Design and testing of a new high-accuracy ultraviolet-visible-near-infrared spectrophotometer.
A new high-accuracy spectrophotometer has been developed at the National Research Council of Canada to measure regular transmittance factors over the spectral range from 200 to 2500 nm. The most significant feature of this automated single-beam instrument is a highly collimated normal-incidence beam geometry, which eliminates the need for polarization corrections or for an averaging sphere for the calibration of regular-transmittance reference materials. The instrument also possesses a large uniformmeasurement beam that minimizes errors caused by sample nonuniformity. We describe the instrument's design and the testing, optimization, and verification procedures that have been carried out for measurements in the visible and near-infrared regions. Systematic errors that have been determined and corrected for include wavelength shifts, stray light, system drift, and nonlinearity. In the visible and near-infrared regions, the overall photometric accuracy is estimated to be 2.5 and 4.0 parts in 10(4), respectively. The wavelength scale is accurate to within +/-0.1 nm with a reproducibility of +/-0.03 nm over its entire design range from 200 to 2500 nm.


[Employment opportunities and job satisfaction in the field of Public Health: a survey among recent graduates of the Hygiene and Preventive Medicine residency in Italy].
We conducted an on-line survey among 255 specialists in Hygiene and Preventive Medicine in Italy who completed their training between October 2014 and July 2016, to assess their training experience, employment opportunities and current job satisfaction. Response rate was 49%. Mean age was 35 years. A high employment rate within two years from obtaining specialist qualification was reported by the 125 specialists who completed the questionnaire (76% are currently employed). The three main work settings of the participating specialists are hospital health directions (37%), universities (19%) and local Prevention Departments (16%). Two thirds (66%) have temporary positions and only 6% permanent positions. Job, pay, and training satisfaction are often below expectations with geographical differences that would need to be further investigated.


Spatially distinct and metabolically active membrane domain in mycobacteria.
Protected from host immune attack and antibiotic penetration by their unique cell envelope, mycobacterial pathogens cause devastating human diseases such as tuberculosis. Seamless coordination of cell growth with cell envelope elongation at the pole maintains this barrier. Unraveling this spatiotemporal regulation is a potential strategy for controlling mycobacterial infections. Our biochemical analysis previously revealed two functionally distinct membrane fractions in Mycobacterium smegmatis cell lysates: plasma membrane tightly associated with the cell wall (PM-CW) and a distinct fraction of pure membrane free of cell wall components (PMf). To provide further insight into the functions of these membrane fractions, we took the approach of comparative proteomics and identified more than 300 proteins specifically associated with the PMf, including essential enzymes involved in cell envelope synthesis such as a mannosyltransferase, Ppm1, and a galactosyltransferase, GlfT2. Furthermore, comparative lipidomics revealed the distinct lipid composition of the PMf, with specific association of key cell envelope biosynthetic precursors. Live-imaging fluorescence microscopy visualized the PMf as patches of membrane spatially distinct from the PM-CW and notably enriched in the pole of the growing cells. Taken together, our study provides the basis for assigning the PMf as a spatiotemporally distinct and metabolically active membrane domain involved in cell envelope biogenesis.


Precursors of functional MHC class I- or class II-restricted CD8alphaalpha(+) T cells are positively selected in the thymus by agonist self-peptides.
The origin and specificity of alphabeta TCR(+) T cells that express CD8alphaalpha have been controversial issues. Here we provide direct evidence that precursors of functional CD8alphaalpha T cells are positively selected in the thymus in the presence of agonist self-peptides. Like conventional positive selection, this agonist selection process requires functional TCR alpha-CPM, whereas it is independent of CD8beta expression. Furthermore, CD8alphaalpha expression on mature, agonist-selected T cells does not imply selection by MHC class I, and CD8alphaalpha(+) T cells can be either class I or class II restricted. Our data define a distinct agonist-dependent, positive selection process in the thymus, and they suggest a function for CD8alphaalpha distinct from the conventional TCR coreceptor function of CD8alphabeta or CD4.


Degradation of perfluoroalkyl substances using UV/Fe0 system with and without the presence of oxygen.
The wide presence of per- and poly-fluoroalkyl substances (PFAS) in the environment is a global concern, thus their degradation is an imminent task. In this study, oxidative and/or reductive degradation of three representative PFAS - perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS) was achieved using nanoscale zero-valent iron (Fe0 NPs) under ultraviolet (UV) light, both with and without the presence of oxygen. Higher degradation and defluorination rates were obtained for a longer chain PFNA compared to PFOA, and a higher removal of PFAS was achieved without the presence of O2 compared to that with O2. The degradation followed first-order reaction kinetics, and obtained the highest rates of 97.6, >99.9, and 98.5% without the presence of O2 for PFOA, PFNA, and PFOS, respectively. The degradation rates increased with an increase in the nanoparticle concentrations in the range of 1-100 mg/L. In addition to fluoride ions, shorter chain perfluorocarboxylic acids (PFCAs) were detected as the main intermediates during PFAS degradation; PFHpS and 6:2 FTS were also detected during PFOS degradation. Hydroxyl radicals (·OH) and superoxide radicals (·O2-) were not involved in the degradation of PFOA, but likely involved in the degradation of PFOS. Emerging contaminants PFAS degradation using the UV/Fe0 system is a cost-effective technology owing to the low cost and recyclability of Fe0 nanomaterials, low energy consumption in the system, and its capability to degrade PFAS both with and without the presence of oxygen. This technology can be potentially applied to treat PFAS-contaminated waters in the environment.


Formulation of immunoassay calibrators in pasteurized albumin can significantly enhance their durability.
Calibrator matrix can have significant effects on the commutability of assay standards and on the maintenance of their integrity. We have observed marked instability in progastrin-releasing peptide (proGRP) assay standards traceable to the bovine serum albumin (BSA) used in matrix formulation. Attempts were made to improve calibrator stability using different albumin pretreatments. Observed analyte recoveries in calibrators prepared with untreated BSA were consistently less than 45% after 1 week of storage at 4 degrees C. Pre-treating the BSA by chromatography on immobilized heparin or benzamidine failed to improve calibrator durability with day 7 recoveries of less than 55%. In marked contrast, calibrators formulated with albumin pasteurized at pH 3.0 displayed remarkable stability. Recoveries of >97% were observed after 4 weeks of storage at either 4 degrees C or room temperature. Even calibrators incubated for 4 weeks at 37 degrees C gave recoveries between 91-106%. This improvement was not seen with BSA pasteurized at neutral pH. Albumin pretreatment is straightforward, easily scalable and dramatically improves calibrator stability. Matrix formulated with acid-pasteurized BSA may prove more generally useful when assays are plagued by poor calibrator durability.


A Fix for a Scalp Varix! A Rare Case of Cirsoid Aneurysm in a Child.
Cirsoid aneurysm (CA) is a rare arteriovenous fistula of the scalp. There exists scant literature on the incidence and approach to CA in children. We describe a case of CA in a 7-year-old boy which was diagnosed by angiography and managed with angiographic embolization followed by surgical excision.


[Theory and methods of clinical assessment of defense mechanisms].
Originally, defense theories had been developed as metapsychological categories. Applied to empirical investigations, however, defense theories have to be adapted to the specific empirical design. A clinical and an empirical theory on defense, for which the same terms are often used, are by no means identical. The clinical and empirical terms have to be matched. An empirical theory on defense should correspond not only to metapsychological categories but be adequate for the research object. Among the most common empirical procedures, clinical ratings of defense mechanisms come closest to clinical judgements, but entail methodological problems. Group ratings underly dynamic group processes which are difficult to control and thus imply a risk. The advantage of such a rating, however, is that affective processes within the rating team may be seen as an extended observational instrument. Despite their methodological restrictions, consensus ratings may be seen as an instrument the further development of which is worthwhile.


Nutritional status as a risk factor in esophageal surgery.
Nutritional condition is one of the factors determining postoperative outcome in esophageal surgery. This study explored the relation between preoperative nutritional status and postoperative infectious complications. From a prospective database, 400 patients who underwent esophageal resection for malignancy were selected. Preoperative nutritional status was assessed by body mass index, prognostic nutritional index (PNI), nutritional risk index (NRI) and weight loss. The association between nutritional parameters and postoperative complications and mortality, gender, age and hospitalization was assessed. PNI and NRI differed between the patients with and without postoperative infectious complications (p = 0.031 and p = 0.009, respectively). However, receiver operating characteristic curves showed that PNI and NRI have a low predictive value for such complications. Also, no associations were found between nutritional parameters and in-hospital mortality. Although mean nutritional parameters were significantly lower, i.e. worse, in patients with neoadjuvant treatment as compared to no such treatment, the incidence of complications did not significantly differ between these treatment groups. Although PNI and NRI correlated negatively with age, no association was found between age and infectious complications. Multivariate analysis of various factors showed the male gender to be the only significant risk factor for development of infectious complications. Preoperative nutritional status established by PNI, NRI, body mass index and weight loss has limited value in predicting complications following esophageal resection.


[The course of Schonlein-Henoch disease in children].
We analysed 79 episodes of Henoch-Schonlein purpura in children. Skin manifestations were present in all cases, abdominal symptoms in 51.9%, arthritis or arthralgia in 41.8% and nephritis in 34.2% of the episodes. Skin rash and haematuria with proteinuria were the longest-lasting symptoms. Skin lesions persisted longer in case of disease relapses (p < 0.05). Typically Henoch-Schonlein purpura is a benign, self-limiting disease.


