Skin disease and age-related cataract.
Dermatological conditions and treatments were analysed in a study comparing cataract patients and stringently matched controls. One thousand patients were taken from the cataract waiting list of a specialist eye hospital. For each patient a matched control of the same gender, half-decade of age, and family doctor but without cataract was selected. Venepunctures and eye examinations were performed on both patients and controls; in addition, questionnaire information was obtained from each. Age-related cataract is significantly associated with dermatological abnormality and its treatment, the former association being more significant and more pronounced after 69 years of age. The association of hydrocortisone use after 69 years of age and cataract, however, remains significant even after adjustments for dermatological abnormality and steroid use, suggesting that even among steroid medications hydrocortisone is particularly strongly associated with cataract.


[Emotions of people living with ostomies: existential comprehension].
The objective of this study was to better understand the emotions of ostomy patients and to reinforce their own moral value as beings-in-the-world, through actions of humanized care. This qualitative study followed the existential phenomenology school of thought and was performed at a teaching hospital in Northwestern Paraná-Brazil. Interviews were performed with 15 ostomy patients receiving care at the stomal therapy outpatient clinic during the months of June and July, 2006. The guiding question was: What does being on ostomy patient mean to you? From the analysis, three existential themes emerged: finding oneself in the world of ostomy; daily life with an ostomy bag; and the importance of spirituality in understanding the situation. It was observed that ostomy patients, in their existentiality, express their vicissitudes differently, revealing how painful or pleasant life events can be to them. It is the nurse's challenge to be mindful of their varying forms of expression.


Effects of leptin on melanin-concentrating hormone expression in the brain of lean and obese Lep(ob)/Lep(ob) mice.
The effect of leptin on the expression of melanin-concentrating hormone (MCH) was investigated in lean and genetically obese Lepob/Lepob mice. Murine leptin was subcutaneously infused using osmotic minipumps. The treatment period extended to 7 days and the daily dose of leptin delivered was 100 microgram/kg of body weight. In situ hybridization was used to assess the effects of leptin infusion on the expression of MCH mRNA. MCH levels in the brain (hypothalamus/thalamus and the remaining part), spleen and testis were measured by radioimmunoassay coupled to HPLC of selected tissue extracts. Leptin significantly reduced final body weight, weight of brown adipose tissue, daily food intake in obese mice but not in lean animals. In obese mice, leptin led to a rapid reduction in food intake which reached statistical significance after only 24 h and which led to a significant reduction in the body weight after 3 days of treatment. Leptin restored the normal circulating levels of glucose and insulin in obese mice. The present results mainly provide evidence for a stimulating effect of leptin infusion on the MCH neuronal system. The hypothalamic/thalamic levels of MCH mRNA and peptide were higher in mice treated with leptin than in mice infused with phosphate-buffered saline. The stimulation of MCH neurons appeared particularly intense in obese mice, in which the effects of leptin infusion led to the reduction in MCH content of neuron fibers and terminals. Leptin did not affect spleen and testis MCH contents. In the light of the acknowledged orexigenic effects of MCH, the results of this study questioned the direct role of MCH in the action of leptin on energy balance. The increase in MCH expression following leptin could occur as a mechanism to compensate the decrease in energy deposition led to by leptin. It may also indicate that MCH mediates the metabolic actions of leptin indirectly or else that leptin influences actions of MCH other than those related to the regulation of energy balance.


[Study of HIV-related neuropsychological impairment: a review of methodological aspects].
Research on the HIV-related neuropsychological impairment has been marked by the variety and discrepancy of results, mainly in regards to asymptomatic phases. These discrepancies have been associated with the different types of methodology used in these studies. In this article, we review the main methodological problems present in studies about HIV-related neuropsychological impairment. Our aim is to gather the suggestions contained in the literature, to help overcome these problems in future studies in the field. These suggestions consider the samples used, the way in which they are selected, their size, the sampling methods used, the risk group studied, the criteria for inclusion/exclusion applied, or the selection of the control group. References are also included for the measuring instruments or neuropsychological tests used, statistical methods and criteria for defining the presence of neuropsychological impairment, and for dealing with confounding factors. There can be no doubt that a precise and thorough examination of these issues will make it possible to achieve more conclusive results on the incidence and nature of HIV-related neuropsychological impairment, and the factors that are associated with it.


Sonographic tracking of trunk nerves: essential for ultrasound-guided pain management and research.
Delineation of architecture of peripheral nerves can be successfully achieved by high-resolution ultrasound (US), which is essential for US-guided pain management. There are numerous musculoskeletal pain syndromes involving the trunk nerves necessitating US for evaluation and guided interventions. The most common peripheral nerve disorders at the trunk region include thoracic outlet syndrome (brachial plexus), scapular winging (long thoracic nerve), interscapular pain (dorsal scapular nerve), and lumbar facet joint syndrome (medial branches of spinal nerves). Until now, there is no single article systematically summarizing the anatomy, sonographic pictures, and video demonstration of scanning techniques regarding trunk nerves. In this review, the authors have incorporated serial figures of transducer placement, US images, and videos for scanning the nerves in the trunk region and hope this paper helps physicians familiarize themselves with nerve sonoanatomy and further apply this technique for US-guided pain medicine and research.


Integrating the dynamical systems theory, the task-oriented approach, and the practice framework for clinical reasoning.
ABSTRACT This paper describes the purposeful integration of dynamical systems theory, the occupational therapy task-oriented approach, and Framework II to inform clinical reasoning. Dynamical systems theory provides the clinician with information about how systems interact to influence motor behavior. The task-oriented approach helps the practitioner to clinically improve motor behavior. Framework II gives the clinician guidance in terms of scope of practice and an overarching goal of intervention. Ideological similarities between these three resources for clinical reasoning include client-centeredness, an emphasis on occupation, and interaction between person, task, and environment. The process of clinical reasoning is illustrated using an integrated practice model applied to a clinical example of an adult with a hand injury requiring transfer of hand dominance.


Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study.
Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (-36.1%) than after sham tDCS (-0.7%). PANSS sum scores decreased significantly more with active (-23.4%) than with sham stimulation (-2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia.


Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophy.
In muscular dystrophies quantitative muscle MRI (qMRI) detects disease progression more sensitively than clinical scores. This prospective one year observational study compared qMRI with clinical scores in Duchenne muscular dystrophy (DMD) to investigate if qMRI can serve as a surrogate outcome measure in clinical trials. In 20 DMD patients the motor function measure (MFM) total and subscores (D1-D3) were done for physical examination, and the fat fraction (MFF) of thigh muscle qMRI was obtained using the two-point Dixon method. Effect sizes (ES) were calculated for all measures. Sample size estimation (SS) was done modelling assumed treatment effects. Ambulant patients <7 years at inclusion improved in the MFM total and D1 score (ES 1.1 and 1.0). Ambulant patients >7 years (highest ES in the MFM D1 subscore (1.2)), and non-ambulant patients (highest ES in the total MFM score (0.7)) worsened. In comparison the ES of QMRI was much larger, e.g. SS estimations for qMRI data were up to 17 fold smaller compared to the MFM total score and up to 7 fold to the D1 subscore, respectively. QMRI shows pathophysiological changes in DMD and might serve as a surrogate outcome measure in clinical trials.


Sex and Age Dependencies of Aqueductal Cerebrospinal Fluid Dynamics Parameters in Healthy Subjects.
To assess the influence of age and sex on 10 cerebrospinal fluid (CSF) flow dynamics parameters measured with an MR phase contrast (PC) sequence within the cerebral aqueduct at the level of the intercollicular sulcus. 128 healthy subjects (66 female subjects with a mean age of 52.9 years and 62 male subjects with a mean age of 51.8 years) with a normal Evans index, normal medial temporal atrophy (MTA) score, and without known disorders of the CSF circulation were included in the study. A PC MR sequence on a 3T MR scanner was used. Ten different flow parameters were analyzed using postprocessing software. Ordinal and linear regression models were calculated. The parameters stroke volume (sex: p < 0.001, age: p = 0.003), forward flow volume (sex: p < 0.001, age: p = 0.002), backward flow volume (sex: p < 0.001, age: p = 0.018), absolute stroke volume (sex: p < 0.001, age: p = 0.005), mean flux (sex: p < 0.001, age: p = 0.001), peak velocity (sex: p = 0.009, age: p = 0.0016), and peak pressure gradient (sex: p = 0.029, age: p = 0.028) are significantly influenced by sex and age. The parameters regurgitant fraction, stroke distance, and mean velocity are not significantly influenced by sex and age. CSF flow dynamics parameters measured in the cerebral aqueduct are partly age and sex dependent. For establishment of reliable reference values for clinical use in future studies, the impact of sex and age should be considered and incorporated.


Apical microleakage of root-end cavities prepared by CO2 laser.
This in vitro study in extracted human teeth was designed to compare the degree of dye penetration of root-end cavities prepared by CO2 laser, ultrasonic retrotip, or rotary instrument. Eighty-two human anterior teeth were prepared and obturated with laterally condensed gutta-percha and sealer. Root-end resection was performed at 90 degrees, 3 mm from apex. Root-end cavities were prepared by CO2 laser beam, ultrasonic retrotips, or bur and were filled with amalgam. The teeth were isolated and immersed in basic fuchsin at 36 degrees C for 48 hours. The roots were split longitudinally and examined by a stereomicroscope. Leakage was quantified by linear measurement of dye penetration with the aid of image-analyzing software. Apical leakage in the CO2 laser group was significantly less than in the ultrasonic retrotip and bur groups. The difference between the ultrasonic and bur groups was insignificant. Based on the results of this in vitro study, application of CO2 laser for root-end cavity preparation appears to decrease the apical leakage.


