Clinical features and treatment of inflammatory bowel disease in a low-incidence area: A hospital-based retrospective cohort study in Taiwan.
Inflammatory bowel disease (IBD) has emerged in the Asia-Pacific area over the past 2 decades. There is a paucity of clinical data regarding real-world experience of patients with IBD from low endemic area such as Taiwan. Therefore, the present study aimed to review the clinical features of patients with IBD form a tertiary center from Taiwan.A total of 163 patients with IBD were identified from the electronic clinical database of Changhua Christian Hospital. Demographic data of the patients and clinical features of the disease pattern were retrospectively reviewed.There was a higher proportion (62.6%) of patients diagnosed with ulcerative colitis (UC). Patients with Crohn disease (CD) and UC had male predominance. The median age of diagnosis was younger in patients with CD than in patients with UC (CD vs UC: 31 vs 40 years, P = .0423). The disease distribution of UC was as follows: E1 (15.7%), E2 (47.1%), and E3 (37.3%). The disease distribution of CD was as follows: L1 (36.1%), L2 (14.8%), L3 (42.6%), and L4 (6.5%). The majority of patients with CD had a complicated presentation with B2 (32.8%) and B3 (32.8%). Patients with CD had a higher bowel resection rate than patients with UC. Patients with CD were more likely to be treated with immunomodulator and biologics and those with UC were more likely to be treated with 5-aminosalicylic acid (5-ASA). A trend of decreased bowel resection for patients with IBD and less severe phenotype of patients with CD were observed after 2015.UC with male predominance was the predominant type of IBD in the study. Patients with CD are likely to have a complicated disease course, requiring a higher demand of biologic therapy than patients with UC.


Specific tumor-derived CCL2 mediated by pyruvate kinase M2 in colorectal cancer cells contributes to macrophage recruitment in tumor microenvironment.
Development of colorectal cancer has been considered as a result of imbalance of pro- and anti-inflammatory intestinal microenvironment accompanied by macrophage recruitment. Despite macrophages are implicated in remodeling tumor microenvironment, the mechanism of macrophage recruitment is not fully elucidated yet. In this study, we reported clinical association of highly expressed pyruvate kinase M2 in colorectal cancer with macrophage attraction. The conditioned medium from Caco-2 and HT-29 cells with depleted pyruvate kinase M2 dramatically reduced macrophage recruitment, which is reversed by addition of, a critical chemotaxis factor to macrophage migration, rCCL2. Silencing of endogenous pyruvate kinase M2 markedly decreased CCL2 expression and secretion by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Endogenous pyruvate kinase M2 interacted with p65 and mediated nuclear factor-κB signaling pathway and mainly regulated phosphorylation of Ser276 on p65 nuclear factor-κB. In addition, inhibition of macrophage recruitment caused by pyruvate kinase M2 silencing was rescued by ectopic expression of p65. Interestingly, pyruvate kinase M2 highly expressed in colorectal cancer tissue, which is correction with macrophage distribution. Taken together, we revealed a novel mechanism of pyruvate kinase M2 in promoting colorectal cancer progression by recruitment of macrophages through p65 nuclear factor-κB-mediated expression of CCL2.


Frequency of suicidal thought and self-destructive behavior among females.
The focus of the present investigation was to examine the importance of a control group in suicide research and to develop an instrument to distinguish between levels of suicidal thought among subjects who had a history of attempted suicide and among a comparison group of nonsuicidal individuals. The sample was comprised of female university students ranging in age from 18 to 25 years. A 31-item questionnaire designed by the investigator was given to 199 students, 20 of whom were found to have histories of one or more previous suicide attempts. The remaining 179 nonsuicidal subjects were divided into two categories based on the frequency of expressed suicidal thought. Fifty individuals were randomly selected from each of these two groups. The three groups (individuals who had attempted suicide, individuals who had not attempted suicide but who thought about suicide on a frequent basis, and individuals who had not attempted suicide and who thought about suicide on an infrequent basis) were compared on the variables of motivation for suicidal thoughts, history of self-destructive behaviors, probability of a future suicide attempt, and age of first suicidal considerations. A chi-square analysis was performed on each of these items in order to assess the extent to which the items discriminated among the three comparison groups. The differences among the three groups on each of the items were found to be statistically significant at less than the .01 level. The results of the study have provided support for the necessity of a distinction between groups within a nonsuicidal comparison population and for the suggestion that there may be a quantitative relationship between the frequency of suicidal thought and the likelihood of attempted suicide.


The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes.
Autophagy is critical for the maintenance of organelle function and intracellular nutrient environment. Autophagy is also involved in systemic metabolic homeostasis, and its dysregulation can lead to or accelerate the development of metabolic disorders. While the role of autophagy in the global metabolism of model organisms has been investigated mostly using site-specific genetic knockout technology, the impact of dysregulated autophagy on systemic metabolism has been unclear. Here, we review recent papers showing the role of autophagy in systemic metabolism and in the development of metabolic disorders. Also included are data suggesting the role of autophagy in human-type diabetes, which are different in several key aspects from murine models of diabetes. The results shown here support the view that autophagy modulation could be a new modality for the treatment of metabolic syndrome associated with lipid overload and human-type diabetes.


Facial Asymmetry Phenotypes in Adult Patients With Unilateral Cleft Lip and Palate and Skeletal Class III Malocclusion Using Principal Component Analysis and Cluster Analysis.
The purpose of this study was to classify and characterize facial asymmetry (FA) phenotypes in adult patients with unilateral cleft lip and palate (UCLP) and skeletal class III malocclusion. The samples comprised 52 adult UCLP patients (36 men and 16 women; mean age, 22.43 y) who had undergone orthognathic surgery for correction of class III malocclusion. After measurement of 22 cephalometric parameters in posteroanterior cephalograms taken 1 month before orthognathic surgery, principal component analysis was performed to obtain 5 representative parameters [deviation (mm) of ANS (ANS-dev), maxillary central incisor contact point (Mx1-dev), and menton (Me-dev); cant (degree) of the maxillary anterior occlusal plane (MxAntOP-cant) and mandibular border (MnBorder-cant)]. K-means cluster analysis was conducted using these representative parameters. The differences in cephalometric parameters among the clusters were statistically analyzed. The FA phenotypes were classified into 4 types: No-cant-and-No-deviation type (cluster-4, n=16, 30.8%); MxMn-cant-MxMn-dev to the cleft-side type (cluster-3, n=4, 7.7%); Mx-cant-Mn-shift to the cleft-side type (cluster-2, n=15, 28.8%); and Mn-cant-Mn-dev to the noncleft-side type (cluster-1, n=17, 32.7%). Asymmetry in the maxilla and/or mandible were observed in 70% of patients. One third of patients (cluster-2 and cluster-3; sum, 36.5%) exhibited significant cant of MxAntOP induced by cleft and cant or shift of the mandible to the cleft side. Another one third of patients (cluster-1, 32.7%) demonstrated significant deviation and cant of the mandible to the noncleft-side despite cleft in the maxilla. This FA phenotype classification might be a basic guideline for diagnosis and treatment planning for UCLP patients.


Infrared multiple photon dissociation spectroscopy of cationized methionine: effects of alkali-metal cation size on gas-phase conformation.
The gas-phase structures of alkali-metal cation complexes of the amino acid methionine (Met) as well as protonated methionine are investigated using infrared multiple photon dissociation (IRMPD) spectroscopy utilizing light generated by a free electron laser. Spectra of Li(+)(Met) and Na(+)(Met) are similar and relatively simple, whereas the spectra of K(+)(Met), Rb(+)(Met), and Cs(+)(Met) include distinctive new bands. Measured IRMPD spectra are compared to spectra calculated at the B3LYP/6-311+G(d,p) level of theory to identify the conformations present in the experimental studies. For Li(+) and Na(+) complexes, the only conformation present is a charge-solvated, tridentate structure that binds the metal cation to the amine and carbonyl groups of the amino acid backbone and the sulfur atom of the side chain, [N,CO,S]. In addition to the [N,CO,S] conformer, bands corresponding to alkali-metal cation binding to a bidentate zwitterionic structure, [CO(2)(-)], are clearly present for the K(+), Rb(+), and Cs(+) complexes. Theoretical calculations of the lowest energy conformations of Rb(+) and Cs(+) complexes suggest that the experimental spectra could also include contributions from two additional charge-solvated structures, tridentate [COOH,S] and bidentate [COOH]. For H(+)(Met), the IRMPD action spectrum is reproduced by multiple low-energy [N,CO,S] conformers, in which the protonated amine group hydrogen bonds to the carbonyl oxygen atom and the sulfur atom of the amino acid side chain. These [N,CO,S] conformers only differ in their side-chain orientations.


Personality, social skills, anomie and delinquency: a self-report study of a group of normal non-delinquent adolescents.
A group of over 200 'normal' adolescents were administered self-report measures of personality (extraversion, neuroticism and psychoticism), social skills, anomie and delinquency in order to establish which of three theories best predicted delinquency. Eysenck's personality factors, particularly psychoticism, correlated most highly with delinquency, while there was no correlation at all between self-reported social skills and delinquency. Overall the males tended to have lower neuroticism but higher psychoticism and anomie scores. The results are discussed in terms of the various psychological theories of delinquency, and the implications of these results for treatment are noted. It was pointed out that because this study was restricted to well-educated, middle class, above-average sixth-form college students the findings may not generalize to a group of convicted or institutionalized offenders. The limitations inherent in self-report measures and in studies of this sort are also considered.


Role of DDX3 in the pathogenesis of inflammatory bowel disease.
When crypt stem cells of the gastrointestinal tract become injured, the result is increased synthesis of pro-inflammatory cytokines and matrix metalloproteinases by their progeny - the colonic epithelium. Chronic inflammation of the gastrointestinal tract is a characteristic of inflammatory bowel disease, which includes Crohn's Disease and Ulcerative Colitis. In our ongoing investigation to decipher the characteristic functions of a RNA helicase gene, DDX3, we identified high DDX3 expression by immunohistochemistry of colon biopsy samples, which included chronic/mild Morbus Crohn, active Morbus Crohn, Chronic/mild Colitis Ulcerosa and active Colitis Ulcerosa in epithelium and stromal compartments. We used a small molecule inhibitor of DDX3, RK-33, on two human colonic epithelial cell lines, HCEC1CT and HCEC2CT and found that RK-33 was able to decrease expression of MMP-1, MMP-2, MMP-3, and MMP-10. Moreover, forced differentiation of a human colonic cancer cell line, HT29, resulted in decreased DDX3 levels, indicating that DDX3 contributes to the modulation of colonic epithelium differentiation. In conclusion, our results revealed novel functions of DDX3 in inflammatory bowel disease and indicate a potential for using RK-33 as a systemic therapy to promote not only differentiation of transformed colonic epithelium but also to reduce MMP expression and thus elicit a decreased inflammatory response.