Speed performance and long-term functional and vocational outcome in a group of young patients with moderate or severe traumatic brain injury.
We studied specific aspects of speed performance in neuropsychological tests and functional and vocational long-term outcome among moderate or severe traumatic brain injury (TBI) patients admitted to a rehabilitation programme. A group of 140 patients with mild, moderate or severe TBI was followed up for a minimum of 5 years in a rehabilitation programme. Severity of TBI was estimated using the Glasgow Coma Scale (GCS) scores on emergency hospital admission. The patients, grouped by age at injury into the categories: 7 or younger, 8-16 and 17 years of age or older, were tested five or more years post-injury with comprehensive neuropsychological tests, including a speed performance test with the Stroop material, the Purdue Pegboard (PB) test and simple visual and auditive reaction times. The outcome variables were functional outcome, as measured by the Glasgow Outcome Scale (GOS) score, and capacity for employment at the end of follow-up, i.e. on average 12 years post-injury. The patients with mild TBI were excluded from further analysis of outcome. The study was carried out at the Kauniala outpatient neurological clinic. In the Stroop test, patients with a GOS score of 3 and patients who were incapable of employment were slower (P = 0.0046 and P = 0.0015, respectively) than those with a GOS score of 1 or 2 and those capable of independent or subsidized employment, respectively. The PB test also differentiated significantly between the patients with a GOS score of 3 and those with a GOS score of 1 or 2 at the end of follow-up (P = 0.0413), and predicted incapacity for employment (P = 0.032), those with worse outcome being slower. Simple reaction times did not differ significantly between the GOS scores at the end of follow-up, and neither did they predict capacity or incapacity for employment. Our data suggest that the Stroop and PB tests can help estimate functional outcome, as measured by the GOS, among patients with initially moderate or severe TBI and who were referred to a rehabilitation programme. The same tests could also be useful in predicting long-term vocational outcome.


Ultrastructural immunocytochemical localization of the asialoglycoprotein receptor in rat hepatocytes.
The asialoglycoprotein receptor is present on the plasma membrane of rat hepatocytes and mediates the endocytosis of exogenous asialoglycoproteins. The intracellular locations of the receptor are incompletely defined, and whether the receptor is present on the canalicular membrane is controversial. To investigate these unresolved issues, we localized the asialoglycoprotein receptor on the surfaces of and within rat hepatocytes in the absence of exogenous asialoglycoprotein. Cryostat sections of perfusion-fixed livers of fasted rats were incubated with peroxidase-labeled antibodies to the rat asialoglycoprotein receptor and were examined by light and electron microscopy. The asialoglycoprotein receptor on the surface of hepatocytes was present on the sinusoidal plasma membrane and was concentrated in coated pits; it was present also on the lateral plasma membrane but was absent from the bile canalicular membrane. Within hepatocytes, the receptor was present in saccules of the Golgi complexes and occasionally in segments of the endoplasmic reticulum. Definite endocytic vesicles containing receptor were absent, and lysosomes were devoid of the receptor. These observations indicate that in the absence of exogenous asialoglycoprotein (a) the asialoglycoprotein receptor on the plasma membrane of hepatocytes is present only on the sinusoidal and lateral surfaces, (b) the receptor is being synthesized and assembled, (c) endocytic internalization of the receptor is minimal or absent, and (d) lysosomes are devoid of the receptor.


Intrafocal pinning of distal radius fractures: a simplified approach.
Distal radius fractures are not often treated by plastic surgeons. At the authors' institution, plastic surgery manages half of all traumas below the elbow, including distal radius and forearm fractures. This opportunity gives the residents a unique perspective for comprehensive training in treating upper extremity injuries. Because a distal radius fracture is the most common fracture of the upper extremity, the authors describe the use of intrafocal pinning as a simple and effective approach in the treatment of extra-articular distal radius fractures (Colles' fractures). They conducted a prospective study of 18 patients with Colles' fractures treated sequentially at their institution from 1998 to 2001 using this technique. They measured ulnar variance and palmar tilt of the distal radius at the time of injury, after closed reduction, immediately postoperatively, and 11 weeks postoperatively. Acceptable distal radius reduction aims to achieve at least neutral ulnar variance and 0-deg palmar tilt. Compared with closed reduction, they achieved superior anatomic reduction with intrafocal pinning: ulnar variance, +2.6 mm vs. -1.4 mm; palmar tilt, -13.3 deg vs. +2.1 deg). These results were stable at the 11-week follow-up. Intrafocal pinning is a valuable tool in the management of Colles' fractures. It is simple to perform and to teach, and it produces results that are superior to closed reduction alone.


Effect of tomato intake on striatal monoamine level in a mouse model of experimental Parkinson's disease.
An ingestion of tomato powder rich in lycopene was examined for its effect on mice with Parkinson's disease-like syndrome induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To assess the preventive effect of tomato against the MPTP-induced selective destruction of dopaminergic nigrostrie, we determined striatal dopamine (DA). A 4-wk ingestion of the experimental diet containing 20% (w/w) lyophilized tomato powders before MPTP treatment prevented a decrease in the DA level. This suggests that the tomato ingestion might serve as a preventive against neurodegenerative diseases such as Parkinson's disease caused by MPTP and other environmental toxins.


Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy.
Conventional activation mapping is difficult without inducible, stable ventricular tachycardia (VT). We evaluated 16 patients with drug refractory, unimorphic, unmappable VT. Nine patients had ischemic and 7 had nonischemic cardiomyopathy. All patients had implantable defibrillators and had experienced 6 to 55 VT episodes during the month before treatment. Patients underwent bipolar catheter mapping during baseline rhythm. The amount of endocardium with an abnormal electrogram amplitude was estimated using fluoroscopy in 3 patients and a magnetic mapping system (CARTO) in 13 patients. For the magnetic mapping, normal endocardium was defined by an amplitude >1.5 mV; this measurement was based on sinus rhythm maps in 6 patients who did not have structural heart disease. Radiofrequency point lesions extended linearly from the "dense scar," which had a voltage amplitude <0.5 mV, to anatomic boundaries or normal endocardium. To limit radiofrequency applications, 12-lead ECG during VT and pacemapping guided placement of linear lesions. No new antiarrhythmic drug therapy was added. The amount of endocardium demonstrating an abnormal electrogram amplitude ranged from 25 to 127 cm(2). A total of 8 to 87 radiofrequency lesions (mean, 55) produced a median of 4 linear lesions that had an average length of 3.9 cm (range, 1.4 to 9. 4 cm). Twelve patients (75%) have been free of VT during 3 to 36 months of follow-up (median, 8 months); 4 patients had VT episodes at 1, 3, 9, and 13 months, respectively. Only one of these patient had frequent VT. Radiofrequency linear endocardial lesions extending from the dense scar to the normal myocardium or anatomic boundary seem effective in controlling unmappable VT.


Changes of Ribulose Bisphosphate Carboxylase/Oxygenase Content, Ribulose Bisphosphate Concentration, and Photosynthetic Activity during Adaptation of High-CO(2) Grown Cells to Low-CO(2) Conditions in Chlorella pyrenoidosa.
Changes of some photosynthetic properties of high-CO(2) grown cells of Chlorella pyrenoidosa during adaptation to low-CO(2) conditions have been investigated. The K(m) value of photosynthesis of the high-CO(2) grown cells for dissolved inorganic carbon was 3.3 millimolar and decreased to 25 to 30 micromolar within 4 hours after transferring to air. In the presence of saturating CO(2) concentrations the photosynthetic activity of the high-CO(2) grown cells was 1.5 times as high as that of the low-CO(2) grown cells. There was a significant rise of the photosynthetic activity during adaptation of the high-CO(2) grown cells to air, followed by a steady decrease. The activity of ribulose 1,5-bisphosphate carboxylase/oxygenase in both the high- and low-CO(2) grown cells was close to the photosynthetic activity of the cells. The concentration of ribulose 1,5-bisphosphate (RuBP) was higher in the low-CO(2) adapting and low-CO(2) grown cells than in the high-CO(2) grown cells regardless of the photosynthetic rate. This seems to be due to an increased RuBP regeneration activity during adaptation followed by maintenance of the new higher concentration. The RuBP level always exceeded the concentration of ribulose 1,5-bisphosphate carboxylase/oxygenase RuBP binding sites in both the high- and low-CO(2) grown cells at any dissolved inorganic carbon concentration.


An open study to compare azithromycin with cefaclor in the treatment of children with acute otitis media.
An open, multicentre study involving 259 children between 6 months and 13 years of age was performed to assess the efficacy and safety of azithromycin and to compare it with cefaclor as treatment of acute otitis media. Patients were randomized to receive either azithromycin 10 mg/kg once daily for 3 days or cefaclor 40 mg/kg daily in divided doses every 8 h for 10 days. Cure or improvement in signs and symptoms was observed in 112/114 (98%) evaluable azithromycin-treated patients and 116/120 (97%) evaluable cefaclor-treated patients on days 11-15. In contrast to cefaclor, however, azithromycin was associated with a significantly (P = 0.033) higher cure rate 1 month after completion of treatment. In those patients who were followed up to days 25-30, the response was satisfactory (cure or improvement) in 31/32 (97%) patients who had received azithromycin and in 31/36 (86%) to whom cefaclor had been administered. Patients tolerated both treatments well and no severe adverse events related to therapy were recorded in either group. The results of this study show that a 3-day, once-daily regimen of azithromycin has comparable clinical efficacy and tolerability to a thrice-daily course of cefaclor administered for 10 days, but the azithromycin is associated with a lower incidence of relapse.


Improvement of hyponatremia in cirrhosis is associated with improved complex information processing.
Hyponatremia, a cause of brain dysfunction and risk factor for hepatic encephalopathy, is frequent in patients with advanced cirrhosis and ascites. The interdependence of liver failure and hyponatremia makes it difficult to separate the effects of each on cognitive function. The objective was to assess whether an increase in plasma sodium in patients with cirrhosis and ascites leads to an improvement in cognitive function. This is a post-hoc analysis of 250 cirrhosis patients without overt hepatic encephalopathy randomized to receive either placebo or satavaptan, a vasopressin V2 antagonist. The exposure was plasma sodium, and the outcome was the trail-making test (TMT) parts A and B, which assesses speed of information processing, performed before the study starts and after 14 days. The results were analyzed by initial and change to final sodium concentration. At entry, the patients with normonatremia exhibited better results on both the TMT-A (median 56 vs 77.5 s for patients with sodium ≤ 130 mmol/L [P = 0.0059]) and the TMT-B (median 127 vs 170 s for patients with sodium ≤ 130 mmol/L [P = 0.0066]), unrelated to age. Improvement of hyponatremia was more common in patients who received satavaptan (59.7%) than placebo (18.5%). Correction of hyponatremia did not shorten the simple TMT-A but markedly improved the complex TMT-B by an average of 20 s compared with 6.5 s in those with continuing hyponatremia (P = 0.02). Liver status measures remained stable during the period reported. These data suggest that improvement of hyponatremia in patients with cirrhosis leads to an increase in the speed of complex information processing.


