Treatment of spontaneous esophageal rupture with transnasal thoracic drainage and temporary esophageal stent and jejunal feeding tube placement.
Spontaneous rupture of the esophagus is a rare but life-threatening thoracic emergency, with high rates of clinical misdiagnosis and mortality. This article summarizes our experience in the treatment of spontaneous esophageal rupture with transnasal thoracic drainage and temporary esophageal stent and jejunal feeding tube placement. We retrospectively assessed the medical records of 19 patients with spontaneous esophageal rupture treated using our intervention protocol. Patients received local anesthesia and sedation prior to undergoing transnasal drainage catheter placement into the thoracic abscess cavity, followed by temporary esophageal stent and jejunal feeding tube placement. After the operation, abscess lavage, nutritional support, and anti-inflammatory treatment were given. The transnasal thoracic drainage catheter, esophageal stent, and feeding tube were removed after the healing of the abscess cavity. In all, 19 covered esophageal stents were placed in 19 patients with spontaneous esophageal rupture. All operations were technically successful. After an average of 84.06 days, the stents were successfully removed from 17 patients. No cases of massive hemorrhage, esophageal rupture, or other complications occurred during stent removal. An 82-year-old patient died of heart failure 2 months after the operation. One patient died of sudden massive hematemesis and hematochezia 55 days after the operation. In one patient, the esophageal injury failed to heal completely. Our treatment protocol is simple, minimally invasive, and efficacious and may be an alternative for patients who are not candidates for surgery, have a high risk of postoperative complications, or wish to undergo minimally invasive surgery. Therapeutic study, level V.


Nebuliser systems for drug delivery in cystic fibrosis.
Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures. Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.


[The effect on other individual presentations of the goldfish by FG7142 injection].
To research the emotional effects on goldfish shoaling behavior, the change in time spent by the stimulus shoal sizes (0, 1, 2, and 5) was investigated. Consequently, as for shoaling behavior, a difference was seen only in the presence of a shoal, independent of size. The experimental goldfish were then injected with beta-carboline (FG7142, N-Methyl-beta-carboline-3-carboxyamide at 0.1, 1, 2, or 4 mg/kg) or the vehicle and exposed to the stimulus fish (1). In the beta-carboline group with the 1 and 2 mg/kg dose, the time spent within 10 cm of the stimulus fish increased compared with the vehicle, and this increase was maintained throughout the trial. In contrast, the time spent was unchanged in the high-dose group (4 mg/kg). The subject fish motility was unchanged in all dose groups. These results are discussed in their relationship to predator avoidance.


A literature review of electronic portal imaging for radiotherapy dosimetry.
Electronic portal imaging devices (EPIDs) have been the preferred tools for verification of patient positioning for radiotherapy in recent decades. Since EPID images contain dose information, many groups have investigated their use for radiotherapy dose measurement. With the introduction of the amorphous-silicon EPIDs, the interest in EPID dosimetry has been accelerated because of the favourable characteristics such as fast image acquisition, high resolution, digital format, and potential for in vivo measurements and 3D dose verification. As a result, the number of publications dealing with EPID dosimetry has increased considerably over the past approximately 15 years. The purpose of this paper was to review the information provided in these publications. Information available in the literature included dosimetric characteristics and calibration procedures of various types of EPIDs, strategies to use EPIDs for dose verification, clinical approaches to EPID dosimetry, ranging from point dose to full 3D dose distribution verification, and current clinical experience. Quality control of a linear accelerator, pre-treatment dose verification and in vivo dosimetry using EPIDs are now routinely used in a growing number of clinics. The use of EPIDs for dosimetry purposes has matured and is now a reliable and accurate dose verification method that can be used in a large number of situations. Methods to integrate 3D in vivo dosimetry and image-guided radiotherapy (IGRT) procedures, such as the use of kV or MV cone-beam CT, are under development. It has been shown that EPID dosimetry can play an integral role in the total chain of verification procedures that are implemented in a radiotherapy department. It provides a safety net for simple to advanced treatments, as well as a full account of the dose delivered. Despite these favourable characteristics and the vast range of publications on the subject, there is still a lack of commercially available solutions for EPID dosimetry. As strategies evolve and commercial products become available, EPID dosimetry has the potential to become an accurate and efficient means of large-scale patient-specific IMRT dose verification for any radiotherapy department.


Megalocornea, macrocephaly, mental and motor retardation (MMMM).
Two patients with macrocephaly, mild mental retardation and megalocornea are reported. Hypotonia, poor coordination and swallowing difficulties were present. One patient was obese and the other had scoliosis. Both had large fleshy ears and long fingers. The spectrum of the mental retardation megalocornea syndrome is not fully defined. These two patients resemble a previously reported case, and although there are distinct differences from patients with familial or sporadic Neuhauser syndrome, these cases may represent clinical variability of that syndrome.


Tandem repeats in protein coding regions of primate genes.
Tandem repeats in GenBank primate nucleotide sequences annotated as protein coding regions are analyzed. It is found that only trinucleotide repeats show repeat enrichment well above the threshold of statistical significance. The statistics are improved by a simultaneous search for repeats on both the amino acid and nucleotide levels. The results of the analyses of natural sequences are interpreted by comparing them with the results of the computer simulation of the model dedicated to protein coding regions. According to the simulation results, a limited set of trinucleotides, that is, cgg, ccg, cag, and gaa repeats coding for polyalanine, polyglycine, polyproline, polyglutamine, and polylysine are prone to proliferation. It is also found that within the repeat regions slippage is more frequent by a factor of 10 than point mutations, whereas the ratio of silent versus recognizable point mutations is approximately the same as elsewhere in coding regions. The trinucleotide repeats cover slightly more than 0.3% of the protein coding regions of genes.


[Combined surgical procedures in strabismus].
This is a study about the simultaneous horizon-to-vertical surgery and about the myopexia associated with the horizontal rectus muscles surgery. The aim of this article is to demonstrate necessity of these simultaneous operations into different etiopathogenetical strabismus forms. A number of 30 patients were included in the first lot. In this cases we used a simultaneous horizontal and vertical rectus muscles surgery interventions. The second lot--163 patients--has been operated through classical methods on rectus associated with myopexia. The action on the etiopathogenetical factors of strabismus explains this favorable results (more than 80% after 6 months) obtained through combinated surgery intervetions. That is why this operations are indicated in any strabismus forms.


Septate uterus: sonographic diagnosis and obstetric complications.
The present study is a report of the authors' sonographic and obstetric experience in seven cases with anatomically confirmed partial uterine septa. Emphasis is placed on the sonographic appearance and the differential diagnosis of a uterine septum. New sonographic findings are described that can resemble the appearance of a uterine septum during pregnancy, including uterine contractions, cystic masses adjacent to the uterine fundus, and a full urinary bladder. Obstetric complications are compared with previous studies. The authors observed one major obstetric complication of fetal malpresentation.


Erythropoietin-mediated decrease of the redox-sensitive transcription factor NF-kappaB is inversely correlated with the hemoglobin level.
The aim of this study was to determine the effect of rh-EPO on the redox-sensitive transcription factor (NF-kappaB) in vivo and in vitro. Ten patients (7 female, 3 male), mean age 69.2 +/- 11 years, with end-stage renal failure and anemia prior to initiation of regular hemodialysis were enrolled and divided into 2 groups (group A "good responder", 7 patients and group B "poor responder", 3 patients) in accordance to the response to rh-EPO therapy. Nuclear binding activity of NF-kappaB was determined in ex vivo isolated mononuclear cells before, 4 and 8 weeks after onset of regular hemodialysis and rh-EPO therapy by electrophoretic mobility shift assays (EMSA). In group A, a reduction of NF-KB binding activity from 100% to 56 +/- 6% was observed within the first four weeks of rh-EPO treatment, while mean hemoglobin rose from 8.2 +/- 0.4 g/dl to 11.1 +/- 0.2 g/dl. However, this effect was abrogated after another 4 weeks of treatment when NF-kappaB signal increased back to 85.2 +/- 10.6% despite consistent mean hemoglobin level of 11.3 +/- 0.4 g/dl. Group B demonstrated a slight increase of NF-kappaB signal from 100% to 129 +/- 18.5%, while mean hemoglobin only moderately rose from 7.6 +/- 0.3 g/dl to 8.3 +/- 0.1 g/dl within the first 4 weeks, and it further rose to 180 +/- 45% after 8 weeks of treatment, while mean hemoglobin (9.5 +/- 0.1 g/dl) remained low. The NF-kappaB binding activity differed significantly when comparing both groups (p = 0.007). Binding activity of Oct-1, serving as control, did not change notably in either group (p = 0.34). In vitro studies showed that rh-EPO did not directly affect NF-KB binding activity in THP-1 cells. However, coincubation of THP-1 cells with erythrocytes led to a reduction of NF-kappaB binding activity only in THP-1 cells with a hemoglobin level adjusted to 11 g/dl compared to 8 g/dl in the presence of rh-EPO. In vivo and in vitro data implicate a complex interaction between rh-EPO, stimulated RBC and the redox-sensitive transcription factor NF-kappaB in mononuclear cells.


[Hyponatremia--should it be ignored or diagnosed?--Case 8/2011].
HISTORY, CLINICAL FINDINGS: A 72-year-old dehydrated female was admitted to our emergency department. She presented with a decreased level of consciousness and had experienced a fall. Her medication included hydrochlorothiazide and amiloride. Laboratory findings showed a severe hyponatremia with a serum sodium concentration of 107 mmol/l and a reduced serum osmolality. Urine sodium and potassium excretion were > 30 mmol/l. A CT scan of the head did not show any signs of trauma. Using a diagnostic algorithm, the diagnosis of a hypotonic hypovolemic hyponatremia due to the intake of diuretics was confirmed. By intravenous infusion of physiological sodium chloride solution and cessation of diuretics, serum sodium concentration was raised gradually. Hereby, the patient`s state of consciousness completely normalized. Hyponatremia represents the most frequent electrolyte disturbance of hospitalized patients. It correlates with neurological deficits, proneness to falling and intrahospital mortality. Due to diagnostic insecurity of many physicians, the finding of a hyponatremia is often ignored or misclassified. Standardized approaches using diagnostic algorithms improve diagnostic accuracy. The here presented algorithm is based on only few parameters: serum and urine osmolality, urine sodium and potassium. Besides gradual raise of serum sodium, therapy of the underlying cause is essential, for example cessation of diuretics. For patients with syndrome of inadequate secretion of antidiuretic hormone (SIADH; hypotonic isovolemic hyponatremia), selective arginin-vasopressin-receptor 2-antagonists (vaptans) are a new therapeutic option. However, due to high costs, we only see an indication for patients with SIADH who are not able to consequently comply with fluid restriction.


