Miracle-dz/UniFAR-FTUs huggingface dataset:
In SAPHO syndrome anti-TNF-alpha therapy may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations.

OBJECTIVES SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare disease combining skin, bone and joint manifestations. In recent years new therapeutic strategies have been tried, among them TNF-alpha-blocking agents. We report our experience with infliximab in four cases of SAPHO syndrome refractory to conventional therapies. METHODS Between 2002 and 2005, four cases of SAPHO syndrome (two females and two males; mean age 49.7 yr) responding poorly to conventional drugs were treated with infliximab. The dose was 5 mg/kg, according to the protocol used in spondyloarthropathies, with infusions at 0, 2 and 6 weeks followed by 6 weeks intervals. No active cutaneous manifestations were present at the time of starting therapy. RESULTS Complete remission of osteoarticular involvement was achieved after the second or third infusion, and the positive response was maintained for up to 12 months. A patient relapsed after discontinuation of infliximab, because of infectious complication. Palmoplantaris pustulosis relapsed in two patients after three and six infusions, respectively; there was slight improvement after discontinuation of anti-TNF-alpha drugs. CONCLUSIONS Infliximab seems to be a very effective therapy for osteoarticular complaints of SAPHO syndrome. Cutaneous involvement responded less favourably, palmoplantaris pustulosis relapse being a possible complication.
Feline Generalized Epilepsy Induced by Tranexamic Acid (AMCA)

Summary: Epileptic activities induced by topical application of tranexamic acid (AMCA) and penicillin to the cortex of 12 cats in acute experiments were compared. Both substances when diffusely applied on a wide cortical area of both hemispheres at very low concentration produced an EEG pattern consisting of spike‐wave bursts similar to the electrographic manifestations seen in feline generalized epilepsy induced by large parenteral doses of sodium penicillin. These epileptic bursts could be triggered by repetitive stimulation of nucleus centralis medialis. Increased concentrations of both AMCA and penicillin led to the appearance of bilaterally synchronous spikes and poly‐spikes which were not further excited by NCM stimulation. Two factors seem to play an important role in eliciting spike‐wave bursts in both models: (1) the area of the cortex exposed to the epileptogenic agent and (2) the concentration of the epileptogenic agent used. The similar effects observed in 5 chronic animals either by intravenous injection of high doses of AMCA or by intramuscular injection of sodium penicillin confirm the results obtained in acute experiments and suggest a new way of inducing feline generalized epilepsy.
Risk of seizures in survivors of newborn heart surgery using deep hypothermic circulatory arrest.

OBJECTIVE To identify pre- and intraoperative variables associated with postoperative acute neurologic events (ANEs), including seizures and coma, in newborn survivors of congenital heart surgery undergoing deep hypothermic circulatory arrest (DHCA), and to risk-stratify this population on the basis of preoperative risk variables for the purpose of designing future neuroprotection trials. METHODS Survivors of newborn heart surgery who were enrolled in a neuroprotection trial provided a comprehensive database for the evaluation of pre- and intraoperative variables that influence the postoperative occurrence of ANEs (seizures or coma). Patients with hypoplastic heart syndrome were excluded. After characterization of the study population, stepwise logistic regression, combined with clinical judgment, was used to identify variables that were most likely to be associated with an increased risk of seizures in the study sample and that were most likely to be generalized to other populations. RESULTS Data were available on 164 nonhypoplastic left heart syndrome survivors who underwent newborn heart surgery using DHCA. ANEs occurred in 31 (18.9%) including "seizures alone" (n = 28), "coma alone" (n = 2) or "seizures and coma" (n = 1). A preoperative risk model was constructed demonstrating that infants with a genetic condition and aortic arch obstruction had a 47.8% risk of ANEs compared with all other remaining infants, who had a 9.9% risk. It was also found that prolonged DHCA time (>or=60 minutes) can be a significant risk for infants who have a preexisting genetic condition; however, infants who have genetic conditions and do not undergo prolonged DHCA time or have an aortic arch obstruction are not at increased risk of ANEs. CONCLUSIONS This study provides new information about the occurrence of ANEs after newborn heart surgery. Seizures or coma, which appeared in approximately 19% of all non-hypoplastic left heart syndrome survivors, were not random events but were significantly associated with specific types of congenital heart disease, the presence of genetic conditions, and prolonged DHCA time. The 3 identified variables permitted individual cases to be assigned to low-, intermediate-, or high-risk categories. Because neonatal seizures are a good surrogate marker of long-term neurologic outcome, these models provide useful information to stratify individual patients for risk of seizures in future neuroprotection trials.
Current treatment options in patients with mastocytosis: status in 2015 and future perspectives

