Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers.
Apocrine carcinomas comprise ∼1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2-based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonapocrine triple-negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for apocrine breast carcinoma. All pure apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty apocrine carcinomas were identified (∼0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for apocrine carcinomas and 56.7 years for NA-TNC. All apocrine carcinomas and no NA-TNC were AR positive. The proportions of apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired.


Occupational stress: risk assessment and fitness for work.
The multidimensional and multifaceted aspects of the problem render the role and activity of the Occupational Health Physician (OHP) extremely complex and delicate, as both appraisal and implications cover a number of different domains (psychology, physiology, sociology, economy, work organisation and law), both in terms of risk assessment and stress evaluation, at collective and individual level. In this context, it is not only important to quantify the "external" work load, but mainly the individual "response", which in most cases is the crucial factor of the imbalance. that is, risk assessment has to be made more in "relative" terms rather than according to "absolute" criteria, and not only from the perspective of medical surveillance, but above all from that of risk prevention. When a health disability potentially connected to stress has to be assessed, there are three steps: a) stress exposure must be clearly assessed, both directly and indirectly; b) disease must be clearly identified; c) the biological plausibility of the relationship between stress and disease must be carefully checked, taking into account that stress disorders are typically psychosomatic and multi-causal. Consequently, cooperation with a psychologist and an accurate psycho-diagnostic approach are necessary, as well as consultation with other specialists and pertinent laboratory and instrumental tests.


Exercise Prescription Practices to Improve Mental Health.
There is growing evidence that higher levels of physical activity are associated with better mental health. Furthermore, interventional studies have shown that exercise may improve symptoms in a number of psychiatric conditions. Despite this evidence, relatively little information is available about how these findings have been translated into clinical practice. The goal of this study was to characterize the exercise prescribing practices of health care providers from different subspecialties and evaluate factors that may influence their prescribing practices. We conducted a cross-sectional survey among faculty and staff from a large academic tertiary care medical center in the southeastern United States. Participants were invited to complete the survey via email or departmental newsletters. Descriptive statistics were used to characterize the sample and ordered logistic regression was used to analyze practices about exercise as a therapy for psychiatric illness. A total of 185 respondents completed the survey. More than half of the providers (58%) reported that they regularly recommend exercise as part of the treatment for patients with psychiatric conditions; however, few providers offered specific exercise instructions (24%) or followed national guidelines (30%). Depression (84.9%) and anxiety (69.2%) were the most common indications for exercise prescription, while insufficient knowledge or training was the most common barrier to prescribing exercise. We also found significant differences in prescription practices depending on the providers' formal clinical degree and their reported personal exercise habits. Exercise is recognized by most clinicians as a therapeutic option for psychiatric conditions. Despite this recognition, only a small proportion provide recommendations consistent with national guidelines or empirical research.


Knee and hip joint biomechanics are gender-specific in runners with high running mileage.
Female runners are reported to be more prone to develop specific knee joint injuries than males. It has been suggested that increased frontal plane joint loading might be related to the incidence of these knee injuries in running. The purpose of this study was to evaluate if frontal plane knee and hip joint kinematics and kinetics are gender-specific in runners with high mileage. 3D-kinematics and kinetics were recorded from 16 female and 16 male runners at a speed of 3 m/s, 4 m/s, and 5 m/s. Frontal plane joint angles and joint moments were ascertained and compared between genders among speed conditions. Across all speed conditions, females showed increased hip adduction and reduced knee adduction angles compared to males (p < 0.003). The initial peak in the hip adduction moment was enhanced in females (p = 0.003). Additionally, the hip adduction impulse showed a trend towards an increase in females at slow running speed (p = 0.07). Hip and knee frontal plane joint kinematics are gender-specific. In addition, there are indications that frontal plane joint loading is increased in female runners. Future research should focus on the relationship of these observations regarding overuse running injuries.


Radical scavenging and antimicrobial activities of Croton zehntneri, Pterodon emarginatus and Schinopsis brasiliensis essential oils and their major constituents: estragole, trans-anethole, β-caryophyllene and myrcene.
The essential oils (EOs) from the Brazilian species Croton zehntneri, Pterodon emarginatus and Schinopsis brasiliensis were examined for their chemical constituents, and antioxidant and antimicrobial activities. The composition of EOs was determined by using gas chromatography coupled with mass spectrometry analysis, while the antioxidant activity was evaluated through the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays. Furthermore, the antimicrobial activity was investigated against Escherichia coli and Pseudomonas aeruginosa (both Gram-negative), Staphylococcus aureus (Gram-positive) and Candida parapsilosis (fungus). The main components of C. zehntneri, P. emarginatus and S. brasiliensis were identified as estragole, trans-anethole, β-caryophyllene and myrcene. Among the EOs, P. emarginatus showed the highest antioxidant activity, with an IC50 of 7.36 mg/mL and a Trolox equivalent antioxidant capacity of 3748 μmol/g determined by DPPH and ORAC assays, respectively. All EOs showed low activities against the bacterial strains tested, whereas the C. zehntneri oil and its main constituent estragole exhibited an appreciable antifungal activity against C. parapsilosis.


The Gambia has eliminated trachoma as a public health problem: Challenges and successes.
Trachoma is the leading infectious cause of blindness in the world and has been known to be a major public health problem in The Gambia for over 60 years. Nationwide blindness surveys, including trachoma, in 1986 and 1996 provided the foundation for a comprehensive plan to implement a trachoma elimination strategy. Impact and pre-validation surveillance surveys in 2011-13 demonstrated that active trachoma was below WHO threshold for elimination but trichiasis remained a public health problem. Trichiasis-only surveys in 2019 demonstrated that trichiasis was below WHO thresholds for elimination and in 2020 the Government of The Gambia completed and submitted its dossier for validation of elimination as a public health problem. Challenges that The Gambia faced on the pathway to elimination included effective use of data for decision making, poor trichiasis surgical outcomes, lack of access to antibiotic treatment for low prevalence districts, high attrition of ophthalmic nurses trained as trichiasis surgeons, unexpected active trachoma in madrassas, the misalignment of elimination of active trachoma and trichiasis, trichiasis in urban settings, and maintaining the quality of surgery post-elimination when trichiasis cases are rare. Elimination of trachoma does not end with the submission of an elimination dossier; The Gambia will need to sustain monitoring and support over the coming years.


MHC class I presentation of live and heat-inactivated Sendai virus antigen in T2Kb cells depends on an intracellular compartment with endosomal characteristics.
T2Kb cells, which do not express TAP1/2 peptide transporters or the low molecular weight protein 2/7 (LMP2/7) proteasomal subunits, can still process and present both live and heat-inactivated Sendai virus (SV). As this operation may also reflect the existence of an alternative processing pathway in normal antigen-presenting cells (APC), the authors have characterized it using intracellular inhibitors and anti-Kb monoclonal antibodies (MoAbs). From the results with lipophilic amines (ammonium chloride, methylamine and chloroquine), cytoskeletal inhibitors (cytochalasin B and vinblastine), and an endoprotease inhibitor (phenylmethylsulfonyl fluoride, PMSF), the authors conclude that the processing of SV antigen in T2Kb cells has endosomal characteristics depending on cellular activities such as uptake, vesicular transport and intracellular-vesicular proteolysis. In addition, internalized 'empty' Kb molecules derived from the T2Kb cell surface appeared to be involved in the presentation of SV antigen, as demonstrated by a protocol using a combination of the Golgi inhibitor brefeldin A(BFA) and anti-Kb antibodies. The results thus indicate that T2Kb cells process SV antigen in an endosomal-like compartment which contain recycling 'empty' Kb molecules.


Animal models in systemic sclerosis.
Systemic sclerosis (SSc) is a complex systemic disease. It is characterised by fibrosis, of the skin and internal organs, as lungs, kidney, heart and gastrointestinal tract. As the aetiology of SSc is unknown, numerous animal models have been developed to better understand the pathogenesis of the disease and to test potentially useful therapeutic interventions. Although several animal models have been described, predominantly in mice, none reproduces precisely all manifestations of SSc. However, all animal models display tissue fibrotic changes similar to those present in SSc. This review is focused on the principal animal models and the molecular pathways involved. Animal models can be divided into two groups. In one group the pathologic phenotype is the result of a genetic mutation ( tight skin 1 and tight skin 2,UCD 200). In the second group, the pathologic alterations are induced in normal animals by manipulation of their immune system (sclerodermatous graft-vs-host disease (Scl GVHD) induced by transplantation, or by administration of exogenous substances). In the future, the development of additional animal models may become important in the further understanding of the alteration of the molecular pathways that regulate a physiologic processes to induce tissue fibrosis, the hallmark of this disease, and to identify and test targeted therapeutic agents.


Complexity of a small non-protein coding sequence in chromosomal region 22q11.2: presence of specialized DNA secondary structures and RNA exon/intron motifs.
DiGeorge Syndrome is a genetic abnormality involving ~3 Mb deletion in human chromosome 22, termed 22q.11.2. To better understand the non-coding regions of 22q.11.2, a small 10,000 bp non-protein-coding sequence close to the DiGeorge Critical Region 6 gene (DGCR6) was chosen for analysis and functional entities as the homologous sequence in the chimpanzee genome could be aligned and used for comparisons. The GenBank database provided genomic sequences. In silico computer programs were used to find homologous DNA sequences in human and chimpanzee genomes, generate random sequences, determine DNA sequence alignments, sequence comparisons and nucleotide repeat copies, and to predicted DNA secondary structures. At its 5' half, the 10,000 bp sequence has three distinct sections that represent phylogenetically variable sequences. These Variable Regions contain biased mutations with a very high A + T content, multiple copies of the motif TATAATATA and sequences that fold into long A:T-base-paired stem loops. The 3' half of the 10,000 bp unit, highly conserved between human and chimpanzee, has sequences representing exons of lncRNA genes and segments of introns of protein genes. Central to the 10,000 bp unit are the multiple copies of a sequence that originates from the flanking 5' end of the translocation breakpoint Type A sequence. This breakpoint flanking sequence carries the exon and intron motifs. The breakpoint Type A sequence seems to be a major player in the proliferation of these RNA motifs, as well as the proliferation of Variable Regions in the 10,000 bp segment and other regions within 22q.11.2. The data indicate that a non-coding region of the chromosome may be reserved for highly biased mutations that lead to formation of specialized sequences and DNA secondary structures. On the other hand, the highly conserved nucleotide sequence of the non-coding region may form storage sites for RNA motifs.