Tumor lysis syndrome induced by tebentafusp.
Tebentafusp, a bispecific T-cell receptor fusion protein directed against gp100 and CD3, can improve survival in patients with metastatic uveal melanoma and was recently approved for the treatment of HLA-A*02:01-positive uveal melanoma patients. Since tebentafusp often induces cytokine-release syndrome, doses must be escalated and patients monitored as inpatients after the first infusions. The occurrence of tumor lysis syndrome, a potentially life-threatening condition, after administration of a single dose of tebentafusp, is reported here. With adequate therapy, including the application of rasburicase, the patient made a full recovery. It is important to raise awareness of the adverse event profile of this new therapeutic approach among healthcare professionals to promptly recognize and treat side effects.


Codon frequencies in 119 individual genes confirm consistent choices of degenerate bases according to genome type.
The poor printing of our previous Figure 2 (1) is corrected. Codon usage in mRNA sequences just published is also given. A new correspondence analysis is done, based on simultaneous comparison in all mRNA of use of the 61 codons. This analysis reinforces our claim that most genes in a genome, or genome type, have the same coding strategy; that is, they show similar choices among synonymous codons, or among degenerate bases (2). Like analysis on frequency variation in the amino acids coded reveals an entirely different pattern.


Innovative new model predicts glucose levels without poking or prodding.
With the prevalence of type II diabetes rising rapidly it has become increasingly apparent that something must be done to stem the tide. While pharmaceutical treatments aimed at lowering average blood sugar are an important tool in this endeavor, it is equally (if not more) important to motivate patients to make healthy diet and exercise choices. Recent advances in non-invasive glucose monitoring suggest that real-time patient feedback may soon be available to help guide daily patient decision-making.


Risperidone alone versus risperidone plus valproate in the treatment of patients with schizophrenia and hostility.
The objective of the study was to compare the antiaggressive efficacy of risperidone monotherapy versus risperidone plus valproate in patients with schizophrenia. This was an 8-week open-label randomized parallel group clinical trial in hospitalized adults diagnosed with schizophrenia and with hostile behavior. Patients were randomly assigned to receive risperidone alone (n=16) or risperidone plus valproate (n=17). To minimize bias, raters were blinded to the assigned treatment arm. Outcome measures included the Positive and Negative Syndrome Scale (PANSS), Buss-Durkee Hostility Inventory (BDHI), Barratt Impulsiveness Scale (BIS), Nurses Observation Scale for Inpatient Evaluation (NOSIE), and the Overt Aggression Scale (OAS). Although significantly fewer patients randomized to monotherapy completed the study (chi(2)=8.62, d.f.=1, P=0.003), no significant differences between monotherapy or combination treatment were observed in change of the BDHI, BIS, NOSIE, PANSS total scores, OAS measures of aggressive behavior or the hostility item of the PANSS. In conclusion, although patients receiving combination treatment were more likely to complete the study, we were unable to detect a meaningful advantage for combination therapy as measured by rating scales.


The 2F5 epitope is helical in the HIV-1 entry inhibitor T-20.
The HIV-1 envelope glycoprotein gp41 is responsible for viral fusion with the host cell. The fusion process, as well as the full structure of gp41, is not completely understood. One of the strongest inhibitors of HIV-1 fusion is a 36-residue peptide named T-20, gp41(638-673) (Fuzeon, also called Enfuvirtide or DP-178; residues are numbered according to the HXB2 gp160 variant) now used as an anti HIV-1 drug. This peptide also contains the immunogenic sequences that represent the full or partial recognition epitope for the broadly neutralizing human monoclonal antibodies 2F5 and 4E10, respectively. Due to its hydrophobicity, T-20 tends to aggregate at high concentrations in water, and therefore the structure of this molecule in aqueous solution has not been previously determined. We expressed a uniformly 13C/15N-labeled 42-residue peptide NN-T-20-NITN (gp41(636-677)) and used heteronuclear 2D and 3D NMR methods to determine its structure. Due to the additional gp41-native hydrophilic residues, NN-T-20-NITN dissolved in water, enabling for the first time determination of its secondary structure at near physiological conditions. Our results show that the NN-T-20-NITN peptide is composed of a mostly unstructured N-terminal region and a helical region beginning at the center of T-20 and extending toward the C-terminus. The helical region is found under various conditions and has been observed also in a 13-residue peptide gp41(659-671). We suggest that this helical conformation is maintained in most of the different tertiary structures of the gp41 envelope protein that form during the process of viral fusion. Accordingly, an important element of the immunogenicity of gp41 and the inhibitory properties of Fuzeon may be the propensity of specific sequences in these polypeptides to assume helical structures.


Use of differential scanning fluorimetry to optimize the purification and crystallization of PLP-dependent enzymes.
Differential scanning fluorimetry (DSF) is a practical and accessible technique that allows the assessment of multiphasic unfolding behavior resulting from subsaturating binding of ligands. Multiphasic unfolding is indicative of a heterogenous protein solution, which frequently interferes with crystallization and complicates functional characterization of proteins of interest. Along with UV-Vis spectroscopy, DSF was used to guide purification and crystallization improvements for the pyridoxal 5'-phosphate (PLP) dependent transaminase BioA from Mycobacterium tuberculosis. The incompatibility of the primary amine-containing buffer 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) and PLP was identified as a significant contributor to heterogeneity. It is likely that the utility of DSF for ligand-binding assessment is not limited to the cofactor PLP but will be applicable to a variety of ligand-dependent enzymes.


A case of early gastric cancer arising from gastritis cystica profunda treated by endoscopic submucosal dissection.
Gastritis cystica profunda (GCP) consists of hyperplasia and cystic dilatation of the gastric glands extending into the submucosa. It occurs in the residual stomach post surgery and in the unoperated stomach. GCP is considered a benign lesion, but there is controversy about its malignant potential. We report a case of early gastric cancer arising from GCP treated by endoscopic submucosal dissection (ESD) in a 55-year-old unoperated man. Upper gastrointestinal endoscopy revealed a 15-mm diameter submucosal tumor (SMT) in the upper corpus of the stomach. The surface had angiotelectasia and slight depression covered with normal mucosa. Neither ulceration nor erosion was seen. Narrow-band imaging endoscopy showed no abnormalities suggesting gastric cancer. Endoscopic ultrasonography visualized the internally low-echoic SMT, harboring tiny cystic lesions, mainly within the second and third layers of the gastric wall. The SMT was removed by ESD to avoid retention and allow for comprehensive diagnosis. It was diagnosed as GCP with partial well-differentiated adenocarcinoma without involvement of the lateral and deep margins, lymphatic invasion, vascular invasion and perineural invasion. The gastric epithelium comprised normal mucosa without dysplasia. ESD seems to be useful for the diagnosis of SMT, including GCP harboring gastric cancer, and avoids unnecessary surgical procedures.


Dynamic structural rearrangements and functional regulation of voltage-sensing phosphatase.
The voltage-sensing phosphatase (VSP) consists of a voltage sensor domain (VSD) and a cytoplasmic catalytic region. The latter contains a phosphatase domain and a C2 domain, showing remarkable similarity to the tumour suppressor enzyme PTEN. In VSP, membrane depolarization induces a conformational change in the VSD, which activates the phosphoinositide phosphatase. The final outcome in VSP is enzymatic activity in the cytoplasmic region, unlike in voltage-gated ion channels where conformational change of the transmembrane pore is induced by the VSD. Therefore, it is crucial to detect structural change in the cytoplasmic catalytic region to gain insights into the operating mechanisms of VSP. This review summarizes a recent study in which a method of genetic incorporation of a non-canonical amino acid, Anap, was used to detect dynamic membrane voltage-controlled rearrangements of the structure of the catalytic region of sea squirt VSP (Ci-VSP). Upon membrane depolarization, both the phosphatase domain and the C2 domain move in a similar time frame, suggesting that the two regions are coupled to each other. Measurement of Förster resonance energy transfer (FRET) between Anap introduced into the C2 domain of Ci-VSP and dipicrylamine in the cell membrane suggested no large movement of the enzyme towards the membrane. Fluorescence changes in Anap induced by different membrane potentials indicate the presence of multiple conformations of the active enzyme.


Associations among Screen Time and Unhealthy Behaviors, Academic Performance, and Well-Being in Chinese Adolescents.
Screen time is negatively associated with markers of health in western youth, but very little is known about these relationships in Chinese youth. Middle-school and high-school students (n = 2625) in Wuhan, China, completed questionnaires assessing demographics, health behaviors, and self-perceptions in spring/summer 2016. Linear and logistic regression analyses were conducted to determine whether, after adjustment for covariates, screen time was associated with body mass index (BMI), eating behaviors, average nightly hours of sleep, physical activity (PA), academic performance, and psychological states. Watching television on school days was negatively associated with academic performance, PA, anxiety, and life satisfaction. Television viewing on non-school days was positively associated with sleep duration. Playing electronic games was positively associated with snacking at night and less frequently eating breakfast, and negatively associated with sleep duration and self-esteem. Receiving electronic news and study materials on non-school days was negatively associated with PA, but on school days, was positively associated with anxiety. Using social networking sites was negatively associated with academic performance, but positively associated with BMI z-score, PA and anxiety. Screen time in adolescents is associated with unhealthy behaviors and undesirable psychological states that can contribute to poor quality of life.


