Contraception and the media: lessons past, present and future.
The rise in social media and the pressure on conventional media to garner online hits has the potential to distort the quality of health information available to the consumer. It should be possible to learn from the 'scares' of the past to develop strategies to counter the effects of misinformation and scaremongering so commonly seen in any discussion of contraceptive risks. That balanced, evidence-based information is available to all couples considering their contraceptive options should be a priority for all clinicians, academics and journalists working in this area.


Effect of maternal exposure to nicotine in the rat on level and binding of somatostatin in brain of developing offspring.
The effect of maternal exposure to nicotine on the level of somatostatin and specific binding in frontoparietal cortex and hippocampus of developing offspring was investigated. Sprague-Dawley rats were injected subcutaneously, throughout the pregnancy and the nursing period, with either: 3 mg/kg nicotine base or saline vehicle. In the offspring of control rats, the level of somatostatin-like immunoreactivity peaked at day 10 in the frontoparietal cortex, whereas the level of immunoreactivity in the hippocampus was the highest on day 30. Maternal exposure to nicotine caused enhanced levels of immunoreactivity in the frontoparietal cortex, on the day of birth and in the hippocampus, up to day 10. The maximum specific binding of somatostatin to the receptors in membranes from the frontoparietal cortex, peaked at 10 days of age in the offspring of control rats. The number of somatostatin receptors in cortical (but not in hippocampal) membranes was significantly decreased in the 0- to 10-day-old offspring of the nicotine-treated rats. Despite transient alterations in the number of somatostatin receptors, the affinity of the sites for somatostatin was consistently unchanged. The levels of somatostatin-like immunoreactivity and the number of somatostatin receptors in the frontoparietal cortex and hippocampus was comparable in the 30-day-old offspring of the control and nicotine-treated rats.


Validation of the Amsterdam Beverage Picture Set: A Controlled Picture Set for Cognitive Bias Measurement and Modification Paradigms.
Alcohol research may benefit from controlled and validated picture sets. We have constructed the Amsterdam Beverage Picture Set (ABPS), which was designed for alcohol research in general and cognitive bias measurement and modification in particular. Here, we first formulate a position on alcohol stimulus validity that prescribes that alcohol-containing pictures, compared to nonalcohol-containing pictures, should induce a stronger urge to drink in heavy drinkers than in light drinkers. Because a perceptually simple picture might induce stronger cognitive biases but the presence of a drinking context might induce a stronger urge to drink, the ABPS contains pictures with and without drinking context. By limiting drinking contexts to simple consumption scenes instead of real-life scenes, complexity was minimized. A validation study was conducted to establish validity, to examine ABPS drinking contexts, and to explore the role of familiarity, valence, arousal, and control. Two hundred ninety-one psychology students completed the Alcohol Use Disorders Identification Test, as well as rating and recognition tasks for a subset of the ABPS pictures. The ABPS was well-recognized, familiar, and heavy drinkers reported a greater urge to drink in response to the alcohol-containing pictures only. Alcohol presented in drinking context did not elicit a stronger urge to drink but was recognized more slowly than alcohol presented without context. The ABPS was found to be valid, although pictures without context might be preferable for measuring cognitive biases than pictures with context. We discuss how an explicit approach to picture construction may aid in creating variations of the ABPS. Finally, we describe how ABPS adoption across studies may allow more reproducible and comparable results across paradigms, while allowing researchers to apply picture selection criteria that correspond to a wide range of theoretical positions. The latter is exemplified by ABPS derivatives and adoptions that are currently under way.


[Ultrasound diagnosis of Crohn disease].
In inflammatory bowel diseases sonography can depict the transformations in the bowel wall structure as well as extramural changes. Certain patterns of altered stratification can be defined which can be helpful in determining disease activity. Crohn's disease is extending very often into the mesenteries and to the serosa, omentum and peritoneum on the other side. Sonography will detect fistulas, abscesses, omental cake and ascites for example. Extraintestinal manifestations like those of the biliary tree, the pancreas, the kidneys can be seen. Color doppler sonography will be able to define disease activity. In differentiating Crohn's disease from infectious enterocolitis and diverticulitis as well as other rare disorders sonography can be useful.


Assessing the accuracy of integral equation theories for nano-sized hydrophobic solutes in water.
Integral equation theories provide an efficient route for computing the solvation free energy (SFE) of molecular systems in water. The accuracy of those theories is usually tested against small molecules via comparison of SFE with reference data. However, tests against larger molecules in the nanometer regime are scarce in literature despite recent applications to such systems. Here, we thus study the accuracy and validity of a commonly used integral equation theory, namely, a three-dimensional reference interaction site model (3D-RISM), by considering the following problems: (1) solvation of a small to large Lennard-Jones particle, (2) binding of planar hydrophobic systems with varying size and hydrophobicity, and (3) self-assembly of amphiphilic molecules into a nanocapsule. The energy representation method is also utilized for comparison. The results show that the 3D-RISM method works successfully for small molecules, while the accuracy degrades systematically with system size and hydrophobicity. The size-dependent error in SFE does not cancel adequately between two solute configurations, resulting in a substantial error in the free energy difference. It is also shown that the free energy profiles for hydrophobic association exhibit a fictitious high-energy barrier, suggesting that care must be taken for studying such systems. The numerical difficulties observed above are discussed based on the relation between hypernetted-chain approximation, classical density functional theory with quadratic expansion, and the size-dependent error arising from the cavity region of the system.


Thermal, cardiovascular & thermogenic responses to mild cold exposure in chronically energy deficient human subjects.
Thirteen young, male adults were investigated for thermal, cardiovascular and metabolic responses to truncal cooling for 40 min. The subjects were divided into two groups [well nourished controls (WN) and chronically energy deficient (CED)] on the basis of anthropometry and socio-economic status. The CED group had significantly greater reductions in peripheral forearm blood flow and surface finger tip temperatures on exposure to cold when compared to the well nourished controls. The CED group also showed a significant rise in oxygen consumption (3.4%), while no thermogenic response was observed in the WN controls. There was no fall in deep body temperature in either group. The study suggests that chronically energy deficient subjects thermoregulate appropriately on exposure to mild cold. The deficiency in insulative body fat is made up for by evoking greater peripheral vasoconstrictor responses as well as thermogenic mechanisms. The study suggests that on exposure to cold, thermoregulation takes precedence over energy conservation in chronically energy deficient subjects.


Rapid detection of Vibrio cholerae O139 Bengal from stool specimens by PCR.
In a previous study using pure bacterial cultures in a PCR assay, a primer pair corresponding to a unique chromosomal region of Vibrio cholerae O139 Bengal generated an amplicon from only V. cholerae O139 Bengal. PCR with the same primer pair was used to screen 180 diarrheal stool specimens. All the 67 V. cholerae O139 culture-positive stool specimens were positive by PCR, and the remaining specimens, which contained either other recognized enteric pathogens or no pathogens, were all negative by PCR.


Mussel-inspired dopamine- and plant-based cardanol-containing polymer coatings for multifunctional filtration membranes.
A series of copolymers [PCD#s, where # is the weight percentage of dopamine methacrylamide (DMA) in polymers] containing mussel-inspired hydrophilic dopamine and plant-based hydrophobic cardanol moieties was prepared via radical polymerization using DMA and 2-hydroxy-3-cardanylpropyl methacrylate (HCPM) as the monomers. PCD#s were used as coating materials to prevent flux decline of the membranes caused by the adhesion of biofoulants and oil-foulants. Polysulfone (PSf) ultrafiltration membranes coated with PCD#s showed higher biofouling resistance than the bare PSf membrane, and the bactericidal properties of the membranes increased upon increasing the content of HCPM units in the PCD#s. Serendipitously, the PSf membranes coated with the more or less amphiphilic PCD54 and PCD74, having the optimum amount of both hydrophilic DMA and hydrophobic HCPM moieties, showed noticeably higher oil-fouling resistance than the more hydrophilic PCD91-coated membrane, the more hydrophobic PCD0-coated membrane, and the bare PSf membrane. Therefore, multifunctional coating materials having biofouling- and oil-fouling-resistant and bactericidal properties could be prepared from the monomers containing mussel-inspired dopamine and plant-based cardanol groups.


Visual perception can account for the close relation between numerosity processing and computational fluency.
Studies have shown that numerosity processing (e.g., comparison of numbers of dots in two dot arrays) is significantly correlated with arithmetic performance. Researchers have attributed this association to the fact that both tasks share magnitude processing. The current investigation tested an alternative hypothesis, which states that visual perceptual ability (as measured by a figure-matching task) can account for the close relation between numerosity processing and arithmetic performance (computational fluency). Four hundred and twenty four third- to fifth-grade children (220 boys and 204 girls, 8.0-11.0 years old; 120 third graders, 146 fourth graders, and 158 fifth graders) were recruited from two schools (one urban and one suburban) in Beijing, China. Six classes were randomly selected from each school, and all students in each selected class participated in the study. All children were given a series of cognitive and mathematical tests, including numerosity comparison, figure matching, forward verbal working memory, visual tracing, non-verbal matrices reasoning, mental rotation, choice reaction time, arithmetic tests and curriculum-based mathematical achievement test. Results showed that figure-matching ability had higher correlations with numerosity processing and computational fluency than did other cognitive factors (e.g., forward verbal working memory, visual tracing, non-verbal matrix reasoning, mental rotation, and choice reaction time). More important, hierarchical multiple regression showed that figure matching ability accounted for the well-established association between numerosity processing and computational fluency. In support of the visual perception hypothesis, the results suggest that visual perceptual ability, rather than magnitude processing, may be the shared component of numerosity processing and arithmetic performance.


Growth of tissue into a porous, low modulus coating on intramedullary nails: an experimental study.
The ingrowth of tissue into a coating of inert, highly porous, low-modulus composite of polytetrafluorethylene polymer and pyrolytic graphite on four-fluted intramedullary nails was used for stabilization of middiaphyseal femoral osteotomies and examined by microangiography. The observations were correlated with information obtained by histologic, microradiographic and tetracycline fluorescence technology. There was rapid healing of the osteotomy. The coating was invaded throughout by blood vessels and fibrous tissue. Invasion by bone was negligible. The composite thus appeared to retain its initial flexibility when implanted into the femoral intramedullary cavity. The force to distract both coated and uncoated nails was measured on intact femora. The unit retention strength increased to an average of 6.3 kg/cm2 up to 24 weeks, which is consistent with reported values. The composite would thus appear to have potential use as a coating for endoprostheses to produce enduring physiologic fixation.


Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona.
Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.


Anti-CD19 Chimeric Antigen Receptor T Cell Therapy With Tisagenlecleucel for Secondary Central Nervous System Lymphoma: A Case Series.
Relapsed or refractory (R/R) large B cell lymphoma (LBCL) presenting as secondary central nervous system lymphoma (SCNSL) carries a poor prognosis, with a median survival time of two to five months. Chimeric antigen receptor (CAR)-T cell therapy has been approved in R/R LBCL, but studies are ongoing to understand its efficacy and safety for SCNSL. Axicabtagene ciloleucel or tisagenlecleucel have been shown to attain high response rates in some retrospective studies; however, response durability continues to be unclear. Our study is a case series of three patients with R/R SCNSL who were treated with tisagenlecleucel. One patient achieved a complete response 30 days after CAR-T therapy but developed disease progression on day +100 imaging. The second patient had a partial response and eventual disease progression with ultimately death. The third patient died from central nervous system complications of CAR-T therapy. Two of the three patients developed immune effector cell-associated neurotoxicity syndrome grade 4 and cytokine release syndrome grade 1 toxicities. Our series of three patients demonstrates that R/R SCNSL can elicit a response with CAR-T therapy, although with a limited duration response.


[Diagnostic usefulness of uterine artery Doppler].
Doppler waves present hemodynamic state of vascular bed. This method is used in a diagnostic of pathological states in pregnancy. Basing on the observation of curve shape of uterine artery blood flow, we may conclude about its vascular resistance, wall tension and amount of blood. Several studies confirmed the opportunity of the use of Doppler uterine artery in a diagnosis and prognosis of complicated pregnancies. The incidence of notch in uterine artery blood flow was observed in pregnancies with incomplete trophoblast invasion and inadequate placentation. Many studies confirmed that bilateral notch might be associated with increased likelihood of different pregnancy complications, particularly pregnancy--induced hypertension (PIH) and intrauterine growth restriction (IUGR). The results of the most recent trials include the possibility of the use Ut-PI in a distinguishing of abnormal biochemical, prenatal tests in chromosomal aberrations and different pathological states in pregnancy such as preeclampsia and fetal hypotrophy.


An exploratory study of obstetrics trainees' experiences of breaking bad news.
Breaking bad news is one of the hardest tasks performed by doctors. The news can significantly impact on the patient's life; however, the process also generates stress for the doctor. The aim of this study was to explore the lived experiences of breaking bad news for obstetrics trainees in Ireland. A qualitative study using interpretative phenomenological analysis (IPA) was performed to capture the experience of breaking bad news for the trainees. Semi-structured interviews were conducted with trainees over Zoom. The transcripts were analysed in line with the IPA framework with the assistance of NVivo software. Seven trainees were interviewed, five at Basic Specialist Training (BST) level and two at Higher Specialist Training (HST) level. Four superordinate themes were identified from the analysis: "the reality of working in obstetrics," "the role of the doctor," "development of communication skills" and "the importance of the patient experience." The trainees described breaking bad news in a variety of clinical contexts. This task could be emotionally draining; however, only two trainees mentioned ways of coping with this. Their formal training was limited with the majority of learning occurring "on the job." This study provides an insight into factors that influence trainees experiences of breaking bad news. The results complemented existing literature and raised questions about how to better support trainees through increased training and psychological support.


The sensitivity and specificity of nonmydriatic digital stereoscopic retinal imaging in detecting diabetic retinopathy.
The objective of this study was to determine the sensitivity and specificity of Joslin Vision Network nonmydriatic digital stereoscopic retinal imaging (NMDSRI) as a screening tool in detecting diabetic retinopathy. We reviewed the records of 244 patients with diabetes who had a dilated funduscopic examination (DFE) and NMDSRI done within 1 year of each other at four locations in the metropolitan Washington, DC, area. The images were transmitted through a local area network to a central reading location where they were graded by a single retinal specialist. Images of 482 eyes from 243 patients were included in the study. Four images did not transmit, and 35% of the images were not gradable. Of the remaining 311 eyes, there was 86% agreement in the grading between NMDSRI and DFE: 227 eyes with no diabetic retinopathy and 40 eyes with diabetic retinopathy. In 46 eyes (15%) there was a disagreement between gradings made by the two techniques. NMDSRI detected diabetic retinopathy in 35 eyes reported as normal by DFE, and in the remaining 11 eyes, the DFE grade was one grade higher than the NMDSRI grade. Adjudicated nonconcordant examinations were within one grade. In the 76 eyes with diabetic retinopathy, retinal thickness could not be assessed in 17 (21%) eyes. When the NMDSRI result was gradable, the overall sensitivity of NMDSRI was 98% and the specificity was 100% for retinopathy within one grade of the DFE. In the limited number of eyes that had diabetic retinopathy with macular edema (six), agreement with the clinical examination was 100%. NMDSRI is a sensitive and specific method for the screening and diagnosis of diabetic retinopathy, which may help improve compliance with the standards of eye care for patients with diabetes.


Ethanol sensitivity of NMDA receptor function in developing cerebellar granule neurons.
The mechanism by which ethanol inhibits the function of the NMDA subtype of glutamate receptor has not been elucidated. One possibility that has been suggested is that NMDA receptor subunit composition influences the sensitivity of the receptor to ethanol. We have taken advantage of developmental changes in subunit composition of the NMDA receptor in cultured neurons to examine possible changes in the effect of ethanol. We found an increase in expression of the NR2A subunit, and a decrease in expression of the NR2B subunit of the NMDA receptor in primary cultures of cerebellar granule neurons over time in culture, with no significant change in NR1 expression. This change in NR2 subunit expression was associated with the expected changes in functional properties of the NMDA receptor (measured as the NMDA-induced increase in intracellular Ca2+), i.e., ifenprodil sensitivity and glycine potency were higher when there was a relatively greater proportion of NR2B in the cultured neurons. However, the potency of ethanol to inhibit NMDA receptor function was lower when there was a greater proportion of NR2B subunits. Previous studies showed that ethanol inhibition of NMDA receptor function in cerebellar granule neurons resulted from an ethanol-induced decrease in potency of the co-agonist, glycine, and that this effect of ethanol was blocked by inhibitors of protein kinase C. Our current results suggest that the lower potency of ethanol to inhibit the response of NMDA receptors when cerebellar granule neurons are expressing a greater proportion of NR2B subunits is a result of the higher affinity of the NMDA receptors for endogenous levels of glycine at this point in time.


Vitamin D status in irritable bowel syndrome and the impact of supplementation on symptoms: what do we know and what do we need to know?
Low vitamin D status is associated with risk of colorectal cancer and has been implicated in inflammatory bowel disease. Irritable bowel syndrome (IBS) is a chronic, relapsing, functional bowel disorder. A nascent literature suggests a role for vitamin D in IBS, but this has not been collated or critiqued. To date, seven studies have been published: four observational studies and three randomised controlled trials (RCTs). All observational studies reported that a substantial proportion of the IBS population was vitamin D deficient. Two intervention studies reported improvement in IBS symptom severity scores and quality of life (QoL) with vitamin D supplementation. There are limited data around the role of vitamin D in IBS. The available evidence suggests that low vitamin D status is common among the IBS population and merits assessment and rectification for general health reasons alone. An inverse correlation between serum vitamin D and IBS symptom severity is suggested and vitamin D interventions may benefit symptoms. However, the available RCTs do not provide strong, generalisable evidence; larger and adequately powered interventions are needed to establish a case for therapeutic application of vitamin D in IBS.


Serum Prooxidant-Antioxidant Balance and hs-CRP in Patients with Clinical and Subclinical Hypothyroidism.
Oxidative stress (OS) is caused by an imbalance between prooxidant substance production and antioxidant defense. OS is involved in physiologic interactions in the body and the pathogenesis of various disorders. This study aimed to evaluate serum prooxidant-antioxidant balance (PAB) as a selective prooxidant, antioxidant defense, and acute phase reactant protein in patients with subclinical and clinical hypothyroidism. This case-control study was conducted in three groups including clinical hypothyroidism (32 patients), subclinical hypothyroidism, (42 cases), and healthy controls (32 individuals). This study was performed in the Endocrine Clinic of Arash Training and Research Hospital, Tehran, 2017. In the study groups, thyroid hormones including T4 and Thyroid Stimulating Hormone (TSH), fasting blood glucose (FBG), lipid profile, PAB, and hs-CRP as inflammatory markers were measured and compared between the groups. Among 106 participants, 95.3% were females, the gender balance was similar across groups and mean age was 30.79 ± 7.65 years. FBG and lipid profile except for cholesterol level were not significantly different between the three study groups. However, cholesterol level in the clinical hypothyroid group was significantly higher than the other two groups. PAB was higher in subclinical hypothyroidism compared to healthy controls after adjustment for age and TSH levels (P value: 0.04) but there was no significant difference in the clinical hypothyroid group in comparison with healthy controls. In addition, there was no significant difference in high-sensitivity C-reactive protein (hs-CRP) between the three study groups. This study suggests that that subclinical hypothyroidism increases PAB in comparison to healthy control which could indicate OS response in patients with subclinical hypothyroidism, respectively.


