Enhancement of N-methyl- D-aspartate receptor-mediated excitatory postsynaptic potentials in the neostriatum after methamphetamine sensitization. An in vitro slice study.
It has been suggested that behavioral methamphetamine sensitization involves changes in cortical excitatory synaptic inputs to neostriatal (Str) projection neurons. To test this, we performed blind whole-cell recording of medium spiny neurons in Str slice preparations. In Str neurons of naive rats, the amplitude of the subcortical white matter stimulation-induced N-methyl- D-aspartate receptor-mediated excitatory postsynaptic potentials (NMDA-EPSPs) was decreased upon hyperpolarization, owing to the voltage-dependent Mg(2+) blockade of NMDA receptor channels. In contrast, the amplitude of the NMDA-EPSPs in Str neurons of rats undergoing methamphetamine withdrawal (MW) did not show the Mg(2+) blockade and was nearly voltage independent over the membrane potential range of -70 to -110 mV. Application of the specific protein kinase C (PKC) activator, phorbol 12, 13- DL-acetate, blocked the voltage-dependent Mg(2+) blockade of NMDA receptor channels in Str neurons of naive rats. Application of the specific activator of cAMP-dependent protein kinase A (PKA), Sp-cAMPS-triethylamine salt, increased the amplitude of the NMDA receptor-mediated EPSPs at the rest but not at hyperpolarized potentials. Coapplication of the PKC and PKA activators yielded NMDA-EPSPs similar to those seen in Str neurons of MW rats. In Str slices of naive rats, tetanic subcortical white matter stimulation induced long-term depression of field potentials. In Str slices treated with the PKC and/or PKA, the same stimulation induced long-term potentiation of field potentials similar to those observed in slices obtained from MW rats. These results suggest that the enhancement of the NMDA receptor-mediated corticostriatal synaptic transmission plays an important role in behavioral methamphetamine sensitization. This enhancement is probably associated with phosphorylation of NMDA receptors mediated by the simultaneous activation of PKC and PKA.


Reproducible activation in BA2, 1 and 3b associated with texture discrimination in healthy volunteers over time.
We aimed to quantify specific location and reproducibility of brain activation associated with discrimination of a moving textured surface in adult healthy volunteers over a 6-month interval. A sensory stimulation device was developed to provide a texture stimulus to the fingertips at a controlled speed and pressure. Repeat measurements of regional cerebral blood flow, using positron emission tomography (PET), were obtained in 10 healthy individuals, aged 33 to 80 years (mean=55.8 years), at scanning sessions separated by 6 months. Stimulation and rest conditions were presented to either the right, dominant (n=5) or left non-dominant (n=5) hand. Activation location was objectively quantified with reference to probabilistic cytoarchitectonic maps. Differences in activation over time and regions of common activation were also quantified. Participants consistently activated Brodmann areas (BA) 2, 3b and 1, somatosensory areas of postcentral gyrus, at initial and 6-month studies: 93.1% of common activation for the right-hand (RH) and 60.6% for left-hand (LH) stimulation group were in these areas. Reproducible activation in BA6, 4a and 4p was also observed for the RH group (6.8% of common activation) and LH group (39.4%). There were no sites of significant difference over time for either hand. Highly consistent location of activation over time suggests that changes in loci of activation may be confidently monitored in adults using this paradigm. Use of probabilistic cytoarchitectonic maps permitted objective quantification of the anatomical location of the core of reproducible activation.


Supportive care needs of individuals with lung cancer.
The main purpose of this study was to identify the range of supportive care needs of patients diagnosed with lung cancer who attended an outpatient, regional cancer centre. Lung cancer has more than a physical impact on those who are diagnosed with the disease, yet relatively little has been reported on their needs beyond those for physical symptom management. A total of 88 patients participated in this study by completing a self-report questionnaire. The data provided clear indication that a range of needs, both physical and psychosocial, exist for this group of patients and, furthermore, remain unmet. Lack of energy, pain, and concern about those close to them were reported most frequently. Patients also expressed distress because of difficulty managing their needs and many indicated wanting help to cope with the challenges they were experiencing. However, a sizeable proportion (45% to 58%) indicated they did not want help from staff at the cancer centre for some need items despite considerable distress arising from those remaining unmet (e.g., lack of energy, fears about cancer spreading, not being able to do the things you used to do). Suggestions for practice and future research are offered to improve the care for this group of patients.


Comparative Evaluation of Hand K-flex Files, Pediatric Rotary Files, and Reciprocating Files on Instrumentation Time, Postoperative Pain, and Child's Behavior in 4-8-year-old Children.
A pulpectomy is regarded as the choice modality of treatment for necrotic teeth. The use of hand files, though popular traditionally as a gold standard, may be challenging due to increased chairside time. Postoperative pain is one of the most common complications of pulpectomy and may be unpleasant for a child/pedodontist. Rotary files were found to reduce instrumentation time, reduce apical extrusion, and in turn reduce pain but there is a lack of studies in primary teeth particularly for pediatric and reciprocating file systems. The increased number of options available today makes it a dilemma for the operator to choose a suitable file system. The study aimed to evaluate and compare the instrumentation time, postoperative pain, and effect on child's behavior among three groups, i.e., hand K-flex files (group I), pediatric rotary files (group II), and reciprocating files (group III). A total of 75 primary molar teeth after meeting inclusion criteria were randomly allocated into three groups. During the procedure, step-wise instrumentation time was recorded using a stopwatch. The child's behavior pre- and postoperatively was assessed by an evaluator. The postoperative pain (up to 1 week) was assessed by a questionnaire. The mean age of children taken for the study was 6.03 ± 1.2 years with 46 males and 29 females. The mean biomechanical preparation time was observed to be significantly shorter in the pediatric rotary and reciprocating file groups vs hand K-flex files (p < 0.001**). The postoperative pain after 6 hours had a mean value of 0.88 + 0.9 for the hand K-flex file group which was significantly higher than both rotary file groups (p < 0.05*). The pre- and postoperative behavior revealed no significant difference. The clinical performance of pediatric and reciprocating files was superior, but the choice of file system did not significantly alter behavior. Tyagi R, Khatri A, Kalra N, et al. Comparative Evaluation of Hand K-flex Files, Pediatric Rotary Files, and Reciprocating Files on Instrumentation Time, Postoperative Pain, and Child's Behavior in 4-8-year-old Children. Int J Clin Pediatr Dent 2021;14(2):201-206.


[Treatment expectation of psychosomatic patients and their significance in the polyclinic and consultation service].
Clinical experience has shown, that psychosomatic patients in an outpatient clinic on the one hand and a consultation-liaison-service on the other hand differ in their motivation for psychotherapeutic treatment. We assumed that the patients' expectancies about the helpfulness of the different treatment methods can be a meaningful variable explaining this finding. By means of an empirical investigation we found two factors of expectancies. The first one was concerned with medical treatment, and the second with psychotherapeutic treatment. The two groups of patients showed significant differences in the intensity of these expectancies: in the patients of the Consultation-liaison-service dominated the expectancies concerning medical treatment, while in the patients of the outpatient-clinic the intensity of expectancies concerning psychotherapeutic treatment was significantly higher. The results are discussed on the background of the doctor-patient-interaction.


Dependence of the fluctuation-dissipation temperature on the choice of observable.
On general grounds, a nonequilibrium temperature can be consistently defined from generalized fluctuation-dissipation relations only if it is independent of the observable considered. We argue that the dependence on the choice of observable generically occurs when the phase-space probability distribution is nonuniform on constant energy shells. We relate quantitatively this observable dependence to a fundamental characteristics of nonequilibrium systems, namely, the Shannon entropy difference with respect to the equilibrium state with the same energy. This relation is illustrated on a mean-field model in contact with two heat baths at different temperatures.


HLA system and some neoplastic diseases.
Using the NIH two-phase microlymphocytotoxic test, lymphocytes of patients and control subjects were typed for HLA antigens of A and B loci: A1, 2, 3, 9, 10, 11, 28 (or Aw 19, A30, 31), B5, 7, 8, 12, 13, 14, 15, 17, 18, 21, w22, 27, 35, 40. Patients tested: 1. 75 patients with Wilms' tumour, thereof 35 had their whole families tested, 2. 20 patients with neuroblastoma, 3. 26 patients with neurofibromatosis, thereof 21 had their whole families tested, 4. 166 patients with testicular germinal tumours and 41 children with germinal tumours of diverse localization, 5. 48 individuals with haemangioma, 6. 64 women with breast cancer and 50 with dysplasia. We investigated 490 patients and, with the addition of family studies, another 193 individuals, altogether 683 persons. The results were compared with a group of 301 healthy non-related persons or with a group of 116 healthy non-related men, or with 100 healthy women and, in the family studies, with members of 47 healthy three-member families with healthy children. The chi 2 test with a Yates correction or also Fisher's exact test were used for the purpose. The resultant p was corrected using multiplication by the number of the antigens typed. In some cases we used the relative risk (RR) value. The results can be summed up in the following seven points: 1. Wilms' tumour was found to have no significant association either in our population or family studies. The latter seem to testify rather against this tumour's linkage with HLA. Our study was inconclusive as to the significance of the more frequent incidence of HLA-A1 and/or A9 in the diseased children of those families where one of the parents had at least one of those antigens. It cannot be ruled out as a sign of better prognosis. We regards as indispensable the typing of HLA antigens in patients with Wilms' tumour coincident with an inborn anomaly, as well as in members of those patients' families, and also a conclusive elucidation of the possible association with HLA-A1 and/or A9. No other centre has as yet undertaken any family studies. Consequently our possibilities of comparison with other teams' results were meagre. 2. We point to the possible conceivable relationship between neuroblastoma and HLA-B13. We found this association, albeit non-significant after correction, potentially important, especially after comparisons with the results of an only other existing study.(ABSTRACT TRUNCATED AT 400 WORDS)