Increased serum soluble interleukin 2 receptor levels in patients with viral liver diseases.
Soluble interleukin 2 receptors (sIL 2R) in the sera of patients with viral liver diseases were quantified with a solid-phase enzyme immunoassay using two monoclonal antibodies against the receptors. The sIL 2R levels in patients with acute hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were significantly higher than those in control subjects. In acute hepatitis patients, the high levels of sIL 2R observed during the florid stage returned to normal during remission. Levels in patients with chronic active hepatitis were significantly higher than in those with chronic persistent and lobular hepatitis, and levels observed during the exacerbation phase of chronic hepatitis were higher than they were during remission. Thus, in chronic hepatitis, sIL 2R levels increased in proportion to the inflammatory activity, and correlated well with serum transaminase (glutamic oxaloacetic transaminase: SGOT, glutamic pyruvic transaminase: SGPT) activities, but not with blood urea nitrogen or creatinine concentrations. In patients with a high degree of focal and piecemeal necrosis, serum sIL 2R levels increased further during recombinant interleukin 2 therapy. In post-hepatitic liver cirrhosis and hepatocellular carcinoma, sIL 2R levels correlated with serum cholinesterase and creatinine concentrations, but not with transaminase activities. Measurement of serum sIL 2R levels in patients with liver disease but without renal injury, may help in the diagnosis of inflammation in hepatitis, a process in which interleukin 2 may participate.


Electrochemical study of 3-(N-alkylamino)thiophenes: experimental and theoretical insights into a unique mechanism of oxidative polymerization.
A number of conjugated polymer systems can be generated via electropolymerization, including polythiophenes and polyanilines. While both have been reported to polymerize anodically via radical coupling, the presence of the aniline nitrogen plays a significant role in the mechanism of electropolymerization. In this study, the electropolymerization mechanism of 3-(N-alkylamino)thiophenes, structural hybrids of thiophene and aniline, is studied utilizing experimental and theoretical methods. Synthesis of new short chain 3-(N-alkylamino)thiophenes is discussed, and a mechanism of electropolymerization is proposed whereby oxidation occurs through removal of a nitrogen lone pair electron, followed by a chemical step resulting in radical contribution at the 2-position of the thiophene ring. Coupling of these final radical cations thus results in a typical poly(alpha-alpha'-thiophene) backbone.


High glycated hemoglobin levels and intracranial artery stenosis are predictive factors for early motor worsening events in patients with penetrating artery infarction.
The purpose of this study was to identify typical clinical characteristics to predict early motor worsening (EMW) of patients with penetrating artery infarction. We reviewed 65 consecutive patients with pure motor hemiparesis, sensorimotor stroke, and ataxic hemiparesis. EMW was defined as deterioration by ≥1 point on the National Institutes of Health Stroke Scale for motor function within 5 days of admission. EMW was observed in 22 patients (34%). HbA1c levels were higher in patients with EMW than in those without EMW (7.9 ± 2.6 vs. 6.3 ± 1.6%; p < 0.01). The percentage of EMW patients with intracranial artery stenosis (ICAS) was greater than that of non-EMW patients with ICAS (13/22 patients, 59% vs. 8/43 patients, 19%; p < 0.01). Multivariate logistic regression analysis indicated that HbA1c levels ≥7.0% (OR 3.0, 95% CI 1.5-6.8; p < 0.005) or ICAS (OR 2.3, 95% CI 1.2-4.8; p < 0.05) increased the risk of EMW, and the combination of these factors increased the risk in an additive manner (OR 7.6, 95% CI 2.5-40; p < 0.005). HbA1c levels ≥7.0% and/or ICAS in patients with penetrating artery infarction are associated with EMW.


Cyclic adenosine 3',5'-monophosphate regulates GLUT4 and GLUT1 glucose transporter expression and stimulates transcriptional activity of the GLUT1 promoter in muscle cells.
We have previously reported that innervation-dependent basal contractile activity regulates in an inverse manner the expression of GLUT1 and GLUT4 glucose transporters in skeletal muscle. Based on the facts that muscle innervation decreases and muscle denervation increases cAMP levels, we investigated whether cAMP might mediate the effects of innervation/denervation on glucose transporter expression. Treatment of L6E9 myotubes with 8-bromo-cAMP, forskolin, or monobutyryl-8-bromo-cAMP led to a marked decrease in GLUT4 protein levels; 8-bromo-cAMP also diminished GLUT4 messenger RNA (mRNA), suggesting pretranslational repression. In contrast, L6E9 myoblasts and myotubes responded to 8-bromo-cAMP or forskolin by increasing the cell content of GLUT1 protein. Induction of GLUT1 protein was a consequence of the activation of different mechanisms in myoblast and myotube cells; whereas 8-bromo-cAMP treatment caused a substantial increase in GLUT1 mRNA in myoblasts, no change in GLUT1 mRNA was detected in myotubes. The increase in GLUT1 mRNA in L6E9 myoblasts induced by 8-bromo-cAMP was the result of transcriptional activation, as concluded from transfection analysis of 2.1 kilobases of the rat GLUT1 gene promoter fused to the bacterial chloramphenicol acetyltransferase gene. Furthermore, the stimulatory effect of 8-bromo-cAMP on the transcriptional activity of the GLUT1 promoter required a 33-bp sequence lying 5' upstream of the transcription start site. In all, cAMP inversely regulates GLUT4 and GLUT1 glucose transporter expression in muscle cells. Furthermore, our results suggest that down-regulation of GLUT4 expression and up-regulation of GLUT1 expression in muscle associated with denervation are partly attributable to cAMP.


Cognitive deterioration in patients with early multiple sclerosis: a 5-year study.
The objective was to investigate changes in cognitive functioning in subjects with early multiple sclerosis (MS) over 5 years. Methodological issues associated with longitudinal cognitive research such as practice effects and drop-outs were also examined. Ninety subjects with a diagnosis of clinically isolated syndrome or MS and disease duration from a first symptom of ≤ 6 years participated in the study. Subjects were administered the Brief Repeatable Battery of Neuropsychological Tests in MS, which includes five measures assessing four cognitive domains. As a means of stabilising practice effects, the battery was administered 1-2 weeks apart at enrollment and then annually for up to 5 years. Significant deterioration was found on a measure of working memory and speed of information processing. Significant deterioration was also found on measures of immediate and delayed visual spatial memory. Verbal memory was unchanged over the course of the study. Improved performance was observed on a second measure of speed of information processing and on a measure of verbal fluency. Among subjects with longitudinal follow-up, the drop-out rate was 30%, but subjects who dropped out did not differ from those who completed the study in terms of baseline cognitive performance or the change in cognitive performance from year 1 to year 2. Subjects with early MS showed a deterioration in working memory and visual spatial memory over a period of up to 5 years. Although significant practice effects were associated with several cognitive measures, the Symbol Digit Modality Test may be useful for longitudinal evaluations of cognitive functioning in MS.


Antimicrobial resistance in bacteria isolated from mastitis in dairy cattle in France, 2006-2016.
In dairy cattle, mastitis is the most frequent bacterial disease, and the routine use of antibiotics for treatment and prevention can drive antimicrobial resistance (AMR). The aim of our study was to estimate the levels of AMR of the 3 main bacteria isolated from dairy cattle with mastitis in France (Streptococcus uberis, Escherichia coli, and coagulase-positive staphylococci) and to investigate their changes over time. Data collected between 2006 and 2016 by the French surveillance network for AMR in pathogenic bacteria of animal origin (called RESAPATH) were analyzed. The proportions of mono- and multidrug resistance were calculated and the trends were investigated using nonlinear analyses applied to time series. Over the whole period, the lowest proportions of resistance in S. uberis isolates were observed for oxacillin (2.2%) and gentamicin (2.4%) and most resistance levels were below 20%. The trends in resistance showed some significant variation, mainly for S. uberis, but without a common pattern across the various antibiotics examined. For only 2 combinations of bacteria-antibiotic the trend in resistance showed a continuous increase from 2006 to 2016: tetracycline resistance in S. uberis isolates and third-generation cephalosporin resistance in E. coli isolates. In E. coli, the highest proportions of resistance were observed for amoxicillin (28.1%) and tetracycline (23.1%). Resistance to third-generation cephalosporins in E. coli from dairy cattle was almost nil in 2006, but reached 2.4% in December 2016. This increase is particularly concerning because these antibiotics constitute one of the latest therapeutic alternatives to fight severe infectious diseases in humans. Except for penicillin (33.9%), the proportions of resistance in coagulase-positive staphylococci were below 11% during the whole study period. Multidrug resistance (isolates with acquired resistance to at least one antibiotic in 3 or more antibiotic classes) ranged from 2.4% for coagulase-positive staphylococci to 9.9% for S. uberis. These findings can serve as guidelines for practitioners in the choice of the most appropriate antibiotic according to the prevailing epidemiological context. Ultimately, our results contribute to risk assessment of AMR and provide a baseline for setting up and evaluating control measures and designing strategies to limit AMR.


Using propensity score-based weighting in the evaluation of health management programme effectiveness.
When the randomized controlled trial is unfeasible, programme evaluators attempt to emulate the randomization process in observational studies by creating a control group that is essentially equivalent to the treatment group on known characteristics and trust that the remaining unknown characteristics are inconsequential and will not bias the results. In recent years, adjustment procedures based on the propensity score, such as matching and subclassification, have become increasingly popular. A new technique that has particular appeal for evaluating health management programmes uses the propensity score to create a weight based on the subject's inverse probability of receiving treatment. This weighting mechanism removes imbalances of pre-intervention characteristics between treated and non-treated individuals, and is then used within a regression framework to provide unbiased estimates of treatment effects. This paper presents a non-technical introduction of this technique by illustrating its implementation with data from a recent study estimating the impact of a motivational interviewing-based health coaching on patient activation measure scores in a chronically ill group of individuals. Because of its relative simplicity and tremendous utility, propensity-score weighting adjustment should be considered as an alternative procedure for use with observational data to evaluate health management programme effectiveness.