Isomer-Resolved Reactivity of Organic Peroxides in Monoterpene-Derived Secondary Organic Aerosol.
Organic peroxides play a vital role in the formation, evolution, and health impacts of atmospheric aerosols, yet their molecular composition and fate in the particle phase remain poorly understood. Here, we identified, using iodometry-assisted liquid chromatography mass spectrometry, a large suite of isomer-resolved peroxide monomers (C8-10H12-18O5-8) and dimers (C15-20H22-34O5-14) in secondary organic aerosol formed from ozonolysis of the most abundant monoterpene (α-pinene). Combining aerosol isothermal evaporation experiments and multilayer kinetic modeling, bulk peroxides were found to undergo rapid particle-phase chemical transformation with an average lifetime of several hours under humid conditions, while the individual peroxides decompose on timescales of half an hour to a few days. Meanwhile, the majority of isomeric peroxides exhibit distinct particle-phase behaviors, highlighting the importance of the characterization of isomer-resolved peroxide reactivity. Furthermore, the reactivity of most peroxides increases with aerosol water content faster in a low relative humidity (RH) range than in a high RH range. Such non-uniform water effects imply a more important role of water as a plasticizer than as a reactant in influencing the peroxide reactivity. The high particle-phase reactivity of organic peroxides and its striking dependence on RH should be considered in atmospheric modeling of their fate and impacts on aerosol chemistry and health effects.


[Usefulness of electronic drug registers: Spanish register of patients treated with fingolimod (Gilenya ®)].
This study outlines the design of an electronic register of patients with multiple sclerosis who began treatment with fingolimod in Spain. The system is intended to serve as a tool to monitor its utilisation in daily clinical practice and thus allow optimisation of the way it is used. To establish the profile of patients with multiple sclerosis undergoing treatment with fingolimod and to determine the effectiveness and safety of this treatment in daily clinical practice. An observation-based, retrospective and prospective, multi-centre registry is set up, which will be active for five years. Forty neurologists working in Spain will participate in the project. Patients treated with fingolimod who fulfil the selection criteria will be included in the study. The effectiveness variables that will be evaluated are: disability measured by means of the Expanded Disability Status Scale, the rate of attacks, T1 gadolinium-enhancing lesions and new lesions in T2, and the percentage of patients who were free of activity and those who require concomitant treatments. The tolerability variables that will be evaluated are: the rate of patients who present events and adverse reactions, respectively, with a separate analysis of those presenting after the first dose or that are related to the fingolimod risk management plan and the treatment dropout rate. New pharmaceuticals that have only recently been commercialised require more information about their effectiveness and safety, beyond the controlled environment of a clinical trial. Initiatives involving electronic registries such as the Gilenya register are a solution that can respond to such needs by providing information in the shortest possible time about the most suitable management in order to be able to make the best and most efficient use of it.


Development of farnesyltransferase inhibitors for clinical cancer therapy: focus on hematologic malignancies.
Farnesyltransferase inhibitors (FTIs) target and inhibit the peptide prenylating enzyme farnesyltransferase. This new class of signal transduction inhibitors is being tested clinically in diverse malignancies, with encouraging results in hematololgic malignancies and breast cancer in particuarl. Critical questions have yet to be answered, for example, optimal dose and schedule, disease subgroups most likely to respond, and appropriate combinations with standard cytotoxics and new biologics. Gene profiling studies of malignant target cells obtained during FTI clinical trials will help to identify patients who are likely to respond to FTIs and to develop mechanisms for overcoming FTI resistance. Clinical trials and correlative laboratory studies in progress and under development will define the optimal roles of FTIs in cancer patients.


A photosensitizing fusion protein with targeting capabilities.
The photodynamic treatment for antimicrobial applications or anticancer therapy relies on reactive oxygen species generated by photosensitizing molecules after absorption of visible or near-infrared light. If the photosensitizing molecule is in close vicinity of the microorganism or the malignant cell, a photocytotoxic action is exerted. Therefore, the effectiveness of photosensitizing compounds strongly depends on their capability to target microbial or cancer-specific proteins. In this study, we report on the preparation and preliminary characterization of human recombinant myoglobin fused to the vasoactive intestinal peptide to target vasoactive intestinal peptide receptor (VPAC) receptors. Fe-protoporphyrin IX was replaced by the photosensitizing compound Zn-protoporphyrin IX. Taking advantage of the fluorescence emission by Zn-protoporphyrin IX, we show that the construct can bind prostate cancer cells where the VPAC receptors are expressed.


Factors influencing nurse fatigue during COVID-19: regression vs. fuzzy-set qualitative comparative analysis.
Nurses during COVID-19 who face significant stress and high infection risk are prone to fatigue, affecting their health and quality of patient care. A cross- sectional study of 270 nurses who went to epidemic area to support anti-epidemic was carried out via online survey during the COVID-19 pandemic on November 2021. A web-based cross-sectional survey of 270 nurses in China who traveled to Heihe City in Heilongjiang Province to combat the novel coronavirus epidemic. The researchers collected information on sociodemographic variables, anxiety, transition shock, professionalism, collaboration, hours of work per day, and fatigue. Regression and fuzzy-set Quality Comparative Analysis (fsQCA) evaluated the factors' impact on the nurses' fatigue. Regression analysis showed that the psychological variables significant for fatigue, transition shock (β = 0.687, p < 0.001) and anxiety (β = 0.757, p < 0.001) were positively associated with fatigue, professionalism (β = -0.216, p < 0.001) was negatively associated with fatigue, and among the work-related variables, cooperation (β = -0.262, p < 0.001) was negatively related to fatigue. FsQCA analysis showed that combined effects of work hours, anxiety, and nurses' educational status caused most of the fatigue (raw coverage = 0.482, consistency = 0.896). This study provides two main findings, the one is the greater transition shock experienced during COVID-19 in a new environment, low levels of professionalism, anxiety, and poor nursing teamwork situations lead anti-epidemic nurses to increased fatigue. Second, the fsQCA results showed that anxiety is sufficient for fatigue and that nurses' educational status, daily working hours, and anxiety are the most effective combination of factors.


Serious hazards of transfusion in children (SHOT).
SHOT has been auditing information on transfusion practice for over ten years. Looking at this data allows us to determine the differences in the incidence of hazards seen in children compared to adults and to see which hazards are of particular importance for children of different ages undergoing surgery.


Facile Synthesis of Concave Cuboid Au NCs with Precisely Tunable Dimensions and Mechanistic Insight.
Concave cuboid (CCB) nanostructure is a member of the high-index facet (HIF) nanocrystals (NCs) family, geometrically derived from regular cuboid-excavation of each face. CCB NCs hold some additional characteristics such as surface cavity and sharp edges and corners as compared to its convex counterpart that makes it relatively more active in applications like electrochemical catalysis, surface enhanced Raman spectroscopy (SERS), and plasmonics. To date, there are only few reports available on the synthesis of CCB Au NCs where Br- containing surfactants have been used as a shape directing and stabilizing agent. However, none of them led to decent yield and size tunability. Herein, we report a robust seed mediated growth strategy where cetyltrimethylammonium chloride (CTAC) and tannic acid (TA) have been used as shape-directing/stabilizing and mild reducing agents, respectively. Our method not only allows the high yield fabrication of CCB Au NCs with uniform shape and size but also precise control over dimensions and degree of surface concavity. Moreover, the investigation of growth mechanism revealed that the evolution of CCB Au NCs from cylindrical nanorods (NRs) take place via arrow-headed nanorods and truncated CCB nanostructures. Furthermore, it has been observed that the presence of excess of Cl- is indeed playing a decisive role despite the headgroup of counter cationic part of surfactant. We anticipate that our findings may pave the path to design new synthetic strategies and understand the evolution of new nanostructures.


Effects of sub-chronic antipsychotic drug treatment on body weight and reproductive function in juvenile female rats.
Weight gain caused by some antipsychotics is not only confined to adults but can also adversely affect both children and adolescents. Indeed, olanzapine and risperidone have been associated with extreme weight gain in adolescents even greater than that reported in adults. We have recently shown substantial weight gain in adult female rats following treatment with olanzapine and risperidone but not ziprasidone. The aim of the present study was to compare the effects of several antipsychotics on weight gain and reproductive function in juvenile (aged 7 weeks) female hooded Lister rats. Olanzapine (4 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg), sulpiride (10 mg/kg), haloperidol (0.5 mg/kg) or vehicle was administered i.p. once per day for 21 days. Body weight, food and water intake were measured daily, in addition to the determination of stage of the oestrous cycle. Sub-chronic administration of olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone, significantly increased body weight compared to vehicle-treated animals during weeks 1-3. Sulpiride significantly increased food and water intake. Significantly increased percentage intra-abdominal fat weight was observed in olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone-treated animals. Marked disruption of the oestrous cycle was observed in all but the ziprasidone-treated group, which continued to have regular 4-day oestrous cycles. Weight gain observed in these juvenile animals was 1.5-2 times greater than that previously observed in adult rats. These findings have important implications for the use of antipsychotics in children and adolescent patients.


Evaluating the impact of social support services on tuberculosis treatment default in Ukraine.
Ukraine is among the top 20 highest drug-resistant tuberculosis burden countries in the world. Driving the high drug-resistant tuberculosis rates is an unchecked treatment default rate. This evaluation measures the effect of social support provided to tuberculosis patients at risk of defaulting on treatment during outpatient treatment. Five tuberculosis patient cohorts, served in three oblasts from 2011 and 2012, were constructed from medical records to compare risk factors for default, receipt of social services, and treatment outcome. Regression analyses were used to identify risk factors predictive of treatment default and to estimate the impact of the social support program on treatment default, controlling for risk, disease status, and demographics. In 2012, tuberculosis patients receiving social support in Ukraine reduced their probability of defaulting on continuation treatment by 10 percentage points compared to high-risk patients who did not receive social support in 2012 or 2011. Treatment success rates for the high-risk patients receiving social support were comparable to the low-risk cohorts and significantly improved over the high-risk comparison cohorts. Further research is recommended to quantify the costs and benefits for scaling-up social support services, evaluate social support program fidelity, identify which populations respond best to select services, and what barriers might still exist to achieve better adherence. With that information, tailoring programs to most effectively reach and serve clients in a patient-centered approach may reap substantial rewards for Ukraine.


Design of the high-resolution soft X-ray imaging system on the Joint Texas Experimental Tokamak.
A new soft X-ray diagnostic system has been designed on the Joint Texas Experimental Tokamak (J-TEXT) aiming to observe and survey the magnetohydrodynamic (MHD) activities. The system consists of five cameras located at the same toroidal position. Each camera has 16 photodiode elements. Three imaging cameras view the internal plasma region (r/a < 0.7) with a spatial resolution about 2 cm. By tomographic method, heat transport outside from the 1/1 mode X-point during the sawtooth collapse is found. The other two cameras with a higher spatial resolution 1 cm are designed for monitoring local MHD activities respectively in plasma core and boundary.


