A randomised controlled trial to evaluate the effect of self-administered analgesia on women's experience of outpatient treatment at colposcopy.
To evaluate the effect of self-administered isoflurane and desflurane on women's experience of outpatient treatment at colposcopy. A prospective double-blinded randomised controlled trial. A colposcopy clinic serving a regional population. Three hundred and ninety-six women scheduled for treatment of cervical intraepithelial neoplasia (CIN) by large loop excision of the transformation zone (LLETZ). Self-administration of trial gas during a LLETZ procedure. One hundred and ninety-eight women were randomised to use isoflurane and desflurane and 198 to use placebo. Patient satisfaction, pain and anxiety. The mean pain score for cervical surgery was significantly lower for women using isoflurane and desflurane (22.4) than the placebo arm (29.6) (P= 0.003). There was no significant difference between arms in anxiety levels before or after treatment. More women using isoflurane and desflurane (78%) reported 'total helpfulness' of the trial gas than those using placebo (67%) (P= 0.012). A subgroup analysis of trial participants classified as anxious by Hospital Anxiety and Depression Scale (HADS) score at recruitment showed that using isoflurane and desflurane significantly increased total treatment acceptability, helpfulness of the gas and willingness to undergo a similar procedure at six-month follow up. Satisfaction with outpatient treatment at colposcopy is generally high. The main effect of isoflurane and desflurane evaluated in this trial was to reduce pain. It appeared to be effective for women with clinically significant anxiety and could be offered as an alternative to general anaesthesia.


One-pot synthesis of imines and secondary amines by Pd-catalyzed coupling of benzyl alcohols and primary amines.
Imines and secondary amines were synthesized selectively by controlling reaction conditions for the Pd-catalyzed one-pot reactions of benzyl alcohols with primary amines. The reactions did not require any additives and were effective for a wide range of alcohols and amines.


Angiotensin II--AT1 receptor antagonists: design, synthesis and evaluation of substituted carboxamido benzimidazole derivatives.
A series of 5-(alkyl and aryl)carboxamido benzimidazole derivatives had been designed, synthesized and evaluated for in vitro angiotensin II--AT1 receptor antagonism and in vivo antihypertensive activities. The pharmacological activities were inversely related to the size of alkyl and aryl substituents. It can be suggested that compounds with lower alkyl groups at 5-position of benzimidazole nucleus demonstrated potent antihypertensive activity.


Correlation between biological activity of 30 S subunits of Escherichia coli ribosomes and their conformation changes revealed by optical mixing spectroscopy.
Spectral analysis of light scattered from solutions of 30 S subunits was performed by the method of regularization of the inverse spectral problem. The subunits observed under ionic conditions which preserved their biological activity (200 mM NH4Cl at 1 mM MgCl2) revealed a monodisperse pattern of scattering with diffusion constant D = (1.83 +/- 0.10) X 10(-7) cm2/s. The polydispersity and compaction of 30 S subunits were observed under inactivation ionic conditions (30 mM NH4Cl at 1 mM MgCl2). The number of compacted particles correlates with the irreversible loss of biological activity, the ability of 30 S subunits to bind specific tRNA.


Spermatological characteristics of the family Glypthelminthidae (Digenea, Plagiorchioidea) inferred from the ultrastructural study of Glypthelmins staffordi Tubangui, 1928.
The present study describes the ultrastructural organization of the mature spermatozoon of the digenean Glypthelmins staffordi (Glypthelminthidae) by means of transmission electron microscopy. Live digeneans were collected from the Chinese edible frog (Hoplobatrachus rugulosus) in Udon Thani Province (Thailand). The ultrastructural study reveals that the mature spermatozoon of G. staffordi is a filiform cell, which is tapered at both extremities. It exhibits the Bakhoum et al.'s type IV of spermatozoon of digeneans characterized by the 9+'1' axonemes of trepaxonematan Platyhelminthes, the presence of the association "external ornamentation-cortical microtubules", the external ornamentation located in the posterior part of the anterior region, the arrangement of parallel cortical microtubules in two bundles and with its maximum number located in the anterior part of the sperm cell, and the presence of two mitochondria. Other characteristics are the presence of spine-like bodies, a posterior extremity containing only the nucleus, and the presence of a large amount of glycogen granules. Results of the present study are particularly compared with the existing data in other families of the Plagiorchioidea, namely the Brachycoeliidae, the Haematoloechidae, the Omphalometridae and the Plagiorchiidae.


Atypical neural activity during inhibitory processing in substance-naïve youth who later experience alcohol-induced blackouts.
Alcohol-induced blackouts are associated with the development of alcohol abuse and dependence, so it is important to consider potential neurobiological risk factors for experiencing this problem prior to the onset of substance use. This study examines whether neural activity during inhibitory processing might be atypical in substance-naïve youth who later experience alcohol-induced blackouts. We examined inhibitory processing during fMRI with a go/no-go task that requires withholding a prepotent response in substance-naïve youth who would later transition into heavy drinking (n=40) and youth who remain abstinent (n=20). After approximately 5 years of annual follow-up assessments, youth were classified as nondrinkers (n=20), and heavy drinking youth were classified as having experienced an alcohol-induced blackout (blackout+; n=20) or not (blackout-; n=20). Groups were matched on demographic variables, and youth who experienced blackouts were matched on follow-up substance use. Prior to initiating substance use, blackout+ youth showed greater activation during inhibitory processing than nondrinkers and blackout- youth in frontal and cerebellar brain regions. Mean activation during correct inhibitory responses relative to go responses in the left and right middle frontal gyri at baseline predicted future blackout experience, after controlling for follow-up externalizing behaviors and lifetime alcohol consumption. Substance-naïve adolescents who later experience alcohol-induced blackouts show increased neural effort during inhibitory processing, as compared to adolescents who go on to drink at similar levels but do not experience blackouts and healthy, nondrinking controls, suggesting a neurobiological vulnerability to alcohol-induced memory impairments.


Maternal morbidity after early preterm delivery (23-28 weeks).
Previous research has focused mainly on neonatal outcomes associated with preterm and periviable delivery, but maternal outcomes with preterm delivery are less well described. This study aimed to determine if early preterm delivery results in an increase in maternal morbidity. This is a retrospective cohort study conducted at a tertiary care center over a 5-year time period. Subjects were women identified by review of neonatal intensive care unit admission logs. Women were included if they delivered between 23 0/7 and 28 6/7 weeks' gestation and their neonate was admitted to the neonatal intensive care unit. The prevalence of maternal morbidities was assessed, including blood transfusion, maternal infection, placental abruption, postpartum depression or positive depression screen, hemorrhage, and prolonged maternal postpartum hospitalization. A composite outcome comprising blood transfusion, maternal infectious morbidity, placental abruption, and postpartum depression was developed. Outcomes for women who delivered between 23 0/7 and 25 6/7 weeks' gestation (early group) and 26 0/7 and 28 6/7 weeks' gestation (late group) were compared. Multivariate logistic regression analysis was performed to evaluate contributors to the composite morbidity, controlling for confounding. A total of 82 women met the inclusion criteria: 38 in the early group and 44 in the late group. Maternal demographics were similar between the groups. The early group was significantly more likely to experience composite maternal morbidity (60.5% vs 27.3%; P=.004) and infection (42.1% vs 13.6%; P=.006). Regression analysis determined that delivery at a later gestational age was associated with lower rates of composite morbidity (odds ratio, 0.6; 95% confidence interval, 0.41-0.83). In this study, data suggest that maternal morbidity is higher with delivery at periviable gestational ages. Composite morbidity and maternal infection were more frequent in women who delivered at less than 26 weeks' gestation. The management of women at risk for delivery at early gestational ages should include a discussion of increased maternal complications.


Gene Mutations Linked to Hereditary Angioedema in Solitary Angioedema Patients With Normal C1 Inhibitor.
Chronic recurrent angioedema without wheals (CRA) with normal C1 inhibitor (C1-INH) that is unresponsive to antihistamines may involve patients with recurrent angioedema of unknown cause (ie, so-called non-histaminergic idiopathic angioedema) as well as patients with hereditary angioedema with normal C1-INH (HAEnCI) when HAEnCI occurs in only one family member. To identify patients with one of type of HAEnCI in a group of patients with CRA with normal C1-INH that was unresponsive to antihistamines. A total of 132 patients with CRA and normal C1-INH that was unresponsive to antihistamines underwent mutational and clinical analysis. The presence of hereditary angioedema-specific mutations in Factor XII, plasminogen, ANGPT1, KNG1, MYOF, and HS3ST6 genes was tested by Sanger sequencing. When an HAEnCI-causing mutation was identified, available asymptomatic relatives were genetically tested. In 116 of 132 solitary patients with CRA (87.9%), none of the six HAEnCI-linked mutations could be found. Ten patients (7.6%) had the Factor XII mutation c.983C>A (p.T328K) and six (4.5%) the plasminogen mutation c.988A>G (p.K330E). Other mutations linked to HAEnCI were not found in this patient series. In the 16 families with HAEnCI, 11 asymptomatic carriers of one of the HAEnCI-linked mutations were identified. A search for HAEnCI-linked mutations in patients with solitary CRA may lead to the detection of patients and families with HAEnCI. This is important because family members can be identified who are at risk for developing potentially life-threatening angioedema, although they were previously asymptomatic. Without genetic investigation, the risk for an HAEnCI would have remained undetected in these patients and asymptomatic relatives.


Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C-Si bond functionalization.
3-Silylated furfurals, readily prepared in three steps from biomass-derived furfural and 5-methylfurfural, are converted into 3-silylated 2-furyl carbinols upon condensation with organomagnesium or organolithium reagents. The hydroxy unit of the carbinol adducts can be exploited to promote C3(sp2)-Si bond functionalization through intramolecular activation. Two approaches were contemplated for this purpose. Activation by alkoxides of the C3-SiEt3 or C3-SiMe2 t-Bu bonds was ineffective. Conversely, treatment of the C3-benzyldimethylsilyl-appended derivatives with tetrabutylammonium fluoride led to cyclic siloxanes, which revealed to be competent donors for copper-catalyzed cross-coupling reactions, such as arylation reactions catalyzed by Pd2(dba)3/CuI, as well as allylation and methylation reactions catalyzed by CuI⋅PPh3. C3-Benzyldimethylsilyl-appended furfurals are thus introduced as versatile platforms, providing a modular access to 3-substituted 2-furyl carbinols from renewable feedstock.


Endocrinology and hormone therapy in breast cancer: aromatase inhibitors versus antioestrogens.
Endocrine therapies act by either blocking or downregulating the oestrogen receptor or by reducing oestrogen concentrations around and within the cancer cell. In postmenopausal women, oestrogen suppression is achieved by inhibition of the enzyme aromatase by aromatase inhibitors (AIs). Modern AIs (anastrozole, letrozole and exemestane) are more potent than earlier ones and suppress oestradiol levels in plasma to virtually undetectable concentrations. Recent comparisons of AIs with the most widely used oestrogen receptor blocking drug tamoxifen indicate that, in general, AIs result in increased response rates and greater durations of response. Here, we summarize data supporting the difference between the two types of treatment and attempt to account for the underlying mechanisms that favour AIs.


Gene co-expression modules behind the three-pistil formation in wheat.
Multi-pistil trait in wheat is of great potential value in plant development research and crop breeding. Our previous studies identified the Pis1 locus that causes three pistils in wheat by genetic mapping using multiple DNA marker systems. However, there are still 26 candidate genes on the locus, and the causal gene remains to be found. In this study, we aimed to approach the molecular mechanism of multi-pistil formation. Comparative RNA sequencing (RNA-Seq) during the pistil formation was undertaken in four wheat lines: a three-pistil mutant TP, a single-pistil TILLING mutant of TP (SP), a three-pistil near-isogenic line CM28TP with the background of cultivar Chunmai 28 (CM28), and CM28. Electron microscopic analysis specified probable developmental stages of young spikes for the three-pistil formation. mRNA sequencing in the young spikes of the four lines represented 253 down-regulated genes and 98 up-regulated genes in both three-pistil lines, which included six potential genes for ovary development. Weighted gene co-expression analysis represented three-pistil trait-associated transcription factor-like genes, among which one hub gene, ARF5, was the most highlighted. ARF5 is on the Pis1 locus and an orthologue of MONOPTEROS which mediates tissue development in Arabidopsis. qRT-PCR validation implies that the deficiency of ARF5 underlies the three-pistil formation in wheat.


A higher intramuscular fat in vastus medialis is associated with functional disabilities and symptoms in early stage of knee osteoarthritis: a case-control study.
The characteristics of muscle degeneration in individual quadriceps in early knee osteoarthritis (OA) and the association of muscle quantity and quality on knee dysfunction remain unclear. This study aimed to clarify the characteristics of muscle degeneration in individual quadriceps muscles in early knee OA and elucidate the association of muscle volume and intramuscular adipose tissue (intraMAT) with knee dysfunction, including functional disabilities, symptoms, and joint morphology. Fifty participants were categorized into early knee OA and healthy control groups. 3.0 T magnetic resonance imaging (MRI) using T1-weighted and Dixon methods and 3D SPACE in the thigh muscle and knee joint regions was performed. Quadriceps muscle volume, intraMAT, and whole-organ MRI score (WORMS) were assessed. The Knee Society Score (KSS) was used to evaluate functional disabilities and knee symptoms. Univariate analysis of variance was conducted with covariates to clarify the differences in muscle volume and intraMAT between the two groups. Multiple linear regression analyses were performed using the KSS function and symptom subcategories and WORMS as dependent variables and muscle volume, intraMAT, and the presence of early knee OA as independent variables, such as potential confounders. The quadriceps intraMAT, especially in the vastus medialis (VM), was significantly higher in patients with early knee OA than in healthy controls. The VM intraMAT, not muscle volume, was significantly associated with KSS function [B = - 3.47; 95% confidence interval [CI], - 5.24 to - 1.71; p < 0.001] and symptom scores [B = - 0.63; 95% CI, - 1.09 to - 0.17; p = 0.008], but not with WORMS. These findings suggest that higher VM intraMAT is characteristic of quadriceps muscle degeneration in early knee OA and its increase is associated with functional disabilities and symptoms.


A New Nomogram for Predicting Overall Survival and Assisting Postoperative Adjuvant Treatment Decision-Making in Stage II Oral Tongue Squamous Cell Carcinoma: A Surveillance, Epidemiology and End Results (SEER) Database Analysis.
The survival benefit of postoperative adjuvant treatment (POAT) for stage II oral tongue squamous cell carcinoma (OTSCC) remains controversial. This large SEER-based study aims to establish a prognostic nomogram to visualize the overall survival of these patients and to aid in POAT decision making. The cut-off points of age at diagnosis and examined lymph node number (ELN) were determined using the population-based data from the SEER database. Univariate and multivariate Cox hazards regression models were utilized to identify prognostic factors that were integrated into the establishment of the prognostic nomogram. Patients with stage II OTSCC were then stratified into 3 cohorts based on this nomogram. The survival benefit of POAT was evaluated in these cohorts. Age at diagnosis (with cutoff points of 50 and 75 years) and ELN (with cutoff points of 0 and 22) was significantly associated with the survival outcomes in patients with stage II OTSCC. After the multivariate analysis, 4 factors, including age at diagnosis, sex, ELN, and differentiation grade, were identified as independent prognostic factors. Additionally, a prognostic nomogram with these factors was constructed to predict overall survival and to stratify these patients. Only patients in the high-risk cohort could significantly benefit from postoperative adjuvant treatment. This prognostic nomogram could accurately predict the overall survival of stage II OTSCC patients after curative surgery. Notably, this model could also assist the decision-making of postoperative adjuvant treatment for patients with stage II OTSCC.


Single-peptide DNA-dependent RNA polymerase homologous to multi-subunit RNA polymerase.
Transcription in all living organisms is accomplished by multi-subunit RNA polymerases (msRNAPs). msRNAPs are highly conserved in evolution and invariably share a ∼400 kDa five-subunit catalytic core. Here we characterize a hypothetical ∼100 kDa single-chain protein, YonO, encoded by the SPβ prophage of Bacillus subtilis. YonO shares very distant homology with msRNAPs, but no homology with single-subunit polymerases. We show that despite homology to only a few amino acids of msRNAP, and the absence of most of the conserved domains, YonO is a highly processive DNA-dependent RNA polymerase. We demonstrate that YonO is a bona fide RNAP of the SPβ bacteriophage that specifically transcribes its late genes, and thus represents a novel type of bacteriophage RNAPs. YonO and related proteins present in various bacteria and bacteriophages have diverged from msRNAPs before the Last Universal Common Ancestor, and, thus, may resemble the single-subunit ancestor of all msRNAPs.


Fear of cancer recurrence in males diagnosed with breast cancer.
Fear of cancer recurrence (FCR) is a significant problem for individuals diagnosed with a variety of different cancers. To date, FCR has not been studied in males with breast cancer. The objective of this study was to examine the severity of FCR in males with breast cancer. Males with breast cancer participated in an anonymous online survey and completed the Fear of Cancer Recurrence Inventory-Short Form scale (FCRI-SF). A frequency analysis was used to determine the percentage of participants that fell above or below the clinical cutoff for significant FCR. Regressions explored associations between FCR, age, cancer stage, time since diagnosis, and self-health rating. Fifty-nine participants completed the FCRI-SF. The mean age of the sample was 63.5 and 93% reported their race as white. The mean FCR score was 23.9 and 61% reported clinically significant FCR. More than 80% of the sample experienced at least problematic levels of FCR. Increasing age was associated with decreased FCR. Results of this study suggest that FCR is prevalent in men with breast cancer but larger studies with representative samples should be undertaken to better assess the prevalence of FCR in this population and compare it with other groups of patients. More attention is needed to understand the psychological distress experienced by men diagnosed and treated for breast cancer.


