Identifying effective components for mobile health behaviour change interventions for smoking cessation and service uptake: protocol of a systematic review and planned meta-analysis.
Mobile health (mHealth) interventions for smoking cessation have been shown to be associated with an increase in effectiveness. However, interventions using mobile phones to change people's behaviour are often perceived as complex interventions, and the interactions between several components within them may affect the outcome. Therefore, it is important to understand how we can improve the design of mHealth interventions using mobile phones as a medium to deliver services. Randomised controlled trials (RCTs) of mHealth interventions to support smoking cessation or uptake of smoking cessation services for smokers will be included in this systematic review. A search will be performed by searching MEDLINE, MEDLINE(R) In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, Web of Science, and CINAHL. A search for new publications will be conducted 3 months prior to submission for publication as mHealth is an emerging area of research. A random-effects meta-analysis model will be used to summarise the effectiveness of mHealth interventions. The risk ratio will be used for the primary outcome, self-reported or verified smoking abstinence, and any binary outcomes for uptake of smoking cessation services. The standardised mean difference using Hedges' g will be reported for continuous data. Heterogeneity will be assessed using I 2 statistics. Where feasible, meta-regression analysis using random-effects multilevel modelling will be conducted to examine the association of pre-specified characteristics (covariates) at the study level with the effectiveness of interventions. Publication bias will be explored using Egger's test for continuous outcomes and Harbord and Peters tests for dichotomous outcomes. The funnel plot will be used to evaluate the presence of publication bias. The Cochrane Risk of Bias Tool will be used to assess differences in risks of bias. The results of this systematic review will provide future research with a foundation for designing and evaluating complex interventions that use mobile phones as a platform to deliver behaviour change techniques. PROSPERO CRD42016026918 .


Distinct miRNA Expression Signatures of Primary and Secondary Central Nervous System Lymphomas.
Central nervous system (CNS) lymphoma is a rare and aggressive non-Hodgkin lymphoma that might arise in the CNS (primary CNS lymphoma) or disseminates from a systemic lymphoma to the CNS (secondary CNS lymphoma). Dysregulated expression of miRNAs is associated with various pathologic processes, and miRNA expression patterns may have diagnostic, prognostic, and therapeutic implications. However, miRNA expression is understudied in CNS lymphomas. We performed expression analysis of 798 miRNAs in 73 CNS lymphoma samples using the NanoString platform, followed by an analysis to identify potential diagnostic biomarkers characterizing subgroups and to examine differences based on their primary and secondary nature, molecular subtype, mutational patterns, and survival. Thirty-one differentially expressed miRNAs were identified between primary and secondary groups. In addition, 7 more miRNAs were identified associated with a molecular subtype and 25 associated with mutation status. Using unsupervised clustering methods, a small but distinct primary CNS lymphoma subgroup, with characteristically different expression patterns compared with the rest of the cases was defined. Finally, differentially regulated pathways were identified in the above comparisons and the utility of miRNA expression patterns in predicting survival was assessed. Our study identifies a novel CNS lymphoma subgroup defined by distinct miRNAs, proves the importance of specific miRNAs and pathways in the pathogenesis of CNS lymphomas, and provides the basis for future research in defining potential biomarkers.


Clinical outcome in children after transanal 1-stage endorectal pull-through operation for Hirschsprung disease.
Recently, the transanal 1-stage pull-through operation has been widely used in Hirschsprung disease (HD), and it is obviously superior to traditional approach in early term for its noninversion. However, the procedure is relatively so new that it makes assessment of the functional outcome and stooling patterns difficult. The aim of this study was to evaluate the clinical outcomes of the transanal 1-stage endorectal pull-through operation in the management of rectosigmoid HD. Fifty-eight children (39 boys and 19 girls) aged 12 months to 13 years (mean, 2 years) who underwent transanal 1-stage endorectal pull-through operation for HD were followed up from 6 to 24 months. Clinical outcome was assessed by interviews and questionnaires. All patients had an aganglionic segment confined to the rectosigmoid area which was confirmed by the preoperative barium enema and postoperative pathological examination. Forty-six patients had satisfactory results without complications. In all the children, the mean stool times were 1 to 2 per day; only 4 had mean stool times of 8 to 10 per day. Postoperative soiling was present in 9, constipation in 5, and HD-associated enterocolitis in 3. There were no incontinence, cuff infection, anastomotic leak, and mortality in any of the patients. In the 12 symptomatic patients, there were 4 children with length of aganglionic segment less than 30 cm, and 8 had 30 cm or more. In the 46 asymptomatic patients, 42 had length of aganglionic segment less than 30 cm, and 4 had 30 cm or more. There was a significant difference between the group with less than 30 cm and the group with 30 cm or more of aganglionic segment. For statistical analysis, the Fisher exact test showed P < .05. The transanal 1-stage endorectal pull-through is a feasible and safe procedure in children with rectosigmoid HD. The clinical outcome is satisfactory. A gradual recovery could be noted in the stooling patterns along with the time after surgery. The younger the patient operated on and the shorter the aganglionic segment, the lower do the stooling disorders occur and the faster does the stooling function recover.


Insertion of I-125 seed-loaded stent for inoperable hilar cholangiocarcinoma.
Stent insertion is the most frequently used option to treat malignant biliary obstruction (MBO) patients. Hilar cholangiocarcinoma (HCCA) is the most common disease that causes hilar MBO. To assess the clinical efficacy and long-term outcomes of I-125 seed-loaded stent (ISS) insertion for HCCA patients. Consecutive patients with HCCA underwent either normal stent (NS) or ISS insertion between January 2017 and December 2019. The baseline and treatment data of these two groups were compared. During the period, a total of 93 patients with inoperable HCCA were divided into either NS (n = 48) or ISS (n = 45) insertion groups at our centre. Technical success rates of the NS and ISS insertion were 91.7% and 95.6%, respectively (p = 0.733). Clinical success rates were 93.2% and 100% in the NS and ISS groups, respectively (p = 0.24). Stent dysfunction was observed in 11 and 8 patients in the NS and ISS groups, respectively (p = 0.47). The median stent patency was 143 days and 208 days in the NS and ISS groups, respectively (p < 0.001). All patients died in the follow-up period, with median survival duration of 178 days and 220 days in the NS and ISS groups, respectively (p < 0.001). ISS insertion was the only predictor of longer patency (p = 0.002) and survival (p = 0.01). ISS insertion might achieve longer patency and overall survival in patients with inoperable HCCA as compared with NS insertion.


Birth order and intellectual development: the confluence model in the light of cross-cultural evidence.
For Israeli eighth-grade students of Asian-African origin, achievement decreases as a function of birth order in small families and increases as a function of birth order in large families. This finding cannot be accounted for by differences in developmental rate or size of birth intervals. It can be accounted for by considering the effect of external influences, such as schooling, on intellectual development.


A core genome multilocus sequence typing (cgMLST) analysis of Mycoplasma bovis isolates.
Mycoplasma bovis (M. bovis) is an emerging major bovine pathogen, causing economic losses worldwide in the dairy and beef industry. Whole-genome sequencing (WGS) now allows high resolution for tracing clonal populations. Based on WGS, we developed the core genome multilocus sequence typing (cgMLST) scheme and applied it onto 151 genomes of clonal and non-clonal strains of M. bovis isolated from China, Australia, Israel, Denmark, Canada, and the USA. We used the complete genome of M. bovis PG45 as the reference genome. The pairwise genome comparison of these 151 genome sequences resulted in 478 cgMLST gene targets present in > 99.0 % clonal and non-clonal isolates with 100 % overlap and > 90 % sequence similarity. A total of 478 core genes were retained as cgMLST target genes of which an average of 90.4-99 % were present in 151 M. bovis genomes, while M. agalactiae (PG2) had 17.0 % and M. mycoides subsp. capri (PG3), M. ovipneumoniae (Y98), and M. arginine resulted in 0.0 % of good targets. When tested against the clonal and non-clonal strains, we found cgMLST clusters were congruent with the MLST-defined clonal groups, which had various degrees of diversity at the whole-genome level. Notably, cgMLST could distinguish between clonal and epidemiologically unrelated strains of the same clonal group, which could not be achieved using traditional MLST schemes. Our results showed that ninety-two M. bovis genomes from clonal group isolates had > 10 allele differences and unambiguously differentiated from unrelated outgroup strains. Additionally, cgMLST revealed that there might be several sub-clones of the emerging ST-52 clone. The cgMLST phylogenetic analysis results showed substantial agreement with geographical and temporal information. cgMLST enables the use of next-generation sequencing technology to bovine mycoplasma epidemiology at both the local and global levels. In conclusion, the novel cgMLST scheme not only showed discrimination resolution highly as compared with MLST and SNP cgMLST in sub-typing but also indicated the capability to reveal more population structure characteristics than MLST.


Differences among genotypic frequencies of undisturbed and manipulated populations of Daphnia.
A lake population of Daphnia, and several subpopulations in large plastic enclosures within the lake and manipulated with respect to population densities and nutrient enrichment (acetate, nitrate, phosphate), exhibited differences among genotypic frequencies at the phosphoglucoisomerase locus. The lake and control populations exhibited similar genotypic frequencies which were significantly different from those found in the three manipulated populations. The similarity of the genetic reaction in the manipulated populations may be related to similarity of manipulation. All populations exhibited deviations from Hardy-Weinberg proportions in the form of heterozygote excess.


