 22.9%, p=0.91), the composite of death and MI (9.9% vs. 13.9%, p=0.40), and ST (2.0% vs. 5.1%; p=0.25). CONCLUSIONS During five-year follow-up, routine T-stenting offered no advantage over provisional T-stenting with respect to TLR or MACE. ClinicalTrials.gov Identifier: NCT00288535
Perceived unmet need for mental health care for Canadians with co-occurring mental and substance use disorders.

OBJECTIVE Previous analyses demonstrated an elevated occurrence of perceived unmet need for mental health care among persons with co-occurring mental and substance use disorders in comparison with those with either disorder. This study built on previous work to examine these associations and underlying reasons in more detail. METHODS Secondary data analyses were performed on a subset of respondents to the 2002 Canadian Community Health Survey (unweighted N=4,052). Diagnostic algorithms classified respondents by past-year substance dependence and selected mood and anxiety disorders. Logistic regressions examined the associations between diagnoses and unmet need in the previous year, accounting for recent service use and potential predisposing, enabling, and need factors often associated with help seeking. Self-reported reasons underlying unmet need were also tabulated across diagnostic groups. RESULTS Of persons with a disorder, 22% reported a 12-month unmet need for care. With controls for service use and other potential confounders, the odds of unmet need were significantly elevated among persons with co-occurring disorders (adjusted odds ratio=3.25; 95% confidence interval=1.96-5.37). Most commonly, the underlying reason involved a preference to self-manage symptoms or not getting around to seeking care, with some variation by diagnosis. CONCLUSIONS The findings highlight potential problems for individuals with mental and substance use disorders in accessing services. The elevated occurrence of perceived unmet need appeared to be relatively less affected by contact with the health care system than by generalized distress and problem severity. Issues such as stigma, motivation, and satisfaction with past services may influence help-seeking patterns and perceptions of unmet need and should be examined in future work.
InGaAs/InP double-heterostructure bipolar transistors with near-ideal &#946; versus ICcharacteristic

InGaAs/InP double-heterostructure bipolar transistors (DHBT's) with current gain β ∼ 630 have been realized using gas-source molecular beam epitaxy (GSMBE). These devices exhibit near-ideal β versus I<inf>C</inf>characteristic (i.e., β independent of I<inf>C</inf>) with a small-signal gain<tex>h_{fe} \sim 180</tex>at<tex>I_{C} \sim 2</tex>nA. In comparison, we find<tex>\beta \sim I_{C}^{0.5}</tex>for a high-quality AlGaAs/GaAs HBT grown by OMCVD. The higher emitter injection efficiency at low collector current levels found in the InGaAs/InP DHBT is due to at least a factor 100 smaller surface recombination current.
Effects of Nalidixic Acid on Hamster Knee Cartilage Morphology and Synovial Fluid Composition

Quinolone-induced changes were studied in the knee joints of 4-wk-old female hamsters given intraperitoneal doses of either nalidixic acid (400 mg/kg body weight) or vehicle on days 0 and 1. After euthanasia on day 4, synovial fluid was collected for cytologic evaluation and for analysis of concentrations of hyaluronan, proteoglycans, total protein, and collagen as hydroxyproline. Slides of formalin-fixed decalcified tissues were stained with hematoxylin-eosin or safranin O for histologic scoring of lesion severity. Nine of 10 hamsters treated with nalidixic acid had fissures within articular cartilage of the femur and reduced safranin O staining of matrix indicative of loss of proteoglycans. Synovial membranes from affected joints, however, were not inflamed. Synovial fluid cell counts and cytomorphology were unaffected by treatment. In synovial fluid from 5 of 10 treated hamsters, proteoglycans were elevated by more than 2 SDs above the control group, and individual animal levels correlated with the histologic severity score (r2 = 0.36; p = 0.02). The hyaluronan content of the synovial fluid from treated hamsters was mildly but significantly elevated (p = 0.005), and the histologic severity score again correlated with individual animal levels (r 2 = 0.42; p = 0.01). Hydroxyproline was unaffected by treatment. Although synovial fluid changes and histologic changes were correlated on a group basis, interanimal variability was significant and the magnitude of biochemical changes were far smaller than those that occur during inflammation. Changes in synovial fluid composition are not sufficiently robust to predict cartilage changes in individual animals.
Magnetism in graphene due to single-atom defects: dependence on the concentration and packing geometry of defects

The magnetism in graphene due to single-atom defects is examined by using spin-polarized density functional theory. The magnetic moment per defect due to substitutional atoms and vacancy defects is dependent on the density of defects, while that due to adatom defects is independent of the density of defects. It reduces to zero with decrease in the density of substitutional atoms. However, it increases with decrease in density of vacancies. The graphene sheet with B adatoms is nonmagnetic, but with C and N adatoms it is magnetic. The adatom defects distort the graphene sheet near the defect perpendicular to the sheet. The distortion in graphene due to C and N adatoms is significant, while the distortion due to B adatoms is very small. The vacancy and substitutional atom (B, N) defects in graphene are planar in the sense that there is in-plane displacement of C atoms near the vacancy and substitutional defects. Upon relaxation the displacement of C atoms and the formation of pentagons near the vacancy site due to Jahn–Teller distortion depends upon the density and packing geometry of vacancies.
Nucleotide sequence of bacteriophage f1 DNA