A large-scale stochastic spatiotemporal model for Aedes albopictus-borne chikungunya epidemiology.
Chikungunya is a viral disease transmitted to humans primarily via the bites of infected Aedes mosquitoes. The virus caused a major epidemic in the Indian Ocean in 2004, affecting millions of inhabitants, while cases have also been observed in Europe since 2007. We developed a stochastic spatiotemporal model of Aedes albopictus-borne chikungunya transmission based on our recently developed environmentally-driven vector population dynamics model. We designed an integrated modelling framework incorporating large-scale gridded climate datasets to investigate disease outbreaks on Reunion Island and in Italy. We performed Bayesian parameter inference on the surveillance data, and investigated the validity and applicability of the underlying biological assumptions. The model successfully represents the outbreak and measures of containment in Italy, suggesting wider applicability in Europe. In its current configuration, the model implies two different viral strains, thus two different outbreaks, for the two-stage Reunion Island epidemic. Characterisation of the posterior distributions indicates a possible relationship between the second larger outbreak on Reunion Island and the Italian outbreak. The model suggests that vector control measures, with different modes of operation, are most effective when applied in combination: adult vector intervention has a high impact but is short-lived, larval intervention has a low impact but is long-lasting, and quarantining infected territories, if applied strictly, is effective in preventing large epidemics. We present a novel approach in analysing chikungunya outbreaks globally using a single environmentally-driven mathematical model. Our study represents a significant step towards developing a globally applicable Ae. albopictus-borne chikungunya transmission model, and introduces a guideline for extending such models to other vector-borne diseases.


Delivering person-centred dementia care: Perceptions of radiography practitioners within diagnostic imaging and radiotherapy departments.
Despite abundant literature on the diagnosis of dementia, limited research has explored the lived experiences of radiography practitioners when providing care to people living with dementia in the department. This qualitative study explored the perceptions and compatibility of current professional guidance by both diagnostic imaging and radiotherapeutic radiography practitioners as well as the key stakeholders involved with developing the Society and College of Radiographers clinical practice guidelines for caring for people with dementia. This was a two-phase multi-method study. Fifteen diagnostic imaging and two therapeutic radiography practitioners from across the UK participated with online focus group discussions. Four key stakeholders involved with the development of the Society and College of Radiographers guidelines took part with individual semi-structured interviews. Data analysis included narrative and thematic analysis. Participants from both phases identified enablers and barriers to providing person-centred dementia care. Three superordinate themes were identified linked to (1) Working with care partners, (2) Departmental environmental design, and (3) Communication and interprofessional infrastructure. Many radiography practitioners still feel unprepared when caring for people living with dementia despite the clinical practice guidelines. Care partners were identified as having the potential to help alleviate some of the challenges radiographers faced. Participants were also aware of the impact of the departmental environment and recognised that poor way finding designs could lead to frustration. Radiography practitioners were not always aware that a patient was living with dementia prior to their attendance in the department making it difficult for practitioners to make appropriate accommodations such as additional time at appointments or the departmental environment. Our findings suggest there is a need for profession specific education and training for radiography practitioners to support the provision of person-centred dementia care. There is also a need to support the design of dementia friendly diagnostic imaging and radiotherapy departments.


Ovarian torsion in a 20-year-old patient.
Ovarian torsion is an uncommon gynecological emergency that requires prompt recognition and treatment. It may present with nonspecific signs and symptoms, and should be considered in any female with acute abdominal pain. The diagnosis is based on an awareness of the relevant risk factors, the clinical presentation, and a high index of suspicion. Timely investigation and management can make the difference between ovarian loss and salvage--an outcome of great importance in the population of reproductive age females.


Next-generation sequencing and biomarkers for gastric cancer: what is the future?
Recent years have witnessed an improved understanding of tumour biology and the molecular features of gastric cancer. Remarkable advances in next-generation sequencing technologies have defined the genomic landscape of gastric cancer. In fact, several molecular classifications have been proposed, and distinct molecular subtypes have been identified, which could serve as a roadmap for patient stratification and trials of targeted therapies. At present, clinical trials of new agents, such as receptor tyrosine kinases inhibitors, antibody-drug conjugates and IMAB362 (anti-Claudin 18.2), are ongoing. Furthermore, biomarkers of immune checkpoint inhibitors or combination therapy have been ardently investigated. These developments could facilitate precision medicine for gastric cancer in the near future.


Tumors of the mediastinum.
Tumors of the mediastinum represent a wide diversity of disease states. The location and composition of a mass is critical to narrowing the differential diagnosis. The most common causes of an anterior mediastinal mass include the following: thymoma; teratoma; thyroid disease; and lymphoma. Masses of the middle mediastinum are typically congenital cysts, including foregut and pericardial cysts, while those that arise in the posterior mediastinum are often neurogenic tumors. The clinical sequelae of mediastinal masses can range from being asymptomatic to producing symptoms of cough, chest pain, and dyspnea. This article will review the anatomy of the mediastinum as well as the different clinical, radiographic, and prognostic features, and therapeutic options of the most commonly encountered masses.


[Analysis on 2071 cases excluded from severe acute respiratory syndrome in Beijing].
To examine the characteristics of cases excluded from severe acute respiratory syndrome (SARS) and the reasons for exclusion. 2071 probable or suspected cases excluded from SARS between March and June, 2003 were analyzed. Two-thirds of the excluded cases were males. Construction workers, students and retired people ranked top three in all the occupation categories. Three peaks appeared in the dates of exclusion, and the most obvious one was from June 7 to June 13. There were two peaks in the distribution of time period from onset to exclusion, one was six to ten days and the other was forty-eight to fifty-two days after onset. Patients with history of close contact were more likely to be excluded within fifty days after onset than those without close history of contact. Pneumonia, common cold and lung infection were the leading causes for correction in the 1211 excluded cases. Study on the diagnosis and differential diagnosis should be emphasized.


Temporal trends in hip fracture incidence, mortality, and morbidity in Denmark from 1999 to 2012.
Background and purpose - While development in hip fracture incidence and mortality is well examined, none has yet looked at the temporal trends regarding prevalence of co-morbidities. Therefore we investigated changes in incidence of first hip fracture, co-morbidity prevalence, 30 day- and 1-year mortality in hip fracture patients in the Danish population during the period 1999 to 2012. Patients and methods - Patients >18 years admitted with a fractured hip in Denmark between 1996 and 2012 were identified with data for the period 1999-2012 being analyzed regarding prevalence of co-morbidities, incidence, and mortality. Results - 122,923 patients were identified. Incidence in the whole population declined but sex-specific analysis showed no changes for men. For the whole study population, 30-day and 1-year mortality remained unchanged. Age at time of first hip fracture also remained unchanged. Of the included co-morbidities a decrease in prevalence of malignancy and dementia in women was found while there was an increase in the prevalence of all remaining co-morbidities, except hemi- or paraplegia for both sexes, rheumatic diseases for women, and for men diabetes with complications, myocardial infarction, AIDS/HIV, and malignancy. Interpretation - While hip fracture incidence declined for women it was unchanged for men; likewise, 30-day and 1-year mortality rates together with age at first fracture remained unchanged. When these results are compared with the relatively large increase in the prevalence of co-morbidities, it does not seem likely that the increased disease burden is affecting either the incidence or the mortality.


Heat-Shock Protein Expression in Mytilus californianus: Acclimatization (Seasonal and Tidal-Height Comparisons) and Acclimation Effects.
Heat-shock protein (hsp) expression was examined in gill of field-acclimatized and laboratory-acclimated mussels (Mytilus californianus) from the Oregon coast. Endogenous levels of heat-shock proteins in the 70-kDa class (hsp70 isoforms) and profiles of induction temperature for newly synthesized hsp 70 were measured in freshly field-collected specimens as functions of location height in the intertidal and season, and in mussels after 7 weeks of laboratory thermal acclimation. There were significant differences in endogenous levels of hsp70 as functions of season and collection height. Strong induction of new hsp70 synthesis occurred at body temperatures within the range measured in field specimens. Profiles of hsp70 thermal induction varied significantly with season, but not with height of collection. In contrast to the large differences in hsp70 expression between winter- and summer-acclimatized mussels, no differences related to temperature occurred in the differently acclimated mussels. The differences found between the effects of field acclimatization and laboratory thermal acclimation suggest that the stress response is modulated by environmental factors in addition to body temperature. Thus, caution is required in extrapolating from laboratory acclimation studies to acclimatization effects in field populations. The seasonal and tidal-height variations in the heat-shock response are discussed in the context of energy costs of protein turnover.


Peritoneal lavage in acute pancreatitis. An experimental and clinical study.
Experiments were performed to evaluate the use of peritoneal lavage in dogs, in which an acute non fatal necrotic-hemorrhagic pancreatitis was obtained by means of intraductal sodium-taurocholate injection. A single lavage of 2 liters of a balanced solution 6 hours after the pancreatitis onset produced a temporary biochemical improvement, as evidenced by the amylase, lipase and alcaline phosphatase values. Triple lavage with or without heparin, performed after 6, 18 and 24 hours, produced on the other hand clearcut reduction in mortality rates and long lasting improvement of the biochemical parameters. Two patients with operatively confirmed necrotic hemorrhagic pancreatitis were treated by the lavage method during three days. The treatment resulted in a significant improvement of the clinical condition and the biochemical parameters of both patients.


[Nursing in transmissible diseases: how to approach this topic in nursing graduation?].
This study relates the attempts of the discipline Collective Health Nursing with focus in transmissible diseases to reorganize its teaching object, its theoretical and practical content, and its pedagogical atrategics, as a contribution to the formation of a nursing professional compromised with Collective Health. It describes the context of Collective Health in Brazil and the characteristics needed to improve the implementation of the Unified Health Care System in the Country. It also reports the content and the padagogical strategics used in the discipline and makes a critical analysis of its potentialities and limitations to the proposed goal.


Comparison of the effects of human erythrocyte ghosts and intact erythrocytes on platelet interactions with subendothelium in flowing blood.
We investigated whether ghosts behaved similarly to intact erythrocytes to maintain regular primary hemostasis under flow conditions. To this end we performed perfusion experiments with whole blood in which erythrocytes were replaced by pink ghosts, and platelet interaction with the subendothelial surface of a damaged vessel was morphometrically evaluated. The same objective was sought by means of studies with a platelet function analyzer (PFA-100(TM) instrument). Perfusions performed with control blood reconstituted with intact erythrocytes gave rise to 0.4+/-0.2% contact but not spread platelets, 10.8+/-3.4% adhering and spread platelets, 16.3+/-4.6% platelets in thrombi, with 27.5+/-7.4% of the surface covered. Even though the average diameter of the ghosts was smaller than that of intact erythrocytes (5.3 microm vs. 7.7 microm), the values obtained in perfusions performed with ghosts were similar to those of the erythrocyte controls. Studies performed with the PFA-100(TM) analyzer were consistent with those observed in perfusion studies. The viscosity of control blood was compared with that of blood reconstituted with ghosts. At shear rates lower than 450 s(-1), the viscosity of the ghost samples was higher than that of the controls, but the difference progressively decreased as shear rate increased up to 750 s(-1) (3.61+/-0.15 and 3.71+/-0.17 cP, respectively). In conclusion, the results of our study showed that ghosts behaved similarly to intact erythrocytes in maintaining a normal platelet interaction with digested subendothelium, under conditions of moderate shear rate and constant hematocrit (40%). The rheological activity of ghosts, bodies that are metabolically less active, was sufficient for them to satisfactorily act as substitutes for intact erythrocytes in our system.