Immunohistochemical Localization of Somatostatin in the Brain of Chinese Alligator Alligator sinensis.
In this study, the regional distribution and histological localization of somatostatin (SS) immunoreactive (IR) perikarya and fibers was investigated for the first time in the brain of adult Chinese alligator by immunohistochemical method. The results showed SS-IR perikarya and fibers were widely distributed in various parts of the brain except for olfactory bulbs. In the telencephalon, SS-IR perikarya were predominantly located in the cellular layer and deep plexiform layer of dorsomedial and medial cortex, less in the dorsal and lateral cortex, while SS-IR fibers were found in all layers of the cerebral cortex. SS-IR perikarya and fibers were also detected in the dorsal ventricular ridge, hippocampus cortex, accessory olfactory bulb nuclearus, lenticular nucleus, and caudate nucleus. In the diencephalon, SS-IR perikarya and fibers were mainly present in supraoptic nucleus, paraventricular nucleus of hypothalamus, recessus infundibular nucleus, median eminence, the pineal gland and pituitary gland, in which the IR-fibers were abundant, appearing dot-shaped and varicosity-like. In the mesencephalon, they were present in tectum cortex, ependyma of cerebral aqueduct and the periaqueductal grey matter. Additionally, they were also detected in Purkinje's cellular layer of cerebellum, in the reticularis nucleus and raphe nucleus of medulla oblongata. The distribution pattern of SS-IR perikarya and fibers in the brain of Chinese alligator is generally similar to that reported in other reptiles, but also has some specific features. The wide distribution indicated that SS might be a neurotransmitter or neuromodulator which acts on many kinds of target cells with a wide range of physiological functions. Anat Rec, 300:507-519, 2017. © 2016 Wiley Periodicals, Inc.


[Progress on screening for gastric cancer].
Objective: Gastric cancer, a common gastrointestinal cancer in the world, threatens people's life and health seriously. Early screening is an effective strategy to reduce the incidence and mortality of gastric cancer, which is of great importance for gastric cancer prevention and control. The review systematically searched CNKI, Wanfang Data knowledge service platform, PubMed and EMbase databases, and summarized the current status on screening for gastric cancer worldwide. We found that the screening on gastric cancer was mainly carried out in eastern Asia. Gastroscopy and biopsy were the main screening techniques of gastric cancer. The starting age of screening is 40 years old or above. It is essential to carry out gastric cancer screening and concentrate on high-risk population in China.


A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis.
The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis. Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20). Placebo capsules and enemas were used to maintain a blind procedure. Total DAI scores and abbreviated DAI scores were evaluated at wk 3 and 6, and wk 1 and 2, respectively. Patients recorded the amount of blood in stools, urgency, straining at stools, and abdominal pain in daily diaries. Physicians and patients rated overall improvement at each visit. At wk 6, combination therapy produced a greater improvement (-5.2) in total DAI scores than did either mesalamine enema (-4.4) or mesalamine tablet (-3.9) therapy alone; similar treatment differences were observed at wk 3. Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools. Physicians' and patients' ratings of improvement indicated that combination therapy significantly improved disease status, compared with mesalamine tablet therapy alone. All treatments were well tolerated. The combination of oral and rectal mesalamine therapy was well tolerated and produced earlier and more complete relief of rectal bleeding than oral or rectal therapy alone.


Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia.
Spontaneous organ hemorrhage is the major complication in thrombocytopenia with a potential fatal outcome. However, the exact mechanisms regulating vascular integrity are still unknown. Here, we demonstrate that neutrophils recruited to inflammatory sites are the cellular culprits inducing thrombocytopenic tissue hemorrhage. Exposure of thrombocytopenic mice to UVB light provokes cutaneous petechial bleeding. This phenomenon is also observed in immune-thrombocytopenic patients when tested for UVB tolerance. Mechanistically, we show, analyzing several inflammatory models, that it is neutrophil diapedesis through the endothelial barrier that is responsible for the bleeding defect. First, bleeding is triggered by neutrophil-mediated mechanisms, which act downstream of capturing, adhesion, and crawling on the blood vessel wall and require Gαi signaling in neutrophils. Second, mutating Y731 in the cytoplasmic tail of VE-cadherin, known to selectively affect leukocyte diapedesis, but not the induction of vascular permeability, attenuates bleeding. Third, and in line with this, simply destabilizing endothelial junctions by histamine did not trigger bleeding. We conclude that specifically targeting neutrophil diapedesis through the endothelial barrier may represent a new therapeutic avenue to prevent fatal bleeding in immune-thrombocytopenic patients.


Human oocytes reprogram somatic cells to a pluripotent state.
The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cells affected in degenerative human diseases. Such cells, carrying the patient's genome, might be useful for cell replacement. Here we report that the development of human oocytes after genome exchange arrests at late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, the resultant triploid cells develop to the blastocyst stage. Stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies removal of the oocyte genome as the primary cause of developmental failure after genome exchange.


Mid-infrared supercontinuum generation in supercritical xenon-filled hollow-core negative curvature fibers.
We present an investigation on the generation of supercontinuum in the mid-infrared (mid-IR) spectral region. Namely, we study a silica-based anti-resonant hollow-core fiber which has good guidance properties in the mid-IR filled with supercritical xenon providing the necessary high nonlinearity. Our numerical study shows that by launching a 200 nJ pump of 100 fs centered at 3.70 μm, a supercontinuum that spans from 1.85 to 5.20 μm can be generated. Such sources are potentially useful for applications, such as the remote sensing of various molecules, medical imaging diagnosis, and surgery.


Radiographic pelvimetry--its use and possible radiation risk.
Radiographic pelvimetry is widely used in obstetrics. Every fourth primapara in Sweden is submitted to this radiographic examination. The frequency of the examination in the United States is estimated to a mean of 6% of all deliveries. The use of radiographic pelvimetry is now under intense debate and the missing argument in this discussion is a prospective study of an unselected group of parturients where progress and outcome of labour is referred to known pelvic dimension. Since the value of the method is questioned the frequent use of radiographic pelvimetry is justified only by an almost negligible radiation risk to the mother and her baby. Such a low risk is also an indispensable condition to allow the correct scientific evaluation of radiographic pelvimetry mentioned above. This paper presents the measurement results of absorbed radiation dose with the only radiographic pelvimetry method used in Sweden. The estimated radiation risk of the method, based on these figures, is 1 case of childhood malignancy in 50 000 pelvimetries. This corresponds to 4 years routine use of radiographic pelvimetry in Sweden. The annual incidence of childhood malignancy in Sweden is 220. The maternal risk is estimated to one tenth of the fetal risk.


The Touchstone Process: an ongoing critical evaluation of reiki in the scientific literature.
Reiki is used by a growing number of people but little is known about the scientific basis for its use. The Touchstone Process was developed as an ongoing process to systematically analyze published, peer-reviewed studies of Reiki, the results being made accessible to the public online. Thirteen scientifically qualified experts in the field of Reiki were assembled into 3 teams to retrieve, evaluate, and summarize articles using standardized, piloted evaluation forms. Summaries of 26 Reiki articles, including strengths and weaknesses, were posted on a newly developed Web site (www.centerforreikiresearch.org), together with an overall summary of the status of Reiki research and guidelines for future research: The Touchstone Process determined that only 12 articles were based on a robust experimental design and utilized well-established outcome parameters. Of these articles, 2 provided no support, 5 provided some support, and 5 demonstrated strong evidence for the use of Reiki as a healing modality. There is a need for further high-quality studies in this area.


Design, synthesis, and characterization of (1-(4-aryl)- 1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis.
The novel (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were synthesized by the click reaction of the dihydropyrimidinones, bearing a terminal alkynyl group, with various substituted aryl azides at room temperature using a catalytic amount of Cu(OAc)2 and sodium ascorbate in a 1:2 ratio of acetone and water as a solvent. The newly synthesized compounds were characterized by a number of spectroscopic techniques, such as infrared, liquid chromatography-mass spectrometry, (1)H, and (13)C nuclear magnetic resonance along with single crystal X-ray diffraction. The current procedure for the synthesis of 1,2,3-triazole hybrids with dihydropyrimidinones is appropriate for the synthesis of a library of analogs 7a-l and the method accessible here is operationally simple and has excellent yields. The title compounds 7a-l were evaluated for their in vitro antitubercular activity against H37RV and multidrug-resistant strains of Mycobacterium tuberculosis by resazurin microplate assay plate method and it was found that compound 7d was promising against H37RV and multidrug-resistant strains of M. tuberculosis at 10 and 15 μg/mL, respectively.


Immunomodulation and immunosuppression by human herpesvirus 6A and 6B.
Like other members of the Herpesviridae family, human herpesvirus (HHV)-6A and HHV-6B have developed a wide variety of strategies to modulate or suppress host immune responses and, thereby, facilitate their own spread and persistence in vivo. Long considered two variants of the same virus, HHV-6A and HHV-6B have recently been reclassified as distinct viral species, although the established nomenclature has been maintained. In this review, we summarize the distinctive profiles of interaction of these two viruses with the human immune system. Both HHV-6A and HHV-6B display a tropism for CD4+ T lymphocytes, but they can also infect, in a productive or nonproductive fashion, other cells of the immune system. However, there are important differences regarding the ability of each virus to infect cytotoxic effector cells, as HHV-6A has been shown to productively infect several of these cells, whereas HHV-6B infects them inefficiently at best. In addition to direct cytopathic effects, both HHV-6A and HHV-6B can interfere with immunologic functions to varying degrees via cytokine modulation, including blockade of IL-12 production by professional antigen-presenting cells, modulation of cell-surface molecules essential for T-cell activation, and expression of viral chemokines and chemokine receptors. Some of these effects are related to signaling through and downregulation of the viral receptor, CD46, a key molecule linking innate and adaptive immune responses. Increasing attention has recently been focused on the importance of viral interactions with dendritic cells, which may serve both as targets of virus-mediated immunosuppression and as vehicles for viral transfer to CD4+ T cells. Our deepening knowledge of the mechanisms developed by HHV-6A and HHV-6B to evade immunologic control may lead to new strategies for the prevention and treatment of the diseases associated with these viruses. Moreover, elucidation of these viral mechanisms may uncover new avenues to therapeutically manipulate or modulate the immune system in immunologically mediated human diseases.


