Arbuscular mycorrhizal fungi ameliorate temperature stress in thermophilic plants.
Biotic interactions can affect the distribution of species across environmental gradients, and as air and soil temperatures increase, plant community response may depend on interactions with symbionts. We measured the effect of elevated soil temperatures on mycorrhizal function and on the response of both plant and fungal symbionts, using fungal inoculum isolated from either high-temperature thermal or nonthermal grassland soils. Our source for thermal soils was Yellowstone National Park, USA, where plants experience rooting zone temperatures of 45 degrees C or more. In the greenhouse, we grew three plant species (Dichanthelium lanuginosum, Agrostis scabra, and Mimulus guttatus) with three arbuscular mycorrhizal fungal (AMF) treatments (no AMF, nonthermal AMF, thermal AMF) and two soil temperatures (ambient, elevated). Biomass of the facultative thermal plants Agrostis scabra and Mimulus guttatus decreased by 50% in elevated-temperature soils, and AMF had no effect on measured plant traits. In contrast, the biomass and total root length of the obligate thermal plant Dichanthelium lanuginosum were greater at elevated soil temperatures, but only when mycorrhizal. Both mycorrhizal colonization levels and length of extraradical hyphae (ERH) increased with soil temperature across all host species. The source of the AMF inoculum, on the other hand, did not affect colonization level, ERH length, host plant biomass, or flowering for all host species in either temperature treatment, suggesting that AMF from thermal soils are not specifically adapted to higher temperatures. In the field we collected soil cores to measure in situ depth distributions of D. lanuginosum roots and ERH, and to determine which AMF species were active in plants growing in thermal soils. Roots were limited to soils with an average temperature < or =30 degrees C, while ERH existed in the hottest soils we sampled, averaging 35 degrees C. Molecular analyses of roots indicated that thermal AMF communities were composed of both generalist and possibly unique fungal species. The increase in host plant allocation to AMF, apparent lack of temperature adaptation by AMF, and differential host response to AMF suggest that AMF could be significant drivers of plant community response to increased soil temperature associated with global change.


Adenosine stress high-pitch 128-slice dual-source myocardial computed tomography perfusion for imaging of reversible myocardial ischemia: comparison with magnetic resonance imaging.
Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR). Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64 ± 10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate <63 bpm) or prospective ECG-triggering (heart rate >63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv. Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.


Abnormal sexual differentiation and neoplasia.
The prevalence of neoplasia is increased in individuals with certain disorders of sexual differentiation. Etiology and frequency of neoplasia vary with the particular disorder. In uncomplicated cryptorchidism, the testis is at least 10 times more likely to undergo neoplastic transformation than a normal scrotal testis. Neoplasia probably is a function of both testicular location (intraabdominal) and underlying dysgenetic structure. If cryptorchidism is unilateral, and if orchiopexy has not been performed prior to age 6-10 years, orchiectomy should be encouraged. In those forms of gonadal dysgenesis not associated with a Y chromosome (e.g., 45,X; 45,X/46,XX; 46,XX) there is no definite increase in neoplasia, suggesting that elevated gonadotropin levels per se are not carcinogenic. Gonadal tumors are found in at least 30% of individuals with XY gonadal dysgenesis and are particularly frequent (55%) in H-Y antigen-positive patients. These tumors are almost always gonadoblastomas or dysgerminomas. Similar tumors are found in 15%-20% of 45,X/46,XY individuals. In either situation the neoplastic transformation could be a) secondary to the existence of XY gonadal tissue in an inhospitable environment, or b) integrally related to that process--genetic or cytogenetic--producing the dysgenetic gonads. The risk of neoplasia is sufficiently high that most of these patients should be offered early gonadal extirpation. The prevalence of gonadal tumors is not increased in Klinefelter's syndrome, further indicating that gonadotropins are not carcinogenic per se. However, Klinefelter patients are 20 times more likely to develop a carcinoma of the breast than are 46,XY males. Extragonadal germ cell tumors also are more common. In female pseudohermaphrodites there is probably no increased risk of neoplasia, whereas, in true hermaphrodites neoplasia is unusual but does occur. Neoplasia occurs in patients with complete testicular feminization (complete androgen insensitivity) but rarely in those with incomplete testicular feminization/Reifenstein's syndrome, 5 alpha-reductase deficiency, anorchia, agonadia, or testosterone biosynthetic defects. In complete testicular feminization the risk of malignant tumors is small prior to age 25. After age 25, it is about 2%-5%. Orchiectomy is recommended after pubertal feminization.


Evolution of acceptor stem tRNA recognition by class II prolyl-tRNA synthetase.
Aminoacyl-tRNA synthetases (AARS) are an essential family of enzymes that catalyze the attachment of amino acids to specific tRNAs during translation. Previously, we showed that base-specific recognition of the tRNA(Pro) acceptor stem is critical for recognition by Escherichia coli prolyl-tRNA synthetase (ProRS), but not for human ProRS. To further delineate species-specific differences in acceptor stem recognition, atomic group mutagenesis was used to probe the role of sugar-phosphate backbone interactions in recognition of human tRNA(Pro). Incorporation of site-specific 2'-deoxynucleotides, as well as phosphorothioate and methylphosphonate modifications within the tRNA acceptor stem revealed an extensive network of interactions with specific functional groups proximal to the first base pair and the discriminator base. Backbone functional groups located at the base of the acceptor stem, especially the 2'-hydroxyl of A66, are also critical for aminoacylation catalytic efficiency by human ProRS. Therefore, in contrast to the bacterial system, backbone-specific interactions contribute significantly more to tRNA recognition by the human enzyme than base-specific interactions. Taken together with previous studies, these data show that ProRS-tRNA acceptor stem interactions have co-adapted through evolution from a mechanism involving 'direct readout' of nucleotide bases to one relying primarily on backbone-specific 'indirect readout'.


Computer assisted shared care in hypertension.
A computer assisted shared care scheme for the long term management and follow up of hypertensive patients has been developed in the Grampian Region. The scheme aims at facilitating the exchange of clinically important information between doctors and at achieving target levels of blood pressure with treatment in patients at highest risk of cardiovascular events. The shared care scheme has been well received by the local practitioners. Two hundred and fifty seven patients (18%) of 1426 patients under current long term follow up are assigned to follow up in the hospital aspect of the scheme. At the most recent visit 32% of patients in the hospital aspect and 10% of 1169 patients in the general practice aspect had blood pressure recordings above the target levels of 160/95 mm Hg. The stratification of patients formerly attending hospital clinics into grades of risk has rationalised our follow up procedures to allow the specialist resources to be freed and concentrated on those patients at highest risk and with the most complex problems. This computer assisted patient records system could be applied to other groups of high risk patients in whom long term follow up and surveillance are necessary--for example, patients with diabetes mellitus--and has implications for optimising and monitoring the delivery and outcome of care without overwhelming limited hospital resources.


Respiratory Health Symptoms among Schoolchildren in Relation to Possible Food-Related Risk and Protective Factors.
Respiratory health outcomes are among the top five causes of child morbidity and mortality around the world. We aimed to investigate possible food-related risk and protective factors for respiratory health outcomes in children. Structured questionnaires completed by primary caregivers of 10-year old children were used to collect information on demographics, socio-economic status, house characteristics and child respiratory health status. Upper (URIs) and Lower (LRIs) respiratory illnesses comprised hay fever, and wheezing, asthma and bronchitis, respectively. Eight hundred questionnaires were distributed, 648 retrieved and 420 completed in full (52.5% response rate). The hay fever 6-month prevalence was 22.4% and wheezing had the highest 6-month prevalence among the LRIs (13.8%). The majority of children ate vegetables (75.5%), fruit (69.3%) and chicken or fish (81.7%) regularly. Nearly half of the children (45.5%) regularly ate processed food. Eating processed food regularly was statistical significantly associated with wheeze (Adjusted Odds Ratio (OR) = 2.65; 95% CI: 1.38-5.08), hay fever (OR = 1.62; 95% CI: 1.09-2.64) and bronchitis (OR = 1.27; 95% CI: 1.06-2.56). The study found an association between regular consumption of processed foods and wheeze, hay fever and bronchitis among 10 year old children. The regular consumption of processed food plays a role in adverse respiratory health effects among children and healthy eating is emphasized.


Molecular characterization of the Serratia marcescens OmpF porin, and analysis of S. marcescens OmpF and OmpC osmoregulation.
Serratia marcescens is a nosocomial pathogen with a high incidence of beta-lactam resistance. Reduced amounts of outer-membrane porins have been correlated with increased resistance to beta-lactams but only one porin, OmpC, has been characterized at the molecular level. In this study we present the molecular characterization of a second porin, OmpF, and an analysis of the expression of S. marcescens porins in response to various environmental changes. Two porins were isolated from the outer membrane using urea-SDS-PAGE and the relative amounts were shown to be influenced by the osmolarity of the medium and the presence of salicylate. From a S. marcescens genomic DNA library an 8 kb EcoRI fragment was isolated that hybridized with an oligonucleotide encoding the published N-terminal amino acid sequence of the S. marcescens 41 kDa porin. A 41 kDa protein was detected in the outer membrane of Escherichia coli NM522 carrying the cloned S. marcescens DNA. The cloned gene was sequenced and shown to code for a protein that shared 60-70% identity with other known OmpF and OmpC sequences. The upstream DNA sequence of the S. marcescens gene was similar to the corresponding E. coli ompF sequence; however, a regulatory element important in repression of E. coli ompF at high osmolarity was absent. The cloned S. marcescens OmpF in E. coli increased in expression in conditions of high osmolarity. The potential involvement of micF in the observed osmoregulation of S. marcescens porins is discussed.