Real-time shape evolution of nanoimprinted polymer structures during thermal annealing.
The real-time shape evolution of nanoimprinted polymer patterns is measured as a function of annealing time and temperature using critical dimension small-angle X-ray scattering (CD-SAXS). Periodicity, line width, line height, and sidewall angle are reported with nanometer resolution for parallel line/space patterns in poly(methyl methacrylate) (PMMA) both below and above the bulk glass transition temperature (T(G)). Heating these patterns below T(G) does not produce significant thermal expansion, at least to within the resolution of the measurement. However, above T(G) the fast rate of loss in pattern size at early times transitions to a reduced rate in longer time regimes. The time-dependent rate of polymer flow from the pattern into the underlying layer, termed pattern "melting", is consistent with a model of elastic recovery from stresses induced by the molding process.


Bimolecular fluorescence complementation demonstrates that the c-Fes protein-tyrosine kinase forms constitutive oligomers in living cells.
The c-fes proto-oncogene encodes a unique nonreceptor protein-tyrosine kinase (c-Fes) that contributes to the differentiation of myeloid hematopoietic, vascular endothelial, and some neuronal cell types. Although originally identified as the normal cellular homologue of the oncoproteins encoded by avian and feline transforming retroviruses, c-Fes has recently been implicated as a tumor suppressor in breast and colonic epithelial cells. Structurally, c-Fes consists of a unique N-terminal region harboring an FCH domain, two coiled-coil motifs, a central SH2 domain, and a C-terminal kinase domain. In living cells, c-Fes kinase activity is tightly regulated by a mechanism that remains unclear. Previous studies have established that c-Fes forms high molecular weight oligomers in vitro, suggesting that the dual coiled-coil motifs may regulate the interconversion of inactive monomeric and active oligomeric states. Here we show for the first time that c-Fes forms oligomers in live cells independently of its activation status using a YFP bimolecular fluorescence complementation assay. We also demonstrate that both N-terminal coiled-coil regions are essential for c-Fes oligomerization in transfected COS-7 cells as well as HCT 116 colorectal cancer and K-562 myeloid leukemia cell lines. Together, these data provide the first evidence that c-Fes, unlike c-Src, c-Abl, and other nonreceptor tyrosine kinases, is constitutively oligomeric in both its repressed and active states. This finding suggests that conformational changes, rather than oligomerization, may govern its kinase activity in vivo.


Effects of obesity on reparative function of human adipose tissue-derived mesenchymal stem cells on ischemic murine kidneys.
Obesity is a health burden that impairs cellular processes. Mesenchymal stem/stromal cells (MSCs) are endowed with reparative properties and can ameliorate renal injury. Obesity impairs human MSC function in-vitro, but its effect on their in-vivo reparative potency remains unknown. Abdominal adipose tissue-derived MSC were harvested from patients without ('lean') or with obesity ('obese') (body mass index <30 or ≥30 kg/m2, respectively) during kidney donation or bariatric surgery, respectively. MSC (5 × 105/200 µL) or vehicle were then injected into 129S1 mice 2 weeks after renal artery stenosis (RAS) or sham surgery (n = 8/group). Two weeks later, mice underwent magnetic resonance imaging to assess renal perfusion and oxygenation in-vivo, and kidneys then harvested for ex-vivo studies. Similar numbers of lean and obese-MSCs engrafted in stenotic mouse kidneys. Vehicle-treated RAS mice had reduced stenotic-kidney cortical and medullary perfusion and oxygenation. Lean (but not obese) MSC normalized ischemic kidney cortical perfusion, whereas both effectively mitigated renal hypoxia. Serum creatinine and blood pressure were elevated in RAS mice and lowered only by lean-MSC. Both types of MSCs alleviated stenotic-kidney fibrosis, but lean-MSC more effectively than obese-MSC. MSC senescence-associated beta-gal activity, and gene expression of p16, p21, and vascular endothelial growth factor correlated with recipient kidney perfusion and tissue injury, linking MSC characteristics with their in-vivo reparative capacity. Human obesity impairs the reparative properties of adipose-tissue-derived MSCs, possibly by inducing cellular senescence. Dysfunction and senescence of the endogenous MSC repair system in patients with obesity may warrant targeting interventions to restore MSC vitality.


Suppression of benign prostate hyperplasia by Kaempferia parviflora rhizome.
Kaempferia parviflora rhizome is used as a folk medicine in Thailand for the treatment of various symptoms. In the present study, the inhibitory activities of extract from K. parviflora rhizome against 5α-reductase (5αR) were subjected. Furthermore, the effects of the extract from K. parviflorar hizome in benign prostate hyperplasia (BPH) were studied using the model mice. Preparations of extracts from the rhizomes of K. parviflora, Curcuma zedoaria and Zingiber officinale, and methoxyflavones isolated from K. parviflora was used for 5αR inhibition assay. The effects of K. parviflora extract on growth suppression for the prostates and seminal vesicles were performed based on the Hershberger's method. The K. parviflora extract was administered to castrated mice for 14 days. K. parviflora extract showed more potent inhibitory activity on 5αR than C. zedoaria and Z. officinale extracts. The active principles were identified as 3,5,7,3',4'-pentamethoxyflavone and 5,7,3',4'-tetramethoxyflavone by activity guided fractionation. Furthermore, K. parviflora extract suppressed the weights of prostates and seminal vesicles in BPH model rats by daily administration for 14 days. These results indicate that K. parviflora extract can be a promising agent for the treatment of BPH.


Pathogenesis of atherosclerosis in diabetes and hypertension.
Prevalence of atherosclerotic vascular disease is markedly increased among individuals with diabetes-mellitus and hypertension. Its major clinical manifestations are consequences of atherosclerosis of coronary arteries, cerebral arteries and large arteries of lower extremities. Thus, atherosclerotic vascular disease is the major cause of mortality and significant morbidity in diabetes and hypertension. Dyslipidemia, hyperinsulinemia, and central obesity seem to be associated with increased risk of atherosclerosis, along with the development of hypertension and diabetes (NIDDM). Insulin resistance is the fundamental factor in this situation which has strong genetic predisposition. Accelerated atherosclerosis in diabetes due to mechanism unique to diabetes like non-enzymatic glycation of proteins, oxidative modification of lipoproteins, formation of lipoproteins immune complexes, lipoproteins aggregation, disturbances of cell replication and growth factors and propensity to thrombosis are clearly established. Therapeutic implication for the prevention of atherosclerosis in diabetes and hypertension clearly emphasizes the need to achieve tight control of hyperglycemia, hypertension, and hyperlipidemia in addition to avoiding cigarette smoking and developing obesity.


The estrogen early response gene FOS is altered in a baboon model of endometriosis.
Endometriosis, the presence of a functional endometrium outside of the uterine cavity, is associated with infertility. In our simulated model of pregnancy in baboons with experimental endometriosis, hCG infusion fails to induce expression of the immunoregulatory protein glycodelin. To test the hypothesis that the development of endometriosis is associated with an aberrant endometrial immunological environment, we examined the expression of a series of immunoregulatory genes in endometrium from baboons with and without endometriosis. Six months following intraperitoneal inoculation with menstrual endometrium, eutopic endometrium was surgically collected between Days 9 and 11 postovulation. Control endometrium was similarly collected from disease-free animals. Total RNA was extracted, and biotinylated cDNA probes were hybridized to the SuperArray GEArray Q series Th1/Th2/Th3 cDNA array, representing 96 genes. Gene expression levels were determined using ScanAlyze and GEArray Analyzer software. Seven genes were upregulated, including JUND, FOS, CCL11, NFKB1 and others, in the endometrium from baboons with endometriosis compared with the endometrium from disease-free animals; one gene, IL1R1, was downregulated. Quantitative RT-PCR confirmed upregulation of FOS and CCL11 in endometriotic eutopic endometrium. Immunohistochemical analysis revealed altered levels and distribution of FOS protein in the eutopic endometrium of baboons with induced endometriosis. These data suggest that in an induced model of endometriosis an aberrant eutopic immunological environment results in a decreased apoptotic potential and in rapid alterations in endometrial gene expression. We propose that the reduced fecundity associated with endometriosis has a multifold etiology in spontaneous and induced disease.


Asbestos related mortality in Northern Ireland: 1985-1994.
The association between Belfast and research into the hazardous effects of asbestos exposure goes back many years. This paper aims to update previous papers and review the burden of asbestos related disease in Northern Ireland today. A study was carried out of all deaths in Northern Ireland between 1985 and 1994 inclusive, in which an asbestos related disease was mentioned anywhere on the death certificate. During this 10 year period, 527 asbestos related deaths were recorded; 88 per cent of these were in men. A total of 410 (77.8 per cent) were registered as the primary cause of death but only 405 (76.9 per cent) of cases were the subject of an autopsy. Standardized rates of pleural cancer in males have been increasing at 3.2 per cent per year though the trend was not significant. Lower rates in the last two years may herald the commencement of a decline. Deaths were clustered around the Belfast estuary, the site of Northern Ireland's shipbuilding industry. High proportional mortality ratios were demonstrated for occupations associated with the shipbuilding and construction industries. Evidence is presented that casts doubt on the attribution of peritoneal cancers in females to asbestos exposure. If lung cancers are included, there may be an average of 81 asbestos related deaths in Northern Ireland every year. Asbestos related diseases continue to extract a heavy burden of ill health in Northern Ireland today. There are some indications that the upward trend may be on the wane but confirmation of this will have to await further data. Measures to reduce exposure in the workplace to both asbestos and to tobacco smoke are the only means of reducing this burden.