Mastocytosis is a term referring to a heterogeneous group of disorders characterized by abnormal mast cell (MC) accumulation in the skin and/or internal organs. In children, the disease involves mostly the skin (cutaneous mastocytosis; CM), whereas in adults, the disease is usually systemic (systemic mastocytosis; SM). Advanced SM variants with end‐organ damage and reduced life expectancy have also been described, but are rare. Clinical signs and symptoms in SM result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. As a consequence, treatment of indolent SM aims primarily at the control of symptoms caused by MC mediator release. By contrast, in advanced SM, such as aggressive SM, MC leukemia, and MC sarcoma, intensive (chemo)therapy with or without allogeneic stem cell transplantation has to be considered. In addition, activating mutations in KIT (mostly KIT D816V in adults) are found in most patients with SM, so that targeted therapies aimed at blocking mutant KIT variants or/and downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies in advanced SM.
A very-high-speed low-power low-voltage fully differential CMOS sample-and-hold circuit with low hold pedestal

A new technique for realizing a very-high-speed low-power low-voltage fully differential CMOS sample-and-hold circuit with low hold pedestal is presented. The fully differential double-sampled design relaxes the trade-off between sampling speed and the sampling precision. Simulation results are given to demonstrate the potential advantage of the new technique.
Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.

CONTEXT Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. OBJECTIVE The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. DESIGN AND POPULATION Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. MAIN OUTCOME MEASURES Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). RESULTS Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. CONCLUSION PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.
Peripheral ossifying fibroma--a clinical evaluation of 134 pediatric cases.

PURPOSE Reported clinicopathologic studies on the peripheral ossifying fibroma (POF), a reactive gingival lesion, have not addressed the pediatric population in specific detail. This study, the first devoted to children, investigated the clinical features of a large number of POFs and compared the findings to cases reported in the English language literature. METHODS Detailed clinical and historical information of 134 surgically removed POFs in patients aged 1-19 formed the basis of this study. Clinical manifestations, histogenesis, treatment rationale with pediatric considerations, and biologic behavior were emphasized. RESULTS The POF was found more frequently in females (60%). It had a predilection for the maxillary gingiva (60%) and for the incisor/cuspid region. The average patient age was 14 years. Only 2 (1%) POFs were found to be unequivocally associated with primary teeth. The clinician seldom included the POF in the differential diagnosis. The recurrence rate after surgical excision was 8%. CONCLUSIONS This study revealed that a POF arising from the periodontal ligament of a primary tooth is most likely a rare event. However, the pediatric patient with a POF has special management considerations compared to the adult. Because of the POF behavior pattern, a proper treatment protocol is warranted with close postoperative follow-up.
Poor permeability of morphine 3-glucuronide and morphine 6-glucuronide through the blood-brain barrier in the rat.

To better understand the in vivo pharmacological effects of morphine 3-glucuronide (M3G, a weak opioid antagonist) and morphine 6-glucuronide (M6G, a potent opioid agonist), the permeability of the blood-brain barrier (BBB) for these metabolites was compared with morphine. Tracers were prepared by enzymatic glucuronidation of [N-methyl-3H]morphine. Brain uptake in rats was measured by the internal carotid perfusion technique and after intravenous bolus injections. In the perfusion experiments morphine showed a permeability-surface area product (PS) of 3.52 +/- 0.61 microliter min-1 g-1. Uptake seemed to be mediated by passive diffusion and was not saturable by 100 microM morphine in the perfusate. The BBB permeability of [3H]M3G and [3H]M6G was too low to be quantified after 5 min of perfusion. Brain uptake of [3H]M3G and [3H]M6G 60 min after i.v. bolus injection reached 0.0060 +/- 0.0003% and 0.0030 +/- 0.0005% injected dose per g, respectively. From these brain concentrations and the corresponding plasma concentration-time curves, BBB PS values of 0.14 +/- 0.02 microliter min-1 g-1 and 0.11 +/- 0.01 microliter min-1 g-1, respectively, were calculated. The ratio of BBB PS values is complementary to the analgesic potencies of morphine and M6G after different routes of administration. The low PS of M6G explains why it is approximately equipotent to morphine after systemic injection, although it is about 2 orders of magnitude more potent than morphine after administration directly into the central nervous system.
IP3 and calcium signaling involved in the reorganization of the actin cytoskeleton and cell rounding induced by cigarette smoke extract in human endothelial cells