Predictive Value of Baseline Biochemical Parameters for Clinical Response of Macular Edema to Bevacizumab in Eyes With Central Retinal Vein Occlusion: A Retrospective Analysis.
To evaluate the influence of baseline biochemical parameters on the improvement in best corrected visual acuity (BCVA) and reduction in central foveal thickness (CFT) in patients treated with intravitreal bevacizumab (IVB; Avastin, Genentech, Inc) for macular edema (ME) secondary to central retinal vein occlusion (CRVO). A retrospective study. Seventy eyes of 70 participants with CRVO who underwent IVB for ME and had at least 1 month of follow-up after the last injection were studied. Demographic variables, systolic and diastolic blood pressure (SBP and DBP), BCVA, CFT measured by optical coherence tomography (OCT), and biochemical investigations [hemoglobin, fasting and postprandial blood sugar (FBS and PPBS), lipid profile, blood urea (BU), serum creatinine (SC), glycosylated hemoglobin (HbA1c)] at baseline were noted. IVB need at every visit was based on clinical and OCT parameters. Changes in BCVA (ΔBCVA) and CFT (ΔCFT) from baseline to last injection were estimated. After IVB, there was a statistically significant reduction in mean CFT (P < 0.01). The group of patients with normal BU and SC had more than 2 lines of improvement compared with those with elevated values (P = 0.043 and 0.009, respectively). Other parameters like FBS, PPBS, hemoglobin, HbA1c, and serum lipids were not associated with improvement of BCVA and reduction of CFT. Normal baseline renal parameters (BU and SC) predict better visual outcome after treatment for ME in CRVO and offer additional benefit over and above that obtained with ME reduction.


On the narrative form of simulations.
Understanding complex physical systems through the use of simulations often takes on a narrative character. That is, scientists using simulations seek an understanding of processes occurring in time by generating them from a dynamic model, thereby producing something like a historical narrative. This paper focuses on simulations of the Diels-Alder reaction, which is widely used in organic chemistry. It calls on several well-known works on historical narrative to draw out the ways in which use of these simulations mirrors aspects of narrative understanding: Gallie for "followability" and "contingency"; Mink for "synoptic judgment"; Ricoeur for "temporal dialectic"; and Hawthorn for a related dialectic of the "actual and the possible". Through these reflections on narrative, the paper aims for a better grasp of the role that temporal development sometimes plays in understanding physical processes and of how considerations of possibility enhance that understanding.


Evaluation of the compatibility of a second generation recombinant anthrax vaccine with aluminum-containing adjuvants.
Recombinant protective antigen (rPA) is the active pharmaceutical ingredient in a second generation anthrax vaccine undergoing pre-clinical evaluation. This rPA vaccine differs from the currently licensed vaccine, anthrax vaccine adsorbed (AVA), in that the sole component is a recombinant form of protective antigen (PA). Unlike AVA the rPA vaccine contains no lethal factor (LF) or edema factor (EF), components of the two bipartite toxins, nor many other Bacillus anthracis-related contaminating proteins that are present in AVA. The proposed clinical protocol involves adsorption of the rPA to an aluminum-based adjuvant. The adsorptive characteristics of rPA and two aluminum-containing adjuvants were examined in a physiological buffer with and without EDTA. Based on the pI of rPA (pI=5.6) and the zero charge point of aluminum hydroxide adjuvant (11.5) and aluminum phosphate adjuvant (4.5), it was predicted and demonstrated that rPA bound in a more efficient manner to aluminum hydroxide adjuvant than to aluminum phosphate adjuvant in the physiological buffer. Binding of the rPA to the aluminum hydroxide adjuvant was decreased by increasing amounts of phosphate in the buffer. The adsorptive capacity for rPA onto aluminum hydroxide adjuvant in the physiological buffer and in water were calculated to be 0.46 mg rPA/mg aluminum in DPBS and 0.73 mg rPA/mg aluminum in water. This study also demonstrated that upon desorption from the aluminum hydroxide adjuvant the rPA was physically intact and free of detectable aggregates. Further, the eluted material was biologically active in an in vitro cytotoxicity assay. Desorption was only possible after an overnight incubation of 2-8 degrees C and not after a room temperature incubation reflecting increased contact with the aluminum hydroxide adjuvant over time. These data suggest that the interaction between rPA and aluminum hydroxide adjuvant is predominantly electrostatic in character.


Association of sense of coherence with oral health behaviors and gingival bleeding among adolescents.
Adolescents experience many types of gingival and periodontal diseases, including gingivitis, localized or generalized aggressive periodontitis, and periodontal complications of various systemic diseases. The occurrence of periodontal diseases is not only related to biotic factors but may also be affected by nonbiotic factors such as oral health behaviors and practices. Various factors that influence an individual's health-related behaviors include a psychosocial construct named sense of coherence (SOC). The aim of this study is to investigate the association of SOC with oral health behaviors and gingival bleeding. This was a cross-sectional, analytical study that was done in the school setting. A random sample of 850 adolescents was selected from nine schools of the Faridabad block of Faridabad district (Haryana) through the multistage cluster sampling technique. Methods of data collection included a combination of questionnaire administration and clinical examination. The questionnaire comprised sociodemographic variables, questions related to oral health behaviors, and Antonovsky's SOC scale. The questionnaire was interviewer administered. Unadjusted and adjusted rate ratios of gingival units having bleeding on probing were estimated by Poisson regression multilevel analysis in Statistical Package for the Social Sciences (SPSS) software for Microsoft Office. Adolescents whose mothers had studied <8 years (relative risk [RR] 1.26; 95% confidence interval [CI] 1.04-1.38), who were males (RR 1.198; 95% CI 1.01-1.29), low SOC (RR 15.93; 95% CI 13.06-19.35), and toothbrushing frequency of less than once a day (RR 1.43; 95% CI 1.21-1.67) and children with plaque index >1 (RR 2.765; 95% CI 2.12-3.25) presented with the higher number of gingival units having bleeding. SOC is associated with gingival bleeding through oral health behaviors.


Activated leukocyte cell adhesion molecule expression predicts lymph node metastasis in oral squamous cell carcinoma.
Lymphatic metastasis of oral squamous cell carcinoma (SCC) is important for prognosis and clinical decision making concerning the treatment of the neck but may be difficult to detect. Activated leukocyte cell adhesion molecule (ALCAM), has been shown to correlate with prognosis or tumor grade in different tumor types and may be a predictor of lymphatic metastasis. ALCAM expression at the invasive front in fresh frozen tissue samples of oral SCC's (n=41) was studied immunohistochemically, using a polyclonal antibody directed against ALCAM's extracellular domain. Membranous expression of ALCAM at the invasive front was significantly related to lymph node metastasis (p=0.001, sensitivity 69%, specificity 84%) and tumor grade (p=0.035). There was no significant relationship with tumor thickness (p=0.394). Lymph node status (p=0.030), correlated with 5-year overall survival. A significant relation between ALCAM and prognosis could not be established, due to an insufficient sample size. However, ALCAM expression does appears to increase risk of early death. Membranous ALCAM expression at the invasive front serves as a molecular marker for lymphatic metastasis and may facilitate better treatment choices concerning the neck in patients with oral SCC.


European consumer response to packaging technologies for improved beef safety.
Beef packaging can influence consumer perceptions of beef. Although consumer perceptions and acceptance are considered to be among the most limiting factors in the application of new technologies, there is a lack of knowledge about the acceptability to consumers of beef packaging systems aimed at improved safety. This paper explores European consumers' acceptance levels of different beef packaging technologies. An online consumer survey was conducted in five European countries (n=2520). Acceptance levels among the sample ranged between 23% for packaging releasing preservative additives up to 73% for vacuum packaging. Factor analysis revealed that familiar packaging technologies were clearly preferred over non-familiar technologies. Four consumer segments were identified: the negative (31% of the sample), cautious (30%), conservative (17%) and enthusiast (22%) consumers, which were profiled based on their attitudes and beef consumption behaviour. Differences between consumer acceptance levels should be taken into account while optimising beef packaging and communicating its benefits.


Comprehensive needs assessment tool in cancer (CNAT): the development and validation.
Needs assessment is an important step toward quality and patient-centered cancer care, as it identifies patient need, guiding evidence-based cancer care policy, and maximizing care outcome. This study reports on the development and validation of comprehensive needs assessment tool in cancer (CNAT). The CNAT, 59-item needs assessment tool for cancer was developed and validated in a large scale multi-center survey involving 2,661 cancer patients in ten fairly distributed cancer centers throughout Korea. To ensure content validity of the CNAT, items were derived from major needs assessment tools and input from experts and patients. Exploratory factor analysis confirmed its construct validity and identified seven factors: health care staff, psychological problems, physical symptoms, information, social and religious/spiritual support, practical support, and hospital facilities/services. Cronbach's alpha for the scale was 0.97, and for subscales, it varied from 0.80 to 0.97. Convergent validity was demonstrated by its significant association with the EQ5D. Patients with elevated stress, depressive episodes, or suicidal ideation reported a significantly higher level of psychological and overall need. Known-group validity was also supported by its ability to detect significant differences according to age, gender, education, insurance status, months since diagnosis, and non-surgical anticancer treatment. Needs differed according to SEER stage and cancer type: advanced stage and breast and lung cancer were associated with a greater level of need. The CNAT constitutes a meaningful and valid response to the challenges of cancer care, enabling assessment of need in cancer with a comprehensive yet concise and psychometrically sound tool.


Craniofacial Distraction: Orthodontic Considerations.
A combined surgical and orthodontic approach to midface and mandibular distraction optimizes stability and outcomes. Orthodontic considerations include proper planning of the distraction vector, appropriate device use, and thorough follow-up through the consolidation and postoperative period. The dental occlusion must be managed throughout treatment in order to achieve ideal results.