Investigation on the skin penetration of synthetic amorphous silica (SAS) used in cosmetic products.
Synthetic amorphous silica (SAS) is used as additive in a variety of industrial applications for many decades and has been approved to be used in food, food contact materials, pharmaceuticals, and cosmetics. Due its internal structure, SAS is considered as a nanomaterial, thus it is affected by a general safety discussion. Based on the production process, SAS for cosmetic application is a nanomaterial by the EU Recommendation, although it was not considered as such, because the solely size-dependent definitions of the term "nanomaterial" emerged in recent times first in Recommendation 2011/696/EU. Therefore, former physicochemical and toxicological evaluations of SAS were already performed on nanomaterials, however, without being addressed as such. Safety concerns can only emerge if two criteria, (toxicological) hazard and exposure towards the substance is fulfilled at the same time. In case of SAS, the Scientific Committee on Consumer Safety (SCCS) challenged provided data to be insufficient to draw a conclusion regarding the safety of SAS and thus, requested further investigations, in particular by exploring skin penetration of particulate SAS.Investigation of specific particulate substances in skin penetration tests is an analytical challenge. The number of available analytical techniques that are capable to detect nanomaterials in complex matrices, like receptor fluids from skin penetration testing, are limited and still emerging. In the new studies, a comprehensive set of analytical techniques were used to investigate the skin penetration potential of SAS. Particle-sensitive, element and particle-specific combinations of techniques and different sample preparation procedures, that respected the particulate nature of SAS, were used to detect SAS in receptor fluids directly. In addition, electron microscopic techniques were used to examine different layers of skin to detect adsorbed SAS.The combination of Asymmetric Flow Field-Flow Fractionation (AF4) in combination with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for examination of receptor fluids and Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy (SEM/EDX) for examination of skin itself, were identified as suitable techniques for the detection of SAS in skin penetration tests. Data from literature was used to compare the results of the studies with the outcome of other test systems (other particles, other techniques). Both, the test results, and literature evaluation led to the conclusion, that SAS does not penetrate skin. Based on this outcome and local and systemic dermal toxicity review of SAS, it can be concluded that dermal application of SAS in cosmetic formulations is negligible.


Acceptability of A Virtual Mind-Body Group Intervention for Teen Siblings of Children with Autism Spectrum Disorder.
Teenage siblings of children with autism spectrum disorder (ASD) are at risk of worse mental health outcomes than their peers, yet there have been few interventions focused on improving their psychosocial wellbeing. This study explored the acceptability of an 8-session virtual group mind-body resiliency intervention for teen siblings of children with ASD. We used mixed methods to assess quantitative and qualitative survey results. Participants reported that the intervention had the right amount of sessions (88%), structure (74%), and duration (89%). Most participants felt comfortable during sessions (74%), found it helpful to learn mind-body exercises (74%), and that the intervention helped in coping with stress (71%). Though participants were satisfied with the opportunity to meet peers, they desired more social connection.


Pediatric outpatient intravenous rehydration.
There is considerable variation in emergency department practices concerning the use of intravenous (IV) rehydration. Sixty-eight patients seen in a pediatric emergency room and requiring IV rehydration were studied prospectively. Fifty-eight patients were rehydrated in the emergency room, and 10 were admitted for rehydration. Fluid resuscitation ranged from 14 to 103 ml/kg (mean, 40 ml/kg). Following emergency department rehydration, two patients required subsequent emergency department rehydration, and one patient was admitted for rehydration. To determine outpatient IV rehydration practices, 214 pediatric training programs were surveyed. Of 173 respondents, 77 (44.5%) carry out IV rehydration in the emergency department in less than 5% of cases, and 115 (66.4%) perform it in less than 10% of cases; only 11.7% of programs carry out IV rehydration in the emergency department in most cases requiring such therapy. It is concluded that from the standpoints of cost effectiveness and patient acceptance, outpatient IV rehydration should be considered more often as a treatment option.


Analysis of monoclonal immunoglobulins from bone marrow plasma cells using immunopurification and LC-MS.
Clonal plasma cells secrete immunoglobulins, each with the exact same amino acid sequence, that are referred to as monoclonal immunoglobulins. The monoclonal heavy chain and light chain secreted from clonal plasma cells have the same molecular mass prior to the addition of post-translational modifications (PTMs) since their amino acid sequences are the same. To examine the molecular masses of monoclonal light chains and heavy chains isolated directly from the cytoplasm of bone marrow (BM) plasma cells and compare them to the serum derived monoclonal heavy and light chains. Using immunopurification and LC-MS we compared the molecular masses of immunoglobulins immunopurified from a patient's serum to those immunopurified from the cytoplasm of their BM plasma cells. Our findings demonstrate that the light chain molecular masses were identical whether they were obtained from serum or plasma cell cytoplasm. However, the heavy chain molecular masses did not match in bone marrow and serum due to differences in glycosylation, a common post-translational modification (PTM) found on the heavy chain. The data presented here show that by using LC-MS to analyze monoclonal immunoglobulins (also referred to as miRAMM) additional phenotype information is obtained at the cellular level which is complementary to other more common techniques such as flow cytometry and histopathology.


An audit of study casts used to monitor tooth wear in general practice.
To assess the outcome of compliance of advice sent to patients and dentists about monitoring tooth wear in general practice. Postal questionnaires were sent to 70 patients and their dentists requesting information on the outcome of letters of advice sent to general dental practitioners regarding monitoring tooth wear with study casts. They also requested information about the reasons for the patients' referral, the outcome of treatment and whether study models had been taken. Replies were received from 60 dentists (87%) and 53 patients (75%). Of these, 16 patients and 16 dentists had moved from their recorded address. Study casts were reported as having been taken by 23 dentists (38%) and reported by 18 patients (34%). The most common reason for referral was advice about monitoring the wear and the appearance of their teeth. The compliance of the patients and dentists in monitoring tooth wear by using study casts in general practice was not successful. It raises issues regarding the value of consultant advice letters to this common clinical problem.


Treatment of theophylline intoxication: a model study utilizing peritoneal dialysis.
This study shows that peritoneal dialysis of theophylline-intoxicated rats results in withdrawal of approximately 27% of the administered dose of theophylline in 4 hr. Clinical consequences of this experience are considered.


Characteristics of Idiopathic Subglottic Stenosis in the Elderly.
To compare characteristics of patients ≥65 years presenting with idiopathic subglottic stenosis (iSGS) to patients diagnosed at <65 years. We hypothesize that the groups have similar comorbidities and disease courses. Medical records of patients treated for iSGS at a tertiary care institution from January 2005-September 2022. Patient demographics, time from symptom onset to diagnosis, medical history and comorbidities, and treatment modalities/intervals were recorded and analyzed. Characteristics of patients ≥65 and <65 years at presentation were compared using Chi-square analysis for non-numeric values and the Mann-Whitney U-test for numeric values. One hundred seven patients with iSGS were identified and 16 (15%) were aged ≥65 years (mean age 72.6, 15 female) at presentation. These patients were compared to 91 patients aged <65 years (mean age = 47.6, 90 female). Patients ≥65 years had higher rates of type 2 diabetes mellitus (T2DM) (p = 0.004) and tobacco use (p = 0.004). There were no significant differences in body mass index, gastroesophageal reflux disease, hormone replacement therapy, time from symptom onset to presentation, or length of operative treatment intervals. Patients ≥65 years with iSGS have higher rates of tobacco use, suggesting that alterations in wound healing may play a role in the development of iSGS in this age group. Although rates of T2DM were higher in the elderly group, clinical significance may be limited given the overall higher rate of diabetes mellitus in the elderly population. 4 Laryngoscope, 133:3075-3079, 2023.


Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as inhibitors of the bacterial cell division protein FtsZ.
In an attempt to discover potential antibacterial agents against the increasing bacterial resistance, novel cinnamaldehyde derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method, and their cell division inhibitory activity against four representative strains. In the in vitro antibacterial activity, the newly synthesized compounds generally displayed better efficacy against Staphylococcus aureus ATCC25923 than the others. In particular, compounds 3, 8 and 10 exerted superior or comparable activity to all the reference drugs. In the cell division inhibitory activity, all the compounds showed the same trend as their in vitro antibacterial activity, exhibiting better activity against S. aureus ATCC25923 than the other strains. Additionally, compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with an MIC value of below 1 μg/mL, over 256-fold better than all the reference drugs.


Modular and regioselective synthesis of all-carbon tetrasubstituted olefins enabled by an alkenyl Catellani reaction.
All-carbon tetrasubstituted olefins have been found in numerous biologically important compounds and organic materials. However, regio- and stereocontrolled construction of this structural motif still constitutes a significant synthetic challenge. Here, we show that a modular and regioselective synthesis of all-carbon tetrasubstituted olefins can be realized via alkenyl halide- or triflate-mediated palladium/norbornene catalysis, which is enabled by a modified norbornene containing a C2 amide moiety. This new norbornene co-catalyst effectively suppressed undesired cyclopropanation pathways, which have previously been a main obstacle for developing such reactions. Diverse cyclic and acyclic alkenyl bromides or triflates with a wide range of functional groups can be employed as substrates. Various substituents can be introduced at the alkene C1 and C2 positions regioselectively simply by changing the coupling partners. Initial mechanistic studies provide insights on the rate-limiting step as well as the structure of the actual active ligand in this system.


Role of epigenetic regulatory mechanisms in neonatal hypoxic-ischemic brain injury.
DNA methylation and histone modifications are the most identified modifications that selectively activate or inactivate genes that control cell growth, proliferation, and apoptosis. We hypothesized that alterations in gene expression due to hypoxic-ischemic brain damage was regulated by epigenetic mechanisms including DNA methylation and histone methylation. To test this hypothesis, we established a rat model of HIE. Three groups were defined as hypoxic-ischemic, sham-operated, and control group. The validity of the HIE model used in this study was confirmed by histological and immunohistochemical tests. Gene expressions related with apoptosis and angiogenesis were studied at 0.5, 3, 6 and 24h after HI or sham operation. DNA and histone methylation status was studied in the genes showing significant change in expression. Most of the genes related with apoptosis and angiogenesis (Epo, Epor, Hif 1α, Hif3α, VEGFa, VEGFc, Casp1, Casp9, and Casp8ap2) induced early after HI (30min). All of these genes were unmethylated at the beginning of the insult and in the control group. DNA methylation percentage and histone methylation (H3K36) levels were not correlated with gen expression levels. To our knowledge this is the first study evaluating the role of epigenetic mechanisms in HIE model, therefore the absence of similar studies don't allow us to compare the present results. Further studies investigating different epigenetic mechanisms are needed.