Smoking increases the risk of cardiovascular disorders and leads to damage caused by inflammation and oxidative stress. The actin cytoskeleton is a key player in the response to inflammatory stimuli and is an early target of cellular oxidative stress. The purpose of this study was to investigate the changes in actin cytoskeleton dynamics in human endothelial EA.hy926 cells exposed to cigarette smoke extract (CSE). Immunostaining revealed that CSE exposure resulted in modification of the actin cytoskeleton and led to cell rounding in a dose‐ and time‐dependent manner. In addition, the intracellular calcium concentration was increased by treatment with CSE. Pretreatment with antioxidants (lipoic acid, glutathione, N‐acetyl cysteine, aminoguanidine, α‐tocopherol, and vitamin C) significantly attenuated the CSE‐induced actin cytoskeleton reorganization and cell rounding. Calcium ion chelators (EGTA, BAPTA‐AM AM) and a potent store‐operated calcium channel inhibitor (MRS 1845) also reduced CSE‐induced intracellular calcium changes and attenuated actin cytoskeleton reorganization and cell morphology change. Moreover, the CSE‐induced intracellular calcium increase was suppressed by pretreatment with the inositol trisphosphate receptor (IP3R) inhibitor xestospongin C, the phospholipase C (PLC) inhibitor U‐73122, and the protein kinase C (PKC) inhibitor GF109203X. These results suggest that reactive oxygen species production and intracellular calcium increase play an essential role in CSE‐induced actin disorganization and cell rounding through a PLC–IP3–PKC signaling pathway. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1293–1306, 2016.
Characteristics and circumstances of homicidal acts committed by offenders with schizophrenia

Background. While men with schizophrenia are at higher risk of displaying homicidal behaviours compared with the general population, very little is known about the circumstances related to the triggering of such violent acts among offenders with schizophrenia. The main goal of the present investigation was to describe the surrounding context, psychotic symptoms, target characteristics and other circumstantial factors associated with homicidal acts committed by men with schizophrenia, with or without an additional antisocial personality disorder (APD). Method. Comprehensive clinical and research interviews, as well as multiple sources of information including reports from social workers and police officers, criminal records, witness statements and questionnaires completed by friends, acquaintances and family members were used to determine specific characteristics surrounding the homicidal acts. Results. Overall, a significant majority of homicides were considered as the consequence of psychotic symptoms; they mostly involved someone who knew the offender; and they usually occurred in a private residence. However, the subgroup of offenders with both schizophrenia and APD were less likely to be judged as responding to psychotic symptoms; they assaulted a non-relative more frequently, and they were more likely to have used alcohol and to be involved in an altercation with the victim prior to the incident than offenders without APD. Conclusion. Even for such extreme acts as homicides, the circumstances affecting the occurrence of violence among offenders with schizophrenia may differ when an additional APD diagnosis is present, which would have important implications for prevention and treatment programmes.
Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome.

OBJECTIVE Cushing's syndrome (CS) is difficult to diagnose due to its nonspecific presentation. Diagnostic tests like 24-h urine free cortisol (UFC) and the overnight 1 mg dexamethasone suppression test (DST) lack sufficient sensitivity and specificity. Measurement of nocturnal salivary cortisol (NSC) is an accurate and reproducible test with a high sensitivity for CS. However, its performance in mild CS has not been reported. We present 11 cases of CS with normal or mildly elevated UFC in whom NSC was helpful in making a diagnosis. DESIGN AND METHODS All patients had at least one collection of 24-h UFC and NSC and eight had an overnight 1 mg DST. The number of NSC measurements per patient was determined by the clinical index of suspicion and the results of initial testing. Imaging studies included magnetic resonance imaging (MRI) of pituitary or computer tomography scan of abdomen. RESULTS Only four out of eleven patients had elevations in UFC and none were >2 times the upper limit of normal. Seven out of eight had an abnormal DST. All patients had some elevated NSCs (14-100%). Out of eleven patients, six had an abnormality in the pituitary gland found by MRI and two out of eleven had adrenal masses. The remaining three had normal pituitary MRI but had inferior petrosal sinus (IPS) sampling indicating Cushing's disease. All patients had appropriate surgery, and histopathology of all except one was suggestive of either a cortisol-producing adrenal adenoma or an ACTH-secreting pituitary adenoma. CONCLUSION Neither a normal UFC nor a normal NSC excludes mild CS. Multiple samples (urine/saliva) and DST are needed to make the diagnosis of mild CS.
Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer

Approximately one‐third of patients with metastatic breast carcinoma respond to surgical ablative therapy but the morbidity associated with these procedures has limited their use to highly selected patients. Consequently, a chemical method of adrenal suppression was developed using a potent inhibitor of adrenal steroid synthesis, aminoglutethimide, in combination with a synthetic glucocorticoid, dexamethasone. While this regimen effectively blocked adrenal function, it was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism and reduced the bioavailability of dexamethasone. To overcome this problem, a new regime using aminoglutethimide and hydro‐cortisone, a glucocorticoid less susceptible to altered metabolism, was developed. Kinetic studies confirmed that aminoglutethimide does not interact with hydrocortisone to alter its rate of metabolism. Hormone measurements established that 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily suppressed DHA‐sulfate, androstenedione, estrone, estradiol and aldosterone to a greater extent than the prior protocol using aminoglutethimide and 2–3 mg of dexamethasone. Patients experienced objective tumor regression with equal frequency while receiving the aminoglutethimide‐hydrocortisone regimen or aminoglutethimide and dexamethasone and the overall rate of response in 50 evaluable patients was 38%. Side effects occurred frequently in the first few weeks of treatment but disappeared nearly uniformly thereafter. The present aminoglutethimide‐hydrocortisone regimen is simple, non‐toxic, effective in inhibiting estradiol synthesis and capable of inducing tumor regression as frequently as previously reported with adrenalectomy.
Identification of a Novel Self-Sufficient Styrene Monooxygenase from Rhodococcus opacus 1CP

ABSTRACT Sequence analysis of a 9-kb genomic fragment of the actinobacterium Rhodococcus opacus 1CP led to identification of an open reading frame encoding a novel fusion protein, StyA2B, with a putative function in styrene metabolism via styrene oxide and phenylacetic acid. Gene cluster analysis indicated that the highly related fusion proteins of Nocardia farcinica IFM10152 and Arthrobacter aurescens TC1 are involved in a similar physiological process. Whereas 413 amino acids of the N terminus of StyA2B are highly similar to those of the oxygenases of two-component styrene monooxygenases (SMOs) from pseudomonads, the residual 160 amino acids of the C terminus show significant homology to the flavin reductases of these systems. Cloning and functional expression of His10-StyA2B revealed for the first time that the fusion protein does in fact catalyze two separate reactions. Strictly NADH-dependent reduction of flavins and highly enantioselective oxygenation of styrene to (S)-styrene oxide were shown. Inhibition studies and photometric analysis of recombinant StyA2B indicated the absence of tightly bound heme and flavin cofactors in this self-sufficient monooxygenase. StyA2B oxygenates a spectrum of aromatic compounds similar to those of two-component SMOs. However, the specific activities of the flavin-reducing and styrene-oxidizing functions of StyA2B are one to two orders of magnitude lower than those of StyA/StyB from Pseudomonas sp. strain VLB120.
Venoarterial extracorporeal membrane oxygenation in adult patients: predictors of mortality

Background: Extracorporeal membrane oxygenation is a cardiopulmonary supportive therapy. In this study, we reviewed our experience with extracorporeal membrane oxygenation support and tried to identify measurable values which might predict in-hospital mortality. Methods: From January 2004 through December 2008, 50 of 21,298 adult patients received venoarterial extracorporeal membrane oxygenation. We retrospectively analyzed clinical records of these 50 consecutive patients. Details of demographics, preoperative measurements, clinical characteristics at the time of extracorporeal membrane oxygenation implantation, extracorporeal membrane oxygenation-related complications and in-hospital mortality were collected. Logistic regression analyses were performed to investigate predictors of mortality. A p-value ≤ 0.05 was accepted as significant. Results: Thirty-eight patients were weaned from extracorporeal membrane oxygenation and 33 patients survived to discharge. The overall survival rate was 66%. In a multiple logistic regression analysis, blood lactate level before initiation of extracorporeal membrane oxygenation was a risk factor associated with in-hospital mortality (OR 1.27 95% CI 1.042-1.542). To evaluate the utility of the lactate in predicting mortality, a conventional receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 12.6mmol/L, with an area under the curve of 0.752. The positive and negative predictive values were 73.3% and 83.9%, respectively. Conclusions: Extracorporeal membrane oxygenation is a justifiable alternative treatment for postoperative refractory cardiac and pulmonary dysfunction which could rescue more than sixty percent of otherwise fatal patients. Patients with pre-extracorporeal membrane oxygenation lactate levels above 12.6mmol/L are at higher risks for in-hospital death. Evidence-based therapy for this group of high risk patients is needed.