In utero exposure to second-hand smoke aggravates the response to ovalbumin in adult mice.
Second-hand smoke (SHS) exposure in utero exacerbates adult responses to environmental irritants. We tested the hypothesis that effects of in utero SHS exposure on modulating physiological and transcriptome responses in BALB/c mouse lungs after ovalbumin (OVA) challenge extend well into adulthood, and that the responses show a sex bias. We exposed BALB/c mice in utero to SHS or filtered air (AIR), then sensitized and challenged all offspring with OVA from 19 to 23 weeks of age. At the end of the adult OVA challenge, we evaluated pulmonary function, examined histopathology, analyzed bronchoalveolar lavage fluid (BALF), and assessed gene expression changes in the lung samples. All groups exhibited lung inflammation and inflammatory cell infiltration. Pulmonary function testing (airway hyperresponsiveness [AHR], breathing frequency [f]) and BALF (cell differentials, Th1/Th2 cytokines) assessments showed significantly more pronounced lung responses in the SHS-OVA groups than in AIR-OVA groups (AHR, f; eosinophils, neutrophils; IFN-γ, IL-1b, IL-4, IL-5, IL-10, IL-13, KC/CXCL1, TNF-α), with the majority of responses being more pronounced in males than in females. SHS exposure in utero also significantly altered lung gene expression profiles, primarily of genes associated with inflammatory responses and respiratory diseases, including lung cancer and lung fibrosis. Altered expression profiles of chemokines (Cxcl2, Cxcl5, Ccl8, Ccl24), cytokines (Il1b, Il6, Il13) and acute phase response genes (Saa1, Saa3) were confirmed by qRT-PCR. In conclusion, in utero exposure to SHS exacerbates adult lung responses to OVA challenge and promotes a pro-asthmatic milieu in adult lungs; further, males are generally more affected by SHS-OVA than are females.


Pattern of clopidogrel use in hospitalized patients receiving percutaneous coronary interventions.
The pattern of clopidogrel loading in patients who had undergone percutaneous coronary intervention (PCI) was studied in a retrospective analysis of clinical records. A database of deidentified electronic medical records from hospitals and hospital-affiliated outpatient facilities throughout the United States was analyzed for PCI patients with or without a diagnosis of acute coronary syndrome (ACS) who received clopidogrel loading doses of > or =300 mg between 48 hours before and 6 hours after PCI. A high dose was defined as > or =600 mg, and pretreatment was defined as more than 6 hours before PCI for 300-599 mg and 2 or more hours before PCI for > or =600 mg. Among 6253 PCI patients who met the criteria, there were 2331 with a diagnosis of ACS (ACS-PCI) and 3922 without an ACS diagnosis (elective PCI). Of the ACS-PCI patients, 1359 had ST-segment elevation myocardial infarction (STEMI) and 972 had unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI). A majority of ACS-PCI patients (57%) received a > or =600-mg loading dose, 34% received a 300-mg loading dose, and the rest received a loading dose between 300 and 600 mg. Loading consisted of a single bolus in 75% of patients, two doses in 21.5%, and three or more doses in 3.1%. The first dose was during or after PCI in 56% of the UA/NSTEMI group and in 71% of both the elective PCI and STEMI groups. Among the UA/NSTEMI group, only 33% met criteria for pretreatment. Reported practice patterns of clopidogrel administration before PCI for UA/NSTEMI were not consistent with evidence generated from published clinical trials and guidelines. Recommended pre-treatment with clopidogrel was frequently not practiced.


ST elevation in the lead aVR during exercise treadmill testing may indicate left main coronary artery disease.
exercise treadmill testing (ETT) is the most widely used method for evaluating patients with coronary artery disease. Predicting the left main coronary artery (LMCA) disease before invasive procedures is very important in risk assessment because of its severe clinical outcome. To examine whether ST elevation in lead aVR during ETT may suggest LMCA disease since the lead aVR is the reciprocal lead of LMCA. in this study, 61 patients with positive ETT were included. The study group consisted of 21 patients with ST elevation in lead aVR. Forty patients, also having positive ETT, but without ST elevation in lead aVR comprised the control group. All patients underwent coronary angiography. coronary angiography in the study group revealed significant LMCA stenosis in 16 (76%) patients, whereas LMCA disease was present in only 3 (8%) patients from the control group. There was no significant coronary artery stenosis in 5 patients in the study group and 12 patients in the control group. Of the 16 patients who had LMCA stenosis, 9 had isolated LMCA disease and 7 had additional stenotic lesions in LAD or circumflex coronary arteries. The sensitivity and specificity of ST segment elevation in lead aVR during ETT was 84% and 88%, respectively. The values of positive and negative predictive value of this finding in diagnosing the presence of LMCA were 76% and 93%, respectively. ST segment elevation in lead aVR during ETT may point to a high probability of the presence of LMCA disease.


Economic evaluation of HLA-B*15:02 screening for carbamazepine-induced severe adverse drug reactions in Thailand.
There is strong evidence of an association between the presence of the human leukocyte antigen (HLA)-B*15:02 and two severe adverse drug reactions-Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)-in patients taking carbamazepine (CBZ), a common treatment for patients with epilepsy and neuropathic pain. As a result, there are calls for all patients that are due to undergo CBZ therapy to be screened for this genetic marker before commencing their therapy. This study aims to determine the value for money of HLA-B*15:02 screening compared to the following: (1) administering CBZ therapy without conducting patient screening, and (2) not prescribing CBZ but alternative drugs that are less likely to result in severe reactions, but that come at a higher cost. An economic evaluation was carried out by using a decision tree and Markov models to examine the cost-utility of providing HLA-B*15:02 screening for all patients with either newly diagnosed epilepsy or neuropathic pain in the Thai setting. All transitional probabilities were derived from the national and international literature. The majority of the data on direct medical care costs were collected from 10 community, provincial, and regional hospitals throughout Thailand. Direct non-medical cost and health-related quality of life (HRQoL) data were obtained from interviews that were conducted with 33 patients, some of whom had experienced severe drug reactions. The incremental cost-effectiveness ratio (ICER) of adopting a universal HLA-B*15:02 screening policy was estimated at 222,000 Thai baht, THB/quality-adjusted life year (QALY) gained for epilepsy patients and 130,000 THB/QALY gained for patients with neuropathic pain. Furthermore, we found that 343 patients need to be tested for HLA-B*15:02 allele to prevent one case of SJS/TEN. Universal HLA-B*15:02 screening represents good value for the money in terms of preventing SJS/TEN in CBZ-treated patients with neuropathic pain at the Thai ceiling ratio of 120,000 THB/QALY gained. However, the prevalence of CBZ-induced SJS/TEN in the Thai population and the positive predictive value (PPV) are major factors that influence the cost-effectiveness of HLA-B*15:02 screening. Therefore, an active surveillance system to make a more accurate assessment of the prevalence CBZ-induced SJS/TEN in the Thai population would enhance the generalizability of the results.


Comparison of RAMP and SSR markers for the study of wild barley genetic diversity.
Two molecular marker technologies, random amplified microsatellite polymorphism (RAMP) and simple sequence repeats (SSR), were used to determine genetic diversity of 27 accessions of the wild barley Hordeum vulgare ssp. spontaneum. 19 primer combinations were used to generate RAMP fragments and 16 SSR loci were analysed. A high level of polymorphism was found with both kind of markers as revealed by the mean polymorphism information content (PIC) values obtained: 0.838 and 0.855 for RAMP and SSR, respectively. Genetic dissimilarities between genotypes were estimated from RAMP and SSR data. A lack of correlation was found between both sets of data. This was reflected in the two dendrograms obtained which presented accessions clustered differently. The results suggest that both sets of markers reveal genetic variation induced by different mechanisms. The dendrogram produced from the RAMP dissimilarity estimates showed most of the groups related to the geographic origin of the accessions.


Spin chirality, Berry phase, and anomalous Hall effect in a frustrated ferromagnet.
An electron hopping on non-coplanar spin sites with spin chirality obtains a complex phase factor (Berry phase) in its quantum mechanical amplitude that acts as an internal magnetic field, and is predicted to manifest itself in the Hall effect when it is not cancelled. The present combined work of transport measurement, neutron scattering, and theoretical calculation provides evidence that the gigantic anomalous Hall effect observed in Nd2Mo2O7, a pyrochlore ferromagnet with geometrically frustrated lattice structure, is mostly due to the spin chirality and the associated Berry phase originating from the Mo spin tilting.


Diagnostic performance of Baveno IV criteria in cirrhotic patients with upper gastrointestinal bleeding: analysis of the F7 liver-1288 study population.
The definition of failure to control bleeding agreed upon at the Baveno IV consensus meeting, included the Adjusted Blood Requirement Index [ABRI: number of blood units/(final-initial hematocrit+0.01)]. ABRI ≥0.75 denotes failure. However, timing for hematocrit measurements was not defined. The aims of this study were: (1) to assess the Baveno IV criteria performance to classify treatment success or failure to control bleeding at 5 days, (2) to determine the appropriate timing for hematocrit. Two hundred and forty-two cirrhotic patients with gastrointestinal bleeding were independently classified by three clinical experts according to the Baveno IV criteria, by analysis of the database of a randomized trial. ABRI was calculated by using the closest hematocrit to the 5 day time point from the first trial product administration (ABRI-1) or after the latest transfusion within the 5-day period (ABRI-2). The gold standard for success/failure for 5-day control of bleeding was the clinical judgment of the three independent observers based on all the clinical and follow-up data. Inter-observer agreement for the final outcome assessment was 0.82 and a final consensus was obtained in 236/242 patients. Inter-observer agreement on patient classification with Baveno IV criteria was 0.70 with ABRI-1 and 0.84 with ABRI-2. c-statistics for correct patients classification were 0.86 for ABRI-1, 0.84 for ABRI-2, and 0.88 for Baveno IV criteria without ABRI. ABRI-1 caused misclassification of 27 patients and ABRI-2 of 39. Baveno IV criteria are accurate to assess outcome of patients with variceal bleeding. There is a substantial observer variability linked to timing of hematocrits for ABRI calculation. With the current definition ABRI does not add to the performance of the other criteria.