High concentrations of the melatonin metabolite, N1-acetyl-N2-formyl-5-methoxykynuramine, in cerebrospinal fluid of patients with meningitis: a possible immunomodulatory mechanism.
We evaluated the presence of the melatonin metabolite N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), in cerebrospinal fluid (CSF) of patients with viral meningitis (n = 20) and control samples (n = 8) and correlate AFMK levels with inflammatory markers such as cellularity, protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-8 and IL-1beta levels. A portion of the CSF was extracted with dichloromethane (1:5) and analyzed by high-performance liquid chromatography (HPLC) under standardized conditions for AFMK. AFMK was detected in 16 of 20 CSF samples of patients with viral meningitis; the concentration of AFMK was found to be above the quantification limit (50 nmol/L) in six of these samples. AFMK was not detected in any of the eight control samples. The samples were classified into groups according to AFMK levels: undetectable (<10 nmol/L, group I), detectable but below the quantification limit (< 50 nmol/L, group II), and quantified (>50 nmol/L, group III). Group II presented the highest levels of proteins and IL-8, whereas group III showed the lowest levels of the inflammatory parameters. This study supports our hypothesis that inflammation favors the formation of AFMK and that this compound has immunomodulatory activity in vivo.


Public Health and Economic Consequences of Vaccine Hesitancy for Measles in the United States.
Routine childhood vaccination is declining in some regions of the United States due to vaccine hesitancy, which risks the resurgence of many infectious diseases with public health and economic consequences. There are ongoing policy debates on the state and national level, including legislation around nonmedical (personal-belief) exemptions for childhood vaccination and possibly a special government commission on vaccine safety, which may affect vaccine coverage. To estimate the number of measles cases in US children and the associated economic costs under scenarios of different levels of vaccine hesitancy, using the case example of measles, mumps, and rubella (MMR) vaccination and measles. Publicly available data from the US Centers for Disease Control and Prevention were used to simulate county-level MMR vaccination coverage in children (age 2-11 years) in the United States. A stochastic mathematical model was adapted for infectious disease transmission that estimated a distribution for outbreak size as it relates to vaccine coverage. Economic costs per measles case were obtained from the literature. The predicted effects of increasing the prevalence of vaccine hesitancy as well as the removal of nonmedical exemptions were estimated. The model was calibrated to annual measles cases in US children over recent years, and the model prediction was validated using an independent data set from England and Wales. Annual measles cases in the United States and the associated public sector costs. A 5% decline in MMR vaccine coverage in the United States would result in an estimated 3-fold increase in measles cases for children aged 2 to 11 years nationally every year, with an additional $2.1 million in public sector costs. The numbers would be substantially higher if unvaccinated infants, adolescents, and adult populations were also considered. There was variation around these estimates due to the stochastic elements of measles importation and sensitivity of some model inputs, although the trend was robust. This analysis predicts that even minor reductions in childhood vaccination, driven by vaccine hesitancy (nonmedical and personal belief exemptions), will have substantial public health and economic consequences. The results support an urgent need to address vaccine hesitancy in policy dialogues at the state and national level, with consideration of removing personal belief exemptions of childhood vaccination.


Sex differences of in-hospital outcome and long-term mortality in patients with Takotsubo cardiomyopathy.
Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. It is still unclear whether sex differences may influence long-term prognosis of TTC patients. The purpose of this study was to determine whether sex differences do influence the short- and long-term outcomes of TTC. A total of 114 patients with TTC were admitted to the University Medical Centre Mannheim from January 2003 to September 2015 and entered into the TTC database of the University Medical Centre Mannheim, and retrospectively analyzed. Patients were diagnosed by the Mayo Clinic criteria. All-cause mortality over mean follow-up of 1,529±1,121 days was revealed. Significantly more male patients died within long-term follow-up compared to female TTC patients (log-rank test; P=0.01). Most males died of noncardiac causes. In multivariate Cox regression analysis, the male sex (P=0.02, hazard ratio [HR] 2.8, 95% CI 1.1-7.2), the ejection fraction ≤35% (P=0.01, HR 3.3, 95% CI 1.2-9.2) and glomerular filtration rate <60 mL/min (P<0.01, HR 3.1, 95% CI 1.4-7.0) figured out as independent predictors of the adverse outcome. This study shows that males suffering from TTC reveal a higher long-term all-cause mortality rate than females over a 5 year follow-up period.


Device profile of the SAPIEN 3 transcatheter heart valve in low-risk patients with aortic stenosis: overview of its safety and efficacy.
Transcatheter aortic valve replacement (TAVR) has become a treatment of reference for patients with symptomatic severe aortic stenosis, and the balloon-expandable SAPIEN 3 and SAPIEN 3 Ultra transcatheter heart valve systems are two of the most broadly used worldwide. Lately, TAVR has progressively expanded toward the treatment of low-risk patients. In this review we aimed to describe the main characteristics of the SAPIEN 3 valve, and to delineate the main clinical findings regarding the safety and efficacy associated with this THV system in low-risk patients undergoing TAVR. The approval of THV systems for use in low-risk patients has been a significant step forward in expanding current TAVR indications. Along with procedural refinement and growing operator experience, device iterations implemented in new-generation THV systems have played a vital role in the successful spread of TAVR. The availability of SAPIEN 3 represented an inflection point, as it allows for a predictable positioning and safer navigability while dramatically decreasing the rate of residual paravalvular leakage compared to previous balloon-expandable systems. However, some unresolved issues remain like the relatively high rates of conduction disturbances and the uncertainty about valve performance in the long-term. Future studies are warranted.


Law and public health at CDC.
Public health law is an emerging field in U.S. public health practice. The 20th century proved the indispensability of law to public health, as demonstrated by the contribution of law to each of the century's 10 great public health achievements. Former CDC Director Dr. William Foege has suggested that law, along with epidemiology, is an essential tool in public health practice. Public health laws are any laws that have important consequences for the health of defined populations. They derive from federal and state constitutions; statutes, and other legislative enactments; agency rules and regulations; judicial rulings and case law; and policies of public bodies. Government agencies that apply public health laws include agencies officially designated as "public health agencies," as well as health-care, environmental protection, education, and law enforcement agencies, among others.


Gene amplification induces mucoid phenotype in rec-2 Pseudomonas aeruginosa exposed to kanamycin.
Gene amplification in the chromosome of rec-2 Pseudomonas aeruginosa PAO2003 upon growth on kanamycin-supplemented media led to a stable mucoid phenotype. The chromosomal region controlling alginate biosynthesis was shown to be amplified four to six times as a direct tandem repeat of at least 16.8 kilobase pairs. This amplification was deduced from Southern DNA-DNA hybridization patterns of the chromosomal DNA digested with restriction endonucleases BglII and EcoRI and probed with a cloned DNA segment complementing the alg-22 mutation. The part of the amplified unit carrying the novel DNA joint was cloned. The EcoRI junction fragment was further subcloned and used to probe chromosomes of parental strain PAO2003 and mucoid variant VD2003M. As predicted, the EcoRI junction fragment hybridized to the two chromosomal fragments required to produce the novel junction. Though the mucoid phenotype caused by gene amplification was stable, nonmucoid revertants were obtained at a low frequency on tetracycline-containing media. Southern hybridization of chromosomal DNA from a nonmucoid revertant revealed a reduction in the copy number of amplified DNA. These results suggest a direct relationship between amplification of this chromosomal segment and the induction of mucoidy.


Structure of sickled erythrocytes and of sickle-cell hemoglobin fibers.
Deoxyhemoglobin from patients homozygous for sickle-cell anemia (deoxyhb S) aggregates into long straight fibers. These may extend through most of the length of the sickled cell, forming either square or hexagonally packed bundles with lattice constants of 170-180 A. Each fiber is a tube made up of six thin filaments, which are wound around the tubular surface with a helical pitch of about 3000 A. Each filament is a string of single hemoglobin molecules linked end to end at intervals of 62 A in dry and 64 A in wet fibers. Molecules in neighboring filaments are in longitudinal register so that they form flat hexagonal rings; these rings are stacked so that successive ones are rotated about the fiber axis by 7.3 degrees . The whole structure repeats after about eight rings. In this structure each molecule makes contact with four neighbors. The likely orientation of the molecules and points of contact between them are discussed. Similar filaments are also observed in normal deoxygenated erythrocytes, but in much lower concentration and aggregated into fibers of irregular diameter. No filaments appear in oxygenated sickle, or normal, adult cells, nor in oxygenated or deoxygenated fetal cells.


Performance assessment of human resource by integration of HSE and ergonomics and EFQM management system.
Purpose The purpose of this paper is to present an integrated framework for performance evaluation and analysis of human resource (HR) with respect to the factors of health, safety, environment and ergonomics (HSEE) management system, and also the criteria of European federation for quality management (EFQM) as one of the well-known business excellence models. Design/methodology/approach In this study, an intelligent algorithm based on adaptive neuro-fuzzy inference system (ANFIS) along with fuzzy data envelopment analysis (FDEA) are developed and employed to assess the performance of the company. Furthermore, the impact of the factors on the company's performance as well as their strengths and weaknesses are identified by conducting a sensitivity analysis on the results. Similarly, a design of experiment is performed to prioritize the factors in the order of importance. Findings The results show that EFQM model has a far greater impact upon the company's performance than HSEE management system. According to the obtained results, it can be argued that integration of HSEE and EFQM leads to the performance improvement in the company. Practical implications In current study, the required data for executing the proposed framework are collected via valid questionnaires which are filled in by the staff of an aviation industry located in Tehran, Iran. Originality/value Managing HR performance results in improving usability, maintainability and reliability and finally in a significant reduction in the commercial aviation accident rate. Also, study of factors affecting HR performance authorities participate in developing systems in order to help operators better manage human error. This paper for the first time presents an intelligent framework based on ANFIS, FDEA and statistical tests for HR performance assessment and analysis with the ability of handling uncertainty and vagueness existing in real world environment.