The nucleotide sequence of the DNA of the filamentous coliphage f1 has been determined. In agreement with earlier conclusions, the genome was found to comprise 6,407 nucleotides, 1 less than that of the related phage fd. Phage f1 DNA differs from that of phage M13 by 52 nucleotide changes, which lead to 5 amino acid substitutions in the corresponding proteins of the two phages, and from phage fd DNA by 186 nucleotide changes (including the single-nucleotide deletion), which lead to 12 amino acid differences between the proteins of phages f1 and fd. More than one-half of the nucleotide changes in each case are found in the sequence of 1,786 nucleotides comprising gene IV and the major intergenic region between gene IV and gene II. The sequence of this intergenic region (nucleotides 5501 to 6005) of phage f1 differs from the sequence reported by others through the inclusion of additional single nucleotides in eight positions and of a run of 13 nucleotides between positions 5885 and 5897, a point of uncertainty in the earlier published sequence. The differences between the sequence of bacteriophage f1 DNA now presented and a complete sequence for the DNA previously published by others are discussed, and the f1 DNA sequence is compared with those of bacteriophages M13 and fd.
Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994.

BACKGROUND Air pollution in cities has been linked to increased rates of mortality and morbidity in developed and developing countries. Although these findings have helped lead to a tightening of air-quality standards, their validity with respect to public health has been questioned. METHODS We assessed the effects of five major outdoor-air pollutants on daily mortality rates in 20 of the largest cities and metropolitan areas in the United States from 1987 to 1994. The pollutants were particulate matter that is less than 10 microm in aerodynamic diameter (PM10), ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide. We used a two-stage analytic approach that pooled data from multiple locations. RESULTS After taking into account potential confounding by other pollutants, we found consistent evidence that the level of PM10 is associated with the rate of death from all causes and from cardiovascular and respiratory illnesses. The estimated increase in the relative rate of death from all causes was 0.51 percent (95 percent posterior interval, 0.07 to 0.93 percent) for each increase in the PM10 level of 10 microg per cubic meter. The estimated increase in the relative rate of death from cardiovascular and respiratory causes was 0.68 percent (95 percent posterior interval, 0.20 to 1.16 percent) for each increase in the PM10 level of 10 microg per cubic meter. There was weaker evidence that increases in ozone levels increased the relative rates of death during the summer, when ozone levels are highest, but not during the winter. Levels of the other pollutants were not significantly related to the mortality rate. CONCLUSIONS There is consistent evidence that the levels of fine particulate matter in the air are associated with the risk of death from all causes and from cardiovascular and respiratory illnesses. These findings strengthen the rationale for controlling the levels of respirable particles in outdoor air.
Current and future therapies for gout

ABSTRACT Introduction: Gout is a common disease responsible for recurrent flares triggered by the deposition of monosodium urate crystals secondary to longstanding hyperuricaemia. The management of gout implies both the treatment of flares and the treatment of hyperuricaemia itself. Recent improvement in the understanding of the disease led to the development of new drugs. Areas covered: This review covers data related to ‘old’ treatments of flares and hyperuricaemia, evidence on the recently approved drugs and emerging therapies in development. Expert opinion: Recent data provide a good grasp of the optimal use of colchicine, corticosteroids and NSAIDs for the treatment of flares. Interleukin-1 blocking therapies have an increasing role in the management of difficult-to-treat gout. Sub-optimal use of allopurinol is common and its potency to reduce serum uric acid (SUA) levels is underestimated. Febuxostat effectively reduces SUA levels. New uricosurics, notably lesinurad and arhalofenate, in combination with xanthine oxidase inhibitors, offer promising perspectives to help a greater number of patients achieve sufficient SUA reduction.
Effects of Different Loading Doses of Dexmedetomidine on Bispectral Index under Stepwise Propofol Target-Controlled Infusion