The Development of a Phytopathogenic Fungi Control Trial: Aspergillus flavus and Aspergillus niger Infection in Jojoba Tissue Culture as a Model.
After introducing the idea of using concentrations equal to or less than the minimum inhibition concentration (MIC) of some active chemical compounds for evacuating microbial cells, different types of microbes were evacuated. The original protocol was given the name sponge-like protocol and then was reduced and modified from a microorganism to another to prepare microbial ghosts for various applications such as immunological applications, drug delivery, and isolation of DNA and protein. Fungal pathogens that infect plants critically affect cost effectiveness, quality, and quantity of their production. They kill plant cells and/or cause plant stress. Plant fungal infections can originate from many sources such as infected soil, seeds, or crop debris causing diseases and quality losses around the world with billions of US dollars annually as costs of the associated productivity loss. This study focused on the application of the sponge-like protocol in protecting in vitro tissue cultures of plants against fungal pathogens. This can be useful for research purposes or may be developed to be introduced in field applications. Aspergillus flavus and Aspergillus niger infection in tissue culture of jojoba (Simmondsia chinensis (Link) Schn.) was used as a model to establish the employment of this protocol to control plant fungal diseases. The best conditions for A. flavus and A. niger ghosts production previously mapped by randomization experimental design (reduced Plackett-Burman experimental design) were used to prepare fungal ghosts. SDS, NaOH, NaHCO3, and H2O2 were used in their MIC (+1 level) or minimum growth concentration (MGC, -1 level) according to the determined optimal experimental design. The release of both of DNA and protein from the fungal cells was evaluated spectrophotometrically at 260nm and 280nm, respectively, as an indicator for cell loss of their cytoplasm. Fungal ghost cells were also examined by transmission electron microscopy. After confirming the preparation of high-quality fungal ghost cells, the same conditions were mimicked to control plant fungal infection. Jojoba grown in tissue culture was sprayed with fungal cells (about 103 CFU) as a control experiment or fungal cells followed by treatment with solution (a) represents the fungal ghost cells formation calculated critical concentration (FGCCC) of SDS, NaOH, and NaHCO3 and then treatment with solution (b) represents H2O2 FGCCC. The plant was examined on day 0 (plant grown before any infection or infection followed by treatment), day 5 (plant at day 5 after infection or infection followed by treatment), and day 10 (plant at day 10 after infection or infection followed by treatment). We observed fungal growth in case of control experiments at days 5 and 10 on the tissue culture medium, as well as plant, and the absence of any fungal growth in case of plant treated with FGCCC even after day 10. We recommend using this FGCCC in the form of chemical spraying formulation to treat the plants aiming to control different plant fungal infections in in vitro tissue culture systems or applied in field.


Fast atom bombardment mass spectrometry of metal nucleotide complexes.
The fast atom bombardment mass spectrometry of the beta-gamma complexes of ATP and GTP with cobalt and chromium are reported. Spectra were recorded in the positive ion mode. Ions in the molecular weight region allow identification of the complexes to be made.


Elucidation of the Pathogenesis of Autoinflammatory Diseases Using iPS Cells.
Autoinflammatory diseases are a disease entity caused by the dysregulation of innate immune cells. Typical autoinflammatory diseases are monogenic disorders and often very rare. As a result, there is a relative lack of understanding of the pathogenesis, poor diagnosis and little available treatment. Induced pluripotent stem (iPS) cells are a new technology being applied to in vitro disease modeling. These models are especially useful for the analysis of rare and intractable diseases including autoinflammatory diseases. In this review, I will provide a general overview of iPS cell models for autoinflammatory diseases and a brief description of the results obtained from individual reports.


A longitudinal study on the incidence and transmission patterns of HIV, HBV and HCV infection among drug users in Amsterdam.
In the present study data on the incidence of HBV and HCV were used to indicate the prevalence of and trends in risk behavior, assuming that drug users (DUs) who become infected with HBV or HCV are also at risk for infection with HIV. In addition, we determined to that extent the transmission patterns of HIV, HBV and HCV differed. DUs were selected from a cohort study in Amsterdam, had at least one follow-up visit between December 1985 and September 1989 and reported never to have had homosexual contacts. Among 305 DUs, of whom 70% injected recently, the prevalence of HIV, HBV and HCV were 31%, 68% and 65% respectively. These prevalences were strongly interrelated and the same risk factors were found. The cumulative incidence of either HIV or HBV or HCV was 30% among prevalent HIV-negatives. Despite a previously reported reduction in risk behavior, only the HIV incidence tended to decrease initially, and after 1986 the incidences of HIV, HBV and HCV remained disturbingly high and stable (mean: 4, 9 and 10 per 100 person-years, respectively). As at present HBV appears to be transmitted more heterosexually than HIV in our study group and the HIV-epidemic may follow the HBV-epidemic in its transmission patterns, preventive activities targeted at both injecting and sexual behavior should be expanded.


Nonalcoholic Fatty Pancreas Disease.
Nonalcoholic fatty pancreas disease (NAFPD) describes a phenotype of pancreatic steatosis (PS) that is not caused by alcohol consumption, viral infections, toxins, or congenital metabolic syndromes but is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, or increasing age. NAFPD is a relatively new disease entity, as the clinical significance of fatty infiltration of pancreas has gained attention recently. Clinical consequences of NAFPD remain largely unknown despite clinical associations. This review aims to study similarities and differences between hepatic and PS and explore recent advances in NAFPD.


Insight into the structure of the pUL89 C-terminal domain of the human cytomegalovirus terminase complex.
In a previous study, we identified 12 conserved domains within pUL89, the small terminase subunit of the human cytomegalovirus. A latter study showed that the fragment pUL89(580-600) plays an important role in the formation of the terminase complex by interacting with the large terminase subunit pUL56. In this study, analysis was performed to solve the structure of pUL89(568-635) in 50% H2O/50% acetonitrile (v/v). We showed that pUL89(568-635) consists of four alpha helices, but we did not identify any tertiary structure. The fragment 580-600 formed an amphipathic alpha helix, which had a hydrophobic side highly conserved among herpesviral homologs of pUL89; this was not observed for its hydrophilic side. The modeling of pUL89(457-612) using the recognition fold method allowed us to position pUL89(580-600) within this domain. The theoretical structure highlighted three important features. First, we identified a metal-binding pocket containing residues Asp(463), Glu(534), and Glu(588), which are highly conserved among pUL89 homologs. Second, the model predicted a positively charged surface able to interact with the DNA duplex during the nicking event. Third, a hydrophobic patch on the top of the catalytic site suggested that this may constitute part of the pUL89 site recognized by pUL56 potentially involved in DNA binding.


Bacterial lipopolysaccharide induces mRNA expression of an IkappaB MAIL through toll-like receptor 4.
Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is a nuclear IkappaB protein recently identified as a molecule appearing in immunocompetent organs after administration of bacterial lipopolysaccharide (LPS). Participation of Toll-like receptor (TLR) 4, which is a major form of LPS receptors, in the LPS-induced MAIL expression was investigated. When a human myelomonocytic cell line U937 was treated with phorbol 12-myristate 13-acetate for 3 days, the LPS-induced MAIL expression was much potentiated in parallel with an increase in TLR4 expression. The MAIL induction was attenuated when the cells were treated with a neutralizing antibody against TLR4. The in vivo induction of MAIL in the spleen was smaller in mice having a missense mutation of the Tlr4 gene than in normal control mice. These results collectively indicate that TLR4 contributes, at least in part, MAIL induction after LPS stimulation.


Evaluation of acetone cyanohydrin effect in 'in vitro' inativation of the Ehrlich ascites tumor cells.
To evaluate the antitumor effect of acetone cyanohydrin in Ehrlich ascites tumor cells in vitro. The Ehrlich ascites tumor cells and lymphocytes were incubated with different concentrations of acetone cyanohydrin (0, 0.5, 1.0, 2.0, 10.0, 20.0 and 30.0 microg x mL(-1)), After 1, 2, 3, 4, 18 and 24 hours cell viability tests were performed by the trypan blue method. The results demonstrated a dose-dependent cytotoxic effect against the cells of Ehrlich ascites tumor. The concentrations of 20 and 30 microg x mL(-1) was 100% of cell death in only 1 and 2 hours respectively. In lower doses of 0.5, 1.0 and 2.0 microg x mL(-1) the cytotoxic effect was less intense, increasing gradually with time. At low concentrations of 0.5, 1.0 and 2.0 microg x mL(-1), more than 90% of cell death was observed only after 24 hours of incubation which is the evidence that the tumor cell has the ability to poison cumulatively and irreversibly itself with the acetone cyanohydrin when compared with the results presented by human lymphocytes that the same doses and at the same time of incubation reached a maximum of 30% of cell death, suggesting an activity of rhodanese differentiated between the two cells.


Multicenter case-control study of the role of lens materials and care products on the development of corneal infiltrates.
To evaluate the association of symptomatic soft contact lens (SCL)-related corneal infiltrative events (CIEs) with SCL material, lens care products (LCPs), and other risk factors. Cases with symptomatic CIEs were identified in a retrospective, multicenter case-control study at five academic eye care centers. Each case was matched to three controls each who had received eye care near the time of the case's last full examination at that center but were not matched for demographic or other factors. Infiltrate status was established by an expert panel who were masked to sponsor, SCL, and LCP brand. Stratified analyses were conducted removing all daily disposable (DD) and all extended wear (EW) cases. Clinical records from 166 patients with symptomatic CIEs and known EW status were included. Cases used >50 SCL brands and >10 LCP brands. Increased risk in univariate analysis for LCP was not significant after adjustment for other factors. In the multivariate analysis of all cases, use of reusable SCLs (4.03×; 95% C.I. 1.12 to 14.67) and EW (3.98×; 2.32 to 6.84) increased risk and patient age (per year older) was protective (0.96×; 0.94 to 0.98). Among daily wear cases (n = 102 cases), use of reusable SCLs (12.46×; 1.54 to 100.62) and silicone hydrogel (SiHy) (1.99×; 1.06 to 3.75) and age (0.95×: 0.92 to 0.97) were associated. Without DD cases (n = 162), EW (4.42×; 2.53 to 7.70), SiHy use (1.84×; 1.03 to 3.29), and patient age (0.96× 0.94 to 0.98) were significant factors. No specific SCL or LCP brands were associated with increased risk. In this community-based trial, younger patients were at increased risk of infiltrative events. DD lenses were protective relative to reusable lenses. Overnight use increased risk in all analyses and silicone hydrogels increased risk in daily wearers, regardless of LCP brand. Improvements in lens storage case hygiene and environment may be a mechanism for reducing risk of CIEs related to SCL use.