Precision of a new ocular biometer in children and comparison with IOLMaster.
To assess the repeatability and reproducibility of AL-Scan in agreement with those by the IOLMaster in healthy children, two skilled operators measured ocular parameters in 58 children. The parameters included keratometry (K) values, anterior chamber depth (ACD), axial length (AL), central corneal thickness (CCT), pupil diameter (PD), and corneal diameter (CD). The cohort comprised of 32 boys and 26 girls. The AL-Scan measurements showed high repeatability, as the test-retest repeatability (TRT) values of AL, CCT, ACD, Kf, Ks, Km, CD, and PD were 0.09 mm, 5.1 μm, 0.04 mm, 0.28 D, 0.24 D, 0.21 D, 0.39 mm, and 0.22 mm, respectively. The within-subject coefficient of variation (CoV) was low (<0.35%) and the intraclass correlation coefficients (ICC) of all parameters were >0.85. The interobserver reproducibility was excellent with low values of TRT and ICC > 0.95. The CoV of AL, CCT, ACD, and K was <0.22%. The 95% limits of agreement between the AL-Scan and the IOLMaster were narrow for all parameters except for CD. The repeatability and reproducibility of the new biometer, Al-Scan, was excellent for all parameters and can be routinely used in children to measure the biometric values.


Transcriptome analysis uncovers Arabidopsis F-BOX STRESS INDUCED 1 as a regulator of jasmonic acid and abscisic acid stress gene expression.
The ubiquitin 26S proteasome system (UPS) selectively degrades cellular proteins, which results in physiological changes to eukaryotic cells. F-box proteins are substrate adaptors within the UPS and are responsible for the diversity of potential protein targets. Plant genomes are enriched in F-box genes, but the vast majority of these have unknown roles. This work investigated the Arabidopsis F-box gene F-BOX STRESS INDUCED 1 (FBS1) for its effects on gene expression in order elucidate its previously unknown biological function. Using publically available Affymetrix ATH1 microarray data, we show that FBS1 is significantly co-expressed in abiotic stresses with other well-characterized stress response genes, including important stress-related transcriptional regulators. This gene suite is most highly expressed in roots under cold and salt stresses. Transcriptome analysis of fbs1-1 knock-out plants grown at a chilling temperature shows that hundreds of genes require FBS1 for appropriate expression, and that these genes are enriched in those having roles in both abiotic and biotic stress responses. Based on both this genome-wide expression data set and quantitative real-time PCR (qPCR) analysis, it is apparent that FBS1 is required for elevated expression of many jasmonic acid (JA) genes that have established roles in combatting environmental stresses, and that it also controls a subset of JA biosynthesis genes. FBS1 also significantly impacts abscisic acid (ABA) regulated genes, but this interaction is more complex, as FBS1 has both positive and negative effects on ABA-inducible and ABA-repressible gene modules. One noteworthy effect of FBS1 on ABA-related stress processes, however, is the restraint it imposes on the expression of multiple class I LIPID TRANSFER PROTEIN (LTP) gene family members that have demonstrated protective effects in water deficit-related stresses. FBS1 impacts plant stress responses by regulating hundreds of genes that respond to the plant stress hormones JA and ABA. The positive effect that FBS1 has on JA processes and the negative effect it has on at least some ABA processes indicates that it in part regulates cellular responses balanced between these two important stress hormones. More broadly then, FBS1 may aid plant cells in switching between certain biotic (JA) and abiotic (ABA) stress responses. Finally, because FBS1 regulates a subset of JA biosynthesis and response genes, we conclude that it might have a role in tuning hormone responses to particular circumstances at the transcriptional level.


Psychometric evaluation of the modified 19-item Bengali version of WHOQOL scale using Rasch analysis: a cross-sectional study of a rural district in Bangladesh.
This investigation aims to validate the psychometric properties of the modified 19-item Bengali version World Health Organization Quality of Life (WHOQOL) instrument in a typical healthy rural population in Bangladesh. The cross-sectional investigation collected 300 adults aged 18-85 years from Narail, a rural district of Bangladesh using a multi-stage cluster random sampling technique. Face-to-face interviews were conducted between July and August 2018 using an Android phone installed with a mobile data collection application CommCare. SPSS version 25; IBM. and a Rasch analysis software RUMM2030 were used for analyses. Results showed good overall fit, as indicated by a significant item-trait interaction with Bonferroni corrected p values, for physical ([Formula: see text] =32.13, p = 0.041), psychological ([Formula: see text] =14.93, p = 0.529), social ([Formula: see text] =12.62, p = 0.397), and environmental ([Formula: see text] =22.01, p = 0.339) domains. Item fit residual (IFR) values for all domains were within the desired limits, indicating no deviation from the expected relationship between the individual items and the rest of the items of the scale. Person fit residual (PFR) values also showed no person misfit among the samples, indicating item threshold are suitable for Rasch analysis. Reliability of the three domains of the 19-item WHOQOL scale was very good as indicated by a person separation index (PSI) = 0.873 and Cronbach's Alpha (CA) = 0.881 for physical domain, PSI = 0.739 and CA = 0.746 for psychological domain, and PSI = 0.753 and CA = 0.781 for environmental domain. The social domain (PSI = 0.650 and CA = 0.669) had below acceptable reliability. All items in each domain had ordered thresholds except one item of the environmental domain. All four domains of the 19-item WHOQOL scale showed unidimensionality and was free from local dependency. Each domain also showed similar functioning for adults and older adults, males and females, no education and at least primary level of education, low and high socio-economic conditions. The 19-item modified WHOQOL scale is confirmed as an efficient screening tool for measuring QoL among healthy rural Bangladeshi people. The scale could be implemented more widely. In particular, validations are required for diseases-specific population in Bangladesh to measure the Health Related Quality of life (HR-QoL) assessments for people suffering from chronic or other diseases.


Monte Carlo docking of protein-DNA complexes: incorporation of DNA flexibility and experimental data.
A Monte Carlo simulation program (MONTY) has been developed to dock proteins onto DNA. Protein and DNA interact via square-well potentials for hydrogen bond and van der Waals interactions. The effect of the inclusion of DNA flexibility and experimentally derived restraints has been tested on members of the helix-turn-helix family of DNA binding proteins. Unwinding and bending the DNA double helix improves the number of correctly retrieved hydrogen bonds in simulations starting from the 434 cro protein monomer complexed with a standard B-DNA OR1 half-site. Agreement with phosphate ethylation interference and mutagenesis data is rewarded with energy bonuses. This protocol was tested on protein-DNA complexes of 434 cro, lac headpiece and a mutant lac headpiece resembling the gal repressor headpiece with the recognition helices in correct and reversed orientations in the DNA major groove. The inclusion of experimental data gives an improved convergence of the correctly oriented structures and allows for an easier discrimination between correctly and incorrectly docked complexes.


Heterogeneity in lymphokine profiles of CD4+ and CD8+ T cells and clones activated in vivo and in vitro.
Analysis of lymphokine mRNA expression and protein secretion by about 100 short-term alloreactive T-cell clones revealed marked heterogeneity in the combinations of lymphokines synthesized. This finding argues against a simple model in which T cells express either an unrestricted (Th0) or a restricted (Th1 or Th2) lymphokine profile. Lymphokine titers appeared to be normally distributed, with the percentage of positive clones for any one product determined by the threshold of detection. Accordingly, the observation that CD4+ clones on average produced higher titers of most lymphokines than CD8+ clones indicated that apparent differences between the lymphokine profiles of these two subsets were quantitative rather than qualitative. Patterns of lymphokine gene expression detected in whole tissues or by analysis of single cells and clones were markedly influenced by in vivo priming. Relative levels of expression of IL-4, IFN-gamma and GM-CSF in lymphoid tissues differed in mice undergoing a GvHR or following contact sensitization with OX or immunization with KLH in adjuvant. Consistent with the finding that IL-4 was the major lymphokine mRNA detected in lymph nodes of KLH-primed mice, most short-term KLH-specific clones derived from such mice also expressed IL-4. A similar approach to the detection of lymphokine-secreting T-cell precursors activated late in L. major infection showed that most clones from the L. major-resistant strain, C57BL/6, secreted IFN-gamma without IL-4 whereas most clones from the susceptible strain, BALB/c, secreted IL-4 without IFN-gamma. Differences were also noted in anti-CD3-induced IL-3 production at the single-cell level between CD8+ cells activated in the GvHR or against a tumor allograft. Con A-induced, filler cell-dependent cloning of CD4+ T cells from unprimed mice gave rise both to IFN-gamma-producing and to IL-4-producing clones. A requirement for an undefined, filler cell-dependent signal for development of IL-4-secreting clones was suggested by the finding that clones of normal CD4+ and CD8+ T cells activated in an anti-CD3-induced, filler cell-free system exclusively produced IFN-gamma and IL-3 without detectable IL-4 or IL-6. With a view to developing a single-cell approach to the analysis of lymphokine profiles of in vivo-activated T cells, sensitive assays for IL-3 and other lymphokines were used to measure secreting cells activated in the GvHR or against a tumor allograft.(ABSTRACT TRUNCATED AT 400 WORDS)


Rational design of potent and selective NH-linked aryl/heteroaryl cathepsin K inhibitors.
Prior reports from our laboratories have identified the nonpeptidic inhibitor 2 as a potent and selective Cathepsin K (Cat K) inhibitor. Modelling studies suggested that the introduction of a NH linker between the P3 aryl and P2 leucinamide moieties would allow the formation of a H-bond with the Gly66 residue of Cat K, hopefully increasing potency. Aniline 4 was thus synthesized and showed improved potency over its predecessor 2. Further modelling concluded that a 2-substituted five membered ring could more adequately place the P3 moiety of 4 into the S3 pocket of Cat K. The synthesis of the 2-substituted thiophene 5 confirmed this hypothesis by displaying a slight increase in potency against Cat K (>10-fold increase in potency vs 2) and a good selectivity profile against Cathepsins B, L, and S. This rationally designed inhibitor 5 also displayed increased potency in a functional bone resorption assay (10nM) versus 2 (95 nM).