Anti-inflammatory effects of methanol extract of Canarium lyi C.D. Dai & Yakovlev in RAW 264.7 macrophages and a murine model of lipopolysaccharide-induced lung injury.
Canarium lyi C.D. Dai & Yakovlev (CL) is a member of the Anacardiaceae family. To the best of our knowledge, no studies on its anti-inflammatory effects have yet been reported. In the present study, we investigated the protective effects of CL on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced acute lung injury (ALI) mice. CL attenuated the production of LPS-stimulated inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and interleukin-6 (IL-6). Furthermore, CL suppressed phosphorylation of the inhibitor κB-α (IκB-α), p38, c-Jun terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as the translocation of the nuclear factor-κB (NF-κB) p65 subunit into the nucleus. For the in vivo efficacy, the effect of CL on a mouse model of LPS-induced acute lung injury was assessed. CL treatment of the mice significantly inhibited the inflammatory cell recruitment and pro-inflammatory cytokine production in bronchoalveolar lavage fluids (BALF). CL-treated mice also showed a marked inhibition of cyclooxygenase-2 (COX-2) and phosphorylation of IκB and p65. In addition, CL attenuated lung histopathological changes in LPS-induced ALI mice. In conclusion, our results suggest that CL is a potential therapeutic candidate for the treatment of inflammatory diseases, including pneumonia.


[Free vascular pedicle iliac bone graft for reconstruction of mandibular defect with ECT scan monitor].
Thirteen patients with mandibular defects after radical resection of mandibular cancer from Apr. 1984 to May 1987 are reported. There were 9 males and 4 females. The defects were repaired by free vascular pedicle iliac bone grafts. Of these patients, 11 satisfactorily healed as the grafted bone was examined by ECT scan autoradiography. The latter is considered as a reliable objective monitor and a scientific parameter to evaluate the viability of the grafted bone. Wide surgical indication, improved post-operative function, shortened treatment course in one-stage repair are favorable to the patients.


Single-crystal metastable high-temperature C2/c clinoenstatite quenched rapidly from high temperature and high pressure.
The high-temperature clinoenstatite (HT-CEn) is one of the most important MgSiO3 pyroxene polymorphs, but the details of its structure and stability have been uncertain. The single crystal of the C2/c HT-CEn end-member is firstly synthesized by rapid pressure-temperature quenching from 15-16 GPa and 1173-2173 K. The single-crystal X-ray diffraction analysis shows unusual bonding distances and static disorder of the atoms frozen in this metastable structure. The degree of kinking of the silicate tetrahedral chains is 175° for HT-CEn. The chain angle for HP-CEn is substantially smaller (135°), but the angle for L-CEn is in the opposite direction at -160° (= 200°). The degree of kinking increases by being curved by more than 180° for the transition from HT-CEn to L-CEn. As for the reverse change from the expansion to the stretch, a potential barrier exists at the point of the continuity. It is suggested that the reason why a structure can be quenched under ambient conditions is as follows: the present HT-CEn single crystal has been formed by the isosymmetric phase transition from the high-pressure C2/c clinoenstatite (HP-CEn). The presence of HT-CEn from HP-CEn in natural rocks is an indicator of quenching history, which leads to the possibility that it exists in shocked meteorites and impact materials.


Investigation of predictor factors of the nursing students attitudes toward parents' participation in care.
A positive attitude toward family-centered care practices should be developed in undergraduate education. This study aimed to investigate nursing students' attitudes toward parental participation in child patient care and the factors that influence it. This study was a descriptive cross-sectional study. The study data were collected from the nursing department of a university located in the west of Turkey. The study was conducted with 260 nursing students. The descriptive Features Form, Family-Centered Care Practices Form, and Parental Participation Attitude Scale were used in data collection. The students' average parental participation attitude in care scores was at a moderate level. It has been determined that gender, hospitalization experience, education on family-centered care, and support from instructors in family-centered care practices had a positive effect on the student's attitudes toward parental participation in care (p < 0.05). The regression analysis showed gender and family-centered care education as predictors of student' attitudes toward parent participation in care. It was found that students' attitudes toward parental participation in the care of child patients were at an indecision level and not at the desired grade, and it was affected by gender, hospitalization experience, education, and instructor support. The development of family-centered care practices should begin in nursing education. It is recommended that detailed attention be given to topics related to family-centered care in nursing education, and seminars be organized on this subject. Thus, nursing students can both develop a positive attitude toward family-centered care and learn to work together with the family.


Characterization of primate antibody responses to administered murine monoclonal immunoglobulin.
Murine monoclonal antibodies (MAb) are currently being assessed for their utility as tools in cancer management. Anti-murine immunoglobulin responses have been observed in many patients receiving monoclonal antibody treatment. In this study, we evaluated the response of primates to the administration of a monoclonal antibody. MAb B6.2, an antibody generated against a human breast tumor metastasis, was used as a prototype MAb. Baboons were inoculated with MAb B6.2 whole IgG, Fab', or F(ab')2 fragments. Blood samples were drawn at periodic intervals post-inoculation and the sera collected. Anti-murine immunoglobulin responses were detected using a solid-phase radioimmunoassay. The specificity of the antibody response was analyzed to determine if the response was directed against the species of origin of the MAb (species specificity), against the class of the MAb (isotype specificity), or against the hypervariable region of the MAb (idiotype specificity). We found that primates develop a humoral immune response against all three forms of the monoclonal antibody [IgG, Fab', and F(ab')2]. Furthermore, this antibody response demonstrated a high degree of specificity for the antigen binding site suggesting an idiotypic specificity. Using a competitive radioimmunoassay, the antibody response was found to interfere with antigen binding of MAb B6.2. These studies suggest that monoclonal antibody treatment can generate an anti-idiotypic response which may alter the efficacy of this mode of treatment.


Pushing the boundaries of digital social contact: Experiences of people with disabilities and their social networks during the COVID-19 pandemic.
During the COVID-19 pandemic, many people with intellectual disabilities living in care facilities could not receive visitors. Health authorities suggested the use of digital social contact as an alternative for in-person visits. We examined how people with intellectual disabilities living in care facilities experienced the use of digital social contact with their informal social network throughout 2020. Residents, their relatives, volunteer visitors, direct support staff, and care facility managers (N = 283) completed an online questionnaire, of whom 35 participated in an interview. Video calling and in-person visits were among the most common forms of staying in touch. Experiences with digital social contact depended on residents' abilities and support needs, and on preconditions, such as staff availability. The first phases of the pandemic led to experiences of possibilities and benefits of using digital social contact as complementary to in-person contact for people with different levels of intellectual disability, also after the pandemic.


Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer.
The mature human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer is produced by proteolytic cleavage of a precursor and consists of three gp120 exterior and three gp41 transmembrane subunits. The metastable Env complex is induced to undergo conformational changes required for virus entry by the binding of gp120 to the receptors, CD4 and CCR5/CXCR4. An isoleucine-to-proline change (I559P) in the gp41 ectodomain has been used to stabilize soluble forms of HIV-1 Env trimers for structural characterization and for use as immunogens. In the native membrane-anchored HIV-1BG505 Env, the I559P change modestly decreased proteolytic maturation, increased the non-covalent association of gp120 with the Env trimer, and resulted in an Env conformation distinctly different from that of the wild-type HIV-1BG505 Env. Compared with the wild-type Env, the I559P Env was recognized inefficiently by polyclonal sera from HIV-1-infected individuals, by several gp41-directed antibodies, by some antibodies against the CD4-binding site of gp120, and by antibodies that preferentially recognize the CD4-bound Env. Some of the gp120-associated antigenic differences between the wild-type HIV-1BG505 Env and the I559P mutant were compensated by the SOS disulfide bond between gp120 and gp41, which has been used to stabilize cleaved soluble Env trimers. Nonetheless, regardless of the presence of the SOS changes, Envs with proline 559 were recognized less efficiently than Envs with isoleucine 559 by the VRC01 neutralizing antibody, which binds the CD4-binding site of gp120, and the PGT151 neutralizing antibody, which binds a hybrid gp120-gp41 epitope. The I559P change completely eliminated the ability of the HIV-1BG505 Env to mediate cell-cell fusion and virus entry, and abolished the capacity of the SOS Env to support virus infection in the presence of a reducing agent. These results suggest that differences exist between the quaternary structures of functional Env spikes and I559P Envs.


Congenital amusias.
In contrast to the sophisticated music processing reported in the general population, individuals with congenital amusia show deficits in music perception and production. Congenital amusia occurs without brain damage, sensory or cognitive deficits, and has been suggested as a lifelong deficit with genetic origin. Even though recognized for a long time, this disorder has been systematically studied only relatively recently for its behavioral and neural correlates. The currently most investigated hypothesis about the underlying deficits concerns the pitch dimension, notably with impaired pitch discrimination and memory. Anatomic and functional investigations of pitch processing revealed that the amusic brain presents abnormalities in the auditory and inferior frontal cortices, associated with decreased connectivity between these structures. The deficit also impairs processing of pitch in speech material and processing of the time dimension in music for some of the amusic individuals, but does not seem to affect spatial processing. Some studies suggest at least partial dissociation in the disorder between perception and production. Recent studies revealed spared implicit pitch perception in congenital amusia, supporting the power of implicit cognition in the music domain. Current challenges consist in defining different subtypes of congenital amusia as well as developing rehabilitation programs for this "musical handicap."