Nuclear import inhibitor N-(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection.
In the absence of approved therapeutics, Zika virus (ZIKV)'s recent prolific outbreaks in the Americas, together with impacts on unborn fetuses of infected mothers, make it a pressing human health concern worldwide. Although a key player in viral replication in the infected host cell cytoplasm, ZIKV non-structural protein 5 (NS5) appears to contribute integrally to pathogenesis by localising in the host cell nucleus, in similar fashion to NS5 from Dengue virus (DENV). We show here for the first time that ZIKV NS5 is recognized with high nanomolar affinity by the host cell importin α/β1 heterodimer, and that this interaction can be blocked by the novel DENV NS5 targeting inhibitor N-(4-hydroxyphenyl) retinamide (4-HPR). Importantly, we show that 4-HPR has potent anti-ZIKV activity at low μM concentrations. With an established safety profile for human use, 4-HPR represents an exciting possibility as an anti-ZIKV agent.


Catalytic CO2 gasification of rubber seed shell-derived hydrochar: reactivity and kinetic studies.
In this study, hydrothermal carbonization (HTC) of a biomass was used as a means to improve the physicochemical properties of rubber seed shell (RSS) and enhance its reactivity in the char-CO2 gasification reaction, known as the Boudouard reaction (C + CO2 ↔ 2CO). Hydrochar samples were developed by hydrothermal treatment of RSS, without separating the solid residue from the liquid product, at 433, 473, 513, and 553 K under autogenous pressure. The CO2 gasification reactivity of the developed hydrochars was then investigated at different heating rates (5, 10, 20, and 30 K/min) by the non-isothermal thermogravimetric method. The hydrochars revealed higher reactivity and improved gasification characteristics compared to the untreated biomass, while the hydrochar which was filtered from the liquid slurry showed lower reactivity compared to the untreated biomass. This was due to the chemical and structural evolutions of the biomass during hydrothermal treatment as indicated by various analyses. The gasification reactivity of the hydrochar was substantially enhanced by introduction of a catalyst (NaNO3) during HTC. Kinetic analysis of the char-CO2 gasification reaction was carried out by applying Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS), and Starink isoconversional methods, and thermodynamic parameters were also determined. The activation energy of the Na-loaded RSS hydrochar in CO2 gasification (120-154 kJ/mol) was considerably lower than that of the untreated biomass (153-172 kJ/mol). Thermodynamic studies also confirmed the promoting effect of hydrothermal treatment and catalyst impregnation on enhancement of reactivity of the virgin biomass and reduction of gasification temperature.


Valorisation of agri-food waste to fertilisers is a challenge in implementing the circular economy concept in practice.
The area of agricultural wastes valorisation to fertilizers is attracting growing attention because of the increasing fertilizer prices of fertilizers and the higher costs of waste utilization. Despite the scientific and political interest in the concept of circular economy, few studies have considered the practical approach towards the implementation of elaborated technologies. This article outlines innovative strategies for the valorisation of different biobased wastes into fertilizers. The present work makes a significant contribution to the field of new ideas for waste biomass management to recover significant fertilizer nutrients. These results emphasize the importance of the biomass use as a base of renewable resources, which has recently gained special importance, especially in relation to the outbreak of pandemia and war. Broken supply chains and limited access to deposits of raw materials used in fertilizer production (natural gas, potassium salts) meant that now, as never before, it has become more important and feasible to implement the idea of a circular economy and a green deal. We have obtained satisfactory results that demonstrate that appropriate management of biological waste (originating from agriculture, food processing, aquaculture, forest, pharmaceutical industry, and other branches of industry, sewage sludge) will not only reduce environmental nuisance (reducing waste heaps), but will also allow recovery of valuable materials, such as nitrogen (especially valuable amino acids), phosphorus, potassium, microelements, and biologically active substances with properties that stimulate plant growth. The results reported here provide information on production of biobased plant protection products (bioagrochemicals) from agri-food waste. This work reports an overview of biopesticides and biofertilisers production technologies and summarizes their properties and the mechanisms of action.


Parameterization and validation of a new AMBER force field for an oxovanadium (IV) complex with therapeutic potential implications in Alzheimer's disease.
The scarcity of efficient force fields to describe metal complexes may be a problem for new advances in medicinal chemistry. Thus, the development of force fields for these compounds can be valuable for the scientific community, especially when it comes to molecules that show interesting outputs regarding potential treating of diseases. Vanadium complexes, for instance, have shown promising results towards therapeutics of Alzheimer's Disease, most notably the bis(maltolato)oxovanadium (IV). Therefore, the mainly goal of this work is to develop and validate a new set of parameters for this vanadium complex from a minimum energy structure, obtained by DFT calculations, where great results of the new force field are found when confronted with experimental and quantum reference values. Moreover, the new force field showed to be quite effective to describe the molecule of under study whilst GAFF could not describe it effectively. In addition, a case study points out hydrogen bonds in the vanadium complex-PTP1B system.


Pain and pain management experiences following spinal cord injury - a mixed methods study of Australian community-dwelling adults.
There is a high prevalence of persistent pain following SCI yet insights into its impact and the quality of pain care are limited. We aimed to explore, in-depth, the problem of persistent pain in Australian community-dwelling adults with a spinal cord injury (SCI). Our objectives were to investigate (i) how individuals experience persistent pain, (ii) how they experience pain care and (iii) the concordance between clinical practice guidelines for managing pain and reported care practices. We conducted a mixed-methods convergent parallel study. Adults with SCI and persistent pain completed a survey (n = 43); a subset of participants completed interviews (n = 10). We analysed the data from each method separately and then integrated the findings. Results indicated that the life impact of persistent pain is variable but it can be more disabling than physical impairments and compound a sense of isolation and despair. Community-based management was reported to predominantly have a pharmacological focus, with occurrences of opioid misuse apparent in the data. Access to expert, comprehensive and individualised care was frequently reported as inadequate. While some people with SCI and persistent pain can effectively self-manage their pain, for others the impact on quality of life is profound and complex care needs are commonly unmet.IMPLICATIONS FOR REHABILITATIONPersistent pain is a common consequence of SCI and profoundly impacts quality of life.Complex pain care needs are commonly unmet.Individuals require regular, comprehensive, biopsychosocial assessment.The effectiveness of pain management strategies must be monitored on an ongoing basis.Opportunities for personal self-management support must be available long-term.


Comparison of isokinetic and isoinertial lifting tests as predictors of maximal lifting capacity.
This study compared the relationship between isokinetic lifting test (ILT) performance and a maximal operational lifting test (OLT) with that between an isoinertial progressive lifting test (PLT) and OLT. Fifty subjects performed the ILT, PLT and OLT after familiarization trials. OLT was defined as the weight of the heaviest crate that could be lifted to 1.34 m with a progressive, incremental test. ILT performance was the force generated during a single maximal simulated lift on an isokinetic dynamometer. PLT performance was the maximal weight lifted to 1.52 m with a progressive, incremental protocol on a weight stack. OLT was highly correlated with ILT (r = 0.96) and PLT (r = 0.97); the standard error was similar for both linear regression equations. The results demonstrate that a single maximal voluntary lift on an isokinetic dynamometer is as good a predictor of OLT as in the PLT presently used in military recruit centers.


Relationship between body size traits and carcass traits with primal cuts yields in Hanwoo steers.
This study was conducted to evaluate the correlation between body size traits, carcass traits, and primal cuts in Hanwoo steers. Sixty-one beef carcasses were classified for conformation and primal cut weight. Additionally, carcass weight, fat thickness, carcass dimensions, and longissimus muscle area were determined to complement the grading. The average live weight and cold carcass weight were 759 and 469 kg, respectively. The mean carcass meat, fat, and bone proportions were 551, 298, and 151 g/kg, respectively. Primal cuts weights showed significant positive correlations (p<0.001) of 0.42 to 0.82 with live weight, carcass weight, and longissimus muscle area and a significant negative correlation with carcass fat (without shank, -0.38 to -0.10). Primal cut weights were positively correlated (p<0.01) with carcass length (0.41 to 0.77), forequarter length (0.33 to 0.57), 6th lumbar vertebrae-heel length (0.33 to 0.59), 7th cervical vertebrae carcass breadth (0.35 to 0.58), 5th to 6th thoracic vertebrae breadth (0.36 to 0.65), 7th to 8th thoracic vertebrae girth (0.38 to 0.63), and coxae girth (0.34 to 0.56) and non-significantly related to cervical vertebrae length and coxae thickness. There was a high correlation among live weight, carcass weight, longissimus muscle area, carcass length, 7th cervical vertebrae carcass breadth, 5th to 6th thoracic vertebrae breadth, and 7th to 8th thoracic vertebrae girth of the primal cuts yield. The correlation between fat and primal cut yields was highly significant and negative. Carcass length and 7th to 8th thoracic vertebrae girth, appear to be the most important traits affecting primal cut yields.


Isolated aortic root dilation in homocystinuria.
Vascular complications in homocystinuria have been known for many years, but there have been no reports to date on involvement of the ascending aorta. We conducted a cross-sectional study of patients with homocystinuria, known to a single metabolic centre, and evaluated in 2016 with a transthoracic echocardiogram. Aortic root dilation was defined as Z-score ≥ 2.0 SD, and graded mild (Z-score 2.0-3.0), moderate (Z-score 3.01-4.0) and severe (Z-score > 4.0). The study population included 34 patients, median age of 44.3 years (IQR 33.3-52.2), 50% males, 69% diagnosed aged <18 years and 29% pyridoxine-responsive. Eight (24%) had a history of hypertension. Seven patients (21%) were found to have a dilation of the aortic root, mild in two cases (6%), moderate in four (12%) and severe in one (3%). None had dilation of the ascending aorta. Significant aortic regurgitation, secondary to moderate aortic root dilation, was documented in two patients. A single patient had significant mitral regurgitation due to prolapse of both valve leaflets, as well as mild aortic root dilation. Comparing patients with a dilation of the aortic root to those without, there were no significant clinical, laboratory or echocardiographic differences, with the only exception being that the diameter of the ascending aorta was larger in the group with a dilated aortic root, albeit within normal limits. A subset of patients with homocystinuria have isolated dilation of the aortic root similar to that observed in Marfan syndrome.