Primary and secondary nonvariceal upper gastrointestinal bleeding.
Upper gastrointestinal (UGI) bleeding is associated with a mortality rate of up to 14% in emergency hospital admissions (primary bleeding), and up to 28% in hospitalized patients (secondary bleeding). To characterize and compare the clinical pictures and outcome of primary and secondary nonvariceal UGI bleeding. A retrospective, case-control design was used. The files of all consecutive patients admitted to our tertiary academic center between January 1, 2001 and December 31, 2002 for UGI bleeding were reviewed for demographic and clinical data, treatment details, number of blood transfusions, endoscopic procedures, surgical procedures, and mortality. Compared to primary UGI bleeding, secondary bleeding was associated with female sex, older age, more chronic diseases, intake of more drugs, hospitalization in internal medicine departments, longer hospital stay, fewer endoscopic procedures, and less Helicobacter pylori-related peptic ulcer disease. Total mortality rate in the secondary bleeders was 30.3% versus 4.6% in the primary bleeders (P<0.0001). There was no significant difference between primary and secondary bleeders in treatment with nonsteroidal anti-inflammatory agents or aspirin, severity of bleeding, or death related to gastrointestinal bleeding. Despite the significant differences in the clinical picture of primary and secondary bleeders, the severity of bleeding appear to be similar in both groups. Although there was a trend towards a higher gastrointestinal-related mortality in secondary bleeders, it was not statistically significant.


Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations.
Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53-intact tumors (P ≪ 10-10), and shRNA-mediated knockdown of RPGs activated p53 in TP53-wild-type cells. In contrast, we did not see negative selection of RPG deletions in TP53-mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically.


Circulating soluble vascular cell adhesion molecule 1: relationships with residual renal function, cardiac hypertrophy, and outcome of peritoneal dialysis patients.
Vascular cell adhesion molecule 1 (VCAM-1) is involved in leukocyte-endothelial cell interaction and has a pivotal role in inflammation. Whether it contributes to excessive mortality in dialysis patients remains uncertain. In this study, we examined circulating soluble VCAM-1 (sVCAM-1) in relation to different clinical and biochemical parameters, as well as mortality and cardiovascular events, in peritoneal dialysis (PD) patients. Values for serum sVCAM-1, together with C-reactive protein (CRP), homocysteine, albumin, lipid profile, blood hemoglobin, and indices of dialysis adequacy, were determined at study baseline, and echocardiography was performed in 160 long-term PD patients. Patients were followed up for a mean of 35 +/- 16 (SD) months. Serum sVCAM-1 levels were elevated in our continuous ambulatory PD (CAPD) patients and showed a negative correlation with residual glomerular filtration rate (GFR; P < 0.001) and low-density lipoprotein (LDL) cholesterol level (P = 0.004), but a positive correlation with left ventricular mass index (P = 0.025). Using Kaplan-Meier analysis, overall survival rates at 2 years were 96.2%, 75.2%, and 50.6% for patients in the lower, middle, and upper tertiles of sVCAM-1 levels, respectively (P < 0.0001). Fatal and nonfatal cardiovascular event-free survival rates were 58.2%, 56.9%, and 19.4% for patients in the lower, middle, and upper tertiles, respectively (P < 0.0001). Using Cox regression analysis with adjustment for confounding covariates, every 100-ng/mL increase in sVCAM-1 level was associated with 8% (95% confidence interval, 1.03 to 1.13) and 5% (95% confidence interval, 1.00 to 1.10) increases in risk for death and fatal and nonfatal cardiovascular events, respectively. Its significance for all-cause mortality remained with additional adjusting for LDL cholesterol level, but was lost when adjusting for residual GFR. Its association with cardiovascular events became insignificant when adjusting for LDL cholesterol level or residual GFR. Furthermore, patients with both sVCAM-1 and CRP levels elevated at the 50th percentile or greater were associated with the greatest death and fatal and nonfatal cardiovascular event rates compared with those with either CRP or sVCAM-1 level elevated at the 50th percentile or greater. Circulating sVCAM-1 levels show an important link with residual renal function, LDL cholesterol level, and cardiac hypertrophy in CAPD patients. Furthermore, residual renal function, which correlates inversely with circulating sVCAM-1 level, shows an important association with all-cause mortality and cardiovascular events and displaces sVCAM-1 level from the models for all-cause mortality and future cardiovascular events in CAPD patients. Additional study is needed to explore possible mechanistic links between inflammation, soluble adhesion molecules, residual renal function, and cardiac hypertrophy in CAPD patients.


Impact of primary and specialty care integration via asynchronous communication.
To describe and evaluate the impact of primary and specialty care integration via asynchronous communication at a large integrated healthcare system. In January 2014, Geisinger's primary care providers (PCPs) were given access to an asynchronous communication tool, Ask-a-Doc (AAD), that enabled direct communication with specialists in 14 medical specialties and 5 surgical specialties. Internal data were collected to assess PCPs' acceptance and use of the tool, as well as satisfaction. Insurance claims data were obtained to assess the impact on healthcare utilization and cost. A retrospective analysis of health plan claims data was conducted among those patients who had at least 1 specialist visit with 1 of the participating specialties between January 2014 and December 2016. A set of difference-in-differences multivariate linear regression models with patient fixed effects was estimated, in which those who were not exposed to AAD served as the comparison group. Acceptance and use of AAD among PCPs gradually increased over time but varied by specialty. AAD was associated with an approximately 14% reduction in total cost of care during the first month of follow-up and a 20% reduction (P <.001) during the second month. These reductions in cost of care appeared to be driven by reductions in emergency department visits and physician office visits. Geisinger's AAD experience suggests that the integration of primary and specialty care via the use of a highly reliable and efficient asynchronous communication system can potentially lead to reductions in avoidable care and more efficient use of specialty care.


Positron emission tomography/magnetic resonance imaging (PET/MRI): An update and initial experience at HC-FMUSP.
The new technology of PET/MRI is a prototype of hybrid imaging, allowing for the combination of molecular data from PET scanning and morphofunctional information derived from MRI scanning. Recent advances regarding the technical aspects of this device, especially after the development of MRI-compatible silicon photomultipliers of PET, permitted an increase in the diagnostic performance of PET/MRI translated into dose reduction and higher imaging quality. Among several clinical applications, PET/MRI gains ground initially in oncology, where MRI per se plays an essential role in the assessment of primary tumors (which is limited in the case of PET/CT), including prostate, rectal and gynecological tumors. On the other hand, the evaluation of the lungs remains an enigma although new MRI sequences are being designed to overcome this. More clinical indications of PET/MRI are seen in the fields of neurology, cardiology and inflammatory processes, and the use of PET/MRI also opens perspectives for pediatric populations as it involves very low radiation exposure. Our review aimed to highlight the current indications of PET/MRI and discuss the challenges and perspectives of PET/MRI at HC-FMUSP.


Nervousness and hysteria of mature female chickens.
A type of abnormal nervousness and hysteria, e.g., adding nests and perches to community cages and and hysteria affecting White Leghorn female chickens 35 or more weeks of age was investigated in nine experiments. Experimental flocks in which the malady consistently occurred were housed in large group (community) cages. Limited information was obtained on three cases in commercial flocks housed on the floor. Social pressure resulting from high population density appeared to be primary causative factor, with pain apparently contributing to the final break to hysteria. Claw removal at one day of age prevented hysteria but not nervousness in one experiment. Colored light, feeding added niacin or a mild tranquilizer were not successful preventives. Short term feeding of a high level of niacin, claw trimming and forced molting afforded relief in some cases while a heavy sedative was ineffective as a curative. Modification of the environment to reduce social pressure was successful in preventing nervousness and hysteria, e.g., adding nests and perches to community cages and moving flocks to less crowded housing. Strain differences in tendency to develop hysteria were demonstrated. There were positive indications of physiological changes associated with hysteria.


Medicare payment options for rural hospitals: the name game.
Within the framework of Medicare laws and regulations governing payments for acute-care services are various options affecting payments to individual hospitals, many of which are directed at rural hospitals. Several changes in the classifications for sole community hospitals, Medicare-dependent hospitals, and rural referral centers have been implemented through the Balanced Budget Act (BBA) of 1997 and subsequent legislation. The critical access hospital classification implemented through the BBA makes available on a national level the former rural primary care hospital classification. Each of these four classifications provides for different payment enhancements.


[Serum nitric oxide as an additional criterion for evaluating the course of leptospirosis].
The blood level of nitric oxide (NO) was studied during an infectious process in 107 patients with leptospirosis. The content of NO was estimated from the level of the final stable nitrogen cycle metabolite--nitrite was estimated by the Griss reaction. Infectious toxic shock (57%), disseminated intravascular coagulation syndrome (31%), respiratory distress syndrome (36%), and acute renal and hepatic failure (76%) were observed in the examinees. A combination of 3-4 of the above abnormalities was noted in 49% of the patients. There were elevated blood nitrite levels at the onset of the disease in patients with leptospirosis with signs of infectious toxic shock (15.3+/-2.79 micromol/l). In patients with a poor or complicated rehabilitative period, the high levels of nitrite were retained or its concentration repeatedly increased at weeks 3-4 of the disease. It has been shown that the measurements of blood nitrite levels may be used as an additional diagnostic criterion for evaluating the course of leptospirosis.