Preliminary results of multicenter phase II trial of docetaxel (Taxotere) in combination with doxorubicin as first line chemotherapy in Indonesian patients with advanced or metastatic breast cancer.
Docetaxel and doxorubicin have produced a high degree of activity in previously untreated/treated patients with metastatic breast cancer (MBC). The efficacy of Taxotere (T) single agent as 2nd line chemotherapy is well established in large randomized phase III studies. The objective of this study is to confirm the efficacy and safety of a combination of Taxotere with doxorubicin as 1st line chemotherapy in Indonesian MBC patients. TREATMENT AND METHOD: Eighteen patients age < or = 70 years with advanced or metastatic breast cancer (MBC) with no prior taxane chemotherapy or prior cumulative doxorubicin (D) of no more than 250 mg/m2 and no heart disease were enrolled in this phase II study of D (50 mg/m2) IV bolus followed one hour later by Taxotere (T) 60 mg/m2 IV infusion over 1 hour every 3 weeks for 6 cycles treatments. A 3-day oral corticosteroid premedication was administered starting one day before the infusion of each cycle. Left ventricular ejection fraction (LVEF) was evaluated at baseline and after cycle 6. 18 patients (pts) have been treated with 108 cycles administered. Median age was 46 years (31-58), WHO PS 0 = 50%, 1 = 50% and number of organs involved were: 2 (72%), 3 (22%) and 4 (6%). After 3 cycles, partial (PR) and no change (NC) responses occurred in 15 pts (83.3%) and 3 pts (16.7%). The best overall response after 6 cycles, including complete (CR) and partial (PR) responses, occurred in 13 pts (72.2%) including 3 CRs and 10 PRs. Two patients with extensive liver metastases at the baseline had a complete disappearance after 6 cycles. No patients developed congestive heart failure (CHF). Grade 3/4 hematological toxicities included leukopenia in 18 pts (100%), febrile neutropenia in 6 pts (33%), leukopenia with infection in 2 pts (11%), leukopenia with fever in 1 pt (5.5%), and anemia in 6 pts (33.3%). Nonhematological toxicities grade 3/4 included alopecia (61%), asthenia (4.6%), nausea/vomiting (2.7%), pain (2.7%), stomatitis (2.7%), and diarrhoea (0.9%). Leukopenia was generally of short duration, occurred mainly during the first and second cycle, and did not require any dose reduction. There was one death due to progressive disease after six cycles of treatment. Taxotere--doxorubicin combination is very active in the first-line treatment of MBC, seems to be especially effective in patients with liver metastases, and is associated with a manageable toxicity profile.


Circadian genomics of the chick pineal gland in vitro.
Chick pinealocytes exhibit all the characteristics of a complete circadian system, comprising photoreceptive inputs, molecular clockworks and an easily measured rhythmic output, melatonin biosynthesis. These properties make the in vitro pineal a particularly useful model for exploring circadian control of gene transcription in a pacemaker tissue, as well as regulation of the transcriptome by primary inputs to the clock (both photic and noradrenergic). We used microarray analysis to investigate the expression of approximately 8000 genes within cultured pinealocytes subjected to both LD and DD. We report that a reduced subset of genes was rhythmically expressed in vitro compared to those previously published in vivo, and that gene expression rhythms were lower in amplitude, although the functional distribution of the rhythmic transcriptome was largely similar. We also investigated the effects of 6-hour pulses of light or of norepinephrine on gene expression in free-running cultures during both subjective day and night. As expected, both light and norepinephrine inhibited melatonin production; however, the two treatments differentially enhanced or suppressed specific sets of genes in a fashion that was dependent upon time of day. Our combined approach of utilizing a temporal, photic and pharmacological microarray experiment allowed us to identify novel genes linking clock input to clock function within the pineal. We identified approximately 30 rhythmic, light-responsive, NE-insensitive genes with no previously known clock function, which may play a role in circadian regulation of the pineal. These are candidates for future functional genomics experiments to elucidate their potential role in circadian physiology. Further, we hypothesize that the pineal circadian transcriptome is reduced but functionally conserved in vitro, and supports an endogenous role for the pineal in regulating local rhythms in metabolism, immune function, and other conserved pathways.


Clinician perceptions of an electronic medical record during the first year of implementaton in emergency services.
The objectives of this study were to measure clinician perceptions of the recently implemented electronic medical record (EMR) system in a pediatric emergency department and off-site urgent care centers and to determine how user perceptions changed over time. Physicians and nurses from the emergency department/urgent care center were recruited to complete an online survey at 3 points in time: 30 to 89 days (wave 1), 90 to 179 days (wave 2), and 180 to 270 days after implementation (wave 3). Potential predictors of initial satisfaction studied included effort expectancy, performance expectancy, social support, and facilitating conditions, along with user demographics and general attitudes toward technology. Bivariate relationships with satisfaction were assessed using the Wilcoxon rank sum test and correlation analysis. A final multivariate linear regression model was calculated. Change in satisfaction over time was tested using a Wilcoxon signed rank test. A total of 71 clinicians completed the surveys. Initial satisfaction was strongly associated with perceptions of training and support (facilitating conditions) and with perceived usefulness (performance expectancy). Satisfaction was not associated with user sex, age, or role (physician vs nurse). No significant change was found in any satisfaction measure at wave 2 or 3; however, satisfaction with functionality trended higher and satisfaction with reliability trended lower over the course of use. Satisfaction with an EMR at its launch generally persisted through the first year of use. Implementation plans must maximize the likelihood of achieving positive early impressions of training, support, and performance to engender high user satisfaction with the EMR.


Time-frequency analysis of single-sweep event-related potentials by means of fast wavelet transform.
A time-frequency decomposition was applied to the event-related potentials (ERPs) elicited in an auditory oddball condition to assess differences in cognitive information processing. Analysis in the time domain has revealed that cognitive processes are reflected by various ERP components such as N1, P2, N2, P300, and late positive complex. However, the heterogeneous nature of these components has been strongly emphasized due to simultaneously occurring processes. The wavelet transform (WT), which decomposes the signal onto the time-frequency plane, allows the time-dependent and frequency-related information in ERPs to be captured and precisely measured. A four-octave quadratic B-spline wavelet transform was applied to single-sweep ERPs recorded in an auditory oddball paradigm. Frequency components in delta, theta, and alpha ranges reflected specific aspects of cognitive information processing. Furthermore, the temporal position of these components was related to specific cognitive processes.


Assessment centers versus cognitive ability tests: Challenging the conventional wisdom on criterion-related validity.
Separate meta-analyses of the cognitive ability and assessment center (AC) literatures report higher criterion-related validity for cognitive ability tests in predicting job performance. We instead focus on 17 samples in which both AC and ability scores are obtained for the same examinees and used to predict the same criterion. Thus, we control for differences in job type and in criteria that may have affected prior conclusions. In contrast to Schmidt and Hunter's (1998) meta-analysis, reporting mean validity of .51 for ability and .37 for ACs, we found using random-effects models mean validity of .22 for ability and .44 for ACs using comparable corrections for range restriction and measurement error in the criterion. We posit that 2 factors contribute to the differences in findings: (a) ACs being used on populations already restricted on cognitive ability and (b) the use of less cognitively loaded criteria in AC validation research. (PsycINFO Database Record


Is it discriminatory to require hospital staff to be clean shaven to facilitate the effective wearing of personal protective equipment?
National Health Service employers are subject to legal duties to protect the health and safety of their employees and third parties who come into contact with their staff. In order to discharge these duties, National Health Service employers must implement a range of protective measures to mitigate risk. One such measure is to require staff to wear personal protective equipment, including respiratory protective equipment, in certain circumstances. This is of particular importance during the Covid-19 pandemic. However, the presence of facial hair has a negative impact on the effectiveness of respiratory protective equipment. This article discusses whether a requirement to be clean shaven could amount to discrimination under the Equality Act 2010.


Investigation of deformability, viscosity, and aggregation of mPEG-modified erythrocytes.
Several techniques for the development of a universal blood type are under investigation in order to address the vast shortage of blood required during times of crisis and for those receiving chronic transfusions. Recently, the covalent attachment of methoxypolyethylene glycol (mPEG) has received attention as a means to conceal the major and minor blood antigens that can invoke an immune response. We have utilized a simple method to covalently bind mPEG to the surface of red blood cells and monitored the rheological properties including cellular deformability and suspension viscosity as a function of shear rate and aggregation. In order to simulate the deformability of mPEG-modified erythrocytes through small blood vessels, we have studied the flow of cells through a nickel-mesh membrane with a pore size of 5.8 microns. Using a gravity-based nickel-mesh filtration device, dilute solutions of red blood cells were filtered through a membrane. The pressure drop was monitored with time. We have examined the filterability of whole blood, washed erythrocytes, mPEG-altered erythrocytes, and mixtures of altered erythrocytes with whole blood. Results from this apparatus have suggested that there is a significant decrease in deformability using mPEG-modified erythrocytes compared to unaltered red blood cells at identical concentrations. Increasing the ratio of modified cells to unmodified cells resulted in decreased deformability of the suspension. Viscosity measurements of mPEG-modified red cells have shown a shear-thinning property, while results of aggregation measurements indicate reduced aggregation compared to whole blood.