Wear of Morse taper and external hexagon implant joints after abutment removal.
The aim of this in vitro study was to evaluate the removal torque values on abutments and the morphological wear aspects of two different dental implant joints after immersion in a medium containing biofilm from human saliva. Twenty implant-abutment assemblies were divided into four groups in this study: (A) Morse taper free of medium containing biofilm, and (B) after contact with a medium containing biofilm from human saliva; (C) External Hexagon free of medium containing biofilm, and (D) after contact with medium containing biofilm from human saliva. The abutments were firstly torqued to the implants according to the manufacturer´s recommendations, using a handheld torque meter. Groups B and D were immersed into 24 well-plates containing 2 ml BHI medium with microorganisms for 72 h at 37 °C under microaerophilic conditions. After detorque evaluation, the abutments were removed and the implants were analyzed by scanning electron microscopy (SEM) and profilometry. On the detorque evaluation, the torque values decreased for the external hexagon implants and increased for the Morse taper implants. However, the values were lower when both implant-abutment assemblies were in contact with a medium containing biofilm from human saliva. The wear areas of contacting surfaces of the implants were identified by SEM. The highest average roughness values were recorded on the surfaces free of biofilm. The medium containing biofilm from human saliva affected the maintenance of the torque values on Morse taper and external hexagon abutments. Additionally, the removal of abutment altered the inner implant surfaces resulting in an increase of wear of the titanium-based connection.


[Application of SIR model in forecasting and analyzing for SARS].
An SIR epidemic model is applied on the research of SARS. Parameters in the model are estimated and forecasted by two methods. Time-varying estimated parameters are also compared for Beijing and Hong Kong SARS epidemic situations.


Aversion-resistant fentanyl self-administration in mice.
Animal models of compulsive drug use that continues despite negative consequences can be used to investigate the neural mechanisms of addiction. However, models of punished or aversion-resistant opioid self-administration are notably lacking. We sought to develop an aversion-resistant, oral fentanyl self-administration paradigm. In Experiment 1, C57BL/6J male and female, adult mice consumed fentanyl (10 μg/mL) in a two-bottle drinking in the dark task and escalating concentrations of quinine were added to the bottles. In Experiment 2, mice were trained to administer oral fentanyl (10 μg/mL) in an operant response task. Quinine was next added to the fentanyl solution in escalating concentrations. In Experiment 3, mice were trained to respond for oral fentanyl or fentanyl adulterated with 500 μM quinine on every session. In Experiment 4, mice were trained to respond for a 1% sucrose solution before introduction of quinine. Quinine reduced two-bottle choice consumption in males but not in females. Both sexes demonstrated the ability to detect the selected concentrations of quinine in fentanyl. In the operant chamber, mice responded robustly for oral fentanyl but introduction of quinine at any stage of training was insufficient to reduce responding. In contrast, quinine reduced responding for sucrose at concentrations above 250 μM. Mice will respond for and consume oral fentanyl in both a two-bottle choice and an operant response task. Quinine is detectable in fentanyl but mice will continue to respond for and consume fentanyl with quinine in both paradigms. These data support the use of these models in behavioral studies of compulsive-like opioid use.


Relationships between oral sensory feedback skills and adaptation to delayed auditory feedback.
The relationship between adaptation to delayed auditory feedback (DAF) and oral sensory feedback as measured by tasks of oral form discrimination (OFD) was investigated. In addition, the interactions between OFD ability and attempts to heighten subjects' awareness of oral feedback while speaking under DAF conditions by giving instruction to subjects as well as the condition of instruction itself were studied with adaptation to DAF as the dependent variable. Analyses of the data indicated a relationship between OFD ability and adaptation to DAF and an interaction between OFD ability and instruction. The study's rationale and results are discussed within the context of servosystem theory.


Metabolomics strategy assisted by transcriptomics analysis to identify biomarkers associated with schizophrenia.
Metabolomics strategy was perform to identify the novel serum biomarkers linked to schizophrenia with the assistance of transcriptomics analysis. Two analytical platforms, UPLC-Q-TOF MS/MS and 1H NMR, were used to acquire the serum fingerprinting profiles from a total of 112 participants (57 healthy controls and 55 schizophrenia patients). The differential metabolites were primarily selected after statistical analyses. Meanwhile, GSE17612 dataset downloaded from GEO database was implemented WGCNA analysis to discover crucial genes and corresponding biological processes. Based on metabolomics analysis, the metabolic distinctions were explored under the aid of transcriptomics. Then using Boruta algorithm identified the biomarkers, and LASSO regression analysis and Random Forest algorithm were used to evaluate the performance of the diagnostic model constructed by biomarkers selected. A total of four metabolites (α-CEHC, neuraminic acid, glyceraldehyde and asparagine) were selected as the biomarkers to establish diagnosis model. The performance of this model showed a higher accuracy rate to distinguish schizophrenia patients from healthy controls (area under the receive operating characteristic curve, 0.992; precision recall curve, 1.000, the mean accuracy of random forest algorithm, 95.00%). A four-biomarker model (α-CEHC, neuraminic acid, glyceraldehyde and asparagine) seems to be a good model for diagnosing schizophrenia patients. It might be helpful to guide the future studies on permitting early intervention designed to prevent disease progression.


Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of titanium oxide-enriched peptides for detection of aged organophosphorus adducts on human butyrylcholinesterase.
Exposure to nerve agents or organophosphorus (OP) pesticides can have life-threatening effects. Human plasma butyrylcholinesterase (BChE) inactivates these poisons by binding them to Ser198. After hours or days, these OP adducts acquire a negative charge by dealkylation in a process called aging. Our goal was to develop a method for enriching the aged adduct to facilitate detection of exposure. Human BChE inhibited by OP toxicants was incubated for 4 days to 6 years. Peptides produced by digestion with pepsin were enriched by binding to titanium oxide (TiO2) and analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. It was found that with two exceptions, all aged OP adducts in peptide FGES198AGAAS were enriched by binding to Titansphere tips. Cresyl saligenin phosphate yielded two types of aged adduct, cresylphosphate and phosphate, but only the phosphate adduct bound to Titansphere. The nerve agent VR yielded no aged adduct, supporting crystal structure findings that the VR adduct on BChE does not age. The irreversible nature of aged OP adducts was demonstrated by the finding that after 6 years at room temperature in sterile pH 7.0 buffer, the adducts were still detectable. It was concluded that TiO2 microcolumns can be used to enrich aged OP-modified BChE peptide.


Effect of suplatast tosilate on goblet cell metaplasia in patients with asthma.
Goblet cell metaplasia is a pathologic characteristic of asthma, associated with excess mucus secretion. Interleukin (IL)-4 and IL-13 plays an important role in mucus hypersecretion. Suplatast tosilate (suplatast), an antiallergic agent, is a Th2 cytokine inhibitor that suppresses the synthesis of IL-4, IL-5, IL-13, and eosinophilic airway inflammation. We examined the effects of suplatast on mucus production in bronchial biopsy specimens taken from asthmatic subjects. Oral suplatast 300 mg daily, or placebo was administered for 3 months in a double-blind, parallel-group study in 25 patients with asthma. Biopsy specimens were evaluated at before and after treatment for alcian blue/period acid-Schiff (AB/PAS), MUC5AC staining in bronchial epithelium and IL-4+, IL-13+ cells as well as inflammatory cells in lamina propria. There were significant decreases in the percentage of AB/PAS (P < 0.01) and MUC5AC (P < 0.01) stained area in the suplatast group. These changes were accompanied by significant decreases in IL-4+ and IL-13+ cells in suplatast-treated subjects. Additionally, we have observed that the number of infiltrating eosinophils and CD4+ T cells significantly decreased. These findings suggest that suplatast prevents goblet cell metaplasia through modulation of Th2 cytokine production and the recruitment of eosinophils and CD4+ T cells in the asthmatic airways.


Ordered phosphorylation of a duplicated minimal recognition motif for cAMP-dependent protein kinase present in cardiac troponin I.
Cardiac troponin I contains two adjacent serines in sequence after three arginine residues thus making up a minimally duplicated recognition motif for cAMP-dependent protein kinase. In a synthetic peptide, PVRRRSSANY, the two serine residues are phosphorylated sequentially with the intermediate formation of a monophosphorylated species according to the following reaction sequence: Peptide k1----Peptide-P k2----Peptide-P2. The calculated rat constants are: k1 = 0.435.min-1 and k2 = 0.034.min-1. Sequence analyses of the monophosphopeptide and its tryptic fragments show that the predominant monophosphoform carries phosphate at the second serine.


Primary debulking surgery versus neo-adjuvant chemotherapy in stage III/IV ovarian cancer: Comparison of perioperative morbidity and survival data in Pakistani women.
To compare the peri-operative morbidity and survival rates between ovarian cancer patients treated with two different approaches. The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised data related to patients with advanced stage ovarian carcinoma treated between 1999 and 2008. Medical records were reviewed and relevant demographic, clinical, surgical, pathologic and follow-up information was acquired. Progression-free survival and overall survival rates were compared between patients who underwent primary debulking surgery and those who had received neo-adjuvant chemotherapy before surgery. SPSS 19 was used for statistical analysis. Of the total 118 patients, 78(66%) had undergone primary debulking surgery and 40(34%) had received neo-adjuvant chemotherapy. The mean age and pre-operative carcinoma antigen-125 level were similar. The debulking group had 74(94.8%) patients with stage 3, and 4(5.1%) patients with stage 4 disease, while the other group had 32(80%) and 8(20%) with stage 3and 4 respectively. The frequency of optimal debulking was 42(56.8%) in the former group against 27(79.4%) in the latter (p=0.01). Duration of surgery, estimated blood loss >1500ml and stay at the intensive care unit were not statistically different (p>0.05). Rate of Urinary tract, bowel injury and bowel resections were also similar. There was no difference in the progression-free survival in both groups (p>0.05). Neo-adjuvant chemotherapy followed by interval debulking produced comparable survival rates and peri-operative complications.