[From the study of biochemical changes in ischemic and reperfused skeletal muscle to the controlled reperfusion of limbs in patients with acute severe ischemia].
The reperfusion of a limb which has been submitted to a severe and prolonged period of ischemia may be followed by dramatic local and systemic complications. The results of several experimental studies have given insights on the biochemical and physiopathological alterations occurring in the ischemic and reperfused skeletal muscle. Therefore the technique of the controlled limb reperfusion has been developed. we present the results obtained in two patients with this technique. Two patients were admitted for a limb-threatening ischemia consecutive to embolism. After removal of the thrombi with a Fogarty's catheter and before reperfusion with the normal blood, a controlled limb reperfusion was performed by mixing the systemic blood with a crystalloid solution in order to obtain a hyperosmolar, hypocalcemic, alcalotic and substrate-enriched (aspartate and glutamate) reperfusate. This reperfusate was infused during 30 min with a roller pump into the deep and superficial femoral arteries. The delivery conditions (temperature, flow and reinjection pressure) were closely monitored. In both cases, no post-operative complication was observed and the pedal pulses were restored after the operation. Complete recovery of the motor and sensitive functions were observed and the patient were discharged at the 10th post-operative day.


[Inulicin inhibits activation and expression of vascular remodeling enzymes induced by de-endothelium].
To observe the effects of inulicin on the neointimal hyperplasia and expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) after balloon injury in rat aorta. The intimal hyperplasia model was replicated by balloon injury. The histological changes in vascular wall were observed by HE staining. MMP-2 activation was tested by gelatin zymogram analysis; MMP-2 and TIMP-2 expression was detected by Western blot and immunohistochemistry analysis. Neointimal hyperplasia induced by balloon injury was significantly inhibited by inulicin. The proteolytic activity and the expression of MMP-2 and ratio of MMP-2 and TIMP-2 were also returned to control level by inulicin after balloon injury. Inulicin inhibits hyperplasia of neointima by modulating the balance of MMP-2 and TIMP-2.


Medication for psychosis--consumption and consequences: the second Australian national survey of psychosis.
Most people diagnosed with a psychotic disorder will be prescribed psychotropic medication. The second Australian national survey of psychosis provided a unique opportunity to examine the pharmacological treatment of psychotic disorders from the perspective of the consumer. The aim of this paper is to report on medication use, adherence and perceived efficacy, and to describe side effect profiles. Data on self-reported medication use in the 4 weeks prior to interview, including type, duration, adherence, side effects and helpfulness was collected from participants interviewed in the course of the second Australian national survey of psychosis. The majority (91.6%) of participants were using psychotropic medication: 89.0% of people aged 18-34 years and 93.5% of people aged 35-64 years. The most commonly used class of medication was antipsychotic medication (81.6%). In addition, 37.4% were using antidepressants, 26.7% were using mood stabilisers and 17.8% were using anxiolytics/hypnotics. Polypharmacy was common with almost two-thirds (63.4%) using more than one class of medication and over a quarter (28.1%) of people with schizophrenia using more than one antipsychotic. Many participants (84.4%) reported experiencing side effects. The side effect profile of people using atypical antipsychotics was on average better than that of people using typical antipsychotics. Most people (85.2%) felt their medication relieved their mental health symptoms and most (88.2%) medication was taken as prescribed. Many people with a psychotic disorder are receiving antipsychotics, with a substantial proportion also taking antidepressants, mood stabilisers and anxiolytics/hypnotics. Medication use differs by age group, diagnostic group and course of illness. Many people using antipsychotics describe significant impairment in their everyday life as a result of medication side effects. Users of typical antipsychotics reported more side effects and more impairment than people using atypical antipsychotics. Most of our participants were prescribed psychotropic medications, and most reported that they were taking them.


Müllerianosis of the urinary bladder: report of three new cases.
We report three new cases of müllerianosis of the urinary bladder. We present three cases of women in the third decade of life, two of them presenting hematuria and pelvic pain, and the third was referred to perform a recto-vaginal endometriosis surgical procedure. Diagnosis was made by ultrasound and cystoscopy in the first and second case, and by CT scan in the endometriosis case. Müllerianosis of the urinary bladder is described as the presence of müllerian remnants (endometrial, endosalpinx and endocervix) in the bladder wall. Diagnosis is made as a result of a pathologic study of the resected lesions. Although a relapse of the disease is infrequent, it can happen, and close monitoring of the patients must be performed. Müllerianosis of the bladder is a rare condition and differential diagnosis must be done with benign and malignant bladder lesions because it can affect the muscularis propia. It mostly presents as lower urinary tract symptoms and hematuria that can be cyclic. Transurethral resection is the treatment of choice in superficial and focal lesions. In the case of infiltration of the bladder muscle, and depending on the extension of the disease, partial cystectomy may be necessary.


Elimination of a Postoperative Brace Does Not Increase Complications Following Hip Arthroscopy.
Background The practice of routine postoperative bracing to limit abduction and internal rotation, along with weight-bearing restrictions after hip arthroscopy (HA), varies significantly among surgeons. It is unclear whether the use of a postoperative brace improves short-term outcomes in patients undergoing HA. The purpose of this study was to determine the differences in patient outcomes before and after eliminating routine usage of a postoperative brace. Methods A retrospective review was conducted of 176 adult patients undergoing HA by a single, high-volume surgeon. The no-brace protocol was implemented in October 2020. The patients were divided into two groups: pre-implementation (January-October 2020) and post-implementation (October 2020-April 2021). Twenty-three patients that used a brace during the post-implementation period were excluded. All patients had weight-bearing restrictions with crutches for three weeks postoperatively. The primary endpoint was any complication in the first six weeks postoperatively. Results There were no significant differences in demographics between groups, although the body mass index in the brace group was higher (28.1 vs. 26.4 kg/m2, p = 0.066) and the rate of additional procedures performed was higher in the brace group (55.2% vs. 40.1%, p = 0.056). There was no significant difference in postoperative outcomes between groups when looking at 90-day emergency department visits (1.7% vs. 0%, p = 0.548), complications at two (1.7% vs. 1.7%, p = 1.000) and six weeks (0% vs. 1.7%, p = 0.341) postoperatively, all complications in the first six weeks (1.7% vs. 1.7%, p = 1.000), and continued pain at six weeks (10.3% vs. 16.7%, p = 0.238). Conclusion The brace and no-brace groups were similar demographically. Patients undergoing HA with no brace and crutches experienced no significant differences in pain or complications in comparison to those receiving a traditional bracing protocol. Routine use of a postoperative brace may not be necessary in this population.


Expansion of natural killer cells in peripheral blood in a Japanese elderly with human T-cell lymphotropic virus type 1-related skin lesions.
Natural killer (NK) cells were proposed to play an important role in the pathogenesis of human T-cell lymphotropic virus type 1- (HTLV-1-) associated neurologic disease. Our patient was a 77-year-old Japanese man, who had been treated for infective dermatitis associated with HTLV-1 for nearly 10 years. When referred to us, he had facial eczema/edema as well as extensive dermatitis at the neck/upper chest and nuchal area/upper back regions. Dermal lesions had CD3+CD4+ cells, but no NK cells. Flow cytometry of his peripheral blood showed a phenotype of CD2+ (97%), CD3+ (17%), CD4+ (12%), CD7+ (94%), CD8+ (6%), CD11c+ (70%), CD16+ (82%), CD19+ (0%), CD20+ (0%), CD56+ (67%), HLA-DR+ (68%), and NKp46+ (36%). Absolute numbers of CD56+NK cells in the peripheral blood were in a range of 986/μL-1,270/μL. The expanded NK cells in the peripheral blood are considered to be reactive, to maintain the confinement of the HTLV-1-positive CD4+ cells in the skin, and to prevent the progression of the disease.


Advances in therapeutic CRISPR/Cas9 genome editing.
Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. The tremendous success of the CRISPR/Cas9 genome editing tool is powered by the ease design principle of the guide RNA that targets Cas9 to the desired DNA locus, and by the high specificity and efficiency of CRISPR/Cas9-generated DNA breaks. Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in vivo in animal models and ex vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports.


A study on related factors of hardcore smokers.
This study attempted to provide basic data for future smoking cessation policies and anti-smoking programs by analyzing related factors of hardcore smokers. This study is a cross-sectional, descriptive survey of the 2019 Community Health Survey conducted by the Korean Ministry of Health and Welfare. There were 11,817 smokers, and the propensity matching method was used based on factors related to hardcore smokers in previous studies. Consequently, a higher probability to be included as hardcore smokers was observed in subjects who had a higher level of stress perception (odds ratio [OR] = 17.59, 95% CI [10.18, 30.38]), perceived their body shape as chubby (OR = 12.84, 95% CI [8.39, 19.66]) or obese (OR = 7.03, 95% CI [4.90, 10.09]), walking participation rate for more than 10 min a day (OR = 1.09, 95% CI [1.03, 1.15]), and had a high degree of depression (OR = 1.43, 95% CI [1.37, 1.49]). It is necessary to approach smoking-related policies separately between general and hardcore smokers. Finally, more effective smoking cessation policies must be found by identifying the characteristics of hardcore smokers.


Clinical applications of free flap transfer in the burn patient.
Free microvascular flap transfer is indicated in situations in which flap coverage is required and no local flap is available. The technique of transfer of a groin flap based on the superficial circumflex iliac vessels was described. The procedure has been applied to two patients with acute electrical burns with extensive soft-tissue loss, three patients with scar contractures, and one with osteoradionecrosis. Satisfactory results were achieved in all patients. The procedure is contraindicated if recipient or donor vessels are abnormal or inadequate, and in the face of fulminating infection, general debility, and obesity. With scrupulous attention to indications and contraindications, the procedure is safe, reliable, and a valuable addition to the surgeon's armamentarium.