Background and Purpose: Stepwise propofol target-controlled infusion (TCI) can achieve a less disturbed condition of hemodynamics and respiration. Its combination with dexmedetomidine may have some advantages for patients. We studied the effects of different loading doses of dexmedetomidine on the bispectral index (BIS) under stepwise propofol TCI. Methods: Forty patients were randomly assigned into groups D<sub>1.0</sub>, D<sub>0.5</sub>, D<sub>0.25</sub> and D₀, in which dexmedetomidine at 1.0, 0.5, 0.25 or 0 µg•kg<sup>–1</sup> was infused over 10 min followed by 0.5 µg•kg<sup>–1</sup>•h<sup>–1</sup> and stepwise propofol TCI, which was administered with target effect site concentration (Ce) at 0.5 µg•ml<sup>–1</sup>, and increased until 2.5 µg•ml<sup>–1</sup> by 1.0 µg•ml<sup>–1</sup> after 5 min reaching target Ce. BIS, heart rate, MAP, pulse oxygen saturation, RR and end-tidal carbon dioxide pressure were recorded before loading dose (T₀), at 5 min (T<sub>5 min</sub>) and 10 min (T<sub>10 min</sub>) after starting infusion, after 5 min reaching Ce of 0.5, 1.5 and 2.5 µg•ml<sup>–1</sup> (T<sub>p0.5</sub>, T<sub>p1.5</sub> and T<sub>p2.5</sub>). Results: BIS values in group D<sub>1.0</sub> were significantly lower compared with those in group D₀ since T<sub>10 min</sub> and those in groups D<sub>0.5</sub> and D<sub>0.25</sub> since T<sub>p0.5</sub>. In group D<sub>1.0</sub>, heart rate decreased significantly at T<sub>5 min</sub> and T<sub>10 min</sub>, heart rate at T<sub>10 min</sub> was significantly lower compared with that in group D₀. MAP remained stable during the loading dose infusion and decreased to some degree after propofol infusion in all groups. Changes in pulse oxygen saturation, RR and end-tidal carbon dioxide pressurewere similar among the groups without respiration depression. Conclusion: A loading dose of dexmedetomidine of 1.0 µg•kg<sup>–1</sup>, not 0.5 µg•kg<sup>–1</sup> or less, over 10 min followed by 0.5 µg•kg<sup>–1</sup>•h<sup>–1</sup> can definitely decrease the BIS under stepwise propofol TCI with clinically stable blood pressure and without respiration depression, while attention should be paid to decreased heart rate.
VIP Neurotrophism in the Central Nervous System: Multiple Effectors and Identification of a Femtomolar‐Acting Neuroprotective Peptide

Abstract: Vasoactive intestinal peptide has neurotrophic and growth‐regulating properties. As in the case of many neurotrophic molecules, VIP also has neuroprotective properties, including the prevention of cell death associated with excitotoxicity (NMDA), beta‐amyloid peptide, and gp120, the neurotoxic envelope protein from the human immunodeficiency virus. The neurotrophic and neuroprotective properties are mediated in part through the action of glial‐derived substances released by VIP. These substance include cytokines, pro tease nexin I, and ADNF, a novel neuroprotective protein with structural similarities to heat‐shock protein 60. Antiserum against ADNF produced neu ronal cell death and an increase in apoptotic neurons in cell culture. A 14 amino acid peptide (ADNF‐14) derived from ADNF has been discovered that mimics the survival‐promoting action of the parent protein. These studies support the conclusion that VIP, PACAP, and associated molecules are both important regulators of neurodevelopment and strong candidates for therapeutic development for the treatment of neurodegenerative disease.
Analysis of the effects of tumor necrosis factor inhibitors on human hematopoiesis

Truncated soluble fragments of tumor necrosis factor (TNF) receptors have recently been isolated from human serum and urine. These shed forms of TNF receptors bind TNF‐α and lymphotoxin and inhibit various effects of TNF in culture. In this study, we evaluated the role of these molecules in the hematopoietic system. TNF‐α and lymphotoxin inhibited colony forming units granulocyte‐macro‐phage (CFU‐GM) and burst forming units‐erythroid (BFU‐E) in a dose‐dependent fashion at concentrations ranging from 1 to 5,000 U/ml and 25 to 250 U/ ml, respectively. TNF‐α exerted a similar dose‐dependent inhibitory effect on a CD34 enriched marrow cell population, suggesting that its effect is not mediated through CD34∼ accessory ceils. Its suppressive effect was partially reversed by anti‐TNF‐α neutralizing antibodies, thus proving its specificity. Two shed forms of TNF receptors, TNF binding protein (TNF‐bp) and TNF receptor fusion protein (TNFR‐fc), had no significant effect on CFU‐GM proliferation. Both molecules, however, significantly reversed the inhibitory effect of TNF‐α (p < 0.015 and p < 0.03, respectively), whereas they had no effect on the lymphotoxin‐induced CFU‐GM growth inhibition. These results indicate that TNF‐bp and TNFR‐fc may modulate the inhibitory effects of TNF‐α in the hematopoietic system.
Intravenous Immunoglobulin as Therapy for Pediatric Guillain-Barré Syndrome

Seven children with Guillain-Barré syndrome were treated with intravenous immunoglobulin. Median patient age was 5.8 years. A standard dosage of 0.4 g/kg/day for 5 days was administered. Clinical improvement occurred on average within 2.4 ± 1.3 days of beginning intravenous immunoglobulin. One child required mechanical ventilation for 7 days. Eight comparable children with Guillain-Barré syndrome at our institution in a prior study treated with plasmapheresis alone had similar clinical results. However, the need for admission to the pediatric intensive care unit and duration of pediatric intensive care unit stay were lower in the intravenous immunoglobulin treated group (P < .05). There were no complications with intravenous immunoglobulin therapy except for a brief episode of hypotension in one patient. Review of the literature identified 74 additional children with Guillain-Barré syndrome successfully receiving intravenous immunoglobulin therapy. We suggest intravenous immunoglobulin as initial therapy for pediatric Guillain-Barré syndrome, because it appears equally as effective as plasmapheresis and is associated with fewer complications. (J Child Neurol 1997;12:376-380).