Autoimmunity in rheumatoid arthritis. An approach via a study of B lymphocytes.
In this article the relationship between the cellular elements of the immune response and inflammation are examined with reference to the B lymphocyte repertoire. Evidence is presented that, in addition to an environment in the joint that favors localization and activation of auto-reactive B lymphocytes, the circulating B lymphocyte pool in rheumatoid arthritis is abnormally enriched in cells that bear a receptor for mouse erythrocytes and possess CD5 antigen. B lymphocytes with these novel phenotypic markers secrete autoantibodies and are found in abundance in fetal lymphoid tissues and cord blood; analogous cells in the mouse belong to a distinct lineage and are implicated in allotype- and idiotype-restricted interactions. It is postulated that a subset of B lymphocytes is of primary importance in the etiopathogenesis of rheumatoid disease.


Secure adaptive topology control for wireless ad-hoc sensor networks.
This paper presents a secure decentralized clustering algorithm for wireless ad-hoc sensor networks. The algorithm operates without a centralized controller, operates asynchronously, and does not require that the location of the sensors be known a priori. Based on the cluster-based topology, secure hierarchical communication protocols and dynamic quarantine strategies are introduced to defend against spam attacks, since this type of attacks can exhaust the energy of sensor nodes and will shorten the lifetime of a sensor network drastically. By adjusting the threshold of infected percentage of the cluster coverage, our scheme can dynamically coordinate the proportion of the quarantine region and adaptively achieve the cluster control and the neighborhood control of attacks. Simulation results show that the proposed approach is feasible and cost effective for wireless sensor networks.


A velocity map imaging spectrometer for measuring absolute differential cross sections for ion-induced electron emission from molecules.
In this paper, we present a newly developed crossed beam experimental setup that utilizes the velocity map imaging (VMI) technique to simultaneously measure both the kinetic energy and emission angle of electrons emitted from atoms or molecules upon ion collision. The projectile ion beam with keV to MeV kinetic energy orthogonally crosses the neutral target beam produced by an effusion cell. The emitted electrons are extracted and analyzed by a multi-electrode VMI spectrometer. By monitoring the target density, the projectile ion beam intensity, and the beams' overlap, we are able to measure absolute differential cross sections for collision-induced electron emission from molecules. The characterization of the setup and the methodology will be presented as well as first results for electron emission from uracil upon 0.98 MeV/u 12C4+ collision.


[Current problems of delivering medical care on ships].
Medical personnel of ships has been liquidated during the period of public health reforms, and in accordance with International Regulations of Floating Safety, sailors now have to be trained to render first medical care and care of victims on board the ship. This paper discusses the problems essential for such training of sailors and presents the experience gained by the first worldwide department of marine medical training of sailors at S. O. Makarov State Navy Academy. Basic characteristics of navy legislation are presented. Special attention is paid to general laws and laws essential for this sphere.


Disease caused by Mycoplasma mycoides subspecies mycoides LC in Hungarian goat herds.
The occurrence of a goat disease caused by Mycoplasma mycoides subsp. mycoides LC in Hungary is reported. The disease occurred in two goat herds in the spring of 1999. In one herd 25% of the 4-12 weeks old kids (10 animals) while in the other herd 33% of the 6-12 weeks old kids (20 animals) became affected. The goat kids developed polyarthritis. The most severe lesions developed in the carpal joints. All animals died after 3-8 days of disease. Four dead kids were necropsied. All of them had serofibrinous and purulent polyarthritis, and in two animals bronchopneumonia, fibrinous pleuritis and meningitis were also found. In the articular exudates the presence of mycoplasmas was detected by PCR using a general mycoplasma primer. Mycoplasmas were cultured from the joints of all animals, from the abdominal parenchymal organs of two kids and from the lungs of one animal. The cultured mycoplasmas grew in strikingly large colonies, proved to be glucose positive, arginine negative and phosphatase positive, and liquefied the coagulated serum. They survived incubation at 45 degrees C for more than 24 h. Based upon their biochemical properties, the results of the immunofluorescence (IF) and growth inhibition tests and the sequence analysis of the PCR product, the cultured strains were identified as M. mycoides subsp. mycoides LC. Animals purchased in the previous autumn had been introduced to both farms. The disease may have been introduced with asymptomatic carrier animals, as earlier no similar disease had been observed at either farm.


Analysis of the outbreak of the novel coronavirus COVID-19 dynamic model with control mechanisms.
The mathematical models of infections are essential tools in understanding the dynamical behavior of disease transmission. In this paper, we establish a model of differential equations with piecewise constant arguments that explores the outbreak of Covid-19 including the control mechanisms such as health organizations and police supplements for the sake of controlling the pandemic spread and protecting the susceptible population. The local asymptotic stability of the equilibrium points, the disease-free equilibrium point, the apocalypse equilibrium point and the co-existing equilibrium point are analyzed by the aide of Schur-Cohn criteria. Furthermore and by incorporating the Allee function at time t, we consider the extinction case of the outbreak to analyze the conditions for a strong Allee Effect. Our study has demonstarted that the awareness of the police personal and the management of professional health organizations play a vital role to protect the susceptible class and to prevent the spreading. Numerical simulations are presented to support our theoretical findings. We end the paper by a describtive conclusion.


Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome.
Marfan syndrome (MFS) is an autosomal-dominant disorder of connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mortality is often due to aortic dissection and rupture. We investigated the structural and functional properties of the heart and aorta in a [Fbn1C1039G/+] MFS mouse using high-resolution ultrasound (echo) and optical coherence tomography (OCT). Echo was performed on 6- and 12-month old wild type (WT) and MFS mice (n = 8). In vivo pulse wave velocity (PWV), aortic root diameter, ejection fraction, stroke volume, left ventricular (LV) wall thickness, LV mass and mitral valve early and atrial velocities (E/A) ratio were measured by high resolution echocardiography. OCT was performed on 12-month old WT and MFS fixed mouse hearts to measure ventricular volume and mass. The PWV was significantly increased in 6-mo MFS vs. WT (366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p = 0.003) and 12-mo MFS vs. WT (459.5 ± 42.3 vs. 205.3 ± 30.3 cm/s; p< 0.0001). PWV increased with age in MFS mice only. We also found a significantly enlarged aortic root and decreased E/A ratio in MFS mice compared with WT for both age groups. The [Fbn1C1039G/+] mouse model of MFS replicates many of the anomalies of Marfan patients including significant aortic dilation, central aortic stiffness, LV systolic and diastolic dysfunction. This is the first demonstration of the direct measurement in vivo of pulse wave velocity non-invasively in the aortic arch of MFS mice, a robust measure of aortic stiffness and a critical clinical parameter for the assessment of pathology in the Marfan syndrome.


Developing patient group directions for medicines management.
This article explores the development and use of patient group directions in the supply and administration of medicines. It provides an overview of the classification of medicines and differentiates between a patient specific direction and a patient group direction. The use of patient group directions in the NHS and private sector, and the medicines that can be included in such a directive, are discussed.


A young-onset frontal dementia with dramatic calcifications due to a novel CSF1R mutation.
Neuroimaging and genomic analysis greatly aid in the identification of young-onset dementia antemortem. We present the case of a 33-year-old female with a 2-year rapid decline to dementia and immobility marked by personality change, executive deficits including compulsions, attention deficit, apraxia, Parkinsonism, and pyramidal signs. She had unique and dramatic calcifications and confluent white matter changes on imaging and was found to have a novel mutation in the colony stimulating factor 1 receptor gene causing adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Here, we review ALSP and briefly discuss differential diagnoses.


[Refugee movements in the post-Cold War era].
"This article briefly describes the scope and dimensions of contemporary refugee movements by analyzing some of the forces which shape these flows. Democratization, problems of nationality and minority rights, and structural, political, economic, environmental and social changes in the post-Cold War world (especially in large parts of the developing world and in Eastern Europe and the former Soviet Union), are likely to result in growing numbers of refugees and internally displaced persons in the years ahead. Refugees and asylum seekers are increasingly regarded not only as a major humanitarian challenge but as a political problem and a threat to the national security of Western states. Refugee policy involves much more than defining or adjudicating claims for asylum, safe haven and refugee status for those who seek to enter or stay in the West. It is now apparent that an effective response to these issues will have to involve major Western foreign policy and international actions." (SUMMARY IN ENG)


[Tako-tsubo syndrome without typical anamnesis].
A 77-year-old female in severe emotional distress was admitted to Coronary Care Unit with typical features of acute coronary syndrome, namely severe chest pain, high cardiac necrosis markers and ST-elevation in ECG. Due to the lack of significant changes in coronary arteries in coronary angiography the contractile function of the heart muscle was assessed in echocardiographic examination. That allowed to diagnose tako-tsubo cardiomyopathy. This condition is commonly triggered by stress. This case report puts emphasis on anamnesis, which is often underestimated when diagnosing tako-tsubo syndrome.