Patient Preferences for Outcomes Following DCIS Management Strategies: A Discrete Choice Experiment.
Ductal carcinoma in situ (DCIS), a nonobligate precursor of breast cancer, is often aggressively managed with multimodal therapy. However, there is limited research on patients' preferences for trade-offs among treatment-related outcomes such as breast appearance, side effects, and future cancer risk. We sought to investigate whether women consider treatment features aside from cancer risk when making treatment choices for ductal carcinoma in situ and if so, to what degree other features influence these decisions. A discrete choice experiment was administered to participants in a comprehensive cancer screening mammography clinic. The experimental design was used to generate constructed health profiles resulting from different management strategies. Health profiles were defined by breast appearance, severity of infection within the first year, chronic pain, hot flashes, and risk of developing or dying from breast cancer within 10 years. One hundred ninety-four women without a personal history of breast cancer completed the choice task. Across 10 choice questions, 29% always selected the health profile with a lower risk of invasive breast cancer (ie, dominated on cancer risk), regardless of the effects of treatment. For nonrisk dominators, breast cancer risk remained the most important factor but was closely followed by chronic pain (24% [95% CI, 20 to 28]) and infection (22% [95% CI, 18 to 25]). Depending on treatment outcomes, the tolerable increase in breast cancer risk was as high as 3.4%. Most women were willing to make some trade-offs between invasive cancer risk and treatment-related outcomes. Our findings highlight the importance of shared decision-making weighing risks and benefits between patient and provider management of low-risk disease.


Lipid Deprivation Induces a Stable, Naive-to-Primed Intermediate State of Pluripotency in Human PSCs.
Current challenges in capturing naive human pluripotent stem cells (hPSCs) suggest that the factors regulating human naive versus primed pluripotency remain incompletely defined. Here we demonstrate that the widely used Essential 8 minimal medium (E8) captures hPSCs at a naive-to-primed intermediate state of pluripotency expressing several naive-like developmental, bioenergetic, and epigenomic features despite providing primed-state-sustaining growth factor conditions. Transcriptionally, E8 hPSCs are marked by activated lipid biosynthesis and suppressed MAPK/TGF-β gene expression, resulting in endogenous ERK inhibition. These features are dependent on lipid-free culture conditions and are lost upon lipid exposure, whereas short-term pharmacological ERK inhibition restores naive-to-primed intermediate traits even in the presence of lipids. Finally, we identify de novo lipogenesis as a common transcriptional signature of E8 hPSCs and the pre-implantation human epiblast in vivo. These findings implicate exogenous lipid availability in regulating human pluripotency and define E8 hPSCs as a stable, naive-to-primed intermediate (NPI) pluripotent state.


Comparison of 1.0-, 1.5-, and 2.0-pitch abdominal helical computed tomography in evaluation of normal structures and pathologic lesions.
The authors performed a comprehensive prospective clinical trial comparing 1.0-, 1.5-, and 2.0-pitch abdominal helical computed tomography (CT) in the evaluation of normal and pathologic structures/lesions. Seventy-five consecutive patients were randomized by computer into one of three equal groups: helical CT pitch 1.0, 1.5, and 2.0. The imaging parameters and contrast enhancement of all 75 patients were kept constant. The 75 studies were masked, placed into a randomized order, and evaluated by five separate experienced radiologists who rated visualization of 25 normal structures and up to five pathologic findings per patient using a scale of 1 (not seen) to 5 (very well seen/very sharp margins). There were no statistical differences in 1.0- and 1.5-pitch abdominal CT scans when assessing the display of normal and pathologic lesions. In addition, helical pitch 1.0 and 1.5 studies were equivalent for both normal and pathologic structures/lesions, whereas equivalency was not demonstrated for helical pitch 2.0 studies. Overall study assessment questions again found equivalency between helical 1.0- and 1.5-pitch studies. Abdominal CT performed with pitches of 1.0 and 1.5 are equivalent. Because of its advantages, we advocate the routine use of an extended pitch (1.5) in routine abdominal CT. Further studies are required to evaluate the usefulness of the helical 2.0-pitch technique.


[Comprehensive Diagnosis of Mantle Cell Lymphoma].
To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL). The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed. 144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL. Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.


Vesicular Stomatitis Virus Transcription Is Inhibited by TRIM69 in the Interferon-Induced Antiviral State.
Interferons (IFNs) induce the expression of interferon-stimulated genes (ISGs), many of which are responsible for the cellular antiviral state in which the replication of numerous viruses is blocked. How the majority of individual ISGs inhibit the replication of particular viruses is unknown. We conducted a loss-of-function screen to identify genes required for the activity of alpha interferon (IFN-α) against vesicular stomatitis virus, Indiana serotype (VSVIND), a prototype negative-strand RNA virus. Our screen revealed that TRIM69, a member of the tripartite motif (TRIM) family of proteins, is a VSVIND inhibitor. TRIM69 potently inhibited VSVIND replication through a previously undescribed transcriptional inhibition mechanism. Specifically, TRIM69 physically associates with the VSVIND phosphoprotein (P), requiring a specific peptide target sequence encoded therein. P is a cofactor for the viral polymerase and is required for viral RNA synthesis, as well as the assembly of replication compartments. By targeting P, TRIM69 inhibits pioneer transcription of the incoming virion-associated minus-strand RNA, thereby preventing the synthesis of viral mRNAs, and consequently impedes all downstream events in the VSVIND replication cycle. Unlike some TRIM proteins, TRIM69 does not inhibit viral replication by inducing degradation of target viral proteins. Rather, higher-order TRIM69 multimerization is required for its antiviral activity, suggesting that TRIM69 functions by sequestration or anatomical disruption of the viral machinery required for VSVIND RNA synthesis.IMPORTANCE Interferons are important antiviral cytokines that work by inducing hundreds of host genes whose products inhibit the replication of many viruses. While the antiviral activity of interferon has long been known, the identities and mechanisms of action of most interferon-induced antiviral proteins remain to be discovered. We identified gene products that are important for the antiviral activity of interferon against vesicular stomatitis virus (VSV), a model virus that whose genome consists of a single RNA molecule with negative-sense polarity. We found that a particular antiviral protein, TRIM69, functions by a previously undescribed molecular mechanism. Specifically, TRIM69 interacts with and inhibits the function of a particular phosphoprotein (P) component of the viral transcription machinery, preventing the synthesis of viral messenger RNAs.


[Precipitation of the antigens of the causative agents of plague, glanders and melioidosis using aqueous saline extracts of various plant species].
The interaction of the aqueous saline extracts of 55 plant species with the antigens of the causative agents of plague, glanders and melioidosis in the reaction of immunodiffusion (RID) in gel has been studied. The aqueous saline extracts obtained from the seeds of 12 plant species have been revealed to possess precipitating capacity. At the same time these extract have been found to ensure, as a rule, RID with several antigens under test.


Antisocial Behavior in Juvenile Offenders: A Development Bioecological Approach.
This review analyzes the bioecological model of human development as a comprehensive framework of adolescent antisocial behavior. Variables such as family and peers with antisocial backgrounds, antisocial peer attitudes, alcohol consumption, offensive behavior, education level, perception of safety in the community, and attention deficit hyperactive disorder, are discussed. This review supports the bioecological model as a plausible framework for understanding antisocial behavior during adolescence.


The mRNA for a proteinase inhibitor related to the HI-30 domain of inter-alpha-trypsin inhibitor also encodes alpha-1-microglobulin (protein HC).
Inter-alpha-trypsin inhibitor (ITI) is a 180 kd serine proteinase inhibitor found in human serum. Treatment of 180 kd ITI with trypsin releases a 30 kd fragment (HI-30) which contains the anti-proteolytic activity of the high molecular weight form. We have isolated a cDNA clone from a human liver library which codes for HI-30, and have determined its DNA sequence. The mRNA not only codes for HI-30 but also another serum protein, alpha-1-microglobulin, which has not been previously associated with ITI or HI-30. The alpha-1-microglobulin sequence is found in the amino-terminus of the protein and is preceded by a signal sequence. HI-30 is found at the carboxy-terminus. The two protein sequences are separated by two arginine residues.


[Urinary neopterin levels in patients with genitourinary tract malignancies].
Neopterin is released from macrophages upon stimulation with gamma-interferon, secreted by activated T cell. Therefore it has been recognized as a useful indicator of the activation of the T cell-macrophage system. Increased neopterin levels are observed in patients with acute graft rejections, viral infections, auto-immune diseases and several malignancies. Urinary neopterin concentrations were determined in patients with genitourinary tract malignancies to evaluate the usefulness of neopterin as a tumor marker. Urinary neopterin concentrations were determined by high-performance liquid chromatography in 90 patients with genitourinary tract malignancies and 28 patients with benign urological tumors and 34 healthy subjects. Increased urinary neopterin levels were observed in 52% of the patients with genitourinary tract malignancies and 7% with benign urological tumors. The positivity rate in patients with renal cell carcinoma (RCC), renal pelvic and ureteral tumor, bladder tumor (BT), prostatic carcinoma (PC) and testicular tumor was 68%, 80%, 47% and 30%, respectively. The difference in the urinary neopterin levels between low and high stages was highly significant (p < 0.0005) in patients with RCC (stage I-II vs. stage III-IV) and BT (T1S-1 VS. T2-4). The urinary neopterin levels were also correlated with the tumor grade in patients with RCC and PC. Our study suggests that urinary neopterin levels may supplement laboratory examinations for patients with genitourinary tract malignancies, providing useful information in evaluating the tumor stage and follow-up of the disease.


Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.
Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to 7-days following CIE. Weighted Gene Correlated Network Analysis (WGCNA) was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis showed that long-lasting gene regulation occurred 7-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC) and hippocampus. Across all brain regions, however, ethanol-responsive expression changes occurred mainly within the first 8-hours after removal from ethanol. Bioinformatics analysis showed that neuroinflammatory responses were seen across multiple brain regions at early time-points, whereas co-expression modules related to neuroplasticity, chromatin remodeling, and neurodevelopment were seen at later time-points and in specific brain regions (PFC or HPC). In PFC a module containing Bdnf was identified as highly CIE responsive in a biphasic manner, with peak changes at 0 hours and 5 days following CIE, suggesting a possible role in mechanisms underlying long-term molecular and behavioral response to CIE. Bioinformatics analysis of this network and several other modules identified Let-7 family microRNAs as potential regulators of gene expression changes induced by CIE. Our results suggest a complex temporal and regional pattern of widespread gene network responses involving neuroinflammatory and neuroplasticity related genes as contributing to physiological and behavioral responses to chronic ethanol.


Shifting liberal and conservative attitudes using moral foundations theory.
People's social and political opinions are grounded in their moral concerns about right and wrong. We examine whether five moral foundations--harm, fairness, ingroup, authority, and purity--can influence political attitudes of liberals and conservatives across a variety of issues. Framing issues using moral foundations may change political attitudes in at least two possible ways: (a) Entrenching: Relevant moral foundations will strengthen existing political attitudes when framing pro-attitudinal issues (e.g., conservatives exposed to a free-market economic stance) and (b) Persuasion: Mere presence of relevant moral foundations may also alter political attitudes in counter-attitudinal directions (e.g., conservatives exposed to an economic regulation stance). Studies 1 and 2 support the entrenching hypothesis. Relevant moral foundation-based frames bolstered political attitudes for conservatives (Study 1) and liberals (Study 2). Only Study 2 partially supports the persuasion hypothesis. Conservative-relevant moral frames of liberal issues increased conservatives' liberal attitudes.


Detection of collagen synthesis by human osteoblasts on a tricalcium phosphate hydroxyapatite: an X-ray photoelectron spectroscopy investigation.
The effect of a hydroxyapatite-tricalcium phosphate (HA) material on collagen synthesis by human osteoblasts was investigated using X-ray photoelectron spectroscopy (XPS). To this aim, thin HA slices were exposed to osteoblasts harvested from three different patients, for 20 days and then analyzed by XPS. Platinum plates were also exposed to the cells for comparison, and control tests were performed on both materials using cell-free media. XPS analysis supported by standard spectra of some polyaminoacids and of collagen deposited on HA suggested that a deposition of collagen occurred on the HA slices in the presence of osteoblasts. On the other hand, only an aspecific deposition of proteins was observed on platinum and when cell-free media were used. These data were confirmed evaluating collagen synthesis by [(3)H]proline incorporation of osteoblasts exposed to HA.


Insulin-positive, Glut2-low cells present within mouse pancreas exhibit lineage plasticity and are enriched within extra-islet endocrine cell clusters.
Regeneration of insulin-producing β-cells from resident pancreas progenitors requires an understanding of both progenitor identity and lineage plasticity. One model suggested that a rare β-cell sub-population within islets demonstrated multi-lineage plasticity. We hypothesized that β-cells from young mice (postnatal day 7, P7) exhibit such plasticity and used a model of islet dedifferentiation toward a ductal epithelial-cell phenotype to test this theory. RIPCre;Z/AP(+/+) mice were used to lineage trace the fate of β-cells during dedifferentiation culture by a human placental alkaline phosphatase (HPAP) reporter. There was a significant loss of HPAP-expressing β-cells in culture, but remaining HPAP(+) cells lost insulin expression while gaining expression of the epithelial duct cell marker cytokeratin-19 (Ck19). Flow cytometry and recovery of β-cell subpopulations from whole pancreas vs. islets suggest that the HPAP(+)Ck19(+) cells had derived from insulin-positive, glucose-transporter-2-low (Ins(+)Glut2(LO)) cells, representing 3.5% of all insulin-expressing cells. The majority of these cells were found outside of islets within clusters of <5 β-cells. These insulin(+)Glut2(LO) cells demonstrated a greater proliferation rate in vivo and in vitro as compared to insulin(+)Glut2(+) cells at P7, were retained into adulthood, and a subset differentiated into endocrine, ductal, and neural lineages, illustrating substantial plasticity. Results were confirmed using RIPCre;ROSA- eYFP mice. Quantitative PCR data indicated these cells possess an immature β-cell phenotype. These Ins(+)Glut2(LO) cells may represent a resident population of cells capable of forming new, functional β-cells, and which may be potentially exploited for regenerative therapies in the future.


Fish stress become visible: a new attempt to use biosensor for real-time monitoring fish stress.
To avoid fish mortality and improve productivity, the physiological conditions including stress state of the cultured fish must be monitored. As an important indicator of stress, glucose concentrations are monitored using in vitro blood analysis. The physiological processes of fish under environmental conditions are harsher in many ways than those experienced by terrestrial animals. Moreover, the process of anaesthetizing and capturing the fish prior to analysis may produce inaccurate results. To solve these problems, we developed wireless biosensor system to monitor the physiological condition of fish. This system enables artificial stress-free and non-lethal analysis, and allows for reliable real-time monitoring of fish stress. The biosensor comprised Pt-Ir wire as the working electrode and Ag/AgCl paste as the reference electrode. Glucose oxidase was immobilized on the working electrode using glutaraldehyde. We used the eyeball interstitial sclera fluid (EISF) as the in vivo implantation site of the sensor, which component concentration correlates well with that of blood component concentration. In the present study, we investigated stress due to alterations in water chemistry, including dissolved oxygen, pH, and ammonia-nitrogen compounds. Stress perceived from behavioural interactions, including attacking behaviour and visual irritation, was also monitored. Water chemistry alterations induced increases in the glucose concentration (stress) that decreased with removal of the stimulus. For behavioural interactions, stress levels change with avoidance, sensory behaviour and activity. We believe that the proposed biosensor system could be useful for rapid, reliable, and convenient analysis of the fish physiological condition and accurately reflects the stress experienced by fish.


Molecular epidemiology of HIV type 1 in a rural community in southwest Uganda.
The molecular epidemiology of a population-based cohort in a cluster of 15 villages in southwestern Uganda was investigated by sequencing part of the p24 gag gene and performing heteroduplex mobility assays (HMAs) of the V3 region of the env gene. Sequence and HMA data, obtained for 69 and 88 proviruses, respectively, showed that the clade A and D viruses were present at a ratio of about 0.67:1. No other clades were detected. Thirteen (22%) of 59 proviruses for which both gag and env data were obtained appeared to be recombinants. Although both clade A and D viruses were present in 13 of the villages, their distribution was unequal: for example, from env data 59% of clade A viruses were found in the eastern villages, compared with only 27% of clade D viruses. Phylogenetic (maximum likelihood) analysis of the p24 gag sequences showed a total of five clusters supported by bootstrap resampling values above or close to 75%. Four clusters were sexual partners, but there was no known sexual contact between the persons in the other cluster. The DNA sequences showed between 0.5 and 8.3% divergence from the cohort clade A or D consensus sequences. The sequences were not closely related to those published for other clade A or D proviruses.


A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell activation.
TRAC-1 (T cell RING (really interesting new gene) protein identified in activation screen) is a novel E3 ubiquitin ligase identified from a retroviral vector-based T cell surface activation marker screen. The C-terminal truncated TRAC-1 specifically inhibited anti-TCR-mediated CD69 up-regulation in Jurkat cells, a human T leukemic cell line. In this study, we show that TRAC-1 is a RING finger ubiquitin E3 ligase with highest expression in lymphoid tissues. Point mutations that disrupt the Zn(2+)-chelating ability of its amino-terminal RING finger domain abolished TRAC-1's ligase activity and the dominant inhibitory effect of C-terminal truncated TRAC-1 on TCR stimulation. The results of in vitro biochemical studies indicate that TRAC-1 can stimulate the formation of both K48- and K63-linked polyubiquitin chains and therefore could potentially activate both degradative and regulatory ubiquitin-dependent pathways. Antisense oligonucleotides to TRAC-1 specifically reduced TRAC-1 mRNA levels in Jurkat and primary T cells and inhibited their activation in response to TCR cross-linking. Collectively, these results indicate that the E3 ubiquitin ligase TRAC-1 functions as a positive regulator of T cell activation.


Hemodynamic alterations in chronically conscious unrestrained diabetic rats.
Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dtmax and dP/dtmin of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.


Mycobacterial heparin-binding haemagglutinin adhesion-induced interferon & antibody for detection of tuberculosis.
Mycobacterial heparin-binding haemagglutinin adhesin (HBHA) plays an important role in humoral and cellular immune response and is a potential diagnostic tool for tuberculosis (TB) serodiagnosis. This study was carried out to assess the usefulness of HBHA in TB clinics for differential diagnosis of pulmonary and extra-pulmonary TB (PTB, EPTB). In this study, 165 outpatients and 133 healthy volunteers were included to investigate the role of HBHA in TB diagnosis including the serodiagnostic tests and the interferon-γ release assays (IGRAs). The healthy volunteers were all without BCG vaccination including 73 subjects with purified protein derivative (PPD) (-) and 60 ones with PPD (+) (that is P-B- and P+B-). Of all the 165 outpatients 77 were PTB and 88 were EPTB. HBHA protein was used for serodiagnostic tests and IGRAs in peripheral blood mononuclear cells. HBHA-specific antibody levels in the serum of healthy subjects were significantly different from the patients with PTB or EPTB (P<0.05). HBHA specific antibody levels in PTB patients could differentiate from EPTB with limited sensitivity (77.08%; 95%CI, 62.69 to 87.97%) and specificity (87.50%; 95%CI, 74.75 to 95.27%). IFN-γ levels in the healthy (P+B- and P-B-) groups were significantly different (P<0.01) with a detection sensitivity of 84.8% (95%CI, 68.54 to 93.02%) and specificity of 80.7% (95%CI, 65.22 to 92.62%). The PTB and EPTB subjects showed no difference in IFN-γ production. HBHA serodiagnostic test with IGRAs had the limited potential for use as auxiliary tools for the differential diagnosis of PTB and EPTB, since both methods showed low sensitivity and specificity.


