Nigrosome 1 visibility at susceptibility weighted 7T MRI-A dependable diagnostic marker for Parkinson's disease or merely an inconsistent, age-dependent imaging finding?
Visualisation of nigrosome 1, a substructure of the healthy substantia nigra, was restricted in susceptibility weighted MR imaging in almost all patients with Parkinson's disease studied so far. The purpose of this study was to determine the degree of visibility of this substructure in subjects without Parkinson's disease and to examine the potential link between increasing brain iron accumulation with age and its detectability. In 46 subjects (21 women, 25 men; 19 to 75 y; mean age: 44.5; SD: 15.6) examined with susceptibility weighted MR imaging at 7T visibility of nigrosome 1 was rated and classified. We assessed differences related to age and to signal intensities in the substantia nigra, red nucleus and putamen as correlates of the individual iron concentration. In 93% nigrosome 1was at least unilaterally clearly present. In 24% at least one-sided limited visibility was observed. Using predefined classification criteria the specificity of the visibility across all age groups reached approximately 94%. We found no correlation with increasing iron concentrations with age. Aging with a related increase in iron concentration probably does not affect the visibility of nigrosome 1 at 7T SWI MRI. Our results support the role of this feature as a future differential diagnostic tool but further large-scale prospective studies are needed to better define the extent of a "limited visibility" to which an individual can be considered healthy.


A multidimensional approach to identifying the physical qualities of male English regional academy rugby union players; considerations of position, chronological age, relative age and maturation.
Interpreting the physical qualities of youth athletes is complex due to the effects of growth, maturation and development. This study aimed to evaluate the effect of position, chronological age, relative age and maturation on the physical qualities of elite male academy rugby union players. 1,424 participants (n = 2,381 observations) from nine Rugby Football Union regional academies prospectively completed a physical testing battery at three time points, across three playing seasons. Anthropometrics, body composition, muscular power, muscular strength, speed, aerobic capacity and running momentum were assessed. Positional differences were identified for all physical qualities. The largest effect sizes were observed for the associations between chronological age (d = 0.65-0.73) and maturation (d = -0.77 to -0.69) and body mass related variables (i.e. body mass and running momentum). Relative strength, maximum velocity and aerobic capacity were the only models to include two fixed effects with all other models including at least three fixed effects (i.e. position and a combination of chronological age, relative age and maturation). These findings suggest a multidimensional approach considering position, chronological age, relative age and maturation is required to effectively assess the physical qualities of male age grade rugby union players. Therefore practitioners should use regression equations rather than traditional descriptive statistic tables to provide individualised normative comparisons thus enhancing the application of testing results for talent identification and player development.Highlights Practitioners should record and incorporate position, chronological age, relative age and maturation into the physical evaluation of elite academy rugby union players.The regression equations provided within this study offer highly generalisable comparative values that are specific to a players chronological and biological development.Through the use of enhanced player evaluation practitioners will be able to make more informed decisions surrounding talent identification and athlete development.


Optimal Design of Wavelength Selective Thermal Emitter for Thermophotovoltaic Applications.
We theoretically and numerically demonstrate optimal design of wavelength selective thermal emitter using one-dimensional (1D) and two-dimensional (2D) metal-dielectric gratings for thermophotovoltaic (TPV) applications. Proposed design consists of tungsten (W) and silicon dioxide (SiO2) gratings which can withstand high temperatures. Radiative properties of 1D grating were calculated using a numerical method, while effective medium approximation was used for 2D gratings. Optimal designs were obtained such that output power is maximum for GaSb photovoltaic (PV) cell at emitter temperature of 1500 K and radiated energy for longer wavelengths is limited to a low value. A constrained optimization was performed using genetic algorithm (GA) to arrive at optimal design.


Evaluating the sustainable traffic flow operational features of an exclusive spur dike U-turn lane design.
The traditional U-turn design has significantly improved traffic operations for relieving traffic congestion. However, the U-turn diversion and merge segments still cause traffic conflicts and delays. In this paper, an exclusive spur dike U-turn lane (ESUL) is proposed with the aim of addressing the disadvantages of the traditional U-turn design. ESUL provides a separate U-turn lane to diverge, decelerate, U-turn, accelerate and merge without interacting with through traffic. The effectiveness of ESUL is demonstrated through a field data investigation, simulation and analysis with VISSIM software. The proposed design is evaluated in terms of three parameters: travel time, delay and number of stops. Compared to the traditional U-turn design, ESUL can reduce travel time by 29.15%, delay by 66.70% and the number of stops by 100% at most. The results showed that ESUL has better performance than the traditional U-turn design and could be implemented to reduce traffic congestion and the potential hazards caused by U-turn maneuvers.


S100A4 in cancer progression and metastasis: A systematic review.
Metastasis is the leading cause of cancer-related death and directly associates with cancer progression, resistance to anticancer therapy, and poor patient survival. Current efforts focusing on the underlying molecular mechanisms of cancer metastasis attract a special attention to cancer researchers. The epithelial-mesenchymal transition is a complex of molecular program during embryogenesis, inflammation, tissue fibrosis, and cancer progression and metastasis. S100A4, an important member of S100 family proteins, functions to increase the tumor progression and metastasis. The molecular mechanisms of S100A4 involving in the progression and metastasis are diverse in various malignant tumors. Detection of S100A4 expression becomes a promising candidate biomarker in cancer early diagnosis and prediction of cancer metastasis and therefore, S100A4 may be a therapeutic target. This review summarized up to date advancement on the role of S100A4 in human cancer development, progression, and metastasis and the underlying molecular events and then strategies to target S100A4 expression experimentally.


Prognostic value of ST2 in myocardial infarction.
Soluble Suppression of Tumorigenicity 2 (ST2) is a biomarker of myocardial fibrosis increasingly recognized as a predictor of morbidity and mortality in heart failure. Its role in the prognosis after a myocardial infarction has not been validated to date. To evaluate the prognostic value of ST2 for in-hospital morbidity and mortality after myocardial infarction. We conducted a longitudinal prospective study including 74 patients admitted for an acute uncomplicated cardiac myocardial infarction at Habib Thameur hospital between April and October 2016. ST2 blood samples were drawn until 72 hours post admission .The primary endpoint was the occurrence of a major cardiovascular event during hospitalization. Patients' mean age was 61.28 ± 13 years-old with a sex ratio of 1.8. The reason for admission was acute coronary syndrome with persistent ST segment elevation in 54% of cases and non-ST segment elevation acute myocardial infarction in 46% of cases. The ST2 assay was positive in 78% of cases with a mean value of 122.43 ± 95.72 ng/ ml. Left ventricular dysfunction was observed in 47% of cases. Fifteen per cent of the patients had a 3 vessel-disease, 24% a 2 vessel-disease and 34% a 1 vessel-disease. Twenty-six percent had at least one major cardiovascular event. In-hospital mortality was 10%. In multivariate analysis, ST2 was an independent factor associated with the occurrence of major cardiovascular events (RR = 2, p = 0.04). The cutoff value of ST2 of 35 ng/ml had a sensitivity of 95%, a specificity of 30% (AUC = 0.672, CI 0.546-0.798, p = 0.024), a negative predictive value of 100% and a positive value of 33%. A significant correlation was found between ST2 and troponin, blood glucose on admission, CRP and left ventricular ejection fraction (respectively: r = 0.398, p <0.0001, r = 0.281, p = 0.015, r = 0.245, p = 0.039, r = -0.401, p <0.0001). The measurement of ST2 after a myocardial infarction constitutes a new prognostic indicator of in-hospital morbidity and mortality.


(-) Epigallocatechin Gallate (EGCG) Prevents Lipid Changes and Collagen Abnormalities in Chronic Ethanol-Fed Rats.
ABSTRACT The objective of the study is to examine the influence of (-) epigallocatechin gallate (EGCG), a green tea component, on lipid and collagen abnormalities in chronic ethanol-fed rats. Solubility properties, aldehyde content, fluorescence, and peroxidation were analyzed in collagen samples isolated from liver. Chronic alcoholism (6 g/kg/day x 60 days) was associated with fatty liver and collagen accumulation. Significant alterations in the levels of lipids (cholesterol, phospholipids, free fatty acids, and triglycerides) and total collagen were observed in liver. Collagen obtained from ethanol-fed rats showed alterations in solubility properties, increased fluorescence, peroxidation, and aldehyde content. Coadministration of EGCG along with ethanol significantly reduced the levels of liver lipids and collagen, improved the solubility properties of collagen, and caused a reduction in cross-linking as evidenced by a decrease in fluorescence, peroxidation, and aldehyde content. Histology of liver sections of ethanol-fed rats showed accumulation of fat and collagen, which were largely prevented by EGCG administration. The possible mechanisms in the protective action of EGCG in alcoholic liver disease are suggested and discussed.


Downregulation of a chloroplast-targeted beta-amylase leads to a starch-excess phenotype in leaves.
A functional screen in Escherichia coli was established to identify potato genes coding for proteins involved in transitory starch degradation. One clone isolated had a sequence very similar to a recently described chloroplast-targeted beta-amylase of Arabidopsis. Expression of the gene in E. coli showed that the protein product was a functional beta-amylase that could degrade both starch granules and solubilized amylopectin, while import experiments demonstrated that the beta-amylase was imported and processed into pea chloroplasts. To study the function of the protein in transitory starch degradation, transgenic potato plants were generated where its activity was reduced using antisense techniques. Analysis of plants reduced in the presence of this beta-amylase isoform showed that their leaves had a starch-excess phenotype, indicating a defect in starch degradation. In addition, it was shown that the antisense plants degraded only 8-30% of their total starch, in comparison with 50% in the wild type, over the dark period. This is the first time that a physiological role for a beta-amylase in plants has been demonstrated.