Exploration of Human Activity Recognition Using a Single Sensor for Stroke Survivors and Able-Bodied People.
Commonly used sensors like accelerometers, gyroscopes, surface electromyography sensors, etc., which provide a convenient and practical solution for human activity recognition (HAR), have gained extensive attention. However, which kind of sensor can provide adequate information in achieving a satisfactory performance, or whether the position of a single sensor would play a significant effect on the performance in HAR are sparsely studied. In this paper, a comparative study to fully investigate the performance of the aforementioned sensors for classifying four activities (walking, tooth brushing, face washing, drinking) is explored. Sensors are spatially distributed over the human body, and subjects are categorized into three groups (able-bodied people, stroke survivors, and the union of both). Performances of using accelerometer, gyroscope, sEMG, and their combination in each group are evaluated by adopting the Support Vector Machine classifier with the Leave-One-Subject-Out Cross-Validation technique, and the optimal sensor position for each kind of sensor is presented based on the accuracy. Experimental results show that using the accelerometer could obtain the best performance in each group. The highest accuracy of HAR involving stroke survivors was 95.84 ± 1.75% (mean ± standard error), achieved by the accelerometer attached to the extensor carpi ulnaris. Furthermore, taking the practical application of HAR into consideration, a novel approach to distinguish various activities of stroke survivors based on a pre-trained HAR model built on healthy subjects is proposed, the highest accuracy of which is 77.89 ± 4.81% (mean ± standard error) with the accelerometer attached to the extensor carpi ulnaris.


Response of irritable bowel syndrome with constipation patients administered a combined quebracho/conker tree/M. balsamea Willd extract.
The aim of this case series was to retrospectively examine the symptom response of irritable bowel syndrome with constipation (IBS-C) patients administered an herbal extract in a real-world setting. Twenty-four IBS-C patients in a community office practice were provided a combination over-the-counter dietary supplement composed of quebracho (150 mg), conker tree (470 mg) and M. balsamea Willd (0.2 mL) extracts (Atrantil™) and chose to take the formulation for a minimum of 2 wk in an attempt to manage their symptoms. Patient responses to the supplement were assessed by visual analogue scale (VAS) for abdominal pain, constipation and bloating at baseline and at 2 wk as part of standard-of-care. Patient scores from VAS assessments recorded in medical chart data were retrospectively compiled and assessed for the effects of the combined extract on symptoms. Sign tests were used to compare changes from baseline to 2 wk of taking the extract. Significance was defined as P < 0.05. Twenty-one of 24 patients (88%) responded to the dietary supplement as measured by individual improvements in VAS scores for abdominal pain, bloating and constipation symptoms comparing scores prior to administration of the extract against those reported after 2 wk. There were also significant improvements in individual as well as mean VAS scores after 2 wk of administration of the combined extract compared to baseline for abdominal pain [8.0 (6.5, 9.0) vs 2.0 (1.0, 3.0), P < 0.001], bloating [8.0 (7.0, 9.0) vs 1.0 (1.0, 2.0), P < 0.001] and constipation [6.0 (3.0, 8.0) vs 2.0 (1.0, 3.0), P < 0.001], respectively. In addition, 21 of 24 patients expressed improved quality of life while taking the formulation. There were no reported side effects to administration of the dietary supplement in this practice population suggesting excellent tolerance of the formulation. This pilot retrospective analysis of symptom scores from patients before and after consuming a quebracho/conker tree/M. balsamea Willd extract may support the formulation's use in IBS-C.


Depressive disorders in the Arabian Gulf Cooperation Council countries: a literature review.
To determine the contributions from the six Arabian Gulf Cooperation Council (GCC) countries to the national scientific literature on depressive disorders. This literature review identified all of the published studies on all major depressive disorders as cited on the PubMed® and APA PsycInfo® databases from inception to 31 December 2016 from the six GGC countries. Data were extracted using a standardized form. The study compared the volume of research production between the countries by calculating an index that allowed for the country population size. A total of 28 studies met the inclusion criteria. Saudi Arabia headed the list of publications (10 articles) followed by the United Arab Emirates (n = 6), Kuwait (n = 5), Qatar (n = 3); and Bahrain and Oman produced two articles each. Only six out of the 28 (21.4%) studies included a random sample or adopted good sampling strategies. The majority of studies (24 of 28; 85.7%) were cross-sectional in design. Only one study clearly stated the use of the DSM-4 criteria for diagnosis. The scientific literature published by the GCC countries on depressive disorders is scant and lacking scientific depth. These findings should be considered as a wake-up call for public health researchers, mental health workers and policymakers.


Extracellular SQSTM1 as an inflammatory mediator.
Excessive inflammation may lead to irreparable injury and even death, but the key mediators and underlying mechanisms remain unclear. Our recent findings indicate that SQSTM1/p62 (sequestosome 1), a well-known macroautophagy/autophagy receptor, is a lethal inflammatory mediator of sepsis and septic shock. The release of SQSTM1 occurs during tissue damage or microbial invasion through two main ways: one is passive and the other is active. Passive release occurs in the context of GSDMD-mediated pyroptosis. Active SQSTM1 secretion requires two basic steps: the first step is the expression and phosphorylation of SQSTM1 mediated by STING1/STING/TMEM173, and then the unconventional secretion of SQSTM1 by secretory lysosomes. After release, the extracellular SQSTM1 binds to membrane receptor INSR to activate glycolysis, leading to subsequent production of pro-inflammatory cytokines in a transcription factor NFKB-dependent manner. Functionally, genetic deletion or pharmacological inhibition of the SQSTM1-INSR pathway limits tissue damage, systemic inflammation, organ failure, and death in experimental sepsis models in mice. Moreover, the activation of the SQSTM1-INSR pathway is related to the severity of sepsis in patients. These findings highlight a pathological role of extracellular SQSTM1 in infection, inflammation, and immunity.


Inhibition of stored Ca2+ release disrupts convergence-related cell movements in the lateral intermediate mesoderm resulting in abnormal positioning and morphology of the pronephric anlagen in intact zebrafish embryos.
Ca(2+) is a highly versatile intra- and intercellular signal that has been reported to regulate a variety of different pattern-forming processes during early development. To investigate the potential role of Ca(2+) signaling in regulating convergence-related cell movements, and the positioning and morphology of the pronephric anlagen, we treated zebrafish embryos from 11.5 h postfertilization (hpf; i.e. just before the pronephric anlagen are morphologically distinguishable in the lateral intermediate mesoderm; LIM) to 16 hpf, with a variety of membrane permeable pharmacological reagents known to modulate [Ca(2+)](i). The effect of these treatments on pronephric anlagen positioning and morphology was determined in both fixed and live embryos via in situ hybridization using the pronephic-specific probes, cdh17, pax2.1 and sim1, and confocal imaging of BODIPY FL C(5)-ceramide-labeled embryos, respectively. We report that Ca(2+) released from intracellular stores via inositol 1,4,5-trisphosphate receptors plays a significant role in the positioning and morphology of the pronephric anlagen, but does not affect the fate determination of the LIM cells that form these primordia. Our data suggest that when Ca(2+) release is inhibited, the resulting effects on the pronephric anlagen are a consequence of the disruption of normal convergence-related movements of LIM cells toward the embryonic midline.


Geographic variation in rodent-flea relationships in the presence of black-tailed prairie dog colonies.
We characterized the relationship between fleas and their rodent hosts in the presence of prairie dog colonies and compared them to adjacent assemblages away from colonies. We evaluated the rodent-flea relationship by quantifying prevalence, probability of infestation, flea load, and intensity of fleas on rodents. As prairie dog burrows provide refugia for fleas, we hypothesized that prevalence, flea load, and intensity would be higher for rodents that are associated with black-tailed prairie dog colonies. Rodents were trapped at off- and on-colony grids, resulting in the collection of 4,509 fleas from 1,430 rodents in six study areas. The rodent community composition varied between these study areas. Flea species richness was not different between prairie dog colonies and the surrounding grasslands (p = 0.883) but was positively correlated with rodent species richness (p = 0.055). Prairie dog colonies did not increase the prevalence of fleas (p > 0.10). Flea loads on rodents did not vary between off- and on-colony grids at three of the study areas (p > 0.10). Based on the prevalence, infestation rates, and flea loads, we identified Peromyscus maniculatus, Onychomys leucogaster, and two Neotoma species as important rodent hosts for fleas and Aetheca wagneri, Orchopeus leucopus, Peromyscopsylla hesperomys, Pleochaetis exilis, and Thrassisfotus as the most important fleas associated with these rodents. Prairie dog colonies did not seem to facilitate transmission of fleas between rodent hosts, and the few rodent-flea associations exhibited significant differences between off- and on-colony grids.


The role of the host response in periodontal disease progression: implications for future treatment strategies.
In this paper, we review the relevant aspects of host responses in periodontal diseases as we understand them today. Discussion will focus on neutrophil function, lymphocytes and the immune response, macrophage function, cytokines and complement, fibroblasts and growth factors, and regeneration. Recent literature and concepts will be presented with an emphasis on future directions and application to treatment regimens.