Long-term results of Amatsu tracheoesophageal shunt: Follow-up of more than 5 years.
The Amatsu tracheoesophageal shunt (ATES) represents a nonprosthesis surgical option for voice restoration in laryngectomized patients. However, data regarding the long-term efficacy of ATES are lacking. Retrospective, single-institution study. Between 2001 and 2010, 16 patients with laryngeal cancer underwent total laryngectomy with ATES at the Hyogo Cancer Center (Akashi, Hyogo, Japan). Of these, 11 achieved long-term tracheoesophageal speech that was maintained for a follow-up exceeding 5 years (range 75-161 months; median 95 months). All patients were male and ranged from 46 to 74 years of age at the time of ATES surgery. Of 11 eligible patients, eight were able to speak intelligibly with ATES at last follow-up. Regarding aspiration, three patients experienced no leakage, and six experienced mild leakage of saliva without medical intervention at last follow-up. Almost all patients maintained an unchanged degree of voice quality (9 of 11) and leakage (8 of 11). The favorable voice restoration and low aspiration rates achieved in this study appear to support the long-term efficacy of ATES. 4. Laryngoscope, 128:1395-1397, 2018.


Diagnostic Accuracy of Biomarkers and International Ovarian Tumor Analysis Simple Rules in Diagnosis of Ovarian Cancer.
This study investigated whether combining International Ovarian Tumor Analysis (IOTA) Simple Rules with tumor biomarkers would improve the diagnostic accuracy for early detection of adnexal malignancies. Receiver operating characteristic curve analysis of suspected adnexal tumors was performed in 226 women admitted for surgery at the University Clinical Center of Kosovo. Primary outcome was the diagnostic accuracy of the combination of adnexal mass biomarkers and IOTA Simple Rules. IOTA Simple Rules combined with biomarker indications increased the diagnostic accuracy of classifying adnexal masses. Data analysis of individual measures showed that ferritin had the lowest rate of sensitivity.


Spindle cell carcinoma of the breast: four cases and review of the literature.
The clinical and morphologic features of four cases of spindle cell carcinoma of the breast are presented, and the comparable features of 35 previously reported cases are reviewed. All tumors contained histologically malignant squamous carcinoma that tended to blend with a spindle cell "pseudosarcomatous" stroma. Patients with this rare tumor tend to present at the same age as patients with other histologic types of breast carcinoma, but the spindle cell tumors are somewhat larger. Although the number of reported patients is too small to serve as a basis for firm conclusions, the prognosis appears similar to that for patients with conventional infiltrating duct carcinoma of the breast.


Observations questioning a protective role for breast-feeding in severe rotavirus diarrhea.
To investigate whether breast-feeding protects children against rotavirus diarrhea (RVD), we compared rates of breast-feeding by age and enteric pathogens among 2,276 children with diarrhea 0-4 years of age who attended a diarrhea hospital in Bangladesh. Infants 0-5 months were less likely to be breast-fed than children 6-11 months of age suggesting that some protection against diarrhea with all agents was associated with early breast-feeding. In every age group studied, breast-feeding was more common among children with RVD than among children with non-RVD whereas it was less common among children with cholera and shigellosis. Twenty percent of breast milks consumed by infants less than 1 year of age had high levels of neutralizing activity (greater than or equal to 320) to the Wa strain of rotavirus but this activity did not appear to be protective since the 30 infants with RVD consumed milk which had titers that did not differ significantly from those consumed by 44 infants with diarrhea of other cause. Despite the prolonged breast-feeding which is common in Bangladesh, the mean age of hospitalization with RVD is approximately the same as in countries where the duration of breast-feeding is quite short. None of these 3 independent observations support a protective role for breast-feeding against rotavirus diarrhea after the first months of life.


Optimum organ volume ranges for organs at risk dose in cervical cancer intracavitary brachytherapy.
To analyze the optimum organ filling point for organs at risk (OARs) dose in cervical cancer high-dose-rate (HDR) brachytherapy. In a retrospective study, 32 locally advanced cervical cancer patients (97 insertions) who were treated with 3D conformal external beam radiation therapy (EBRT) and concurrent chemotherapy during 2010-2013 were included. Rotterdam HDR tandem-ovoid applicators were used and computed tomography (CT) scanning was performed after each insertion. The OARs delineation and GEC-ESTRO-based clinical target volumes (CTVs) contouring was followed by 3D forward planning. Then, dose volume histogram (DVH) parameters of organs were recorded and patients were classified based on their OARs volumes, as well as their inserted tandem length. The absorbed dose to point A ranged between 6.5-7.5 Gy. D0.1cm(3) and D2cm(3) of the bladder significantly increased with the bladder volume enlargement (p value < 0.05). By increasing the bladder volume up to about 140 cm(3), the rectum dose was also increased. For the cases with bladder volumes higher than 140 cm(3), the rectum dose decreased. For bladder volumes lower than 75 cm(3), the sigmoid dose decreased; however, for bladder volumes higher than 75 cm(3), the sigmoid dose increased. The D2cm(3) of the bladder and rectum were higher for longer tandems than for shorter ones, respectively. The divergence of the obtained results for different tandem lengths became wider by the extension of the bladder volume. The rectum and sigmoid volume had a direct impact on increasing their D0.1cm(3) and D2cm(3) , as well as decreasing their D10, D30, and D50. There is a relationship between the volumes of OARs and their received doses. Selecting a bladder with a volume of about 70 cm(3) or less proved to be better with regards to the dose to the bladder, rectum, and sigmoid.


Determination of selenium species in beetroot juices.
Over the past years, there is an increasing demand for healthy, natural foods. Due to the high content of betalains, beetroots are widely used in the food industry as a natural colorant. In this study, beetroot juices are shown as a great source of selenium compounds. The juices were purchased from a local store and the ecological one was purchased form organic street market. The content of organic selenium species, as well as betalains, were evaluated using hydrophilic interaction liquid chromatography (HILIC) chromatography. The concentrations of selenomethionine (SeMet) and methylselenocysteine (MeSeCys) in analyzed juices were comparable except for juice from ecological cultivation. In that case, the concentration of SeMet is the highest of all studied juices, but simultaneously the concentration of MeSeCys was the lowest one. No traces of major inorganic species of Se, such as Se(IV) and Se(VI) was detected. The reducing power of juices evaluated by Folin-Ciocalteu assay was in range 50.78-166.7 mg GA/L. Juices obtained from beetroot from ecological cultivation showed the highest ability to scavenge the 1,1-diphenyl-2- picrylhydrazyl (DPPH) radicals. There was a correlation between the yellow pigment content and the presence of selenocysteine in studied juices.


Regulatory effects of the Uty/Ddx3y locus on neighboring chromosome Y genes and autosomal mRNA transcripts in adult mouse non-reproductive cells.
In addition to sperm-related genes, the male-specific chromosome Y (chrY) contains a class of ubiquitously expressed and evolutionary conserved dosage-sensitive regulator genes that include the neighboring Uty, Ddx3y and (in mice) Eif2s3y genes. However, no study to date has investigated the functional impact of targeted mutations of any of these genes within adult non-reproductive somatic cells. We thus compared adult male mice carrying a gene trap within their Uty gene (UtyGT) to their wild-type (WT) isogenic controls, and performed deep sequencing of RNA and genome-wide profiling of chromatin features in extracts from either cardiac tissue, cardiomyocyte-specific nuclei or purified cardiomyocytes. The apparent impact of UtyGT on gene transcription concentrated mostly on chrY genes surrounding the locus of insertion, i.e. Uty, Ddx3y, long non-coding RNAs (lncRNAs) contained within their introns and Eif2s3y, in addition to possible effects on the autosomal Malat1 lncRNA. Notwithstanding, UtyGT also caused coordinate changes in the abundance of hundreds of mRNA transcripts related to coherent cell functions, including RNA processing and translation. The results altogether indicated that tightly co-regulated chrY genes had nonetheless more widespread effects on the autosomal transcriptome in adult somatic cells, most likely due to mechanisms other than just transcriptional regulation of corresponding protein-coding genes.


Transsphenoidal microsurgical results of female patients with prolactinomas.
We investigated surgical cure rate and surgical complications of patients with macroprolactinomas who desired pregnancy to evaluate the efficacy of transsphenoidal surgery. Surgical cure rate was investigated in 138 female patients who were under 40 years old. We found a significant correlation between serum prolactin levels and adenoma volume (r=0.004; p<0.0001), adenoma volume and age (r=-0.213; p<0.03), and proliferative index of the adenoma and age (r=-0.15; p<0.007). Seventy-seven out of 81 patients with enclosed macroadenoma were considered cured, and therefore the overall surgical cure rate was 95%. However, during long-term follow-up, recurrence of adenomas with hyperprolactinemia was seen in 5 out of 81 patients (6%), and the long-term cure rate in patients with enclosed macroadenomas was 89%. Adenomas that did not invade the cavernous sinus showed a significantly higher surgical curability and lower serum prolactin levels, and a smaller size than those adenomas that invaded the cavernous sinus. The long-term surgical cure rate was found to be 89% and this success rate far surpasses the complication rate of 39% during pregnancy by dopamine agonist therapy. Thus, transsphenoidal surgery should be considered as a first-line treatment for female patients who desire pregnancy.


Are the proposed substance P receptor sub-types, substance P receptors?
Recently, a number of laboratories have postulated the existence of receptor sub-types for substance P. This review is intended to represent a critical appraisal of these reports. In the majority of cases, the evidence for the existence of receptor sub-types has been obtained from observed potency differences of agonists. The problems with this approach are discussed. In addition, information obtained through substance P antagonists, binding studies and investigations of second messenger systems is presented and discussed in relation to the above receptor subdivisions. It is concluded that the present results are consistent with the existence of three receptor sub-types; however, it is suggested that substance P is the natural agonist for only one of these receptors, and that substance K and tuftsin may be the transmitters for the other two receptor sub-types.


Digital holography-based 3D particle localization for single-molecule tweezer techniques.
We present a three-dimensional (3D) imaging technique for the fast tracking of microscopic objects in a fluid environment. Our technique couples digital holographic microscopy with three-dimensional localization via parabolic masking. Compared with existing approaches, our method reconstructs 3D volumes from single-plane images, which greatly simplifies image acquisition, reduces the demand on microscope hardware, and facilitates tracking higher densities of microscopic particles while maintaining similar levels of precision. We demonstrate utility of this method in magnetic tweezer experiments, opening their use to multiplexed single-molecule force spectroscopy assays, which were previously limited by particle crowding and fast dissociation times. We propose that our technique will also be useful in other applications that involve the tracking of microscopic objects in three dimensions, such as studies of microorganism motility and 3D flow characterization of microfluidic devices.