Evaluation of the Prognostic Value of Long Noncoding RNAs in Lung Squamous Cell Carcinoma.
Lung squamous cell carcinoma (LUSC) is the most common type of lung cancer accounting for 40% to 51%. Long noncoding RNAs (lncRNAs) have been reported to play a significant role in the invasion, migration, and proliferation of lung cancer tissue cells. However, systematic identification of lncRNA signatures and evaluation of the prognostic value for LUSC are still an urgent problem. In this work, LUSC RNA-seq data were collected from TCGA database, and the limma R package was used to screen differentially expressed lncRNAs (DElncRNAs). In total, 216 DElncRNAs were identified between the LUSC and normal samples. lncRNAs associated with prognosis were calculated using univariate Cox regression analysis. The overall survival (OS) prognostic model containing 10 lncRNAs and the disease-free survival (DFS) prognostic model consisting of 11 lncRNAs were constructed using a machine learning-based algorithm, systematic LASSO-Cox regression analysis. We found that the survival rate of samples in the high-risk group was lower than that in the low-risk group. Results of ROC curves showed that both the OS and DFS risk score had better prognostic effects than the clinical characteristics, including age, stage, gender, and TNM. Two lncRNAs (LINC00519 and FAM83A-AS1) that were commonly identified as prognostic factors in both models could be further investigated for their clinical significance and therapeutic value. In conclusion, we constructed lncRNA prognostic models with considerable prognostic effect for both OS and DFS of LUSC.


A two-hybrid system based on chimeric operator recognition for studying protein homo/heterodimerization in Escherichia coli.
The development of a convenient and promising alternative to the various two-hybrid methods that are used to study protein-protein interactions is described. In this system, a lambdoid chimeric operator is recognized by a hybrid repressor formed by two chimeric monomers whose C-terminal domains are composed of heterologous proteins (or protein domains). Only if these proteins efficiently dimerize in vivo is a functional repressor formed able to bind the chimeric operator and shut off the synthesis of a downstream reporter gene. This new approach was tested with several interacting proteins ranging in size from less than 100 to more than 800 amino acids and, to date, no size or topology limit has been detected.


Benefits of Playing Numerical Card Games on Head Start Children's Mathematical Skills.
Low-income preschoolers have lower average performance on measures of early numerical skills than middle-income children. The present study examined the effectiveness of numerical card games in improving children's numerical and executive functioning skills. Low-income preschoolers (N=76) were randomly assigned to play a numerical magnitude comparison card game, a numerical memory and matching card game, or a shape and color matching card game across four 15-minute sessions. Child who played either of the numerical games improved their numeral identification skills, while only children who played the numerical magnitude comparison game improved their symbolic magnitude comparison skills. These improvements were maintained eight weeks later. The results suggest that a brief, low-cost intervention can successfully improve the numerical skills of low-income children.


Wide spectrum detection of precarcinogens in short-term bioassays by simultaneous superinduction of multiple forms of cytochrome P450 isoenzymes.
The use of Aroclor 1254 to induce S9 liver fractions is a standard method for conducting short-term genotoxicity assays. An alternative induction procedure, using beta-naphthoflavone (beta-NF), as a safe (non-carcinogenic) substitute for polychlorinated biphenyls, combined with sodium phenobarbital (PB), was found to be equally effective. The aim of this work is to realize a novel schedule of induction for the preparation of metabolizing systems containing a wider spectrum of induced cytochrome P450s. Five inducers of different 'classes' such as PB (class IIB P450s), beta-NF (IA), isosafrol (IA2), ethanol (IIE1) and pregnenolone 16 alpha-carbonitrile (IIIA) were injected daily both separately (to achieve maximal monooxygenase induction) in male and female mice. Induction was monitored using specific P450-linked activities. In the optimal schedule for complete induction, the various monooxygenases were greater (2- to 4-fold) than those achieved by the classical schedule. More than a 14-fold increase of total P450 and 3.3-fold increase of NADPH-cytochrome (P450) c-reductase activity, over those uninduced, account for the above increase. For example, there was a marked increase in the deethylation of ethoxyresorufin (37-fold) compared to the uninduced mice that was considerably higher than classical induction (8-fold over uninduced). On the contrary, phase II reactions i.e. epoxide hydrolase, glutathione S-transferase, glutathione S-epoxide transferase and UDP-glucuronosyl transferase, examined to compare the phase I/phase II ratios in the traditional and proposed procedures, were increased to a lesser extent (2-fold over uninduced). No significant sex differences were seen. Five precarcinogens specifically metabolized by each of the induced P450s elicited a higher mutagenicity response in the presence of superinduced fractions with respect to the classical one, when tested on Salmonella typhimurium (cyclophosphamide, benzo[alpha]pyrene, 2-naphthylamine and dimethylnitrosamine) or Saccharomyces cerevisiae D7 strain (diethylstilbestrol). These novel metabolizing biosystems, with an enhanced spectrum of induced P450s and oxidative/post-oxidative reaction rates, are recommended for detecting unknown xenobiotics in genotoxicity studies.


Bone tumors of the foot: epidemiology and diagnosis.
The authors reviewed 260 cases of bone tumors localized in the foot and treated at the Tumor Center of the Rizzoli Orthopaedic Institute: 191 were benign and 58 malignant and 11 metastasis. There was predilection for the hindfoot (57%), followed by the forefoot (33%) (prevalently the metatarsals). Localizations in the midfoot were rare (10%). Osteoid osteoma was observed in 26% of all of the tumors of the foot and in 35% of the benign forms. Among malignant neoplasms Ewing's sarcoma (27.5%) was the most frequent. Conservative surgery, which was always carried out in benign tumors, was also performed in some of the malignant ones, having an early diagnosis and a correct preoperative study. The indications and the limits of the different imaging techniques available are reported (bone scan, arteriography, CAT, MRI), and the role of biopsy in the definitive diagnosis of these neoplasms in discussed.


Topical anti-inflammatory activity of human recombinant epidermal growth factor.
The topical anti-inflammatory activity of epidermal growth factor (EGF) was evaluated in inflammation models induced by 12-Otetradecanoylphorbol-13-acetate, croton oil and arachidonic acid. When EGF (1.5, 3 or 6 microg/ear) was coapplied with each inflammatory agent, there was a dose-related decrease in inflammation as assessed by ear punch weights, myeloperoxidase activity as well as by histopathological studies. The precise anti-inflammatory action of EGF is yet unclear, but we believe that interference with arachidonic acid metabolism may play an important role.


Measurement invariance of the people of Color Racial Identity Attitudes Scale with Asian Americans.
Racial identity has been linked to a number of important psychological outcomes, including perceptions of racism, self-esteem, and psychological well-being in Asian American populations. Although the People of Color Racial Identity Attitudes Scale (PRIAS; Helms, 1995) is the most widely used measure in Asian American racial identity research, numerous competing measurement models of the PRIAS have been identified in independent Asian American samples. Therefore, this study tested these competing PRIAS measurement models and also examined PRIAS measurement invariance across generational status, gender, and ethnicity using a combined sample of 1,946 Asian American college students and community adults. Study findings demonstrated the superiority of a 12-item 4-factor PRIAS measurement model that was consistent with Helms's original racial identity theory, suggesting that the PRIAS operates in an equivalent manner across generational status, gender, and ethnicity. Study limitations and future directions for research are discussed.


Long-term Effect of Losartan on Kidney Disease in American Indians With Type 2 Diabetes: A Follow-up Analysis of a Randomized Clinical Trial.
To determine whether early administration of losartan slows progression of diabetic kidney disease over an extended period. We conducted a 6-year clinical trial in 169 American Indians with type 2 diabetes and urine albumin/creatinine ratio <300 mg/g; 84 participants were randomly assigned to receive losartan and 85 to placebo. Primary outcome was a decline in glomerular filtration rate (GFR; iothalamate) to ≤60 mL/min or to half the baseline value in persons who entered with GFR <120 mL/min. At enrollment, GFR averaged 165 mL/min (interquartile range 49-313 mL/min). During the trial, nine persons reached the primary outcome with a hazard ratio (HR; losartan vs. placebo) of 0.50 (95% CI 0.12-1.99). Participants were then followed posttrial for up to 12 years, with treatment managed outside the study. The effect of losartan on the primary GFR outcome was then reanalyzed for the entire study period, including the clinical trial and posttrial follow-up. After completion of the clinical trial, treatment with renin-angiotensin system inhibitors was equivalent in both groups. During a median of 13.5 years following randomization, 29 participants originally assigned to losartan and 35 to placebo reached the primary GFR outcome with an HR of 0.72 (95% CI 0.44-1.18). Long-term risk of GFR decline was not significantly different between persons randomized to early treatment with losartan and those randomized to placebo. Accordingly, we found no evidence of an extended benefit of early losartan treatment on slowing GFR decline in persons with type 2 diabetes.


Late pregnancy and rat choriocarcinoma cells inhibit nocturnal prolactin surges and serotonin-induced prolactin release.
The purpose of the present study was to determine the effect of hormonal secretion by trophoblast cells on serotonin-induced release of PRL in both pregnant and nonpregnant rats. In the first experiment, three compounds that effectively lead to stimulation of serotonin receptors were injected ip or intraarterially between 0900-1200 h on day 8 or 16 of pregnancy. These included the serotonin precursor 5-hydroxytryptophan (20 mg/kg BW); a releasor of serotonin, fenfluramine (10 mg/kg BW); and a serotonin S2 receptor agonist, DOI (2,5-dimethoxy-4-iodophenyl-2-aminopropane-HCl; 500 micrograms/kg BW). When injected on day 8, these treatments significantly (P less than 0.01) increased the level of plasma PRL within 30 min after the injection. However, on day 16 the same treatments could not induce any change in the plasma PRL level. In the second experiment, rat choriocarcinoma (Rcho) cells, which secrete placental lactogen I in vivo, were injected beneath the kidney capsule on day 1 of pregnancy. Control pregnant rats injected with the cell culture medium RPMI-1640 containing 20% FBS continued to have a nocturnal PRL surges on days 7, 8, and 9, with the peak value of plasma PRL occurring at 0400 h. Rats injected with the cells had Rcho tumors at the site of injection when analyzed on day 9. These rats also had significantly (P less than 0.05) reduced nocturnal PRL surges on days 7 and 8 of pregnancy compared to the control animals, and on day 9, the PRL surge was completely blocked. In another group of day 9 pregnant rats containing Rcho tumors, DOI-induced PRL release was blocked by Rcho cells, whereas in controls, plasma PRL increased from 5 to 47 ng/ml. The final experiment tested whether the presence of Rcho cells affected serotonergic- or TRH (1 microgram/rat)-induced PRL release in cyclic rats that were ovariectomized 1 day before drug injection. Injection of Rcho cells 8 days earlier completely inhibited 5-hydroxytryptophan- or DOI-induced PRL release, but did not affect TRH-induced PRL release. These results indicate that the absence of PRL surges after midpregnancy may be due in part to the inability of serotonin to stimulate PRL at this time compared to early pregnancy. Secretion of placental lactogens or other PRL-like peptides from the placenta in the pregnant rat may be antagonistic to the normal stimuli that cause the PRL surges of early pregnancy, resulting in a loss of surges.