Radiological placement of chest ports in pediatric oncology patients.
A single center's procedural and follow-up results of radiological chest port placement in pediatric oncology patients are presented. Between July 2002 and December 2003, 37 children (20 boys, 17 girls; age range, 4 months to 16 years; mean 6.7 years) underwent chest port placement. All patients received only one port through the internal jugular vein access, and all of the implantations were performed in the interventional radiology suite. Our database and electronic charts were retrospectively reviewed to obtain follow-up data. All chest ports were successfully implanted. The mean catheter life was 223 days (range: 15-450 days), with a total of 8,258 catheter days. Twenty-eight ports are still in use, four patient deceased, one port was prematurely removed because of a late infection, and four patients were lost to follow-up. Infection rate was 2.7% (0.12/1,000 catheter days). Malfunction due to partial catheter thrombosis and fibrin sheath formation was observed in three patients (8.1% or 0.36/1,000 catheter days), and all were relieved with rt-TPA dwell. None of the ports were revised or removed because of blockage, malposition or difficulty accessing the port. The peri-procedural complication rate was 0%. Chest ports in children can be inserted in interventional radiology suites under imaging guidance with high rates of technical success. The rates of infection and complications are comparable to that of surgically placed ports.


Identification of the C-Terminal GH5 Domain from CbCel9B/Man5A as the First Glycoside Hydrolase with Thermal Activation Property from a Multimodular Bifunctional Enzyme.
Caldicellulosiruptor bescii encodes at least six unique multimodular glycoside hydrolases crucial for plant cell wall polysaccharides degradation, with each having two catalytic domains separated by two to three carbohydrate binding modules. Among the six enzymes, three have one N- or C-terminal GH5 domain with identical amino acid sequences. Despite a few reports on some of these multimodular enzymes, little is known about how the conserved GH5 domains behave, which are believed to be important due to the gene duplication. We thus cloned a representative GH5 domain from the C-terminus of a multimodular protein, i.e. the bifunctional cellulase/mannanase CbCel9B/Man5A which has been reported, and expressed it in Escherichia coli. Without any appending CBMs, the recombinant CbMan5A was still able to hydrolyze a variety of mannan substrates with different backbone linkages or side-chain decorations. While CbMan5A displayed the same pH optimum as CbCel9B/Man5A, it had an increased optimal temperature (90°C) and moreover, was activated by heating at 70°C and 80°C, a property not ever reported for the full-length protein. The turnover numbers of CbMan5A on mannan substrates were, however, lower than those of CbCel9B/Man5A. These data suggested that evolution of CbMan5A and the other domains into a single polypeptide is not a simple assembly; rather, the behavior of one module may be affected by the other ones in the full-length enzyme. The differential scanning calorimetry analysis further indicated that heating CbMan5A was not a simple transition state process. To the best knowledge of the authors, CbMan5A is the first glycoside hydrolase with thermal activation property identified from a multimodular bifunctional enzyme.


Extremely stable soluble high molecular mass multi-protein complex with DNase activity in human placental tissue.
Human placenta is an organ which protects, feeds, and regulates the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. We have obtained and analyzed for the first time an extremely stable multi-protein complex (SPC, ∼ 1000 kDa) from the soluble fraction of three human placentas. By gel filtration on Sepharose-4B, the SPC was well separated from other proteins of the placenta extract. Light scattering measurements and gel filtration showed that the SPC is stable in the presence of NaCl, MgCl2, acetonitrile, guanidinium chloride, and Triton in high concentrations, but dissociates efficiently in the presence of 8 M urea, 50 mM EDTA, and 0.5 M NaCl. Such a stable complex is unlikely to be a casual associate of different proteins. According to SDS-PAGE and MALDI mass spectrometry data, this complex contains many major glycosylated proteins with low and moderate molecular masses (MMs) 4-14 kDa and several moderately abundant (79.3, 68.5, 52.8, and 27.2 kDa) as well as minor proteins with higher MMs. The SPC treatment with dithiothreitol led to a disappearance of some protein bands and revealed proteins with lower MMs. The SPCs from three placentas efficiently hydrolyzed plasmid supercoiled DNA with comparable rates and possess at least two DNA-binding sites with different affinities for a 12-mer oligonucleotide. Progress in study of placental protein complexes can promote understanding of their biological functions.


Emerging pharmacologic therapies for prostate cancer.
The last decade has seen explosive growth in the therapy of prostate cancer. Three areas of therapeutics are emerging: 1) new compounds with novel uses; 2) available compounds with new applications; and 3) new compounds applied to established indications. The novel compounds target specific receptor sites of cancer pathways and attack cancer cells with less effect on normal tissue. Earlyphase trials with compounds targeting the endothelin-A and EGF receptors have shown encouraging results in hormone-refractory prostate cancer. In addition, the Early Prostate Cancer Trial of over 8000 men is currently underway to determine the benefit of adjuvant androgen ablation with bicalutamide in men with localized prostate cancer. Early results show a significant 42% reduction in the progression of the disease in the bicalutamide treatment arm. Further, in large, phase 3 clinical trials in patients needing androgen ablation, the GnRH antagonist abarelix caused no testosterone surge and demonstrated a significantly more rapid decline in serum testosterone to the castrate level than did an LHRH agonist analogue. Abarelix should thus have application as a monotherapy in patients who need a rapid onset of action or are at high risk of complications from the clinical flare seen with LHRH agonists. Abarelix also uniquely caused a sustained decline in serum FSH levels, which have been shown in vitro to stimulate prostate cancer cell growth. If these favorable effects can be duplicated in patients, abarelix might also offer a survival benefit.


Essential role of surface-bound complement factor H in controlling immune complex-induced arthritis.
Factor H (fH) is an endogenous negative regulator of the alternative pathway (AP) that binds polyanions as well as complement activation fragments C3b and C3d. The AP is both necessary and sufficient to develop collagen Ab-induced arthritis (CAIA) in mice; the mechanisms whereby normal control of the AP is overcome and injury develops are unknown. Although primarily a soluble circulating protein, fH can also bind to tissues in a manner dependent on the carboxyl-terminal domain containing short consensus repeats 19 and 20. We examined the role of fH in CAIA by blocking its binding to tissues through administration of a recombinant negative inhibitor containing short consensus repeats 19 and 20 (rfH19-20), which impairs fH function and amplifies surface AP activation in vitro. Administration of rfH19-20, but not control rfH3-5, significantly worsened clinical disease activity, histopathologic injury, and C3 deposition in the synovium and cartilage in wild-type and fH(+/-) mice. In vitro studies demonstrated that rfH19-20 increased complement activation on cartilage extracts and injured fibroblast-like synoviocytes, two major targets of complement deposition in the joint. We conclude that endogenous fH makes a significant contribution to inhibition of the AP in CAIA through binding to sites of immune complex formation and complement activation.


Dynamic nuclear polarization and ESR hole burning in As doped silicon.
We present an experimental study of the Dynamic Nuclear Polarization (DNP) of 29Si nuclei in silicon crystals of natural abundance doped with As in the temperature range 0.1-1 K and in a strong magnetic field of 4.6 T. This ensures a very high degree of electron spin polarization, extremely slow nuclear relaxation and optimal conditions for realization of Overhauser and resolved solid effects. We found that the solid effect DNP leads to the appearance of a pattern of holes and peaks in the ESR line, separated by the super-hyperfine interaction between the donor electron and 29Si nuclei closest to the donor. On the contrary, the Overhauser effect DNP mainly affects the remote 29Si nuclei having the weakest interaction with the donor electron. This leads to the appearance of a very narrow (≈3 mG wide) hole in the ESR line. We studied relaxation of the holes after burning, which is caused by the nuclear spin diffusion. Analyzing the dynamics of the hole in the spectrum with a simple one-dimensional diffusion model leads to a value of the diffusion coefficient D = 8(3) × 10-9 G2 s-1. Our data indicate that the spin diffusion is not completely prevented even in the frozen core near the donors. The emergence of the narrow hole after the Overhauser DNP may be explained by a partial "softening" of the frozen core caused by decoupling of the donor electron and remote 29Si nuclei.


Peripheral victims of the Herald of Free Enterprise disaster.
We report on an unexpected phenomenon following the Herald of Free Enterprise disaster. A series of cross-channel ferry workers referred by their GPs to the Folkestone Mental Health Team, during the three years after the disaster, presented with post-traumatic stress disorder, despite having no direct contact with the disaster as survivors, bereaved relatives or helpers. A retrospective case study is described of 14 ferry crew members presenting with PTSD. Thirteen completed the GHQ60. Evidence is presented of severe functional impairment in this group. It is argued that these subjects are indirect victims of the Herald of Free Enterprise disaster. Ways in which the 'ripples outward' of a major marine accident might extend to such peripheral victims are discussed.


Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal fluid.
B-vitamins (folate, B(12)) are important micronutrients for brain function and essential cofactors for homocysteine (HCY) metabolism. Increased HCY has been related to neurological and psychiatric disorders. We studied the role of the B-vitamins in HCY metabolism in the brain. We studied blood and cerebrospinal fluid (CSF) samples from 72 patients who underwent lumbar puncture. We measured HCY, methylmalonic acid (MMA), and cystathionine by gas chromatography-mass spectrometry; S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) by liquid chromatography-tandem mass spectrometry; and the B-vitamins by HPLC or immunoassays. Concentrations were lower in CSF than serum or plasma for HCY (0.09 vs 9.4 micromol/L), SAH (13.2 vs 16.8 nmol/L), cystathionine (54 vs 329 nmol/L), and holotranscobalamin (16 vs 63 pmol/L), whereas concentrations in CSF were higher for MMA (359 vs 186 nmol/L) and SAM (270 vs 113 nmol/L; all P <0.05). CSF concentrations of HCY correlated significantly with CSF folate (r = -0.46), CSF SAH (r = 0.48), CSF-albumin (r = 0.31), and age (r = 0.32). Aging was also associated with lower concentrations of CSF-folate and higher CSF-SAH. The relationship between serum and CSF folate depended on serum folate: the correlation (r) of serum and CSF-folate was 0.69 at serum folate <15.7 nmol/L. CSF concentrations of MMA and holotranscobalamin were not significantly correlated. CSF and serum/plasma concentrations of vitamin biomarkers are significantly correlated. Older age is associated with higher CSF-HCY and CSF-SAH and lower CSF-folate. These metabolic alterations may be important indicators of low folate status, hyperhomocysteinemia, and neurodegenerative diseases.