Insights into the regulation of bacteriophage endolysin: multiple means to the same end.
Antibiotics are the molecules of choice to treat bacterial infections. However, because of the rapid emergence of drug-resistant bacteria, alternative modes of combating infections are being envisaged. Bacteriophages, which infect and lyse bacterial cells, may function as effective antimicrobial agents. Most bacteriophages produce their own peptidoglycan hydrolase called endolysin or lysin, which breaks down the cell wall of bacteria and aids in the release of newly assembled virions. Here, we discuss several findings that help us in understanding how endolysins are regulated. We observe that there is no common mechanism that is followed in all cases. Many different modes of activity regulation have been observed in endolysins, including regulation of protein expression, translocation across the cell membrane and post-translational modifications. These processes not only demonstrate how endolysins are made dependent on other accessory proteins and non-protein factors for their synthesis, translocation across the cytoplasmic membrane and activity, but also show how autoregulation helps in maintaining the enzyme in an inactive form. Various regulatory mechanisms that are discussed are particularly applicable to endolysins. Nevertheless, a detailed study of these methods opens new avenues of investigation in the area of protein translocation systems and the novel ways of enzyme activation and regulation in bacteria.


Test-retest reliability of stride time variability while dual tasking in healthy and demented adults with frontotemporal degeneration.
Although test-retest reliability of mean values of spatio-temporal gait parameters has been assessed for reliability while walking alone (i.e., single tasking), little is known about the test-retest reliability of stride time variability (STV) while performing an attention demanding-task (i.e., dual tasking). The objective of this study was to examine immediate test-retest reliability of STV while single and dual tasking in cognitively healthy older individuals (CHI) and in demented patients with frontotemporal degeneration (FTD). Based on a cross-sectional design, 69 community-dwelling CHI (mean age 75.5 ± 4.3; 43.5% women) and 14 demented patients with FTD (mean age 65.7 ± 9.8 years; 6.7% women) walked alone (without performing an additional task; i.e., single tasking) and while counting backward (CB) aloud starting from 50 (i.e., dual tasking). Each subject completed two trials for all the testing conditions. The mean value and the coefficient of variation (CoV) of stride time while walking alone and while CB at self-selected walking speed were measured using GAITRite® and SMTEC® footswitch systems. ICC of mean value in CHI under both walking conditions were higher than ICC of demented patients with FTD and indicated perfect reliability (ICC > 0.80). Reliability of mean value was better while single tasking than dual tasking in CHI (ICC = 0.96 under single-task and ICC = 0.86 under dual-task), whereas it was the opposite in demented patients (ICC = 0.65 under single-task and ICC = 0.81 under dual-task). ICC of CoV was slight to poor whatever the group of participants and the walking condition (ICC < 0.20), except while dual tasking in demented patients where it was fair (ICC = 0.34). The immediate test-retest reliability of the mean value of stride time in single and dual tasking was good in older CHI as well as in demented patients with FTD. In contrast, the variability of stride time was low in both groups of participants.


[Toxic shock syndrome in a 14-year-old girl].
The toxic shock syndrome in a 14-year old girl is described. This syndrome occurs most frequently - but not exclusively - in the teens and young women during the first days of menstruation, if tampons are used. The patients are acutely ill with high fever, diarrhea and/or vomiting, with a rash, with loss of consciousness, and signs of shock (occasionally shock lung syndrome and renal insufficiency). During convalescence desquamation of hands and feet shows up. Patients with much less severe symptoms have been seen. The primary lesion is a local infection (e.g. vaginitis) with staphylococcus aureus, the symptoms being caused by staphylococcal toxins. Early recognition and immediate therapy are important for a better prognosis. The therapy consists of removal of the tampon, i.v. fluids including albumin, and the administration of a beta-lactamase-resistant antibiotic.


Impact of obesity on hospital complications and mortality in hospitalized patients with hyperglycemia and diabetes.
Obesity is associated with increased risk of diabetes, hypertension and cardiovascular mortality. Several studies have reported increased length of hospital stay and complications; however, there are also reports of obesity having a protective effect on health, a phenomenon coined the 'obesity paradox'. We aimed to investigate the impact of overweight and obesity on complications and mortality in hospitalized patients with hyperglycemia and diabetes. This retrospective analysis was conducted on 29 623 patients admitted to two academic hospitals in Atlanta, Georgia, between January 2012 and December 2013. Patients were subdivided by body mass index into underweight (body mass index <18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (>30 kg/m(2)). Hyperglycemia was defined as a blood glucose >10 mmol/L during hospitalization. Hospital complications included a composite of pneumonia, acute myocardial infarction, respiratory failure, acute kidney injury, bacteremia and death. A total of 4.2% were underweight, 29.6% had normal weight, 30.2% were overweight, and 36% were obese. 27.2% of patients had diabetes and 72.8% did not have diabetes (of which 75% had hyperglycemia and 25% had normoglycemia during hospitalization). A J-shaped curve with higher rates of complications was observed in underweight patients in all glycemic groups; however, there was no significant difference in the rate of complications among normal weight, overweight, or obese patients, with and without diabetes or hyperglycemia. Underweight is an independent predictor for hospital complications. In contrast, increasing body mass index was not associated with higher morbidity or mortality, regardless of glycemic status. There was no evidence of an obesity paradox among inpatients with diabetes and hyperglycemia.


Position of the head is not associated with changes in horse vision.
It has become accepted that the horse cannot see directly in front when the nose is lowered and must therefore rely on the rider. We tested the hypothesis that this conclusion would be correct only if the horse did not adjust the eyeball horizontal axis to changes of the head position. The results of the present study suggest that it is unlikely that horses have limited vision in relation to their head position when driven by the rider, and that the horse maintains the optimal horizontal eyeball position regardless of head position relative to the ground.


Method and technique of life events research in depression and anxiety.
Methodological aspects still have a decisive impact on the putative etiological role of life events in clinical research. Questions of a diagnostic nature also serve to complicate this kind of research still further, in this present review in particular, when it deals with depression and/or anxiety. The relationship between life events and disturbed behavior also depends on additional variables, such as personality factors and social support. It is for this reason that detailed specification of the concepts used in life events research would seem to be necessary. And finally--when more than two variables are present--the simultaneous application of a number of statistical models is worthy of recommendation.


Pyrrolizine-5-carboxamides: Exploring the impact of various substituents on anti-inflammatory and anticancer activities.
Towards optimization of the pyrrolizine-5-carboxamide scaffold, a novel series of six derivatives (4a-c and 5a-c) was prepared and evaluated for their anti-inflammatory, analgesic and anticancer activities. The (EZ)-7-cyano-6-((4-hydroxybenzylidene)amino)-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4b) and (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5b) bearing the electron donating methyl group showed the highest anti-inflammatory activity while (EZ)-6-((4-chlorobenzylidene)amino)-7-cyano-N-phenyl-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5a) was the most active analgesic agent. Cytotoxicity of the new compounds was evaluated against the MCF-7, A2780 and HT29 cancer cell lines using the MTT assay. Compounds 4b and 5b displayed high anticancer activity with IC50 in the range of 0.30-0.92 μmol L-1 against the three cell lines, while compound (EZ)-N-(4-chlorophenyl)-7-cyano-6-((4-hydroxybenzylidene)-amino)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4c) was the most active against MCF-7 cells (IC50 = 0.08 μmol L-1). Both the anti-inflammatory and anticancer activities of the new compounds were dependent on the type of substituent on the phenyl rings. Substituents with opposite electronic effects on the two phenyl rings are preferable for high cytotoxicity against the MCF-7 and A2780 cells. COX inhibition was suggested as the molecular mechanism of the anti-inflammatory activity of the new compounds while no clear relationship could be observed between COX inhibition and anticancer activity. Compound 5b, the most active against the three cell lines, induced dose-dependent early apoptosis with 0.1-0.2 % necrosis in MCF-7 cells. New compounds showed promising drug-likeness scores while the docking study revealed high binding affinity to COX-2. Taken together, this study highlighted the significant impact of the substituents on the anti-inflammatory and anticancer activity of pyrrolizine-5-carboxamides, which could help in further optimization to discover good leads for the treatment of cancer and inflammation.


The Diversity of Serum Anti-DSG3 IgG Subclasses Has a Major Impact on Pemphigus Activity and Is Predictive of Relapses After Treatment With Rituximab.
We studied the distribution and in vitro pathogenicity of anti-DSG3 IgG subclasses during the course of pemphigus vulgaris (PV). We longitudinally studied the distribution of anti-DSG3 IgG subclasses (before versus after treatment) in sera from PV patients, using an addressable-laser bead immunoassay (ALBIA). The in vitro pathogenicity of corresponding sera was tested using keratinocyte dissociation and immunofluorescence assays. Sixty-five sera were assessed at baseline (33 from patients treated with rituximab and 32 with corticosteroids). Sixty-three percent of these baseline sera contained 2 or more anti-DSG3 IgG subclasses versus 35.7% of sera from patients in complete remission (CR) and 75.0% of sera from patients with persistent disease activity after treatment. IgG4 was the most frequently detected anti-DSG3 IgG subclass, both in patients with disease activity and in those in CR. The presence of three or more anti-DSG3 IgG subclasses was predictive of relapse, in particular when it included IgG3, with a positive predictive value of 62.5% and a negative predictive value of 92%. While anti-DSG3 IgG4 Abs from sera collected before treatment were most often pathogenic, anti-DSG3 IgG4 from sera collected after treatment were pathogenic only after adjusting their titer to the one measured before treatment. The IgG3 fraction containing anti-DSG3 Abs also had an in vitro pathogenic effect. The disappearance of the pathogenic effect of some sera after removal of anti-DSG3 IgG3 suggested an additional effect of this IgG subclass. The serum levels and number of anti-DSG3 IgG subclasses drive the pathogenic effect of pemphigus sera and may predict the occurrence of relapses.