The value of systematic reviews as research activities in medical education.
Medical residents and postdoctoral fellows are often required to conduct and publish original research as part of their medical education. However, their relative lack of experience, time, money, and sometimes supervision in conducting original research often results in research of modest quality on topics of limited importance. Such research may also consume scarce resources from the sponsoring institution. Manuscripts describing such research are often unremarkable, although most are submitted for publication, where editors and peer reviewers will spend time evaluating them. Systematic reviews of the literature, however, offer similar training in the scientific method, are relatively inexpensive to conduct, teach critical appraisal of the literature, give trainees a thorough command of the topic studied, and provide even new investigators the opportunity to make important contributions to the literature. Systematic reviews of the literature should thus be acceptable alternatives to original research assignments for most trainees in medical education programs. The author reviews the characteristics of systematic reviews, outlines the steps in conducting them, identifies the lessons learned from completing each step, and compares the advantages and disadvantages of systematic reviews with those of conducting original research.


Female adnexal tumor of probable Wolffian origin.
Female adnexal tumor of probable Wolffian origin (FATWO) is a rare neoplasm arising from the remnants of the mesonephric duct. We report here a case of FATWO in a 70-year-old woman arising from the broad ligament and confirmed on immunohistochemistry. Most of these tumors behave in a benign fashion but certain histological features like hypercellularity, cellular pleomorphism and nuclear atypia as seen in the index case may increase the rate of recurrence and metastasis. Therefore, close follow-up is recommended for FATWO.


Short article: Management of ruptured hepatocellular carcinoma in a European tertiary care center.
Spontaneous rupture is a rare complication of hepatocellular carcinoma (HCC). Treatment options consist of transcatheter arterial embolization (TAE), hepatic resection, and conservative therapy. The best approach is under debate. This study presents a review of clinical data of patients with a ruptured HCC admitted to a European tertiary care center. Eleven patients were included; six (55%) had underlying cirrhosis. The majority of patients (73%) had no previous history of HCC. Spontaneous HCC rupture was diagnosed using abdominal computed tomography with or without a diagnostic paracentesis. Computed tomography showed one or two tumors in eight (73%) patients; the other patients had multiple tumors or diffuse infiltrative HCC. Seven (64%) patients were initially treated by TAE and one (9%) patient underwent hepatic resection. The remaining three (27%) patients, all of whom had liver cirrhosis, received conservative therapy. Two patients initially treated by TAE underwent a delayed resection and ultimately received systemic therapy. Overall, at the end of the follow-up period, three patients were still alive at 84, 991, and 1026 days after the initial presentation. Eight (73%) patients had died after a median of 88 days (range 7-417). One year after presentation, none of the conservatively treated patients was alive compared with three out of seven (43%) patients treated with TAE with or without delayed resection. Patients with a spontaneously ruptured HCC have a poor prognosis. In selected patients, however, prolonged survival is possible using TAE as initial therapy with or without a delayed resection and systemic therapy.


Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice.
Aging is an important risk factor for post-stroke infection, which accounts for a large proportion of stroke-associated mortality. Despite this, studies evaluating post-stroke infection rates in aged animal models are limited. In addition, few studies have assessed gut microbes as a potential source of infection following stroke. Therefore we investigated the effects of age and the role of bacterial translocation from the gut in post-stroke infection in young (8-12 weeks) and aged (18-20 months) C57Bl/6 male mice following transient middle cerebral artery occlusion (MCAO) or sham surgery. Gut permeability was examined and peripheral organs were assessed for the presence of gut-derived bacteria following stroke. Furthermore, sickness parameters and components of innate and adaptive immunity were examined. We found that while stroke induced gut permeability and bacterial translocation in both young and aged mice, only young mice were able to resolve infection. Bacterial species seeding peripheral organs also differed between young (Escherichia) and aged (Enterobacter) mice. Consequently, aged mice developed a septic response marked by persistent and exacerbated hypothermia, weight loss, and immune dysfunction compared to young mice following stroke.


Survival of poliovirus in New Zealand green-lipped mussels, Perna canaliculus, on refrigerated and frozen storage.
Poliovirus survival in live and frozen mussels during storage was assessed by both viral culture and molecular methods. Live New Zealand green-lipped mussels were incubated overnight at 20 degrees C in an aerated tank of filtered seawater seeded with the poliovirus 2 (PV2) vaccine strain. An extraction and concentration method that preserved viral infectivity was used to recover PV2 taken up by the mussels at day 0, at day 2 after storage at 4 degrees C, and at days 7, 14, and 28 after storage at -20 degrees C. This method allowed both culture and molecular analysis to be carried out. Presence of intact PV2 in each batch of mussels was determined by a pan-enterovirus specific reverse transcription-polymerase chain reaction (RT-PCR) and confirmed by dot-blot hybridization. Survival of infectious PV2 was determined by the monolayer plaque assay. After 48 h at 4 degrees C, infectious PV2 levels were 81% of the original level detected in the mussels. Infective virus levels then declined to 66, 53, and 44% after storage at -20 degrees C for 7, 14, and 28 days, respectively. Generic RT-PCR methods were 10 times more sensitive than cell culture techniques for virus detection but did not give information on virus infectivity. The survival of infectious pathogenic viruses in fresh and frozen mussels on storage constitutes a potential health risk and so is a major concern for public health authorities.


SARS-CoV-2/COVID-19 pandemic: first wave, impact, response and lessons learnt in a fully integrated Regional Blood and Tissue Bank. A narrative report.
The COVID-19 pandemic is placing blood and tissue establishments under unprecedented stress, putting its capacity to provide the adequate care needed at risk. Here we reflect on how our integrated organisational model has faced the first impact of the pandemic and describe what challenges, opportunities and lessons have emerged. The organisational model of the Catalan Blood and Tissue Bank (Banc de Sang i Teixits, BST) is described. The new scenario was managed by following international recommendations and considering the pandemic in a context of volatility, uncertainty, complexity, and ambiguity (VUCA), allowing rapid measures to be taken. These aimed to: ensure donor safety, promote proper responses to patients' needs, ensure the health and well-being of personnel, and prepare for future scenarios. The BST has adapted its activities to the changes in demand. No shortage of any product or service occurred. Donor acceptance, safety and wellbeing were maintained except for tissue donation, which almost completely stopped. To support the health system, several activities have been promoted: large-scale convalescent plasma (CP) production, clinical trials with CP and mesenchymal stromal cells, massive COVID-19 diagnoses, and participation in co-operative research and publications. Haemovigilance is running smoothly and no adverse effects have been detected among donors or patients. Several elements have proven to be critical when addressing the pandemic scenario: a) the early creation of a crisis committee in combination with technical recommendations and the recognition of a VUCA scenario; b) identification of the strategies described; c) the integrated donor-to-patient organisational model; d) active Research and Development (R&D); and e) the flexibility of the staff. It is essential to underline the importance of the need for centralised management, effective contingency strategies, and early collaboration with peers.


Cardiorespiratory coupling in young healthy subjects.
To quantify the presence of cardiorespiratory interaction in a group of 41 healthy subjects performing a subset of the Ewing test battery. We measure the empirical distribution of the cardiorespiratory coupling time (RI), defined as the time from inspiration onset to R peaks in the ECG. The study protocol is a subset of the Ewing test battery. The respiratory function was measured with a thoracic belt and heart rate was obtained from a two channel ECG measurement. Both series of fiducial points were determined using custom software. Additionally, we determine the presence of cardiorespiratory coupling (CRC) and cardiorespiratory interaction (CRI) using Shannon entropy, synchrograms and coordigrams. We observe that the RI distribution is asymmetric and nonuniform. These features are a manifestation of the causal relation between heart action and respiration. The preceding R peak strongly affects a position of inspiration onset. From the asymmetry of the RI distribution we conclude that this relation is stronger than the relation between inspiration onset and the following R peak. We use a suitable choice of surrogate data to prove that the result cannot be falsified. We observe a dual structure of the RI histograms, which may be related to the respiratory rhythmogenesis. We compare the sensitivity of RI histograms with other measures of CRI and CRC. In 46% of subjects, CRC appears in at least one stage of the examination, most often in resting states. In states of increased stress-orthostasis or physical (exercise)-the strength of coupling is visibly diminished. The nonuniform structure of the RI histogram is more sensitive to the presence of CRI than synchrograms or coordigrams are, as is well visible in the group averages. We also refer to the question of the most proper mathematical description of cardiorespiratory dynamics (phase domain or time domain). Finally, we formulate the hypothesis that the arterial blood pressure is a common driver of cardiac and respiratory rhythms. Analysis of the asymmetry of RI histograms is an interesting and sensitive method to study cardiorespiratory interaction and autonomic balance, in order to assess physical and mental health. The dual structure of the RI histograms which we have observed suggests the possible presence of a twofold mechanism for respiratory rhythmogenesis, as proposed by Galletly and Larsen.


Noninvasive diagnosis of hepatocellular carcinoma in cirrhotic liver: current guidelines and future prospects for radiological imaging.
Noninvasive imaging has become the standard for hepatocellular carcinoma (HCC) diagnosis in cirrhotic patients. Typical imaging features of HCC such as arterial wash-in and venous wash-out deliver very high specificity and acceptable sensitivity even in nodules from 1 to 2 cm in diameter. However, limitations apply specifically in hypovascular HCC, for which the addition of new techniques such as diffusion-weighted magnetic resonance imaging (DW-MRI) or hepatobiliary MRI is helpful. Whereas DW-MRI adds to both the sensitivity and specificity, hepatobiliary MRI additionally contributes valuable information in cirrhotic patients on the histopathology of small lesions, including early HCC and high-grade dysplastic nodules. Biopsy of small, atypical lesions is associated with a high rate of false-negative findings and should be used only after careful consideration in selected patients. Here, we review the current international guidelines on HCC diagnosis as well as the latest developments in imaging that may contribute to safe detection and accurate characterization of suspicious nodules in patients with liver cirrhosis.