Postmenopausal Hormone Therapy and Risk of Stroke: Impact of the Route of Estrogen Administration and Type of Progestogen.
The benefit/risk analysis of hormone therapy in postmenopausal women is not straightforward and depends on cardiovascular disease. Evidence supports the safety of transdermal estrogens and the importance of progestogens for thrombotic risk. However, the differential association of oral and transdermal estrogens with stroke remains poorly investigated. Furthermore, there are no data regarding the impact of progestogens. We set up a nested case-control study of ischemic stroke (IS) within all French women aged 51 to 62 years between 2009 and 2011 without personal history of cardiovascular disease or contraindication to hormone therapy. Participants were identified using the French National Health Insurance database, which includes complete drug claims for the past 3 years and French National hospital data. We identified 3144 hospitalized IS cases who were matched for age and zip code to 12 158 controls. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Compared with nonusers, the adjusted ORs of IS were1.58 (95% CI, 1.01-2.49) in oral estrogen users and 0.83 (0.56-1.24) in transdermal estrogens users (P<0.01). There was no association of IS with use of progesterone (OR, 0.78; 95% CI, 0.49-1.26), pregnanes (OR, 1.00; 95% CI, 0.60-1.67), and nortestosterones (OR, 1.26; 95% CI, 0.62-2.58), whereas norpregnanes increased IS risk (OR, 2.25; 95% CI, 1.05-4.81). Both route of estrogen administration and progestogens were important determinants of IS. Our findings suggest that transdermal estrogens might be the safest option for short-term hormone therapy use.


Evaluation of conventional Doppler fetal cardiac function parameters: E/A ratios, outflow tracts, and myocardial performance index.
Structural evaluation of the fetal heart is well established. Functional evaluation using pulsed-wave Doppler may also be performed. E/A ratios express the relationship between the maximal velocities of the E and A waveforms of ventricular filling. In normal fetuses, E/A ratios are usually <1 but show a constant increment during gestation, mainly related to the increment of the E wave. In intrauterine growth restriction (IUGR) fetuses, E/A ratios are lower compared to values in normally grown fetuses at the same gestational age. Cardiac outflows provide information on the time-velocity integral that, combined with the vessel area, allows calculation of the left and right cardiac outputs. In normal fetuses there is a predominance of the right ventricle (55-60%) in contributing to the combined cardiac output. In IUGR fetuses this predominance shifts to the left ventricle in order to increase the flow to the upper part of the fetal body and brain. The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function. The MPI is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome.


Availability of Vitamins and Minerals in Tablet Form.
A human bioassay method has been used to determine the availability of vitamins resistant to an in vitro disintegration test. Wide variations in absorption were noted among individuals in one study.


Structure-CaSR-Activity Relation of Kokumi γ-Glutamyl Peptides.
Modulation of the calcium sensing receptor (CaSR) is one of the physiological activities of γ-glutamyl peptides such as glutathione (γ-glutamylcysteinylglycine). γ-Glutamyl peptides also possess a flavoring effect, i.e., sensory activity of kokumi substances, which modifies the five basic tastes when added to food. These activities have been shown to be positively correlated, suggesting that kokumi γ-glutamyl peptides are perceived through CaSRs in humans. Our research is based on the hypothesis that the discovery of highly active CaSR agonist peptides will lead to the creation of practical kokumi peptides. Through continuous study of the structure-CaSR-activity relation of a large number of γ-glutamyl peptides, we have determined that the structural requirements for intense CaSR activity of γ-glutamyl peptides are as follows: existence of an N-terminal γ-L-glutamyl residue; existence of a moderately sized, aliphatic, neutral substituent at the second residue in an L-configuration; and existence of a C-terminal carboxylic acid, preferably with the existence of glycine as the third constituent. By the sensory analysis of γ-glutamyl peptides selected by screening using the CaSR activity assay, γ-glutamylvalylglycine was found to be a potent kokumi peptide. Furthermore, norvaline-containing γ-glutamyl peptides, i.e., γ-glutamylnorvalylglycine and γ-glutamylnorvaline, possessed excellent sensory activity of kokumi substances. A novel, practical industrial synthesis of regiospecific γ-glutamyl peptides is also required for their commercialization, which was achieved through the ring opening reaction of N-α-carbobenzoxy-L-glutamic anhydride and amino acids or peptides in the presence of N-hydroxysuccinimide.


Phenotypic heterogeneity is an evolutionarily conserved feature of the endothelium.
Mammalian endothelial cells (ECs) display marked phenotypic heterogeneity. Little is known about the evolutionary mechanisms underlying EC heterogeneity. The last common ancestor of hagfish and gnathostomes was also the last common ancestor of all extant vertebrates, which lived some time more than 500 million years ago. Features of ECs that are shared between hagfish and gnathostomes can be inferred to have already been present in this ancestral vertebrate. The goal of this study was to determine whether the hagfish endothelium displays phenotypic heterogeneity. Electron microscopy of the aorta, dermis, heart, and liver revealed ultrastructural heterogeneity of the endothelium. Immunofluorescent studies demonstrated marked differences in lectin binding between vascular beds. Intravital microscopy of the dermis revealed histamine-induced adhesion of leukocytes in capillaries and postcapillary venules, but no such adhesion in arterioles. Together, these data suggest that structural, molecular, and functional heterogeneity of the endothelium evolved as an early feature of this cell lineage.


Absolute Configuration of the Cytotoxic Marine Alkaloid Monanchocidin A.
The absolute configuration of the cytotoxic guanidine alkaloid monanchocidin A with 11 stereogenic centers from the marine sponge Monanchora pulchra was determined as 5 R, 8 S, 10 S, 13 R, 14 S, 15 R, 19 R, 23 R, 37 S, 42 S, 43 R after extensive reductive degradation and conversion of the resulting alcohols to MTPA derivatives.


Bedside videoscopic placement of feeding tubes: development of fiberoptics through the tube.
Transpyloric small intestine feeding tube placement can be difficult and tedious. Currently accepted techniques are associated with disadvantages and risk. The purpose of this study is to describe the development of a new technique: bedside videoscopic placement using fiberoptics through the tube. Prospective, descriptive case study. Intensive care unit in a teaching hospital. Subjects were divided into two groups: a) group 1: eight healthy volunteers (seven male, one female); b) group 2: nine critically ill patients (six male, three female; eight of these patients were intubated). Standard 12-Fr (4.0-mm) feeding tubes (n = 19) were placed. Two patients from group 2 had feeding tubes placed on two separate occasions. The feeding tubes were inserted by the oral (n = 8) or nasal (n = 11) route under direct vision, using a 6.7-Fr (2.2-mm) fiberoptic scope through the feeding tube. We visualized enteric structures clearly through the feeding tube in all subjects and patients. Based on visual landmarks, we advanced the feeding tube through the pylorus and into the duodenum in all individuals. Transpyloric tube placement was confirmed videoscopically (n = 19) and radiographically (n = 18). In three subjects from group 1, the feeding tube entered the first part of the duodenum, while, in the remainder of the subjects, the tube passed into or beyond the second portion of the duodenum. In eight (73%) of 11 attempts on the nine critically ill patients from group 2, the feeding tubes were advanced to the distal duodenum or jejunum. The time required for placement in group 2 ranged from 2 to 43 mins (mean 18 +/- 12 [SD]). The feeding tubes remained in place 10 +/- 4 days and patients met their estimated caloric needs within 24 hrs. Residual volumes of nutrition in the small bowel were < 5 mL. There were no documented episodes of aspiration. This new technique has the potential for rapid, accurate, and safe feeding tube placement in patients requiring nutritional support.


Fatty acid elongation in yeast--biochemical characteristics of the enzyme system and isolation of elongation-defective mutants.
Elongation of long-chain fatty acids was investigated in yeast mutants lacking endogenous de novo fatty acid synthesis. In this background, in vitro fatty acid elongation was dependent strictly on the substrates malonyl-CoA, NADPH and a medium-chain or long-chain acyl-CoA primer of 10 or more carbon atoms. Maximal activity was observed with primers containing 12-14 carbon atoms, while shorter-chain-length acyl-CoA were almost (octanoyl-CoA) or completely (hexanoyl-CoA, acetyl-CoA) inactive. In particular, acetyl-CoA was inactive as a primer and as extender unit. The Michaelis constants for octanoyl-CoA (0.33 mM), decanoyl-CoA (0.83 mM) lauroyl-CoA (0.05 mM), myristoyl-CoA (0.4 mM) and palmitoyl-CoA (0.13 mM) were determined and were comparable for fatty acid synthesis and elongation. In contrast, the affinity of malonyl-CoA was 17-fold lower for elongation (Km = 0.13 mM) than for the fatty acid synthase (FAS) system. With increasing chain length of the primer (> or = 12:0), fatty acid elongation becomes increasingly sensitive to substrate inhibition. Due to the activation of endogenous fatty acids, ATP exhibits a stimulatory effect at suboptimal but not at saturating substrate concentrations. In the yeast cell homogenate, the specific activity of fatty acid elongation is about 10-20-fold lower than that of de novo fatty acid synthesis. The same elongation activity is observed in respiratory competent and in mitochondrially defective cells. The products of in vitro fatty acid elongation are fatty acids of 15-17 or 22-26 carbon atoms, depending on whether tridecanoyl-CoA or stearoyl-CoA is used as a primer. In vitro, the elongation products are converted in part, by alpha-oxidation, to their odd-chain-length lower homologues or are hydrolyzed to fatty acids. In contrast, no odd-chain-length elongation products or very-long-chain fatty acids (VLCFA) shorter than 26:0 are observed in vivo. Hence, VLCFA synthesis exhibits a higher processivity in vivo than in the cell homogenate. In addition, the in vivo process appears to be protected against side reactions such as hydrolysis or alpha-oxidation. Yeast mutants defective in 12:0 or 13:0 elongation were derived from fas-mutant strains according to their failure to grow on 13:0-supplemented media. In vivo, 12:0 elongation was reduced to 0-10% of the normal level, while 16:0 elongation and VLCFA synthesis were unimpaired. It is concluded that yeast contains either two different elongation systems, or that the respective mutation interferes differentially with medium-chain and long-chain fatty acid elongation. The yeast gene affected in the elongation-defective mutants was isolated and, upon sequencing, identified as the known ELO1 sequence. It encodes a putative membrane protein of 32-kDa molecular mass with no obvious similarity to any of the known FAS component enzymes.