Realization of a polymer nanowire optical transducer by using the nanoimprint technique.
An optical transducer using an integrated optics polymer nanowire is proposed. The nanoimprint technique is used to fabricate an OrmoComp nanowire with 1.0 μm width and 0.5 μm height, but the resulting sidewalls are not perfectly vertical. Maximum sensitivity is achieved by enhancing the evanescent field in the cladding region. The possible mode fields and power confinement of the nanowire are studied with respect to their structural dimensions, the operating wavelength, and the cladding material by using the H-field finite element method. The attenuation coefficient is extracted and calculated over the different cladding media, specifically air, water, and glycerol solution. It is observed that the scattering caused due to the surface roughness is the dominant effect that provides a larger attenuation coefficient.


Optimal Combination of Mother Wavelet and AI Model for Precise Classification of Pediatric Electroretinogram Signals.
The continuous advancements in healthcare technology have empowered the discovery, diagnosis, and prediction of diseases, revolutionizing the field. Artificial intelligence (AI) is expected to play a pivotal role in achieving the goals of precision medicine, particularly in disease prevention, detection, and personalized treatment. This study aims to determine the optimal combination of the mother wavelet and AI model for the analysis of pediatric electroretinogram (ERG) signals. The dataset, consisting of signals and corresponding diagnoses, undergoes Continuous Wavelet Transform (CWT) using commonly used wavelets to obtain a time-frequency representation. Wavelet images were used for the training of five widely used deep learning models: VGG-11, ResNet-50, DensNet-121, ResNext-50, and Vision Transformer, to evaluate their accuracy in classifying healthy and unhealthy patients. The findings demonstrate that the combination of Ricker Wavelet and Vision Transformer consistently yields the highest median accuracy values for ERG analysis, as evidenced by the upper and lower quartile values. The median balanced accuracy of the obtained combination of the three considered types of ERG signals in the article are 0.83, 0.85, and 0.88. However, other wavelet types also achieved high accuracy levels, indicating the importance of carefully selecting the mother wavelet for accurate classification. The study provides valuable insights into the effectiveness of different combinations of wavelets and models in classifying ERG wavelet scalograms.


Genomic Imprinting.
Genomic imprinting is the inheritance out of Mendelian borders. Many of inherited diseases and human development violates Mendelian law of inheritance, this way of inheriting is studied by epigenetics. The aim of this review is to analyze current opinions and options regarding to this way of inheriting. Epigenetics shows that gene expression undergoes changes more complex than modifications in the DNA sequence; it includes the environmental influence on the gametes before conception. Humans inherit two alleles from mother and father, both are functional for the majority of the genes, but sometimes one is turned off or "stamped" and doesn't show in offspring, that gene is imprinted. Imprinting means that that gene is silenced, and gene from other parent is expressed. The mechanisms for imprinting are still incompletely defined, but they involve epigenetic modifications that are erased and then reset during the creation of eggs and sperm. Genomic imprinting is a process of silencing genes through DNA methylation. The repressed allele is methylated, while the active allele is unmethylated. The most well-known conditions include Prader-Willi syndrome, and Angelman syndrome. Both of these syndromes can be caused by imprinting or other errors involving genes on the long arm of chromosome 15. Genomic imprinting and other epigenetic mechanisms such as environment is shown that plays role in offspring neurodevelopment and autism spectrum disorder.


Tracking the Progression of the Simulated Bronze Disease-A Laboratory X-ray Microtomography Study.
The internal three-dimensional characteristics of X-ray microtomography (micro-CT) has great application potential in the field of bronze corrosion. This work presents a method of simulating bronze disease based on an in situ micro-CT image to study the characteristics of the oxidative hydrolysis reactions of copper(I) chloride and copper(II) chloride dihydrate. A series of high-resolution reconstruction images were obtained by carrying out micro-CT at three key points throughout the experiment. We found that the reactions of copper(I) chloride and copper(II) chloride dihydrate showed different characteristics at different stages of the simulation in the micro-CT view. The method proposed in this work specifically simulated one single type of bronze corrosion and characterized the evolution characteristics of simulated bronze disease. It provides a new perspective to investigate bronze disease and can help improve the subsequent use of micro-CT to distinguish real bronze corrosions.


Signature quantization and representations of compact Lie groups.
We discuss some applications of signature quantization to the representation theory of compact Lie groups. In particular, we prove signature analogues of the Kostant formula for weight multiplicities and the Steinberg formula for tensor product multiplicities. Using symmetric functions, we also find, for type A, analogues of the Weyl branching rule and the Gel'fand-Tsetlin theorem.


Circularly Polarized Microscopy of Thin Films of Chiral Organic Dyes.
We introduce an optical microscopy technique, circularly polarized microscopy or CPM, able to afford spatially resolved electronic circular dichroism (ECD) of thin films of chiral organic semiconductors through a commercial microscope equipped with a camera and inexpensive optics. Provided the dichroic ratio is sufficiently large, the spatial resolution is on the order of the μm and is only limited by the magnification optics integrated in the microscope. We apply CPM to thin films of small chiral π-conjugated molecules, which gave rise to ordered aggregates in the thin layer. Primarily, conventional ECD can reveal and characterize chiral supramolecular structures and possible interferences between anisotropic properties of solid samples; however, it cannot generally account for the spatial distribution of such properties. CPM offers a characterization of supramolecular chirality and of commingling polarization anisotropies of the material, describing their local distribution. To validate CPM, we demonstrated that it can be adopted to quantify the local ECD of samples characterized by intense signals, virtually on any standard optical microscope.


The pediatric surgeon-patient relationship.
Though technical aspects of surgical practice are commonly emphasized, communication is the most frequent "procedure" employed by surgeons. A good patient-physician relationship enhances the quality of surgical care by improving outcomes and patient and family satisfaction. There are general principles that can enhance communication with all children and families. Employing a developmentally sensitive approach that adjusts communication style based on a child's cognitive abilities and emotional concerns can further enhance the relationship with children of different ages. These communication skills can be learned and are improved by practice and self-reflection.


"Building the plane while flying it" Reflections on pandemic preparedness and response; an organisational case study.
The COVID-19 pandemic provided a unique opportunity to learn about acute health organisations experiences implementing a pandemic response plan in real-time. This study was conducted to explore organisational leader's perspectives and experience activating a COVID-19 pandemic response plan in their health service and the impact of this on service provision, clinicians, and consumers. This study was conducted at a large metropolitan health service in Australia that provides acute, subacute, and residential aged care services. Semi-structured interviews were conducted with 12 key participants from the COVID-19 leadership team between November-January 2021/2022. A semi-structured interview guide was developed to explore how the health service developed a clinical governance structure, policy and procedures and experience when operationalising each element within the Hierarchy of Controls Framework. Thematic analysis was used to code data and identify themes. A cross-sectional survey of frontline healthcare workers on the impacts and perceptions of infection control practices during the COVID-19 pandemic, was also completed in 2021 with 559 responses. Twelve organisational leaders completed the semi-structured interviews. Key themes that emerged were: (1) Building the plane while flying it, (2) A unified communications strategy, (3) Clinicians fear 'my job is going to kill me', (4) Personal Protective Equipment (PPE) supply and demand, and (5) Maintaining a workforce. When surveyed, front-line healthcare workers responded positively overall about the health services pandemic response, in terms of communication, access to PPE, education, training, and availability of resources to provide a safe environment. Health service organisations were required to respond rapidly to meet service needs, including implementing a pandemic plan, developing a command structure and strategies to communicate and address the workforce needs. This study provides important insights for consideration when health service leaders are responding to future pandemics. Future pandemic plans should include detailed guidance for acute and long-term care providers in relation to organisational responsibilities, supply chain logistics and workforce preparation.


Legal and Ethical Consideration in Artificial Intelligence in Healthcare: Who Takes Responsibility?
The legal and ethical issues that confront society due to Artificial Intelligence (AI) include privacy and surveillance, bias or discrimination, and potentially the philosophical challenge is the role of human judgment. Concerns about newer digital technologies becoming a new source of inaccuracy and data breaches have arisen as a result of its use. Mistakes in the procedure or protocol in the field of healthcare can have devastating consequences for the patient who is the victim of the error. Because patients come into contact with physicians at moments in their lives when they are most vulnerable, it is crucial to remember this. Currently, there are no well-defined regulations in place to address the legal and ethical issues that may arise due to the use of artificial intelligence in healthcare settings. This review attempts to address these pertinent issues highlighting the need for algorithmic transparency, privacy, and protection of all the beneficiaries involved and cybersecurity of associated vulnerabilities.


A novel staphylococcal enterotoxin B subunit vaccine candidate elicits protective immune response in a mouse model.
Staphylococcal enterotoxin B (SEB), produced by the gram-positive bacterium Staphylococcus aureus, is responsible for food poisoning and toxic shock syndrome, and is considered a potential bioterrorism agent. Unfortunately, still now no approved vaccines are available against SEB. In this study, we constructed a series of nontoxic SEB mutants (mSEBs) and examined whether these mSEBs provide protective immunity against SEB challenge. These mSEB vaccine candidates did not demonstrate superantigen activity in mouse splenocyte cultures. Immunization with the vaccine candidates triggered the production of IgG-antibodies with neutralizing activity. In addition, increased production of IgG1 and IgG3 was observed after immunization, which signifies both Th1- and Th2-induced immune responses. Among the vaccine candidates tested, S9, a double mutant (N23A and Y90A) and S19, a quadruple mutant (N23A, Y90A, R110A, and F177A), demonstrated complete protection against a lethal SEB challenge. Altogether, our results strongly suggest that these mSEBs could be an effective recombinant SEB vaccine candidates for further/future preclinical and clinical studies.


[Primary malignant melanoblastoma of the esophagus (author's transl)].
Clinical and morphological aspects based on the observation of one case of oesophageal melanoblastoma are discussed. We want to point out that the characteristic morphology of the tumor enables us to exclude melanoma metastases and thus give an exact diagnosis. The importance of oesophagoscopy for the preoperative diagnosis is emphasized; radical resection is recommended for therapy.