A new tool for inorganic nitrogen speciation study: simultaneous determination of ammonium ion, nitrite and nitrate by ion chromatography with post-column ammonium derivatization by Nessler reagent and diode-array detection in rain water samples.
The paper presents a new method for a simultaneous determination of inorganic nitrogen species in the oxidized (NO2-, NO3-) and reduced (NH4+) form in rain water samples. The method is based on a system of nitrogen species separation employing ion exchange and diode-array detection. The ions are separated in a strong ion-exchanger, nitrites and nitrates are determined directly at 208 and 205 nm, respectively, while the ammonium ions are determined in the column hold-up time after a post-column derivatization by the Nessler reagent, at 425 nm. The use of a diode-array detector permits a simultaneous identification of the inorganic nitrogen species in 8 min. The detection limits obtained are: NO2-, 0.1 mg L(-1); NO3-, 0.05 mg L(-1); NH4+, 1 mg L(-1). The method proposed has been successfully used for speciation analysis of inorganic nitrogen in precipitation.


Education Theory Made Practical: Creating open educational resources via an apprenticeship model.
Clinical faculty may have limited knowledge of education theories and best practices in health professions education. Many faculty development programs focus on passive learning with limited application to practice. There is a need for more active engagement for early career educators. We created an apprenticeship-based electronic book series focused on translating education theories into practical applications for clinician educators. Chapters were authored by teams of two to four geographically separated early career educators, who were tasked with explaining an education theory and relating it to their educational practice. The chapters underwent internal peer review, followed by open peer review as a blog post and eventual publication. Usage data were collected, and surveys were sent to authors and end-users. Six volumes (60 total chapters) have been created to date by 180 unique authors and 17 editors over a 6-year period. There have been 65,571 total blog page views and 17,180 total book downloads across the five published volumes. Authors reported an increase in their perceived knowledge (pre 2.6 ± 1.7 vs. post 7.2 ± 1.1, mean difference 4.5/9.0, 95% confidence interval [CI] 4.0-5.0, p < 0.001) after writing their chapter. Authors also reported career benefits including authorship for academic advancement/promotion and developing an area of education theory expertise. End-users also reported a mean increase in their perceived knowledge (pre 4.4 ± 2.5 vs. post 7.3 ± 1.4, mean difference 2.9/9.0, 95% CI 2.1-3.8, p < 0.001) after reading a chapter. The Education Theory Made Practical electronic book series represents a proof of concept for an apprenticeship-based model to teach education theory, while also creating scholarship and open access resources for the broader community.


Effects of diet energy level and tomato powder consumption on antioxidant status in rats.
Evaluate the influence of tomato powder in diets differing in energy level on antioxidant status in blood and liver of rats. Twenty-four adult male Wistar rats weighing 150-180 g were placed four groups (n=6). For 28 days, animals were fed a diet that was either hyper energetic or hypo energetic. Some diets were supplemented with tomato powder. Liver and blood were collected for analysis of antioxidant enzymes, non-enzymatic antioxidants, thiobarbituric acid reactive species, ubiquinol 9, alpha-tocopherol, lycopene and beta-carotene. Data were analysed by two-way ANOVA. Food intake and thiobarbituric acid-reactive substances contents in liver and plasma were significantly decreased by tomato powder at both energy levels. After tomato powder supplementation, the hepatic levels of ubiquinol 9, alpha-tocopherol, lycopene and beta-carotene were significantly enhanced. In plasma, only the contents of lycopene and beta-carotene were enhanced. The erythrocytic and hepatic activities of catalase were lower, while those of glutathione peroxidase were higher after the ingestion of tomato powder. Total and reduced glutathione contents in liver showed lower levels in cafeteria-fed rats compared to the hypo energetic diet. The data suggest that the lycopene and beta-carotene component in the tomato power supplement might be beneficial for the prevention of oxidative damage in rats fed both types of energetic diets.


[Bioethics reflection on prioritization and rationing of health care: between social utility and equity].
Since health needs outweigh the available resources, choices are imperative. It is thus necessary to set limits, criteria, and standards in order to prioritize the supply, the recipients, and the services to be provided. Ethical alternatives are discussed for the prioritization and rationing of health care, focusing on the principles of equity and social utility.


Validation of the Spanish Acne Severity Scale (Escala de Gravedad del Acné Española--EGAE).
Several acne grading systems have been described, but consensus is lacking on which shows superiority. A standardized system would facilitate therapeutic decisions and the analysis of clinical trial data. To assess the feasibility, reliability, validity and sensitivity to change of the Spanish Acne Severity Scale (EGAE). A Spanish, multicentre, prospective, observational study was performed in patients with facial, back or chest acne assessed using EGAE, Leeds Revised Acne Grading system (LRAG) and lesion count. Clinicians answered 4 questions regarding EGAE use and time employed. Patients were evaluated at baseline and after 5±1 weeks. Four additional blinded observers, all dermatologists, evaluated patients' pictures using EGAE and LRAG. In total, 349 acne locations were assessed in 328 patients. Of the dermatologists, 95.6% (CI: 92.9-97.5%) reported that EGAE was easy to use, and 75% used it in <3 minutes. Interobserver reliability of the EGAE scale was shown by a Kendall's W of 0.773 (p<0.001). EGAE and LRAG scales showed a high correlation (Spearman's correlation>0.85; p<0.001). EGAE mean score in treatment-compliant patients was significantly lower at follow-up than at baseline (2.14 vs. 1.57, p<0.001, Cohen's d=0.35).The pre-post-treatment difference in EGAE mean score in non-compliant patients was not significant (1.44 vs. 1.32, p<0.102) and Cohen's d was lower (0.19) than in compliant patients. The use of EGAE to evaluate acne grade in daily clinical dermatological practice in Spanish centres has shown feasibility, high interobserver reliability, concurrent validity and sensitivity to detect treatment effects.


A silver staining method for the detection of polymorphic proteins in minute bloodstains after isoelectric focusing.
A silver staining method has been developed to study polymorphic proteins in bloodstains after isoelectric focusing. This method is highly sensitive and permits the detection of polymorphic proteins (i.e. alpha 1-antitrypsin, Gc and Tf C subtypes) in bloodstains as small as 0.2 microliter or less. The method is simple and reproducible and can be used after immunofixation. Blood stains can be identified after longer storage periods than is possible by using conventional staining methods.


X-ray tomography data of White Etching Cracks (WEC).
This data article contains lab-based micro-computed tomography (μCT) data of cracks and crack networks in 4 different bearings, mainly from wind turbines, which formed the basis for the crack analysis reported in Danielsen et al. (Danielsen et al., 2019).


Correction for contaminant fluorescence in frequency-domain fluorometry.
We describe a general method to correct for contaminant fluorescence when using the technique of frequency-domain fluorometry. The method can be applied regardless of the origin of the background signal, from scattered light, impurity fluorescence, or both. The procedure requires measurement of the frequency-dependent phase and modulation of the background at enough frequencies to approximate the decay law of the background. We also describe a general method to propagate the uncertainties in the measured phase and modulation values into the corrected values. This propagation is necessary to ensure proper weighting of the frequency-dependent data in the least-squares fitting algorithms. The practical usefulness of this correction method is demonstrated using frequency-domain data for one and two component mixtures which were deliberately contaminated with scattered light and/or other fluorophores.


Forensic application of inverse and reverse projection photogrammetry to determine subject location and orientation when both camera and subject move relative to the scene.
We present a case study of a mountain bicycle accident captured by the rider's chest-mounted action camera. The objective of the investigation was to determine the orientation of the bicycle relative to the ground and the location of the rider's center of gravity relative to the bicycle. The problem faced in the investigation was that the camera was moving relative to the scene and rider, and the bicycle was moving relative to the camera. Inverse photogrammetry was used to determine the location and orientation of the camera relative to the scene. Reverse projection photogrammetry applied to an exemplar bicycle provided an estimate of the location and orientation of the bicycle relative to the camera. The rider's position and orientation relative to the camera were estimated by comparing synchronized side views and chest-mounted action camera views of the rider's movements, recorded during a trail descent prior to the accident.


Utilization of overground exoskeleton gait training during inpatient rehabilitation: a descriptive analysis.
Overground exoskeleton gait training (OEGT) after neurological injury is safe, feasible, and may yield positive outcomes. However, no recommendations exist for initiation, progression, or termination of OEGT. This retrospective study highlights the clinical use and decision-making of OEGT within the physical therapy plan of care for patients after neurological injury during inpatient rehabilitation. The records of patients admitted to inpatient rehabilitation after stroke, spinal cord injury, or traumatic brain injury who participated in at least one OEGT session were retrospectively reviewed. Session details were analyzed to illustrate progress and included: "up" time, "walk" time, step count, device assistance required for limb swing, and therapist-determined settings. Surveys were completed by therapists responsible for OEGT sessions to illuminate clinical decision-making. On average, patients demonstrated progressive tolerance for OEGT over successive sessions as shown by increasing time upright and walking, step count, and decreased assistance required by the exoskeleton. Therapists place preference on using OEGT with patients with more functional dependency and assess feedback from the patient and device to determine when to change settings. OEGT is terminated when other gait methods yield higher step repetitions or intensities, or to prepare for discharge. Our descriptive retrospective data suggests that patients after neurological injury may benefit from OEGT during inpatient rehabilitation. As no guidelines exist, therapists' clinical decisions are currently based on a combination of knowledge of motor recovery and experience. Future efforts should aim to develop evidence-based recommendations to facilitate functional recovery after neurological injury by leveraging OEGT.


Intraorbital abducens nerve schwannoma.
Schwannomas of the abducens nerve are extremely rare tumors. The tumor may be located within the cavernous sinus or more often at the prepontine region. However, literature research has identified only one case of isolated schwannoma of the orbit, arising from the terminal branches of the abducens nerve to the lateral rectus muscle. This is only the second report of an abducens nerve schwannoma located entirely intraconal. We report a case of an intraorbital abducens nerve schwannoma in a 42-year-old man with no signs of neurofibromatosis. The lesion resulted in progressive diplopia and focal abducens palsy. The clinical, radiologic, and pathologic features are presented. We point the particular aspects and discuss the possible treatments and approaches to preserve nerve function. Being a benign lesion, one of the goals has always been total removal. The knowledge of the correct anatomic features made us believe that the VI nerve function could be preserved. Our case is the first example of a total removal with eye abduction preserved. Because of that, we believe that it is reasonable to aim for these goals in future cases.