Search for DQ2.5 and DQ8 alleles using a lower cost technique in patients with type 1 diabetes and celiac disease in a population of southern Brazil.
To evaluate the frequency of DQ2.5 and DQ8 alleles using the Tag-single-nucleotide polymorphism (Tag-SNP) technique in individuals with type 1 diabetes mellitus (T1DM) and celiac disease (CD) in southern Brazil. In a prospective design, we performed the search for DQA1*0501 and DQB1*0201 alleles for DQ2.5 and DQB1*0302 for DQ8 through Real-Time Polymerase Chain Reaction (RT-PCR) technique, using TaqMan Genotyping Assays (Applied Biosystems, USA). The diagnosis of CD was established by duodenal biopsy and genotypic determination performed by StepOne Software v2.3. Allelic and genotypic frequencies were compared between groups using Chi-square and Fisher's exact tests and the multiple comparisons using Finner's adjustment. Three hundred and sixty two patients with a median age of 14 years were divided into 3 groups: T1DM without CD (264); T1DM with CD (32) and CD without T1DM (66). In 97% of individuals with T1DM and CD and 76% of individuals with CD without T1DM, respectively, the alleles DQ2.5 and/or DQ8 were identified (p < 0.001). DQ2.5 was more common in individuals with CD (p = 0.004) and DQ8 was more common in individuals with type 1 diabetes (p = 0.008). The evaluation of the alleles for DQ2.5 and DQ8 by Tag-SNP technique showed a high negative predictive value among those with T1DM, similar to that described by the conventional technique. The high frequency of DQ8 alleles in individuals with T1DM did not allow differentiating those at higher risk of developing T1DM.


Behavioural effects of the neonicotinoid insecticide thiamethoxam on the predatory insect Platynus assimilis.
Little information is available regarding sublethal effects of neonicotinoids on insect predators, many of which perform important roles in ecosystem functioning and biocontrol. In this study, dose-dependent sublethal effects of a dietary administered neonicotinoid insecticide thiamethoxam on two basic behaviours, locomotion and feeding, were quantified in the carabid Platynus assimilis (Coleoptera, Carabidae) using automated video-tracking and weighing of consumed food, respectively. Acute toxicity tests showed that, when orally administered, the LD50 of thiamethoxam for P. assimilis beetles was 114.5 ng/g. Thiamethoxam at 108.1 ng/g caused a short-term locomotor hyperactivity within several hours of treatment. Next day after exposure to the insecticide, all the beetles were in a state of locomotor hypoactivity independent of the administered dose ranging from 1.1 to 108.1 ng/g. Reduction in clean food consumption rate (CFCR) is another altered behavioural endpoint of poisoned insect predators as first demonstrated in this study. On the first day of thiamethoxam administration, a remarkable reduction in feeding only occurred in beetles treated at 108.1 ng/g but on the next day, this negative effect appeared even at doses ten to a hundred-fold lower. Recovery from locomotion abnormalities and reduced feeding took several days. Both locomotor activity and CFCR are sensitive and valuable ecotoxicological biomarkers of carabids which should be taken into account in Integrated Pest Management programs where optimal combination of reduced insecticide use and biological control by predatory insects is crucial to achieve best results.


Transient variations in the serum concentrations of cell adhesion molecules following retroperitoneal laparoscopic and open radical nephrectomy for localized renal-cell carcinoma.
To evaluate differences in the serum concentrations of cell adhesion molecules (CAMs) after retroperitoneal laparoscopic and conventional open radical nephrectomies for localized renal-cell carcinoma (RCC). A total of 62 patients with stage T(1)N(0)M(0) RCC were randomized to either a retroperitoneal laparoscopic radical nephrectomy group (n=31) or an open group (n=31). Serum levels of soluble cluster of differentiation 44 splice variant 6 (sCD44v6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble epithelial cadherin (sE-cadherin) were determined independently by enzyme linked immunosorbent assay (ELISA) preoperatively, and on postoperative days 1 and 5. In addition, follow-up results were compared. On postoperative day 1, sCD44v6, sICAM-1, and sVCAM-1 levels increased significantly compared with preoperative levels in both groups (P<0.05). sE-cadherin levels decreased compared with preoperative levels in both groups without statistically significant differences (P>0.05). sCD44v6 levels in the retro-laparoscopy group were significantly higher than in the open group (P<0.05), while sICAM-1, sVCAM-1, and sE-cadherin levels showed no statistically significant differences between both groups (P>0.05). On postoperative day 5, all parameters in both groups were similar to preoperative values (P>0.05). Follow-up ranged from 7 to 18 months postoperatively in all 62 patients, with a 100% cancer-specific survival rate in each group. Although postoperatively higher serum concentrations of CAMs in both groups and significantly elevated sCD44v6 in the retro-laparoscopy group may be facilitated, the differences in CAMs between both groups are small and transient. Together with the similar follow-up results, this further supports previous studies that failed to show a difference in the oncologic outcomes between open and laparoscopic radical nephrectomy and provides a probable molecular mechanism.


Improvement in the amine glass platform by bubbling method for a DNA microarray.
A glass platform with high sensitivity for sexually transmitted diseases microarray is described here. An amino-silane-based self-assembled monolayer was coated on the surface of a glass platform using a novel bubbling method. The optimized surface of the glass platform had highly uniform surface modifications using this method, as well as improved hybridization properties with capture probes in the DNA microarray. On the basis of these results, the improved glass platform serves as a highly reliable and optimal material for the DNA microarray. Moreover, in this study, we demonstrated that our glass platform, manufactured by utilizing the bubbling method, had higher uniformity, shorter processing time, lower background signal, and higher spot signal than the platforms manufactured by the general dipping method. The DNA microarray manufactured with a glass platform prepared using bubbling method can be used as a clinical diagnostic tool.


Micropolitics of race and ethnicity in women's prisons in two political contexts.
Research over the past two decades has focused on the topic of race as important for understanding order and compliance in men's prisons. However, relatively little research considers how subjective understandings of imprisonment are influenced by race, particularly in the case of women prisoners. The current study analyses 139 interviews conducted with women prisoners in California and England in order to determine how race and ethnicity shape prisoners' experiences and abilities to cope with institutional confinement. Findings suggest that women's understandings of their racial identities differ substantially in these two contexts. In California, where the conditions of confinement are more extreme and white women assume a minority status, racial identity emerges as a salient factor in coping with the adversities of prison life. By contrast, in England, it is the women of colour, and particularly foreign nationals, who have a greater appreciation of the role of race and ethnicity in their daily lives. These findings have implications for our understanding of how prisoners draw on their lived experiences to make sense of their carceral worlds.


Effects of feeding early-harvested orchardgrass-perennial ryegrass mixed silage instead of heading stage harvested timothy silage on digestion and milk production in dairy cows.
We evaluated the effects of replacement of heading stage harvested timothy silage with early-harvested orchardgrass-perennial ryegrass mixed (OP) silage while maintaining or reducing concentrate input on dry matter intake (DMI), milk production, nutrient digestibility, and N balance in dairy cows. Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design with three dietary treatments: TYL, a diet containing timothy silage where forage-to-concentrate ratio (FC) was 50:50; OPL, a diet containing OP silage where FC ratio was 50:50; and OPH, a diet containing OP silage where FC ratio was 60:40. We observed that an equal replacement of timothy with OP silage increased DMI, milk yield, milk protein production, and nutrient digestibility but decreased milk fat content (TYL versus OPL). We observed that replacing timothy with OP silage while reducing concentrate input increased milk fat and protein yield, nutrient digestibility, and feed efficiency and reduced urinary N loss with no effect on DMI or milk fat content (TYL versus OPH). These results show that replacing timothy with OP silage can be a good approach to improve milk production, feed efficiency, and N utilization and reduce concentrate input. However, milk fat depression should be considered when an equal substitution is performed.


Comparisons between oral and intraperitoneal 1,25-dihydroxyvitamin D3 therapy in children treated with peritoneal dialysis.
Recent studies in adults have suggested that parenteral 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may have advantages over oral therapy in the management of renal osteodystrophy. The purpose of this study was to determine whether there were clear differences between oral and IP 1,25(OH)2D3 treatments in children who did not pose a treatment problem. Seven children (5 males, 2 females, aged 1.8 to 16 years, median 4.8 years) undergoing peritoneal dialysis were initially treated with oral 1,25(OH)2D3 for a one month equilibration period They were randomly assigned to 3 months of either oral or intraperitoneal (IP) therapy with 1,25(OH)2D3 followed by 3-months-treatment using the alternative route. No significant differences in serum creatinine, phosphate, or parathyroid hormone concentrations were found between the different routes of administration in the patients. No significant differences in height standard deviation scores or renal osteodystrophy scores were found over the six-month study. Paired oral and IP pharmacokinetic studies were performed on these 7 patients and 2 other children who had been treated for at least 2 months using either oral or IP 1,25(OH)2D3. Serum was taken prior to one of the usual 1,25(OH)2D3 doses and 0.5, 1.5, 3, 6, and 24 h afterward. The highest measured concentrations of 1,25(OH)2D3 were found at 1.5 h for both oral and IP treatments (mean Cmax [SD]: oral 116 [23] pmol/l, IP 121 [24] pmol/l, p > 0.05). The AUC's for oral and IP therapy were similar (1701 [276] and 1645 [301] pmol/h/l, respectively). In the paired pharmacokinetic studies no significant differences were found between oral and IP treatments for the serum half life (27.4 [11.6] h and 19.2 [8.1] h, respectively) and total body clearance (15.3 [2.1] h and 18.4 [3.3] h, respectively) of 1,25(OH)2D3. In children who respond appropriately to oral 1,25(OH)2D3 there is no biological advantage to the use of IP 1,25(OH)2D3.


A Case of Angioimmunoblastic T-cell Lymphoma That Mimics As Autoimmune Diseases and Infections.
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive malignancy with a presentation like either autoimmune diseases, drug reactions, or infections. We hereby present a unique case of AITL. A 61-year-old Caucasian male with a past medical history of chronic obstructive pulmonary disease (COPD) presented to the emergency department with a rash over his bilateral knees, shortness of breath, and productive cough of few days. He was managed for suspected COPD exacerbation associated with community-acquired pneumonia. On the day of admission patient was having an itchy maculopapular rash, ecchymosis on the left flank, and generalized lymphadenopathy. Physical exam showed generalized lymphadenopathy. Laboratory tests revealed leukocytosis, thrombocytopenia and were positive for multiple autoantibodies. Epstein-Barr virus polymerase chain reaction and hepatitis B virus core antibody were positive. Skin biopsy revealed findings suggestive of a small vessel vasculitis. Inguinal lymph node biopsy showed AITL. The patient recovered with chemotherapy. The case illustrates that clinical presentation of AITL mimics rheumatologic disorders and infections. This complexity could arise from the follicular T helper cell, which is an important checkpoint for B cell activation and differentiation. Additionally, skin involvement is one of the important findings of AITL and a variety of lesions have been reported as skin manifestations.