The community management of chylous fistula using a pancreatic lipase inhibitor (orlistat).
We describe two innovative ideas in the treatment of iatrogenic chyle leak. The first is the early use of a pancreatic lipase inhibitor (Orlistat) to reduce fat absorption and chyle production, with consequent faster fistula healing. The second is the treatment of these patients at home in the community by district nurses backed by the hospital staff. This domiciliary approach has a positive psychological effect on the patient, permits the patient to take responsibility for their treatment, and reduces hospital length of stay minimising patient exposure to nosocomial infections.


The mutual cooperation of blood platelets and lymphocytes in the development of autoimmune thyroid diseases.
Autoimmune thyroid diseases include several distinct clinical entities, mainly Graves' disease and Hashimoto's thyroiditis. An incompetent immune response directed against the body's own tissues, and the production of antibodies against specific cell antigens accompanied by chronic inflammation, all occur in autoimmune thyroid diseases. The autoimmune process is induced by genetic and environmental factors that are difficult to identify and generates the development of concomitant diseases in other systems. Leukocyte activation and overproduction of inflammatory mediators, as well as improper levels of thyroid hormones, play an essential role in the chronic course of these diseases. The development of autoimmune thyroid diseases results from the impairment of the regulatory and suppressor functions of T-cells or NK cells and activation of B cells, or from the changes in the number of those cells. Many reports have shown the significant role of platelet-leukocyte interaction in inflammation. Autoantibodies react with target antigens in different kinds of cells, including blood platelets, and autoimmune processes can modulate the mutual cooperation of blood platelets and lymphocytes. The activity of blood platelets and lymphocytes is reciprocally regulated. It has been suggested that blood platelets can influence lymphocyte function by direct contact with receptors, and indirectly via soluble mediators. The interactions of platelet-immune cells (neutrophils, monocytes, lymphocyte and dendritic cells) can have a potent enhancing effect on immune cells functions.


Spinal cholinergic alpha-2 adrenergic interactions in analgesia and hemodynamic control: role of muscarinic receptor subtypes and nitric oxide.
Intrathecal injection of neostigmine enhances antinociception from clonidine while it counteracts clonidine-induced hypotension. This study further examined the pharmacology of neostigmine-clonidine interactions in the spinal cord and focused on the roles of muscarinic receptor subtypes and local nitric oxide synthesis. Spinal neostigmine counteracted clonidine-induced decreases in blood pressure and heart rate in conscious sheep and this effect was blocked by spinal injection of the M2 muscarinic antagonist, AFDX-116, but not by the M1 muscarinic antagonist, pirenzepine. Carbamylcholine injected spinally alone increased blood pressure and heart rate and these effects and neostigmine's hemodynamic interaction with clonidine were blocked by spinal injection of the nitric oxide synthase inhibitor, N-methyl-L-arginine. The authors also investigated antinociceptive interactions by using a mechanical pressure stimulus on the forelimb of conscious sheep. Spinal clonidine produced dose-dependent antinociception, which was enhanced by neostigmine and antagonized by N-methyl-L-arginine. NADPH diaphorase staining of sheep spinal cord revealed dense localization to the superficial dorsal horn and the intermediolateral cell column. These results suggest that counteraction of spinal clonidine-induced hypotension by neostigmine is due to stimulation of spinal M2 muscarinic receptors and synthesis of nitric oxide. Nitric oxide synthesis is also necessary for clonidine-induced antinociception in sheep.


Two Postmodernisms in Rheumatology.
While randomization is an essential tool of data collection and interpretation, it can be misused. One such misuse is using a subgroup of a data set for validation purposes after randomizing the whole data set into two groups after which we attempt to validate the outcome data from one group with the outcome in the other. This surely validates only the randomization process. Two examples are given from disease criteria reports from Behçet's syndrome and gout. P-values are misunderstood and misused, and this is usually in the direction of investigators trying to show significant differences in their studies. Another, less criticized, misuse of the p-value is when the investigators try to use an insignificant and close to unity p-value as evidence for no difference. This author calls this a postmodern p-value.


Glucose intolerance: the hidden danger in hypertensives!
Both systemic hypertension and abnormalities of glucose metabolism are independent recognised risk factors for the development of cardiovascular morbidity and mortality, but their effects become additive when they coexist. Hypertension and glucose intolerance increase arterial stiffness and lead to cardiac structural and functional changes such as left ventricular hypertrophy and diastolic dysfunction of the left ventricle. Oral glucose tolerance tests have shown that 58% of patients with systemic hypertension who have no cardiac history and who are not known to have diabetes, suffer from unrecognised abnormalities of glucose metabolism i.e. either diabetes or impaired glucose tolerance. Using the fasting plasma glucose level and/or glycated haemoglobin concentration to diagnose glucose intolerance in patients with systemic hypertension is insufficient because of their low sensitivity for the diagnosis of diabetes and their inability to identify impaired glucose tolerance. It is important to recognise abnormalities of glucose metabolism early in patients with systemic hypertension in order to implement appropriate management and avoid further complications. Failure to identify glucose intolerance results in serious underestimation of the cardiovascular risk of these patients and denies patients primary preventative measures, which are based on risk assessment. All patients referred to Hypertension Clinics for the management of raised blood pressure should therefore be investigated by glucose tolerance test.


Bacterial carbohydrate structure database 3: principles and realization.
Bacterial carbohydrate structure database (BCSDB) is an open-access project that collects primary publication data on carbohydrate structures originating from bacteria, their biological properties, bibliographic and taxonomic annotations, NMR spectra, etc. Almost complete coverage and outstanding data consistency are achieved. BCSDB version 3 and the principles lying behind it, including glycan description language, are reported.


Fungal sinusitis: progression of disease in immunosuppression--a case report.
Fungal sinusitis is a disease which can be grouped into invasive and noninvasive forms. The invasive entities include the acute/fulminant and chronic/indolent forms. The noninvasive entities include the fungus ball and allergic forms. The noninvasive forms, however, can develop into invasive disease under certain immunosuppressive states. The patient in this case report had the fungus ball form of fungal sinusitis which evolved into chronic, and then the acute/fulminant form approximately two weeks after undergoing cadaver-donor kidney transplantation. Due to the patient's immunosuppressed state, the fungus spread beyond the sinus region and eventually lead to fulminant disseminated disease. The severity of the fungal disease corresponded directly to the severity of the patient's immunosuppression.


Advanced Multicompartment Diffusion MRI Models and Their Application in Multiple Sclerosis.
Conventional MR imaging techniques are sensitive to pathologic changes of the brain and spinal cord seen in MS, but they lack specificity for underlying axonal and myelin integrity. By isolating the signal contribution from different tissue compartments, newly developed advanced multicompartment diffusion MR imaging models have the potential to detect specific tissue subtypes and associated injuries with increased pathologic specificity. These models include neurite orientation dispersion and density imaging, diffusion basis spectrum imaging, multicompartment microscopic diffusion MR imaging with the spherical mean technique, and models enabled through high-gradient diffusion MR imaging. In this review, we provide an appraisal of the current literature on the physics principles, histopathologic validation, and clinical applications of each of these techniques in both brains and spinal cords of patients with MS. We discuss limitations of each of the methods and directions that future research could take to provide additional validation of their roles as biomarkers of axonal and myelin injury in MS.


Linomide blocks angiogenesis by breast carcinoma vascular endothelial growth factor transfectants.
The blocking of angiogenesis provides a novel therapeutic target to inhibit tumour spreading. In this study, we investigated the effect of linomide on angiogenesis induced in vivo by highly angiogenic breast carcinoma cells. The rabbit cornea was used to assess neovascular growth in the absence of a tumour mass. MCF-7 cells stably transfected with the cDNA encoding for vascular endothelial growth factor 121 (VEGF121) (V12 clone) were used to elicit a potent VEGF-dependent corneal angiogenesis. After tumour cell implant, albino rabbits received 100 mg kg(-1) day(-1) linomide for 5 consecutive days. Daily observation of neovascular progression indicated that linomide blocked angiogenesis. The antiangiogenic effect of linomide was apparent within 48 h from the beginning of the treatment and was both angiosuppressive and angiostatic. The block of neovascular growth lasted over 10 days from treatment suspension, and preformed vessels, which had regressed, remained dormant, suggesting the persistence of unfavourable conditions for capillary progression. Linomide (50-200 microg ml[-1]) was not cytotoxic in vitro on resting capillary endothelial cells but blocked endothelial cell replication induced by VEGF. Our data indicate that linomide can efficiently and persistently block VEGF-dependent angiogenesis in vivo in the absence of a growing tumour mass. These data suggest that linomide could be a chemopreventive drug in breast cancer patients and a valuable tool in clinical settings in which metastatic spreading occurs in the absence of a detectable tumour mass.


[Possibilities and limitations of drugs to protect the liver].
In this paper preventive liver protective agents for the prophylaxis of hepatopathies due to functional stress, and curative protective agents for therapy of existing liver damage are distinguished. Preventive liver protective agents are key substances in the metabolism of proteins, carbohydrates, lipids, and sulfur. For curative liver protective agents, inhibitors of RNA and protein synthesis, calcium antagonists and inhibitors of sulfhydryl (-SH) containing enzymes are proposed and substantiated.