Religious Social Identity as an Explanatory Factor for Associations between More Frequent Formal Religious Participation and Psychological Well-Being.
Guided by social identity theory, this study investigated having a closer identification as a member of one's religious group as an explanatory mechanism for linkages between more frequent formal religious participation and better subjective psychological well-being (more positive affect, less negative affect, and more life satisfaction). Multivariate regression models were estimated based on data from 3,032 participants, ages 25 to 74, in the 1995 National Survey of Midlife in the U.S. (MIDUS). Results provided support for the mediating effect of religious social identity on the associations between more frequent religious service attendance and all three dimensions of psychological well-being examined. Given the lack of previous empirical attention to social identity within the literature on religiosity and mental health, these findings contribute to our understanding of self, religion, and health, while also pointing to the importance of continuing to draw on well developed social psychological theory in investigations of linkages between religion and health.


Hyperphosphatasia with mental retardation syndrome type 4 in three unrelated South African patients.
Hyperphosphatasia with mental retardation syndrome (HPMRS) is a rare autosomal recessive disorder caused by pathogenic variants in genes involved in glycosylphosphatidylinositol metabolism that result in a similar phenotype. We describe the first three patients with HPMRS from sub-Saharan Africa. Detection was assisted by Face2Gene phenotype matching and confirmed by the presence of elevated serum alkaline phosphatase. All three patients had severe intellectual disability, absent speech, hypotonia and palatal abnormality (cleft palate in two, very high-arched palate in one), no or minimal brachytelephalangy, and high serum alkaline phosphatase levels. Additional findings included seizures in two, and brain imaging abnormalities in two. In all three patients HPMRS was a top-20 gestalt match using Face2Gene. The overall phenotype is consistent with descriptions in the literature of HPMRS type 4, although not specific to it. Whole exome sequencing in the index patient and his mother detected a candidate variant in a homozygous state in the index patient (PGAP3:c.557G>C, p.Arg186Thr) and heterozygous in the mother. Further variant interpretation indicated pathogenicity. Sanger sequencing of another two patients identified the same homozygous, pathogenic variant, confirming a diagnosis of HPMRS type 4. The shared homozygous variant in apparently unrelated families, and in the absence of consanguinity, suggests the possibility of genetic drift due to a population bottleneck effect, and further research is recommended.


Identification of chemosensitivity nodes for vinblastine through small interfering RNA high-throughput screens.
Discovering chemosensitivity pathways or nodes is an attractive strategy for formulating new drug combinations for cancer. Microtubules are among the most successful anticancer drug targets. Therefore, we implemented a small interfering RNA (siRNA) synthetic lethal screen targeting 5520 unique druggable genes to identify novel chemosensitivity nodes for vinblastine, a microtubule-destabilizing agent used clinically. We transiently transfected human glioblastoma cells with siRNAs for 48 h and then treated cells with a sublethal concentration of vinblastine. Forty-eight hours later, we analyzed cell viability and, using a series of statistical methods, identified 65 gene products that, when suppressed, sensitized glioblastoma cells to vinblastine. After completion of the secondary assays, we focused on one siRNA, B-cell lymphoma extra large (BCL-xL), because of its role in the intrinsic apoptosis signaling pathway as well as the availability of pharmacological inhibitors. We found that nontoxic concentrations of 4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide (ABT-263), an inhibitor of the BCL-2 family members (BCL-2, BCL-xL, and BCL-w), sensitized glioblastoma and non-small-cell lung cancer cells to vinblastine and induced apoptosis through the intrinsic cell death pathway. These results illustrate the usefulness of unbiased siRNA screens as a method for identifying potential novel anticancer therapeutic combinations.


H. pylori infection in non-ulcer patients--to treat or not to treat. The case against treatment.
Heretofore regarded as a strict pathogen, recent identification of multiple mutants of H. pylori, varying in pathogenicity, genomic composition, antigenic structure and other characteristics, has led to speculation that not all strains of the organism merit elimination. Affecting half the world's population, H. pylori appears to cause clinically significant disease in <20% of cases. The costs of eradicating harmless infection in over 2 billion people are prohibitive, particularly in countries lacking resources, and are questionable even in advanced countries where infection, gastritis and related diseases are declining as social conditions improve. Major controversies surround empiric eradication of helicobacter infection in patients with asymptomatic gastritis or non-specific dyspepsia. Apart from cost, and feasibility, there are concerns that widespread campaigns to eradicate H. pylori might cause major increases in esophageal reflux disease and esophageal adenocarcinoma, while causing some serious iatrogenic illness and increasing antibiotic resistance, with uncertain consequences to affected populations.


High expression of MAGE-C1 gene in colorectal cancer is associated with its poor prognosis.
The aim of this study was to explore the relationship between melanoma antigen gene C1 (MAGE-C1) expression and the prognosis for colorectal cancer (CRC), and to establish a mathematical model to comprehensively evaluate the prognosis of patients with CRC. MAGE-C1 was selected by bioinformatics for its greater expression differences in CRC patients. Immunohistochemistry (IHC) was used to detect the expression level of MAGE-C1 in tissue samples of 156 patients with CRC. Kaplan-Meier analysis was employed to assess the relationship between MAGE-C1 and the prognosis of patients with CRC. Univariate and multivariate Cox regression models analyzed the factors affecting the prognosis of CRC patients. Also, the clinicopathological characteristics of patients and genes with clinical concern were integrated to establish a model to comprehensively predict the prognosis of patients with CRC. MAGE-C1 was found to be highly expressed in 28.8% of CRC patients. MAGE-C1 expression was associated with tumor size, number, and metastasis. Survival analysis showed that CRC patients with high expression of MAGE-C1 had a poor prognosis. Regression analysis demonstrated that MAGE-C1 protein status, T stage, differentiation, Kirsten rat sarcoma (KRAS) status, and v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) status were the independent factors influencing the overall survival of patients with CRC. Meanwhile, MAGE-C1 combined with clinicopathological characteristics and hotspot gene mutations could be used to evaluate the prognosis of CRC. Our study shows that MAGE-C1 is differentially expressed in patients with CRC and affects the prognosis of patients. The combination of MAGE-C1, clinicopathological characteristics, and genes with clinical concern can be used to assess the prognosis of CRC.


WHO in the 1970s and 1980s--a user's view.
The author reflects on 24 years of involvement in WHO activities, and their effect on her own life and on the maternal and child health services in Malaysia.


Brachymetacarpia and brachymetatarsia: do we need to operate?
Brachymetacarpia and brachymetatarsia are rare congenital presentations denoted by shortening of metacarpals and metatarsals respectively, in which the deformity usually presents around childhood/early adolescence.The aetiology is usually congenital besides several other syndromic or endocrinologic associations.Cosmetic issues such as absence of a normal-looking knuckle while making a fist or disruption of finger-tip curvature besides functional issues are the main indications for surgical intervention in brachymetacarpia.In the foot, apart from cosmetic issues, pain due to transfer metatarsalgia as well as callosities along with toe deformities which lead to difficulty of using footwear are the main indications for intervention.Lengthening of the affected bone, either acute with grafting or gradual, is the mainstay of treatment. Gradual lengthening can be either single-stage as in callotasis, or two-stage where the primary procedure is followed by bone grafting after the length has been achieved.Adolescence, specifically between 12 and 15 years, is the preferred period for surgical intervention in these cases. Cite this article: EFORT Open Rev 2021;6:15-23. DOI: 10.1302/2058-5241.6.200087.


[Hormonal treatment of carcinoma of the prostate].
Efficacy of orchiectomy and intravenous administration of diethylstilbestrol diphosphate (DESP) for the treatment of prostatic carcinoma was evaluated on 184 patients treated between 1975 to 1989. The patients were between 49 to 88 years old with a mean age of 73.4 +/- 8.3 years. Clinical stage was A in 9.8%, B in 12%, C in 26.6% and D in 51.6%. The histologically well, moderately and poorly differentiated adenocarcinoma were observed in 20.9, 29.4 and 49.7%, respectively. The 5-year survival rate of stage A, B, C and D calculated with the Kaplan-Meier method were 90, 49, 60 and 34%, respectively. The 5- and 10-year survival rate of the patients who had received orchiectomy was 53 and 24%, respectively, while that of the patients without orchiectomy was 38 and 14%, respectively. The 5 and 7-year survival rate of the patients treated with intravenous administration of DESP was 54 and 34%, respectively while that of the patients without DESP was 46 and 31%, respectively. These findings suggest that orchiectomy and intravenous administration of DESP in any form prolonged patient survival compared with only oral administration of estrogens or antiandrogens. Reactivation was seen in 24 (40%) of the 60 patients under sufficient observation. Clinical relapse occurred within an average of 32.3 +/- 26.4 months after primary hormonal manipulation. The average time to relapse in stage D was shorter than that in stage B and C. Reactivation was observed in the patients on interrupted treatment earlier than in the patients on continuous administration of drugs. Cardiovascular death followed by endocrine therapy was 7.4% in this study.


Melioidosis of the central nervous system; impact of the bimABm allele on patient presentation and outcome.
The autotransporter protein Burkholderia intracellular motility A (BimA) facilitates the entry of Burkholderia pseudomallei into the central nervous system (CNS) in mouse models of melioidosis. Its role in the pathogenesis of human cases of CNS melioidosis is incompletely defined. Consecutive culture-confirmed cases of melioidosis at two sites in tropical Australia after 1989 were reviewed. Demographic, clinical and radiological data of the patients with CNS melioidosis were recorded. The bimA allele (bimABm or bimABp) of the B. pseudomallei isolated from each patient was determined. Of the 1587 cases diagnosed at the two sites during the study period, 52 (3.3%) had confirmed CNS melioidosis; 20 (38.5%) had a brain abscess, 18 (34.6%) had encephalomyelitis, 4 (7.7%) had isolated meningitis and 10 (19.2%) had extra-meningeal disease. Among the 52 patients, there were 8 (15.4%) deaths; 17/44 (38.6%) survivors had residual disability. The bimA allele was characterized in 47/52; 17/47 (36.2%) had the bimABm allele and 30 (63.8%) had the bimABp allele. Patients with a bimABm variant were more likely to have a predominantly neurological presentation (odds ratio (OR) (95% confidence interval (CI)): 5.60 (1.52-20.61), p=0.01), to have brainstem involvement (OR (95%CI): 7.33 (1.92-27.95), p=0.004) and to have encephalomyelitis (OR (95%CI): 4.69 (1.30-16.95), p=0.02. Patients with a bimABm variant were more likely to die or have residual disability (odds ratio (95%CI): 4.88 (1.28-18.57), p=0.01). The bimA allele of B. pseudomallei has a significant impact on the clinical presentation and outcome of patients with CNS melioidosis.