Plasma Sphingolipids are Associated With Gait Parameters in the Mayo Clinic Study of Aging.
Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function. We examined the cross-sectional association between plasma ceramides, sphingosine-1-phosphate (S1P), and ceramide/S1P ratios and gait, a robust measure of physical function, in 340 clinically normal participants aged 70 years and older enrolled in the Mayo Clinic Study of Aging. GAITRite® instrumentation was used to measure gait speed, cadence, step width, double support time, and intra-individual stride time variability. Based on previous studies, we hypothesized that higher plasma levels of ceramide C16:0 would be associated with worse gait. Multivariable adjusted linear regression models revealed that higher levels of ceramide C16:0 were associated with slower gait speed, decreased cadence, and increased double support time. These results suggest an association between plasma ceramide C16:0 and physical function. Longitudinal studies are needed to determine whether elevated ceramide C16:0 can be utilized as a prognostic marker for functional decline.


Pulmonary Abscess as a Complication of Transbronchial Lung Cryobiopsy.
We present the case of a 49-year-old man who developed pulmonary abscess as a complication of transbronchial lung cryobiopsy. He had been receiving prednisone therapy, but otherwise had no specific risk factors for lung abscess. Cryobiopsy is a novel technique for obtaining peripheral lung parenchymal tissue for the evaluation of diffuse parenchymal lung diseases. Cryobiopsy is being increasingly proposed as an alternative to surgical lung biopsy or conventional bronchoscopic transbronchial forceps biopsy, but the safety profile of the procedure has not been fully appreciated. Pulmonary abscess has been rarely reported as a complication of other bronchoscopic procedures such as endobronchial ultrasound-guided needle biopsy, however, to our knowledge this is the first reported case of pulmonary abscess complicating peripheral lung cryobiopsy.


Knowledge and expectations of patients in palliative care: issues regarding communication with people affected by life-threatening diseases.
Different social norms influence the type and amount of information transmitted to palliative care patients. In Italy disclosure rate is low and medical decisions are often mediated by the family since communication of diagnosis and prognosis is viewed as harmful and brutal. Aims of our study were to assess palliative care patients' knowledge about their diagnosis and prognosis and expectations; and to evaluate possible differences between palliative care patients with and without cancer. 232 palliative care in-patients participated to the study and were interviewed about their knowledge about his/her diagnosis and prognosis, and about cure and disease expectations, perceived family/social support. Overall, 45.4% of the patients knew their diagnosis and 35.3% had partial knowledge of it; 39.2% knew their prognosis. When the prognosis was fatal, only few patients explicitly referred to it (22.0%). Expectations during admission to the palliative care unit were: return back home after symptom management (61.6%), increase personal autonomy (51.3%), and pain relief (45.2%). Family/social support was frequently perceived as good (84.0%). Patients with cancer less frequently knew their diagnosis (44.7% vs. 52.9%) and prognosis (37.7% vs. 64.7%) compared to patients with a non-cancer diagnosis. About half of our patients were unaware of their diagnosis, although, in reality, about one-third of the patients had some knowledge, albeit partial, of their diagnostic and therapeutic course. What to tell or not to tell in palliative care is still controversial and stems from a tailored intervention involving the patient, his/her family and professionals and silence may be more effective than intrusive communication in helping a patient to approach death with tolerable knowledge and dignity.


Safety of drugs used for the treatment of Crohn's disease.
Medications in treating Crohn's disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn's disease in adult patients. The authors performed a literature search until October 2018 to examine safety data on thiopurines, methotrexate, anti-TNFα agents, vedolizumab and ustekinumab. The authors focused on 'trial' and 'real-world' data for the biologic agents. Safety in pregnancy and the elderly are also presented. Available data in CD suggest that immunosuppressive medications are relatively safe, although there are concerns about an elevated risk of serious infections, skin cancer and lymphoma particularly with thiopurines and anti-TNFα agents. Data on vedolizumab and ustekinumab suggest these newer biologic agents are well tolerated; however, longer term data in CD are required to identify risks with extended use. Apart from methotrexate, there appear to be no adverse congenital outcomes with exposure of drugs during pregnancy.


Knife-edge scanning measurements of subwavelength focused light beams.
This note describes a convenient working technique for measuring the minimum size focused spot formed by a lens system. The technique is routinely capable of measurement precision of better than ?lambda. The theory of knife-edge scanning is presented, and the relationship of the measured spot profile to the actual spot profile is shown to be relatively insensitive to the acceptance solid angle of the photodetector. Finally, some typical results of high resolution microscope objectives are presented.


PERMANENT GENETIC RESOURCES: Isolation and characterization of microsatellite markers in the white-faced capuchin monkey (Cebus capucinus) and cross-species amplification in other New World monkeys.
Seventeen polymorphic microsatellite loci were identified for white-faced capuchin monkeys from an enriched genomic library in addition to one locus found through cross-species comparisons. In a sample of 187 wild individuals, these loci exhibited an average of five alleles and an observed heterozygosity of 0.62. The combined probability of exclusion of a random individual from parentage was 0.99. These loci were screened in 23 other New World monkeys and an average of seven loci was variable per species, suggesting that these loci could be of use in studies of other Neotropical primates.


Childhood factors associated with increased risk for mood episode recurrences in bipolar disorder-A systematic review.
Bipolar Disorder (BD) is a recurrent illness associated with high morbidity and mortality. The frequency of mood episode recurrence in BD is highly heterogeneous and significantly impacts the person's psychosocial functioning and well-being. Understanding the factors associated with mood recurrences could inform the prognosis and treatment. The objective of this review is to summarize the literature on factors, present during childhood, that influence recurrence. A systematic review of PubMed (1946-2017) and PsycINFO (1884-2017) databases was conducted to identify candidate studies. Search terms included bipolar disorder, episodes, predictors, recurrences, and course. Study characteristics, risk for bias, and factors associated with recurrence were coded by two raters according to predetermined criteria. Twenty child studies and 28 adult studies that retrospectively evaluated childhood variables associated with mood recurrences were included. Early age of onset, low socioeconomic status, comorbid disorders, inter-episode subsyndromal mood symptoms, BD-I/II subtypes, presence of stressors, and family history of BD were associated with higher number of recurrences. Risk factors and mood recurrences were assessed and defined in different ways, limiting generalizability. Multiple factors are associated with increased risk of mood episode recurrence in BD. Interventions targeting modifiable factors could reduce the impact of BD. For example, treatment of comorbid disorders and subsyndromal mood symptoms, coupled with appropriate cognitive behavioral and family-focused therapies could ameliorate risk related to many clinical factors. When coupled with social services to address environmental factors, the number of episodes could be reduced and the course of BD significantly improved.


Relayed Heteroatom Group Transfer: A Structural Reorganization between Bisthioester and Triaminophosphine to α,α-Disulfenylamide.
Simultaneous multiple displacements of organic molecules can lead to a large structural reconstruction with increased complexity that would be difficult to access otherwise. Whereas double displacement such as olefin metathesis is well-established, higher-order versions remain much more challenging, because of their intrinsic thermodynamic disadvantages. Here, we describe a newly discovered relayed heteroatom group transfer process between bisthioesters and triaminophosphines as an unusual example of a formal triple displacement. Through the oxygen/nitrogen exchange between the two simple starting materials, in addition to the 1,2-sulfur migration of a putative carbene intermediate, an organized relocation of the O/S/N groups proceeded to give a variety of α,α-disulfenylamides with excellent efficiency under ambient conditions. The experimental and computational mechanistic studies revealed the sequence of the relayed group shifts via an α,α-disulfenyl phosphonium enolate intermediate as well as the dual role of triaminophosphine as both an oxygen acceptor and a nitrogen donor.


Regulation of mesangial cell hexokinase activity by PKC and the classic MAPK pathway.
Phorbol esters increase glucose (Glc) uptake and utilization in a variety of cell types, and, in some cells, these changes have been attributed to increased Glc phosphorylation and better functional coupling of hexokinases (HKs) to facilitative Glc transporters. Phorbol esters are potent mesangial cell mitogens, but their effects on HK-catalyzed Glc phosphorylation and metabolism are unknown. When examined in murine mesangial cells, active, but not inactive, phorbol esters increased HK activity in a time- and dose-dependent manner. Maximal induction of HK activity at 12-24 h was accompanied by parallel increases in both Glc utilization and lactate production and was blocked by the specific MEK1/2 inhibitor PD-98059 (IC(50) approximately 3 microM). This effect involved early activation of protein kinase C (PKC), MEK1/2, and ERK1/2, and the prolonged time course of subsequent HK induction was attributable, in part, to requirements for ongoing gene transcription and de novo protein synthesis. Mesangial cell HK activity thus exhibits novel regulatory behavior involving both PKC and classic MAPK pathway activation, suggesting specific mechanisms whereby PKC activation may influence Glc metabolism.