Children with congenital Zika syndrome: symptoms, comorbidities and gross motor development at 24 months of age.
Children with congenital Zika syndrome (CZS) maintain severe motor impairments at the end of the first year of life. Presence of certain symptoms and comorbidities increase these children's vulnerability. To evaluate gross motor function of a group of Brazilian children with CZS at 24 months of age and to investigate the association between the presence of CZS symptoms and comorbidities with gross motor development. Fifty children with CZS participated in the study. Information was collected from medical charts, and gross motor development was evaluated by the Gross Motor Function Measure (GMFM)-88. GMFM-88 scores were compared among comorbid groups. Three subgroups of children were identified by cluster analysis, based on information from head circumference at birth, symptoms, comorbidities and gross motor function. Significant associations (p < 0.001) were observed between number of comorbidities/symptoms and dimensions A (r = -0.57) and B (r = -0.58) of the GMFM-88. Children were grouped into 3 clusters, with different gross motor skills. Children with epilepsy and dysphagia composed the cluster with smaller median scores for dimensions A and B of the GMFM-88. The presence of CZS symptoms and comorbidities compromise the gross motor repertoire of children with CZS at 24 months.


Pharyngocutaneous fistula after salvage laryngectomy: impact of interval between radiotherapy and surgery, and performance of bilateral neck dissection.
Pharyngocutaneous fistula is a serious complication of total laryngectomy. The purpose of this study was to examine predisposing factors at our institution. We conducted a retrospective review of 94 consecutive patients undergoing total laryngectomy. Cases with hypopharyngeal primary tumors or undergoing extended hypopharyngeal resection with flap augmentation of the pharynx were excluded. Seventy-four cases met inclusion criteria. A total of 25.7% patients developed a pharyngocutaneous fistula. The fistula rate was higher after salvage laryngectomy than after primary surgery (34.0% vs 11.1%; p = .05). Among salvage laryngectomies, performance of laryngectomy within 1 year of completion of radiotherapy (p = .006) and performance of concomitant bilateral neck dissection (p = .02) were significant risk factors for development of a fistula. Radiation dose, addition of chemotherapy, use of pectoralis major myofascial flap, preoperative tracheostomy, primary puncture, primary tumor subsite, and initial T classification were not significant. Interval between completion of radiotherapy and surgery is significantly associated with pharyngocutaneous fistula after salvage total laryngectomy.


Contrast-enhanced ultrasound-guided sentinel lymph node biopsy in early-stage breast cancer: a prospective cohort study.
This study evaluated the identification efficiency of contrast-enhanced ultrasound (CEUS) for sentinel lymph nodes (SLN) to accurately represent the axillary node status in early-stage breast cancer. In total, 109 consecutive consenting patients with clinically node-negative and T1-2 breast cancer were included in this study. All patients received CEUS to identify SLN before surgery, and a guidewire was deployed to locate SLN in those who were successfully explored by CEUS. The patients underwent sentinel lymph node biopsy (SLNB), and the blue dye was used to trace SLN during the surgery. The decision to perform axillary lymph node dissection (ALND) depended on the intraoperative pathological identification of SLN by CEUS (CE-SLN). The concordance rate of pathological status between CE-SLN and dyed SLN was calculated. The CEUS detection rate was 96.3%; CE-SLN failed in 4 patients. Among the remaining 105 successful identifications, 18 were CE-SLN positive by intraoperative frozen section, and one with CE-SLN micrometastasis was diagnosed by paraffin section. No additional lymph node metastases were found in CE-SLN-negative patients. The concordance rate of pathological status between CE-SLN and dyed SLN was 100%. CEUS can accurately represent the status of axillary lymph nodes in patients with clinically node-negative and small tumor burden breast cancer.


Mechanisms of the placebo response in pain in osteoarthritis.
Administration of a placebo associates with symptomatic improvement in many conditions--the so-called placebo response. In this review we explain the concept of placebo response, examine the data that supports existence in osteoarthritis (OA), and discuss its possible mechanisms and determinants. A Pubmed literature search was carried out. Key articles were identified, and their findings discussed in a narrative review. Pain, stiffness, self-reported function and physician-global assessment in OA clearly improve in response to placebo. However, more objective measures such as quadriceps strength and radiographic progression appear less responsive. Although not directly studied in OA, contextual effects, patient expectation and conditioning are believed to be the main mechanisms. Neurotransmitter changes that mediate placebo-induced analgesia include increased endogenous opioid levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost all parts of the brain involved in pain processing are influenced during placebo-induced analgesia. Determinants of the magnitude of placebo response include the patient-practitioner interaction, treatment response expectancy, knowledge of being treated, patient personality traits and placebo specific factors such as the route and frequency of administration, branding, and treatment costs. Clearer understanding of the neurobiology of placebo response validates its existence as a real phenomenon. Although routine administration of placebo for symptomatic improvement is difficult to justify, contextual factors that enhance treatment response should be employed in the management of chronic painful conditions such as OA where available treatments have only modest efficacy.


Morphology and release of lysozyme following exposure of rabbit lung macrophages to nickel or cadmium in vitro.
Lung macrophages lavaged from 7 rabbits were incubated with 0, 3, 6, 12 and 24 micrograms/ml of nickel as NiCl2 and macrophages from 4 rabbits were incubated with 0, 0.1, 1, 3 and 6 micrograms/ml of cadmium as CdCl2. After 2 days lysozyme activity in the medium in which the macrophages were cultivated, was estimated using a technique with agar plates prepared with heat-killed Micrococcus lysodeikticus. Macrophage morphology was examined by scanning and transmission electron microscopy. For nickel there was a dose-related inverse relationship between the lysozyme activity and concentration of nickel. Many macrophages exposed to the higher nickel concentrations had a rounded form and, thus, the surface area of each cell which came in contact with the glass appeared to be less than that for control macrophages. There was, however, no increase in the number of macrophages detached from their glass support. Cadmium exposure did not influence lysozyme levels of activity, in spite of morphological indications of cell toxicity. From the present study we conclude that the decreased lysozyme activity seen previously in vivo after nickel inhalation is likely to be due to a direct effect of nickel ions on macrophages and that the increased lysozyme activity seen in vivo after cadmium inhalation is probably a secondary effect, subsequent to inflammation.


The relationship between pharmacists' tenure in community setting and moral reasoning.
To explore the relationship between pharmacists' tenure in the community setting and their moral reasoning abilities. Systematic random sample design. A large southeastern city in the United States. 450 independent and chain community pharmacists identified from the state board of pharmacy list of licensed community pharmacists. A mailed questionnaire that included a well-known moral reasoning instrument and collected demographic information. Moral Reasoning abilities and tenure of community pharmacists. As a group, community pharmacists with greater years of tenure in community practice scored significantly lower on moral reasoning than those pharmacists with fewer years of tenure (p=0.016). Four plausible explanations for the results are given including: a) a selection of lower ethical reasoners and/or an exodus of higher ethical reasoners from the community setting; b) a retrogression in the moral reasoning skills as community pharmacists obtain tenure in this setting; c) differences between the low and high moral reasoning groups may be due to a cohort effect; and d) the obtained practitioner sample may not have been representative of the population of community pharmacists.


Cloning and expression of the gene encoding Lactobacillus casei folylpoly-gamma-glutamate synthetase in Escherichia coli and determination of its primary structure.
A genomic library of Lactobacillus casei DNA containing 10,000 individual clones was constructed in the plasmid pUC13. The gene encoding the L. casei folylpolyglutamate synthetase was isolated from the library by complementation of a folC mutant of Escherichia coli. The gene was expressed in E. coli from its own promoter and produced amplified folylpolyglutamate synthetase activity with properties identical with those of the purified L. casei enzyme. The absence of dihydrofolate synthetase activity and the preferential utilization of 5,10-methylenetetrahydrofolate, rather than 10-formyltetrahydrofolate as folate substrate, distinguishes this activity from the E. coli folylpolyglutamate synthetase-dihydrofolate synthetase. A protein of Mr = 43,000, identical with that of purified L. casei folylpolyglutamate synthetase, was expressed in maxicells containing the complementing plasmid. The nucleotide sequence of the folylpolyglutamate synthetase gene was determined. An open reading frame of 1,284 bases was found predicting a protein product of 428 amino acids with Mr = 44,169. The predicted amino acid sequence of the gene is 33% homologous to that of the E. coli folylpolyglutamate synthetase. Primer extension studies indicate that the transcription initiation site is at -59 base pairs, relative to the initiation ATG codon of the folylpolyglutamate synthetase gene, suggesting that the gene is transcribed independently of upstream genes. A second open reading frame was found downstream of the folylpolyglutamate synthetase open reading frame, overlapping the final codon by 1 base pair. This downstream gene may be co-transcribed with the folylpolyglutamate synthetase gene.


Lifelong moderate running training increases the incidence and severity of osteoarthritis in the knee joint of C57BL mice.
Inbred C57BL male mice express a high incidence of spontaneous osteoarthritis of the knee joint at the age of 18 months. We used this strain of mice to find out the effects of life-long, moderate running exercise on the health of articular cartilage and the incidence of osteoarthritis. Male mice (294) were divided into controls and runners. The runners were trained daily between 2 and 18 months of age. The speed was 13.3 m/min and the distance on a flatbelt treadmill was 1,000 m/day. The mice were sacrificed at the ages of 2, 6, 10, 14, and 18 months. The knee joints were sectioned in frontal direction and the osteoarthritic changes were graded using a conventional light microscope. The reproducibility of the grading method was tested by calculating the extended kappa-coefficient for the results of six researchers. The incidence of osteoarthritis at the age of 18 months increased from 72% in controls to 88% in runners in the medial tibial condyles (P < 0.05), and from 80 to 96% in the lateral tibial condyles (P < 0.001). The incidence of the most severe osteoarthritic changes rose from 16% in controls to 36% in runners in the medial tibial condyles, and from 4 to 36% in the lateral tibial condyles. According to our results, the moderate, long-lasting running exercise accelerates the development of osteoarthritis in the knee joints of C57BL mice.