Arbuscular mycorrhizal fungi improve uptake and control efficacy of carbosulfan on Spodoptera frugiperda in maize plants.
Inoculation of arbuscular mycorrhizal (AM) fungi in soil can promote the uptake of nutrients and xenobiotics by plants. In this study, the effects of arbuscular mycorrhizal fungi (including Glomus intraradices and Glomus mossea) on the growth of maize, the uptake of carbosulfan and the control efficacy on Spodoptera frugiperda were investigated through maize seed coating. Results from the pot experiment showed that carbofuran reduced the mycorrhizal colonization of AM fungi in the early stage of the experiment. The inhibiting effect disappeared in 21-49 DAP, whereas the mycorrhizal colonization rate under the G. intraradices treatment was maintained at ≈90%. Compared with noninoculated treatment, the fresh weights of roots in G. intraradices and G. mosseae treatments increased by 20-41% and 10-23%, respectively. Mycorrhizal treatment could significantly increase the transmission rates (root/soil and leaf/stem) and the carbosulfan accumulation in maize. During the harvest period, the control efficacy against S. frugiperda in mycorrhizal treatment was significantly higher than that in noninoculated treatments (P < 0.05) in both Guangzhou and Nanning. Inoculation with AM could accelerate the degradation process of carbofuran in soil and the propagation of carbofuran from soil to plants. Glomus intraradices showed more pronounced effects than G. mosseae on both plant growth and carbosulfan content in plants and soil. The experimental results showed that inoculation of AM fungi increased the accumulation of carbofuran in plants, improved the effective utilization rate and enhanced the control efficacy against S. frugiperda. © 2021 Society of Chemical Industry.


The Forward Testing Effect is Reliable and Independent of Learners' Working Memory Capacity.
The forward testing effect refers to the finding that retrieval practice of previously studied information enhances learning and retention of subsequently studied other information. While most of the previous research on the forward testing effect examined group differences, the present study took an individual differences approach to investigate this effect. Experiment 1 examined whether the forward effect has test-retest reliability between two experimental sessions. Experiment 2 investigated whether the effect is related to participants' working memory capacity. In both experiments (and each session of Experiment 1), participants studied three lists of items in anticipation of a final cumulative recall test. In the testing condition, participants were tested immediately on lists 1 and 2, whereas in the restudy condition, they restudied lists 1 and 2. In both conditions, participants were tested immediately on list 3. On the group level, the results of both experiments demonstrated a forward testing effect, with interim testing of lists 1 and 2 enhancing immediate recall of list 3. On the individual level, the results of Experiment 1 showed that the forward effect on list 3 recall has moderate test-retest reliability between two experimental sessions. In addition, the results of Experiment 2 showed that the forward effect on list 3 recall does not depend on participants' working memory capacity. These findings suggest that the forward testing effect is reliable at the individual level and affects learners at a wide range of working memory capacities alike. The theoretical and practical implications of the findings are discussed.


Microfluidic electrocapture-assisted mass spectrometry of membrane-associated polypeptides.
To isolate membrane-associated proteins, which play diverse structural, catalytic, and regulatory roles in cells, they are often initially solubilized in detergents. Although detergents are essential for purifying membrane proteins, they tend to interfere strongly with subsequent analyses. A microfluidic method is presented here that surmounts this problem, allowing well-resolved mass spectra of test membrane-associated polypeptides, and their complexes with ions and detergents, to be acquired. As a front-end module it allows access to other advanced mass spectrometric strategies to be utilized toward defining biomolecular interactions. This opens up a new avenue for studying complexation and analysis of membrane proteins of general importance.


Analysis of monoclonal antibodies to prostate-specific antigen: reactivity with native and recombinant prostate-specific antigen.
Epitope mapping analysis was performed on 53 antibodies submitted to the ISOBM TD-3 PSA Workshop. Western blotting and N-terminal amino acid sequencing, using both native and recombinant human prostate-specific antigen (rPSA), identified four different epitope groups for native PSA. Under reducing conditions native PSA was not recognized by 18/53 antibodies suggesting they reacted with conformation-dependent epitopes. Nine other antibodies reacted with a rPSA polypeptide doublet of 34-35 kD corresponding to different rPSA glycoforms. From sequence mapping studies 22/53 antibodies bound epitopes within amino acid residues 25-85, 3/53 antibodies bound to epitopes within residues 86-220, while 10/53 antibodies bound epitopes within residues 221-261. These results indicate that there are multiple immunogenic epitopes localized on the PSA molecule.


[Psychosomatic relationships in patients with primary fibromyalgia syndrome].
This clinical and psychological study involved 100 patients aged 24-51 years with primary fibromyalgia syndrome (PFS). The patents exhibited clinical manifestations of neurotic disorders, low level of subjective control, dysadaptive attitude toward the disease, and an intense spectrum of protective psychological mechanisms. The main clinical manifestations of PFS correlated with psychological status of the patients. It is concluded that objective evaluation of clinical conditions of PFS patients requires integrated psychosomatic assessment of their health status.


Client characteristics associated with not keeping appointments for public health nursing home visits.
Home visits have been identified as an intervention strategy for high-risk pregnant women. A necessary component of this intervention strategy is for the women to be home for the visit with the nurse. The purpose of this study was to identify factors associated with women not keeping their home visit appointments with a public health nurse. Subjects were 232 low-income high-risk pregnant women who received at least one home visit by a public health nurse. Younger age, more stressful life events, receipt of medical assistance, inadequacy of prenatal care, noncompliance with health recommendations, and longer gestational time were associated with not keeping public health nursing appointments. While this study provides some insight into the factors associated with women not keeping their appointments with the public health nurse, further investigation is warranted to identify strategies to reduce the incidence of not-kept appointments.


Upstream elements of the MHC class II E beta gene active in B cells.
The MHC class II (Ia) molecules are heterodimeric cell surface glycoproteins that have a limited tissue distribution and are essential for an Ir. These proteins are known to both display a limited tissue distribution and be responsive to up-regulation by cytokines such as IL-4. To begin to identify the molecular basis for both of these phenomena in B cells, we performed a deletional analysis of the upstream region of the murine E beta gene. We show that there are several cooperating positive as well as negative control elements in the E beta upstream region. The sequence between -2679 and -66 is a strong transcriptional element containing several sequences that act synergistically as positive elements. The negative elements are located more proximal to the transcription start site. Furthermore, two consensus motifs, termed X and Y, which are located in the proximal upstream region of all class II genes, are necessary for the transcriptional activity of more distal elements. Additionally, we identify an IL-4-responsive element located within 666 bp upstream of the transcription initiation site.


Design of Ru(II) Complexes Based on Anthraimidazoledione-Functionalized Terpyridine Ligand for Improvement of Room-Temperature Luminescence Characteristics and Recognition of Selective Anions: Experimental and DFT/TD-DFT Study.
In this work we report synthesis and characterization of three rigid and linear rodlike monometallic Ru(II) complexes based on a terpyridine ligand tightly connected to 9,10-anthraquinone electron-acceptor unit through phenyl-imidazole spacer. The motivation of designing these complexes is to enhance their excited-state lifetimes at room temperature. Interestingly it is found that all three complexes exhibit luminescence at room temperature with excited-state lifetimes in the range of 1.6-52.8 ns, depending upon the coligand as well as the solvent. Temperature-dependent luminescence investigations indicate that the energy gap between the emitting 3MLCT state and nonemitting metal-centered state 3MC in the complexes increased enormously compared with parent [Ru(tpy)2]2+. In addition, by taking advantage of the imidazole NH proton(s), which became appreciably acidic upon combined effect of electron accepting anthraquinone moiety as well as metal ion coordination, we also examined anion recognition and sensing behaviors of the complexes in organic, mixed aqueous-organic as well as in solid medium through different optical channels such as absorption, steady-state and time-resolved emission, and 1H NMR spectroscopic techniques. In conjunction with the experiment, computational investigation was also employed to examine the electronic structures of the complexes and accurate assignment of experimentally observed spectral and redox behaviors.


Examination of inertial cavitation of Optison in producing sonoporation of chinese hamster ovary cells.
The objective of this project was to elucidate the relationship between ultrasound contrast agents (UCAs) and sonoporation. Sonoporation is an ultrasound-induced, transient cell membrane permeability change that allows for the uptake of normally impermeable macromolecules. Specifically, this study will determine the role that inertial cavitation plays in eliciting sonoporation. The inertial cavitation thresholds of the UCA, Optison, are compared directly with the results of sonoporation to determine the involvement of inertial cavitation in sonoporation. Chinese hamster ovary (CHO) cells were exposed as a monolayer in a solution of Optison, 500,000 Da fluorescein isothiocyanate-dextran (FITC-dextran), and phosphate-buffered saline (PBS) to 30 s of pulsed ultrasound at 3.15-MHz center frequency, 5-cycle pulse duration and 10-Hz pulse repetition frequency. The peak rarefactional pressure (P(r)) was varied over a range from 120 kPa-3.5 MPa, and five independent replicates were performed at each pressure. As the P(r) was increased, from 120 kPa-3.5 MPa, the fraction of sonoporated cells among the total viable population increased from 0.63-10.21%, with the maximum occurring at 2.4 MPa. The inertial cavitation threshold for Optison at these exposure conditions has previously been shown to be in the range 0.77-0.83 MPa, at which sonoporation activity was found to be 50% of its maximum level. Furthermore, significant sonoporation activity was observed at pressure levels below the threshold for inertial cavitation of Optison. Above 2.4 MPa, a significant drop in sonoporation activity occurred, corresponding to pressures where >95% of the Optison was collapsing. These results demonstrate that sonoporation is not directly a result of inertial cavitation of the UCA, rather that the effect is related to linear and/or nonlinear oscillation of the UCA occurring at pressure levels below the inertial cavitation threshold.