Rural dementia carers: formal and informal sources of support.
Primary carers provide much of the day-to-day care for community-dwelling people living with dementia (PWD). Maintaining that contribution will require a more in-depth understanding of the primary carer role and the support needs that flow from that role. This study explored patterns of formal and informal support utilisation by people caring for a PWD in a rural-regional context. In-depth semi-structured interviews were conducted with 18 rural primary carers of a PWD and thematically analysed. Participant primary carers' almost total commitment to, and absorption in their role and their assumption of ultimate responsibility for the PWD's wellbeing meant that external social context, such as rurality, became less relevant. Carer networks effectively contracted to those key individuals who were central to supporting them in their caring task. External sources of support were tightly managed with strong boundaries around the provision of direct care to the PWD largely excluding all but professional providers. Primary carers are generally categorised along with other family and friends as informal care. However, in assuming primary responsible for the care and wellbeing for the PWD they effectively become the key care provider, suggesting that it would be productive in both research and practice to treat primary carers as key members of a care partnership alongside professional carers, rather than as adjuncts to formal care and/or another client.


Moving alcohol prevention research forward-Part II: new directions grounded in community-based system dynamics modeling.
Given the complexity of factors contributing to alcohol misuse, appropriate epistemologies and methodologies are needed to understand and intervene meaningfully. We aimed to (1) provide an overview of computational modeling methodologies, with an emphasis on system dynamics modeling; (2) explain how community-based system dynamics modeling can forge new directions in alcohol prevention research; and (3) present a primer on how to build alcohol misuse simulation models using system dynamics modeling, with an emphasis on stakeholder involvement, data sources and model validation. Throughout, we use alcohol misuse among college students in the United States as a heuristic example for demonstrating these methodologies. System dynamics modeling employs a top-down aggregate approach to understanding dynamically complex problems. Its three foundational properties-stocks, flows and feedbacks-capture non-linearity, time-delayed effects and other system characteristics. As a methodological choice, system dynamics modeling is amenable to participatory approaches; in particular, community-based system dynamics modeling has been used to build impactful models for addressing dynamically complex problems. The process of community-based system dynamics modeling consists of numerous stages: (1) creating model boundary charts, behavior-over-time-graphs and preliminary system dynamics models using group model-building techniques; (2) model formulation; (3) model calibration; (4) model testing and validation; and (5) model simulation using learning-laboratory techniques. Community-based system dynamics modeling can provide powerful tools for policy and intervention decisions that can result ultimately in sustainable changes in research and action in alcohol misuse prevention.


Dynamic multimodal holograms of conjugated organogels via dithering mask lithography.
Polymeric materials have been used to realize optical systems that, through periodic variations of their structural or optical properties, interact with light-generating holographic signals. Complex holographic systems can also be dynamically controlled through exposure to external stimuli, yet they usually contain only a single type of holographic mode. Here, we report a conjugated organogel that reversibly displays three modes of holograms in a single architecture. Using dithering mask lithography, we realized two-dimensional patterns with varying cross-linking densities on a conjugated polydiacetylene. In protic solvents, the organogel contracts anisotropically to develop optical and structural heterogeneities along the third dimension, displaying holograms in the form of three-dimensional full parallax signals, both in fluorescence and bright-field microscopy imaging. In aprotic solvents, these heterogeneities diminish as organogels expand, recovering the two-dimensional periodicity to display a third hologram mode based on iridescent structural colours. Our study presents a next-generation hologram manufacturing method for multilevel encryption technologies.


The cioAB genes from Pseudomonas aeruginosa code for a novel cyanide-insensitive terminal oxidase related to the cytochrome bd quinol oxidases.
The structural genes for the cyanide-insensitive terminal oxidase (CIO) of Pseudomonas aeruginosa were sequenced. The locus comprised two open reading frames, cioA and cioB, coding for gene products of 488 and 335 amino acid residues with predicted molecular masses of 54241 and 37016 Da respectively. These genes were encoded by a 2.7 kb transcript and probably comprise an operon. Upstream of a major transcriptional start site is a -10 promoter region and, approximately at nucleotides -50 and +13, there are sequences homologous to the binding site of the transcriptional regulator Anr. The deduced amino acid sequences of CioA and CioB are homologous to the cytochrome bd quinol oxidases of Escherichia coli and Azotobacter vinelandii. However, no cytochrome d-like signals were found in wild-type P. aeruginosa strains. An atypical cytochrome d-like signal was seen under low-aeration growth conditions but only in strains in which the cioAB genes were present on a high-copy-number plasmid. The appearance of these cytochrome d-like signals was not paralleled by a concomitant increase in CIO activity. These data support the hypothesis that the CIO of P. aeruginosa does not contain haem d. This raises the possibility that there is a family of bacterial quinol oxidases related to the cytochrome bd of E. coli that can differ in their haem composition from the E. coli paradigm.


Stability of symptom clusters and sentinel symptoms during the first two cycles of adjuvant chemotherapy.
Ascertaining the stability of symptom clusters and identifying sentinel symptoms have been top priorities in symptom cluster research. Identifying sentinel symptoms would help to determine the underlying mechanisms of symptom clusters and facilitate effective symptom management. This study aimed to evaluate the stability of symptom clusters during the 1st and 2nd cycles of adjuvant chemotherapy (CTx) and to identify sentinel symptoms. This is a secondary data analysis of data from the Paradigm Shift in Chemotherapy-Induced Nausea and Vomiting (PS-CINV) study. Data utilized were from cancer patients who received adjuvant chemotherapy and completed symptom evaluation in the 1st and 2nd cycles (N = 209). The severity of 20 symptoms was evaluated on a 0-to-10 numeric rating scale. Principal component and hierarchical cluster analyses identified symptom clusters, and principal variable analysis identified sentinel symptoms. Among 20 symptoms, 13 symptoms formed 4 symptom clusters in the 1st cycle: a physical-psychological (pain, dyspnea, sleep disturbance, anxiety, depression), a gastrointestinal (nausea, loss of appetite, taste change), a fatigue-cognitive (fatigue, difficulty concentrating, drowsiness), and a urosexual (urinary problem, sexual problem) symptom cluster. During the 2nd cycle, stable symptom clusters were identified, with merging of the physical-psychological and fatigue-cognitive symptom clusters, resulting in three clusters. Sentinel symptoms were identified in the following order: anxiety, loss of appetite and fatigue (1st cycle) and loss of appetite, depression, and fatigue (2nd cycle). Symptom clusters demonstrated phase-specific stability. The current study identified a core set of symptoms that form stable symptom clusters during the 1st and 2nd cycles of CTx. Principal variable analysis identified sentinel symptoms which could facilitate efficient symptom management.


Alcohol consumption and mammographic density in the Danish Diet, Cancer and Health cohort.
We examined the association between alcohol consumption and mammographic density (MD) considering in detail the time of exposure and the type of alcohol. Of 5,356 women (4,489 post-menopausal) from the Danish Diet, Cancer and Health cohort (1993-1997) who attended mammographic screening in Copenhagen (1993-2001), we used MD (mixed/dense or fatty) assessed at the first screening after cohort entry. Alcohol consumption was assessed at the time of recruitment. Logistic regression was used to estimate associations [odds ratios (OR), 95% confidence intervals (CI)] between alcohol consumption and MD. The mean age was 56.2 years, 56.5% of women had mixed/dense MD, and 91.8% were alcohol consumers. There was no association between current alcohol consumption and MD at baseline (age 50-65, on average 1 year before MD assessment) neither between age at drinking initiation and MD, in the fully adjusted model. There was a borderline statistically significantly increased OR of having mixed/dense MD in women who consumed > 7 drinks/week at age 20-29 (1.31, 95% CI 1.00-1.72) compared to non-drinkers in this age group, and no effect of drinking at age 30-39, 40-49 or after > 50 years, when adjusting for current drinking. However, when considering different types of alcohol, drinking spirits at age 20-29 was positively associated with mixed/dense breast (3-7 drinks/week: OR 1.74, 95% CI 1.12-2.72); >7 drinks/week: (OR 1.76, 95% CI 0.73-4.23). No consistent pattern was found with beer, wine, or fortified wine. We found higher MD among women with high alcohol consumption in early adulthood (ages 20-29), in those drinking spirits.


A 2018 Italian and Romanian Survey on Subclinical Hypothyroidism in Pregnancy.
Pregnancy induces changes in thyroid function, and thyroid dysfunction during gestation is associated with adverse outcomes. We examined the management of subclinical hypothyroidism and chronic autoimmune thyroiditis in pregnancy among Italian and Romanian endocrinologists. Members of the Associazione Medici Endocrinologi (AME) and Romanian Society of Endocrinology (RSE) were invited to participate in a web-based survey investigating the topic. A total of 902 individuals participated in the survey, 759 of whom completed all sections. Among the respondents, 85.1% were aware of the 2017 American Thyroid Association guidelines about thyroid disease and pregnancy, and 82.9% declared that thyroid-stimulating hormone (TSH) screening at the beginning of pregnancy should be warranted. In a patient negative for peroxidase antibodies, 53.6% considered 2.5 mIU/L and 26.2% considered 4.0 mIU/L as the upper normal limit of TSH, and 50% would treat a patient with TSH 3.5 mIU/L with levothyroxine. About 20% did not suggest iodine supplementation. Isolated hypothyroxinemia detected in the first trimester would be treated by 40.8%. In patients undergoing ovarian stimulation, a TSH < 2.5 mIU/L would be targeted by 70%. Respondents globally appeared well informed about the management of thyroid autoimmunity and subclinical hypothyroidism in pregnancy. A more aggressive attitude in implementing iodine supplementation would be desirable. Most endocrinologists were convinced about an evident association between mild thyroid impairment and adverse outcomes in pregnancy, thus using a TSH value of 2.5 mIU/L as the threshold for diagnosing hypothyroidism and starting levothyroxine in pregnant women.