Attacks on Heartbeat-Based Security Using Remote Photoplethysmography.
The time interval between consecutive heartbeats (interpulse interval, IPI) has previously been suggested for securing mobile-health solutions. This time interval is known to contain a degree of randomness, permitting the generation of a time- and person-specific identifier. It is commonly assumed that only devices trusted by a person can make physical contact with him/her, and that this physical contact allows each device to generate a similar identifier based on its own cardiac recordings. Under these conditions, the identifiers generated by different trusted devices can facilitate secure authentication. Recently, a wide range of techniques have been proposed for measuring heartbeats remotely, a prominent example of which is remote photoplethysmography (rPPG). These techniques may pose a significant threat to heartbeat-based security, as an adversary may pretend to be a trusted device by generating a similar identifier without physical contact, thus bypassing one of the core security conditions. In this paper, we assess the feasibility of such remote attacks using state-of-the-art rPPG methods. Our evaluation shows that rPPG has similar accuracy as contact PPG and, thus, forms a substantial threat to heartbeat-based-security systems that permit trusted devices to obtain their identifiers from contact PPG recordings. Conversely, rPPG cannot obtain an accurate representation of an identifier generated from electrical cardiac signals, making the latter invulnerable to state-of-the-art remote attacks.


Effects of supplementing different ratios of omega-3 and omega-6 fatty acids in western-style diets on cow's milk protein allergy in a mouse model.
This study investigated the effects of supplementing different ratios of omega-6 and omega-3 fatty acids (O6H = 10:1, O3O6 = 4:1, and O3H = 1:4) to western-style diets on cow β-lactoglobulin (BLG) induced allergic reactions in Balb/c mice. Three-week-old mice were randomly assigned to three diet groups (n = 20/group). At 9 wk of age, half of the mice from each dietary treatment (n = 10) were intraperitoneally (i.p.) sensitized with three weekly doses of BLG and alum while the remaining half from each group was sham sensitized (controls). One week after the final sensitization, all mice were orally challenged with BLG. Elevated BLG-specific serum Igs were observed in all sensitized and challenged mice. IFN-γ, MCP-1, and IL-12p40 concentrations from lymphocytes of mesenteric lymph nodes were highest in O3H mice, compared to O3O6 and O6H mice. O6H mice had the highest IL-4 concentrations from splenic lymphocytes and a significantly lower rectal temperature after the challenge in comparison to O3O6 and O3H mice. Our results suggest that the ω-3 PUFA rich diets alleviated the severity of allergic reactions, and may modulate immune response toward T helper cell (Th)1-favoured immune response while the ω-6 PUFA rich diet exhibited no allergy alleviation with a stronger Th2 polarized immune response.


Dental Implant Corrosion Products May Accumulate in the Human Body.
Corrosion products resulting from the degradation of the dental implant surface due to biological fluids and infection may accumulate in the body and lead to clinical consequences. The primary aim of this study is to measure the accumulation of dental implant corrosion products in the human body and the secondary aim is to estimate the association between corrosion products and fatigue. This study was designed as a prospective cross-sectional and was conducted with patients presenting at to the Department of Oral and Maxillofacial Surgery. The study included patients with Grade IV dental implants made of pure titanium (Ti) at the bone level and Grade V abutments composed of Ti, aluminum (Al), and vanadium (V). Individuals possessing different metallic implants and those prone to metal exposure were not included in the study. Blood and hair samples were procured from each participant and subsequently analyzed. The predictor variable is implant exposure, and it was divided into 3 groups; Group I, patients with healthy dental implants; Group II, patients with peri-implantitis; Control Group, individuals without dental implants. The primary outcome variables are Al, Ti, V levels in blood and hair samples and the secondary outcome variable is the fatigue questionnaire score. Age and gender, along with the dental implant number and duration of exposure within the study groups, are utilized as covariates. Groups were compared using the Kruskal-Wallis and Mann-Whitney U-tests. Spearman's correlation coefficient determined relationships between groups, signifying significance with P values <.05. The sample consisted of 30 patients aged 18 to 68, with 53% being female and 47% male. The differences among the 3 groups in the median values of blood Ti, V; hair Al, Ti, V; and fatigue questionnaire scores were not statistically significant (P > .05). However, the median blood Al value was statistically higher in Group II (P < .05). While the presence of healthy dental implants may not affect the accumulation of Al, Ti, and V within the body, patients with peri-implantitis exhibited elevated blood Al levels, possibly due to infection influencing the corrosion process.


A Further Study on Mining DNA Motifs Using Fuzzy Self-Organizing Maps.
Self-organizing map (SOM)-based motif mining, despite being a promising approach for problem solving, mostly fails to offer a consistent interpretation of clusters with respect to the mixed composition of signal and noise in the nodes. The main reason behind this shortcoming comes from the similarity metrics used in data assignment, specially designed with the biological interpretation for this domain, which are not meant to consider the inevitable noise mixture in the clusters. This limits the explicability of the majority of clusters that are supposedly noise dominated, degrading the overall system clarity in motif discovery. This paper aims to improve the explicability aspect of learning process by introducing a composite similarity function (CSF) that is specially designed for the k -mer-to-cluster similarity measure with respect to the degree of motif properties and embedded noise in the cluster. Our proposed motif finding algorithm in this paper is built on our previous work robust elicitation algorithms for discovering (READ) [1] and termed READ Deoxyribonucleic acid motifs using CSFs (READ(csf)), which performs slightly better than READ and shows some remarkable improvements over SOM-based SOMBRERO and SOMEA tools in terms of F-measure on the testing data sets. A real data set containing multiple motifs is used to explore the potential of the READ(csf) for more challenging biological data mining tasks. Visual comparisons with the verified logos extracted from JASPAR database demonstrate that our algorithm is promising to discover multiple motifs simultaneously.


A Longitudinal Study of Violent Behavior in a Psychosis-Risk Cohort.
There is a lack of insight into the relationships between violent ideation, violent behavior, and early, particularly attenuated, psychosis. Our aims were to examine the relationships between baseline violent behavior and violent ideation and outcome violent behavior and conversion to psychosis in at-risk individuals. We longitudinally assessed 200 individuals at clinical high risk for psychosis for violent ideation and violent behavior using the Structured Interview for Psychosis-Risk Syndromes (SIPS), and rated these according to MacArthur Community Violence categories. Fifty-six individuals (28%) reported violent ideation at baseline, 12 (6%) reported violent behavior within 6 months pre-baseline, and 8 (4%) committed acts of violence during the follow-up time period. Information about violent ideation was obtained only by indirect, but not direct, inquiry about violent ideation. Both violent ideation and violent behavior at baseline significantly predicted violent behavior (RR=13.9, p=0.001; RR=8.3, p=0.003, respectively) during follow-up, as well as a diagnosis of psychosis (RR=2.3 and 2.4, respectively; both p<0.001), independent of more than 40 clinical and demographic variables. The targets of the subjects' violent ideation at baseline were completely different than their subsequent targets of violent behavior. Violent behavior occurred within 7 days (SD 35 days) of a diagnosis of syndromal psychosis. These data suggest that checking carefully for violent ideation and behavior in clinical high-risk patients is essential, as these have predictive value for conversion to psychosis and likelihood of violence in the future.


[Decompression sickness in divers treated at the Israel Naval Medical Institute between the years 1992 to 1997].
Clinical characteristics of 125 divers treated for decompression sickness (DCS) in the hyperbaric multiplace chambers of this Institute during 1992-1997 were analyzed retrospectively. In 62 (51%) the diagnosis was DCS Type I (joint pain or skin involvement) and in 60 (49%) DCS Type II (neurological, inner ear or pulmonary disease). Risk factors for the evolution of DCS were depth and duration of the dives involving accidents, violation of recommendations of the decompression tables, and repeated dives. Results were available for 112 of the 125 patients. 54 of them (48%) recovered completely, and another 54 recovered partially; 4 did not respond to treatment. Inner ear DCS was less responsive to hyperbaric oxygen treatment (p = 0.0001). There was significant improvement of neurological function in those with severe neurological injury (p = 0.0001). Rapid diagnosis and transportation of divers with DCS to a hyperbaric chamber is of crucial importance.


Dimensional reductions of a cardiac model for effective validation and calibration.
Complex 3D beating heart models are now available, but their complexity makes calibration and validation very difficult tasks. We thus propose a systematic approach of deriving simplified reduced-dimensional models, in "0D"-typically, to represent a cardiac cavity, or several coupled cavities-and in "1D"-to model elongated structures such as muscle samples or myocytes. We apply this approach with an earlier-proposed 3D cardiac model designed to capture length-dependence effects in contraction, which we here complement by an additional modeling component devised to represent length-dependent relaxation. We then present experimental data produced with rat papillary muscle samples when varying preload and afterload conditions, and we achieve some detailed validations of the 1D model with these data, including for the length-dependence effects that are accurately captured. Finally, when running simulations of the 0D model pre-calibrated with the 1D model parameters, we obtain pressure-volume indicators of the left ventricle in good agreement with some important features of cardiac physiology, including the so-called Frank-Starling mechanism, the End-Systolic Pressure-Volume Relationship, as well as varying elastance properties. This integrated multi-dimensional modeling approach thus sheds new light on the relations between the phenomena observed at different scales and at the local versus organ levels.


[Typology of therapy-resistant states in schizophrenia].
Clinical regularities in the formation of resistance to therapy in schizophrenic patients make it possible to identify 4 groups of therapy resistance: (1) resistance due to clinical factors (regularities of the process); (2) resistance due to both clinical and therapeutical factors (predicted insufficient cure); (3) resistance due to therapeutic factors in connection with adaptation to drugs and therapeutic errors (inadequate or insufficiently intensive treatment); (4) idiopathic resistance. This systematics of states resistant to therapy may contribute to differentiation of their treatment.