Distant metastases from sinonasal cancer.
Distant metastases from sinonasal malignancy are generally a rare event except in the terminal stages of the diseases and many patients die from recurrence before the secondaries become clinically manifest. Sinonasal neoplasia covers a diverse range of pathologies, some of which have a greater tendency to spread than others, in particular adenoid cystic carcinoma, malignant melanoma and some of the sarcomas. Notwithstanding this, the frequency with which systemic metastases occurs is such that screening at presentation could not be regarded as cost-effective and is consequently only instituted in the presence of specific symptoms.


Activation of CD16+ effector cells by rheumatoid factor complex. Role of natural killer cells in rheumatoid arthritis.
The role of natural killer (NK) cells in rheumatoid arthritis (RA) remains unclear. A pathogenetic function of rheumatoid factors (RF) also has not been defined. In the present studies, natural killer (NK) cells were examined as a model for FC gamma receptor type III-positive (FC gamma RIII+) cells, with regard to their interaction with RF. NK cell antigen CD16 (FC gamma RIII) and CD56 expression and functional NK and antibody-dependent cell-mediated cytotoxicity (ADCC) activity were compared in peripheral blood lymphocytes and autologous synovial fluid lymphocytes (SFL) of RA patients. Peripheral blood lymphocytes and SFL showed normal CD56 expression. In contrast, both the frequency and the density of CD16 antigen were decreased in SFL. Furthermore, diminished NK cytotoxicity and a significant decrease in ADCC were observed in SF NK cells. In subsequent in vitro studies with normal fresh NK cells, it was demonstrated that IgG-containing RF complexes from RA patients induced a modulation of FC gamma RIII structure from the NK cell surface, a decrease in NK activity, and a complete loss of ADCC. When purified RF was incubated with NK-enriched cell lines from RA patients, increased transcription and subsequent production of interferon-gamma and tumor necrosis factor alpha were observed. These data suggest a direct involvement of RF complexes in the pathogenetic process of chronic inflammation in RA.


Characterization of the porcine homologue to human platelet glycoprotein IIb-IIIa (CD41/CD61) by a monoclonal antibody.
Human gpIIb-IIIa or CD41/CD61 is a Ca(2+)-complex dependent heterodimer, abundant on platelets, that plays a key role in hemostasis. This report describes a murine monoclonal antibody, JM2E5, able to recognize and immunoprecipitate the gpIIb/IIIa surface glycoprotein from porcine platelets. Immunoprecipitation analysis showed an antigen molecular weight of 115 and 85 kDa under nonreducing conditions, and of 110, 100 and 25 kDa under reducing conditions. Immunohistochemistry analyses of frozen sections from several porcine lymphoid organs gave specific staining on platelets. EDTA treated platelets were studied by flow cytometry indicating that the epitope recognized was Ca(2+)-complex independent. Western-blotting experiments with porcine platelet extracts gave an antigen molecular weight of 85 kDa under nonreducing conditions, thus localizing the epitope recognized by JM2E5 on the complex light chain gpIIIa or CD61. JM2E5 was also cross-reacting with human, bovine and horse platelets, as shown by flow cytometry. This mAb would allow further studies on this important adhesion molecule on horses, ruminants and pigs, and it should be especially useful as a general anti-porcine platelet reagent.


Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis.
Rat liver perisinusoidal lipocytes (PL) cultured on uncoated plastic transform spontaneously within 6-10 d to myofibroblastlike cells (MFBlC). Parallel to the transformation the TGF alpha- and TGF beta 1-mRNA expression increased and was highest in MFBlC. Competitive radioligand binding assays demonstrated that in contrast to untransformed PL the MFBlC synthesize and secrete transforming growth factor (TGF)-alpha (15 fmol/cell per 24 h) and predominantly the latent form of TGF beta 1 (0.2 fmol/cell per 24 h). Medium conditioned by MFBlC (MFBcM) significantly stimulated PL proliferation with little effect on PL proteoglycan synthesis. By transient acidification of the MFBcM, known to activate the latent form of TGF beta 1, the stimulatory effect on PL proteoglycan synthesis was enhanced and furthermore PL transformation (measured by expression of iso-alpha smooth muscle actin and loss of retinylpalmitate) was accelerated. Preincubation of this medium with neutralizing antibodies to TGF beta resulted in (a) the growth inhibitory effect was converted to a growth stimulation and (b) the stimulatory effect on proteoglycan synthesis was abolished. In summary our data indicate that progressive activation of PL on plastic (transformation to MFBlC) leads to an enhanced expression of the TGF alpha- and TGF beta 1-mRNAs and secretion of the corresponding proteins. Medium conditioned by MFBIC stimulates proliferation, transformation, and PG synthesis of untransformed PL. These mechanisms are suggested to be relevant in self perpetuation of liver fibrogenesis.


Autoimmune Encephalitis in Postpartum Psychosis.
Significant immunological alterations have been observed in women with first-onset affective psychosis during the postpartum period. Recent studies have highlighted the possibility that a subset of patients with first-onset severe psychiatric episodes might suffer from undiagnosed autoimmune encephalitis. Therefore, the authors performed a three-step immunohistochemistry-based screening for CNS autoantibodies in a large cohort of patients with postpartum psychosis and matched postpartum comparison subjects. Ninety-six consecutive patients with postpartum psychosis and 64 healthy postpartum women were included. Screening for antibodies in patient serum was performed using immunohistochemistry. Samples showing any staining were further examined by immunocytochemistry using live hippocampal neurons and cell-based assays to test for anti-N-methyl-d-aspartate (NMDA) receptor antibodies. Cell-based assays for all other known CNS antigens were performed in those samples with immunocytochemistry labeling but negative for NMDA receptor antibodies. Four patients (4%) with neuropil labeling suggestive for extracellular antigen reactivity were identified. Serum samples from all four patients showed clear extracellular labeling of live hippocampal neurons. Two women had the specific staining pattern characteristic for anti-NMDA receptor antibody positivity, which was confirmed by cell-based assays. Neither patient with anti-NMDA receptor antibody positivity had evidence of an ovarian teratoma. The other two patients tested negative by cell-based assays for all known CNS antigens. None of the matched postpartum comparison subjects had confirmed neuronal surface antibodies. The two patients with anti-NMDA receptor antibodies both showed extrapyramidal symptoms following initiation of treatment with low-dose haloperidol. In patients with acute psychosis during the postpartum period, systematic screening for anti-NMDA receptor autoantibodies should be considered. The acute onset of severe atypical psychiatric symptoms in young female patients should raise the index of suspicion for anti-NMDA receptor encephalitis, particularly in the setting of neurological symptoms, including extrapyramidal side effects of antipsychotic treatment.


Case control and historical cohort study of diarrhea associated with administration of trimethoprim-potentiated sulphonamides to horses and ponies.
Trimethoprim-potentiated sulphonamides (TPS) are among the most frequently administered antimicrobials in equine medicine. Anecdotally, TPS has been implicated as a cause of mild to moderate diarrhea in horses. The purpose of this study was to document the prevalence of diarrhea in horses receiving TPS, to characterize the severity of the diarrhea, and to identify any other factors associated with the development of diarrhea. A 2-part study was designed to identify the prevalence of diarrhea associated with TPS in our clinic population. Part I was a case-control retrospective study of 135 records over a 10.5-year period from January 1, 1980 through June 30, 1990. Part II was a historical cohort study of 784 records over a 37-month period from July 1, 1990 through July 31, 1993. There was no significant difference in the occurrence of diarrhea associated with TPS therapy in either study. The occurrence of diarrhea was 21% and 3% in parts I and II, respectively. Significant factors identified in association with diarrhea in part I were duration of hospital stay, and antibiotic therapy other than TPS or penicillin. Significant factors identified in part II included other antibiotic therapy, penicillin therapy, and combined penicillin and TPS therapy. Diarrhea does occur after the administration of antibiotics, most likely because of the alteration of the patient's normal intestinal flora. Diarrhea was noted in association with administration of TPS in this study; however, its prevalence was not significantly different than that in horses receiving other antibiotics, such as penicillin and its derivatives.


Effects of argon atoms on the self-absorption and the intensity of hg 2537-a radiation in hg + ar discharges.
A study was made of the feasibility of increasing the efficiency of fluorescent lamps at high powers by increasing the Hg 2537-A resonance radiation through a reduction of self-absorption. Specifically, we attempted to reduce the Hg 2537-A self-absorption by introducing a higher pressure of a foreign gas (argon) to alter the Hg 2537-A absorption line shape and width by collision broadening. The intensity of the Hg 2537-A line in Hg + Ar discharges was measured as an independent function of mercury pressure (0.7 mTorr to 27 mTorr), argon pressure (5 Torr to 400 Torr), and dc input power (5.5 W to 97 W). A detailed theoretical analysis indicates that there are four ways that additional argon reduces the Hg 2537-A self-absorption: (1) The Hg 2537-A line gets broader simply because the additional argon atoms increase the Hg-Ar collision frequency; (2) adding argon causes the gas temperature to rise and this drives the Hg-Ar collision frequency still higher; (3) the rise in gas temperature also causes an increase in the Hg 2537-A doppler width; (4) the additional argon changes the Hg 2537-A line shape from doppler dominated to a collision dominated profile. The experiments demonstrate, however, that no gain is achieved in the Hg 2537-A intensity with the addition of extra argon in spite of the beneficial effect on the self-absorption escape rate. This advantage is apparently offset by the argon's reduction of the electron energy which leads to fewer mercury atoms excited to the Hg 6(3)P(1) state.