Maternally reported fetal activity levels and developmental diagnoses.
Retrospective maternal report of fetal activity level was compared with developmental diagnosis in 608 consecutively referred children. Maternal history of fetal activity level was also obtained from 140 unmatched well children in a general pediatric clinic. Fetal hyperactivity was positively associated with a diagnosis of child hyperactivity, and fetal hypoactivity was positively associated with a diagnosis of mental retardation in the children. Maternal histories of fetal activity level in the control group weakened the strength of the association between fetal hyperactivity and child hyperactivity but did not affect the association between fetal hypoactivity and mental retardation in children.


Critical evaluation of various forms of therapy for idiopathic calcium stone disease.
The results are presented of the dietary management, alone or in association with thiazides and/or allopurinol, evaluated in 143 idiopathic calcium stone formers after a mean follow-up of 18 months. Diet alone proved to be effective in the prevention of stone relapses. The addition of thiazide and/or allopurinol provided mild improvements of urine environment but seemed to give no further clinical benefits irrespective of underlying metabolic abnormalities.


Cell cycle synchronization and analysis of apoptosis-related gene in skin fibroblasts from domestic cat (Felis silvestris catus) and kodkod (Leopardus guigna).
The kodkod population is in constant decrease and the somatic cell nuclear transfer (SCNT) might help to preserve the genetic pool of this species. The cell cycle synchronization of donor cells plays a crucial role in SCNT. The objective of this research was to evaluate two different methods for quiescence induction, serum starvation (SS) and contact inhibition (CI), both for 1, 3 and 5 days, on skin fibroblast from domestic cat and kodkod. Flow cytometry analysis revealed that in domestic cat, SS and CI, both at 3 and 5 days, increased the percentage of fibroblasts in G0/G1 compared to growing cells (GC) (p < .05). In kodkod, only SS for 3 and 5 days and CI for 1 and 3 days increased the percentage of fibroblasts in G0/G1 compared to GC (p < .05). Viability analysis by differential staining revealed that SS for 5 days decreased the proportion of live fibroblasts in domestic cat and kodkod (p < .05). Regarding gene expression analysis, in domestic cat fibroblasts, no differences were found in the BAX/BCL2 ratio in SS and CI (both at 1, 3 and 5 days) compared to GC. In kodkod fibroblasts, BAX/BCL2 ratio was increased in CI at 3 and 5 days compared to SS at 3 and 5 days (p < .05). In conclusion, in kodkod fibroblasts SS for 5 days and CI after 3 days might have a negative impact on cellular viability. According to these results, we suggest SS for 3 days for cell cycle synchronization in kodkod fibroblasts.


How does the changing profile of infants who are referred for extracorporeal membrane oxygenation affect their overall respiratory outcome?
Extracorporeal membrane oxygenation has been shown to be effective in term neonates with severe but reversible lung disease within the context of randomized, controlled trials. Extracorporeal membrane oxygenation now has been open to a wider population of infants in the United Kingdom, and other treatments have become available. The population referred for extracorporeal membrane oxygenation, therefore, has changed. The aims of this study were to (1) compare respiratory outcomes of infants who received extracorporeal membrane oxygenation in recent years with those from 10 years ago and (2) determine whether respiratory outcome varied with diagnostic group. All infants who were referred to a single extracorporeal membrane oxygenation center and were <12 months old during a 7-year period were eligible. One year after extracorporeal membrane oxygenation, lung volume, airway conductance, maximum expiratory flow, and indices of tidal breathing were measured. A total of 106 infants (77% of those eligible) were tested, and results were compared with those of 51 infants referred for extracorporeal membrane oxygenation as part of the original United Kingdom extracorporeal membrane oxygenation trial. Lung volume was not different, but there was a strong trend for the infants who were seen in more recent years to have better forced expiratory flow and specific airway conductance. Restricting analysis to the major subgroup (meconium aspiration) confirmed these findings. When divided into diagnostic subgroups, infants who required extracorporeal membrane oxygenation for respiratory distress syndrome or who were >2 weeks old when extracorporeal membrane oxygenation was commenced had a poorer respiratory outcome than others. The respiratory outcome of infants who were treated beyond the tightly regulated criteria of the United Kingdom trial remains good and even shows a trend toward improvement. Certain subgroups require extracorporeal membrane oxygenation for longer and have poorer pulmonary function when followed up.


Duality between different geometries of a resonant level in a Luttinger liquid.
We prove an exact duality between the side-coupled and embedded geometries of a single level quantum dot attached to a quantum wire in a Luttinger liquid phase by a tunneling term and interactions. This is valid even in the presence of a finite bias voltage. Under this relation the Luttinger liquid parameter g goes into its inverse, and transmittance maps onto reflectance. We then demonstrate how this duality is revealed by the transport properties of the side-coupled case. Conductance is found to exhibit an antiresonance as a function of the level energy, whose width vanishes (enhancing transport) as a power law for low temperature and bias voltage whenever g > 1, and diverges (suppressing transport) for g < 1. On-resonance transmission is always destroyed, unless g is large enough.


Mucormycosis causing palatal necrosis and orbital apex syndrome.
A case of mucormycosis causing palatal necrosis and orbital apex syndrome is reported successfully treated with systemic antifungal therapy, surgical debridement and control of underlying disease process. After one year of follow-up patient is blind with anatomically preserved right eye and ptosis as well as having palatal obturator. Mucormycosis should be considered in differential diagnosis of palatal necrosis and orbital apex syndrome.


Pneumatosis coli mimicking colorectal cancer.
Pneumatosis coli (PC) is a rare condition of the gastrointestinal tract involving extraluminal gas confined within the bowel wall. We report the case of a 40-year-old gentleman presenting clinically and endoscopically with suspected colorectal cancer. In light of the patient's red flag symptoms, and carpet of polyps seen endoscopically, surgical management by an anterior resection was performed with the patient making a successful recovery. Histological analysis of the resected specimen confirmed pneumatosis coli with no evidence of colonic neoplasia. Although PC can be an incidental finding in asymptomatic patients and considered a benign condition, it can also present as a life-threatening emergency with bowel necrosis and obstruction requiring emergency surgical intervention. Also, when PC mimics malignancy, surgical management is the most appropriate step to ensure that the diagnosis of cancer is not missed.


Water-deficit impact on fatty acid and essential oil composition and antioxidant activities of cumin (Cuminum cyminum L.) aerial parts.
This study is designed to examine the effect of water deficit on growth, fatty acid and essential oil composition, and antioxidant activities of Cuminum cyminum aerial part extracts. Plants were treated with different levels of water deficit: control (C), moderate water deficit (MWD), and severe water deficit (SWD). Plant growth (height, fresh and dry matter weights) as well as yield components were significantly increased under moderate water deficit and conversely reduced at severe level. Total fatty acid content decreased significantly with severity of constraint. Drought reduced considerably the proportions of major fatty acids and the unsaturated to saturated fatty acid ratio. The essential oil yield was 0.14% (based on the dry weight); it increased by 2.21-fold at MWD but decreased by 42.8% under SWD in comparison to the control. Drought results in the modification of the essential oil chemotype from 1-phenyl-1-butanol to 1-phenyl-1,2-ethanediol. Antioxidant activities of the acetone extracts were determined by two complementary test systems, namely, DPPH and β-carotene/linoleic acid. The highest activity was exhibited by moderately stressed plants and was reduced significantly under SWD. In control plants, the total phenolic amount was 10.23 mg GAE/g DW, which increased by 1.5-fold under MWD and decreased by 42% under SWD.


Alcohol, postprandial plasma glucose, and prognosis of hepatocellular carcinoma.
To identify factors associated with prognosis of hepatocellular carcinoma (HCC) after initial therapy. A total of 377 HCC patients who were newly treated at Katsushika Medical Center, Japan from January 2000 to December 2009 and followed up for > 2 years, or died during follow-up, were enrolled. The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis. A similar analysis was performed in 282 patients with tumor stage T1-T3. Additionally, factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence. Finally, 214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels, and differences in their causes of death were examined. On multivariate Cox proportional hazards regression analysis, the following were significantly associated with survival: underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C, hazard ratio (HR): 0.603, 95% CI: 0.417-0.874, P = 0.0079], HCC stage (T1/T2 vs T3/T4, HR: 0.447, 95% CI: 0.347-0.576, P < 0.0001), and mean postprandial plasma glucose after initial therapy (< 200 vs ≥ 200 mg/dL, HR: 0.181, 95% CI: 0.067-0.488, P = 0.0008). In T1-T3 patients, uninterrupted alcohol consumption after initial therapy (no vs yes, HR: 0.641, 95% CI: 0.469-0.877, P = 0.0055) was significant in addition to underlying liver disease stage (non-cirrhosis/Child-Pugh A vs B/C, HR: 0649, 95% CI: 0.476-0.885, P = 0.0068), HCC stage (T1 vs T2/T3, HR: 0.788, 95% CI: 0.653-0.945, P = 0.0108), and mean postprandial plasma glucose after initial therapy (< 200 mg/dL vs ≥ 200 mg/dL, HR: 0.502, 95% CI: 0.337-0.747, P = 0.0005). In patients without local recurrence, time from initial to subsequent therapy for newly emerging HCC was significantly longer in the "postprandial glucose within 200 mg/dL group" than the "postprandial glucose > 200 mg/dL group" (log-rank test, P < 0.05), whereas there was no difference in the period between the "non-alcohol group" (patients who did not drink regularly or those who could reduce their daily consumption to < 20 g) and the "continuation group" (drinkers who continued to drink > 20 g daily). Of 214 T1-T3 patients who died during the observation period, death caused by other than HCC progression was significantly more frequent in "group AL" (patients in the continuation and postprandial glucose within 200 mg/dL groups) than "group N" (patients in the non-alcohol and postprandial glucose within 200 mg/dL groups) (P = 0.0016). This study found that abstinence from habitual alcohol consumption and intensive care for diabetes mellitus were related to improved prognosis in HCC patients.