Patients with invasive lobular breast cancer are less likely to undergo breast-conserving surgery: a population based study in the Netherlands.
The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC). Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the NCR. All patients underwent BCS or primary mastectomy without neoadjuvant treatment and proportions per year were calculated. Logistic regression analysis with adjustment for period, age, nodal status and tumor size was performed to determine the impact of histology on the likelihood of undergoing BCS. A total of 152,574 patients underwent surgery in the period between 1990 and 2010, of which 89 % had IDC and 11 % had ILC. In the group of IDC with pT1 and pT2 tumors combined, 54 % underwent BCS compared with 43 % of patients with ILC (p < 0.0001). The proportion of patients with IDC treated by BCS increased from 46 % in 1990 to 62 % in 2010. The BCS rate among ILC patients increased from 39 % in 1990 to 48 % in 2010. Patients with ILC were less likely to undergo BCS compared with patients with IDC (odds ratio 0.69; 95 % confidence interval 0.66-0.71). The incidence of BCS for patients with IDC or ILC is rising in The Netherlands. However, the increase of BCS is less explicit in patients with ILC, with a higher chance of undergoing mastectomy compared with patients with IDC.


Implication of Row Orientation Changes on Fruit Parameters of Vitis vinifera L. cv. Riesling in Steep Slope Vineyards.
Row orientation, among others, is a crucial factor in determining grapevine performance and health status, thus affecting berry components that form the basis of the later wine profile. However, the literature about the impact of changes in row orientation at steep slope sites on grapevine fruit composition as well as the differentiation between canopy sides hardly exists. Thus, the aim of this work was to gain knowledge about the impact of row orientation in steep slope vineyards on selected primary and secondary metabolites in berries of Vitis vinifera L. cv. Riesling. Samples were taken from both canopy sides of different row orientations of terraced and downslope vineyards in steep slopes. Free amino acids in the juice and flavonols in the berry skin had a positive correlation to sunlight exposure. Furthermore, grapevines showed adaptations to constantly higher light conditions, e.g., physiologically in reduction in chlorophyll content or protective mechanisms resulting in a lower susceptibility to sunburn damage. Thus, grapevine fruit parameters are affected by row orientation change in steep slopes.


The large glycoprotein subunit of the skeletal muscle voltage-sensitive calcium channel. Deglycosylation and development.
Deglycosylation was used to assess the size of the core polypeptide of the large alpha 2-glycoprotein subunit of the 1,4-dihydropyridine-sensitive calcium channel from rabbit skeletal muscle. The extent of glycosylation was assessed by measuring the shift in apparent molecular mass of the alpha 2 component following electrophoresis in sodium dodecyl sulphate/polyacrylamide gels, using anti-(alpha 2-subunit) monoclonal antibody staining of immunoblots. Chemical deglycosylation with trifluoromethanesulphonic acid produced a shift in apparent molecular mass of the alpha 2 component from Mr 140,000 to Mr 105,000, consistent with a carbohydrate content of approximately 25%. Enzymatic treatments were insufficient to deglycosylate the alpha 2 subunit fully, possibly due to the inaccessibility of glycosidic bonds to enzyme attack. Enzymatic deglycosylation procedures did, however, reduce the 1,4-dihydropyridine-binding activity of transverse-tubule membranes. Neuraminidase alone or together with endo-beta-N-acetylglucosaminidase (endoglycosidase F) reduced the number of sites for (+)[3H]PN 200-110 by 73 +/- 2% and 77 +/- 5% respectively, with no change in apparent dissociation constant, implying a possible role for the glycosylated subunits in the binding of 1,4-dihydropyridines to the calcium-channel complex. The development of the alpha 2 component in rat skeletal muscle was shown to be indistinguishable from the appearance of 1,4-dihydropyridine binding activity consistent with the involvement of the alpha 2 subunit in the calcium-channel complex at all stages of development.


Hypertensive crisis in children: an experience in a single tertiary care center in Korea.
Hypertensive crisis is a medical emergency that can cause acute damage to multiple end-organs. However, relatively little is known on the etiology, treatment, and outcomes of hypertensive crisis in Korean children. The aim of this study was to determine the etiologies and efficacy of drugs for hypertensive crisis in children during the past 5 years at a single center in Korea. We analyzed data from 51 children with hypertensive crisis during the period between January 1, 2010 and April 1, 2014. The patients were divided into two groups: those diagnosed with a hypertensive emergency (hypertension with organ injury, n = 31) and those diagnosed with a hypertensive urgency (hypertension without organ injury, n = 20). Baseline etiologies and risk factors were compared between the two groups. In addition, systolic and diastolic blood pressures were evaluated at 1, 2, 4, and 5 hours after the administration of intravenous antihypertensive drugs. Kidney injury and cancer were the common causes in patients with hypertensive crisis. Cardiovascular complications (cardiac hypertrophy) (p = 0.002), central nervous system complications (p = 0.004), and retinopathy (p = 0.034) were more frequently observed in children with hypertensive emergency than those with hypertensive urgency. However, the proportion of renal complications was similar in both groups. Hydralazine was most commonly used in both groups to control acute increasing blood pressure at first. However, it was often ineffective for controlling abrupt elevated blood pressure. Therefore, intravenous antihypertensive drugs were changed from hydralazine to nicardipine, labetalol, or nitroprusside to control the high blood pressure in 45.1 % of the patients. Particularly, in patients with hypertensive crisis, there was no significant difference in reduction of systolic and diastolic blood pressure and in improvement of clinical outcomes between nicardipine and labetalol administration. Close blood pressure monitoring and careful examinations should be mandatory in children with underlying disease, especially renal diseases and cancer. Furthermore, both nicardipine and labetalol may be effective antihypertensive drug in lowering high blood pressure in children with hypertensive crisis.


Smoking Beliefs Among Chinese Secondary School Students: A Theory-Based Qualitative Study.
China has the world's greatest number of smokers but theory-based smoking interventions are rare. To develop an effective intervention, understanding the determinants of Chinese adolescent smoking is crucial. The Theory of Planned Behavior (TPB) is empirically supported to predict and assist in informing intervention strategies to change health-related behaviors. Based on the TPB, the elicitation of shared smoking beliefs among adolescents can inform future intervention designs among this at-risk population. We investigated the beliefs from six focus groups (N = 30) of one senior secondary school in Kunming, Yunnan Province, China. We used semi-structured questions based on the TPB framework, including prompts about behavioral (advantages and disadvantages), normative (important referents), and control (barriers and facilitators) beliefs. Following the Consensual Qualitative Research (CQR) methodology, data were discussed until consensus was reached. Auditing was undertaken by an external researcher. Seven domains (advantages, disadvantages, approvers, disapprovers, facilitators, barriers, and smoker images) were examined. Smoking as a gendered behavior, smoking as influenced by cultural and environmental contexts, smoking as a strategy to cope with stress, and awareness of the harm of smoking, are highlighted themes across domains. Data suggested an extended-TPB framework as an appropriate approach to adopt when addressing smoking beliefs among the target population. These beliefs can be utilized to inform future school-based interventions and public health campaigns targeting smoking among Chinese adolescents. A modified TPB approach has potential for future smoking interventions among Chinese adolescents. Beliefs elicited in this study form a strong basis for designing a location- and population-specific antismoking programme.


How Reliable are Test Numbers for Revealing the COVID-19 Ground Truth and Applying Interventions?
The number of confirmed cases of COVID-19 is often used as a proxy for the actual number of ground truth COVID-19-infected cases in both public discourse and policy making. However, the number of confirmed cases depends on the testing policy, and it is important to understand how the number of positive cases obtained using different testing policies reveals the unknown ground truth. We develop an agent-based simulation framework in Python that can simulate various testing policies as well as interventions such as lockdown based on them. The interaction between the agents can take into account various communities and mobility patterns. A distinguishing feature of our framework is the presence of another 'flu'-like illness with symptoms similar to COVID-19, that allows us to model the noise in selecting the pool of patients to be tested. We instantiate our model for the city of Bengaluru in India, using census data to distribute agents geographically, and traffic flow mobility data to model long-distance interactions and mixing. We use the simulation framework to compare the performance of three testing policies: Random Symptomatic Testing (RST), Contact Tracing (CT), and a new Location-Based Testing policy (LBT). We observe that if a sufficient fraction of symptomatic patients come out for testing, then RST can capture the ground truth quite closely even with very few daily tests. However, CT consistently captures more positive cases. Interestingly, our new LBT, which is operationally less intensive than CT, gives performance that is comparable with CT. In another direction, we compare the efficacy of these three testing policies in enabling lockdown, and observe that CT flattens the ground truth curve maximally, followed closely by LBT, and significantly better than RST.


The role of routine assays of serum amylase and lipase for the diagnosis of acute abdominal pain.
We aimed to evaluate the role of routine measurements of serum amylase and lipase in the diagnosis of acute abdominal pain. We identified all patients who had serum amylase and lipase assays over a 62-day period at a single university teaching hospital and reviewed their case notes. We excluded 58 of the 1598 patients on grounds of ineligibility (< 18 years of age and those transferred from other hospitals). A complete data set was obtained for 1520 (98.7%) of the remaining 1540 patients. Only 9.1% of requests were based on a clinical suspicion of acute pancreatitis. Of the 44 (2.9%) patients who had acute pancreatitis, only 28 (63.6%) had an associated rise in serum amylase and/or lipase 3 times above the maximum reference range, the remainder being diagnosed radiologically. At this cut-off range, the sensitivity and specificity for serum amylase were 50% and 99%, and those for serum lipase 64% and 97%, respectively. Routine measurements of serum amylase and lipase are unhelpful in the diagnosis of acute abdominal pain unless there is clinical suspicion of acute pancreatitis. In these patients, assay of lipase alone is preferable to assay of amylase alone or both enzymes.


Cytologic features of hepatoid carcinoma of the ovary: a case report with immunocytologic evaluation of HepPar1.
Hepatoid carcinoma is a rare, primary neoplasm of the ovary characterized by histologic, immunobistochemical and analytical evidence of hepatic differentiation. Reflecting the rarity of this entity, few cytologic descriptions are available. A 65-year-old woman presented with an abdominopelvic mass, peritoneal implants and elevated levels of CA-125 and a-fetoprotein (AFP). Cytologic examination of the ascitic fluid revealed cellular samples of polygonal cells in trabecular and papillary groups. Neoplastic cells were predominantly monomorphous, but some groups exhibited marked cellular atypia. A few trabecular groups showed peripheral endothelial rimming. Histologically, the neoplasm had evident hepatocellular differentiation, with a solid, trabecular growth of polygonal, eosinophilic cells with well-defined boundaries. The cells were immunoreactive with keratins, AFP and HepPar1. Retrospectively, HepPar1 was tested in cytologic samples, with a positive result. As occurs with other hepatocellular neoplasms, the hepatic differentiation that characterizes this unusual neoplasm may not be easily recognizable in effusion samples. However, there are some features that, in addition to an elevated AFP value, may help to suggest the diagnosis. A predominant trabecular arrangement with occasional endothelial rimming and HepPar1 immunoreactivity, consistent with hepatic differentiation, are unusual in common surface epithelial ovarian tumors.