A novel transforming growth factor-beta receptor-interacting protein that is also a light chain of the motor protein dynein.
The phosphorylated, activated cytoplasmic domains of the transforming growth factor-beta (TGFbeta) receptors were used as probes to screen an expression library that was prepared from a highly TGFbeta-responsive intestinal epithelial cell line. One of the TGFbeta receptor-interacting proteins isolated was identified to be the mammalian homologue of the LC7 family (mLC7) of dynein light chains (DLCs). This 11-kDa cytoplasmic protein interacts with the TGFbeta receptor complex intracellularly and is phosphorylated on serine residues after ligand-receptor engagement. Forced expression of mLC7-1 induces specific TGFbeta responses, including an activation of Jun N-terminal kinase (JNK), a phosphorylation of c-Jun, and an inhibition of cell growth. Furthermore, TGFbeta induces the recruitment of mLC7-1 to the intermediate chain of dynein. A kinase-deficient form of TGFbeta RII prevents both mLC7-1 phosphorylation and interaction with the dynein intermediate chain (DIC). This is the first demonstration of a link between cytoplasmic dynein and a natural growth inhibitory cytokine. Furthermore, our results suggest that TGFbeta pathway components may use a motor protein light chain as a receptor for the recruitment and transport of specific cargo along microtublules.


Study of the mechanism of MF1 ATPase inhibition by fluorosulfonylbenzoyl inosine, quinacrine mustard, and efrapeptin using intermediate 18O exchange as a probe.
The mitochondrial F1-ATPase (MF1) is known to be largely or totally inhibited by combination or reaction with one fluorosulfonylbenzoyl inosine (FSBI), quinacrine mustard, or efrapeptin per enzyme. Measurements were made with 18O in attempt to ascertain if the weak catalytic activity remaining after exposure to excess of these reagents was due to retention of some activity by the enzyme modified by these inhibitors. Any such activity could have different characteristics that might be revealed by the distribution of [18O]Pi isotopomers formed from [gamma-18O]ATP. The MF1 inhibited by FSBI showed progressive appearance of two new catalytic pathways as inhibition proceeded. Both pathways appeared to be operative in the enzyme after one beta subunit per enzyme had been modified by FSBI. A high exchange pathway showed no detectable change as ATP concentration was lowered. The lower exchange pathway showed an increase in the amount of exchange with lowering of the ATP concentration, similar to the cooperative behavior observed with the unmodified enzyme. With excess ATP more product was formed by the low exchange pathway, showing that compulsory alternation between two catalytic sites was not retained. The behavior can be explained by the ability of the modified beta subunit to undergo binding changes similar to those occurring in catalysis, with the other two beta subunits catalyzing sluggish hydrolysis by different pathways because of the asymmetry introduced by the modification. Inhibition by quinacrine mustard also resulted in the appearance of two new pathways, somewhat similar to those from FSBI inhibition. In contrast, activity remaining with excess efrapeptin present showed only one pathway like that of the native enzyme. This can be attributed to a low equilibrium concentration of free enzyme and total inhibition of MF1 combined with efrapeptin.


PD-L1 immunohistochemistry comparison of 22C3 and 28-8 assays for gastric cancer.
Nivolumab and pembrolizumab are promising therapies for gastric adenocarcinoma. The 22C3 and 28-8 pharmDx immunohistochemistry assays for programmed death ligand-1 scoring criteria have been developed. This study compared the programmed death ligand-1 staining patterns of gastric adenocarcinoma evaluated by the 22C3 and 28-8 pharmDx assays. Tissue microarray analysis was performed for 226 patients with gastric adenocarcinoma who underwent curative surgery. Interobserver concordance between the 22C3 and 28-8 pharmDx assays was assessed to compare the dichotomized expression values. Programmed death ligand-1 positivity was assessed by combined positive score and tumor proportion score. Immunohistochemistry for deficient mismatch repair proteins and Epstein-Barr virus-encoded RNA in situ hybridization was examined. Programmed death ligand-1 positivity with a combined positive score ≥5 was detected in 63 patients (28%) by the 22C3 pharmDx assay, and in 45 patients (20%) by the 28-8 pharmDx assay. A pairwise comparison of the 22C3 and 28-8 pharmDx assays showed 87% of pairs were concordant and 11% higher expressions for the 22C3 pharmDx assay, with strong concordance (kappa score =0.881 with a combined positive score cutoff of 5). The programmed death ligand-1 positivity rate (range, 3-5%) of the tumor proportion score was markedly lower than that of the combined positive score in the two assays. Programmed death ligand-1 positivity of the combined positive score in these two assays was associated with mismatch repair proteins and Epstein-Barr virus status. There was no significant difference in the overall survival between programmed death ligand-1, mismatch repair proteins, and Epstein-Barr virus status. The study findings suggest the potential interchangeability of the 22C3 and 28-8 pharmDx assays to determine programmed death ligand-1 expression levels in gastric adenocarcinoma patients.


[KCNQ1 mutation in patients with lone atrial fibrillation].
Recent studies suggest that mutation of the slow delayed rectifier potassium channel [I(Ks)] contributes to familial atrial fibrillation (FAF). In the current study, we explored the potential association between KCNQ1 polymorphism with lone AF (LAF). Clinical data and blood samples were collected from 95 Han Chinese patients with LAF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified four known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 95 LAF patients and 190 healthy controls. Three new variations were identified in KCNQ1 from 95 sporadic LAF including 1 in 5'UTR(c.-22T > C), 1 in exon9 synonymous mutation (c.1008C > T) and 1 in intron region (c.1590 + 31A > T). These variations were heterozygous and not presented in 190 healthy controls. Highly significant difference was detected between LAF group and control groups in rs760419 polymorphism. Logistic regression revealed that rs760419 was independent risk factor for LAF(OR = 2.056, P = 0.001). KCNQ1 mutation is associated with LAF and rs760419 polymorphism is a susceptible marker for LAF.


State of the Art in Hepatic Dysfunction in Pregnancy.
Hepatic dysfunction in pregnant women is always challenging for the obstetrician, as the spectrum of hepatic abnormalities can be very large and have various implications, both for mother and fetus. There is a diagnostic and therapeutic polymorphism of hepatic dysfunction in pregnancy and insufficient knowledge related to the etiopathogenesis and epidemiology of this disease. The clinical forms of hepatic dysfunction encountered in pregnancy can vary from liver diseases related to pregnancy (e.g., HELLP syndrome, intrahepatic cholestasis, hyperemesis gravidarum, or acute fatty liver of pregnancy) to de novo ones occurring in pregnancy, and pre-existing liver disease (cholelithiasis, Budd-Chiari syndrome, and cirrhosis). We performed a systematic literature search over 10 years. The review protocol assumed a search of two databases (PubMed®/MEDLINE and Web of Science Core Collection). The strategy regarding the management of these diseases involves multidisciplinary teams composed of different specialists (obstetricians, gastroenterologists and anesthetists) from specialized tertiary centers. Despite the improving prognosis of pregnant women with liver diseases, the risk of maternal-fetal complications remains very high. Therefore, it is necessary to ensure careful monitoring by a multidisciplinary team and to inform the patients of the potential risks.


Rat adrenal zona fasciculata cell electrophysiological responses to ACTH and gamma-MSH vary with age.
A comparison was made of the resting membrane potential (MP) as well as the MP responses to K+, ACTH and gamma-MSH of superfused adrenocortical, zona fasciculata cells from young (Y) and old (O) male rats. The resting MP of these cells did not vary with age. However, the MP responses to altered extracellular [K+] varied significantly with age. A prolonged biphasic depolarization was observed following ACTH administration; these responses were significantly reduced in O cells. In contrast, stimulation with gamma-MSH did not consistently elicit depolarization in the Y but caused a consistent and prominent depolarization in O cells. These findings suggest that aging is associated with changes in primary membrane events which could explain the reduced ACTH-stimulated steroidogenesis associated with age. Elevated cellular responses to gamma-MSH may contribute to a maintenance of, or increase in, circulating corticosterone levels in aged rats.


HIV epidemiology and treatment - 1999.
Potent antiretroviral treatment has led to a dramatic decrease in HIV-associated morbidity and mortality. This paper reviews (1) current recommendations for the initiation of antiretroviral therapy, (2) the natural history of HIV infection after initiation of treatment, and (3) toxicity and resistance issues.


[Static volume contrast imaging (VCI)--clinical implications in obstetrics and gynecology].
We present a new form of data image processing obtained through three-dimensional scanning named static volume contrast imaging (VCI) and discuss its technique and clinical implications in obstetrics and gynecology.


Where do youth in foster care receive information about preventing unplanned pregnancy and sexually transmitted infections?
Adolescents in foster care are at risk for unplanned pregnancy and sexually transmitted infections, including HIV infection. A study using a qualitative method was conducted to describe how and where foster youth receive reproductive health and risk reduction information to prevent pregnancy and sexually transmitted infections. Participants also were asked to describe their relationship with their primary health care provider while they were in foster care. Nineteen young adults, recently emancipated from foster care, participated in individual interviews. Using grounded theory as the method of analysis, three thematic categories were generated: discomfort visiting and disclosing, receiving and not receiving the bare essentials, and learning prevention from community others. Recommendations include primary health care providers providing a confidential space for foster youth to disclose sexual activity and more opportunities for foster youth to receive reproductive and risk prevention information in the school setting.


Swallowing disorders in head and neck cancer patients treated with radiotherapy and adjuvant chemotherapy.
The nature of swallowing problems was examined in nine patients treated primarily with external-beam radiation and adjuvant chemotherapy for newly diagnosed tumors of the head and neck. All subjects underwent videofluorographic examination of their swallowing. Three analyses were completed, including the following: observations of motility disorders, residue, and aspiration; temporal analyses; and biomechanical analyses. Oropharyngeal swallow efficiency was calculated for the first swallow of each bolus. Swallow motility disorders were observed in both the oral and pharyngeal stages. Seven of the nine patients demonstrated reduced posterior tongue base movement toward the posterior pharyngeal wall and reduced laryngeal elevation during the swallow. Oropharyngeal swallow efficiency measures were significantly lower in the nine irradiated patients than in age-matched normal subjects. Between patients and normal subjects, significant differences were found in the measures of timing and distance of pharyngeal structural movements during the swallow, as well as in the measures of coordination during the swallow. Although treatment of head and neck cancer with external-beam radiation is designed to provide cancer cure and preserve organ functioning, oral and pharyngeal motility for swallow can become compromised if external-beam radiation treatment is provided to either the larynx or tongue base regions.