Induction of selective autophagy in cells replicating hepatitis C virus genome.
Hepatitis C virus (HCV) infection is known to induce autophagy, but the mechanism of autophagy induced by HCV remains controversial. Here, we investigated the characteristics of autophagy induced by HCV infection. First, to examine the involvement of autophagy-related gene (ATG) proteins in HCV-induced LC3 lipidation, we established ATG5, ATG13 or ATG14 knockout (KO) Huh7.5.1 cell lines and confirmed that the accumulation of lipidated LC3 was induced in an ATG13- and ATG14-independent manner. On the other hand, HCV infectivity was not influenced by deficiencies in these genes. We also confirmed that LC3-positive dots were co-localized with ubiquitinated aggregates, and deficiency of ATG5 or ATG14 enhanced the accumulation of ubiquitinated aggregates compared to that in the restored cells, suggesting that HCV infection induces ATG5- and ATG14-dependent selective autophagy. Moreover, LC3-positive ubiquitinated aggregates accumulated near the site of the replication complex. We further examined autophagy flux in cells replicating HCV RNA using bafilomycin or E64d, and found that the increase of LC3 lipidation by treatment with bafilomycin or E64d was impaired in HCV-replicating cells, suggesting that autophagy flux is inhibited by the progress of HCV infection. Our present study suggests that (1) HCV RNA replication induces selective autophagy and (2) the progress of HCV infection impairs autophagy flux.


Natural selection on a carbon cycling trait drives ecosystem engineering by Sphagnum (peat moss).
Sphagnum peat mosses have an extraordinary impact on the global carbon cycle as they control long-term carbon sequestration in boreal peatland ecosystems. Sphagnum species engineer peatlands, which harbour roughly a quarter of all terrestrial carbon, through peat accumulation by constructing their own niche that allows them to outcompete other plants. Interspecific variation in peat production, largely resulting from differences in tissue decomposability, is hypothesized to drive niche differentiation along microhabitat gradients thereby alleviating competitive pressure. However, little empirical evidence exists for the role of selection in the creation and maintenance of such gradients. In order to document how niche construction and differentiation evolved in Sphagnum, we quantified decomposability for 54 species under natural conditions and used phylogenetic comparative methods to model the evolution of this carbon cycling trait. We show that decomposability tracks the phylogenetic diversification of peat mosses, that natural selection favours different levels of decomposability corresponding to optimum niche and that divergence in this trait occurred early in the evolution of the genus prior to the divergence of most extant species. Our results demonstrate the evolution of ecosystem engineering via natural selection on an extended phenotype, of a fundamental ecosystem process, and one of the Earth's largest soil carbon pools.


Co-administration of a Rhododendron tomentosum extract does not affect mercury tissue concentrations and excretion rate in methylmercury-treated adult male rats.
Consumption of fish/seafood is clearly linked to higher mercury levels in human tissue samples. However, correlations between methylmercury (MeHg) intakes calculated from dietary surveys and mercury body burdens are usually weak and can vary across populations. Different factors may affect MeHg absorption, distribution, metabolism and excretion, including co-exposures to phytochemicals and antibiotics, which were shown to affect mercury body burdens in rodents. Based on the observation that rat pups developmentally exposed to MeHg and a Rhododendron tomentosum extract (Labrador Tea) presented significantly higher blood mercury levels at weaning compared to pups exposed to MeHg alone, the modulation of MeHg toxicokinetics by Labrador Tea was further investigated in adult rats. Total mercury levels were quantified in the blood, liver, kidney and feces of adult male rats exposed to MeHg (1.2 mg/kg bodyweight/day, for 3 weeks) administered either alone or in combination with Labrador Tea (100 mg/kg bodyweight/day) or with an antibiotics cocktail (to inhibit MeHg demethylation by gut bacteria). While the reduced fecal excretion and higher blood mercury levels expected from antibiotics-treated rats were observed, mercury levels in samples from Labrador Tea-treated rats were not significantly different from those measured in samples from rats exposed to MeHg alone.


Colonization of root cells and plant growth promotion by Piriformospora indica occurs independently of plant common symbiosis genes.
Arbuscular mycorrhiza (AM) fungi (Glomeromycota) form symbiosis with and deliver nutrients via the roots of most angiosperms. AM fungal hyphae are taken up by living root epidermal cells, a program which relies on a set of plant common symbiosis genes (CSGs). Plant root epidermal cells are also infected by the plant growth-promoting fungus Piriformospora indica (Basidiomycota), raising the question whether this interaction relies on the AM-related CSGs. Here we show that intracellular colonization of root cells and intracellular sporulation by P. indica occurred in CSG mutants of the legume Lotus japonicus and in Arabidopsis thaliana, which belongs to the Brassicaceae, a family that has lost the ability to form AM as well as a core set of CSGs. A. thaliana mutants of homologs of CSGs (HCSGs) interacted with P. indica similar to the wild-type. Moreover, increased biomass of A. thaliana evoked by P. indica was unaltered in HCSG mutants. We conclude that colonization and growth promotion by P. indica are independent of the CSGs and that AM fungi and P. indica exploit different host pathways for infection.


Perception-action coupling in complex game play: Exploring the quiet eye in contested basketball jump shots.
The duration of the final fixation before movement initiation - a gaze strategy labelled quiet eye - has been found to explain differences in motor expertise and performance in precision tasks. To date, research only addressed this phenomenon in situations without adversarial constraints. In the present study, we compared the quiet-eye behaviour of intermediately-skilled and highly-skilled basketball players in defended vs. undefended game situations. We predicted differences in quiet-eye duration as a function of skill and performance particularly resulting from late quiet-eye offsets. Results indicated performance-enhancing effects of long quiet-eye durations in the defended but not in the undefended game situation. Furthermore, in line with our prediction, later quiet-eye offsets were associated with superior performance elucidating the phenomenon's relevance in online-demanding motor tasks. Further, earlier quiet-eye onsets were linked to successful performance supporting earlier suggestions that it is not only the duration but also the timing that matters. These findings not only extend the positive effects of the quiet eye in motor performance to dynamic game-play situations but also support the role of the quiet eye in response to programming and information processing respectively.


Disaster Relief: A Look Into the Pharmacist's Role.
After hurricane Matthew devastated southeastern North Carolina on October 8, 2016, health care providers and medical volunteers from various regions in North Carolina and from other surrounding states pulled together to initiate emergency medical services. Along with other healthcare providers, pharmacists played a key role in relief efforts. By using their broad knowledge of medicine and healthcare to efficiently utilize limited resources, pharmacists were vital in providing patient care. Their skills and knowledge make them a valuable resource in disaster relief.


Offspring produced from orthotopic transplantation of chicken ovaries.
The loss of avian genetic variation and the threat of disease lend urgency to the cryopreservation of remaining poultry stocks. However, techniques for freezing ova and embryos are not available for birds, and the recovery of genetic material has been a major obstacle to cryopreservation. To overcome this problem, we transplanted chicken ovarian tissue just after hatch with or without subsequent treatment of the recipient with an immunosuppressant. Nine of 12 hens in the nonimmunosuppressed group and 6 of 9 birds in the immunosuppressed group produced eggs, whereas 3 hens in each group produced donor-derived offspring. These results suggest that transplantation of ovarian tissue of chickens is possible if performed just after hatch. This finding should allow efficient cryopreservation of female germ cells in chickens with regeneration in live birds. In addition, ovarian transplantation could be useful for studies in genetics or developmental biology or could provide convenient access to the female germline for genetic manipulation.


Simple non-invasive assessment of advanced glycation endproduct accumulation.
The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL). Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62, p</=0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were above the 95% CI of the mean value in control subjects, and correlated with age, diabetes duration, mean HbA(1)c of the previous year and creatinine levels. The AFR offers a simple alternative to invasive measurement of AGE accumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation.


'An accident waiting to happen' - experiences of police officers, paramedics, and mental health clinicians involved in 911-mental health crises: a cross-sectional survey.
Police and ambulance staff are increasingly asked to help people experiencing mental health crises, but they often feel under-prepared. The single frontline service approach is time-intensive and risks a coercive pathway to care. The emergency department is the default location for transfers by police or ambulance involving a person involved in a mental health crisis, despite being viewed as suboptimal. Police and ambulance staff struggled keeping up with the mental health demand, reporting inadequate mental health training, little enjoyment and negative experiences when trying to access help from other services. Most mental health staff had adequate mental health training and enjoyed their work, but many experienced difficulties getting help from other services. Police and ambulance staff found it hard to work with mental health services. The combination of limited training, poor interagency referral processes, and difficulties accessing support from mental health services means that when police and ambulance services attend mental health crises alone, distress may be heightened and prolonged. Enhanced mental health training for first responders and more streamlined referral processes may improve process and outcomes. Mental health nurses have key skills that could be utilized in assisting police and ambulance staff who attend 911 emergency mental health calls. New models such as co-response teams, whereby police, mental health clinicians and ambulance staff respond conjointly should be trialled and evaluated. INTRODUCTION: First responders are increasingly called to assist people experiencing mental health crises but little research exists canvassing multi-agency perspectives of such work. To understand the views of police officers, ambulance and mental health staff attending mental health or suicide-related crises in Aotearoa New Zealand and to discover how they experience current models of cross-agency collaboration. A descriptive cross-sectional survey involving mixed methods. Quantitative data were analysed using descriptive statistics and free text by content analysis. Participants included 57 police officers, 29 paramedics and 33 mental health professionals. Mental health staff felt adequately trained, but only 36% described good processes for accessing inter-agency support. Police and ambulance staff felt undertrained and unprepared. Accessing mental health expertise was considered difficult by 89% of police and 62% of ambulance staff. Frontline services struggle managing mental health-related 911 emergencies. Current models are not working well. Miscommunication, dissatisfaction and distrust exist between police, ambulance and mental health services. The single-agency frontline response may be detrimental to service users in crisis and under-utilizes the skills of mental health staff. New ways of inter-agency cooperation are required, such as co-located police, ambulance and mental health nurses responding in partnership.