Expression of the Cholecystokinin-B Receptor in Neoplastic Gastric Cells.
Gastric cancer is an important disease due to its high mortality. Despite the decline in frequency, most cases are discovered late in its course, and most of the cancer patients die within a few years of diagnosis. In addition to Helicobacter pylori gastritis, gastrin is considered an important factor in the development of this disease, and thus, cholecystokinin-B receptor (CCKBR) becomes of interest. The aim of our study was to explore whether CCKBR is expressed in stomach cancers. Thirty-seven tumors from 19 men and 18 women diagnosed with either adenocarcinoma or neuroendocrine neoplasm (NENs) were included in this study. The tumors were classified into 29 adenocarcinomas and eight NENs. Immunohistochemistry with antibodies against chromogranin A (CgA), synaptophysin and CCKBR, and in situ hybridization with probes against CgA, CCKBR and histidine decarboxylase were used to further explore these tumors. Thirty-three (89%) of the tumors expressed CCKBR protein, whereas only 20 (54%) of all tumors expressed CCKBR mRNA. Of the 20 tumors expressing CCKBR mRNA, eight were NENs and 12 were adenocarcinoma. The highest amount of CCKBR was expressed in NEN. Interestingly, a high degree of co-expression of CCKBR and CgA was observed when the two markers were examined together with in situ hybridization. In conclusion, we found that all eight NENs expressed CCKBR and neuroendocrine markers in a majority of tumor cells. The same markers were also expressed in a proportion of adenocarcinomas supporting the view that gastrin is important in the development of gastric cancer.


Adaptive thermoregulation in golden spiny mice: the influence of season and food availability on body temperature.
We studied the effect of food supplementation during summer and winter in seminatural field conditions on thermoregulation of a desert rodent, the golden spiny mouse Acomys russatus. We hypothesized that (a) under natural food availability (control conditions), mice will use less precise thermoregulation (i.e., an increase in the variance of body temperature [T(b)]) during winter because of low ambient temperatures (T(a)'s) and low food availability and during summer because of low food and water availability; (b) food supplementation will result in more precise thermoregulation during winter, but the effect will be smaller during summer because variation in T(b) in summer is also driven by water availability during that period. We found that under natural food availability, spiny mice thermoregulated more precisely during summer than during winter. They spent more time torpid during summer than during winter even when food was supplemented (although summer nights are shorter), allowing them to conserve water. Supplementing food resulted in more precise thermoregulation in both seasons, and mice spent less time torpid. In summer, thermoregulation at high T(a)'s was less precise, resulting in higher maximum T(b)'s in summer than in winter and when food was supplemented, in accord with the expected effect of water shortage on thermoregulation. Our results suggest that as expected, precise thermoregulation is beneficial when possible and is abandoned only when the costs of homeothermy outweigh the benefits.


Continuous-variable quantum computing in optical time-frequency modes using quantum memories.
We develop a scheme for time-frequency encoded continuous-variable cluster-state quantum computing using quantum memories. In particular, we propose a method to produce, manipulate, and measure two-dimensional cluster states in a single spatial mode by exploiting the intrinsic time-frequency selectivity of Raman quantum memories. Time-frequency encoding enables the scheme to be extremely compact, requiring a number of memories that are a linear function of only the number of different frequencies in which the computational state is encoded, independent of its temporal duration. We therefore show that quantum memories can be a powerful component for scalable photonic quantum information processing architectures.


Building a Common Language to Facilitate Discussion Among Stakeholders in Work Disability: A Consensus Group Approach.
Work disability stakeholders may not share the same understanding and solutions among themselves or with researchers, causing misunderstandings and hindering collaboration regarding solutions for preventing work disability. To reduce such differences, this study sought to build a common vocabulary among stakeholders and researchers, using a transdisciplinary research framework. A consensus method based on a constructivist approach was used. A theoretical sampling method was applied to identify researchers or stakeholders representing one of the four systems in the work disability paradigm. A preliminary set of definitions for key terms was assessed using a Web-based questionnaire. It documented participants' level of agreement with each term's inclusion and relevance in the field, and the clarity of the definition, while soliciting suggestions for other terms or clearer definitions. Disagreements were discussed at group meetings, yielding consensus on the final terms and definitions. Eleven stakeholders representing patients, employers, unions, healthcare professionals, and legislative and insurance systems, along with 10 multidisciplinary researchers, participated. The questionnaire yielded initial consensus on the inclusion and definitions of 49 terms, and 109 suggestions mostly for modified definitions (average = 6 suggestions/term). Two preliminary terms were excluded and three terms were added. Ultimately, 80 terms and their definitions yielded consensus. The process we used to build a common vocabulary was carried out within a transdisciplinary framework. It required a constructivist approach, promoting idea exchanges among participants and co-construction of generally agreed results. The results were rooted in local contexts, thus ensuring the same reference points, regardless of participants' different understandings.


Multiple Non-Essential Transition Metals Are Accumulated in Carotid Atherosclerotic Plaques: Missing Link in Atherosclerosis?
Population studies revealed that metal exposure through food, environment, and smoking was related with increased risk of cardiovascular disease. In this study, we determined complex chemical elements in surgical carotid endarterectomy specimens and carotid tissues from autopsies without atherosclerosis. Atherosclerotic plaques from 41 endarterectomies and normal carotid tissue from 30 autopsies were collected and elemental composition was determined by inductively coupled plasma optical emission spectrometry (ICP-OES) method. Eleven (26.8%) patients never smoked in carotid endarterectomy group. One patient was brass souvenir worker and one was goldsmith and others did not have direct contact with metals in the carotid endarterectomy group. Na, Cu, Mn, Bi, Co, Mo, Ni, Pb, Sb, Se, Sn, Ti, and W levels were not different between two groups. Bi, Co, Mo, Pb, Ti, and W were below the detection limit of ICP-OES in both groups. Concentrations of Mg, K, Ca, P, Fe, B, Zn, Al, As, Cr, Pt, and Hg were significantly higher in carotid endarterectomies than normal carotid tissue samples. Cd and S values were significantly higher in autopsy samples. There is significant multiple non-essential transition metal accumulation in atherosclerotic carotid endarterectomy plaques. The cardiovascular consequences of metal toxicity have not been researched adequately due to large emphasis on the role of cholesterol in atherosclerosis. High level of non-essential transition metal elements in the carotid atherosclerotic plaques may add the missing link of atherogenesis and may necessitate new treatment and prevention strategies in carotid disease if confirmed by further research.


The effect of tandem substitutions on the correlation between synonymous and nonsynonymous rates in rodents.
Nonsynonymous substitutions in DNA cause amino acid substitutions while synonymous substitutions in DNA leave amino acids unchanged. The cause of the correlation between the substitution rates at nonsynonymous (K(A)) and synonymous (K(S)) sites in mammals is a contentious issue, and one that impacts on many aspects of molecular evolution. Here we use a large set of orthologous mammalian genes to investigate the causes of the K(A)-K(S) correlation in rodents. The strength of the K(A)-K(S) correlation exceeds the neutral theory expectation when substitution rates are estimated using algorithmic methods, but not when substitution rates are estimated by maximum likelihood. Irrespective of this methodological uncertainty the strength of the K(A)-K(S) correlation appears mostly due to tandem substitutions, an excess of which is generated by substitutional nonindependence. Doublet mutations cannot explain the excess of tandem synonymous-nonsynonymous substitutions, and substitution patterns indicate that selection on silent sites is the likely cause. We find no evidence for selection on codon usage. The nature of the relationship between synonymous divergence and base composition is unclear because we find a significant correlation if we use maximum-likelihood methods but not if we use algorithmic methods. Finally, we find that K(S) is reduced at the start of genes, which suggests that selection for RNA structure may affect silent sites in mammalian protein-coding genes.


The "small, dark tonsil" in patients presenting with metastatic cervical lymphadenopathy from an unknown primary.
When squamous cell carcinoma (SCC) involves the palatine tonsils, they are generally enlarged and demonstrate intermediate to high signal intensity on T2-weighted MR images and enhance after gadolinium administration. We have identified two patients with SCC of the tonsil where the affected tonsil has low signal intensity on T2-weighted MR images and is smaller than the contralateral normal tonsil. We present the "small, dark tonsil" as an alternative imaging presentation of SCC and a new sign to look for when evaluating the patient with metastatic lymphadenopathy from an unknown primary tumor.


Effects of A School-Based Intervention on BMI and Motor Abilities in Childhood.
Obesity in childhood is increasing worldwide. To combat overweight and obesity in childhood, the school-based Children's Health InterventionaL Trial (CHILT) project combines health education and physical activity. This paper examines the effect of intervention on the body mass index (BMI) and motor abilities after 20.8 ± 1.0 months in 12 randomly selected primary schools compared with 5 randomly selected control schools. The anthropometric data were assessed, BMI was calculated. Coordination was determined by lateral jumping and endurance performance by a 6-minute run. No difference in the prevalence of overweight and obesity was found between the intervention (IS) and control schools (CS) either at baseline or following intervention (each p > 0.05). The increase in the number of lateral jumps was significantly higher in the IS than in the CS (p < 0.001). For the 6-minute run the increase in distance run was significantly improved in IS (p = 0.020). All variables were controlled for gender and age. Overweight and obese children in both IS and CS produced significantly lower scores in coordination and endurance tasks than normal and underweight children during both examinations (each p ≤ 0.001), adjusted for gender and age. Preventive intervention in primary schools offers an effective means to improve motor skills in childhood and to break through the vicious circle of physical inactivity - motor deficits - frustration - increasing inactivity possibly combined with an excess energy intake and weight gain. To prevent overweight and obesity these measures have to be intensified. Key PointsSchool-based prevention improves motor abilities in primary school children.The incidence of obesity is not influenced by school-based intervention.To prevent obesity in early childhood the measures have to be intensified and parents should be included.