[Usefulness of measuring serum IGG antibodies against A60 mycobacterial antigen for diagnosis of tuberculosis].
Measurement of antimycobacterial antibody may be used as potential diagnostic tool in tuberculosis. The aim of the study was to evaluate the diagnostic value of serum IgG level against A60 mycobacterial antigen measured by ELISA method. Material consisted of 144 persons divided into 5 groups (76 tuberculosis patients, 20 sarcoidosis patients, 17 lung cancer patients, 8 patients with mycobacterial infections other than tuberculosis and 23 healthy controls). In the tuberculosis group there were 50 culture positive cases and 26 culture negative ones, 43 new cases and 32 chronic cases. Positive results were obtained in 51% of tuberculosis patients. Sensitivity increased to 62% in culture positive group and 63% in chronic cases. Specificity of the test was 96%. The results indicate that Immunozyme Mycobacterium test is a valuable tool in tuberculosis diagnosis.


aRNA-longSAGE: a new approach to generate SAGE libraries from microdissected cells.
Large-scale gene expression analyses of microdissected primary tissue are still difficult because generally only a limited amount of mRNA can be obtained from microdissected cells. The introduction of the T7-based RNA amplification technique was an important step to reduce the amount of RNA needed for such analyses. This amplification technique produces amplified antisense RNA (aRNA), which so far has precluded its direct use for serial analysis of gene expression (SAGE) library production. We describe a method, termed 'aRNA-longSAGE', which is the first to allow the direct use of aRNA for standard longSAGE library production. The aRNA-longSAGE protocol was validated by comparing two aRNA-longSAGE libraries with two Micro-longSAGE libraries that were generated from the same RNA preparations of two different cell lines. Using a conservative validation approach, we were able to verify 68% of the differentially expressed genes identified by aRNA-longSAGE. Furthermore, the identification rate of differentially expressed genes was roughly twice as high in our aRNA-longSAGE libraries as in the standard Micro-longSAGE libraries. Using our validated aRNA-longSAGE protocol, we were able to successfully generate longSAGE libraries from as little as 40 ng of total RNA isolated from 2000-3000 microdissected pancreatic ductal epithelial cells or cells from pancreatic intraepithelial neoplasias.


Understanding the challenges faced by Michigan's family farmers: race/ethnicity and the impacts of a pandemic.
Michigan is a critical agricultural state, and small family farms are a crucial component of the state's food sector. This paper examines how the race/ethnicity of the family farm owners/operators is related to farm characteristics, financing, and impacts of the pandemic. It compares 75 farms owned/operated solely by Whites and 15 with People of Color owners/operators. The essay examines how farmers finance their farm operations and the challenges they face doing so. The article also explores how the Coronavirus-19 (COVID-19) pandemic affected farming operations, the financial viability of farms, and how farmers responded to the challenges posed by the pandemic. The study found that People of Color farm owners/operators were younger than White farm owners/operators. The People of Color farm owners/operators tended to manage smaller farms for shorter periods than White farm owners/operators. Though two-thirds of the Farmers of Color owned their farms, they were more financially vulnerable than White farm owners/operators. The farmers studied had difficulty obtaining loans to finance their farms. Farmers reported increasing requests from people for food assistance during the pandemic. Farmers responded to the pandemic by participating in government programs such as the Farm to Families Food Box Program that purchased their produce. It allowed farmers to supply emergency food assistance programs with products from their farms. The products went to families receiving food assistance from soup kitchens, food banks, and other community-based nonprofits.


Evaluation of the effect of tooth type and canal configuration on crown size in mandibular premolars by cone-beam computed tomography.
To achieve success in treatment, one cannot ignore the knowledge of pulp anatomy. Mandibular premolars are considered to be the most difficult teeth for endodontic therapy due to high variability in their canal morphology. It is possible that a relation exists between the crown size and the number of extra canals in these teeth, so this in vitro study aims to investigate the relationship between the crown size and the uncommon morphology of mandibular premolars using Cone-Beam Computed Tomography (CBCT). Eighty three extracted mandibular human premolars were exposed to radiation using the CBCT device. Root canal configuration was categorized according to the Vertucci's classification. The crown size was measured in three axial, coronal and sagittal sections. Finally, the relation between these two factors was evaluated with variance analysis (two-way ANOVA) and chi-square. The most common canal type in the mandibular first and second premolars are type I (71% and 76%, respectively), followed by type V (29% and 22%, respectively). No significant relationship was found between the crown size and extra canals in mandibular premolars (P>0.05). In this in vitro study, the average crown size in two-canalled second premolars was less than that in first premolars with a single canal; although the difference was not statistically significant. The research hypothesis was therefore rejected in both first and second mandibular premolars.


Ultrasound attenuation estimation using backscattered echoes from multiple sources.
The objective of this study was to devise an algorithm that can accurately estimate the attenuation along the propagation path (i.e., the total attenuation) from backscattered echoes. It was shown that the downshift in the center frequency of the backscattered ultrasound echoes compared to echoes obtained in a water bath was calculated to have the form Deltaf=mf(o)+b after normalizing with respect to the source bandwidth where m depends on the correlation length, b depends on the total attenuation, and f(o) is the center frequency of the source as measured from a reference echo. Therefore, the total attenuation can be determined independent of the scatterer correlation length by measuring the downshift in center frequency from multiple sources (i.e., different f(o)) and fitting a line to the measured shifts versus f(o). The intercept of the line gives the total attenuation along the propagation path. The calculations were verified using computer simulations of five spherically focused sources with 50% bandwidths and center frequencies of 6, 8, 10, 12, and 14 MHz. The simulated tissue had Gaussian scattering structures with effective radii of 25 mum placed at a density of 250 mm(3). The attenuation of the tissue was varied from 0.1 to 0.9 dB / cm-MHz. The error in the attenuation along the propagation path ranged from -3.5+/-14.7% for a tissue attenuation of 0.1 dB / cm-MHz to -7.0+/-3.1% for a tissue attenuation of 0.9 dB / cm-MHz demonstrating that the attenuation along the propagation path could be accurately determined using backscattered echoes from multiple sources using the derived algorithm.


A non-invasive photographic modification for recording early vascular development in the chick.
The chick embryo shell-less culture technique allows continuous observation and access to the developing vessels of the area vasculosa (AV); hence, its value as an angiogenesis assay system. The main drawback of the method is that adequately contrasted photographs cannot be achieved without injection of a contrast medium which kills the embryo making further observation of the same specimen impossible. Furthermore, injection prior to 72 h incubation has a high failure rate. In an attempt to overcome these problems, we explored the possibility of using a high-contrast photographic process. Embryos were explanted into shell-less culture after 48 h incubation and photographed through a stereo microscope. After trials with different films we found that Kodalith ortho Type 3 (Kodak) and Technical Pan film (Kodak) produced images of the vasculature which were identical in contrast and detail to India-ink-injected specimens photographed with conventional film. In addition, excellent images could be recorded as early as 48 h of incubation.


Cavitands with mobile walls.
Deep cavitands having three fixed walls and one mobile wall were prepared. The longer wall, built from a quinoxaline spacer, showed enhanced NMR spectra of guests, but the shorter wall based on a benzene spacer showed tighter binding and slower exchange of guests.


Retrospective cohort study of accident outcomes for individuals who have successfully undergone driver assessment following stroke.
The occupational role of 'driver' is highly valued. Stroke can have a significant impact on an individual's ability to drive safely. Multi-disciplinary driver assessments are conducted to assess the safety of post-stroke individuals returning to driving, however, little follow-up of drivers following successful assessment has been performed. The objective of this study was to investigate whether passing a multi-disciplinary driving assessment following stroke predicted medium- to long-term safe and confident driving. A retrospective cohort study with primary data collection through structured telephone interviews was undertaken. Respondents were individuals post-stroke aged 18-74years who had successfully passed a multi-disciplinary driver assessment. Forty-five respondents were interviewed an average of 20months following the assessment. Forty individuals were still driving. Twenty-five driving respondents reported driving in conditions that indicated confident driving. Confident driving was measured by driving frequency and distance, night driving, freeway driving and driving alone. The frequency of accidents and incidents suggests that 95% (n=38) of drivers are 'safe'. Eight respondents reported accidents, one of which was major. In two accidents the respondent was 'at fault'. A crash rate of 222 per 100,000 drivers is within the confidence interval for similar accidents in New South Wales. The results of this small cohort study suggest that a multi-disciplinary driver assessment may be effective in identifying people following stroke with the ability to drive safely and confidently.


[Quantitative relationships of intra- and interspecific competition in Cryptocarya concinna].
The monsoon evergreen broad-leaved forest (MEBF) in Dinghushan Nature Reserve (DNR) has been considered as a zonal vegetation in lower subtropical China, with a history of more than 400 years. In this paper, the intra- and interspecific competition intensity in Cryptocarya concinna, one of the constructive species in MEBF in DNR was quantitatively analyzed by Hegyi single-tree competition index model. The results showed that the intraspecific competition intensity in C. concinna decreased gradually with increasing tree diameter. For C. concinna, its intraspecific competition was weaker than its interspecific competition with Aporosa yunnanensis. The competition intensity of interspecific competition with C. concinna followed the order of A. yunnanensis > Schima superba > Gironniera subaequalis > Acmena acuminatissima > Castanopsis chinensis > Syzygium rehderianum > Pygeum topengii > Blastus cochinchinensis > Sarcosperma laurinum > Pterospermum lanceaefolium > Cryptocarya chinensis. The relationship of the DBH of objective tree and the competition intensity between competitive tree and objective tree in the whole forest and C. concinna population nearly conformed to power function, while that between other competitive tree and the objective C. concinna tree conformed to logarithm function. There was a significantly negative correlation between the competition intensity and the DBH of objective tree.


Covalent surface modification of a titanium alloy with a phosphorylcholine-containing copolymer for reduced thrombogenicity in cardiovascular devices.
Our objective was to develop a surface modification strategy for a titanium alloy (TiAl6V4) to provide thromboresistance for surfaces in rigorous blood-contacting cardiovascular applications, such as that found in ventricular assist devices. We hypothesized that this could be accomplished by the covalent attachment of a phospholipid polymer, poly(2-methacryloyloxyethylphosphorylcholine (MPC)-co-methacryl acid) (PMA). TiAl6V4 was H2O plasma treated by radio frequency glow discharge, silanated with 3-aminopropyltriethoxysilane (APS), and ammonia plasma treated to increase surface reactivity. The TiAl6V4 surface was then modified with PMA via a condensation reaction between the amino groups on the TiAl6V4 surface and the carboxyl groups on PMA. The surface composition was verified by X-ray photoelectron spectroscopy, confirming successful modification of the TiAl6V4 surfaces with APS and PMA as evidenced by increased Si and P. Plasma treatments with H2O and ammonia were effective at further increasing the surface reactivity of TiAl6V4 as evidenced by increased surface PMA. The adsorption of ovine fibrinogen onto PMA-modified surfaces was reduced relative to unmodified surfaces, and in vitro ovine blood contact through a rocking test revealed marked reductions in platelet deposition and bulk phase platelet activation relative to unmodified TiAl6V4 and polystyrene controls. The results indicate that the PMA-modification scheme for TiAl6V4 surfaces offers a potential pathway to improve the thromboresistance of the blood-contacting surfaces of cardiovascular devices.