Characterization of the effects of retinoic acid on vasoactive intestinal polypeptide gene expression in neuroblastoma cells.
The neuropeptide vasoactive intestinal polypeptide (VIP) has a broad range of functions, and its expression has been correlated with neuronal differentiation. Here we present data on the effects of retinoic acid (RA), a known modulator of neuronal differentiation, on VIP gene expression in the human neuroblastoma cell line NB-1. Morphological data, surprisingly, indicate that these cells are not differentiated concomitant with the increase in VIP gene expression. RA was found to exert a concentration-dependent induction of peptides derived from the VIP precursor molecule, prepro-VIP. The effect at both the messenger RNA (mRNA) level, evaluated by Northern blots, and the peptide level, measured by RIAs, was found to be slow and long lasting. No changes in the processing of prepro-VIP were observed using gel chromatography and RIAs specific for various prepro-VIP sequences. Also, the expression of mRNA for the prohormone-processing enzyme PC2, present in these cells, was not altered by RA. The lag period preceding the increase in VIP mRNA led to experiments with the translational inhibitor cycloheximide showing an indirect effect of RA on VIP mRNA expression. Northern blots revealed that at least three mRNAs encoding RA receptor were expressed and rapidly induced by RA in the cells, thus making them possible candidates for the intermediate protein(s) required from the induction of VIP gene expression.


Isoflurane but Not Halothane Prevents and Reverses Helpless Behavior: A Role for EEG Burst Suppression?
The volatile anesthetic isoflurane may exert a rapid and long-lasting antidepressant effect in patients with medication-resistant depression. The mechanism underlying the putative therapeutic actions of the anesthetic have been attributed to its ability to elicit cortical burst suppression, a distinct EEG pattern with features resembling the characteristic changes that occur following electroconvulsive therapy. It is currently unknown whether the antidepressant actions of isoflurane are shared by anesthetics that do not elicit cortical burst suppression. In vivo electrophysiological techniques were used to determine the effects of isoflurane and halothane, 2 structurally unrelated volatile anesthetics, on cortical EEG. The effects of anesthesia with either halothane or isoflurane were also compared on stress-induced learned helplessness behavior in rats and mice. Isoflurane, but not halothane, anesthesia elicited a dose-dependent cortical burst suppression EEG in rats and mice. Two hours of isoflurane, but not halothane, anesthesia reduced the incidence of learned helplessness in rats evaluated 2 weeks following exposure. In mice exhibiting a learned helplessness phenotype, a 1-hour exposure to isoflurane, but not halothane, reversed escape failures 24 hours following burst suppression anesthesia. These results are consistent with a role for cortical burst suppression in mediating the antidepressant effects of isoflurane. They provide rationale for additional mechanistic studies in relevant animal models as well as a properly controlled clinical evaluation of the therapeutic benefits associated with isoflurane anesthesia in major depressive disorder.


A Homology Based Model and Virtual Screening of Inhibitors for Human Geranylgeranyl Transferase 1 (GGTase1).
Protein prenylation is a post translational modification that is indispensable for Ras-Rho mediated tumorigenesis. In mammals, three enzymes namely protein farnesyltransferase (FTase), geranylgeranyl transferase1 (GGTase1), and geranylgeranyl transferase2 (GGTase2) were found to be involved in this process. Usually proteins of Ras family will be farnesylated by FTase, Rho family will be geranylgeranylated by GGTase1. GGTase2 is exclusive for geranylgeranylating Rab protein family. FTase inhibitors such as FTI- 277 are potent anti-cancer agents in vitro. In vivo, mutated Ras proteins can either improve their affinity for FTase active site or undergo geranylgeranylation which confers resistance and no activity of FTase inhibitors. This led to the development of GGTase1 inhibitors. A well-defined 3-D structure of human GGTase1 protein is lacking which impairs its in silico and rational designing of inhibitors. A 3-D structure of human GGTase1 was constructed based on primary sequence available and homology modeling to which pubchem molecules library was virtually screened through AutoDock Vina. Our studies show that natural compounds Camptothecin (-8.2 Kcal/mol), Curcumin (-7.3 Kcal/mol) have higher binding affinities to GGTase-1 than that of established peptidomimetic GGTase-1 inhibitors such as GGTI-297 (-7.5 Kcal/mol), GGTI-298 (-7.5 Kcal/mol), CHEMBL525185 (-7.2 Kcal/mol).


Serum exosomal miR-34a as a potential biomarker for the diagnosis and prognostic of hepatocellular carcinoma.
Background: Circulating exosomal microRNAs (miRNAs) are considered as potentially non-invasive biomarkers for early detection and prognosis of cancers. Due to the lack of highly sensitive and specific molecular markers, a lot of patients with hepatocellular carcinoma are diagnosed in advanced stages. This study aims to explore the expression mode and clinical detection value of serum exosomal miR-34a in HCC, providing new potential targets and theoretical basis for the early diagnosis and prognosis monitoring of hepatocellular carcinoma. Methods: The expression of serum exosomal miR-34a in 60 HCC patients before and after operation and 60 healthy examiners was abstracted and detected by ultracentrifugation and real-time quantitative PCR. Using ROC analysis, Kaplan-Meier survival analysis and Cox regression analysis, the value of serum exosomal miR-34a on diagnosis and prognosis in HCC patients was assessed. Results: The expression level of serum exosomal miR-34a in preoperative patients was reduced significantly comparing with that in healthy examiners and postoperative patients (P<0.01; P<0.05). Moreover, the decrease of serum exosomal miR-34a was correlated significantly with differentiation degree, TNM stage, tumor infiltration depth and lymph node metastasis(P<0.05), but had no statistical differences with gender, age, ALT, AST, viral infection, cirrhosis and tumor size of HCC patients (P>0.05). At the same time, the combination of serum exosomal miR-34a and α-fetoprotein (AFP) showed high capability on diagnosis to distinguish healthy examiners and HCC patients through ROC analysis. The overall survival of patients with lower expression of serum exosomal miR-34a was worse than that of patients with high level expression by Kaplan-Meier survival analysis (P<0.05). Univariate and multivariate Cox regression analysis both showed that serum exosomal miR-34a was independently related to OS. Conclusions: Collectively, serum exosomal miR-34a is significantly down-regulated in HCC patients and might be a novel noninvasive biomarker for diagnosis and prognosis of HCC.


Analysis of the complete mitochondrial genome sequence of Japanese butterflyfish, Chaetodon nippon (Chaetodontiformes, Chaetodontidae).
Japanese butterflyfish (Chaetodon nippon) belong to the family Chaetodontidae and order Chaetodontiformes. It has circular mitochondrial genome of 16,507 bp in length with 55.4% of A + T content and has 37 genes, including 22 tRNA, 2 rRNA, and 13 protein-coding genes, in addition to a control region. The results of phylogenetic analysis indicated that the C. nippon, C. wiebeli, C. auripes, C. auriga, C. octofasciatus, C. speculum, and C. modestus are closely related to each other. The findings of this study will provide useful genetic information for further phylogenetic and taxonomic classifications of Chaetodontidae.


The use of IRAMUTEQ software for data analysis in qualitative research.
To describe the use of IRAMUTEQ software in qualitative data analysis. A description for using a software program as a tool to support data processing in qualitative research, carried out in 2015. Data collection was done through interviews using a semi-structured script. Twenty-one (21) companions participated in the study. The five classes resulting from data processing by the software allowed for analysis and interpretation of the nursing performance with the parturient as an active participant in the process of labor and delivery, and in the role of companion in this period. The use of IRAMUTEQ software as a tool for processing qualitative data through the Descending Hierarchical Classification emerged classes and a connection between them, which further allowed for secure and credible data analysis. It is necessary to explore the other possibilities of using this tool in greater depth.


Correspondence between adolescent report, parent report, and teacher report of manic symptoms.
To examine differences between source-specific manic symptoms. In total, 104 consecutive adolescent outpatient referrals were evaluated for their psychiatric status using a questionnaire based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders that was completed by parents, teachers, and youths. Approximately one third of the youths met symptom criteria for mania by at least one informant; however, only 38% of these met such criteria by at least two informants. Youths who had manic symptoms according to two informants were significantly more symptomatic both on mental status exam and in other dimensions of psychopathology than youths who did not have corroborated manic symptoms. Cross-informant agreement was generally poor when symptoms were scored dimensionally. Manic symptoms are relatively nonspecific in outpatient samples. Using more than one informant increases the likelihood of selecting subjects with serious and possibly manic disorders.


Endotoxin-induced shock in the rat. A role for C5a.
Administration of endotoxin from gram-negative bacteria to rats results in systemic hypotension, an increased hematocrit, and decreased numbers of circulating leukocytes (polymorphonuclear), monocytes, and platelets. These potentially lethal physiologic changes may be partially attributed to complement activation and generation of anaphylatoxins by the endotoxin (LPS). We demonstrated an elevation in the plasma levels of both C3a and C5a in LPS-treated rats. Injection of 5 micrograms C5ades Arg (rat) into rats produced effects similar to those induced by LPS, including decreased mean arterial pressure (systemic hypotension) and decreased numbers of circulating polymorphonuclear leukocytes, monocytes, and platelets. Unlike the response to LPS, C5a did not increase the hematocrit, indicating little effect on vascular permeability at the doses used. When LPS-treated animals were pretreated with F(ab')2 fragments of rabbit anti-rat C5a, no changes were measured in the circulating cell counts compared with LPS alone; however a significant improvement in the mean arterial pressure and a decrease in hematocrit was observed. We conclude that LPS-induced (septic) shock in the rat may result, in part, from the effects of complement activation and particularly from the generation of C5a. The influence of C5a on the LPS effect in the rat appears to enhance both the hypotensive (mean arterial pressure) and vascular permeability (hematocrit) responses. These results appear to support and confirm earlier observations that anti-human C5a increased survival in a septic-shock monkey model by eliminating circulating C5a and presumably thereby reducing the effects of endotoxin on blood pressure. Our results demonstrate that C5a plays a significant role in the hemodynamic changes associated with endotoxin-induced shock. Neutralization of C5a with specific antibodies may reduce the hypotensive response to endotoxin sufficiently to prevent lethal septic shock both in animals and in man.