[A brain tissue bank in a neuropathology laboratory. Basic methodology].
The Meixoeiro Hospital Brain Bank (BB) was established at the end of 2002. A BB is a tissue collection and storage system, established under the best conditions to carry out prospective morphological, biochemical or molecular studies. The BB should ideally be supported by a donor program, although samples may also be obtained from autopsy material from patients with neurodegenerative diseases. Recruitment of control cases from brains without neurological diseases is basic. The main goal of a BB is to provide brain tissue for research. Each case requires accurate clinical data, a definite diagnosis and optimal conditions of tissue preservation. The use of protocols to standardize the handling and processing of tissues, data recruitment and neuropathological diagnosis is fundamental to assure the quality and homogeneity of samples. Close collaboration between neuropathologists, neurologists and other specialists is essential in all the process. Although important advances in the tissue banking field have been achieved, the number of donors in Spain still remains low. Stronger institutional support as well as public awareness through better diffusion of the information is necessary to increase the number of donors and improve BB development.


Epigenetic silencing of a Ca(2+)-regulated Ras GTPase-activating protein RASAL defines a new mechanism of Ras activation in human cancers.
Ras has achieved notoriety as an oncogene aberrantly activated in multiple human tumors. Approximately 30% of all human tumors express an oncogenic form of this GTPase that is locked in an active conformation as a result of being insensitive to Ras GTPase-activating proteins (GAPs), proteins that normally regulate the inactivation of Ras by enhancing its intrinsic GTPase activity. Besides oncogenic mutations in Ras, signaling by wild-type Ras is also frequently deregulated in tumors through aberrant coupling to activated cell surface receptors. This indicates that alternative mechanisms of aberrant wild-type Ras activation may be involved in tumorigenesis. Here, we describe another mechanism through which aberrant Ras activation is achieved in human cancers. We have established that Ras GTPase-activating-like protein (RASAL), a Ca(2+)-regulated Ras GAP that decodes the frequency of Ca(2+) oscillations, is silenced through CpG methylation in multiple tumors. With the finding that ectopic expression of catalytically active RASAL leads to growth inhibition of these tumor cells by Ras inactivation, we have provided evidence that epigenetically silencing of this Ras GAP represents a mechanism of aberrant Ras activation in certain cancers. Our demonstration that RASAL constitutes a tumor suppressor gene has therefore further emphasized the importance of Ca(2+) in the regulation of Ras signaling and has established that deregulation of this pathway is an important step in Ras-mediated tumorigenesis.


Hand-Assisted Laparoscopic Hysterectomy for Large Uteri.
To determine whether laparoscopic hand-assisted hysterectomy for a large uterus had different surgical outcomes compared with traditional open hysterectomy. Retrospective cohort study (Canadian Task Force classification II-2). Academic tertiary care hospital. Women who had undergone laparoscopic hand-assisted hysterectomy for a large uterus were included as the hand-assist group. The control group comprised patients with similar final specimen weight (>1 kg), characteristics (body mass index, age), and surgical history, who underwent open hysterectomy for a large uterus. Laparoscopic hysterectomy using a hand-assist port for laparoscopic portion of the case. The 2 groups were similar in terms of specimen weight (median, 1765.5 g for hand-assist vs 1215.50 g for controls; p = .29). In univariate analysis, the median operating time was longer in the hand-assist group compared with controls (241.5 minutes vs 185.0 minutes; p = .002), whereas median length of stay was shorter in the hand-assist group (1.0 day vs 3.0 days; p < .0001). These differences remained significant after adjustment for potential confounders in multivariable analysis (p < .05). There was no difference in estimated blood loss (p > .05) between the 2 groups, although the change in hemoglobin was less in the hand-assist group compared with controls in multivariable analysis (adjusted mean.74 vs. 1.8; p = .04). Complications were divided into intraoperative complications (transfusion, consultation, bowel injury, bladder injury, ureter injury, and other), hospital postoperative complications (reoperation, transfusion, slow return of bowel function, ileus, poor pain control, fever of unknown origin, venous thromboembolism, pneumonia, and neuropathy), and complications after discharge (readmission, wound infection). The 2 groups had a similar low rate of complications (p > .05). Laparoscopic hand-assist hysterectomy is a feasible alternative to open hysterectomy in patients with a large uterus.


Hearing Aid Benefit in Patients with Mild Sensorineural Hearing Loss: A Systematic Review.
Untreated sensorineural hearing loss (SNHL) is associated with chronic health-care conditions, isolation, loneliness, and reduced quality of life. Although hearing aids can minimize the negative effects of SNHL, only about one in five persons with SNHL seeks help for communication problems. Many persons wait 10 yr or more from the time they first notice a problem before pursuing amplification. Further, little information about the benefits of amplification is available for persons with mild SNHL (MSNHL), who likely defer treatment even longer. To conduct a systematic review to weigh the evidence regarding benefits derived from the use of amplification by adults with MSNHL. Systematic review with meta-analysis. Adult hearing aid wearers with bilateral average pure-tone thresholds ≤45 dB HL at 500, 1000, 2000, and 4000 Hz. PubMed, Cumulative Index to Nursing and Allied-Health Literature, Cochrane Collaboration, and Google Scholar were searched independently by the authors during September 2013. The authors used a consensus approach to assess the quality and extract data for the meta-analysis. Of 106 articles recovered for full-text review, only 10 met inclusion criteria (at least Level IV of evidence and involved and reported separate pre-/postfitting hearing aid outcomes for patients with MSNHL). Included studies involved mainly middle-aged to elderly patients using hearing aids of various styles and circuitry. Results from all of the studies indicated positive benefits from amplification for patients with MSNHL. Data from five studies were suitable for a meta-analysis, which produced a small-to-medium effect size of 0.85 (95% confidence intervals = 0.44-1.25) after adjusting for a small publication bias. This evidence confirmed benefits from the use of amplification in adults with MSNHL. Evidence exists supporting the notion that adults with MSNHL benefit from hearing aids. This information is important and useful to audiologists, patients, and third-party payers, even considering that most of the studies in this systematic review were limited, somewhat dated, and used analog and early digital technology available when the studies were conducted. Clinical recommendations may be even stronger as future studies become available for patients fit with modern styles and high-technology hearing aids.


Empathy is key in the development of moral injury.
Background: Moral injury is a relatively new field within psychotraumatology that focuses on understanding and treating psychosocial symptoms after exposure to potentially morally injurious events (PMIE's). There are currently three models of the development of moral injury which centre around the influence of attributions, coping and exposure. While the capacity for empathy is known to underlie moral behaviour, current models for moral injury do not explicitly include empathy-related factors. Objective: This paper aims to make a case for complementing current models of the development of moral injury with the perception-action model of empathy (PAM). Method: In this paper, the perception-action mechanism of empathy and the empathic behaviour that it may initiate, are described. The PAM states that perception of another person's emotional state activates the observer's own representations of that state. This forms the basis for empathic behaviour, such as helping, by which an observer tries to alleviate both another person's and their own, empathic, distress. In this paper it is proposed that in PMIE's, empathic or moral behaviour is expected but not, or not successfully, performed, and consequently distress is not alleviated. Factors known to influence the empathic response, including attention, emotion-regulation, familiarity and similarity, are hypothesized to also influence the development of moral injury. Results: Two cases are discussed which illustrate how factors involved in the PAM may help explain the development of moral injury. Conclusions: As empathy forms the basis for moral behaviour, empathy-related factors are likely to influence the development of moral injury. Research will have to show whether this hypothesis holds true in actual practice.


Osteogenic Potential of Human Dental Pulp Stem Cells (hDPSCs) Growing on Poly L-Lactide-Co-Caprolactone and Hyaluronic Acid (HYAFF-11TM) Scaffolds.
Bone tissue engineering using different scaffolds is a new therapeutic approach in regenerative medicine. This study explored the osteogenic potential of human dental pulp stem cells (hDPSCs) grown on a hydrolytically modified poly(L-lactide-co-caprolactone) (PLCL) electrospun scaffold and a non-woven hyaluronic acid (HYAFF-11™) mesh. The adhesion, immunophenotype, and osteogenic differentiation of hDPSCs seeded on PLCL and HYAFF-11™ scaffolds were analyzed. The results showed that PLCL and HYAFF-11™ scaffolds significantly supported hDPSCs adhesion; however, hDPSCs' adhesion rate was significantly higher on PLCL than on HYAFF-11™. SEM analysis confirmed good adhesion of hDPSCs on both scaffolds before and after osteogenesis. Alizarin red S staining showed mineral deposits on both scaffolds after hDPSCs osteogenesis. The mRNA levels of runt-related transcription factor 2 (Runx2), collagen type I (Coll-I), osterix (Osx), osteocalcin (Ocn), osteopontin (Opn), bone sialoprotein (Bsp), and dentin sialophosphoprotein (Dspp) gene expression and their proteins were higher in hDPSCs after osteogenic differentiation on both scaffolds compared to undifferentiated hDPSCs on PLCL and HYAFF-11™. These results showed that PLCL scaffolds provide a better environment that supports hDPSCs attachment and osteogenic differentiation than HYAFF-11™. The high mRNA of early osteogenic gene expression and mineral deposits observed after hDPSCs osteogenesis on a PLCL mat indicated its better impact on hDPSCs' osteogenic potential than that of HYAFF-11™, and hDPSC/PLCL constructs might be considered in the future as an innovative approach to bone defect repair.