Breast conservative surgery: is it appropriate for locally advanced breast cancer following downstaging by neoadjuvant chemotherapy? A pathological assessment.
The application of breast conserving surgery to down-staged cases with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a controversial issue with a variable incidence of locoregional failures. In this study, the response of LABC to NACT was assessed pathologically and the eligible candidates for breast conserving surgery were identified retrospectively. The efficacy of preoperative clinical examination and mammography in detecting these pathological changes were also evaluated. The study included 41 LABC cases. They received NACT (FAC) and were then subjected to a mastectomy. The cases were examined clinically and by mammography before starting treatment and immediately before surgery. Residual tumours in the mastectomy specimens were correlated with the pretreatment and preoperative clinical and mammographic findings in order to assess the efficacy of these tools for detection of NACT-induced changes. After 3 cycles of NACT, 78% of women showed an objective response. However, only 25% of them would have been eligible for breast conserving surgery. The remaining responders had an increased incidence of either multifocality and or peritumoural in situ carcinoma. Both clinical examination and mammography were inadequate for detection of these chemotherapy-induced changes and hence for selecting suitable candidates for breast conservation. This study has shown that tumour regression by NACT is probably induced by a process of tumour segmentation and is associated with an increased incidence of ductal in situ lesions in the original tumour bearing area.


PD-L1/PD-1 check-point in gastric carcinoma with lymphoid stroma case report with immunochemical study.
Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1-programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes. The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery.


Electrotransfer of RNAi-based oligonucleotides for oncology.
For more than a decade, there has been tremendous growth in our understanding of RNA interference (RNAi). The potent ability that small oligonucleotides have in gene silencing makes them desirable as novel cancer therapeutics, but many biological barriers exist for their efficient delivery into target cells or tissues. Electropulsation (EP) appears to be a promising method for cancer-associated gene therapy. EP is the direct application of electric pulses to cells or tissues that transiently permeabilize the plasma membranes, allowing efficient in vitro and in vivo cytoplasmic delivery of exogenous molecules. The present review reports on the type of therapeutic RNAi-based oligonucleotides that can be electrotransferred, the mechanism of their electrotransfer and the technical settings for pre-clinical purposes.


Synthesis and biological evaluation of (±)-hippolachnin and analogs.
Due its unique structure and its reported potent antifungal activity, the marine polyketide hippolachnin A (1) has attracted much attention in the synthetic community. Herein, we describe the development of a concise, diversifiable and scalable synthesis of the racemic natural product, which serves as a platform for the generation of bioactive analogues. Biological testing of our synthetic material did not confirm the reported antifungal activity of hippolachnin A but unraveled moderate activity against nematodes and microbes.


Research note: use of consecutive carcass rinses and a most probable number procedure to estimate salmonellae contamination of inoculated broilers.
Two similar trials were conducted to evaluate the accuracy of the whole carcass rinse technique in combination with a most probable number (MPN) procedure for estimating the number of salmonellae on postchill broilers. Birds were reared in litter-floored pens and inoculated with Salmonella typhimurium (10(8) cfu/mL) on Days 2, 7, and 14. In each of the two trials six carcasses were consecutively rinsed four times. Each carcass was rinsed with 100 mL of sterile water in sterile plastic bags using an automated shaking device. Salmonellae were enumerated using a three-tube MPN procedure in selenite cystine broth. There were no statistical differences in log10 MPN salmonellae per milliliter of recovered rinse fluid due to trial or consecutive rinse. In several cases salmonellae were not recovered in the initial rinse but were recovered from consecutive rinses of the same carcass. A large amount of variation in MPN levels of salmonellae among individual carcasses occurred within each consecutive rinse. The data suggested that only a percentage of the total salmonellae present on a postchill carcass were recovered with each consecutive rinse, and the organisms were firmly attached prior to processing.


beta-1,3-Endoglucanase from Soybean Releases Elicitor-Active Carbohydrates from Fungus Cell Walls.
Two enzymes from soybean (Glycine max L. Merr. cv Harosoy 63) cotyledons released elicitor-active carbohydrates from cell walls of the phytopathogenic fungus Phytophthora megasperma f.sp. glycinea. They were identified as isoenzymes of beta-1,3-endoglucanase (EC 126.96.36.199) with isoelectric points of pH 8.7 and 10.5. The pI 10.5 enzyme was extracted in the greatest amount and was isolated as a homogeneous protein of about 33,000 daltons as determined by gel filtration and sodium dodecyl sulfategel electrophoresis. The purified enzymes hydrolyzed several beta-1,3-glucans in a strictly random manner, but degraded neither beta-1,6- nor beta-1,4-glucans.


In vitro investigation of a standardized dried extract of Citrullus colocynthis on liver toxicity in adult rats.
A standardized extract of Citrullus colocynthis used as an oral natural laxative in folk medicine was tested for its influence on liver function parameters in vitro. Cytochrome P450 (CYP) dependent production of reactive oxygen species (ROS) under the influence of Citrullus colocynthis extract was investigated by means of stimulated lipid peroxidation (LPO), H2O2 formation and amplified chemiluminescence in rat liver microsomes. In rat liver 9000 x g supernatants 4 monooxygenase reactions mediated by different CYP forms were measured. Putative hepatotoxic effects of Citrullus colocynthis extract were measured by means of potassium and GSH concentrations in and LDH leakage from precision-cut rat liver slices. For possible hepatoprotective effects the influence of the extract on carbon tetrachloride-induced changes of these parameters was investigated. Citrullus colocynthis extract in concentrations higher than 10 microg/ml incubation mixture proved to inhibit lipid peroxidation and ROS-production as well as CYP1A-, 2B- and 3A-dependent reactions with typical substrates. In contrast, H2O2 production was not reduced under the influence of the extract, a slight but significant increase was seen. Citrullus colocynthis extract was found to be free of hepatotoxic effects in concentrations up to 100 microg/ml incubation mixture when liver slices were incubated in William's medium E for 22 hours. All viability parameters used were not influenced by the extract of Citrullus colocynthis. Carbon tetrachloride induced hepatotoxicity could not be prevented or alleviated. Moreover, the damage was sometimes enhanced by higher extract concentrations.


Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition.
To explore hepatoprotective role and underlying mechanisms of Trillium tschonoskii Maxim (TTM), 36 rats were randomly divided into control, CCl4-induced liver injury model, and biphenyl dimethyl dicarboxylate (DDB) and low-, moderate-, and high-dose TTM treatment groups. After CCl4-induced model establishment, the rats from DDB and TTM groups were administrated with DDB at 0.2 g/kg per day and TTM at 0.1, 0.5, and 1.0 g/kg per day, while the rats from control and model groups were administrated with saline. After 5 days of treatments, all rats were sacrificed for determining serum ALT and AST levels and liver index, examining histopathological changes in liver through HE and TUNEL staining, and evaluating TNF-α and IL-6 mRNA expression by real-time PCR, and caspase-3, Bcl-2, and Bax expression by Western blot. Results indicated that CCl4 could induce acute liver injury and abnormal liver function in rats with obvious hepatomegaly, increased liver index, high ALT and AST levels, up-regulated TNF-α and IL-6, and overexpressed Bax and caspase-3. However, DDB and TTM could execute protective role in CCl4-induced liver injury in rats through reducing ALT and AST levels, rescuing hepatomegaly, down-regulating inflammatory factors and inhibiting hepatocyte apoptosis in a dose-dependent manner. Therefore, TTM has obvious protective role in CCl4-induced liver injury of rats through inhibiting hepatocyte apoptosis.


Curcumin-loaded hydrogel nanoparticles: application in anti-malarial therapy and toxicological evaluation.
The present investigation involved preparation of hydrogel nanoparticles using a combination of hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone. The objective was to exploit the size and hydrophilic nature of the formulated nanocarriers to enhance absorption and prolong the rapid clearance of curcumin due to possible evasion of the reticulo-endothelial system. Reproducible nanoparticles of size around 100 nm, a fairly narrow distribution and encapsulation efficiency of 72%, were produced by the solvent emulsion-evaporation technique. This optimized system was further subjected to freeze-drying. The freeze-dried product was readily reconstituted with distilled water. The reconstituted product exhibited a size and distribution similar to that before freeze-drying, drug content of greater than 99% and presence of amorphous drug when analyzed by differential scanning calorimetry (DSC) which may result in possible improved absorption of curcumin. In vivo anti-malarial studies revealed significant superior action of nanoparticles over curcumin control suggesting the possibility of the formulation being employed as an adjunct anti-malarial therapy along with the standard therapy. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A battery of genotoxicity studies was conducted to evaluate the nongenotoxic potential of the developed formulation thus indicating the possibility of the formulation being employed for prolonged duration.