[Maternal determination of fetal movements. A sure and simple method of monitoring the pregnancy].
Counting of fetal movements (FM) by the mother-to-be was first recommended by Sadovsky in 1973. Objective studies have demonstrated that 82 to 87 p. cent of FM visible on cardio-topographic tracings or in ultrasound recordings are indeed felt by the pregnant woman. Currently, two protocols are employed: Cardiff's method (counting of 10 FM beginning at 9 a.m.) and Sadovsky's method (counting of FM for one hour at three different times of day). From a practical standpoint, a sudden increase in the incidence of vigorous and forceful movements followed by their stoppage corresponds to compression of the umbilical cord. A decrease in FM may represent a fetal malformation or intrauterine fetal asphyxia. The positive predictive value of counting of FM by the patient in the detection of fetal distress is 64 to 78 p. cent, with a decrease in fetal activity preceding changes in fetal cardiac rhythm by 12 to 96 hours. This simple, sure and readily applicable method ensures continuous monitoring of fetal behavior, while clinical or electronic monitoring is necessarily discontinuous.


An introduction to physical therapy modalities.
Timely and appropriate rehabilitation of musculoskeletal injuries is the most effective way of restoring full function and decreasing the likelihood of recurrence of the same injury. Application of specific physical therapy modalities and therapeutic exercises is based on the stages of healing. A typical physical therapy protocol progresses sequentially through the following phases: pain control, restoring range of motion, restoring strength, neuromuscular retraining, and return to full activity. The commonly used modalities reviewed here include heat, cold, ultrasound, phonophoresis, iontophoresis, and electrical stimulation. In this article we provide a basic review of physical therapy modalities.


Virion swelling is not required for cotranslational disassembly of cowpea chlorotic mottle virus in vitro.
The mechanism by which virions of cowpea chlorotic mottle virus (CCMV) disassemble and allow for translation of the virion RNA is not well understood. Previous models have suggested that virion swelling is required to expose the virion RNA for translation in a process referred to as cotranslational disassembly (M. Brisco, R. Hull, and T. M. A. Wilson, Virology 148:210-217, 1986; J. W. Roenhorst, J. W. M. van Lent, and B. J. M. Verduin, Virology 164:91-98, 1988; J. W. Roenhorst, J. M. Verduin, and R. W. Goldbach, Virology 168:138-146, 1989). Previous work in our laboratory has identified point mutations in the CCMV coat protein which result in virions with altered swelling characteristics (J. Fox, F. G. Albert, J. Speir, and M. J. Young, Virology 227:229-233, 1997; J. M. Fox, X. Zhao, J. A. Speir, and M. J. Young, Virology 222:115-122, 1996). The wild-type and mutant CCMV virions were used to correlate virion swelling with the ability of virion RNA to be translated in a cell-free wheat germ extract. Mutant virions unable to swell (cpK42R) are as infectious as wild-type virions in vivo, and the levels of translated encapsidated virion RNA are similar to those of wild-type virions in vitro. Mutant virions capable of swelling but not of disassembling in vitro (cpR26C) are noninfectious and have severely reduced levels of translation of the encapsidated virion RNA in vitro. These studies suggest that virion swelling is not required for the cotranslational disassembly of CCMV. Additionally, the results indicate that there is a pH-dependent structural transition in the virion, other than swelling, that results in the RNA's being exposed for translation in vitro. An alternative model suggesting that cotranslational disassembly of CCMV involves presentation of the virion RNA through the virion fivefold axis is proposed.


Use of clozapine in primary care.
While clozapine represents a revolutionary advance in the treatment of schizophrenia, it carries with it a formidable side-effect profile. Agranulocytosis may indeed be life-threatening to a small number of patients. The nurse practitioner must be aware of this and other side effects in order to competently care for patients with psychiatric problems. It is also essential that there be a collaborative relationship between the nurse practitioner and a mental health provider. Only through appropriate consultation and referral will the needs of psychiatric patients be met in a timely and comprehensive manner.


Revisiting the Distribution of Thaumetopoea pityocampa (Lepidoptera: Notodontidae) and T. pityocampa ENA Clade in Greece.
In the present work, we sampled individuals of the processionary pine moth, Thaumetopoea pityocampa (Denis and Schiffermüller; Lepidoptera: Notodontidae) from different areas of Greece between 2014 and 2016. These samples were sequenced for a 760-bp long mtDNA COI locus and the haplotypes retrieved clearly showed that the occurrence of T. pityocampa in Greece is being considerably restricted, with only 8 individuals out of the 221 exhibiting T. pityocampa haplotypes and the rest being identified as T. pityocampa ENA clade haplotypes. To that, one haplotype in particular exhibited the highest abundance and broadest geographic distribution, occurring both in mainland and on islands. Our data suggest a rather recent and rapid population expansion of the ENA clade in Greece and a concomitant recent displacement of T. pityocampa. It thus seems that the relation between T. pityocampa and T. pityocampa ENA clade needs to be further and thorough analyzed before the taxonomic status of T. pityocampa ENA clade can be concluded with confidence.


Coexistence of actinomycosis and sialolithiasis in the submandibular gland.
Actinomycosis of the submandibular gland is unusual. A 55-year-old male presented with a right, painless submandibular mass of four-year duration. Physical examination revealed a 4 x 3-cm mass in the submandibular region. Ultrasonography-guided fine needle aspiration from the lesion showed microorganisms compatible with actinomyces colonies in the glandular tissue. The diagnosis was made as actinomycosis of the right submandibular gland accompanied by sialolithiasis. The patient was treated with penicillin G (10 million U/day) for three months, followed by 3 g/day oral penicillin for six months. After this medication, physical examination showed no decrease in the size of the mass and the clinical features remained unchanged. Submandibular gland excision under general anesthesia was performed.


Towards an inclusive cervical cancer screening strategy: approaches for reaching socioeconomically disadvantaged women.
Barriers to prevention and early detection of cancer among the socioeconomically disadvantaged are important areas for public health focus. A community coalition was established in North York, Ontario, to identify a suitable primary prevention initiative, cervical screening among young women of lower economic status. Two pilot communities were selected for the project. Community members, key informants and service providers participated in a series of individual and focus group meetings to identify barriers that impede cervical screening. The benefits and challenges of such a project will be importance to practitioners eager to work collaboratively on primary prevention initiatives. This article will be of interest to nurses wanting to foster a community coalition approach to program design, planning, implementation and evaluation. It will also assist nurses with utilizing needs-based assessment in their work. Although the findings relate to a population of women in a large urban centre, the results will be useful for nurses and other health professionals planning to engage in work related to cervical screening.


Stent thrombosis in patients treated with thienopyridines: clinical description of 10 cases.
Subacute stent thrombosis (SAST) is a major thrombotic complication of coronary stenting. Its occurrence has been substantially reduced by thienopyridine treatment. However, information on clinical profile of patients with SAST in clopidogrel era is limited. In order to define the incidence and factors predisposing to stent thrombosis, we analyzed the computerized angiographic database of three interventional cardiology centers. Out of a total number of 5903 percutaneous coronary interventions (PCIs) with stent implantation, we found 10 patients with SAST (0.17%). The indication for PCI was usually an early invasive approach (90%) during an acute coronary syndrome. All patients were treated with an apparently optimal antithrombotic regimen (90% received heparin or LMWH and 70% received IIb/IIIa receptor inhibitors and all given aspirin). In each of the patients, we could identify high-risk angiographic findings. SAST presentation was always clinically significant with definite myocardial infarction in 100% of cases. 80% of cases occurred during the first six days post PCI. Two patients had a recurrent event. Finally, despite earlier reports of atorvastatin-mediated inhibition of clopidogrel activation we did not find any patient with SAST taking both drugs. Thus, patients with stent thrombosis during thienopyridine treatment usually exhibit high-risk angiographic features. Prospective studies should be performed to elucidate drug interactions that may reduce clopidogrel efficacy and contribute to stent thrombosis.


Effect of acibenzolar-S-methyl phototransformation on its elicitation activity in tobacco cells.
The plant activator acibenzolar-S-methyl (BTH) undergoes phototransformation when exposed to solar radiation. Here we investigated the changes in its elicitation properties on BY-2 tobacco cells at different stages of the photochemical reaction. Both pure BTH and formulated BTH were irradiated in controlled conditions to achieve different extents of conversion. Both pure BTH (900 μM) and Bion® (0.4 g.L-1) induced BY-2 cell death, but BTH photoconverted to an extent of 25 ± 3% lowered the cell death rate. A kinetic study of β-1,3-glucanase and chitinase activities was conducted on BY-2 extracellular medium. Exposure of tobacco cells to either pure BTH or Bion® resulted in a significant increase in the activities of both defense enzymes, which peaked 48 h after the treatment. The pathogenesis-related (PR) protein activities were quantified 48 h after elicitation for a range of phototransformed BTH solutions. The enzyme activities were reduced when BY-2 cells were treated with solutions in which BTH conversion was 22 ± 3%, 42 ± 3% and 100 ± 3%, but were not affected by the solution in which BTH was phototransformed at 60%, suggesting that some of the secondary photoproducts also exhibit eliciting properties. Solar irradiation of BTH thus impairs its elicitation properties, but this impairment depends strongly on the extent of phototransformation.


SOCS: negative regulators of cytokine signaling for immune tolerance.
Cytokines are important intercellular communication tools for immunity. Many cytokines promote gene transcription and proliferation through the JAK/STAT (Janus kinase/signal transducers and activators of transcription) and the Ras/ERK (GDP/GTP-binding rat sarcoma protein/extracellular signal-regulated kinase) pathways, and these signaling pathways are tightly regulated. The SOCS (suppressor of cytokine signaling) family members are representative negative regulators of JAK/STAT-mediated cytokine signaling and regulate the differentiation and function of T cells, thus being involved in immune tolerance. Human genetic analysis has shown that SOCS family members are strongly associated with autoimmune diseases, allergy and tumorigenesis. SOCS family proteins also function as immune-checkpoint molecules that contribute to the unresponsiveness of T cells to cytokines.