Gastrointestinal parasites in the immunocompromised.
Parasites and other infections have many effects on the gastrointestinal tract of individuals who are immunocompromised. Few reviews focus on parasitic infections, which are covered here. The review first examines recent advances in our understanding of the taxonomy, diagnosis and treatment of pathogens such as cryptosporidia, cyclospora, isospora and microsporidia, which are recognized causes of diarrhoea in the immunocompromised, and discusses possible links between amoebiasis and HIV. The complex interactions of both intact and abnormal immune systems with helminth infections such as hookworm and strongyloidiasis, and with trematode infections such as schistosomiasis, are receiving increasing attention. These are discussed, together with the novel concept of using live helminths to treat inflammatory bowel disease. Parasitic infections remain a significant problem for immunocompromised individuals in resource-poor settings, and further work is needed to develop accessible diagnostic tests and to improve our understanding and management of their pathogenic effects. New concepts about the interactions of helminths with host immunity suggest the need for collection of further epidemiological and clinical data to unravel the complexities of such immunological interactions.


[THE INTERPRETATION OF RESULTS OF DETECTION OF AGENTS OF VIRAL DIARRHEA IN REAL-TIME MODE].
The study was carried out to establish values of parameters characterizing concentrations of pathogens (threshold cycle - Ct) correlating with acute phase of viral gastroenteritis. The groups of patients with sporadic and group morbidity of acute intestinal infections were examined. The reagents kits Amplience (The central research institute of epidemiology, Russia), in real-time format polymerase chain reaction were applied to detect Rotavirus grA, Norovirus GII, Astrovirus, Adenovirus grF, Shigella spp, EIEC, Salmonella spp, Campylobacter spp (thermophilic group).The analysis was applied to distribution of Ct depending on isolated and combined detection ofpathogens in clinical samples. The evaluation was implemented concerning effect on Ct values of both inhibitors of polymerase chain reaction contained in feces and application of various amplifiers such as Rotor-Gene Q (QIAGEN, Germany), CFX96 (Bio-Rad, USA), "DT-96" (DNA technology, Russia). The risks of cross contamination during carrying out of investigations are evaluated. The asymmetric or bi-modal character of distribution of Ct values related to cases of combined detection of several pathogens is established. The following indicators are established common for patients with mono-infections (Ct mean ± SD): Rotavirus grA (Ct 20.63 ± 6.35; n = 978), Norovirus GII Astrovirus (Ct 21.06 ± 6.54; n = 54), Adenovirus grF (Ct 8.42 ± 2.4; n = 42). The corresponding values for victims of infective episodes amounted to Norovirus GII (24.19 ± 5.29; n = 447) and Rotavirus grA (18.65 ± 4.16; n = 50). The recommendations are presented concerning practical interpretation of results of real-time polymerase chain reaction. The indirect characteristic of content of pathogens in samples of clinical material derived from real-time polymerase chain reaction provides important information about association of pathogen with acute phase of disease. The high informativeness of given type of investigations support possibility of its effective implementation not only doing etiologic diagnostic but also in case of isolation of pathogen in clinically healthy individuals and examination of objects of environment.


The electrochemical regeneration of NAD(+) revisited.
An actual yield of 99.97% (i.e., 3000 potential regenerating cycles) has been obtained for the electrochemical regeneration of NAD(+). The deactivation of the coenzyme is not related to the number of cycles; it is only time dependent. For biotechnological applications, these results show that electrochemical regeneration can compete with enzymatic regeneration for selective oxidation by dehydrogenases.


A review of selected nutrition & health surveys in India.
Assessment of the status of health and nutrition of a population is imperative to design and implement sound public health policies and programmes. The various extensive national health and nutrition surveys provide national-level information on different domains of health. These provide vital information and statistics for the country, and the data generated are used to identify the prevalence and risk factors for the diseases and health challenges faced by a country. This review describes the various national health and nutrition surveys conducted in India and also compares the information generated by each of these surveys. These include the National Family Health Survey, District Level Household Survey, Annual Health Survey, National Nutrition Monitoring Bureau Survey, Rapid Survey on Children and Comprehensive National Nutrition Survey.


Enhancement of Exciton-Phonon Scattering from Monolayer to Bilayer WS2.
Layered transition metal dichalcogenides exhibit the emergence of a direct bandgap at the monolayer limit along with pronounced excitonic effects. In these materials, interaction with phonons is the dominant mechanism that limits the exciton coherence lifetime. Exciton-phonon interaction also facilitates energy and momentum relaxation, and influences exciton diffusion under most experimental conditions. However, the fundamental changes in the exciton-phonon interaction are not well understood as the material undergoes the transition from a direct to an indirect bandgap semiconductor. Here, we address this question through optical spectroscopy and microscopic theory. In the experiment, we study room-temperature statistics of the exciton line width for a large number of mono- and bilayer WS2 samples. We observe a systematic increase in the room-temperature line width of the bilayer compared to the monolayer of 50 meV, corresponding to an additional scattering rate of ∼0.1 fs-1. We further address both phonon emission and absorption processes by examining the temperature dependence of the width of the exciton resonances. Using a theoretical approach based on many-body formalism, we are able to explain the experimental results and establish a microscopic framework for exciton-phonon interactions that can be applied to naturally occurring and artificially prepared multilayer structures.


Cellular interactions between L-arginine and asymmetric dimethylarginine: Transport and metabolism.
This study was aimed to examine the effect of L-arginine (ARG) exposure on the disposition of asymmetric dimethylarginine (ADMA) in human endothelial cells. Although the role of ADMA as an inhibitor of endothelial nitric oxide synthase (eNOS) is well-recognized, cellular interactions between ARG and ADMA are not well-characterized. EA.hy926 human vascular endothelial cells were exposed to 15N4-ARG, and the concentrations of 15N4-ARG and ADMA in the cell lysate and incubation medium were determined by a liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) assay. Nitric oxide (NO) production was estimated by utilizing cumulative nitrite concentration via a fluorometric assay. Cells incubated with 15N4-ARG exhibited enhanced nitrite production as well as 15N4-ARG cellular uptake. These changes were accompanied by a decrease in cellular ADMA level and increase in extracellular ADMA level, indicating an efflux of endogenous ADMA from the cell. The time courses of ADMA efflux as well as nitrite accumulation in parallel with 15N4-ARG uptake were characterized. Following preincubation with 15N4-ARG and D7-ADMA, the efflux of cellular 15N4-ARG and D7-ADMA was significantly stimulated by high concentrations of ARG or ADMA in the incubation medium, demonstrating trans-stimulated cellular transport of these two amino acids. D7-ADMA metabolism was inhibited in the presence of added ARG. These results demonstrated that in addition to an interaction at the level of eNOS, ARG and ADMA may mutually influence their cellular availability via transport and metabolic interactions.


Reproducibility and accuracy of three methods for assessment of demineralization depth of the occlusal surface: an in vitro examination.
This laboratory study of 100 occlusal surfaces investigated the reproducibility and accuracy of a visual ranked caries scoring system, an electronic caries scoring system (ECM) using a continuous conductance scale, and a radiographic ranked caries scoring system. Histological examination of the teeth served as a gold standard to validate the ability of each system to assess lesion depth and predict softened, demineralized dentine. After training, 3 examiners carried out each scoring system on two separate occasions. Kappa values for visual, ECM and radiographic ranked scoring systems showed good inter- and intra-examiner reproducibility levels and acceptable limits of agreement for ECM readings. When scoring systems were tabulated against histological scores there was a high correlation between the visual and ECM methods and lesion depth in both enamel and dentine, but radiographic examination could not detect enamel caries. When compared to the histological scoring, the Spearman correlation coefficients for the visual scoring ranged between 0.87 and 0.93, for the ECM between 0.80 and 0.85 and for the radiographic scoring system between 0.76 and 0.78. No tooth scored as visually sound had histological evidence of dentine caries. Soft dentine corresponded to demineralization involving the middle third of the dentine or more which was related to visual cavity formation or an ECM reading above 9 (score 3 or 4). The radiograph was an excellent predictor of soft dentine. In conclusion, the new visual system appears promising, but takes time to learn. The reproducibility and accuracy for the ECM is acceptable while radiographs miss early occlusal lesions.


Severe hip and knee pain in a man with chronic tophaceous gout.
Gout is a common rheumatologic condition with characteristic clinical presentations during the acute arthritis and chronic tophaceous stages. Because of this, there is a tendency to overlook rare but important conditions which are independent of, but can co-exist with gout. This case of severe hip and knee pain in a patient with tophaceous gout takes the reader on a problem-solving exercise which simulates the analytical processes and decisions made in the clinic.


Changing pattern of sensitization in Croatia to aeroallergens in adult population referring to allergy clinic during a period of 15 years.
Published data indicate that during the last decades there is a possible change in the pattern of sensitization to different aeroallergens in adult population with atopy. The aim of this investigation was based on the hypothesis that during last 15 years there has been a change in the structure of prevalence of sensitization to different aeroallergens in adult population of Zagreb and its surroundings with atopy. Medical records from outpatient allergy clinic were screened for the period 1991-2004. We included 794 patients during years 1991-1994, 814 patients during years 1995-1999, and 969 patients during years 2000-2004. Following data were analyzed: age, gender, education level, residence, referral diagnosis, dominant symptoms, results of skin-prick test (SPT), total and specific serum immunoglobulin E. As risk factors for allergic sensitization we determined the decade of birth (p < 0.0001), male gender (p < 0.008), level of education (p < 0.0001), and place of residence (p < 0.05). Proportion of sensitized individuals to pollen significantly increased from the period 1991-1994 towards 2000-2004 (p < 0.001 for the trend) with a significant increase in the proportion of sensitized individuals to weed pollen (p = 0.002 for the trend) while the proportion of sensitized to other two groups of pollen (grasses and trees) was not significantly different. A significant increase in the proportion of sensitized individuals was determined for sensitization to ragweed pollen (p = 0.004 for the trend), and to mugwort (p = 0.005 for the trend). Despite all its limitations primarily based on the selection bias the results of this study are conclusive about the significant change in the proportion of sensitization to different aeroallergens and different pollen groups and individual pollen species during the investigated 15-year time interval.


Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the Endocytosis Pathway Analysis and Intracellular Localization.
Using renewable and biocompatible natural-based resources to construct functional biomaterials has attracted great attention in recent years. In this work, we successfully prepared a series of steroid-based cationic lipids by integrating various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile and efficient synthetic approach. The plasmid DNA (pDNA) binding affinity of the steroid-based cationic lipids, average particle sizes, surface potentials, morphologies and stability of the steroid-based cationic lipids/pDNA lipoplexes were disclosed to depend largely on the steroid skeletons. Cellular evaluation results revealed that cytotoxicity and gene transfection efficiency of the steroid-based cationic lipids in H1299 and HeLa cells strongly relied on the steroid hydrophobes. Interestingly, the steroid lipids/pDNA lipoplexes inclined to enter H1299 cells mainly through caveolae and lipid-raft mediated endocytosis pathways, and an intracellular trafficking route of "lipid-raft-mediated endocytosis→lysosome→cell nucleic localization" was accordingly proposed. The study provided possible approach for developing high-performance steroid-based lipid gene carriers, in which the cytotoxicity, gene transfection capability, endocytosis pathways, and intracellular trafficking/localization manners could be tuned/controlled by introducing proper steroid skeletons/hydrophobes. Noteworthy, among the lipids, Cho-Arg showed remarkably high gene transfection efficacy, even under high serum concentration (50% fetal bovine serum), making it an efficient gene transfection agent for practical application.


Inaugural Survey on Practice Patterns of Orbital Floor Fractures for American Oral and Maxillofacial Surgeons.
In recent years, several studies have reported on practitioners' preferences for the treatment of orbital floor fractures, showing widely varying practice patterns. The purpose of the present study was to identify the practice patterns among oral and maxillofacial surgeons involved in the management of orbital floor fractures in the United States and compare them with the available published data. An anonymous survey was created and electronically mailed to surgeons. We also reviewed the published data on orbital floor fractures using a PubMed and MEDLINE search. The responses to the survey were analyzed using descriptive statistics. The factors that had the greatest influence on the surgeon's decision to operate were a defect size > 2 cm2, enophthalmos, entrapment, and persistent diplopia. The most common surgical approach reported was a preseptal transconjunctival approach (32.0%), followed by the subciliary (27.9%) and postseptal transconjunctival (26.2%) approaches. The most commonly reported implant for orbital reconstruction was titanium (65.4%), followed by Medpor (43.7%) and composite Medpor and titanium (26.4%). The review of the published data showed a consensus among many of the operative indications mentioned, including a large defect size, enophthalmos, clinical entrapment, and persistent diplopia. Oral and maxillofacial surgeons in the United States have a wide range of practice habits in the management of orbital floor fractures. Although the quality of the available evidence is poor, it supports a consistent approach to the management of orbital floor fractures in terms of the indications and surgical approach. The choice of reconstructive material and timing of repair remain more controversial. A clear need exists for improvement in the available data to help guide and set standards of care for the specialties managing orbital floor fractures.


LC-MS/MS method for simultaneous determination of flavonoids and physalins in rat plasma: Application to pharmacokinetic study after oral administration of Physalis alkekengi var. franchetii (Chinese lantern) extract.
A rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of luteolin, luteolin-7-O-β-D-glucopyranoside, physalin A, physalin D and physalin L in rat plasma. Scutellarein and dexamethasone were used as the internal standards (IS). Plasma samples were prepared by liquid-liquid extraction with ethyl acetate. The five constituents were separated on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm). A gradient elution procedure was used with acetonitrile (A)-0.1% aqueous formic acid (B). Mass spectrometric detection was performed in negative ion multiple reaction monitoring mode with an electrospray ionization (ESI) source. This method showed good linearity (r2 > 0.997) over a concentration range of 2.0-500 ng/mL with a lower limit of quantification of 2.0 ng/mL for all five compounds. The inter- and intra-day accuracy ranged from 91.7 to 104%, and precisions (RSD) were <6.46% for all analytes. The extraction recoveries of all analytes were >85%. This validated method was successfully applied for the first time to the pharmacokinetic study of five ingredients after oral administration of 70% ethanol extract of Chinese lantern in rats.


Metagenomic insights into the microbial cooperative networks of a benz(a)anthracene-7,12-dione degrading community from a creosote-contaminated soil.
Genotoxicity of PAH-contaminated soils can eventually increase after bioremediation due to the formation and accumulation of polar transformation products, mainly oxygenated PAHs (oxy-PAHs). Biodegradation of oxy-PAHs has been described in soils, but information on the microorganisms and mechanisms involved is still scarce. Benz(a)anthracene-7,12-dione (BaAQ), a transformation product from benz(a)anthracene frequently detected in soils, presents higher genotoxic potential than its parent PAH. Here, using sand-in-liquid microcosms we identified a specialized BaAQ-degrading subpopulation in a PAH-contaminated soil. A BaAQ-degrading microbial consortium was obtained by enrichment in sand-in-liquid cultures with BaAQ as sole carbon source, and its metagenomic analysis identified members of Sphingobium, Stenotrophomonas, Pusillimonas, Olivibacter, Pseudomonas, Achromobacter, and Hyphomicrobiales as major components. The integration of data from metabolomic and metagenomic functional gene analyses of the consortium revealed that the BaAQ metabolic pathway was initiated by Baeyer-Villiger monooxygenases (BVMOs). The presence of plasmid pANTQ-1 in the metagenomic sequences, identified in a previous multi-omic characterization of a 9,10-anthraquinone-degrading isolate recovered from the same soil, suggested the occurrence of a horizontal gene transfer event. Further metagenomic analysis of the BaAQ-degrading consortium also provided insights into the potential roles and interactions within the consortium members. Several potential auxotrophies were detected, indicating that relevant nutritional interdependencies and syntrophic associations were taking place within the community members, not only to provide suitable carbon and energy sources, but also to supply essential nutrients and cofactors. Our work confirms the essential role that BVMO may play as a detoxification mechanism to mitigate the risk posed by oxy-PAH formation during bioremediation of contaminated soils.


Bone geometry and strength are adapted to muscle force in children and adolescents perinatally infected with HIV.
To determine if bone health is compromised in perinatally HIV-infected youth. We assessed BMC at the proximal femur, lumbar spine and total body using DXA in perinatally HIV-infected youth (n=31; 9-18y). Using pQCT, we assessed muscle CSA, total and cortical bone area, cortical BMD and thickness and strength strain index at the tibial shaft. Thirty and 18 participants returned at 12- and 24-months, respectively. We calculated age- and sex-specific z-scores for the HIV-infected youth using data from a healthy cohort (n=883; 9-18y). At baseline, height and MCSA were reduced in HIV-infected youth (-0.79 to -0.23, p<0.05). BMC z-scores adjusted for height and lean mass were lower than controls at all sites except the lumbar spine (-0.57 to -0.27, p<0.05). Bone area and strength z-scores were not different from zero after adjusting for tibial length and MCSA. In contrast, cortical BMD z-scores were greater in HIV-infected youth (0.46, p=0.011). Z-scores for all bone outcomes showed positive trends over time in HIV-infected youth. Although HIV infection may be associated with bone mass deficits during growth, bone geometry and strength appear adapted to muscle force. Further, deficits in bone mass may dissipate over time in this population.


Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma.
Blindness affects 60 million people worldwide. The leading causes of irreversible blindness include age-related macular degeneration, retinal vascular diseases and glaucoma. The unique features of the eye provide both benefits and challenges for drug discovery and delivery. During the past decade, the landscape for ocular drug therapy has substantially changed and our knowledge of the pathogenesis of ophthalmic diseases has grown considerably. Anti-angiogenic drugs have emerged as the most effective form of therapy for age-related macular degeneration and retinal vascular diseases. Lowering intraocular pressure is still the mainstay for glaucoma treatment but neuroprotective drugs represent a promising next-generation therapy. This Review discusses the current state of ocular drug therapy and highlights future therapeutic opportunities.


Genetic diversity and accession structure in European Cynara cardunculus collections.
Understanding the distribution of genetic variations and accession structures is an important factor for managing genetic resources, but also for using proper germplasm in association map analyses and breeding programs. The globe artichoke is the fourth most important horticultural crop in Europe. Here, we report the results of a molecular analysis of a collection including globe artichoke and leafy cardoon germplasm present in the Italian, French and Spanish gene banks. The aims of this study were to: (i) assess the diversity present in European collections, (ii) determine the population structure, (iii) measure the genetic distance between accessions; (iv) cluster the accessions; (v) properly distinguish accessions present in the different national collections carrying the same name; and (vi) understand the diversity distribution in relation to the gene bank and the geographic origin of the germplasm. A total of 556 individuals grouped into 174 accessions of distinct typologies were analyzed by different types of molecular markers, i.e. dominant (ISSR and AFLP) and co-dominant (SSR). The data of the two crops (globe artichoke and leafy cardoon) were analyzed jointly and separately to compute, among other aims, the gene diversity, heterozygosity (He, Ho), fixation indexes, AMOVA, genetic distance and structure. The findings underline the huge diversity present in the analyzed material, and the existence of alleles that are able to discriminate among accessions. The accessions were clustered not only on the basis of their typology, but also on the basis of the gene bank they come from. Probably, the environmental conditions of the different field gene banks affected germplasm conservation. These outcomes will be useful in plant breeding to select accessions and to fingerprint varieties. Moreover, the results highlight the particular attention that should be paid to the method used to conserve the Cynara cardunculus germplasm and suggest to the preference of using accessions from different gene banks to run an association map.


A Potential Prognostic Biomarker for Glioma: Aldo-Keto Reductase Family 1 Member B1.
Aldo-keto reductase family 1 member B1 (AKR1B1) plays a vital role in tumor development and is involved in the tumor immune process. However, its role in glioma cell is poorly studied. This study's aim was to assess the role of AKR1B1 in glioma through bioinformatics analysis. The AKR1B1 expression data and corresponding clinical data of glioma were collected from the Cancer Genome Atlas (TCGA) database. The R packages were used for data integration, extraction, analysis, and visualization. According to the median value of the risk score, all patients were divided into high-risk and low-risk groups to draw the Kaplan-Meier (KM) survival curves and to explore the level of immune infiltration. The expression of AKR1B1 was significantly elevated in glioma tissues compared to normal tissues (P < 0.001). The high expression of AKR1B1 was significantly associated with WHO grade (P < 0.001), IDH status (P < 0.001), 1p/19q codeletion (P < 0.001), primary therapy outcome (P = 0.004), and age (P < 0.05). Kaplan-Meier survival analysis found that OS (HR = 3.75, P < 0.001), DSS (HR = 3.85, P < 0.001), and PFI (HR = 2.76, P < 0.001) were lower in patients with glioma with high AKR1B1 expression than in the group with low AKR1B1 expression. Based on GESA, six pathways (including interferon gamma signaling, signaling by interleukins, cell cycle checkpoints, cytokine receptor interaction, cell adhesion molecules (CAMs), and cell surface interactions) at the vascular wall were identified as significantly different between the two groups. Moreover, highly expressed AKR1B1 was associated with immune cell infiltration. AKR1B1 plays a key role in glioma progression and prognosis and, therefore, serves as a potential biomarker for prediction of patients' survival.