Self-care symptom management strategies for auditory hallucinations among inpatients with schizophrenia at a Veterans' Hospital in Taiwan.
The purpose of this study was to explore self-care management strategies for auditory hallucinations (AHs) among inpatients with schizophrenia. Self-report and semistructured questionnaires were used to identify 36 self-management strategies of 200 inpatients with schizophrenia living at a veterans' hospital in Taiwan. The most commonly used management category was behavioral change and the most commonly used strategy was ignoring the AHs. The most common resource for strategies was self-learning. These results can help broaden health care providers' understanding about self-care management strategies for coping with AHs among inpatients with schizophrenia. Developing a manual containing selected self-care strategies and incorporating those strategies into cognitive-behavioral psychotherapy could be useful and beneficial to patients experiencing AHs.


Minimal residual disease in breast cancer and gynecological malignancies: phenotype and clinical relevance.
In breast cancer, about 35% of patients without any clinical signs of overt distant metastases already have disseminated tumor cells in bone marrow aspirates at the time of primary therapy. A significant prognostic impact of these disseminated tumor cells has been shown by many international studies: patients with tumor cells in their bone marrow have a significantly worse prognosis than those without them. Even in malignancies where the skeletal system is not a preferred location for distant metastasis, such as ovarian cancer, early presence of minimal residual disease (MRD) is correlated with poor patient outcome. Thus, besides analysis of the primary tumor, detection of MRD can be used for assessment of patient prognosis and for prediction or monitoring of response to systemic therapy. Disseminated tumor cells are also the targets for novel tumor biological therapy approaches such as specific antibody-based therapies against target cell-surface antigens such as HER2, Ep-CAM (17-1A), and uPA-R. In breast cancer, a first antibody-based tumor therapy against HER2 (Herceptin) has already been approved for clinical use in recurrent disease. However, patient selection for such tumor biological therapies becomes rather difficult due to phenotype changes, which may manifest themselves as differences between primary lesion and disseminated tumor cells. Therefore, not only identification of disseminated tumor cells but even more so their characterization at the protein and gene levels have become increasingly important. In conclusion, characterization of tumor biological properties of disseminated tumor cells allows identification of patients with breast cancer or gynecological malignancies at risk for relapse who are likely to benefit from systemic treatment and/or novel tumor biological therapy approaches.


[Monitoring of Fluid Therapy].
Fluid and volume therapy is of paramount importance in anaesthesia and intensive care medicine. Fluid replacement as well as volume therapy can cause hypervolemia with deleterious consequences. Therefore, a prerequisite for an adequate volume therapy is the assessment of fluid responsiveness. Several monitoring techniques for evaluation of volume status and of volume responsiveness are currently used. However, there are several limitations of the different monitoring techniques that the user should be aware of. An algorithm can be helpful for a structured approach in monitoring volume therapy.


Highly selective and sensitive tool for the detection of Hg(II) using 3-(Trimethoxysilyl) propyl methacrylate functionalized Ag-Ce nanocomposite from real water sample.
Mercury and its derivates cause distinct toxicity and it is detrimental to the ecosystem where the excessive concentration contributes towards the environmental pollutants. The current study reported a colorimetric method for the detection of Hg(II) ion with high specificity and selectivity using Ag-Ce nanocomposite (NC) functionalized by 3-(Trimethoxysilyl) propyl methacrylate. The synthesized Ag-Ce NC was characterized by using double beam UV-visible spectrophotometer, zeta sizer, EDS, TEM, FT-IR, XRD and particle size analyzer. The synthesized particle possessed an average particle size of 27 ± 1 nm and zeta potential of -39.32 ± 3 mV. The brownish yellow colored Ag-Ce NC changed to colorless in presence of Hg(II) where the colorimetric detection was extremely specific and superior towards Hg(II) ion on comparing the tests with other metal ions. An excellent linear correlation was observed between absorbance (395 nm) and Hg(II) concentrations (1 nM-10 μM) (R2 = 0.988) with LOD of 0.03 nM. A cotton swab based probe was prepared for selective, elegant and low cost colorimetric method to detect Hg(II). The parametric study was performed for optimizing the suitable condition. The colorimetric probe developed by this study for Hg(II) detection using Ag-Ce NC shows excellent practical applicability.


Prenatal diagnosis of cleft palate: contribution of color Doppler ultrasound.
The antenatal diagnosis of cleft palate by ultrasound can sometimes be difficult by conventional B-mode imaging, especially when the tongue is in its normal position. We describe two cases which illustrate the value of color Doppler in the antenatal diagnosis of cleft palate. In the first case, at 32 weeks' gestation, there was a large defect with a massive passage of flow extending from the buccal cavity into one of the nasal fossae. In the second case, at 22 weeks' gestation, a parasagittal view demonstrated the fetal tongue to be in the normal position, but there was an abnormal trajectory off low from the buccal cavity into one of the nasal fossae followed by an exit at the level of the cleft. Although a cleft lip was demonstrated on B-mode imaging, we would not have been able to make the diagnosis of cleft palate without color Doppler. This is the first report describing the contribution of color Doppler to the antenatal diagnosis of cleft palate.


Green algae in alpine biological soil crust communities: acclimation strategies against ultraviolet radiation and dehydration.
Green algae are major components of biological soil crusts in alpine habitats. Together with cyanobacteria, fungi and lichens, green algae form a pioneer community important for the organisms that will succeed them. In their high altitudinal habitat these algae are exposed to harsh and strongly fluctuating environmental conditions, mainly intense irradiation, including ultraviolet radiation, and lack of water leading to desiccation. Therefore, green algae surviving in these environments must have evolved with either avoidance or protective strategies, as well as repair mechanisms for damage. In this review we have highlighted these mechanisms, which include photoprotection, photochemical quenching, and high osmotic values to avoid water loss, and in some groups flexibility of secondary cell walls to maintain turgor pressure even in water-limited situations. These highly specialized green algae will serve as good model organisms to study desiccation tolerance or photoprotective mechanisms, due to their natural capacity to withstand unfavorable conditions. We point out the urgent need for modern phylogenetic approaches in characterizing these organisms, and molecular methods for analyzing the metabolic changes involved in their adaptive strategies.


The clinical significance of an autoimmune response against glutamic acid decarboxylase.
Glutamic acid decarboxylase is attracting much interest because of its putative involvement in two clinical disorders: stiffman syndrome and insulin-dependent diabetes. Here we discuss the clinical significance of an autoimmune response against GAD and consider how such information may help identify the disease mechanisms of these disorders.


Repression of promoters for the mouse insulin-like growth factor II-encoding gene (Igf-2) by products of the Wilms' tumour suppressor gene wt1.
We have investigated actions of the Wilms' tumour suppressor zinc finger transcription factor, WT1, on promoters of the mouse insulin-like growth factor II-encoding gene (Igf-2). Two variant forms of WT1 repressed the two major Igf-2 promoters (P2 and P3) in transient transfection assays. WT1-binding sites were characterised in both these promoters and in the transcribed region downstream from P2, exon 2. In each of these regions, there was a pair of WT1-binding sites, and mutational analysis of the exon-2 sites indicated that both were required for full repression. Cooperative binding of WT1 to these sites might explain the dominant-negative mutations of WT1 observed in some Wilms' tumours and Denys-Drash syndrome cases.


Stillbirths, neonatal and post-neonatal mortality by race, birthweight and gestational age.
The birthweight and gestational age specific mortality of singleton Aboriginal and White infants born in Western Australia during the period 1980-86 is described. The analyses are based on the approximately 8000 Aboriginal and 143,000 White births notified through the Western Australia Midwives' system, which were linked to perinatal and infant death records. Overall, stillbirth, neonatal and post-neonatal mortality risks were significantly higher (P < 0.01) for Aboriginals than Whites. However, for specific birthweights and gestational ages, particularly for infants of lower birthweight and shorter gestations, Aboriginals had lower mortality risks than Whites. The ratio of Aboriginal to White mortality risks tended to increase with advancing age of death, suggesting that longer exposure to the well-documented poorer social and environmental conditions of Aboriginal infants increased the mortality risk.


Is hypophosphataemia an independent predictor of mortality in critically ill patients with bloodstream infection? A multicenter retrospective cohort study.
Hypophosphataemia affects up to one-third of patients in the intensive care unit (ICU) and is particularly common during sepsis. Experimental data suggest that hypophosphataemia leads to an acquired dysfunction of leukocytes, thus promoting infections and increasing the risk of death during sepsis. The aim of our study was to investigate the association between hypophosphataemia and mortality in critically ill patients with a bloodstream infection (BSI). We performed a retrospective study in three ICUs during an 18-month period. All adults with a BSI diagnosed in the ICU were eligible. Patients with and without hypophosphataemia, defined as phosphataemia below 0.8 mmol/L, were compared. A multivariate survival analysis using a Cox proportional hazard regression model was conducted to study the association between hypophosphataemia and 90-d mortality. Among the 3783 patients admitted to the three participating ICUs within the 18-month study period, 203 met the inclusion criteria and 193 were analysed. Fifty-four patients had hypophosphataemia. After adjusting for confounders, hypophosphataemia was significantly associated with a twofold increased risk of 90-d mortality (hazard ratio = 2.10 [1.177-3.80], p = 0.013). This association is particularly strong in patients without shock. Hypophosphataemia was independently associated with a twofold increase in 90-d mortality in ICU patients with a BSI. These results suggest that investigators and physicians should include phosphataemia as a predictor of the severity of BSIs. Further research is warranted to better understand this association and to determine the potential benefits of systematic monitoring of phosphataemia and phosphorus supplementation. NCT03529058.