Author Correction: Epigallocatechin gallate, folic acid, vitamin B12, and hyaluronic acid significantly increase apoptosis and p53 expression in HeLa cells.
Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (11): 5240-5245-DOI: 10.26355/eurrev_202306_32642-PMID: 37318498-published online on June 13, 2023. After publication, the authors discovered that Prof. C. Gentili's affiliation was wrong as he has never been a member of the Italian Society of Colposcopy and Cervicovaginal Pathology (SICPCV). The authors never found the mistake during the review process nor requested a correction before publication. Therefore, the second affiliation has been corrected as follows: Pathologist, Independent Practitioner, Carrara, Italy. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32642.


The quality of hospital work environments and missed nursing care is linked to heart failure readmissions: a cross-sectional study of US hospitals.
Threats to quality and patient safety may exist when necessary nursing care is omitted. Empirical research is needed to determine how missed nursing care is associated with patient outcomes. The aim of this study was to examine the relationship between missed nursing care and hospital readmissions. Cross-sectional examination, using three linked data sources-(1) nurse survey, (2) patient discharge data from three states (California, New Jersey and Pennsylvania) and (3) administrative hospital data- from 2005 to 2006. We explored the incidence of 30-day readmission for 160 930 patients with heart failure in 419 acute care hospitals in the USA. Logistic regression was used to assess the effect of missed care on the odds of readmission, adjusting for patient and hospital characteristics. The most frequently missed nursing care activities across all hospitals in our sample included talking to and comforting patients (42.0%), developing and updating care plans (35.8%) and educating patients and families (31.5%). For 4 of the 10 studied care activities, each 10 percentage-point increase in the number of nurses reporting having missed the activity was associated with an increase in the odds of readmission by 2-8% after adjusting for patient and hospital characteristics. However, missed nursing care was no longer a significant predictor of readmission once adjusting for the nurse work environment, except in the case of the delivery of treatments and procedures (OR 1.08, 95% CI 1.02 to 1.14). Missed care is an independent predictor of heart failure readmissions. However, once adjusting for the quality of the nurse work environment, this relationship is attenuated. Improvements in nurses' working conditions may be one strategy to reduce care omissions and improve patient outcomes.


Isolation and characterization of the follicle-stimulating hormone beta subunit gene and 5' flanking region of the Chinook salmon.
In this study we have isolated the follicle-stimulating hormone beta subunit gene from the Chinook salmon (csFSHbeta). This gene encodes for a protein that is highly similar to those isolated from other salmonids and shares all of the structural constraints seen in mammalian gonadotropins, including twelve conserved cysteines and a putative N-linked glycosylation site. The organization of the gene follows the conserved pattern regarding the numbers and positions of the introns, although the csFSHbeta gene contains a particularly large 6.2-kb first intron due to the inclusion of several transposon-like elements. Isolation of 1.2 kb of the 5' flanking region of the csFSHbeta gene and subsequent analysis in silico have revealed a number of putative elements which appear highly conserved in teleost FSHbeta gene promoters and are thus likely involved in basal and hormone-induced transcriptional regulation. The functionality of this 1.2-kb fragment in driving expression of a reporter gene and its response to GnRH was shown in gonadotropes, while the overexpression of AP-1 factors, Sf-1, estrogen receptor or Smad1 revealed that the promoter is responsive to these transcription factors. Our current study has opened the way for future analysis to verify the role of these factors in mediating hormonally induced transcription of this gene.


Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder.
Autism spectrum disorder (ASD) is characterized by core deficits in social behavior, communication, and behavioral flexibility. Several lines of evidence indicate that oxytocin, signaling through its receptor (OXTR), is important in a wide range of social behaviors. In attempts to determine whether genetic variations in the oxytocin signaling system contribute to ASD susceptibility, seven recent reports indicated association of common genetic polymorphisms in the OXTR gene with ASD. Each involved relatively small sample sizes (57 to 436 families) and, where it was examined, failed to identify association of OXTR polymorphisms with measures of social behavior in individuals with ASD. We report genetic association analysis of 25 markers spanning the OXTR locus in 1,238 pedigrees including 2,333 individuals with ASD. Association of three markers previously implicated in ASD susceptibility, rs2268493 (P = 0.043), rs1042778 (P = 0.037), and rs7632287 (P = 0.016), was observed. Further, these genetic markers were associated with multiple core ASD phenotypes, including social domain dysfunction, measured by standardized instruments used to diagnose and describe ASD. The data suggest association of OXTR genetic polymorphisms with ASD, although the results should be interpreted with caution because none of the significant associations would survive appropriate correction for multiple comparisons. However, the current findings of association in a large independent cohort are consistent with previous results, and the biological plausibility of participation of the oxytocin signaling system in modulating social disruptions characteristic of ASD, suggest that functional polymorphisms of OXTR may contribute to ASD risk in a subset of families.


Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice.
Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.


Cell death induced by MPPa-PDT in prostate carcinoma in vitro and in vivo.
Lack of effective photosensitizers has become a major limit for extensive application of photodynamic therapy. In this study, the photocytotoxicity and mode of death induced by a newly developed photosensitizer MPPa, a derivative of chlorophyll a, were investigated in PC-3M cell line, a highly metastatic variant of poorly differentiated androgen-independent proctanec adenocarcinoma PC-3. MTT reduction assay was used to measure cytotoxicity in both PC-3M and HUVEC, after which a flow cytometer was used to measure apoptotic rate and cell cycle, and then Caspase-3, -8, -9 were investigated. Finally, an animal model was set up to embody the curative effect and for histopathological examinations. The photocytotoxicity of MPPa showed both light- and drug-dose dependent characteristics and no significant dark cytotoxicity was observed in PC-3M cells. In HUVEC, MPPa exhibited an obviously low cytotoxicity. By other in vitro studies, we found MPPa-PDT induced apoptotic mainly via the mitochondrial/Caspase-9/Caspase-3 pathway and could restrain the cell cycle progression from the more sensitive G0/G1-phases. In vivo, the tumour growth was significantly inhibited after PDT, and many apoptotic cells could be seen by histopathological examinations. These results indicate the death way of cells induced by MPPa is mainly via mild apoptotic and the cure effect is obvious, suggesting that MPPa is a potential photosensitizer of photodynamic therapy for prostate cancer.


Growth curve and diet density affect eating motivation, behavior, and body composition of broiler breeders during rearing.
The aim of this work has been to assess the effect of diet density [control (CON) or 15% diluted (DIL)] and growth curve [recommended by the genetic line (RBW) or 15% heavier (HBW)] and their interaction on BW uniformity, feeding motivation, behavior, and body composition of broiler breeder pullets. A total of 3,000 one-day-old female breeders Ross 308, distributed in 20 pens, was randomly assigned to each treatment. Feed allowance was weekly adjusted to reach the desired BW. Feed was provided as pelleted (zero to 3 wk) and crumble (4 to 19 wk). Time eating was measured at 7, 11, and 19 weeks. A feeding rate test was performed after 11 weeks. Behavior was observed at 9 and 15 wk, by visual scan. At 6, 13, and 19 wk of age, one bird/pen was slaughtered for weighing different organs and analyzing the composition of empty whole bodies. Treatments did not affect BW uniformity; relative weights of the ovary, oviduct, or gizzard; or protein content of empty BW. Time eating varied with the growth curve at 19 wk (P < 0.05), HBW pullets spent 19 more min eating than RBW pullets. DIL led to 4 and 8 more min eating at 19 wk for pullets of RBW and HBW (P < 0.05), respectively. Pullets fed DIL consumed 30% (P < 0.05) less during the feeding rate test when kept on a restricted regimen, and they had lower compensatory energy intake after ad libitum feeding than those fed CON, indicating lower feeding motivation. Behavior was affected by the age and by the time of the d measured, but it did not change with the treatments. Birds spent most time pecking objects (50%), feeding (28%), and drinking (17%). Pullets fed DIL had 8% lower breast yield at different ages and higher empty digestive tracts at 6 weeks. Body composition varied with age; fat content increased from 12.7 to 15.9 to 19.8% for 6, 13, and 19 wk, respectively. The lowest body fat was observed for RBW pullets fed DIL (P = 0.003) at 19 weeks. Feeding DIL diets to HBW pullets could be done to increase the time spent eating and reduce their feeling of hunger without negative effects on body composition. However, its influence on behavior and BW uniformity was not proved.


Say What? Quantifying and Classifying Jargon Use During Inpatient Rounds.
Although plain language is recognized as essential for effective communication, research reveals that medical providers regularly use jargon terminology that may be misunderstood by patients. Little is known, however, about the types and frequency of jargon used in the pediatric inpatient setting. We aimed to quantify jargon use by medical team members during inpatient family-centered rounds (FCRs) and to identify the most common categories of jargon used. One of 3 trained medical students audited FCRs on a general pediatric service once weekly for 12 weeks, recording and categorizing jargon used with a published classification framework. Jargon usage was classified by category and quantified by using descriptive statistics. Rates were calculated by patient encounter and per minute. Feedback was provided to rounding teams after each observation. During 70 observed FCR patient encounters, there were a total of 443 jargon words or phrases spoken, of which 309 (70%) were not explicitly defined to the patient or family by the health care provider team. The mean number of undefined jargon words or phrases used per patient was 4.3 (±1.7), with a mean of 0.4 (±0.1) uses of undefined jargon per minute. The most common categories of undefined jargon used include technical terminology (eg, bronchiolitis), medical vernacular (eg, cultures), and abbreviations and acronyms (eg, NPO for "nothing by mouth") at 34%, 30%, and 17%, respectively. Undefined medical jargon was used frequently by health care providers during pediatric FCRs. We found it was feasible to measure provider jargon use and to use a jargon classification scheme to provide real-time, concrete feedback.