[Response of human growth hormone to anesthesia induction with propofol].
Although there are distinct differences in both pharmacokinetics and chemical structure, propofol has sedative effects similar to those of benzodiazepines. Both diazepam and thiopental, commonly used agents for inducing anaesthesia, show some typical neuroendocrine effects such as liberation of human growth hormone (hGH) in addition to their well-known influences on the cardiovascular system. It was our aim to examine the endocrine response of hGH after induction of anaesthesia with propofol and to compare any possible effects with those of diazepam and thiopental. The study was performed on 30 non-premedicated patients, who underwent plastic-surgery (mean age: x = 35 +/- 8.3 years, mean body weight: x = 68.9 +/- 23.2 kg). No signs of endocrine disturbances were found in the patients prior to the study. Patients were divided in a random fashion into 3 groups of 10 persons each: In group 1 propofol was given in a bolus injection (2 mg/kg) and then by infusion for a period of 10 min (0.2 mg/kg/min). In group 2 diazepam (0.3 mg/kg) and in group 3 thiopental (5 mg/kg) were administered as a bolus to induce anesthesia. All patients were intubated immediately after induction of anesthesia and then relaxed using vecuronium (1 mg/kg). Ventilation was performed mechanically during the entire operative period (N2O/O2 - FiO2:0.33, tidal volume 10 ml/kg, respiratory rate: 14/min). To maintain anesthesia halothane (0.5-1.0 vol.-%) and meperidine (0.75 mg/kg) were added 15 min after induction.(ABSTRACT TRUNCATED AT 250 WORDS)


Polymer- and dendrimer-coated magnetic nanoparticles as versatile supports for catalysts, scavengers, and reagents.
The work-up of chemical reactions by standard techniques is often time consuming and energy demanding, especially when chemists have to guarantee low levels of metal contamination in the products. Therefore, scientists need new ideas to rapidly purify reaction mixtures that are both economically and environmentally benign. One intriguing approach is to tether functionalities that are required to perform organic reactions to magnetic nanoparticles, for example, catalysts, reagents, scavengers, or chelators. This strategy allows researchers to quickly separate active agents from reaction mixtures by exploiting the magnetic properties of the support. In this Account, we discuss the main attributes of magnetic supports and describe how we can make the different nanomagnets accessible by surface functionalization. Arguably the most prominent magnetic nanoparticles are superparamagnetic iron oxide nanoparticles (SPIONs) due to their biologically well-accepted constituents, their established size-selective synthesis methods, and their diminished agglomeration (no residual magnetic attraction in the absence of an external magnetic field). However, nanoparticles made of pure metal have a considerably higher magnetization level that is useful in applications where high loadings are needed. A few layers of carbon can efficiently shield such highly reactive metal nanoparticles and, equally important, enable facile covalent functionalization via diazonium chemistry or non-covalent functionalization through π-π interactions. We highlight carbon-coated cobalt (Co/C) and iron (Fe/C) nanoparticles in this Account and compare them to SPIONs stabilized with surfactants or silica shells. The graphene-like coating of these nanoparticles offers only low loadings with functional groups via direct surface modification, and the resulting nanomagnets are prone to agglomeration without effective steric stabilization. To overcome these restrictions and to tune the dispersibility of the magnetic supports in different solvents, we can introduce dendrimers and polymers on Co/C and Fe/C platforms by various synthetic strategies. While dendrimers have the advantage of being able to array all functional groups on the surface, polymers need fewer synthetic steps and higher molecular weight analogues are easily accessible. We present the application of these promising hybrid materials for the extraction of analytes or contaminates from complex aqueous solutions (e.g. waste water treatments or blood analytics), for metal-, organo-, and biocatalysis, and in organic synthesis. In addition, we describe advanced concepts like magnetic protecting groups, a multistep synthesis solely applying magnetic reagents and scavengers, and thermoresponsive self-separating magnetic catalysts. We also discuss the first examples of the use of magnetic scaffolds manipulated by external magnetic fields in flow reactors on the laboratory scale. These hold promise for future applications of magnetic hybrid materials in continuous flow or highly parallelized syntheses with rapid magnetic separation of the applied resins.


Lipoyl Ester Terminated Star PLGA as a Simple and Smart Material for Controlled Drug Delivery Application.
PLGA, a copolymer of lactide and glycolide, is one of the most used biodegradable polymers that find a wide range of biomedical applications including drug delivery and tissue engineering. However, in spite of remarkable advancement, nanotherapeutics based on PLGA might have drawbacks of inadequate stability, drug leakage, and slow drug release at the tumor site, which reduces its targeting ability and therapeutic efficacy. Here, we report that direct modification of star PLGA ends with lipoic acid, a natural antioxidant present in our human body, affords a smart material (sPLGA-LA) that forms reversibly crosslinked and bioresponsive multifunctional nanoparticles (sPLGA XNPs). Interestingly, sPLGA XNPs obtained in the presence of 23.0 wt % PEG-PDLLA displayed a small hydrodynamic size of 73 ± 1.2 nm, high stability against dilution and 10% serum, while fast destabilization under a reductive environment. Moreover, sPLGA XNPs achieved efficient loading of lipophilic anticancer drug model, doxorubicin (DOX), at a theoretical drug loading content of 13.3 wt %, giving DOX-loaded sPLGA XNPs with reduced drug leakage under physiological conditions as well as significantly accelerated drug release under 10 mM glutathione condition compared with both linear and star PLGA controls (denoted as lPLGA NPs and sPLGA NPs, respectively). Confocal microscopy and flow cytometry displayed obviously stronger DOX fluorescence in B16F10 melanoma cells treated with DOX-loaded sPLGA XNPs than with lPLGA and sPLGA counterparts. MTT assays revealed that DOX-sPLGA XNPs caused 2.4- and 4.2-fold higher antitumor activity toward B16F10 cells than DOX-sPLGA NPs and DOX-lPLGA NPs, respectively. Notably, in vivo pharmacokinetics studies showed prolonged circulation time and significantly improved AUC for DOX-sPLGA XNPs over lPLGA NPs control. Hence, lipoyl ester terminated star PLGA emerges as a simple and smart material for better-controlled anticancer drug delivery.


Cellular imaging: a key phenotypic screening strategy for predictive toxicology.
Incorporating phenotypic screening as a key strategy enhances predictivity and translatability of drug discovery efforts. Cellular imaging serves as a "phenotypic anchor" to identify important toxicologic pathology that encompasses an array of underlying mechanisms, thus provides an effective means to reduce drug development failures due to insufficient safety. This mini-review highlights the latest advances in hepatotoxicity, cardiotoxicity, and genetic toxicity tests that utilized cellular imaging as a screening strategy, and recommends path forward for further improvement.


Association between junk food consumption and mental health in a national sample of Iranian children and adolescents: the CASPIAN-IV study.
The consumption of high energy and low nutritional content foods, which are known as junk foods, has increased. The aim of this study was to evaluate the association between junk food intake and mental health in a national sample of Iranian children and adolescents. Data were obtained from a surveillance system entitled CASPIAN-IV (Childhood and Adolescence Surveillance and Prevention of Adult Non communicable Disease) study of school students, ages 6 to 18 y in Iran. The students and their parents completed two sets of reliable questionnaires obtained from Global School Health Survey translated to Persian. The student questionnaire comprised several questions such as psychiatric distress (worry, depression, confusion, insomnia, anxiety, aggression, and worthless) and violent behaviors (physical fighting, being a victim, and bullying). The junk foods consisted of sweets, sweetened beverages, fast foods, and salty snacks. In the sample of 13 486 children and adolescents, the frequency of junk food consumption was significantly associated with psychiatric distress (P < 0.001). There was a significant association between violent behaviors and intake of junk foods (P < 0.001) except for sweets, whereas the association between sweetened beverages consumption and being a victim was not significant (P > 0.05). Additionally, the results of logistic regression showed that daily consumption of sweetened beverages and snacks significantly increased the odds of self-reported psychiatric distress. Also, daily consumption of salty snacks was significantly associated with violent behavior, including physical fighting (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.21-1.60), being a victim (OR, 1.19; 95% CI, 1.04-1.37), and bullying (OR, 1.55; 95% CI, 1.32-1.82). Junk food consumption may increase the risk for psychiatric distress and violent behaviors in children and adolescents. Improvement of eating habits toward healthier diets may be an effective approach for improving mental health.


Acute myocardial damage after electrical injury assessed by MRI.
Electrical injuries are not uncommon, and electrical shock-induced cardiac damage can be life-threatening. We present the case of a young patient who suffered from acute myocardial damage due to an occupational electric shock. Myocardial damage was assessed by very early (day 4) and repeated (up to month 18) MRI. Clinical management and patient risk estimation in such a setting are challenging because data on similar non-lethal cases and practice recommendations are scarce in the literature.


Evidence and expertise in the management of polycythemia vera and essential thrombocythemia.
Major causes of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET) are represented by thrombosis and bleeding, progression to myelofibrosis and transformation to acute leukemia. Myelosuppressive therapy, preferentially with hydroxyurea, can reduce the rate of vascular complications, but there is some concern about an increased rate of leukemic transformation with this agent. Therefore, management of these disorders poses a significant challenge, and a risk-oriented therapeutic approach should be strictly followed to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established risk factors for cardiovascular events are represented by older age and previous thrombosis, whereas impact of novel biological factors, including leukocytosis and JAK2V617F mutational status and/or mutational burden, is under active investigation. Low-risk PV patients should be managed only with phlebotomy and aspirin, whereas high-risk patients should also receive cytotoxic therapy. Regarding the management of ET, there is no clear indication for intervention in low-risk patients, whereas high-risk patients should be managed with chemotherapy. Other therapeutic options, such as interferon-alpha or anagrelide, may find place in selected patients including those who are resistant/intolerant to hydroxyurea. Finally, there is great expectation for novel drugs targeting the constitutively active JAK2/STAT pathway.