[Relationship between clinical findings of patients with bullous pemphigoid and antigens recognized by their circulating antibasement membrane zone antibodies].
Clinical features and extent of bullous pemphigoid lesions differed widely among patients. The pathogenic role of anti-BPAG2 antibodies has been recently demonstrated. The aim of this study was to analyze the relationship between clinical features of bullous pemphigoid patients and the antigens recognized by their serum. One hundred and twelve bullous pemphigoid patients were included in this prospective multicenter study. Inclusion criteria were the following: 1) diagnosis of bullous pemphigoid established on the presence of 3 of the 4 clinical features of bullous pemphigoid, histological picture of bullous pemphigoid and positive direct immunofluorescence; 2) serum available for immunoblotting studies. The clinical and biological findings were prospectively recorded on standard forms. Sera were collected and analyzed using indirect immunofluorescence and immunoblotting on human epidermal extracts. Analysis of patient's clinical features depending on the antigens recognized by their serum showed that patients whose serum contained anti-BPAG1 antibodies had more frequently pruritus, blisters on the lower limbs and a positive indirect immunofluorescence. Patients whose serum contained anti-BPAG2 antibodies had blisters more frequently localized on the head, and a more frequently negative indirect immunofluorescence. Patients whose serum was negative by immunoblotting had less frequently urticarial and/or eczematous lesions, bullae less frequently localized on the lower part of the trunk, abdomen and lower limbs, lower eosinophilia and a more frequently negative indirect immunofluorescence. Patients with circulating anti-BPAG1 antibodies exhibited the most typical, clinical and biological features of bullous pemphigoid.


What are the risk factors for groin strain injury in sport? A systematic review of the literature.
Groin injury is among the most common cited injuries in the sports of ice hockey, soccer, Australian Rules football, calisthenics and cricket. There are very few prospective studies examining risk factors for groin strain injury in sport. There is support for an association of previous injury and greater abductor to adductor strength ratios as well as sport specificity of training and pre-season sport-specific training, as individual risk factors in groin strain injury in athletes. Core muscle weakness or delayed onset of transversus abdominal muscle recruitment may increase the risk of groin strain injury. Debate exists in the literature regarding the role of adductor strength and length as well as age and/or sport experience as risk factors for groin injury. There is no strong evidence to support a causal association for any of these risk factors and groin injury.


Bifunctional Oxygen Reduction/Oxygen Evolution Activity of Mixed Fe/Co Oxide Nanoparticles with Variable Fe/Co Ratios Supported on Multiwalled Carbon Nanotubes.
A facile strategy is reported for the synthesis of Fe/Co mixed metal oxide nanoparticles supported on, and embedded inside, high purity oxidized multiwalled carbon nanotubes (MWCNTs) of narrow diameter distribution as effective bifunctional catalysts able to reversibly drive the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR) in alkaline solutions. Variation of the Fe/Co ratio resulted in a pronounced trend in the bifunctional ORR/OER activity. Controlled synthesis and in-depth characterization enabled the identification of an optimal Fe/Co composition, which afforded a low OER/OER reversible overvoltage of only 0.831 V, taking the OER at 10 mA cm-2 and the ORR at -1 mA cm-2 . Importantly, the optimal catalyst with a Fe/Co ratio of 2:3 exhibited very promising long-term stability with no evident change in the potential for both the ORR and the OER after 400 charge/discharge (OER/ORR) cycles at 15 mA cm-2 in 6 m KOH. Moreover, detailed investigation of the structure, size, and phase composition of the mixed Fe/Co oxide nanoparticles, as well as their localization (inside of or on the surface of the MWCNTs) revealed insight of the possible contribution of the individual catalyst components and their synergistic interaction in the catalysis.


Zero-point energies, the uncertainty principle, and positivity of the quantum Brownian density operator.
High-temperature and white-noise approximations are frequently invoked when deriving the quantum Brownian equation for an oscillator. Even if this white-noise approximation is avoided, it is shown that if the zero-point energies of the environment are neglected, as they often are, the resultant equation will violate not only the basic tenet of quantum mechanics that requires the density operator to be positive, but also the uncertainty principle. When the zero-point energies are included, asymptotic results describing the evolution of the oscillator are obtained that preserve positivity and, therefore, the uncertainty principle.


Study of rare encounters in a membrane using quenching of cascade reaction between triplet and photochrome probes with nitroxide radicals.
Measurements of active encounters between molecules in native membranes containing ingredients, including proteins, are of prime importance. To estimate rare encounters in a high range of rate constants (rate coefficients) and distances between interacting molecules in membranes, a cascade of photochemical reactions for molecules diffusing in multilamellar liposomes was investigated. The sensitised cascade triplet cis-trans photoisomerisation of the excited stilbene involves the use of a triplet sensitiser (Erythrosin B), a photochrome stilbene-derivative probe (4-dimethylamino-4'-aminostilbene) exhibiting the phenomenon of trans-cis photoisomerisation, and nitroxide radicals (5-doxyl stearic acid) to quench the excited triplet state of the sensitiser. Measurement of the phosphorescence lifetime of Erythrosin B and the fluorescence enhancement of the stilbene-derivative photochrome probe, at various concentrations of the nitroxide probe, made it possible to calculate the quenching rate constant k(q)= 1.1 x 10(15) cm2 M(-1) s(-1) and the rate constant of the triplet-triplet energy transfer between the sensitiser and stilbene probe k(T)= 1.0 x 10(12) cm2 M(-1) s(-1). These values, together with the data on diffusion rate constant, obtained by methods utilising various theoretical characteristic times of about seven orders of magnitude and the experimental rate constants of about five orders of magnitude, were found to be in good agreement with the advanced theory of diffusion-controlled reactions in two dimensions. Because the characteristic time of the proposed cascade method is relatively large (0.1 s), it is possible to follow rare collisions between molecules and free radicals in model and biological membranes with a very sensitive fluorescence spectroscopy technique, using a relatively low concentration of probes.


A versatile web app for identifying the drivers of COVID-19 epidemics.
No versatile web app exists that allows epidemiologists and managers around the world to comprehensively analyze the impacts of COVID-19 mitigation. The http://covid-webapp.numerusinc.com/ web app presented here fills this gap. Our web app uses a model that explicitly identifies susceptible, contact, latent, asymptomatic, symptomatic and recovered classes of individuals, and a parallel set of response classes, subject to lower pathogen-contact rates. The user inputs a CSV file of incidence and, if of interest, mortality rate data. A default set of parameters is available that can be overwritten through input or online entry, and a user-selected subset of these can be fitted to the model using maximum-likelihood estimation (MLE). Model fitting and forecasting intervals are specifiable and changes to parameters allow counterfactual and forecasting scenarios. Confidence or credible intervals can be generated using stochastic simulations, based on MLE values, or on an inputted CSV file containing Markov chain Monte Carlo (MCMC) estimates of one or more parameters. We illustrate the use of our web app in extracting social distancing, social relaxation, surveillance or virulence switching functions (i.e., time varying drivers) from the incidence and mortality rates of COVID-19 epidemics in Israel, South Africa, and England. The Israeli outbreak exhibits four distinct phases: initial outbreak, social distancing, social relaxation, and a second wave mitigation phase. An MCMC projection of this latter phase suggests the Israeli epidemic will continue to produce into late November an average of around 1500 new case per day, unless the population practices social-relaxation measures at least 5-fold below the level in August, which itself is 4-fold below the level at the start of July. Our analysis of the relatively late South African outbreak that became the world's fifth largest COVID-19 epidemic in July revealed that the decline through late July and early August was characterised by a social distancing driver operating at more than twice the per-capita applicable-disease-class (pc-adc) rate of the social relaxation driver. Our analysis of the relatively early English outbreak, identified a more than 2-fold improvement in surveillance over the course of the epidemic. It also identified a pc-adc social distancing rate in early August that, though nearly four times the pc-adc social relaxation rate, appeared to barely contain a second wave that would break out if social distancing was further relaxed. Our web app provides policy makers and health officers who have no epidemiological modelling or computer coding expertise with an invaluable tool for assessing the impacts of different outbreak mitigation policies and measures. This includes an ability to generate an epidemic-suppression or curve-flattening index that measures the intensity with which behavioural responses suppress or flatten the epidemic curve in the region under consideration.


Comparison of persistence rates with angiotensin-converting enzyme inhibitors used in secondary and primary prevention of cardiovascular disease.
On average, 50% of patients are noncompliant with drugs for chronic health problems, despite their proven efficacy. It is therefore essential to have real-world data to devise suitable methods for improving persistence with these therapies. To measure and compare persistence rates with the angiotensin-converting enzyme inhibitors (ACEIs) in primary and secondary prevention and their determinants. Two cohorts were reconstructed from the Régie de l'assurance maladie du Québec's databases. The subjects had to be newly treated with ACEIs between January 1, 1998 and December 31, 2000. The primary prevention cohort consisted of 4596 hypertensive patients and the secondary prevention cohort of 1620 patients. The cumulative persistence rates were determined by the Kaplan-Meier method. The determinants of nonpersistence were evaluated with a Cox regression model. The 1-year persistence rates for the nonexclusive use of antihypertensive agents by initial prescribed agent: enalapril, fosinopril, lisinopril, quinapril, and ramipril were 66%, 64%, 69%, 65%, and 72% in the secondary prevention cohort, and of 66%, 72%, 71%, 72%, and 75% in the primary prevention cohort. The adjusted 1.5-year nonpersistence rates in primary prevention were higher for quinapril and enalapril than for ramipril. In secondary prevention all of the ACEIs were equivalent in nonpersistence rate. In secondary prevention cohort, having dyslipidemia, respiratory disease, >or=4 different classes of drugs/month increase the rate of persistence. Among, the primary prevention cohort, the fact of having diabetes, dyslipidemia, respiratory disease, using >or=4 different classes of drugs/month or prior hospitalization increased significantly the rate of persistence. For both cohorts, the fact of having high number of oral doses/day or elevated health-care resource utilization decreased significantly the rate of persistence. The 1.5-year persistence rate was low compared with the threshold of 80% generally accepted. The high-risk patients were less likely to discontinue their treatment. These results can be of help in devising methods for improving the effectiveness of these drugs in routine practice.