[Protective effects of d-, l-, and dl-3-n-butylphthalide on neuronal damage induced by hypoxia/hypoglycemia in cultured rat cortical neurons].
The effects of l-3-n-butylphthalide(l-NBP) and d-3-n-butylphthalide(d-NBP) on hypoxia/hypoglycemia-induced cytotoxicity in primary cultured rat cortical neurons were studied. l-NBP and d-NBP(1-100 mumol.L-1) were shown to inhibit hypoxia/hypoglycemia-induced LDH release, decrease the percent of cell death and improve the damaged cellular morphology at 10 mumol.L-1 concentration. In addition, l-NBP, d-NBP and dl-NBP were also found to significantly reduce the liberation of polyribosomes from the neuronal rough endoplasmic reticulum and disaggregation of polyribosomes induced by hypoxia/hypoglycemia. These data suggest that l-NBP, d-NBP and dl-NBP can remarkably protect cultured neurons against hypoxia/hypoglycemia induced damage.


Antibodies to serotype 9V exhibit novel serogroup cross-reactivity following infant pneumococcal immunization.
Cross-reactivity within the pneumococcal immune response was examined in this study. Significant cross-reactivity between serotypes 9V, 15B and 19A was identified in infant post-immunization serum that could not be effectively titrated during specific IgG measurements. Pre-absorption using serotype 9V inhibited this cross-reactivity and normalized titratability in the WHO ELISA for serotypes 15B and 19A. However, this did not affect functional avid IgG and was associated with fewer pneumococcal conjugate vaccine (PCV) doses, suggesting that cross-reactive antibodies were of low avidity. The results in this study have important implications for assessment of vaccine immunogenicity.


MiR-29c downregulates tumor-expressed B7-H3 to mediate the antitumor NK-cell functions in ovarian cancer.
B7-H3 is a member of the B7 family of immune checkpoint molecule. Although B7-H3 has been shown to regulate T cell-mediated peripheral immune response, whether it also correlated with NK cell exhaustion in ovarian cancer remains unclear. The purpose of this study was to explore the mechanism of B7-H3 regulating NK-cell proliferation and function. To investigate the relationship between B7-H3 expression and the NK-cell function in ovarian cancer, human ovarian tumor tissues and cell lines were first examined the protein and mRNA expression of B7-H3 by quantitative real-time PCR (qRT-PCR), Immunohistochemistry and Western-blot assays. Then we established B7-H3 knockout cell lines and measured the cytotoxicity of NK cells on these cells by LDH release assay and Flow Cytometry. In addition, we analyzed B7-H3 in the regulation of glycolysis and glycolysis-related proteins by Glycolysis Stress Test, Glucose Consumption Assay and Western-blot. Moreover, luciferase reporter assay was used to confirm the directly regulation of miR-29c to B7-H3. Finally, we carried out in vivo experiments. We observed that tumor-expressed B7-H3 inhibits NK-cell function in vitro and in vivo, and is associated with glycolysis of ovarian cancer cell. Therapeutically, B7-H3 blockade prolonged the survival of SKOV3 tumor-bearing mice. In addition, miR-29c improved the anti-tumor efficacy of NK-cell by directly targeting B7-H3 in vitro were observed, but not in vivo. Our results demonstrate that miR-29c downregulates B7-H3 to inhibit NK-cell exhaustion and associated with glycolysis, which suggest that NK cells may be a new target of anti-B7-H3 therapy in ovarian cancer patients.


[The law to combat violence against women].
Concern about the issue of violence against women emerged in society in the second half of the 20th century. The development of networks of associations favours the creation of laws to defend women's rights on a national level and to respond to the European convention. While it is not easy for victims to assert their rights, a protection order is a key tool for protecting women. Through their actions, health professionals can facilitate the use of existing mechanisms.


Probing Biothiols Using a Red-Emitting Pyridoxal Derivative by Adopting Copper(II) Displacement Approach and Cell Imaging.
An aggregation-induced emission (AIE) active Schiff base L was obtained by reacting pyridoxal and 2-hydroxy-1-naphthaldehyde with p-phenylenediamine in two simple steps. The colorimetric, UV/VIS and fluorescence studies of L revealed that the yellow emissive L (λem =540 nm, λex =450 nm) in pure DMSO turned to a red-emissive L, when the poor solvent fraction (HEPES buffer, 10 mM, pH 7.4) was increased above 50 % in DMSO. The SEM and DLS results indicated the formation of self-aggregates of L that restricted the intramolecular motion and promoted the excited state intramolecular proton transfer (ESIPT) process. The cations sensing ability of the AIEgen L was explored in HEPES buffer (5 % DMSO, 10 mM, pH 7.4), where Cu2+ selectively quenched the fluorescence at 608 nm due to the chelation-enhanced fluorescence quenching (CHEQ) effect with an estimated sensitivity limit of 0.9 μM. Subsequently, the in situ formed AIEgen L-Cu2+ complex was applied for the cascade detection of glutathione (GSH), cysteine (Cys) and homocysteine (Hcy). The decomplexation of Cu2+ from the AIEgen L-Cu2+ by GSH, Cys and Hcy restored the quenched fluorescence emission of AIEgen L at 608 nm. With this Cu2+ displacement approach, the concentration of Cys, Hcy and GSH can be detected down to 2.8 μM, 3.12 μM and 2.0 μM, respectively. The practical utility of AIEgen L and AIEgen L-Cu2+ was examined by monitoring the selective analytes in real environmental and biological samples, and also applied successfully for the cell imaging applications.


Experimental analysis of the relationship between charge movement components in skeletal muscle of Rana temporaria.
Experiments were performed to ascertain whether the monotonic (q beta) and delayed (q gamma) components of non-linear charge in skeletal muscle membranes form a sequential system, or are the result of separate, independent processes. The non-linear capacitance studied in a large number of fibres increased with fibre diameter. This dependence was attributable to tetracaine-sensitive (q gamma) but not to tetracaine-resistant (q beta and q alpha) charge. The kinetics and total quantity of q gamma charge moving in response to voltage steps from varying pre-pulse potentials to a fixed probe potential remained constant despite variations in the size of the early q beta decay. The kinetics of the delayed (q gamma) charging current obtained from a single 20 mV depolarizing step were compared with the sum of the responses to two 10 mV steps adding to the same voltage excursion. The respective transients superimposed only if one of the 10 mV steps did not reach the voltage at which q gamma first appears. In the two preceding experiments, total charge was conserved. These results are consistent with separate and functionally independent q beta and q gamma systems of potential-dependent charge, with q gamma residing in the transverse tubules and q beta on surface membrane. The findings can be discussed in terms of a contractile 'activator' with a steep sensitivity to voltage that begins only with depolarization beyond a level close to the actual mechanical threshold.


Repeated sequence specific to human males.
Restriction enzyme analysis and nucleic acid hybridisation show that there is a repeated sequence in human male DNA which is not present in human female DNA. This sequence is shown to constitute about 50% of the DNA in the Y chromosome and is a simple tandemly repeated DNA.


Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats.
Since the discovery of endogenous cannabinoid signaling, the number of studies exploring its role in health and disease has increased exponentially. Fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of the endocannabinoid anandamide, has emerged as a promising target for anxiety-related disorders. FAAH inhibitors (e.g., URB597) increase brain levels of anandamide and induce anxiolytic-like effects in rodents. Recent findings, however, questioned the efficacy of URB597 as an anxiolytic. We tested here the hypothesis that conflicting findings are due to variations in the stressfulness of experimental conditions employed in various studies. We found that URB597 (0.1-0.3 mg/kg) did not produce anxiolytic effects when the aversiveness of testing procedures was minimized by handling rats daily before experimentation, by habituating them to the experimental room, or by employing low illumination during testing. In contrast, URB597 had robust anxiolytic effects when the aversiveness of the testing environment was increased by eliminating habituation to the experimental room or by employing bright lighting conditions. Unlike URB597, the benzodiazepine chlordiazepoxide (5 mg/kg) had anxiolytic effects under all testing conditions. The anxiolytic effects of URB597 were abolished by the cannabinoid CB1-receptor antagonist AM251, showing that they were mediated by CB1 receptors. Close inspection of experimental conditions employed in earlier reports suggests that conflicting findings with URB597 can be explained by different testing conditions, such as those manipulated in the present study. Our findings show that FAAH inhibition does not affect anxiety under mildly stressful circumstances but protects against the anxiogenic effects of aversive stimuli.


Ethanolaminephosphate side chain added to glycosylphosphatidylinositol (GPI) anchor by mcd4p is required for ceramide remodeling and forward transport of GPI proteins from endoplasmic reticulum to Golgi.
Glycosylphosphatidylinositol (GPI) anchors of mammals as well as yeast contain ethanolaminephosphate side chains on the alpha1-4- and the alpha1-6-linked mannoses of the anchor core structure (protein-CO-NH-(CH(2))(2)-PO(4)-6Manalpha1-2Manalpha1-6Manalpha1-4GlcNH(2)-inositol-PO(4)-lipid). In yeast, the ethanolaminephosphate on the alpha1-4-linked mannose is added during the biosynthesis of the GPI lipid by Mcd4p. MCD4 is essential because Gpi10p, the mannosyltransferase adding the subsequent alpha1-2-linked mannose, requires substrates with an ethanolaminephosphate on the alpha1-4-linked mannose. The Gpi10p ortholog of Trypanosoma brucei has no such requirement. Here we show that the overexpression of this ortholog rescues mcd4Delta cells. Phenotypic analysis of the rescued mcd4Delta cells leads to the conclusion that the ethanolaminephosphate on the alpha1-4-linked mannose, beyond being an essential determinant for Gpi10p, is necessary for an efficient recognition of GPI lipids and GPI proteins by the GPI transamidase for the efficient transport of GPI-anchored proteins from the endoplasmic reticulum to Golgi and for the physiological incorporation of ceramides into GPI anchors by lipid remodeling. Furthermore, mcd4Delta cells have a marked defect in axial bud site selection, whereas this process is normal in gpi7Delta and gpi1. This also suggests that axial bud site selection specifically depends on the presence of the ethanolaminephosphate on the alpha1-4-linked mannose.