Nicotine administration significantly alters accumbal dopamine in the adult but not in the adolescent rat.
Many drug-dependent adults began using drugs during adolescence. In fact, adolescent drug users are more likely to become drug-dependent adults than those abstaining from drug use until after the age of 18. Because of this, recent research has begun to investigate the consequences of adolescent drug use. Specifically, research has begun to focus on the behavioral effects of drugs on the developing brain and the development of drug addiction. The present study examined the responsiveness of the mesolimbic dopamine (DA) pathway during development through the use of in vivo microdialysis. Specifically, it was determined whether nicotine-induced accumbal DA release differs between adolescent and adult rats. To assess nicotine's effects across age, animals received acute or repeated nicotine at early adolescence (postnatal day (PND) 35), late adolescence (PND 45), or young adulthood (PND 60). Findings suggest that there are significant differences between adolescent and adult animals in their dopaminergic response to nicotine. Adult animals had an enhanced DA response to acute nicotine challenge, an effect absent in adolescence. Additionally, this nicotine-induced increase in adults was not apparent after repeated nicotine treatment. These results provide insight into how the adolescent brain responds to nicotine and may also provide evidence as to how prolonged nicotine use affects normal brain development and responsiveness.


Dermoid of the oral cavity: case report with histopathology correlation and review of literature.
Dermoid cysts are rare masses of the oral cavity derived from ectodermal elements. These are benign, slow-growing tumors that are typically asymptomatic but cause complications of inflammation or dysphagia, dystonia, and airway encroachment due to mass effects. We report the case of a 17 year old female with a painless mass in the left side of the oral cavity. Ultrasound findings demonstrated non-specific findings of a cystic lesion, and definite diagnosis was made with contrast-enhanced CT and intraoperatively with pathologic confirmation. This retrospective report highlights the challenges in evaluating masses of the oral cavity with imaging and provides a comprehensive discussion on imaging of oral masses on various imaging modalities to guide diagnosis and management.


Metabolic disturbances in diabetic cardiomyopathy.
It has been established that diabetes results in a cardiomyopathy, and increasing evidence suggests that an altered substrate supply and utilization by cardiac myocytes could be the primary injury in the pathogenesis of this specific heart muscle disease. For example, in diabetes, glucose utilization is insignificant, and energy production is shifted almost exclusively towards beta-oxidation of free fatty acids (FFA). FFA's are supplied to cardiac cells from two sources: lipolysis of endogenous cardiac triglyceride (TG) stores, or from exogenous sources in the blood (as free acid bound to albumin or as TG in lipoproteins). The approximate contribution of FFA from exogenous or endogenous sources towards beta-oxidation in the diabetic heart is unknown. In an insulin-deficient state, adipose tissue lipolysis is enhanced, resulting in an elevated circulating FFA. In addition, hydrolysis of the augmented myocardial TG stores could also lead to high tissue FFA. Whatever the source of FFA, their increased utilization may have deleterious effects on myocardial function and includes the abnormally high oxygen requirement during FFA metabolism, the intracellular accumulation of potentially toxic intermediates of FFA, a FFA-induced inhibition of glucose oxidation, and severe morphological changes. Therapies that target these metabolic aberrations in the heart during the early stages of diabetes could potentially delay or impede the progression of more permanent sequelae that could ensue from otherwise uncontrolled derangements in cardiac metabolism.


Inhibition of self-observing activity in psychoanalytic treatment.
The author examines the topic of inhibition of self-observing function in some patients arising from conflicts over aggression. The author's thesis is that conflicts over aggression can interfere with the patient's task of shifting from passively reporting spontaneously occurring associations to actively reflecting on his thoughts in an analysis. This can result in the patient remaining in the role of passive reporter of his associations while ceding to the analyst the role of aggressive interpreter of the patient's psychic functioning. The active ego functions necessary for understanding and integration are inhibited, compromising the potential for growth and change. Clinical vignettes illustrate a close process analytic process to this phenomenon.


The influence of surface roughness and surface dynamics on the attachment of Methicillin-Resistant Staphylococcus aureus onto orthodontic retainer materials.
Staphylococci species have been isolated from removable orthodontic retainers. The aims of this study were to determine the most suitable device to analyze surface roughness of autopolymerized acrylic and thermoplastic materials and whether the surface dynamics of these materials influences the attachment of Methicillin-Resistant Staphylococcus aureus (MRSA). Clinically simulated samples of autopolymerized acrylic and thermoplastic material were first evaluated using laser non-contact, stylus mechanical profilometries and atomic force microscopy (AFM) followed by contact angle measurement to characterize their surface dynamics. Finally, an in vitro biofilm assay was carried out using a constant depth film fermentor to assess biofilm attachment. The results showed a significant difference between the roughness values obtained from the tested profilometers with the AFM exhibiting the most consistent roughness values. MRSA tended to accumulate initially within the microscopic irregularities of autopolymerized acrylic samples whereas acid-base and electron donor interactions influenced the bacterial attachment onto the thermoplastic samples.


[Ehlers-Danlos syndrome IV: phenotype variation].
In three female patients, 20, 4 and 29 years of age, Ehlers-Danlos syndrome (EDS) IV was diagnosed on the basis of a deficiency of collagen III with among other things a hyperextensible skin and joints and easy bruising. Severity of symptoms varies considerably per patient. EDS comprises 10 types. Type IV is the most severe type because of its often lethal complications like arterial rupture. Deficiency of collagen III is also seen in EDS patients without the classical severe EDS IV phenotype. It is suggested to restrict collagen III analysis to patients who are suspected of having classical EDS IV.


Chiral pharmacokinetics of Rac-flurbiprofen and pharmacodynamics of anabolic bone response in the normal rat.
The route of administration of the NSAID, flurbiprofen (sq vs. po) resulted in positive and negative results respectively with regard to enhanced cancellous and cortical bone accumulation in the immature rat. This pharmacokinetic study was an effort to understand the pharmacodynamic difference between the two routes of administration observed when the same dose range of drug, given as single daily doses, had been employed in both studies. Conventional chiral pharmacokinetics were evaluated in young rats. A significant difference was observed in the Tmax of the active (S)-enantiomer by both administration routes (sq 4 h and po 1 h). The bioavailability, as evaluated by AUCs favored the sq route as expected. The plasma concentrations over 18 h, at steady state, for one po dose group (0.5 mg/kg/day) fell well within the therapeutic window described by the 0.1 and 0.5 mg/kg sq doses which had demonstrated anabolic bone activity. Oral dosing had exhibited no significant bone activity. We conclude that the pharmacodynamic difference between routes of administration cannot be simply explained on a pharmacokinetic basis. Consequently, experiments detailing the pharmacodynamics and pharmacokinetics of single and multiple dose administration of aryl-propionic acids in normal and osteopenic states need further pharmacologic study.


Building Nurse Manager Well-being by Reducing Healthcare System Demands.
The National Academies of Medicine consensus study committee reported that US healthcare workers experience high levels of burnout resulting from external pressures on the healthcare system and the organization of work. Nurse managers are especially susceptible to burnout. This column provides evidence-based strategies to improve the work environment, reduce the burden of job demands, and promote well-being among nurse managers.


Identifying Levorphanol Ingestion Using Urine Biomarkers in Health Care Patients.
Levorphanol is a long-acting opioid analgesic that is an optical isomer of dextrorphan, a metabolite of the over-the-counter cough suppressant dextromethorphan. Providers prescribing levorphanol for pain management may need to assess compliance through urine drug testing, as this agent is subject to abuse. Therefore, it is important to differentiate between dextromethorphan and levorphanol ingestion. This article is the first to report urine concentrations of levorphanol/dextrorphan and 3-hydroxymorphinan in human urine and assesses the need for an enantiomeric analysis to distinguish between dextromethorphan and levorphanol ingestion. Retrospective data review. Medication compliance test results were reviewed for 521 urine samples submitted to Aegis Sciences Corporation between July 2014 and July 2016. Samples were included in this analysis if dextromethorphan or levorphanol testing was requested by the ordering provider. Urine samples were hydrolyzed with beta-glucuronidase and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An enantiomeric analysis to distinguish levorphanol from dextrorphan and (-)-3-hydroxymorphinan (norlevorphanol) from (+)-3-hydroxymorphinan was not performed. Nineteen urine samples with levorphanol listed as prescribed had median levorphanol/dextrorphan and 3-hydroxymorphinan concentrations of 1,881 ng/mL and 141 ng/mL, respectively. One-quarter of the urine samples with dextromethorphan listed as prescribed did not have any detectable dextromethorphan or 3-methoxymorphinan. An enantiomeric analysis was not utilized with the LC-MS/MS testing method; therefore, levorphanol could not be differentiated from dextrorphan, and (-)-3-hydroxymorphinan could not be differentiated from (+)-3-hydroxymorphinan. The hepatic and renal function for these patients was unknown; however, both could impact the metabolism, distribution, and excretion of levorphanol biomarkers in urine. The dextromethorphan and/or levorphanol dose and timing of last ingestion was also not assessed. It may be impossible to distinguish between levorphanol and dextromethorphan ingestion based on urine biomarkers, unless dextromethorphan or 3-methoxymorphinan is present or an enantiomeric analysis is performed. Therefore, the potential exists for patients prescribed levorphanol to ingest dextromethorphan and appear compliant with levorphanol therapy. This should prompt clinicians to consider the parameters of their laboratory's testing method when interpreting levorphanol drug test results. Levorphanol, dextrorphan, dextromethorphan, 3-hydroxymorphinan, urine testing, urine concentration, drug testing, medication compliance testing.