Interpersonal change following intensive inpatient treatment.
Persons admitted for inpatient psychiatric care often present with interpersonal difficulties that disrupt adaptive social relations and complicate the provision of treatment. Whereas domains of psychosocial functioning in this population demonstrate clear growth in response to intervention, the impact of treatment on more complex patterns of interpersonal behavior has been largely overlooked within the existing literature. Interpersonal profiles characteristic of psychiatric inpatients were identified in the current study to determine rates of transition to adaptive functioning following hospitalization. Personality disturbance was assessed in 513 psychiatric inpatients using the Inventory of Interpersonal Problems. Scores were analyzed within a series of latent profile models to isolate unique interpersonal profiles at admission and at discharge. Longitudinal modeling was then employed to determine rates of transition from dysfunctional to adaptive profiles. Relationships with background characteristics, clinical presentation, and treatment response were explored. Normative, Submissive, and Hostile/Withdrawn profiles emerged at both admission and discharge. Patients in the Normative profile demonstrated relatively moderate symptoms. Submissive and Hostile/Withdrawn profiles were related to known risk factors and elevated psychopathology. Approximately half of the patients who had been identified as Submissive or Hostile/Withdrawn transitioned to the Normative profile by discharge. Transition status evidenced modest associations with background characteristics and clinical presentation. Treatment engagement and reduction of clinical symptoms were strongly associated with adaptive transition. Maladaptive interpersonal profiles characteristic of psychiatric inpatients demonstrated categorical change following inpatient hospitalization. Enhanced therapeutic engagement and overall reductions in psychiatric symptoms appear to increase potential for interpersonal change.


Dual effect of a Tn917 insertion into the Bacillus subtilis sacX gene.
The most common effect of transposon insertion is the inactivation of genes. However, in some cases, transposons can activate in cis the expression of genes in the neighbourhood of their integration site. We previously described an insertion of the transposon Tn917 into the Bacillus subtilis sacXY locus. sacX and sacY encode respectively a negative and a positive regulator involved in induction by sucrose of the exoenzyme levansucrase. Data in this paper show that the Tn917 insertion had two effects: it inactivated sacX and it increased the transcription of sacY. The latter effect involved one or several elements internal to the transposon.


Engineering the smallest 3D symmetrical bright and dark focal spots.
A simple roadmap is established for the construction of the smallest three-dimensional (3D) isotropic focal spots. It is achieved in a 4Pi configuration by imposing a restriction/condition of equal transverse and longitudinal spot sizes to determine the position of an annular aperture and then optimize its size. The calculations were performed for cylindrically symmetric radial, azimuthal, and circular polarizations for the cases of in-phase and out-of-phase counter-propagating beams as well as when a vortex was added to the beams. A diffraction-limited bright 3D isotropic spot containing solely longitudinal or transverse electric field components is obtained, while the 3D dark spot can be formed from one of two complementary combinations, each containing both transverse and longitudinal field components.


Obscure recurrent gastrointestinal bleeding: a revealed mystery?
Nowadays, capsule endoscopy (CE) is the first-line procedure after negative upper and lower gastrointestinal (GI) endoscopy for obscure gastrointestinal bleeding (OGIB). Approximately, two-thirds of patients undergoing CE for OGIB will have a small-bowel abnormality. However, several patients who underwent CE for OGIB had the source of their blood loss in the stomach or in the colon. The aim of the present study is to determine the incidence of bleeding lesions missed by the previous gastroscopy/colonoscopy with CE and to evaluate the indication to repeat a new complete endoscopic workup in subjects related to a tertiary center for obscure bleeding before CE. We prospectively reviewed data from 637/1008 patients underwent to CE for obscure bleeding in our tertiary center after performing negative gastroscopy and colonoscopy. CE revealed a definite or likely cause of bleeding in stomach in 138/637 patients (yield 21.7%) and in the colon in 41 patients (yield 6.4%) with a previous negative gastroscopy and colonoscopy, respectively. The lesions found were outside the small bowel in only 54/637 (8.5%) patients. In 111/138 patients, CE found lesions both in stomach and small bowel (small-bowel erosions in 54, AVMs in 45, active small-bowel bleeding in 4, neoplastic lesions in 3 and distal ileum AVMs in 5 patients). In 24/41 (58.5%) patients, CE found lesions both in small bowel and colon (multiple small-bowel erosions in 15; AVMs in 8 and neoplastic lesion in 1 patients. All patients underwent endoscopic therapy or surgery for their nonsmall-bowel lesions. Lesions in upper or lower GI tract have been missed in about 28% of patients submitted to CE for obscure bleeding. CE may play an important role in identifying lesions missed at conventional endoscopy.


Consensus on the Use of Hyaluronic Acid Fillers from the Cohesive Polydensified Matrix Range: Best Practice in Specific Facial Indications.
As the treatment indications for the Cohesive Polydensified Matrix® hyaluronic acid (CPM-HA) portfolio continue to expand and diversify, injectors new to the range or those who are expanding the treatments they offer may be unsure of the optimal product and injection technique for specific facial areas. Each product in the CPM-HA portfolio has been intentionally designed to provide the best physical properties for a specific indication and target tissue. This document has been developed to provide a comprehensive, one-stop reference for clinicians using the portfolio. An international panel of experts in the field of aesthetic medicine convened to develop guidelines on effective and safe injection technique when performing treatments with the CPM-HA range of soft-tissue fillers. Consensus members considered treatment indications in the upper, middle and lower face. Landmark deficiencies and anatomical considerations are described for each indication and consensus recommendations provided on the optimal product, injection depth and treatment technique. This is supplemented by the experts advice on avoidance of complications. Throughout, an evidence-based approach to selection of products and injection techniques is provided. The result is a fully tailored approach to a range of indications covering the full portfolio of CPM-HA products, including the newest addition for skin revitalization. The recommendations in this consensus document are provided to assist clinicians in the selection of CPM-HA products, administration techniques and depths of injection with the aim of providing seamless and natural treatment results, enhanced safety and patient satisfaction.


A Validated HPLC-MS/MS Method for Quantification of Methotrexate and Application for Therapeutic Drug Monitoring in Children and Adults with Non-Hodgkin Lymphoma.
A simple, rapid and reliable method to quantify methotrexate (MTX) in human plasma by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established and validated in two laboratories. Sample separation was achieved on a Synergi Hydro-RP column (50 mm×2.0 mm, 2.5 μm) with a gradient elution program in 3.5 min after a simple protein precipitation with methanol (MeOH) and acetonitrile (ACN) (1:1). About 5 mM ammonium formate aqueous solution with 0.2% formic acid and ACN were used as mobile phase with a flow rate of 0.5 mL/min at 40 °C. Mass spectrometry detection using AB Sciex Triple Quad 4500 mass spectrometer (4500 QQQ) and Qtrap 5500 mass spectrometer (5500 Q-trap) were both characterized by electrospray ionization (ESI) for positive ions in multiple reaction-monitoring (MRM) mode. Quantitative ion pairs were m/z 455.1→m/z 308.0 for MTX and m/z 248.1→m/z 121.0 for tinidazole (TNZ) used as internal standard (IS). Linear calibration curves were generated over the range of 5-1000 ng/mL (r2> 0.99) on both the 4500 QQQ and 5500 Q-trap, both of the intra- and inter-batch precision were less than 7.67% and accuracy ranged from 96.33% to 108.94%. The recovery and matrix effect were 82.20-93.98% and 102.69-105.28%, respectively. An analytical method transfer was achieved by re-verification in two laboratories to ensure stability and reproducibility and this method has been applied for therapeutic drug monitoring (TDM) successfully in children and adults with NHL, and during routine TDM, two delayed elimination of MTX cases were observed and analyzed.


Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling.
Sleep fragmentation (SF) is a highly prevalent condition and a hallmark of sleep apnea, a condition that has been associated with increased cancer incidence and mortality. In this study, we examined the hypothesis that sleep fragmentation promotes tumor growth and progression through proinflammatory TLR4 signaling. In the design, we compared mice that were exposed to sleep fragmentation one week before engraftment of syngeneic TC1 or LL3 tumor cells and tumor analysis four weeks later. We also compared host contributions through the use of mice genetically deficient in TLR4 or its effector molecules MYD88 or TRIF. We found that sleep fragmentation enhanced tumor size and weight compared with control mice. Increased invasiveness was apparent in sleep fragmentation tumors, which penetrated the tumor capsule into surrounding tissues, including adjacent muscle. Tumor-associated macrophages (TAM) were more numerous in sleep fragmentation tumors, where they were distributed in a relatively closer proximity to the tumor capsule compared with control mice. Although tumors were generally smaller in both MYD88(-/-) and TRIF(-/-) hosts, the more aggressive features produced by sleep fragmentation persisted. In contrast, these more aggressive features produced by sleep fragmentation were abolished completely in TLR4(-/-) mice. Our findings offer mechanistic insights into how sleep perturbations can accelerate tumor growth and invasiveness through TAM recruitment and TLR4 signaling pathways.


Hypoxia-Driven Immune Escape in the Tumor Microenvironment.
The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical outcome, increased tumor heterogeneity, emergence of resistant clones and evasion of immune detection. Additionally, hypoxia-driven cell death pathways have traditionally been thought of as tolerogenic processes. However, as researchers working in the field of immunotherapy continue to investigate and unveil new types of immunogenic cell death (ICD), it has become clear that, in some instances, hypoxia may actually induce ICD within a tumor. In this review, we will discuss hypoxia-driven immune escape that drives poor prognostic outcomes, the ability of hypoxia to induce ICD and potential therapeutic targets amongst hypoxia pathways.