Mapping the transition state for ATP hydrolysis: implications for enzymatic catalysis.
Phosphoryl transfer, typically involving high energy phosphate donors such as ATP, is the most common class of biological reactions. Despite this, the transition state for phosphoryl transfer from ATP in solution has not been systematically investigated. Characterization of the transition state for the uncatalyzed hydrolysis of ATP would provide a starting point for dissection of enzyme-catalyzed reactions. We examined phosphoryl transfer from ATP, GTP and pyrophosphate to a series of alcohols; these reactions are analogous to the phosphorylation of sugars and other biological alcohols and to the hydrolysis of ATP. The Brønsted beta(nucleophile) value of 0.07 is small, indicating that there is little bond formation between the incoming nucleophile and the electrophilic phosphoryl group in the transition state. Coordination of Mg2+ has no measurable effect on this value. The Brønsted beta(leaving group) value of -1.1 for phosphoryl transfer to water from a series of phosphoanhydrides is large and negative, suggesting that the bond between phosphorous and the leaving group oxygen is largely broken in the transition state. Uncatalyzed hydrolysis of ATP in solution occurs via a dissociative, metaphosphate-like transition state, with little bond formation between nucleophile and ATP and substantial cleavage of the bond between the gamma-phosphoryl moiety and the ADP leaving group. Bound Mg2+ does not perturb the dissociative nature of the transition state, contrary to proposals that enzyme-bound metal ions alter this structure. The simplest expectation for phosphoryl transfer at the active site of enzymes thus entails a dissociative transition state. These results provide a basis for analyzing catalytic mechanisms for phosphoryl transfer.


E-selectin early overexpression induced by allogeneic activation in isolated mouse lung.
The interaction between host lymphocytes and graft endothelial cells plays an important role in graft rejection. Using our model of isolated ventilated lung from female mouse perfused with fresh blood from either isogeneic or allogeneic male mouse for 3 hours without noticeable ischemia, we have investigated the kinetics of the early events after endothelial cell triggering by E-selectin engagement. Isogeneic perfusion induced nonspecific endothelial cell activation, which was characterized by up-regulation of E-selectin, intercellular adhesion molecule (ICAM)-1, and of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, and lymphotoxin-alpha (mRNAs by real-time polymerase chain reaction). Allogeneic perfusion was characterized after 3 hours by an additional loose adhesion of lymphocytes mediated by the E-selectin and related to the allogeneic activation of endothelial cells. These in turn expressed the I-A molecule (immunostaining). ICAM-1 and lymphocyte function-associated antigen (LFA)-3 mRNA levels were significantly increased in lung extracts after 2 hours, then vascular cell adhesion molecule (VCAM)-1 and TNF-alpha mRNAs after 3 hours without evidence of TNF-alpha production (enzyme-linked immunoadsorbent assay). The major participation of the E-selectin in early allogeneic activation by way of the protein kinase (PK)C pathway was confirmed by using a neutralizing anti-CD62E monoclonal antibody or the inhibitory PKC 19-31 fragment. Altogether, our results demonstrate that E-selectin expression (1) is not a consequence of TNF-alpha triggering, (2) up-regulates its own expression and expression of I-A, VCAM-1, TNF-alpha, and lymphotoxin-alpha mRNAs, and (3) down-regulates expression of LFA-3 and ICAM-1 mRNAs. In conclusion, in our physiologic model, the E-selectin highly participates in the loose adhesion of allogeneic lymphocytes and in the early activation of endothelial cell and therefore in structural and functional lung alterations.


Common and distinct amygdala-function perturbations in depressed vs anxious adolescents.
Few studies directly compare amygdala function in depressive and anxiety disorders. Data from longitudinal research emphasize the need for such studies in adolescents. To compare amygdala response to varying attention and emotion conditions among adolescents with major depressive disorder (MDD) or anxiety disorders, relative to adolescents with no psychopathology. Case-control study. Government clinical research institute. Eighty-seven adolescents matched on age, sex, intelligence, and social class: 26 with MDD (14 with and 12 without anxiety disorders), 16 with anxiety disorders but no depression, and 45 without psychopathology. Blood oxygen level-dependent signal in the amygdala, measured by means of event-related functional magnetic resonance imaging. During imaging, participants viewed facial expressions (neutral, fearful, angry, and happy) while attention was constrained (afraid, hostility, and nose-width ratings) or unconstrained (passive viewing). Left and right amygdala activation differed as a function of diagnosis, facial expression, and attention condition both when patients with comorbid MDD and anxiety were included and when they were excluded (group x emotion x attention interactions, P < or = .03). Focusing on fearful face-viewing events, patients with anxiety and those with MDD both differed in amygdala responses from healthy participants and from each other during passive viewing. However, both MDD and anxiety groups, relative to healthy participants, exhibited similar signs of amygdala hyperactivation to fearful faces when subjectively experienced fear was rated. Adolescent MDD and anxiety disorders exhibit common and distinct functional neural correlates during face processing. Attention modulates the degree to which common or distinct amygdala perturbations manifest in these patient groups, relative to healthy peers.


Negative serology: could exclude the diagnosis of brucellosis?
Two cases of brucellar spondylodiscitis of the lumbar area were presented. Although both cases showed typical radiological changes, serological tests could not detect Brucella agglutinating antibodies. One of the patients was bacteremic and Brucella spp. was identified from blood culture. In the second patient needle biopsy was required for definite diagnosis. Although small, serologic tests have a certain rate of false negative results in brucellosis. Thus, a negative serology should not exclude the diagnosis of brucellosis, as it is demonstrated in the current cases.


A modification of the Johnson-Neyman technique comparing two regressions, applied to treatment effects dependent on baseline levels.
Treatment effects can often depend on baseline (pre-treatment) variables. This is ignored in many studies, or else the relationship is removed statistically by analysis of covariance. The latter method, however, assumes that slopes are equal and also loses information on the base-line contribution. Instead, the Johnson-Neyman technique does not assume that slopes are equal and furthermore permits examination of the baseline contribution. The method was devised for education research and is here extended to biological studies. However, the method assumes that variances are equal for the regressions, which might not be always so. The mmodification proposed accommodates inequalities of variance, whether intrinsic to the regressions or resulting from differences in group size. The Johnson--Neyman technique is discussed in relation to alternative analyses and, in appropriate situations, is considered to yield more information. Furthermore, with the refinement described, it involves even fewer assumptions and becomes more powerful.


Revealing the relationship of couples facing prophylaxis of vertical transmission of HIV.
To reveal the behavior of couples who face prophylaxis of vertical transmission of HIV. This study, based on Heidegger's theory of phenomenology, included 14 participants (7 couples), who received prophylaxis against HIV vertical transmission. The study was conducted from February 2011 to December 2012 in a prenatal outpatient and child care unit at a hospital in the countryside of Rio Grande do Sul, Brazil. Given the possibility of infection and of having a child, the couples revealed the existential movement of staying together to face the situation. The couple learn to take care of themselves in order to be able to care for and become involved with the baby. In this relationship, they teach themselves how to be a family. The inclusion of men in women's health care process, with both serving as a unit, makes it possible to develop assistance in the context of considering the family as being a participant in care.


Neurological update: cognitive rehabilitation in multiple sclerosis.
Cognitive impairment is a common and debilitating symptom in multiple sclerosis (MS). There is limited evidence that disease-modifying therapies are effective in treating cognitive dysfunction. Cognitive rehabilitation is a promising approach to treat cognitive dysfunction in MS, gaining empirical support over the last 10 years. The current review will provide a brief overview of cognitive rehabilitation in MS. Overall, there is evidence that cognitive rehabilitation programs (either restorative or compensatory) are efficacious in treating MS-related cognitive dysfunction. Clinicians should consider this low-cost, low-risk, yet effective treatment approach for their patients.