[An interferon-like substance derived from bird fibroblasts in the treatment of human recurrent herpes simplex].
In a clinical study lasting 15 months 42 patients suffering from herpes simplex were locally treated with an interferonlike substance prepared on avian fibroblast cultures. In 90% of all cases a certain improvement was achieved. In 60% reduced intensity and in 57% a shortening of prodromal symptoms was established, reduced dimensions of skin lesions were noted in 75%. In 21 patients only abortive forms without vesicles appeared. The mean duration of the herpetic episodes was reduced from 10.1 days to 4.5 days. Finally the possible mechanism of this favourable effect are discussed.


Prednisone and long-term damage in systemic lupus erythematosus: Which is the threshold dose? A pilot study.
We aimed to study the daily dose of glucocorticoids in the first month associated with damage after 5 years of systemic lupus erythematosus (SLE) diagnosis; and to assess the daily dose of prednisone during the first year, over which damage after 5 years could be predicted. A retrospective cohort study of SLE patients from the diagnosis and up to 5 years of follow-up was performed. Cumulative prednisone doses in the first month (T1m), at 1 year (T12m), and at 5 years (T5y) were calculated. Damage was estimated using the SLICC index and activity by the SLEDAI-2K. Damage at T5y was categorized as "present" or "absent". To determine the cutoff point of prednisone dose for the first month and for the first year of treatment, related to damage at 5 years, a ROC curve was done. A logistic regression was performed to control damage at 5 years by the activity levels, anti-DNA titers, and the corticosteroid burden between 1 and 5 years. Forty-eight patients were included with a mean age of 42.4 (12.6) years; 46 (95.8%) were female. The cumulative dose in T1m associated with greater sensitivity and specificity in the ROC curve (1.54; AUC 0.793; 95% CI: 0.66-0.92) to predict glucocorticoid-related damage at 5 years of follow-up was 980mg, which leads to a daily dose for the first month of 32.6 mg/day. The daily dose during the first year associated with damage at 5 years, allowed to calculate an optimal cutoff point of 7.38 mg/day, with a sensitivity of 92.9% (AUC 0.695, 95% CI: 0.52-0.86) to predict damage at 5 years. In the logistic regression, this estimate was maintained, controlling for SLEDAI-2K and for positivity or not of anti-DNA antibodies and for the cumulative dose of prednisone between T5y and T12m. This pilot study allows to estimate a threshold dose of 32.6 mg/day during the first month and 7.38 mg/day during the first year, over which the risk of permanent damage is high at 5 years, regardless of the activity levels and the glucocorticoid doses considered between the first and the fifth year of follow-up.


Has the New York State triplicate benzodiazepine prescription regulation influenced sedative-hypnotic overdoses?
A retrospective analysis of sedative-hypnotic overdoses reported to the New York City Poison Control Center (NYCPCC) for the years 1988 and 1989 was performed to evaluate the effects of the triplicate benzodiazepine (BZ) prescription program on the incidence and severity of sedative hypnotic overdoses. Although total BZ overdoses fell slightly, from 1,294 in 1988 to 1,265 in 1989, a statistically significant increase in non-benzodiazepine (NBZ) sedative-hypnotic overdoses, from 111 in 1988 to 144 in 1989, was noted. No difference in clinical outcomes between the two years could be demonstrated. These results suggest that the restriction of BZ failed to reduce the incidence or severity of sedative-hypnotic overdose, largely because of the substitution of similar nonrestricted agents.


Distribution Pattern and Climate Preferences of the Representatives of the Cosmopolitan Genus Sirthenea Spinola, 1840 (Heteroptera: Reduviidae: Peiratinae).
The main goal of this study was to predict, through the use of GIS tool as ecological niche modelling, potentially suitable ecological niche and defining the conditions of such niche for the representatives of the cosmopolitan genus Sirthenea. Among all known genera of the subfamily Peiratinae, only Sirthenea occurs on almost all continents and zoogeographical regions. Our research was based on 521 unique occurrence localities and a set of environmental variables covering the whole world. Based on occurrence localities, as well as climatic variables, digital elevation model, terrestrial ecoregions and biomes, information about the ecological preferences is given. Potentially useful ecological niches were modelled using Maxent software, which allowed for the creation of a map of the potential distribution and for determining climatic preferences. An analysis of climatic preferences suggested that the representatives of the genus were linked mainly to the tropical and temperate climates. An analysis of ecoregions also showed that they preferred areas with tree vegetation like tropical and subtropical moist broadleaf forests biomes as well as temperate broadleaf and mixed forest biomes. Therefore, on the basis of the museum data on the species occurrence and ecological niche modelling method, we provided new and valuable information on the potentially suitable habitat and the possible range of distribution of the genus Sirthenea along with its climatic preferences.


Ventricular-arterial coupling in patients with heart failure treated with cardiac resynchronization therapy: may we predict the long-term clinical response?
To evaluate the effects of cardiac resynchronization therapy (CRT) on ventricular-arterial coupling (VAC) in patients with refractory congestive heart failure (HF), left bundle brunch block, and sinus rhythm. The ratio between arterial elastance (Ea) and left ventricular end-systolic elastance (Ees), the so-called VAC, defines the efficiency of the myocardium in pumping blood. Seventy-eight patients were studied with echocardiography before CRT, and 1 year later. End-systolic elastance was calculated according to the method of Chen. Arterial elastance (ratio of the systolic pressure to the stroke volume), end-systolic volume (ESV), and quality of life (QoL) (Minnesota Living with Heart Failure Questionnaire) were assessed at the baseline and after 1 year. Patients with a reduction>15% of ESV or a decrease>33% in QoL score were considered responders to CRT. QRS duration and interventricular delay were significantly reduced with CRT compared with baseline (156+/-2 vs. 195+/-3 ms, P<0.001; and 25+/-2 vs. 55+/-3 ms, P<0.001, respectively). Arterial elastance/Ees decreased significantly on CRT (2.47+/-1.48 vs. 1.41+/-0.87, P<0.0001). The lowering of Ea/Ees was congruent to a decrease in intraventricular delay (83.1+/-55.7 vs. 28.4+/-49.5 ms, P<0.0001) and an increase in ejection fraction (26+/-6.3 vs. 36.9+/-8.0%, P<0.0001). Responders to CRT were 74 and 71% of the overall patient population, considering as endpoint QoL or ESV, respectively. The analysis of VAC showed a baseline cut-off value of 2, above which 88% and 69% of patients responded to CRT, considering as endpoint QoL or ESV, respectively. The non-invasive assessment of VAC may be proposed as an immediate, easy, and optimal tool for quantifying the effect of CRT in patients with HF.


Conformational changes of recombinant Ca2+-ATPase studied by reaction-induced infrared difference spectroscopy.
Recombinant Ca(2+)-ATPase was expressed in Saccharomyces cerevisiae with a biotin-acceptor domain linked to its C-terminus by a thrombin cleavage site. We obtained 200 μg of ~ 70% pure recombinant sarcoendoplasmic reticulum Ca(2+)-ATPase isoform 1a (SERCA1a) from a 6-L yeast culture. The catalytic cycle of SERCA1a was followed in real time using rapid scan FTIR spectroscopy. Different intermediate states (Ca2 E1P and Ca2 E2P) of the recombinant protein were accumulated using different buffer compositions. The difference spectra of their formation from Ca2 E1 had the same spectral features as those from the native rabbit SERCA1a. The enzyme-specific activity for the active enzyme fraction in both samples was also similar. The results show that the recombinant protein obtained from the yeast-based expression system has similar structural and dynamic properties as native rabbit SERCA1a. It is now possible to apply this expression system together with IR spectroscopy to the investigation of the role of individual amino acids.


Appetite Regulation In Relation To Energy Provision.
Appetite control is a very complex process which influences the short term feeding behaviour and a long term adaptive process that responds to the energy input. Appetite control and food intake is influenced by a combination of behavioural, psychological and neuro-endocrine influences. For identification of articles search engines of the databases EMBASE, OVID, Pub med and MEDLINE were used for papers published from 2002 to 2015 in English language. The higher endogenous peptide YY (PYY) and cholecystokinin (CCK) and lower ghrelin levels are not always associated with subjective feelings of fullness or hunger and a decreased energy intake which highlights the fact that appetite control and food intake is a very intricate process. When food is ingested, numerous physiological, hormonal, social and psychological processes are triggered in an intricate manner. Therefore, it can be said that ghrelin, PYY and CCK are just few pieces, which contributes to the process of appetite control and energy intake.


Victim and offender accounts of interpersonal conflict: autobiographical narratives of forgiveness and unforgiveness.
Participants wrote 2 narratives that described an incident in which they angered or hurt someone (offender) or in which someone angered or hurt them (victim) and the offense was forgiven or not forgiven. Victims portrayed the offense as continuing (open), and offenders portrayed the offense as over (closed). Forgiveness narratives portrayed offenses as closed and with positive outcomes; however, for some victims, forgiveness coincided with continued anger, suggesting incomplete forgiveness. Dispositional empathy was associated with more benign interpretations of offenses, and situational empathy (e.g., for the offender) was associated with victims' forgiveness. In contrast, offenders' empathy for victims was associated with less self-forgiveness. Thus, both victim or offender role and forgiveness must be considered to understand narratives of interpersonal offenses.


Reducing Allostatic Load in Depression and Anxiety Disorders: Physical Activity and Yoga Practice as Add-On Therapies.
The allostatic load (AL) index constitutes a useful tool to objectively assess the biological aspects of chronic stress in clinical practice. AL index has been positively correlated with cumulative chronic stress (physical and psychosocial stressors) and with a high risk to develop pathological conditions (e.g., metabolic syndrome, cardiovascular pathology, inflammatory disorders) and the so-called stress-related psychiatric disorders, including anxiety and depressive disorders. Chronic stress has negative effects on brain neuroplasticity, especially on hippocampal neurogenesis and these effects may be reversed by antidepressant treatments. Several evidences indicate that non-pharmacological interventions based on physical activity and yoga practice may add synergizing benefits to classical treatments (antidepressant and benzodiazepines) for depression and anxiety, reducing the negative effects of chronic stress. The aim of this review is to provide a general overview of current knowledge on AL and chronic stress in relation to depression and anxiety, physical activity and yoga practice.