Developing a nurse-led service for COPD patients.
A rise in the rate of hospital admissions for patients with COPD has led to the development of nurse-led home care. A study in which a nurse-led team provided domiciliary treatment with ongoing follow-up, was found to be cost-effective and reduced the need for hospital care.


Structure of reduced DsbA from Escherichia coli in solution.
The three-dimensional structure of reduced DsbA from Escherichia coli in aqueous solution has been determined by nuclear magnetic resonance (NMR) spectroscopy and is compared with the crystal structure of oxidized DsbA [Guddat, L. W., Bardwell, J. C. A., Zander, T., and Martin, J. L. (1997) Protein Sci. 6, 1148-1156]. DsbA is a monomeric 21 kDa protein which consists of 189 residues and is required for disulfide bond formation in the periplasm of E. coli. On the basis of sequence-specific 1H NMR assignments, 1664 nuclear Overhauser enhancement distance constraints, 118 hydrogen bond distance constraints, and 293 dihedral angle constraints were obtained as the input for the structure calculations by simulated annealing with the program X-PLOR. The enzyme is made up of two domains. The catalytic domain has a thioredoxin-like fold with a five-stranded beta-sheet and three alpha-helices, and the second domain consists of four alpha-helices and is inserted into the thioredoxin motif. The active site between Cys30 and Cys33 is located at the N terminus of the first alpha-helix in the thioredoxin-like domain. The solution structure of reduced DsbA is rather similar to the crystal structure of the oxidized enzyme but exhibits a different relative orientation of both domains. In addition, the conformations of the active site and a loop between strand beta5 and helix alpha7 are slightly different. These structural differences may reflect important functional requirements in the reaction cycle of DsbA as they appear to facilitate the release of oxidized polypeptides from reduced DsbA. The extremely low pKa value of the nucleophilic active site thiol of Cys30 in reduced DsbA is most likely caused by its interactions with the dipole of the active site helix and the side chain of His32, as no other charged residues are located next to the sulfur atom of Cys30 in the solution structure.


Comorbidity between HTLV-1-associated adult T-cell lymphoma/leukemia and verrucous carcinoma: a case report.
Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV).


Marital Status and Survival in Patients with Penile Cancer.
Purpose: We aimed to reveal the effects of marital status on survival outcomes in patients with penile cancer. Methods: Patients with penile cancer who were diagnosed between 2004 and 2015 were identified by using the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier and Cox regressions were used to analyse the effects of marital status on overall survival (OS) and cancer-specific survival (CSS). Results: Among 3,195 eligible patients with penile cancer, 1,951 (61.1%) patients were married, 365 (11.4%) were divorced or separated, 327 (10.2%) were widowed and 552 (17.3%) were single. The widowed patients had the worst OS median survival time (22 months) and CSS median survival time (23.5 months). Marital status was an independent prognostic factor for OS and CSS of penile cancer patients. The multivariate Cox regression showed that widowed patients exhibited the poorest OS (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.48-2.03, p < 0.001) and the poorest CSS (HR: 1.64; 95% CI: 1.144-1.279, p < 0.001) compared with married patients. Similar results were observed in our centre database and the subgroup analyses based on the SEER stage and grade. Conclusions: In our study, we found that marital status was an independent prognostic factor for survival in patients with penile cancer. Additionally, widowed patients had the lowest OS and CSS compared with married patients.


[Carbohydrate-deficient-glycoprotein syndrome and ophthalmological manifestations].
Carbohydrate-deficient-glycoprotein syndromes are new described multisystemic diseases. We report here the case of a young boy who presented with CDG syndrome Ia associated with typical ocular disorders. This 18-month-old boy presented facial dysmorphism, ataxia, hypotonia and cerebellar hypoplasia. Ocular examination showed esotropia with nystagmoid movements and at fundoscopy signs of retinitis pigmentosa with foveal hypoplasia. Photopic and scotopic electroretinograms were altered. CDG syndromes are metabolic disorders which affect N-glycoprotein synthesis. Clinical manifestations are various: hypotonia, cerebellar hypoplasia, developmental delay, pericardial effusion, etc. Four variants are described; each of them is associated with particular clinical disorders and prognosis. Ocular features are frequently associated (esotropia, retinitis pigmentosa) and especially in CDG syndrome Ia. Esotropia associated with fundus alterations appearing in a multisystemic disorder requires explorations to search for CDG syndrome.


Efficient Delivery of Investigational Antibacterial Agents via Sustainable Clinical Trial Networks.
The economics of antibiotics can be improved by infectious diseases-specific clinical trial networks. While developers would still need to implement an independent phase 1 program as well as studies focused on highly resistant pathogens, standardized procedures in a network focused on usual drug resistance phenotype isolates would permit sharing of controls and would predictably generate high-quality pivotal data for product registration while creating cost and time savings in the range of 30%-40%. This would reduce economic barriers to antibiotic development and contribute to public health.


Surface-alkylated polystyrene monolithic columns for peptide analysis in capillary liquid chromatography-electrospray ionization mass spectrometry.
Macroporous poly(styrene-divinylbenzene) (PS-DVB) monoliths were prepared by in situ polymerization in PEEK, fused silica, or stainless steel tubing having an inner diameter of 75 or 125 microm. A process is described for subsequent alkylation of the flow-contacting surfaces of the monoliths. The process treats all the surfaces including through-pore surfaces of the rigid macroporous monolith with a solution containing a dissolved Friedel-Crafts catalyst, an alkyl halide (1-chlorooctadecane), and an organic solvent. This process produces an improved reversed-phase liquid chromatographic separation of peptides compared to an unmodified monolithic PS-DVB column. The surface octadecylation is not necessary for a reversed-phase separation of proteins since both unmodified and modified columns provide comparable results. Tryptic protein digests, standard proteins, and standard peptides were used to evaluate the monolithic columns by employing electrospray mass spectrometry detection. Potential applications in proteomics studies by mass spectrometry, which use the alkylated monolithic column engaged onto the nanofabricated electrospray ionization chip, are also discussed.


Y box-binding protein 1 induces resistance to oncogenic transformation by the phosphatidylinositol 3-kinase pathway.
Y box-binding protein 1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and of translation. In chicken embryo fibroblasts transformed by the oncoproteins P3k (phosphatidylinositol 3-kinase) or Akt, YB-1 is transcriptionally down-regulated. Expression of YB-1 from a retroviral vector induces a strong cellular resistance to transformation by P3k or Akt but does not affect sensitivity to transformation by other oncoproteins, such as Src, Jun, or Qin. The YB-1-expressing cells assume a tightly adherent, flat phenotype, with YB-1 localized in the cytoplasm, and show a greatly reduced saturation density. Both cap-dependent and cap-independent translation is inhibited in these cells, but the activity of Akt remains unaffected, suggesting that YB-1 functions downstream of Akt. A YB-1 protein with a loss-of-function mutation in the RNA-binding motif no longer binds to the mRNA cap structure, is localized in the cell nucleus, does not induce the flat cellular phenotype, and fails to interfere with P3k- or Akt-induced oncogenic transformation. This mutant also does not inhibit cap-dependent or cap-independent translation. These results suggest that YB-1 acts like a rapamycin mimic, inhibiting translational events that are required in phosphatidylinositol 3-kinase-driven oncogenic transformation.


Chicken or the egg: ST elevation in lead aVR or SYNTAX score.
ST-segment elevation in lead aVR (STEaVR) anticipates left main and/or three-vessel disease (LM/3VD) in patients with acute coronary syndromes. STEaVR is generally reciprocal to and accompanied by ST-segment depression (STD) in the precordial leads. SYNTAX score (SS) is an angiographic scoring system and is widely used to evaluate the severity and complexity of coronary artery disease. The purpose of our study was to assess the relationship between STEaVR and SS. We performed a retrospective analysis of 117 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Electrocardiograms at presentation were reviewed, especially for ST-segment elevation of ≥ 0.05 mV in lead aVR and STD of ≥ 0.05 mV in more than two contiguous leads. All lesions causing ≥ 50% stenosis in a coronary artery with a diameter of ≥ 1.5 mm were included in the SS calculation. SS was divided into two groups: ≥ 23: high, < 23: low. Among the 117 patients, 80 (68.4%) had STEaVR and 37 (31.6%) did not. Patients with STEaVR had a higher SS and higher rate of LM/3VD (85 vs 67.6%, p < 0.001; 86.2 vs 72.9%, p = 0.03, respectively) than those without STEaVR. On multivariate analysis, STEaVR [odds ratio (OR) 1.85; 95% confidence interval (CI): 1.20-3.97, p = 0.03] and STD in leads V1-V4 (OR 2.14; 95% CI: 1.46-4.23, p = 0.002) were independent predictors of a high SS. This study demonstrated that STEaVR was an independent predictor of a high SS.


Oxygen dissociation of whole blood studied polarographically.
The polarographic current of whole blood is in excess of that given by plasma at the same oxygen tension. The magnitude of this difference depends on (a) the oxygen content of the sample and thus is determined by the red blood cell content and by the state of oxygen saturation of hemoglobin, and (b) on the rate of dissociation of oxyhemoglobin and therefore is influenced by changes in pH, pCO(2), and temperature. The total current at 37 degrees C. is proportional to the oxygen content of the sample and can be used to determine the latter. The theoretical basis of the studied phenomena is discussed in detail.