Anticoagulant-Related Nephropathy in Kidney Biopsy: A Single-Center Report of 41 Cases.
In 2009, the first case of acute kidney injury and occlusive red blood cell (RBC) tubular casts associated with a high international normalized ratio in a patient receiving warfarin was identified. This entity, named warfarin-related nephropathy, was later renamed anticoagulant-related nephropathy (ARN) after similar cases with other anticoagulants were described. We provide our 10-year experience with ARN based on a single-center kidney biopsy laboratory. The kidney pathology database at the Ohio State University Wexner Medical Center (OSUWMC) was searched for native kidney biopsy cases consistent with ARN. Clinical data were obtained from patient medical records. Native kidney biopsies evaluated between January 1, 2009, and December 31, 2017 at OSUWMC. Among 8,636 native kidney biopsies reviewed at the OSUWMC, there were 41 (0.5%) patients for whom deterioration in kidney function could not be explained by kidney biopsy findings alone if anticoagulation was not considered. There were 63% men and 95% were white; average age was 62 ± 14 years. Most were on warfarin therapy (N = 28), although cases were also attributed to direct-acting anticoagulants (N = 2), antiplatelet medications (N = 1), heparin or enoxaparin (N = 4), and disseminated intravascular coagulopathy (N = 6). Morphologically, there was acute tubular necrosis and RBC casts. The majority of biopsies had an underlying glomerular disease and many patients had positive serologic test results. In all these cases, the severity of kidney failure, RBC tubular casts, and hematuria were disproportionate to glomerular morphologic changes. Selection bias in the decision to perform a kidney biopsy. ARN is an uncommon diagnosis in kidney pathology practice, but it should be considered when the number of RBC tubular casts is disproportionate to the severity of glomerular changes in a kidney biopsy in patients either receiving anticoagulation therapy or who presented with acute coagulopathy. Our data suggest that anticoagulation aggravates underlying glomerular diseases rather than directly affecting the glomerular filtration barrier.


Idiopathic pulmonary fibrosis related to endothelial injury and antiendothelial cell antibodies.
Mechanisms underlying idiopathic pulmonary fibrosis are not well understood. This paper presents data supporting the hypothesis that microvascular endothelial cell injury and antiendothelial cell antibodies play roles in human idiopathic pulmonary fibrosis. Serologic and pathologic features of 40 patients diagnosed with idiopathic pulmonary fibrosis were evaluated. All patients had open lung biopsies indicating either usual or nonspecific interstitial pneumonitis. All biopsies had morphologic evidence of microvascular injury to the endothelium, and direct immunofluorescence testing revealed variable deposition of IgG, IgM, or IgA within septal microvasculature suggestive of humorally mediated microvascular injury. Ultrastructural studies revealed changes of endothelial cell injury and necrosis and evidence of repetitive episodes of microvascular injury characterized by basement membrane zone collagen deposition and lamellation. Serum samples demonstrated reactivity to multiple endothelial cell antigenic epitopes, and indirect immunofluorescent testing demonstrated a prominent pattern of fluorescence in pulmonary endothelial cell preparations. Serum samples were positive in 37/40 patients for antiphospholipid antibodies with one fourth having positive lupus anticoagulant tests accompanied by thrombotic episodes. In patients with idiopathic pulmonary fibrosis, Factor VIII levels and C-reactive protein levels were also elevated, supporting the presence of endothelial cell injury and inflammation. These data underscore a potential role for immune-based microvascular injury in the evolution of usual or nonspecific interstitial pneumonitis and indicate that those patients have evidence of microvascular injury and endothelial cell necrosis. The high prevalence of antiphospholipid antibodies in these patients may lead to an inherent thrombophilic tendency.


Impact of palliative urinary diversion by percutaneous nephrostomy drainage and ureteral stenting among patients with advanced cervical cancer and obstructive uropathy: a prospective cohort.
Obstructive uropathy is a recognized complication in advanced cervical cancer. Urinary diversion is commonly used to bypass the obstruction and improve renal function. The degree of survival benefit that diversion offers is not well established and its impact on quality of life (QoL) is uncertain. This study considered these factors in order to inform treatment decisions. This study examined a prospective cohort of patients with advanced cervical cancer and obstructive uropathy in Manila, Philippines. Age, cancer treatment status, comorbidities, serum creatinine level, degree of obstructive uropathy and QoL were recorded at baseline. Patients with creatinine values >150 µmol/L, or who were being considered for radiotherapy or nephrotoxic chemotherapy or manifesting uncontrolled or recurrent uropathy-related urinary tract infection, were offered diversion. Follow-up data collection was at 3, 6, 9 and 12 months from cohort entry. Of the 230 patients invited, 205 patients joined the cohort. Complete data were available for 198, of whom 93 underwent diversion, 56 required diversion but elected not to receive it, and 49 did not require it. Although survival at 12 months among those who underwent diversion was no greater than among those who required but elected not to receive the procedure, diversion was associated with significantly improved chance of survival in the shorter term. There was no significant difference in the QoL between the groups throughout the study. With no evidence of an impact on QoL, the decision to offer diversionary surgery might be based solely on a survival benefit, which is modest but potentially important to patients.


Summertime actinic lichenoid eruption (lichen planus actinicus).
A patient with an unusual lichenoid photosensitive eruption is presented. The features differentiating this entity from classic lichen planus, lupus erythematosus, and polymorphous light eruption are discussed. Phototesting confirmed the provocative influence of sunlight. We prefer the name "summertime actinic lichenoid eruption" to that of "lichen planus subtropicus" or "lichen planus actinicus," since this condition is not confined to subtropical countries, and, although light appears to initiate the eruption, its exact relationship to lichen planus is unclear.


Long-term outcome of targeted therapy for low back pain in elderly degenerative lumbar scoliosis.
Treatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment. Patients with de novo DLS, aged ≥ 65 years, who had LBP with visual analog scale (VAS) of ≥ 50 for ≥ 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated. One hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 ± 32.4 and 43.9 ± 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs. Bone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.


[The application of a single-chip-microcomputer in development of intelligent mid-frequency current physiotherapy instrument].
This paper presents a kind of single-chip-microcomputer based mid-frequency current physiotherapy instrument. Its composition, function, hardware and software are briefly introduced.


Impact of an Electronic Medical Record-Based System to Promote Human Immunodeficiency Virus/Hepatitis C Virus Screening in Public Hospital Primary Care Clinics.
United States guidelines recommend that all adolescents and adults be tested for human immunodeficiency virus (HIV) and that persons born between 1945 and 1965 be tested for hepatitis C virus (HCV). We used electronic medical record (EMR) data to identify patients in 3 primary care clinics in Seattle, Washington who met national criteria for routine HCV or HIV testing and had no documented history of prior testing. Clinic staff received daily lists of untested patients with scheduled appointments. We used generalized linear models to compare the percentage of patients tested and newly diagnosed with HIV and HCV in the 18 months before and during the intervention. A total of 16784 patients aged 18-64 and 9370 patients born between 1945 and 1965 received care from January 2011 to December 2015. Comparing the preintervention and intervention periods, the percentage of previously untested patients tested for HIV and HCV increased from 14.9% to 30.8% and from 18.0% to 35.5%, respectively (P < .0001 for both). Despite this increase in testing, there was no change in the percentage of patients newly diagnosed with HIV (0.7% in both periods, P = .96) or HCV (3.6% vs 3.7%, P = .81). We estimate that 1.2%-15% of HCV-infected primary care patients in our medical center are undiagnosed. EMR-based HCV/HIV testing promotion increased testing but not case finding among primary care patients in our medical center. In our institution, most HCV-infected patients are already diagnosed, primarily through risk-based and clinical screening, highlighting the need to concentrate future efforts on increasing HCV treatment.


AUTOLOGOUS RETINAL TRANSPLANT FOR REFRACTORY SEROUS RETINAL DETACHMENT SECONDARY TO OPTIC DISK PIT: A NOVEL SURGICAL APPROACH.
To present a new technique to treat refractory retinal detachment secondary to optic disk pit. An interventional case report. A 25-year-old man with congenital optic disk pit had two failed vitrectomies involving laser around the optic disk, internal limiting membrane peel and flap to plug the disk pit, and gas tamponade to reattach the retina. With all options running out, a further vitrectomy with autologous retinal transplant and silicone oil tamponade was performed to treat the refractory serous retinal detachment; the silicone oil was removed at 6 weeks after the last procedure. The retina remained successfully attached at 6 months postsurgery with the patient maintaining his baseline visual acuity. The use of autologous retinal transplant is a new approach to treat refractory retinal detachment secondary to congenital optic disk anomalies, and adds to our options of dealing with this complex condition when first-line approaches have failed.


Overview of blood-brain barrier dysfunction in methamphetamine abuse.
Methamphetamine (METH) is one of the psychostimulants most widely abused in the world. METH abuse can lead to severe neurotoxicity. The blood-brain barrier (BBB) is a natural barrier separating the central nervous system (CNS) from the peripheral blood circulation, which can limit or regulate the exchange of toxic substances, molecules, ions, etc., to maintain the homeostasis of CNS. Long-term or high dose abuse of METH can cause structural or functional abnormalities of the BBB and increase the risk of neurodegenerative diseases. In this review, we discussed the mechanisms of METH-induced BBB dysfunction, summarized the risk factors that could exacerbate METH-induced BBB dysfunction, and introduced some potential therapeutic agents. It would provide an important basis and direction for the prevention and treatment of BBB dysfunction induced by METH.


Safety culture in anaesthesiology: basic concepts and practical application.
This article starts from a social science viewpoint and reviews the concepts and measurement of safety culture and climate in their original industrial settings and in health care. Typical items measured and generic characteristics of a positive safety culture are described. The role of personality, professional group membership and anaesthesiology-specific knowledge and expertise in shaping notions of risk and safety and safety behaviour are discussed. The difficulties of changing human behaviour are outlined, and the pivotal role which anaesthesiologists can play in promoting a positive safety culture, both individually and within their teams and organisations, is highlighted.