Identification of famous faces and famous names in early Alzheimer's disease. Relationship to anterograde episodic and general semantic memory.
We assessed remote memory in 33 patients with dementia of Alzheimer's type (DAT) with Mini-Mental State Examination (MMSE) scores between 17 and 30, and 30 matched controls using a Famous Faces Test and Famous Names Test designed to assess face recognition, identification and naming, and name recognition and identification, respectively, together with a range of anterograde episodic and semantic memory tests. Patients with DAT were impaired on all components of the remote memory tests, i.e. famous face recognition, identification and naming, and famous name recognition and identification. There was also evidence of a modest temporal gradient, with relatively greater impairment of more recent memory, which may be artefactual resulting from the very insidious onset of their anterograde amnesia. In contrast to the uniform impairment of anterograde memory, there was considerable heterogeneity in performance on remote memory. Although the DAT patient group's performance on remote memory measures was impaired with respect to controls, some patients had significant impairment on all measures, whereas others had intact remote memory. Overall, there was only a weak correlation between dementia severity and remote memory, and no correlation between performance on the Faces and Names tests and measures of anterograde memory. At a cognitive level, the deficit in face and name processing in DAT involved recognition, identification and naming. This would suggest that so called 'face and name recognition units', semantic knowledge of famous persons and post-semantic processing are all affected by the disease. There was also supporting evidence for the concept that recognition of famous faces and names both draw on common sources. Similar results were found for face and name identification. This suggests that face and name recognition units are closely linked, and that identification of a face or name accesses the same central pool of semantic knowledge regarding the famous person. Performance on famous names tests correlated, to a limited degree, with that on general semantic tests, suggesting that knowledge of famous people, at least as accessed by names, is associated with general semantic memory. By contrast, no correlation was found between performance on the famous faces and on other general semantic tasks.


Sodium benzoate-induced repeated episodes of acute urticaria/angio-oedema: randomized controlled trial.
Sodium benzoate (E 211) is widely used to delay yeast spoilage of acidic foods and beverages. Numerous cases of adverse reactions to benzoate have been recorded, but most of the studies that have been conducted lacked proper placebo controls or blinding. The aim of this study is to determine the incidence of intolerance to sodium benzoate among subjects who experienced repeated episodes of acute urticaria/angio-oedema following the ingestion of a meal or a product containing this substance. This was a retrospective study based on the analysis of data from patients reported to have experienced episodes of urticaria, with or without angio-oedema, after ingesting meals or products containing sodium benzoate. At the first visit to the outpatients clinic, a careful history was taken. Patients were then given the following diagnostic tests: tests for IgE for common inhalant allergens and food allergens, and a double-blind, placebo-controlled challenge with sodium benzoate. A total of 47 subjects were enrolled in the study; five (11%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (2%) had a reaction after the ingestion of 75 mg of sodium benzoate without an adverse reaction to placebo. This study shows that the percentage of repeated episodes of acute urticaria/angio-oedema reactions induced by sodium benzoate is very low (2%). In view of our results, we suggest that when faced with patients who have suffered adverse reactions that could be attributed to sodium benzoate, physicians should also carefully evaluate other possible causes.


Effects of surgical treatment for cervical spondylotic myelopathy in patients > or = 70 years of age: a retrospective comparative study.
The objective of this study was to compare efficacy of cervical surgery for myelopathy in patients > or = 70 and < or = 60 years of age. Forty patients > or = 70 years and 50 patients < or = 60 years of age with MRI and CT proven myelopathy were neurologically assessed using the JOA score. Three operative procedures were performed: anterior spinal fusion, laminoplasty, and laminectomy. Postoperatively, patients exhibited comparable outcomes irrespective of age or operative procedure performed. The only exception was the increase in postoperative neurologic complications noted for the older individuals with greater comorbidities.


Simultaneous determination of nandrolone, testosterone, and methyltestosterone by multi-immunoaffinity column and capillary electrophoresis.
A multitarget antibody immunoaffinity column was proposed for the purification and enrichment of nandrolone, testosterone, and methyltestosterone from urine. Nandrolone-3-site substituted antigen was designed and synthesized and the polyclonal antibody was prepared with immunizing rabbits. The stationary phase of the immunoaffinity column was synthesized by covalently bonding the antibodies specific to nandrolone, testosterone, and methyltestosterone onto CNBr-actived Sepharose 4B. The analytes of interest were extracted with a methanol/water mixture in one step. The immunoaffinity column showed high affinity and high selectivity to a class of structurally related compounds. The elution was then transferred to a micellar electrokinetic CE system with a running buffer of sodium borate and sodium cholate for separation and determination. Recoveries of the three steroids from complex matrix were 88-94% with RSD values less than 5.2%. Optimization of the immunoaffinity column purification was achieved and the feasibility of the technique for the analysis of steroid hormone was discussed. The results indicated that the combination of multi-immunoaffinity column and CE was an effective technique, which was rapid, simple, and sensitive for the assay of steroids.


Subcellular distribution of endogenous long chain acylcarnitines during hypoxia in adult canine myocytes.
Previous studies from our laboratory showed a pronounced increase in the sarcolemmal accumulation of long chain acylcarnitines in isolated neonatal rat myocytes after a prolonged (60 minute) hypoxic interval. Because much shorter intervals of hypoxia are associated with electrophysiological alterations in adult cells, the present study was performed to assess the extent of sarcolemmal accumulation of long chain acylcarnitines during hypoxia in adult canine myocytes. Cells were incubated (for 24 hours) with 3H-carnitine and the uniformity of incorporation into carnitine fractions was verified biochemically. Cells were exposed to hypoxia (PO2 < 15 mm Hg) for 10 or 20 minutes in the presence or absence of sodium 2-[5-(4-chlorphenyl)-pentyl]-oxirane-2-carboxylate (POCA; 10 microM), an inhibitor of carnitine acyltransferase I. Cells were processed for electron microscopical autoradiography with a technique to spatially fix endogenous long chain acylcarnitines with selective and complete removal of short chain and free carnitine. Grain distributions were analysed by the maximum likelihood method from digitised micrographs. Total mass of long chain acylcarnitines increased ninefold [42.3(3.3) to 374(42) pmol.mg-1 protein] by 10 minutes of hypoxia and 15-fold [to 632(36) nmol.mg-1 protein] by 20 minutes of hypoxia. Normoxic cells exhibited little long chain acylcarnitines in the sarcolemma, and modest amounts in mitochondria and cytoplasm. In hypoxic cells, content of long chain acylcarnitines in mitochondria and cytoplasm increased by a maximum of twofold. By contrast, long chain acylcarnitines increased 100-fold in the sarcolemma to 4.18 x 10(6) molecules.microns-3 after 10 minutes of hypoxia. The increase in long chain acylcarnitines with hypoxia was completely prevented by pretreatment with POCA. Hypoxia in adult ventricular myocytes induces a rapid and preferential increase in endogenous long chain acylcarnitines within the sarcolemma.


[Psychiatric and cognitive complications arising from subthalamic stimulation in Parkinson's disease].
Subthalamic stimulation is a therapeutic option that can be used to treat advanced cases of Parkinson's disease. However, psychiatric or cognitive disorders have been reported in some patients treated using this technique. Age and a long disease history are two important risk factors for the appearance of these problems. The complications that have been reported include cases of depression, apathy, manias and psychosis. Surgery can also exacerbate the syndrome of addiction to levodopa that is sometimes observed. In contrast, sleep disorders usually improve with this technique. As far as the cognitive sphere is concerned, verbal fluency has been seen to deteriorate and the executive functions become impaired in patients over 69 years of age. These disorders are usually due to a number of different causes and have been attributed to the action of stimulating areas close to the subthalamic nucleus, to the presence of previously existing cognitive or psychiatric problems, to unrealistic expectations about this technique or to the individual's inability to adapt to the functional situation after surgery. Although generally speaking these disorders are not usually serious, they must be borne in mind so that adequate treatment can be indicated.


Anaphylaxis as an adverse event following immunisation in the UK and Ireland.
Anaphylaxis is a rare adverse event following immunisation (AEFI) and unlikely to be detected in prelicensure vaccine trials. Previous retrospective studies have been hampered by the paucity of information available to passive reporting schemes. The aim of the present study was to estimate the incidence and clinical presentation of anaphylaxis as an AEFI using prospective active surveillance. Children under 16 in the UK and Ireland with suspected anaphylaxis as an AEFI were reported through the British Paediatric Surveillance Unit (BPSU) between September 2008 and October 2009. Paediatricians completed questionnaires on presentation, diagnosis, management and outcome. A total of 7 out of 15 reports met criteria for anaphylaxis following immunisation. Four of the seven children reacted more than 30 min after administration of the vaccine. Six children required treatment with intramuscular adrenaline and intravenous fluids, but all made a full recovery. Denominators were not available for all vaccines so an overall incidence was not calculated, however the estimated incidence was 12.0 per 100,000 dose for single component measles vaccine and 1.4 cases per million doses for the bivalent human papilloma virus vaccine (Cervarix, GSK). Anaphylaxis remains a rare adverse event following immunisation. No cases were related to vaccines given as part of the 'routine' infant and preschool immunisation programme, despite over 5.5 million vaccines being delivered in this time period. Some children had delayed onset of symptoms and this should be considered when vaccinating those at higher risk of anaphylaxis.


Developmental regulation of the PsbS gene expression in spinach seedlings: the role of phytochrome.
The PsbS gene product (PSII-S) which is an integral subunit of photosystem II has recently been reported to be a new type of pigment-binding protein [11]. The chlorophylls of the PSII-S protein exhibit weak excitonic coupling and this protein is stable also in the absence of pigments. Here we investigated the expression of the PsbS gene in etiolated spinach seedlings grown either in complete darkness or exposed to light of various qualities. The results obtained reveal that the PsbS gene expression in etiolated spinach plants is subjected to endogenous control. This developmental control occurs at different levels of gene expression and results in transient accumulation of the PsbS transcripts with progressing etiolation. During the first two days after emerging of the cotyledons from the seed coat the steady-state level of the PsbS transcripts is regulated mainly through increased transcriptional activity of the PsbS gene. Prolonged growth of the seedlings in the dark resulted in additional post-transcriptional control of the PsbS transcript level. Translational activity of PsbS mRNA estimated by an integration of mRNA into polysomal complexes shows that the translation rate of PsbS mRNA is less influenced by seedling age. The maximal rate of translation is reached at the first day after cotyledons emergence but the translational activity of PsbS mRNA remains still high (50% of maximum) in 8-day old etiolated spinach plants. In addition to the light-independent developmental control, the PsbS gene expression is positively regulated by phytochrome in etiolated seedlings exposed to light. Red light, however, negatively influences the abundance of PsbS transcripts at post-transcriptional level. Studies on blue or far-red light effects reveal that the accumulation of PsbS transcripts exhibits the characteristics of very-low-fluence responses of the phytochrome receptor.