Comparison of On-Site Versus Remote Mobile Device Support in the Framingham Heart Study Using the Health eHeart Study for Digital Follow-up: Randomized Pilot Study Set Within an Observational Study Design.
New electronic cohort (e-Cohort) study designs provide resource-effective methods for collecting participant data. It is unclear if implementing an e-Cohort study without direct, in-person participant contact can achieve successful participation rates. The objective of this study was to compare 2 distinct enrollment methods for setting up mobile health (mHealth) devices and to assess the ongoing adherence to device use in an e-Cohort pilot study. We coenrolled participants from the Framingham Heart Study (FHS) into the FHS-Health eHeart (HeH) pilot study, a digital cohort with infrastructure for collecting mHealth data. FHS participants who had an email address and smartphone were randomized to our FHS-HeH pilot study into 1 of 2 study arms: remote versus on-site support. We oversampled older adults (age ≥65 years), with a target of enrolling 20% of our sample as older adults. In the remote arm, participants received an email containing a link to enrollment website and, upon enrollment, were sent 4 smartphone-connectable sensor devices. Participants in the on-site arm were invited to visit an in-person FHS facility and were provided in-person support for enrollment and connecting the devices. Device data were tracked for at least 5 months. Compared with the individuals who declined, individuals who consented to our pilot study (on-site, n=101; remote, n=93) were more likely to be women, highly educated, and younger. In the on-site arm, the connection and initial use of devices was ≥20% higher than the remote arm (mean percent difference was 25% [95% CI 17-35] for activity monitor, 22% [95% CI 12-32] for blood pressure cuff, 20% [95% CI 10-30] for scale, and 43% [95% CI 30-55] for electrocardiogram), with device connection rates in the on-site arm of 99%, 95%, 95%, and 84%. Once connected, continued device use over the 5-month study period was similar between the study arms. Our pilot study demonstrated that the deployment of mobile devices among middle-aged and older adults in the context of an on-site clinic visit was associated with higher initial rates of device use as compared with offering only remote support. Once connected, the device use was similar in both groups.


The pathogenesis of septic acute renal failure.
Acute renal failure is a serious condition that affects as many as 20% of ICU patients. The most common causes of acute renal failure in the ICU patient are severe sepsis and septic shock. The mortality of acute renal failure in septic critically ill patients remains high despite our increasing ability to support vital organs. This is partly the result of our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. Accordingly, a review of our current understanding of the pathogenesis of septic acute renal failure is timely and relevant. Throughout the past half century, acute renal failure of acute illness has essentially been considered a hemodynamic disease caused by kidney ischemia, a view derived by findings in animal models. Unfortunately most such models are greatly deficient in that they do not reproduce the high cardiac output, low systemic vascular resistance state typically seen during human sepsis. Furthermore, most models inducing so-called acute tubular necrosis are based on ischemia-reperfusion (renal artery clamping), an event with little relevance to human sepsis. Recent research highlights a new possible and emerging concept for the pathogenesis of septic acute renal failure: acute apoptosis. This concepts fits well with the typical paucity of histologic changes seen in so-called acute tubular necrosis and with growing evidence of a role for apoptosis in organ injury during sepsis and inflammation in general. Furthermore, the authors present evidence that some potential treatments recently shown to affect the mortality of critically ill patients, (activated protein C, intensive insulin treatment, and low-volume mechanical ventilation) might have antiapoptotic activity. This review suggests that, on the evidence available, septic acute renal failure is more likely to be an immune or toxic state rather than simply a hemodynamic condition. The authors speculate that future insights into its pathogenesis might lead to a paradigm shift away from the concept of acute tubular necrosis, which has never been convincingly shown in sepsis, to that of acute tubular apoptosis.


[Intonation and organization of utterances].
Syntactic theories of intonation assume that intonation is congruent to syntax. It is, however, in the cases where it is not that intonation can restructure an utterance and become informative. In a first stage, we identify the prosodic units which play a part in the organisation of utterances. In a second stage, we examine how intonation contributes to the linear and hierarchical structure of utterances. The functioning of prosodic units in semantic and pragmatic organisation of the sentence allows us to bring to light syntactic constraints. This method seems the best way to evaluate the respective interactions of intonation with syntax and pragmatics. These syntactic constraints constitute formal marks which justify the content of prosodic rules (syntactic, semantic, accentual and rhythmic) which make it possible to predict or explain the intonation of utterances.


Anesthetic Management of the Hypertensive Patient: Part II.
Hypertension is an important health challenge that affects millions of people across the world today and is a major risk factor for cardiovascular disease. It is critical that anesthesia providers have a working knowledge of the systemic implications of hypertension. This review article will discuss the medical definitions of hypertension, the physiology of maintaining blood pressure, outpatient treatment of hypertension, anesthetic implications, and the common medications used by anesthesia providers in the treatment of hypertension. Part I provided an overview of hypertension and blood pressure regulation. In addition, drugs predominantly affecting control of hypertension via renal mechanisms such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and renin-inhibiting agents were discussed. In part II, the remaining major antihypertensive medications will be reviewed as well as anesthetic implications of managing patients with hypertension.


Changes in maxillary incisor dental pulp blood flow during intrusion by mini-implants.
The aim of this clinical study was to identify changes in pulpal blood flow (PBF) in human central incisors resulting from short- and long-term intrusive orthodontic forces from mini-implants. A total of 40 sound upper central and lateral incisors in 20 patients scheduled for intrusion for orthodontic reasons were divided into two groups. From each group, 20 teeth were subjected to intrusive force from mini-implants (Group 1 = Light Force: 40 g; Group 2 = Heavy Force: 120 g), whereas the remaining 20 contralateral teeth were not subjected to forces from mini-implants and served as controls. Laser-Doppler flowmetry (LDF) measurements were recorded at baseline and at 3 days and 3 weeks following intrusion. PBF decreased significantly at 3 days (Light Force Group: 7.72 ± 0.50; Heavy Force Group: 7.72 ± 0.52) and then increased towards baseline at 3 weeks (Light Force Group: 10.37 ± 0.58; Heavy Force Group: 10.31 ± 0.45) following intrusion. In other words, despite slight regressive changes in pulpal tissue in the short-term, PBF improved after 3 weeks following intrusion by mini-implants, indicating that the changes observed in PBF is reversible, even following radical incisor intrusion.


Changes on image texture features of breakfast flakes cereals during water absorption.
Normally breakfast cereal flakes are consumed by pouring them into a bowl and covering them with fresh or cold milk. During this process the liquid uptake causes changes in the surface and internal matrix of breakfast cereals that influence texture and integrity. Some breakfast cereal as flakes have a translucent structure that could provide information about the solid matrix and air cells and how they change during liquid absorption. The objective of the study was to assess the image texture changes of corn flakes and frosted flakes during water absorption at 5, 15 and 25 °C, employing 11 image feature textures extracted from grey-level co-occurrence matrix and grey-level run length matrix (at three directions) and to relate the fractal dimension (FD) of images with rupture force (RF) reduction during soaking of both flakes at 5 °C. The most relevant result from principal component analysis calculated with a matrix of 54 (soaking times) × 22 (texture features), shows that it was possible to distinguish an isolated group consisting of different soaking times at the same water temperature in each breakfast cereal flakes evaluated, corroborating that superficial liquid imbibition is important during the liquid absorption process when flakes are soaked. Furthermore, standardized FD could be related to RF in the period when samples tend to search for an equilibrium state.


Beta, or type II error in psychiatric controlled clinical trials.
Fifty-two reportedly "negative" psychiatric controlled clinical trials from 1980-1984 were re-examined to note if large enough samples had been studied to give a high probability (greater than 0.90) of detecting a 20% or 50% improvement in therapeutic response, defined as a reduction in the non-response rate. Forty-four of the trials had a larger than 10% risk of missing a true 20% difference in non-response rates, and with the same risk, 25 of the trials could have missed a 50% difference between treatments. Based on estimates of 90% confidence intervals, a potential 20% difference was possible for 47, and 30 had a potential true difference of 50% in non-response rates between experimental and control conditions. Far more reports describing "non-significant" studies could not be re-examined, due to lack of reporting part or all of the relevant results. The possibility of missing considerable therapeutic improvement, or important clinical differences, because of small sample size demands more concern in psychiatry.


Factors affecting the quality of life of single mothers compared to married mothers.
In this study, we aimed to compare the quality of life (QOL) of single mothers with that of married mothers and to identify the sociodemographic and psychological factors affecting single mothers' QOL. We identified the factors that were similar and different between single and married mothers. We analyzed survey data obtained from 195 single mothers and 357 married mothers living in an urban community in South Korea. The QOL was assessed with the World Health Organization Quality of Life-abbreviated form (WHOQOL-BREF). All participants completed the following self-report questionnaires: the Global Assessment of Recent Stress, the Center for Epidemiologic Studies-Depression Scale, the Scale for Suicide Ideation, the Korean version of the Alcohol Use Disorder Identification Test, and the WHOQOL-BREF. These self-rating scales were used as continuous variables. Multiple linear regression analysis was performed to examine the association of quality of life with the sociodemographic and psychological factors for single and married mothers. Single mothers showed lower QOL than married mothers. Older age, high income and education level, and professional job status were positively correlated with the QOL of single mothers. Residential instability, higher stress levels, depressive symptoms, suicidal ideation, and alcohol-related problems were negatively associated with the QOL of single mothers. Multiple regression analysis suggested that residential instability (public rental housing: β = - 10.779, p < 0.001; Jeonse rental housing: β = - 0.324, p = 0.01) and alcohol-related problems (β = - 0.522, p < 0.001) were independent factors affecting lower QOL, whereas professional job status (β = 8.452, p = 0.037) was independently associated with higher QOL in single mothers. However, these factors were not associated with the QOL of married mothers. Higher education level was independently associated with higher QOL in both groups (β = 3.149, p < 0.033 in single mothers, β = 12.052, p < 0.001 in married mothers). Higher education level was associated with higher QOL in both groups. Unlike in married mothers, type of residence and occupation (related to the economic level) had a significant impact on QOL in single mothers. Alcohol-related problems were significantly correlated to QOL in single mothers compared to married mothers.