Effect of substitution on deep-blue Ir(III) N-heterocyclic carbene (NHC) emitters.
The development of Ir(III)-NHC phosphors that display deep-blue luminescence without sacrificing the high photoluminescence quantum yield (PLQY) has become a pivotal area of research. In this respect, two novel deep-blue Ir-NHC emitters (C1 and C2) with strategically designed pro-carbenic imidazolium ligands (L1 and L2) incorporating a heavy bromine atom at the ligand-scaffold were synthesized in good yields (∼80% for L1, L2 and 65% for C1, C2). The ground and excited state properties of the complexes were photophysically determined and the results were found to be in accordance with theoretical calculations at the DFT and TD-DFT levels. Due to the strong σ-donation of the carbene ligands, complexes C1 and C2 displayed oxidation at low anodic potentials. Both the complexes showed deep-blue emission either in solution (λem ∼ 400-425 nm) or as PMMA-doped films of varying concentrations (λem ∼ 400 nm) with an ∼15 times enhanced PLQY with respect to benchmark Ir-NHC complexes. The strategy of incorporating the heavy bromine atom to reduce the molecular vibrations in C1 and C2 was further supported by ∼250 times reduced non-radiative decay constants (knr) and Huang-Rhys constants of C1 and C2 in comparison to those of the benchmark complexes. These facts were also supported by triplet frequency calculations of C1 and C2 to identify the absence of vibrations.


Correction: Out of the blue finger ischaemia and occult colorectal cancer
Schattner A. Out of the blue finger ischaemia and occult colorectal cancer. BMJ Case Rep 2017 (Epub ahead of print 8 Mar 2017). doi:10.1136/bcr-2016-218779 The correct title of the article is: Out of the blue—finger ischaemia and occult colorectal cancer.


Fatal neurotoxicity of arteether and artemether.
Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. Animals had prolongation of QT interval corrected for rate (QTc) on electrocardiograms (ECGs) with bizarre ST-T segment changes. Prominent neuropathic lesions were noted to be primarily limited to the pons and medulla. Similar lesions with dose-related severity were noted in eight other dogs studied in a second study with intramuscular (IM) administration of AE in sesame oil during a 28-day, dose-ranging study using 5, 10, 15, and 20 mg/kg/day. Injury, graded by a pathologist blinded to the dose group, showed a dose-related, region-specific injury in all animals that was most pronounced in the pons. Further studies in Sprague-Dawley rats using IM administration of AE and artemether (AM) at a dose of 12.5-50 mg/kg/day for 28 days confirmed the onset of a clinical neurologic syndrome with dose-related changes in body weight, activity, and seizure-like activity, stereotypic movement disorders, and ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)


The enlarged translabyrinthine approach for removal of large vestibular schwannomas.
This study was carried out to validate the enlarged translabyrinthine approach for the surgical management of large vestibular schwannomas. A retrospective review of the charts of 53 patients with large tumours removed via the enlarged translabyrinthine approach at the Gruppo Otologico, Piacenza, Italy, during the last five years was carried out. The ability to control large tumours and the achievement of total removal with low morbidity and very few complications, demonstrate that tumour size does not influence the use of the enlarged translabyrinthine approach for managing large tumours.


Modeling and computer simulation of ultrasound imaging systems and human tissues.
A simulator has been developed for an ultrasound linear scan B-mode imaging system. First, a numerical method of calculating field patterns or pulse echo patterns is presented for a full-aperture system with a given transducer geometry in nonattenuating and attenuating media, based on the measured temporal impulse response for a single transducer element immersed in water, and taking into account the variation of attenuation and acoustic velocity in human tissue. The simulator then models and simulates the receiver subsystems in detail using the received pulse echo. In particular, a dynamic inverse filter, to improve the axial resolution, and an unconventional TGC gain function, to reduce the SNR deterioration through logarithmic compression, are proposed. Finally, simulation and experimental results are presented and discussed.


Oligometastatic recurrent prostate cancer detects by fluorine-18-choline positron emission tomography/computed tomography in patients with prostate-specific antigen levels of up to 5 ng/ml.
The aim of this study was to assess the ability of fluorine-18-fluorocholine (F-FCH) PET/computed tomography (CT) to detect oligometastatic disease (OMD) in patients with early recurrence of prostate cancer (PC) [prostate-specific antigen (PSA)≤5 ng/ml]. Between 2010 and 2016, 324 patients with PC and PSA levels of less than or equal to 5 ng/ml were recruited. The mean (SD) age of the patients was 71 (10) years. All patients were treated with a radical prostatectomy±lymphadenectomy. One-hundred and twenty-one patients were under hormonal therapy at the time of PET/CT, whereas 203 were not. The mean (SD) PSA at the time of PET/CT was 1.33 (1.19) ng/ml, the mean (SD) PSA doubling time (PSAdt) was 10 (12) months, and the mean (SD) PSA velocity (PSAvel) was 1.94 (3.31) ng/ml/year. The correlation between continuous and categorical data was assessed using Student's t-test or by analysis of variance and by the χ-test, respectively. Univariate and multivariate analysis was carried out for the identification of clinical variables able to predict the presence of OMD. One-hundred and ninety-three patients had a negative F-FCH PET/CT, whereas 131 (40.4%) had a positive scan. Of these latter patients, 35 had a significant F-FCH uptake in the prostatic fossae, 59 in the lymph nodes, and 37 in bone. PSA levels were significantly different between patients with a positive than those with a negative scan (P<0.001). F-FCH PET/CT was negative in the majority of patients with a PSA of less than or equal to 1 (63.2%) ng/ml. More than 60% of patients with a PSAdt of less than or equal to 6 months had a positive F-FCH PET/CT scan for OMD. PSAvel was higher in patients with a positive scan than those with a negative finding. At univariate analysis, PSA level, PSAdt, and PSAvel were predictors of a positive F-FCH PET/CT for OMD, whereas on multivariate analysis, only PSA level and PSAdt were independent predictors (both P<0.01). Furthermore, PSAdt was the only independent predictor of OMD at the lymph node level. In patients with early recurrence of PC, F-FCH PET/CT is able to detect OMD in 40% of cases. This finding has an important impact on the detection of PC recurrent lesions that could be treated by local therapy to achieve long-term survival or cure.


In vitro nimesulide studies toward understanding idiosyncratic hepatotoxicity: diiminoquinone formation and conjugation.
Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) marketed in more than 50 countries. This drug has caused rare and idiosyncratic but severe hepatotoxicity. The mechanisms associated with and factors responsible for this toxicity remain unknown. One of the nimesulide metabolites identified in human urine is 4-amino-2-phenoxy-methanesulfonanilide (M1). In the current study, we demonstrate that M1 is a stable metabolite that is highly susceptible to facile oxidation by cytochrome P450 enzymes (P450s) to form a reactive diiminoquinone intermediate (M2). Direct detection of M2 was difficult by LC-MS. However, its formation was confirmed indirectly by identification of N-acetyl-cysteine (NAC) adducts of M2. The formation of diiminoquinone M2 was P450 mediated with 2C19 and 1A2 as the two principal P450 enzymes catalyzing M1 oxidation. M1 metabolism irreversibly inhibited 2C19 but activated 1A2 in a time-dependent manner. P450 2C19 exclusively mediated further metabolism of M1 to the amino hydroxynimesulide M3 and its diiminoquinone M4. Similar to M2, M4 is also reactive and can be observed indirectly as its NAC adduct. Nucleophilic addition to diiminoquinone M2 occurs with low regioselectivity, yielding three adducts (the peak area ratio 1:0.08:12). The three regioisomers have the same m/z for [M + H](+), presumably due to nucleophilic addition at the three possible electrophilic sites (C-3, -5, and -6 positions of the sulfonaniline ring). The primary adduct, R, was derived from the attack of the nucleophile at the C-5 position of the sulfonaniline ring and was determined by MS/MS and (1)H and (13)C NMR analyses. The structural assignments were confirmed by chemical synthesis of the adduct R. M2 demonstrated its electrophilic reactivity by selectively alkylating human serum albumin (HSA) at the only free thiol, Cys-34. This suggests the possibility that other proteins may undergo a similar conjugation to form irreversible adducts. Under oxidizing conditions in the presence of cumene hydroperoxide (CHP), the formation of M2 was enhanced, indicating that oxidative stress may accelerate the production of reactive diiminoquinone species (M2 and M4).


[Arthroscopically assisted treatment of acute tibial insertion avulsion fracture of posterior cruciate ligament via posteromedial incision].
To investigate the effectiveness of arthroscopically assisted treatment of acute tibial insertion avulsion fracture of the posterior cruciate ligament (PCL) via posteromedial incision. Between January 2010 and January 2012, 22 patients with acute tibial insertion avulsion of the PCL underwent arthroscopic reduction and fixation via posteromedial incision. There were 14 males and 8 females with an average age of 32 years (range, 18-48 years). The injury causes included traffic accident injury in 14 cases, sport injury in 4 cases, and falling injury in 4 cases. The disease duration ranged from 7 to 16 days (mean, 10 days). Of 22 patient, 14 had simple PCL injury, 6 had PCL injury with meniscus injury, and 2 with cartilage injury. The results of posterior drawer test were positive in all patients. The preoperative Lysholm score was 51.1 +/-3.4. All incisions healed by first intention without infection, deep venous thrombosis of lower limbs, or vessel and nerve injuries. All patients were followed up 12-24 months (mean, 18.4 months). X-ray films showed that all fractures healed with the healing time of 2-4 months (mean, 3 months). The Lysholm score was improved to 96.0 +/-2.2 at 6 months after operation, showing significant difference when compared with preoperative score (t=43.020, P=0.000). Arthroscopically assisted treatment of acute tibial insertion avulsion fracture of the PCL via posteromedial incision is a safe, easy, and effective method.