Group I metabotropic glutamate receptors (mGluRs) modulate visual responses in the superficial superior colliculus of the rat.
Group I metabotropic glutamate receptors (mGluRs) are expressed in cells in the superficial layers of the rat superior colliculus (SSC) and SSC afferents. The purpose of this study was to investigate the physiological effect of Group I mGluR activation on visual responses of SSC neurones using both in vivo and in vitro techniques. In the in vivo preparation, agonists and antagonists were applied by iontophoresis and single neurone activity was recorded extracellularly in anaesthetised rats. Application of the Group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) resulted in a reversible inhibition of the visual response. The effect of DHPG could be blocked by concurrent application of the Group I (mGluR1/mGluR5) antagonist (S)-4-carboxyphenylglycine (4CPG) or mGluR1 antagonist (+)-2-methyl-4-carboxyphenylglycine (LY367385). Application of 4CPG alone resulted in a facilitation of the visual response and this effect was not changed when the visual stimulus contrast was varied. Response habituation was observed when visual stimuli were presented at 0.5 s intervals, but this was not affected by DHPG or 4CPG. In slices of the superior colliculus, stimulation of the optic tract resulted in a field EPSP recorded from the SSC whose duration was increased in the presence of the GABA antagonists picrotoxin and CGP55845. Application of DHPG (5-100 microM) reduced the field EPSP, and this effect could be reversed by the mGluR1 antagonist LY367385 (200 microM), but not by the mGluR5 antagonist MPEP (5 microM). These data show that activation of mGluR1, but probably not mGluR5, can modulate visual responses of SSC neurones in vivo, and that this could be via presynaptic inhibition of glutamate release from either retinal or, possibly, cortical afferents.


Development of functional fish feed with natural ingredients to control heavy metals.
The effects of two natural ingredients, Chinese parsley (CP) and chitosan (CT), on growth, accumulation, and excretion of cadmium in fish body and preservation of essential trace metals in the body were investigated by using rainbow trout that had been fed cadmium-added diet, low and high concentration, for 3 weeks. This pretest confirmed that cadmium was accumulated in the liver, kidney, and intestine of the test fish. The cadmium level of the fish, fed diet with CP or CT, was decreased by 18% and 24%, respectively, compared to that of the fish given the control diet. But CP and CT did not have an influence on normal growth of test fish and the levels of essential trace metals in the body. In addition, the level of cadmium was higher in liver than kidney in the high-cadmium dietary group, indicating the Cd level in kidney follows that of liver as kidney lies in the final stage of metabolism. The cadmium accumulation in the fish body was supposed to be reduced, by giving CP to increase the solubility of Cd to body fluid by conjugation into metallothioneins (MTs), while CT was supposed to be responsible for the physical adsorption of cadmium ions by glucosamine groups.


Using mesoscopic models to design strong and tough biomimetic polymer networks.
Using computational modeling, we investigate the mechanical properties of polymeric materials composed of coiled chains, or "globules", which encompass a folded secondary structure and are cross-linked by labile bonds to form a macroscopic network. In the presence of an applied force, the globules can unfold into linear chains and thereby dissipate energy as the network is deformed; the latter attribute can contribute to the toughness of the material. Our goal is to determine how to tailor the labile intra- and intermolecular bonds within the network to produce material exhibiting both toughness and strength. Herein, we use the lattice spring model (LSM) to simulate the globules and the cross-linked network. We also utilize our modified Hierarchical Bell model (MHBM) to simulate the rupture and reforming of N parallel bonds. By applying a tensile deformation, we demonstrate that the mechanical properties of the system are sensitive to the values of N(in) and N(out), the respective values of N for the intra- and intermolecular bonds. We find that the strength of the material is mainly controlled by the value of N(out), with the higher value of N(out) providing a stronger material. We also find that, if N(in) is smaller than N(out), the globules can unfold under the tensile load before the sample fractures and, in this manner, can increase the ductility of the sample. Our results provide effective strategies for exploiting relatively weak, labile interactions (e.g., hydrogen bonding or the thiol/disulfide exchange reaction) in both the intra- and intermolecular bonds to tailor the macroscopic performance of the materials.


Influence of postmortem time and temperature on osteoinductive activity of demineralized microperforated ethylene oxide-sterilized syngeneic bone implant in the rat.
Bone morphogenetic protein is labile and easily inactivated by many extracorporeal factors. It is crucial to establish whether delay in retrieval of donor bone and ambient holding temperature of the donor body influence osteoinductivity of bone left in situ. Of ten adult rats that were killed, five were kept at 4 degrees and five at room temperature. Femurs were harvested at 24, 36, 48, 72, and 168 hours. After processing, segments were implanted in 20 four-week-old syngeneic rats for 14 days. The level of osteoinduction was evaluated histologically. It was excellent in the 4 degrees group in the 24-, 36-, and 48-hour specimens but less advanced at 72 hours. Bone taken from the room temperature group showed findings identical to those kept at 4 degrees through 36 hours, but osteoinduction was less advanced at 48 hours and absent at 72 hours. No bone formed at 168 hours in either temperature group. The following observations were made. (1) Osteoinductivity of demineralized bone left in situ after death was unexpectedly stable. (2) Retrieval time was extended by donor cooling. (3) Microperforated demineralized bone actively induced new bone formation. (4) Ethylene oxide does not inhibit osteoinduction when correctly applied for sterilization. If confirmed in humans, retrieval of bone to be used for osteoinduction could be delayed for some hours, particularly if the donor was immediately refrigerated. This would increase the effective number of bone tissue donors and utilize an undeveloped resource.


A quantitative risk analysis tool for design/simulation of wastewater treatment plants.
Uncertainty is a central concept in the decision-making process, especially when dealing with biological systems subject to large natural variations. In the design of activated sludge systems, a conventional approach in dealing with uncertainty is implicitly translating it into above-normal safety factors, which in some cases may even increase the capital investments by an order of magnitude. To obviate this problem, an alternative design approach explicitly incorporating uncertainty is herein proposed. A probabilistic Monte Carlo engine is coupled to deterministic wastewater treatment plant (WWTP) models. The paper provides a description of the approach and a demonstration of the general adequacy of the method. The procedure is examined in an upgrade of a conventional WWTP towards stricter effluent standards on nutrients. The results suggest that the procedure can support the decision-making process under uncertainty conditions and that it can enhance the likelihood of meeting effluent standards without entailing above-normal capital investments. The analysis led to reducing the capital investment by 43%, producing savings of more than 1.2 million euro.


Polycystic ovary syndrome and implications for the menopause.
Polycystic ovary syndrome (PCOS) is the most common endocrine condition of premenopausal women and has significant metabolic abnormalities that could have an impact after the menopause. Diabetes mellitus, hyperlipidemia and hyperinsulinemia could potentially affect health in this era of life. Endometrial cancer, due to unopposed estrogen action, is more common where progestins have not been given for menstrual dysfunction. Preventive management earlier in life will avoid postmenopausal problems in PCOS.


Why market-driven forces in our health industry might eventually stumble: what could happen then?
The Republican takeover of Capitol Hill suggests that the payer-driven forces of managed care and the regional networks will serve as the centerpieces to improve the organization, financing, and delivery of our nation's health services. The "voluntary" alliances that are now being forged may stumble when attempting to restrain the inflationary spiral of Medicare and Medicaid expenditures and when seeking to finance the care of an increasing number of uninsured working poor and their dependents. The American health industry can anticipate experiencing increasingly monopolistically competitive environments. The public will eventually demand the formation of state health services commissions to foster a semblance of control. Within this framework, the German decentralized, multipayer, multitier approach, which is self-governing and allows for negotiating reimbursement rates between insurers and providers, offers a preferred model to the traditional American public utility model.


The atrial natriuretic peptide system in rat ovaries.
The atrial natriuretic peptide (ANP) gene is expressed in several extracardiac tissues where ANP is thought to be involved in autocrine or paracrine regulation. The current studies were designed to characterize the ANP system in rat ovaries. ANP content in rat ovaries was estimated by RIA to be 240 +/- 70 pg/mg protein. HPLC revealed the presence of the 28-amino acid circulating peptide as well as the 126-amino acid prohormone, suggesting that the ovaries are a site of ANP synthesis. Indeed, ANP messenger RNA was detected in this tissue by RNase mapping. ANP present in ovarian extracts displaced [125I]ANP from bovine adrenal receptors (R1 class) in a dose-dependent manner and in parallel to the synthetic peptide, indicating that it possesses biological activity. Immunocytochemical studies localized ANP to interstitial cells surrounding the follicles; weaker but specific staining was also observed in the ovum. High affinity ANP receptors (dissociation constant, 0.30 +/- 0.06 nM; maximum binding capacity, 160 +/- 40 fmol/mg protein) were identified in ovarian membranes. Unlabeled ANP but not c-atrial natriuretic factor (a specific agonist of ANP clearance receptors) competed with binding of [125I]ANP to ovarian membranes in a dose-dependent manner, suggesting that ovarian ANP receptors are predominantly of the R1 class. This was confirmed by cross-linking studies with [125I]ANP, which detected a single protein band with a molecular size of about 120 kilodaltons, corresponding to that of the guanylate cyclase-coupled R1 class of receptor. Consistent with the presence of biologically active receptors, ANP markedly enhanced cGMP accumulation (by 15-fold) in ovarian cells. The presence of both local ANP synthesis and high affinity transducing receptors in the ovaries indicates that the peptide plays a local role in ovarian growth or steroidogenesis.