C-terminal fragment of amyloid precursor protein inhibits calcium uptake into rat brain microsomes by Mg2+-Ca2+ ATPase.
Numerous lines of evidence suggest that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid beta peptide (A beta). However, the possible role of other cleaved products of APP is less clear. In this study, the effects of a recombinant carboxy terminal 105 amino acid (CT105) fragment of APP on the calcium uptake by endoplasmic reticulum Mg2+-Ca2+ ATPase, the major mechanism for sequestering calcium in this organelle, were investigated. We found that CT 105 is a potent inhibitor of Mg2+-Ca2+ ATPase of endoplasmic reticulum, whereas A beta shows no effect. These results demonstrate that CT 105 inhibits the ability of brain microsomes to sequester calcium and suggest that this inhibitory effect of CT 105 may contribute to disruption of intracellular calcium concentration, possibly being involved in inducing the neural toxicity characteristic of AD.


Photochemotherapy in the treatment of psoriasis.
This article describes the satisfactory clinical improvement obtained in the majority of a group of 72 patients with psoriasis of various types as a result of the oral and/or topical administration of 8-methoxypsoralen followed by long wavelength ultraviolet irradiation. The irradiation source used was that of conventional longwave UV fluorescent tubes mounted in a specially constructed cubicle. Until such time as the long term effect of this form of photochemotherapy on the cell has been evaluated and the most appropriate regime worked out, it would seem to be important to restrict the amount of irradiation used to that required to produce acceptable maintained clinical improvement.


Implementation of an All-Day Artificial Intelligence-Based Triage System to Accelerate Door-to-Balloon Times.
To implement an all-day artificial intelligence (AI)-based system to facilitate chest pain triage in the emergency department. The AI-based triage system encompasses an AI model combining a convolutional neural network and long short-term memory to detect ST-elevation myocardial infarction (STEMI) on electrocardiography (ECG) and a clinical risk score (ASAP) to prioritize patients for ECG examination. The AI model was developed on 2907 twelve-lead ECGs: 882 STEMI and 2025 non-STEMI ECGs. Between November 1, 2019, and October 31, 2020, we enrolled 154 consecutive patients with STEMI: 68 during the AI-based triage period and 86 during the conventional triage period. The mean ± SD door-to-balloon (D2B) time was significantly shortened from 64.5±35.3 minutes to 53.2±12.7 minutes (P=.007), with 98.5% vs 87.2% (P=.009) of D2B times being less than 90 minutes in the AI group vs the conventional group. Among patients with an ASAP score of 3 or higher, the median door-to-ECG time decreased from 30 minutes (interquartile range [IQR], 7-59 minutes) to 6 minutes (IQR, 4-30 minutes) (P<.001). The overall performances of the AI model in identifying STEMI from 21,035 ECGs assessed by accuracy, precision, recall, area under the receiver operating characteristic curve, F1 score, and specificity were 0.997, 0.802, 0.977, 0.999, 0.881, and 0.998, respectively. Implementation of an all-day AI-based triage system significantly reduced the D2B time, with a corresponding increase in the percentage of D2B times less than 90 minutes in the emergency department. This system may help minimize preventable delays in D2B times for patients with STEMI undergoing primary percutaneous coronary intervention.


Relationship between preoperative symptoms and improvement of quality of life in patients undergoing elective inguinal herniorrhaphy.
Improvement of quality of life (QoL) is the ultimate goal for inguinal hernia repair. Data on QoL before surgery are scarce, and it is not known whether postoperative improvement of QoL relates to preoperative symptoms. Symptoms and self-reported QoL were evaluated and compared with matched control patients from a normal population in 309 male subjects before and 1 year after unilateral open inguinal hernia repair. Before operation, 91 % of patients noted a bulge, whereas 75% had symptoms, most commonly pain (64%); the other 25% were asymptomatic. Physical QoL scores (physical component score) were decreased in patients compared with matched controls (median [interquartile range] PCS 47 [38-53] vs 54 [48-57] P < .05), whereas mental scores (mental component score) were not affected (P = .401). PCS was less in patients with pain compared with those without pain (44 [35-50] vs 53 [48-56] P = .001). In patients without pain, no difference was found compared with control patients (P = .57). At 1 year after surgery, PCS was increased to 55 (53-57) in patients and was slightly greater than control patients (P < .05). The increase was greater in patients who reported preoperative pain (from 44 [35-50] to 55 [52-57] vs from 53 [48-56] to 56 [54-57], P < .00001). MCS did not change after inguinal herniorrhaphy. Preoperative affection as well as postoperative improvement in self-reported physical QoL seems to be strongly associated with preoperative inguinal pain. This finding underscores that occurrence of preoperative pain is an important symptom to evaluate before taking the decision to operate for inguinal hernia.


Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors.
We have previously demonstrated that pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were evaluated in in vitro assays, we observed that this nitrogen atom can be substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when we added a fluorescent dansyl group (compound 13), we were able to show that 13 penetrates the plasma membrane and enters the cytoplasm.


Genetic analysis suggests functional interactions between the N- and C-terminal domains of the TetA(C) efflux pump encoded by pBR322.
Genetic analysis of the tetA(C) gene of pBR322 indicates the importance of two-cytoplasmic loops in the TetA(C) protein (P. McNicholas, I. Chopra, and D. M. Rothstein, J. Bacteriol. 174:7926-7933, 1992). In this study, we characterized second-site suppressor mutations that suggest a functional interaction between these two cytoplasmic regions of the protein.


Reduction of eicosanoid production by essential fatty acid depletion does not attenuate the inflammatory response induced by Pseudomonas aeruginosa pneumonia in rat lung.
Sipid mediators of inflammation have been implicated in the pathogenesis of Pseudomonas aeruginosa (PA) related pulmonary damage in patients with cystic fibrosis. We studied the role of these mediators in a rat model of PA endobronchitis using essential fatty acid deficient (EFAD) animals. Whole blood from EFAD animals produced significantly less leukotriene B4 (LTB4) and hydroxyheptadecatrienoic acid when stimulated ex vivo than did whole blood from control animals (p less than 0.005). Similarly, lung lavage fluid from EFAD animals infected with PA contained less LTB4 and thromboxane B2 (TXB2) than that from control animals. Despite these differences, cellular infiltration of airways in response to PA infection was virtually identical in animals from the regular diet and the EFAD groups. Both EFAD and control animals had a significant increase in white blood cells (WBC) in lung lavage fluid at 1, 3 and 6 days following infection with PA when compared to animals receiving sterile beads. Localized areas of consolidation and nodularity were grossly evident in the lungs of all PA infected animals irrespective of their ability to generate the lipid inflammatory mediators. Microscopic examination of lung sections demonstrated similar changes in all infected animals. We conclude that LTB4 and TXB2 production occurs early in the course of PA pulmonary infection in rats. This early rise in lipid mediators is temporally associated with an influx of WBC into the airways. However, attenuation of eicosanoid production by use of an EFAD diet does not lead to a reduction in the inflammatory response to PA infection.(ABSTRACT TRUNCATED AT 250 WORDS)


Problems associated with the use of cycloheximide to distinguish between animal drug residues bound to protein and those incorporated into protein.
The user of cycloheximide to distinguish between covalently-bound drug residues in animals and residues due to the incorporation of drug fragments into endogenous molecules was explored. The results indicated that cycloheximide prevented the absorption of both glycine and ronidazole from the gastro-intestinal tract, an effect that complicates its use in the characterization of drug residues in animals.


High frequency stimulation alters motor maps, impairs skilled reaching performance and is accompanied by an upregulation of specific GABA, glutamate and NMDA receptor subunits.
High frequency stimulation (HFS) has the potential to interfere with learning and memory. HFS and motor skill training both lead to potentiation of the stimulated network and alter motor map expression. However, the extent to which HFS can interfere with the learning and performance of a skilled motor task and the resulting effect on the representation of movement has not been examined. Moreover, the molecular mechanisms associated with HFS and skilled motor training on the motor cortex are not known. We hypothesized that HFS would impair performance on a skilled reaching task, and would be associated with alterations in motor map expression and protein levels compared to non-stimulated and untrained controls. Long Evans Hooded rats were chronically implanted with stimulating and recording electrodes in the corpus callosum and frontal neocortex, respectively. High frequency theta burst stimulation or sham stimulation was applied once daily for 20 sessions. The rats were divided into five groups: control, HFS and assessed at 1 week post stimulation, HFS and assessed 3 weeks post stimulation, reach trained, and HFS and reach trained. A subset of rats from each group was assessed with either intracortical microstimulation (ICMS) to examine motor map expression or Western blot techniques to determine protein expression of several excitatory and inhibitory receptor subunits. Firstly, we found that HFS resulted in larger and reorganized motor maps, and lower movement thresholds compared to controls. This was associated with an up-regulation of the GABA(A)α1 and NR1 receptor subunits 3 weeks after the last stimulation session only. Stimulation affected skilled reaching performance in a subset of all stimulated rats. Rats that were poor performers had larger rostral forelimb areas, higher proximal and lower distal movement thresholds compared to rats that were good performers after stimulation. Reach training alone was associated with an up-regulation of GABA(A)α1, α2, GluR2, NR1 and NR2A compared to controls. HFS and reach-trained rats showed an up-regulation of GABA(A)α2 compared to stimulated rats that were not reach-trained. Therefore, we have shown that HFS induces significant plasticity in the motor cortex, and has the potential to disrupt performance on a skilled motor task.


Location of the SH group of the alkali light chain on the myosin head as revealed by electron microscopy.
The location of the single cysteinyl residue of the alkali light chain on the myosin head was determined by electron microscopy. The cysteinyl residue of isolated alkali light chain 2 was biotinylated and the light chain was exchanged with that of heavy meromyosin in 4.7 M-NH4Cl. Avidin was attached to the biotin in the heavy meromyosin and the complex was rotary shadowed and observed in the electron microscope. The distance from the head-rod junction to the centre of avidin was 8(+/- 3) nm (mean value +/- standard deviation: n = 105).