Bacterial toxins as versatile delivery vehicles.
An ability to deliver macromolecules into the intracellular compartments of mammalian cells offers enormous potential for development of new therapeutics directed against intracellular targets. Unfortunately, most peptides or proteins are too large to enter the cell cytosol unaided, and any uptake that does occur primarily results in their entry into lysosomes for degradation. However, one group of proteins that possesses an inherent capacity to interact with and enter mammalian cells are bacterial toxins. These are being developed as efficient vehicles for the attachment and intracellular delivery of other macromolecules, including peptides, proteins and DNA. To date, most studies have concentrated on the delivery of immunological epitopes into the endogenous major histocompatibility class I (MHC-I) pathway for development of antiviral or anticancer vaccines. However, opportunities to use toxins to modulate inflammatory autoimmune disorders and cell-specific targeting of DNA for gene therapy illustrates the versatility of toxin molecules as delivery vehicles.


Disseminated tuberculosis manifesting as pulmonary, meningeal and spinal tuberculosis in an immunocompetent patient.
Disseminated tuberculosis is characterised by concurrent tubercular involvement of two or more non-contiguous organs. It is an unusual presentation of tuberculosis, especially in the absence of immunodeficiency. We describe a young, immunocompetent patient who presented with fever, cough, headache, diplopia and paraparesis. On examination, the patient had positive Kernig's sign, right third cranial nerve palsy and bilateral sixth cranial nerve palsy, bilateral lower limb weakness and crepititions on lung auscultation bilaterally. Chest radiogram revealed bilateral pulmonary tuberculosis. CT of brain showed hydrocephalus and MRI of spine showed collapse of lumbar vertebrae with paravertebral cold abscess. Sputum microscopy was positive for acid fast bacilli, cerebrospinal fluid analysis was suggestive of tubercular meningitis and CT-guided biopsy of the vertebral lesions revealed caseating granulomas with acid fast bacilli. The patient received antitubercular therapy with initial treatment with steroids and he improved clinically at the end of a 9-month treatment.


[Early diagnosis of ischemic heart disease in patients with chronic obstructive pulmonary diseases].
To study incidence rate, course features, principles of diagnosis and therapy of ischemic heart disease (IHD) in patients with chronic obstructive pulmonary diseases (COPD). Standard clinical examinations, ECG, chest x-ray, echo-CG, 24-h Holter monitoring, coronarography were performed in 60 patients over 40 years of age with bronchial asthma or chronic obstructive bronchitis. Autopsy data were analyzed for 20 patients who died of COPD. IHD was diagnosed in 53.3% of the examinees. 70% of the patients treated with preductal (trimetasidine) benefited from the treatment: they had less frequent episodes of painless myocardial ischemia. Autopsy material has shown that COPD patients frequently suffer of aortic and coronary atherosclerosis. IHD diagnosis in COPD patients is rather difficult as there are no well-defined correlations between clinical picture of IHD and data of device investigations, IHD is painless more frequently than in general population (in 84.4% of patients in this study). Preductal is a drug of choice for treatment of IHD in COPD patients.


Polyoxometalates in solution: Molecular dynamics simulations on the alpha-PW12O40(3-) Keggin anion in aqueous media.
The Keggin anion, PW12O40(3-), is one of the most representative polyoxometalates (POMs). In recent years increasing theoretical work focused on this family of compounds has explained or even predicted some of their properties using quantum mechanics methods. In this report we applied for the first time molecular dynamics (MD) to the title compound to analyze its interactions with water. We used three atomic charge definitions (Mulliken, ChelpG, and formal charges) to carry out MD simulations. The results show that the terminal oxygens of the cluster are invariably most effectively solvated by water because of their prominent position within the framework. On the other hand, bridging oxygens, which are confined in more internal positions, concentrate a smaller portion of the whole solvation. We investigated the hydrogen bonds existing between water and the cluster, confirming that the terminal positions form more contacts with H2O than any other site of the cluster. In the end, the lifetime of such contacts is longer with bridging oxygens, presumably due to their higher atomic charge.


Influence of animal origin and lineage on survival of Escherichia coli O157:H7 strains in strong and weak acid challenges.
Twenty-five strains of Escherichia coli O157:H7 isolated from humans, cattle, and pigs were maintained in HCl (pH 2.5) and in a volatile fatty acid (VFA) mixture (pH 4.0) for up to 6 h at 37 degrees C to assess their ability to survive in acidic conditions that simulate those of the stomach and ileum, respectively. In HCl, the average group survival of bovine strains was significantly higher than that of porcine and human strains, whereas in VFAs, porcine strains were significantly more resistant than bovine and human strains. Bovine strains exhibited significantly higher average survival in HCl than in VFAs. The average survival of strains classified as octamer-based genome scanning (OBGS) lineage II was significantly superior to that of strains classified as OBGS lineage I in HCl. The group of lineage I strains was more resistant in VFAs compared with lineage II, but only after 6 h of challenge. The possible involvement of urease in acid resistance of E. coli O157:H7 was also examined. Although the strains possessed the ureC gene, as shown by PCR, this gene did not appear to contribute to acid resistance under the conditions tested. The data indicate that there is a relationship between acid resistance and source or lineage of O157:H7 strains.


The clinical spectrum of internuclear ophthalmoplegia in multiple sclerosis.
The eye movements of 100 patients with multiple sclerosis were examined clinically, including a saccade test. Thirty-four cases of internuclear ophthalmoplegia were found, of which 14 were bilateral and 20 were unilateral. Only three patients had full restriction of adduction, whereas 16 had no restriction at all. A continuous dissociated nystagmus was present in one patient only, while in 15 just a few beats of the abducting eye could be observed. In ten cases both restriction of adduction and dissociated nystagmus were lacking, and the diagnosis could only be made with the saccade test, which in all 34 patients showed a clearly visible disjunction of horizontal saccades. In 15 cases, infrared oculography was performed, which in all cases confirmed the clinical findings, and which in some cases disclosed an additional subclinical internuclear ophthalmoplegia on the opposite side.


Risks associated with preoperative anemia and perioperative blood transfusion in open surgery for intracranial aneurysms.
Preoperative anemia may be treated with a blood transfusion. Both are associated with adverse outcomes in various surgical procedures, but this has not been clearly elucidated in surgery for cerebral aneurysms. In this study the authors assessed the association of preoperative anemia and perioperative blood transfusion, separately, on 30-day morbidity and mortality in patients undergoing open surgery for ruptured and unruptured intracranial aneurysms. The authors identified 668 cases (including 400 unruptured and 268 unruptured intracranial aneurysms) of open surgery for treatment of intracranial aneurysms in the 2006-2012 National Surgical Quality Improvement Program, a validated and reproducible prospective clinical database. Anemia was defined as a hematocrit level less than 39% in males and less than 36% in females. Perioperative transfusion was defined as at least 1 unit of packed or whole red blood cells given at any point between the start of surgery to 72 hours postoperatively. The authors separately compared surgical outcome between patients with (n = 198) versus without (n = 470) anemia, and those who underwent (n = 78) versus those who did not receive (n = 521) a transfusion, using a 1:1 match on propensity score. In the matched cohorts, all observed covariates were comparable between anemic (n = 147) versus nonanemic (n = 147) and between transfused (n = 67) versus nontransfused patients (n = 67). Anemia was independently associated with prolonged hospital length of stay (LOS; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4-4.5), perioperative complications (OR 1.9, 95% CI 1.1-3.1), and return to the operating room (OR 2.1, 95% CI 1.1-4.5). Transfusion was also independently associated with perioperative complications (OR 2.4, 95% CI 1.1-5.3). Preoperative anemia and transfusion are each independent risk factors for perioperative complications in patients undergoing surgery for cerebral aneurysms. Perioperative anemia is also associated with prolonged hospital LOS and 30-day return to the operating room.


Enteropathogenic Escherichia coli O103 from rabbit elicits actin stress fibers and focal adhesions in HeLa epithelial cells, cytopathic effects that are linked to an analog of the locus of enterocyte effacement.
Escherichia coli O103, a major agent of weaned-rabbit diarrhea in Western Europe, was previously shown to produce diarrhea and attaching-and-effacing intestinal lesions in experimentally infected rabbits and to possess a homolog of the eaeA gene of enteropathogenic E. coli (EPEC). In the present study, we have shown that although negative in the fluorescent-actin staining test on HeLa cells, prototype rabbit E. coli O103 strain B10 was able to induce an original cytopathic effect (CPE) in the same interaction model. This CPE was characterized by a generalized reorganization of the actin cytoskeleton and the formation of focal adhesions on the entire surface of the target cells. These effects amplified with time, leading to cell death about 5 days after the interaction. They were produced by all rabbit E. coli O103 strains tested, by rabbit-infecting E. coli RDEC-1, and also by two human EPEC isolates. We localized genes associated with CPE by using TnphoA insertion mutagenesis in strain B10. In all five independent CPE-negative mutants that we were able to generate, the insertion was located in a region of the genome homologous to the 35-kb locus of enterocyte effacement (LEE locus) of EPEC E2348/69. The mutants concurrently lost the ability to secrete four major supernatant proteins of 25, 37, 39, and 40 kDa, which were shown by immunoprecipitation to share antigenic determinants with secreted proteins of human EPEC E2348/69. The virulence of one of these mutants (strain B10/CA1) was compared with that of the parental strain in the weaned-rabbit diarrhea model. The mutant was totally deprived of virulence, although it colonized the intestine as efficiently as the parental strain did. This study points to a new pathogenic trait of EPEC strains, which is associated with the LEE locus and, possibly, with in vivo virulence.