Utilization rates of intravenous thrombolysis for acute ischemic stroke in Asian countries:: A systematic review and meta-analysis.
Despite intravenous thrombolysis (IVT) being used for the treatment of acute ischemic stroke (AIS) for over two decades, its accessibility remains limited in various regions of the world. The Asian region, which experiences the highest age-standardized incidence of AIS, currently lacks comprehensive data on the utilization of IVT. This study aimed to provide precise estimates of IVT usage for AIS in Asian countries. A literature search was conducted on PubMed and Google using appropriate search terms. English language, peer reviewed articles published after 2010 were included in the analysis. The pooled proportion was calculated utilizing the DerSimonian and Laird random-effects model. Additionally, a subgroup analysis was conducted, taking into account factors such as the study's country, the economic status of the country, specific Asian regions, publication year (before 2015 and from 2015 onwards), study location, study setting, hospital stroke protocol, and national stroke guidelines. 67 observational studies with 778,046 patients with AIS were included in the meta-analysis. The overall utilization rate of IVT was found to be 9.1%. High-income countries had a higher rate (11.3%) compared to lower-middle-income (8.1%) and upper-middle-income countries (9%). Central and North Asia had the highest rate (17.5%) and Southeast Asia had the lowest rate (6.8%). Studies conducted after 2015 had a higher thrombolysis rate (11.3%) compared to those before 2015 (1.5%). Presence of hospital stroke protocols (10.7%) and national stroke guidelines (10.1%) were associated with higher thrombolysis rates. The overall utilization rate of IVT for AIS in Asia stood at 9.1%, showcasing noteworthy disparities across countries, regions, and income brackets. To improve thrombolysis rates in the region, addressing prehospital delays, increasing public awareness, and implementing stroke protocols and national guidelines are key strategies.


Concomitant ALK translocation and EGFR mutation in lung cancer: a comparison of direct sequencing and sensitive assays and the impact on responsiveness to tyrosine kinase inhibitor.
Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation are considered mutually exclusive in nonsmall-cell lung cancer (NSCLC). However, sporadic cases having concomitant EGFR and ALK alterations have been reported. The present study aimed to assess the prevalence of NSCLCs with concomitant EGFR and ALK alterations using mutation detection methods with different sensitivity and to propose an effective diagnostic and therapeutic strategy. A total of 1458 cases of lung cancer were screened for EGFR and ALK alterations by direct sequencing and flourescence in situ hybridization (FISH), respectively. For the 91 patients identified as having an ALK translocation, peptide nucleic acid (PNA)-clamping real-time PCR, targeted next-generation sequencing (NGS), and mutant-enriched NGS assays were carried out to detect EGFR mutation. EGFR mutations and ALK translocations were observed in 42.4% (612/1445) and 6.3% (91/1445) of NSCLCs by direct sequencing and FISH, respectively. Concomitant EGFR and ALK alterations were detected in four cases, which accounted for 4.4% (4/91) of ALK-translocated NSCLCs. Additional analyses for EGFR using PNA real-time PCR and ultra-deep sequencing by NGS, mutant-enriched NGS increased the detection rate of concomitant EGFR and ALK alterations to 8.8% (8/91), 12.1% (11/91), and 15.4% (14/91) of ALK-translocated NSCLCs, respectively. Of the 14 patients, 3 who were treated with gefitinib showed poor response to gefitinib with stable disease in one and progressive disease in two patients. However, eight patients who received ALK inhibitor (crizotinib or ceritinib) showed good response, with response rate of 87.5% (7/8 with partial response) and durable progression-free survival. A portion of NSCLC patients have concomitant EGFR and ALK alterations and the frequency of co-alteration detection increases when sensitive detection methods for EGFR mutation are applied. ALK inhibitors appear to be effective for patients with co-alterations.


Synthesis and pharmacological evaluation of some 3-(4-methoxyphenyl)-2-substitutedamino-quinazolin-4(3H)-ones as analgesic and anti-inflammatory agents.
A variety of novel 3-(4-methoxyphenyl)-2-substitutedamino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one with a variety of alkyl and aryl ketones. The starting material 2-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one was synthesized from 4-methoxyaniline. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, compounds 2-(1-methylpropylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A1), 2-(1-ethylpropylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A2) and 2-(1-methylbutylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A3) showed moderately more potent analgesic activity and the compound 2-(1-methylbutylidene)-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one (A3) showed moderately more potent anti-inflammatory activity when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.


Cross-cultural adaptation and validation of the Social Comfort Questionnaire for Brazilian adult survivors of burns.
Burn patients may encounter social barriers and stigmatization. The objectives of this study were to adapt the Social Comfort Questionnaire (SCQ) into Brazilian Portuguese and to assess the psychometric properties of the adapted version. Cross-cultural adaptation of the 8 items of the SCQ followed international guidelines. We interviewed 240 burn patients and verified the SCQ internal consistency, test-retest reliability and construct validity, correlating the scores with depression [Beck Depression Inventory (BDI)], affect/body image and interpersonal relationships [Burns Specific Health Scale-Revised (BSHS-R)] and self-esteem [Rosenberg's Self-Esteem Scale (RSES)]. We also performed a confirmatory factor analysis (CFA). The cross-cultural adaptation resulted in minor semantic modifications to the original SCQ version. After CFA, a reduced 6-item version showed satisfactory fit to the one-factor model (RMSEA = 0.05, CFI = 0.99, TLI = 0.99). Cronbach alpha's was 0.80, and test-retest intraclass correlation coefficient was 0.86. The final version presented a strong negative correlation with depression (BDI), and strong positive correlations with affect/body image (BSHS-R), interpersonal relationships (BSHS-R) and self-esteem (RSES) (all p < 0.001). The results showed that the SCQ Brazilian Portuguese adapted version complies with the validity and reliability criteria required for an instrument assessing social comfort in Brazilian burn patients. The Brazilian version yields a single score that is easy to interpret and well understood by patients.


Inflammatory caspases in innate immunity and inflammation.
Caspases are best known for their role in apoptosis. More recently, they have gained prominence as critical mediators of innate immune responses. The so-called 'inflammatory caspases' include human caspase-1, -4, -5 and -12 and murine caspase-1, -11 and -12. Of these, caspase-1 is best characterized and serves as the prototype for our understanding of the processing, activation and function of inflammatory caspases. Like their apoptotic counterparts, inflammatory caspases are produced as inactive zymogens and require activation to become proteolytically active. Caspase-1 is activated within the inflammasome, a large cytosolic protein complex that is induced by a growing number of endogenous, microbial, chemical or environmental stimuli. The importance of caspase-1 in initiating innate immune responses is demonstrated by its role in cleaving pro-IL-1 beta and pro-IL-18 to their biologically active forms. New functions have also been implicated, as these proteases and the mechanisms underlying their activation and regulation emerge as important mediators of human health and disease.


Clustering of 3D-Structure Similarity Based Network of Secondary Metabolites Reveals Their Relationships with Biological Activities.
Developing database systems connecting diverse species based on omics is the most important theme in big data biology. To attain this purpose, we have developed KNApSAcK Family Databases, which are utilized in a number of researches in metabolomics. In the present study, we have developed a network-based approach to analyze relationships between 3D structure and biological activity of metabolites consisting of four steps as follows: construction of a network of metabolites based on structural similarity (Step 1), classification of metabolites into structure groups (Step 2), assessment of statistically significant relations between structure groups and biological activities (Step 3), and 2-dimensional clustering of the constructed data matrix based on statistically significant relations between structure groups and biological activities (Step 4). Applying this method to a data set consisting of 2072 secondary metabolites and 140 biological activities reported in KNApSAcK Metabolite Activity DB, we obtained 983 statistically significant structure group-biological activity pairs. As a whole, we systematically analyzed the relationship between 3D-chemical structures of metabolites and biological activities.


Clinical characteristics of halitosis: differences in two patient groups with primary and secondary complaints of halitosis.
Halitosis, defined as an unpleasant oral odor, has become a health concern among the general public. The objective of this study was to evaluate the diversity of clinical characteristics of halitosis of the patients who visited dental clinics. Sixty-eight patients with primary complaints of halitosis and 19 patients with primary complaints of periodontal diseases but secondary complaints of halitosis were studied by organoleptic examination. The patients with primary complaints were diagnosed as having halitosis in fewer cases than the patients with secondary complaints-25% and 53%, respectively. Patient complaints for halitosis were further categorized, by questionnaire, into three types: Type 1, self-conscious; Type 2, conscious by the indication of others; and Type 3, conscious by presumptions from the attitude of others. Although 80% of the patients of both groups were of Type 1, only 24.1% of the Type 1 patients with primary complaint, in comparison with 50% of the Type 1 patients with secondary complaint, were actually found to have halitosis. The results suggest that the majority of patients with primary complaints of halitosis at the dental clinic did not actually have halitosis, but suffered from an imaginary halitosis due to presumptions based upon others' attitudes. After treatment, these patients were more likely to be dissatisfied than patients who had visited the clinic with halitosis as their secondary complaint.


Alcohol, tobacco and analgesics--Busselton, 1972.
Mass health examinations carried out in Busselton in November and December, 1972, revealed that drinking and smoking were more prevalent amongst men, whereas more women took analgesic drugs. Compared with older age groups more young people consumed alcohol, tobacco and analgesics. Younger people are also taking up smoking and drinking at earlier ages than the older age groups. These findings stress the need for better health education to alter the attitudes of younger people. The people of Busselton would support legislation to allow spot breathalyser tests for drivers, women (70%) providing stronger support than men (57%). This suggests that public opinion could support continuing legislation to combat road accidents. Comparisons between the North Shore, Sydney, and Busselton populations indicated somewhat higher proportions of the urban people were consuming alcohol, tobacco and analgesics, particularly urban women. However, both Australian samples revealed disturbingly high proportions of subjects taking excessive monthly quantities of analgesics (3% to 5%) compared with the United Kingdom (2-8%). Previous reports of the high proportion of Traralgon people taking drugs or medication is supported by the Busselton data, which suggest the Australia requires stricter statutory control of analgesics, compulsory warnings on labels and restriction of sales to pharmacists.