Probing conformational and functional states of human hepatocyte growth factor by a panel of monoclonal antibodies.
HGF-Met signaling contributes to various biological events by controlling cell migration. Since the abnormal activation of Met receptor causes cancer progression, inhibitors such as neutralizing antibodies are regarded as promising therapeutics. HGF is secreted as a single-chain (sc) precursor and is processed by extracellular proteases to generate disulfide-bonded two-chain (tc) HGF. Although this proteolytic processing of HGF is necessary for its biological activity, exactly how the proteolysis leads to the conversion of HGF to the active form is still unclar due to the lack of structural information. In order to gain insights about this point, we generated 6 antibodies against HGF. All antibodies recognized different epitopes on the native HGF protein and showed distinct effects when tested in a cell-based HGF-Met signaling assay. They included one antibody (t1E4) that strongly blocks Met activation by tcHGF, as well as one antibody (t8E4) exclusively recognizing the active tcHGF but not inactive scHGF. Thus, a panel of anti-HGF antibodies suitable for probing the structural mechanism of HGF activation were obtained.


Surgical Techniques and Stoma-related Complications Associated With Emergency Stoma Creation.
Determination of risk factors for stoma-related complications associated with emergency stoma creation may impact on reducing complications and improving the quality of life of ostomy patients; however, there are only few reports on stoma-related complications associated with emergency stoma creation. Our study aimed to identify risk factors associated with stoma-related complications after emergency surgery, and evaluate surgical techniques for good stoma creation in the emergency setting. A retrospective analysis of patient and surgical characteristics was performed in 104 consecutive patients who underwent ileostomy or colostomy as emergency surgery between January 2020 and December 2022 at the Gunma University Hospital. Preoperative stoma site marking was performed in 70 (67.3%) patients. Colostomies and ileostomies were performed in 78 (75.0%) and 26 (25.0%) patients, respectively. The skin bridge technique was used in 13 (12.5%) patients. Stoma-related complications were diagnosed in 62 (59.6 %) patients, with peristomal skin disorders (47.1%) as the most common complication, followed by mucocutaneous separation (31.7%), and stoma retraction (19.2%). In the multivariate analysis, body mass index (BMI) [odds ratio (OR)=5.570, 95% confidence interval (CI)=1.233-25.167, p=0.026], skin bridge technique (OR=0.144, 95% CI=0.031-0.670, p=0.014), and stoma height (OR=0.134, 95% CI=0.038-0.469, p=0.002) were independent risk factors for stoma-related complications after emergency stoma creation. In emergency stoma creation, higher BMI and lower stoma height are associated with stoma-related complications. Using the skin bridge technique could reduce the risk of stoma-related complications after emergency stoma creation.


Abortive γδTCR rearrangements suggest ILC2s are derived from T-cell precursors.
Innate lymphoid cells (ILCs) are a recently identified subset of leukocytes that play a central role in pathogen surveillance and resistance, modulation of immune response, and tissue repair. They are remarkably similar to CD4+ T-helper subsets in terms of function and transcription factors required for their development but are distinguished by their lack of antigen-specific receptors. Despite their similarities, the absence of a surface T-cell receptor (TCR) and presence of ILCs and precursors in adult bone marrow has led to speculation that ILCs and T cells develop separately from lineages that branch at the point of precursors within the bone marrow. Considering the common lineage markers and effector cytokine profiles shared between ILCs and T cells, it is surprising that the status of the TCR loci in ILCs was not fully explored at the time of their discovery. Here, we demonstrate that a high proportion of peripheral tissue ILC2s have TCRγ chain gene rearrangements and TCRδ locus deletions. Detailed analyses of these loci show abundant frameshifts and premature stop codons that would encode nonfunctional TCR proteins. Collectively, these data argue that ILC2 can develop from T cells that fail to appropriately rearrange TCR genes, potentially within the thymus.


Nefopam abuse.
To report 3 patients who abused nefopam, a central analgesic that inhibits serotonin, norepinephrine, and dopamine reuptake. CASE 1: A 42-year-old white woman with migraines started nefopam therapy about 10 years ago. She now obtains nefopam by prescription forgery and self-administers intramuscular nefopam 300 mg/d. She experiences anticholinergic effects of nefopam and, when attempting withdrawal, depressive symptoms. CASE 2: A 40-year-old white woman with osteoporosis has injected 120 mg of nefopam intramuscularly daily for several years. When she tried to increase doses due to worsening of her symptoms, she experienced tremor, involuntary movements, and dry mouth, and became aggressive. She then resumed the initial doses. She now reports symptoms of depression when attempting withdrawal. CASE 3: A 33-year-old white man, with a history of alcohol and benzodiazepine dependence and ileostomy, and an implanted drug delivery system, has been prescribed nefopam. Fifteen days after therapy was initiated, his daily consumption was 840 mg/d, and further increased to 1840 mg/d. He experienced violent behavior, agitation, facial dysesthesia and myoclonus, tremor of fingers, and sweating. He did not attempt withdrawal. The patients described above are drug-dependent according to the Diagnostic and Statistical Manual, 4th Edition. All patients developed a pharmacodynamic tolerance phenomenon, which can develop rapidly. Violent behavior, tremor after massive intake, and depressive symptoms during withdrawal are similar to those reported with psychostimulant abuse. When abused, nefopam has primarily psychostimulant-like effects, which are probably linked to its dopamine reuptake inhibition properties.


Final elucidation of the absolute configuration of the signal metabolite hormaomycin.
The complete absolute configuration of hormaomycin 1 a has been established by HPLC and HPLC/MS experiments with appropriately derivatized 4-propylprolines, (2S,4S)-6 and (2R,4R)-6, as well as 4-(Z)-propenylprolines, cis-5 and trans-5, and also feeding experiments with enantiomerically pure samples of the deuterium-labeled 3-(2'-nitrocyclopropyl)alanine, (2S)-3,3-[D2]15 and (2S)-2,2'-[D2]15, and 4-(Z)-propenylproline 2',4-[D2]-(2S,4R)-5. The latter five amino acids were prepared for the first time and allowed one to unequivocally assign the hitherto unknown absolute configurations of the last four stereocenters in hormaomycin 1 a. As a bonus, some new information about the biosynthesis of this molecule has also been gathered.


Knowledge, attitudes and practices relating to influenza A(H7N9) risk among live poultry traders in Guangzhou City, China.
Live poultry traders (LPTs) have greater risk to avian influenza due to occupational exposure to poultry. This study investigated knowledge, attitudes and practices of LPTs relating to influenza A (H7N9). Using multi-stage cluster sampling, 306 LPTs were interviewed in Guangzhou by a standardized questionnaire between mid-May to June, 2013. Hierarchical logistic regression models were used to identify factors associated with preventive practices and attitudes towards various control measures implemented in live poultry markets against H7N9. Only 46.1% of the respondents recognized risks associated with contacts with bird secretions or droppings, and only 22.9% perceived personally "likely/very likely" to contract H7N9 infection. Around 60% of the respondents complied with hand-washing and wearing gloves, and only 20% reported wearing face masks. Only 16.3% of the respondents agreed on introducing central slaughtering of poultry. Being younger, involving in slaughtering poultry, having longer working hours, less access to H7N9-related information and poorer knowledge, and perceiving lower personal susceptibility to H7N9 infection were negatively associated with preventive practices. Comparing with previous studies conducted when human cases of H5N1 avian influenza infection was first identified in Guangdong, LPTs' perceived susceptibility to novel influenza viruses increased significantly but acceptance for central slaughtering of poultry remained low. Information on avian influenza provided through multiple communication tools may be necessary to promote knowledge among poultry traders. Familiarity with risk may have led to the lower perceived vulnerability to avian influenza and less protective actions among the LPTs particularly for those involving more risky exposure to live poultry. Reasons for the consistently low acceptance for central slaughtering of poultry await further exploration.


Continuous retrograde cerebral perfusion supplies substrates for brain metabolism during hypothermic circulatory arrest.
Ten patients underwent replacement of ascending aorta and/or aortic arch with aneurysm or dissection, using hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP). RCP was administered through the superior vena cava cannula continuously during HCA (15 degrees C to 20 degrees C). Mean HCA time was 32 minutes (range, 18-45 minutes). To assess the metabolic changes during RCP, blood samples were taken from carotid arteries and the superior vena cava cannula simultaneously, five minutes after the onset and five minutes prior to termination of continuous retrograde cerebral perfusion (CRCP) for analysis of blood gas and glucose level. One patient died intraoperatively due to left ventricular failure. Nine patients survived their operations and all except one with stroke due to partial intimal flap obstruction of innominate artery awoke neurologically intact within four to six hours. One patient died on the postoperative fifth day due to septic shock following resection of ischaemic bowel due to dissection involving the mesenteric artery. Oxygen saturation, pH and glucose level were all found to be lower in blood back-bleeding from the carotid arteries than in blood perfused through the superior vena cava cannula at all sampling times during HCA and CRCP (p < 0.05). Although oxygen and glucose extraction is not only from brain tissue, these data demonstrate the efficacy of CRCP in supplying substrates for brain protection. CRCP is a reliable method as an adjunct to HCA for brain protection.


Catalysis by protein acetyltransferase Gcn5.
Gcn5 serves as the defining member of the Gcn5-related N-acetyltransferase (GNAT) superfamily of proteins that display a common structural fold and catalytic mechanism involving the transfer of the acyl-group, primarily acetyl-, from CoA to an acceptor nucleophile. In the case of Gcn5, the target is the ε-amino group of lysine primarily on histones. Over the years, studies on Gcn5 structure-function have often formed the basis by which we understand the complex activities and regulation of the entire protein acetyltransferase family. It is now appreciated that protein acetylation occurs on thousands of proteins and can reversibly regulate the function of many cellular processes. In this review, we provide an overview of our fundamental understanding of catalysis, regulation of activity and substrate selection, and inhibitor development for this archetypal acetyltransferase.


Audit of the views of gynaecological cancer patients regarding follow-up.
The purpose of this study was to audit patients opinions on routine follow-up and discharge from the gynaecology clinic. The setting was the gynaecology clinic of a large district general hospital and the design was a cross-sectional audit analysis using a written questionnaire. The subjects were 103 women attending the gynaecological out patients for review following previous treatment for various gynaecological cancers. Ninety patients took part in the study, of these 36 (40%) wished for 'free access', 29 (32%) wished for routine hospital follow-up, and 25 (28%) wished for discharge but with follow-up by their general practitioner. There were no statistically significant differences in choices between cancer groups. The choice of 'free access'seemed to be an important choice for women. We conclude that routine hospital follow-up of women treated for gynaecological cancer is not the desire of the majority and it appears the women may have different inherent psychological characteristics.