Molecular cloning and expression of a TNF receptor and two TNF ligands in the fish ovary.
Using degenerative primers, partial cDNAs of a TNF (tumor necrosis factor) receptor and two TNF ligands were obtained by PCR of zebrafish and trout cDNAs, or cDNA libraries. These fragments were then used to screen cDNA libraries of appropriate tissues to obtain clones containing full coding sequences. A zebrafish cDNA was obtained that presumably codes for a 438 amino acid ovarian TNF receptor (OTR) that was identified as a death-domain-containing member of the TNF receptor family. On Northern blots, the OTR cDNA hybridized with a 3.4-kb transcript that is abundant in the zebrafish ovary but lightly detected in all other tissues tested. A zebrafish cDNA presumably coding for a 214 amino acid protein with sequence similarity to mammalian TRAIL (TNF-related apoptosis inducing ligand), was also isolated. In addition, a fragment of the brook trout TRAIL homologue was obtained. Finally, a full-length brook trout cDNA, that presumably codes for a 255 amino acid protein with sequence similarity to mammalian TNF-alpha and lymphotoxin-alpha, was isolated. This study is the first report of a death-domain-containing TNF receptor and the first published report of a TNF ligand in fish.


[Impact of the effectiveness of myocardial reperfusion after thrombolytic and spontaneous recanalization of infarct related artery on myocardial recovery in the future].
To assess the efficiency of myocardial reperfusion after thrombolytic and spontaneous recanalization of infarct related artery (IRA) by the serial 12 lead ECG data and its impact on subsequent myocardial recovery. We examined 25 patients with a first Q wave myocardial infarction at hospital and after 1 and 3 years from discharge (13 treated with intravenous thrombolysis, 12 treated conservatively). Four patients treated using thrombolysis and 3 patients treated conservatively were excluded from the analysis due to reocclusion or another myocardial infarction and coronary bypass surgery. The efficiency of myocardial reperfusion was assessed by our original method, based on the intensity of changes in ECG stages. The myocardial recovery was analyzed by quantitative changes in clinical, radiographic, echocardiographic and ECG (the Selvester-Wagner QRS score) data. Clinical and radiographic signs of heart failure decreased in cases of sufficient myocardial reperfusion after thrombolytic and spontaneous recanalization, but increased--in cases of insufficient myocardial reperfusion. Echocardiographic dyssynergic score decreased after 3 years from discharge (79, 67 after 1 and 3 yrs/at discharge (%), respectively, p < 0.00005) in cases of thrombolysis with sufficient myocardial reperfusion but the tendency for increasing (113, 183 after 1 and 3 yrs/at discharge (%), respectively, p = 0.07) was shown in cases of insufficient myocardial reperfusion; although, the QRS score decreased in both subgroups of thrombolysis (89, 36 after 1 and 3 yrs/at discharge (%), respectively, p < 0.01,--with sufficient myocardial reperfusion; 73, 62 after 1 and 3 yrs/at discharge (%), respectively, p < 0.005,--with insufficient myocardial reperfusion). The QRS score normalization after myocardial infarction predicts myocardial functional recovery only in patients with sufficient myocardial reperfusion. Thrombolysis gives positive impact on subsequent myocardial functional recovery only in cases of sufficient myocardial reperfusion; spontaneous recanalization of IRA may give positive impact on myocardial functional recovery in cases of sufficient myocardial reperfusion. Our method of serial ECG interpretation provides the possibility to detect insufficient myocardial reperfusion after thrombolytic and spontaneous recanalization and then the additional mechanical methods of recanalization should be applied.


Changes in the aetiology, clinical presentation and management of acute interstitial nephritis, an increasingly common cause of acute kidney injury.
Acute interstitial nephritis (AIN) is an important cause of acute kidney injury that has experienced significant epidemiological and clinical changes in the last years. The classical presentation, mostly induced by antibiotics and accompanied by evident hypersensitivity manifestations (skin rash, eosinophilia, fever) has been largely replaced by oligosymptomatic presentations that require a higher index of suspicion and are increasingly recognized in the elderly, having non-steroidal anti-inflammatory agents and proton pump inhibitors as frequent offending drugs. Drug-induced AIN continues to be the commonest type, but it requires a careful differential diagnosis with other entities (tubulointerstitial nephritis with uveitis syndrome, IgG4-related disease, drug reaction with eosinophilia and systemic symptom syndrome, sarcoidosis and other systemic diseases) that can also induce AIN. Cortico-dependant, relapsing AIN is a recently recognized entity that poses an important therapeutic challenge. Although corticosteroids are widely used in drug-induced AIN to speed kidney function recovery and avoid chronic kidney disease, their efficacy has not been tested by randomized controlled trials. New diagnostic tests and biomarkers, as well as prospective therapeutic studies are needed to improve AIN diagnosis and management.


Prophylactic immunosuppression with anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 versus OKT3 in liver allografting. A two-year follow-up study.
A prospective trial was conducted in 129 recipients of primary liver transplantation, to compare induction immunosuppression using triple drug therapy (cyclosporine, steroids, and azathioprine; group 1, n = 42), versus triple drug therapy with a 10-day course of OKT3 (group 2, n = 44) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 (group 3, n = 43). Two-year actual patient survival rates were 64%, 79%, and 93% in groups 1, 2, and 3, respectively (1 vs. 2, NS; I vs. III, P = 0.003; 2 vs. 3, NS). Up to 2 years after transplantation, 18%, 44%, and 53% of the grafts in groups 1, 2, and 3, respectively, had not experienced steroid-resistant acute rejection (1 vs. 2, P = 0.002; 1 vs. 3, P = 0.007; 2 vs. 3, NS). The overall incidence of chronic rejection was 4%. OKT3 therapy, but not LO-Tact-1, significantly increased the incidence of cytomegalovirus infections (P = 0.019). In conclusion, immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3, without an increase in the incidence of infections.


Diagnosis and treatment of distal biceps and anterior elbow pain in throwing athletes.
Despite the activity of the musculature around the elbow and the high angular velocity and stresses, distal biceps tendon injury is rare in the overhead athlete. The biomechanics of the throwing motion and electromyographic studies of the elbow provide useful clues as to why the biceps stays relatively healthy. Anterior elbow complaints are not uncommon in this population and can easily be mistaken for distal biceps pathology. In the event that a thrower does demonstrate biceps tendon pathology, it should be treated in a similar fashion to all other athletic individuals. It is more important to review the differential diagnosis for anterior elbow pain when an athlete has symptoms that might be attributed to the distal biceps tendon. Once the other possible causes of biceps-related pain have been evaluated, the sports medicine physician can then proceed with appropriate treatment to return that athlete to the playing field as quickly and safely as possible.


Individual Placement and Support (IPS) for Methadone Maintenance Therapy Patients: A Pilot Randomized Controlled Trial.
Individual Placement and Support (IPS) is an evidence-based employment model for people with severe mental illness, but it has not been evaluated for clients enrolled in substance abuse treatment programs. This study evaluated the effectiveness of IPS for people with opioid use disorders enrolled in an opioid treatment program. Within a randomized controlled experiment, 45 patients receiving methadone maintenance therapy were assigned to either IPS or a 6-month waitlist. The waitlist group received IPS after 6 months. The primary outcome assessed over 1 year compared the attainment of a job for the IPS condition to the waitlist comparison group. During the first 6 months after enrollment, 11 (50%) active IPS participants gained competitive employment compared to 1 (5%) waitlist participant (Χ 2 = 12.0, p < 0.001). Over 12 months of enrollment, 11 (50%) IPS participants gained competitive employment compared to 5 (22%) waitlist participants (Χ 2 = 3.92, p = 0.07). We conclude that IPS holds promise as an employment intervention for people with opioid use disorders in methadone maintenance treatment, but larger trials with longer follow-up are needed.


Sarcopenic Obesity Tendency and Nutritional Status Is Related to the Risk of Sarcopenia, Frailty, Depression and Quality of Life in Patients with Dementia.
The purpose of this study was to investigate the nutritional status of dementia patients and examine the correlation with sarcopenia, frailty, depression, and quality of life. We enrolled patients aged 60 years and over with Mini Mental State Examination (MMSE) scores ≤ 26 (Taiwan), and dementia diagnosed by a neurologist or psychiatrist. Nutritional status was assessed with the Mini Nutritional Assessment (MNA). Muscle mass was measured by dual-energy X-ray absorptiometry. Muscle strength and endurance were evaluated by handgrip, leg-back strength, dumbbell curls, sit to stand test, and gait speed. Quality of life, frailty, and depression status were measured by questionnaires. Patients with moderate dementia (MMSE ≤ 20) had a significantly lower MNA score, muscle function, and quality of life than patients with mild dementia (p < 0.01). A lower MNA score was significantly associated with the risk of frailty (odds ratio: 4.76, p < 0.01), depression (odds ratio: 3.17, p = 0.03), and poor quality of life (odds ratio: 2.73, p < 0.05), and sarcopenia (odds ratio: 3.97, p = 0.03) after adjusting for potential confounders. In conclusion, patients with dementia were at risk of malnutrition, and nutritional status was associated to the risk of sarcopenia, frailty, depression, and quality of life.


A method for estimating the mutation, gene conversion and recombination parameters in small multigene families.
A simple two-locus gene conversion model is considered to investigate the amounts of DNA variation and linkage disequilibrium in small multigene families. The exact solutions for the expectations and variances of the amounts of variation within and between two loci are obtained. It is shown that gene conversion increases the amount of variation within each locus and decreases the amount of variation between two loci. The expectation and variance of the amount of linkage disequilibrium are also obtained. Gene conversion generates positive linkage disequilibrium and the degree of linkage disequilibrium decreases as the recombination rate is increased. Using the theoretical results, a method for estimating the mutation, gene conversion, and recombination parameters is developed and applied to the data of the Amy multigene family in Drosophila melanogaster. The gene conversion rate is estimated to be approximately 60-165 times higher than the mutation rate for synonymous sites.