Perspectives of adolescent and young adults on poverty-related stressors: a qualitative study in Ghana, Malawi and Tanzania.
To define key stressors experienced and coping behaviours within poor agrarian communities in sub-Saharan Africa. Descriptive qualitative study incorporating inductive thematic analysis. 81 participants purposely sampled, stratified by age (adolescents and young adults) and sex SETTING: The study was conducted in villages in Ghana, Malawi, and Tanzania. Stressors were thematically grouped into those directly related to poverty and the lack of basic necessities (eg, food insecurity), and additional stressors (eg, drought) that worsen poverty-related stress. Impacts on functioning, health and well-being and key coping behaviours, both positive and negative, were identified. The findings together inform a more nuanced view of stress within these contexts. Although participants were asked to provide general reflections about stress in their community, the salience of poverty-related stressors was ubiquitously reflected in respondents' responses. Poverty-related stressors affect development, well-being and gender-based violence. Future research should focus on interventions to alleviate poverty-related stress to achieve the United Nations Sustainable Development Goals.


An unusual case of intestinal leiomyositis in a Bernese mountain dog.
A 1-year-old, female Bernese mountain dog was presented to the Veterinary Teaching Hospital of Turin University with a 3-month history of weight loss, intermittent anorexia, vomiting, constipation, and abdominal distension. Full-thickness biopsies from the stomach, duodenum, jejunum and ileum were collected for histological and immunohistochemical examination. Microscopic lesions displayed severe diffuse degeneration and loss of leiomyocytes, with lymphocytic leiomyositis, fibroplasia, angiogenesis, severe diffuse neuronal atrophy, and ganglioneuritis in the myenteric (Auerbach's) plexus. A diagnosis of chronic idiopatic intestinal pseudo-obstruction was made. Response to immunosuppressive therapy was poor and the dog was humanely euthanized. Unique findings were mononuclear infiltration composed predominantly of B-cell, angiogenesis and weak immunoreactivity for neuron-specific enolase.


Combining Social Norms and Social Marketing to Address Underage Drinking: Development and Process Evaluation of a Whole-of-Community Intervention.
Youth alcohol consumption has been steadily declining in Australia, as in other countries; fewer young people are drinking and the age of initiation is increasing. However, young people, their parents and others in their communities continue to believe that adolescent (excessive) drinking is the norm. This perception, and the concurrent misperception that the majority of parents are happy to provide their underage children with alcohol, creates a perceived culture of acceptance of youth alcohol consumption. Young people believe that it is accepted, and even expected, that they will drink; and parents perceive that not providing their adolescent children with alcohol will lead to social exclusion. There is evidence that shifting social norms can have an immediate and lasting effect adolescents' (and adults') alcohol related attitudes and behaviors. This paper reports on a novel, community based social marketing intervention designed to correct misperceptions of alcohol related social norms in an Australian community. The project utilized a social marketing approach, informed by the full complement of Andreasen's social marketing benchmarking criteria, and concurrently targeted adolescents, parents of adolescents and the broader community. Using extensive formative research and multiple evaluation techniques, the study demonstrates that shifts in community social norms are possible and suggests that this approach could be used more widely to support the positive trends in youth alcohol consumption and parental supply.


[Peptide hydrolases with catalytic dyad Ser-Lys. Similarity and distinctions of the active centers of ATP-dependent Lon proteases, LexA repressors, signal peptidases and C-terminal processing proteases].
It is established that ATP-dependent protease Lon family belongs to the serine-lysine peptide hydrolases clan. Significant similarity of amino acid sequences of proteases Lon and repressors LexA in the regions including the catalytic serine and lysine residues is revealed by comparing primary structures of different families of the enzymes with Ser-Lys catalytic dyad. The both Lon and LexA families are shown to be divided into two subfamilies in accordance with the nature of amino acids in the catalytically active serine environment. Putative DNA binding sites are revealed in proteolytic domains of Lon A subfamily. Similarities and distinctions of the all families peptide hydrolases of the clan in the regions of their active centers are discussed.


Is mucosal healing more common than clinical remission in ulcerative colitis? - Is it the truth or only a myth coming from the studies?
The most important goals of the recent therapies of ulcerative colitis (UC) are to induce and maintain clinical remission and to achieve mucosal healing (MH). Rate of endoscopic remission has been shown to be higher than that of clinical remission in large trials like ULTRA and PURSUIT. The aim of our study was to evaluate the correlation between clinical and endoscopic disease activities of UC defined by activity scores. Clinical and endoscopic activities were evaluated in 100 consecutive UC patients. Clinical activities were defined by two activity indices: the Rachmilewitz Activity Index (CAI) and the partial Mayo score. Colonoscopies and patient enrollments were performed by two experienced gastroenterologists and endoscopists. They graded the findings both according to the endoscopic part of the Rachmilewitz Endoscopic Activity Index (EI) and the Mayo endoscopic subscore. MH was defined as Mayo endoscopic subscore and EI of 0. Histological activity was scored by Riley score. Clinical and endoscopic activities showed strong correlations using both scoring systems (p = 0.0029 and p = 0.0001). Endoscopic disease activity also correlated with the histological activity (p ≥ 0.001). Significant correlation was shown between the clinical activity and MH (p = 0.0012 and p ≥ 0.001). No association was showed with the extension of the disease and clinical or endoscopic activity. Assessment of MH is very important for guiding therapy and for evaluation of remission in patients with UC. Our result showed good correlation between the clinical, endoscopic, and histological activities of UC focusing on the importance of evaluating the endoscopic activity of the patients.


Medical Assistance in Dying at a paediatric hospital.
This article explores the ethical challenges of providing Medical Assistance in Dying (MAID) in a paediatric setting. More specifically, we focus on the theoretical questions that came to light when we were asked to develop a policy for responding to MAID requests at our tertiary paediatric institution. We illuminate a central point of conceptual confusion about the nature of MAID that emerges at the level of practice, and explore the various entailments for clinicians and patients that would flow from different understandings. Finally, we consider the ethical challenges of building policy on what is still an extremely controversial social practice. While MAID is currently available to capable patients in Canada who are 18 years or older-a small but important subsection of the population our hospital serves-we write our policy with an eye to the near future when capable young people may gain access to MAID. We propose that an opportunity exists for MAID-providing institutions to reduce social stigma surrounding this practice, but not without potentially serious consequences for practitioners and institutions themselves. Thus, this paper is intended as a road map through the still-emerging legal and ethical landscape of paediatric MAID. We offer a view of the roads taken and considered along the way, and our justifications for travelling the paths we chose. By providing a record of our in-progress thinking, we hope to stimulate wider discussion about the issues and questions encountered in this work.


Evaluation of endoscopic mucosal resection and nodal micrometastasis in pN0 submucosal gastric cancer.
Endoscopic mucosal resection (EMR) is a minimally invasive, standard treatment for intramucosal (early) gastric cancers, but is not standard for submucosal gastric cancers based on existing criteria. We evaluated the possibility of extending EMR as a therapy for submucosal gastric cancers by analyzing nodal micrometastasis through immunohistochemical staining in patients with apparent node-negative submucosal gastric cancer, the patients for whom EMR might be appropriate. We used anti-cytokeratin (AE1/AE3) antibody to immunohistochemically detect nodal micrometastasis that was not identified by routine pathological examination in 162 patients (total, 2048 lymph nodes) with apparent node-negative submucosal gastric cancer. The relationship between the incidence of nodal micrometastasis and clinicopathological factors was analyzed. Micrometastasis was detected in 45 of 2048 nodes (2.2%), representing 31 of 162 patients (19%). A significantly high incidence of nodal micrometastasis was found with submucosal cancers of large size (>2 cm), as well as with tumors that showed lymphatic or venous invasion and deeper submucosal invasion (p<0.0001). Nodal micrometastasis was also recognized in 2 cases of histologically well-differentiated tumors with focal submucosal invasion without venous or lymphatic invasion. Of the 162 patients, only 2 died of recurrent disease regardless of nodal involvement. Based on the present results, risk factors for nodal micrometastasis are tumor size, presence of lymphatic-vascular invasion, and depth of tumor, which are nearly the same as those established in previous pathological studies that used hematoxylin and eosin staining. We conclude that EMR is not recommended for patients with submucosal gastric cancer.


Microlatex test for diphtheria antitoxin.
Microlatex test was used to detect quantitatively the diphtheria antitoxin in the serum samples. Microtiter technique using polystyrene latex particles coated with diphtheria toxoid was found to be more convenient and sensitive than flocculation test using sizable amount of reagents.


Between-site reliability of startle prepulse inhibition across two early psychosis consortia.
Prepulse inhibition (PPI) and reactivity of the acoustic startle response are widely used biobehavioral markers in psychopathology research. Previous studies have demonstrated that PPI and startle reactivity exhibit substantial within-site stability; however, between-site stability has not been established. In two separate consortia investigating biomarkers of early psychosis, traveling participants studies were carried out as a part of quality assurance procedures to assess the fidelity of data across sites. In the North American Prodromal Longitudinal Studies (NAPLS) consortium, eight normal participants traveled to each of the eight NAPLS sites and were tested twice at each site on the startle PPI paradigm. In preparation for a binational study, 10 healthy participants were assessed twice in both San Diego and Mexico City. Intraclass correlations between and within sites were significant for PPI and startle response parameters, confirming the reliability of startle measures across sites in both consortia. There were between-site differences in startle magnitude in the NAPLS study that did not appear to be related to methods or equipment. In planning multisite studies, it is essential to institute quality assurance procedures early and establish between-site reliability to assure comparable data across sites.