An Assessment of Psychological Need in Emergency Medical Staff in the Northern Health and Social Care Trust Area.
Psychological stress is increasingly recognised within emergency medicine, given the environmental and clinical stressors associated with the specialism. The current study assessed whether psychological distress is experienced by emergency medical staff and if so, what is the expressed need within this population? Participants included ambulance personnel, nursing staff, doctors and ancillary support staff within two Accident and Emergency (A&E) departments and twelve ambulance bases within one Trust locality in NI (N = 107). The General Health Questionnaire (GHQ-12, Goldberg, 1972, 1978), Secondary Traumatic Stress Scale (STSS, Bride, 2004) and an assessment of need questionnaire were completed and explored using mixed method analysis. Results showed elevated levels of psychological distress within each profession except ambulance service clinical support officers (CSOs). Elevated levels of secondary trauma symptomatology were also found; the highest were within some nursing grades and junior doctors. Decreased enjoyment in job over time was significantly associated with higher scores. Analysis of qualitative data identified sources of stress to include low morale. A total of 65% of participants thought that work related stressors had negatively affected their mental health. Participants explored what they felt could decrease psychological distress including improved resources and psychoeducation. There were elevated levels of distress and secondary traumatic stress within this population as well as an expressed level of need, on both systemic and support levels.


Choosing between an apple and a chocolate bar: the impact of health and taste labels.
Increasing the consumption of fruit and vegetables is a central component of improving population health. Reasons people give for choosing one food over another suggest health is of lower importance than taste. This study assesses the impact of using a simple descriptive label to highlight the taste as opposed to the health value of fruit on the likelihood of its selection. Participants (N=439) were randomly allocated to one of five groups that varied in the label added to an apple: apple; healthy apple; succulent apple; healthy and succulent apple; succulent and healthy apple. The primary outcome measure was selection of either an apple or a chocolate bar as a dessert. Measures of the perceived qualities of the apple (taste, health, value, quality, satiety) and of participant characteristics (restraint, belief that tasty foods are unhealthy, BMI) were also taken. When compared with apple selection without any descriptor (50%), the labels combining both health and taste descriptors significantly increased selection of the apple ('healthy & succulent' 65.9% and 'succulent & healthy' 62.4%), while the use of a single descriptor had no impact on the rate of apple selection ('healthy' 50.5% and 'succulent' 52%). The strongest predictors of individual dessert choice were the taste score given to the apple, and the lack of belief that healthy foods are not tasty. Interventions that emphasize the taste attributes of healthier foods are likely to be more effective at achieving healthier diets than those emphasizing health alone.


Prophylactic acupuncture treatment during chemotherapy with breast cancer: a randomized pragmatic trial with a retrospective nested qualitative study.
This study investigated the effect of additional prophylactic acupuncture during chemotherapy on quality of life and side effects compared to standard treatment alone in breast cancer patients. In a pragmatic trial, newly diagnosed breast cancer patients were randomized to additional acupuncture treatments over 6 months or standard care alone (control group). The primary outcome was the disease-specific quality of life (FACT-B). Twenty qualitative semi-structured interviews were conducted with ten patients from each group regarding their subjective experiences. A total of 150 women (mean age 51.0 (SD 10.0) years) were randomized. For the primary endpoint, FACT-B total score after 6 months, no statistically significant difference was found between groups (acupuncture: 103.5 (95%, CI 88.8 to 107.2); control (101.4 (- 97.5 to 105.4); difference 2.0 (- 3.4 to 7.5) p = 0.458)). Qualitative content analyses showed that patients in the acupuncture group described positive effects on psychological and physical well-being. For both patient groups, coping strategies were more important than reducing side effects. Breast cancer patients receiving prophylactic acupuncture during chemotherapy did not show better quality of life in the questionnaires in contrast to the reported positive effects in the qualitative interviews. Coping strategies for cancer appear to be important. clinicaltrials.gov; NCT01727362. Prospectively registered 11 July 2012; https://clinicaltrials.gov/ct2/show/NCT01727362 . The manuscript adheres to CONSORT guidelines.


Corticosteroids can help distinguish between Guillain-Barré syndrome and first attack of chronic inflammatory demyelinating neuropathy: an illustrative case report.
To report a case of acquired demyelinating neuropathy that failed to improve upon treatment with intravenous immunoglobulins and plasmapheresis but responded dramatically to corticosteroids, illustrating the occasional difficulty in distinguishing Guillain-Barré syndrome (GBS) from a first attack of chronic inflammatory demyelinating polyneuropathy (CIDP). A 25-year-old previously healthy man was admitted with a 5-day history of ascending areflexic paralysis of all 4 limbs and diagnosed with GBS. On admission, he was administered intravenous immunoglobulins at a dosage of 400 mg/kg/day for 5 days yet continued to worsen. He became quadriparetic by the second week. As there had been no improvement, he was plasmapheresed with 7 sessions of plasma exchange, 50 ml/kg of plasma at each session, including appropriate replacement fluid. After failing to improve within 8 weeks, he was started on intravenous methylprednisolone and a dramatic improvement was observed by the 5th day. He continued to get better on oral prednisolone, was ambulatory with support 4 weeks later and could walk without support on follow-up. This case illustrates that there is a subset of patients initially diagnosed with GBS who do not respond to immunoglobulins or plasmapheresis but do specifically well on steroids. Hence treatment with prednisolone should not be delayed in selective cases of GBS as it may actually be a first episode of CIDP.


Weapon Use in Korean Homicide: Differences Between Homicides Involving Sharp and Blunt Instruments.
On the basis of information regarding 276 homicides committed in South Korea between 1987 and 2008, we compared offenders' and victims' characteristics, injury locations, weapon-related behavior, and offending behavior between homicides involving sharp and blunt instruments. The victims of sharp-force homicide were much younger relative to those of blunt-force homicide. In addition, homicides involving blunt instruments were more likely to be committed by offenders who lived with the victims. Most sharp-force homicides involved injuries to the torso, while blunt-force homicides involved mainly head injuries. Furthermore, perpetrators of sharp-force homicides tended to preselect their weapons, while those of blunt-force homicides were likely to use weapons of opportunity. Logistic regression analysis identified a number of factors, including injury location and body transportation, which significantly predicted weapon type. As this was the first South Korean study to compare sharp- and blunt-force homicides, the results have practical implications for homicide investigations.


Lynch syndrome-associated lung cancer: pitfalls of an immunotherapy-based treatment strategy in an unusual tumor type.
Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of MSH6 gene and an intronic variant in the BRCA2 gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. Despite these premises, the patient was treated with pembrolizumab and she did not benefit from this kind of treatment.


The reporting completeness of a passive safety surveillance system for pandemic (H1N1) 2009 vaccines: a capture-recapture analysis.
Adverse events following pandemic (H1N1) 2009 vaccines ("2009 H1N1 vaccines") in Taiwan were passively reported to the National Adverse Drug Reaction Reporting System. To evaluate the completeness of spontaneous reporting, cases of death, Guillain-Barré syndrome (GBS), convulsion, Bell's palsy, and idiopathic thrombocytopenic purpura (ITP) after 2009 H1N1 vaccination that occurred between November 1, 2009 and August 31, 2010 were selected from the National Adverse Drug Reaction Reporting System (NADRRS) database and an additionally constructed nationwide large-linked database (LLDB), and matched on a unique personal identifier, date of vaccination (within ±7 days), and date of diagnosis (within ±7 days). Overall, matches occurred between the two data sources included 21 for death, 5 for GBS, 19 for convulsion, 22 for Bell's palsy, and 5 for ITP. The Chapman capture-recapture estimated spontaneous reporting completeness within 0-42 days of vaccination was 4% for death, 71% for GBS, 3% for convulsion, 9% for Bell's palsy, and 15% for ITP. For the interval ≥43 days after vaccination, reporting completeness was 0.1% for death, 14% for GBS, 0.1% for convulsion, <0.1% for Bell's palsy, and 0% for ITP. The estimated-to-expected ratio for Bell's palsy in the interval 0-42 days after vaccination was 1.48 (95% CI 1.11-1.98). Reporting completeness was higher for GBS than other adverse events after 2009 H1N1 vaccination. Linking the NADRRS to existing data sources in a capture-recapture analysis can be considered as an alternative to enhance Taiwan's postlicensure safety assessment of other routine vaccines. Nevertheless, the possibility of an increased risk for Bell's palsy detected by capture-recapture analyses needs further evaluation by controlled studies.


Carriership of a defective tenascin-X gene in steroid 21-hydroxylase deficiency patients: TNXB -TNXA hybrids in apparent large-scale gene conversions.
Steroid 21-hydroxylase deficiency is caused by a defect in the CYP21A2 gene. CYP21A2, the adjacent complement C4 gene and parts of the flanking genes RP1 and TNXB constitute a tandemly duplicated arrangement in the central (class III) region of the major histocompatibility complex. The typical number of repeats of the CYP21/C4 region is two, with one repeat carrying CYP21A2 and the other carrying the highly homologous pseudogene CYP21A1P. By comparison with this standard, three categories of CYP21A2 defects have traditionally been distinguished: CYP21A2 deletions, large-scale gene conversions of CYP21A2 into a structure similar to CYP21A1P, and smaller mutations in CYP21A2 (also derived from CYP21A1P, by means of small-scale gene conversions). The genetic mechanisms suggested by these designations have originally been inferred from the layout of the haplotypes involved and were later confirmed by observation of deletions and small mutations, but not large-scale conversions, as de novo events. Apparent large-scale conversions account for the defect in 9 out of 77 chromosomes in our patient group. We here demonstrate that 4 out of these 9 'conversions' extend into the flanking TNXB gene, which encodes tenascin-X. This implies that approximately 1 in every 10 steroid 21-hydroxylase deficiency patients is a carrier of tenascin-X deficiency, which is associated with a recessive form of the Ehlers-Danlos syndrome. Currently available data on the structure of 'deletion' and 'large-scale conversion' chromosomes strongly suggests that both are the result of the same mechanism, namely unequal meiotic crossover. Since it is unlikely that the term 'large-scale gene conversion' describes a mechanism that actually occurs between the CYP21A2 and CYP21A1P genes, we propose the discontinuation of that terminology.