Airways obstruction in patients with long-term asthma consistent with 'irreversible asthma'.
To describe a series of eight patients with long-term asthma and pulmonary function consistent with "end-stage," irreversible obstruction. Retrospective descriptive analysis of patients with severe asthma. A university-based allergy-immunology service with a large population of corticosteroid-dependent patients with asthma. Eight patients with long-standing asthma and apparently irreversible airways obstruction despite long-term oral and inhaled corticosteroid therapy. Pulmonary function data, radiographic studies including chest radiograph and high-resolution CT of the chest, and serologic analysis to rule out allergic bronchopulmonary aspergillosis and alpha1-antitrypsin deficiency had been performed as indicated, and these results were obtained through chart review. The age of the patients ranged from 41 to 58 years, with a mean duration of asthma of 39 years (SD = 12.4 years). No patient had evidence of any other pulmonary disease process. The mean duration of daily or alternate-day oral corticosteroid treatment was 15.8 years (SD=11.8 years). Despite intensive pharmacotherapy, all patients had an FEV1 57% (42+/-12%) with marked small airways disease as reflected in the forced expiratory flow between 25% and 75% of the FVC. Three of the eight patients demonstrated an accelerated decline in FEV1 despite continuous systemic corticosteroids. We have described a series of eight patients with long-standing asthma who demonstrate irreversible airways obstruction despite long-term systemic and inhaled corticosteroids. The term "end-stage asthma" or irreversible asthma might be applied to these patients in whom fixed obstruction has occurred in the absence of other pulmonary diseases.


Label-free quantitative proteomics analysis of Humulus scandens (Lour.) Merr. leaves treated by an odor compound of Periploca sepium Bunge.
The odor compound from Periploca sepium Bunge, 2-hydroxy-4-methoxy-benzaldehyde (HMB), is an allelochemical agent and is one of the least investigated isomers of vanillin. In this study, we used label-free quantitative proteomics analysis technology to investigate the effect of HMB on the protein expression of Humulus scandens (Lour.) Merr. leaves in July 2019 on Guiyang. A total of 269 proteins of 624 identified proteins were differentially expressed, among which 21.18% of the proteins were up-regulated and 32.71% down-regulated. These proteins were classified into 11 cell components and more than 20% of differentially expressed proteins were located in cell membrane and chloroplast. Functional classification analysis showed that 12 molecular functions were altered upon HMB treatment, and the ratio of catalytic activity was the highest (19.53%). At least 12 biological functions were affected, which involved small molecule metabolic processes, organic substance metabolic processes, gene expression, and photosynthesis. Our data provide resources and insights into the biochemical mechanism by which HMB kills weeds.


Genetic Differences between Physical Injury Patients With and Without Post-traumatic Syndrome: Focus on Secondary Findings and Potential Variants Revealed by Whole Exome Sequencing.
Sudden traumatic physical injuries often cause psychological distress, which may be associated with chronic disability. Although considerable effort has been expended to identify genetic predictors of post-traumatic stress disorder (PTSD) after traumatic events, genetic predictors of psychological distress in response to severe physical injuries have been yet to be elucidated using whole exome sequencing (WES). Here, the genetic architecture of post-traumatic syndrome (PTS), which encompasses a broad range of psychiatric disorders after traumatic events including depression, anxiety disorder, acute stress disorder, and PTSD, was explored using WES in severely physically injured patients, focusing on secondary findings and potential PTS-related variants. In total, 141 severely physically injured patients were consecutively recruited, and PTS was evaluated within 1 month of the injury. Secondary findings were analyzed according to PTS status. To identify PTS-related variants, genome-wide association analyses and the optimal sequencing kernel association test were performed. Of the 141 patients, 88 (62%) experienced PTS. There were 108 disease-causing variants in severely physically injured patients. As secondary findings, the stress- and inflammation-related signaling pathways were enriched in the PTS patients, while the glucose metabolism pathway was enriched in those without PTS. However, no significant PTS-related variants were identified. Our findings suggest that genetic alterations in stress and inflammatory pathways might increase the likelihood of PTS immediately after severe physical injury. Future studies with larger samples and longitudinal designs are needed.


Anesthetic agent propofol inhibits myeloid differentiation factor 88-dependent and independent signaling and mitigates lipopolysaccharide-mediated reactive oxygen species production in human neutrophils in vitro.
Engagement of toll-like receptor 4 (TLR4) can activate the myeloid differentiation factor 88 (MyD88)/toll-interleukin-1-resistance domain-containing adapter-inducing interferon-β (TRIF) dependent pathways, inducing production of reactive oxygen species (ROS) in neutrophils. Propofol (PPF) has both anti-oxidant and anti-inflammatory properties. However, the molecular mechanism by which PPF influences human neutrophil function is yet to be elucidated. This study aimed to investigate the influence of PPF on lipopolysaccharide (LPS)-induced reactive oxygen species production in human neutrophils. We isolated neutrophils from the peripheral blood of 10 healthy male donors. Neither 1 µg/ml LPS nor 10-150 μmol/L PPF influenced the rate of neutrophil apoptosis, but PPF significantly inhibited LPS-mediated reactive oxygen species production in a dose-dependent manner. PPF inhibited LPS-induced expression of MyD88, tumor necrosis factor receptor-associated factor 6, and TRIF, but not the expression of interferon regulatory factor 3 or phosphorylation of p47(phox), p38-mitogen-activated protein kinase, and nuclear factor (NF)-κB, particularly in the neutrophils in which MyD88 or TRIF had been silenced by siRNA. The inhibitory effect of PPF on LPS-induced activation of p47(phox), p38-mitogen-activated protein kinase, and NF-κB was partially antagonized by over-expression of MyD88 or TRIF in neutrophils. These observations provide insights into the mechanisms responsible for the anti-inflammatory properties of PPF. PPF reduces LPS-induced production of reactive oxygen species in neutrophils via inhibiting expression of MyD88 and TRIF signaling.


Introduction to effective mentorship for early-career research scientists.
Diversifying the scientific workforce remains a national priority due to the continued lack of representation from underrepresented individuals in STEM fields. Quality mentoring has been identified as a stimulus to enhance not only research success, but also recruitment and retention of underrepresented groups pursuing STEM careers. Utilizing the Entering Mentoring training curriculum framework, this report provides a brief synopsis and key takeaways from the 2019 NIH-ASCB Accomplishing Career Transition (ACT) workshop, "Introduction to Effective Mentorship for Scientists" for 30 senior postdoctoral and early-career faculty researchers from historically underrepresented racial and ethnicity backgrounds. In addition, effective strategies and best practices to enhance STEM mentoring for early-career researchers are provided, which have practical applications for diverse mentoring relationships across disciplines, career stages, and mentee types.


An evidence-based review of the surgical treatment of gastric adenocarcinoma.
The management of gastric adenocarcinoma continues to evolve. Chemotherapy is being increasingly used in both the neoadjuvant and adjuvant setting. Surgical resection of the stomach and regional lymph nodes remains the mainstay of potentially curative therapy, but significant regional differences persist in the surgical management. This review provides an update on the current literature regarding the preoperative evaluation and staging, extent of gastric resection, extent of lymph node resection, and adjuvant therapy for patients with gastric adenocarcinoma.


Extranodal Rosai-Dorfman disease of bone, subcutaneous tissue and paranasal sinus mucosa with a review of its pathogenesis.
We report an unusual case of extranodal Rosai-Dorfman disease presenting in a 36-year-old man with lesions of bone, subcutaneous tissue of the arm and maxillary sinus mucosa unassociated with lymphadenopathy or systemic symptoms. These lesions appeared metachronously within a 6-month period. The diagnostic light microscopic and immunohistochemical findings and pathogenesis of this interesting disease are discussed.


Repeated effects of the neurotensin receptor agonist PD149163 in three animal tests of antipsychotic activity: assessing for tolerance and cross-tolerance to clozapine.
Neurotensin is an endogenous neuropeptide closely associated with the mesolimbic dopaminergic system and shown to possess antipsychotic-like effects. In particular, acute neurotensin receptor activation can inhibit conditioned avoidance response (CAR), attenuate phencyclidine (PCP)-induced prepulse inhibition (PPI) disruptions, and reverse PCP-induced hyperlocomotion. However, few studies have examined the long term effects of repeated neurotensin receptor activation and results are inconsistent. Since clinical administration of antipsychotic therapy often requires a prolonged treatment schedule, here we assessed the effects of repeated activation of neurotensin receptors using an NTS1 receptor selective agonist, PD149163, in 3 behavioral tests of antipsychotic activity. We also investigated whether reactivity to the atypical antipsychotic clozapine was altered following prior PD149163 treatment. Using both normal and prenatally immune activated rats generated through maternal immune activation with polyinosinic:polycytidylic acid, we tested PD149163 in CAR, PCP (1.5mg/kg)-induced PPI disruption, and PCP (3.2mg/kg)-induced hyperlocomotion. For each paradigm, rats were first repeatedly tested with vehicle or PD149163 (1.0, 4.0, 8.0mg/kg, sc) along with vehicle or PCP for PPI and hyperlocomotion tests, then challenged with PD149163 after 2 drug-free days. All rats were then challenged with clozapine (5.0mg/kg, sc). During the repeated test period, PD149163 exhibited antipsychotic-like effects in all three models. On the PD149163 challenge day, prior drug treatment only caused a tolerance effect in CAR. This tolerance in CAR was transferrable to clozapine, as it enhanced clozapine tolerance in the same group of animals. Although no tolerance effect was seen in the PD149163 challenge for the PCP-induced hyperlocomotion test, the clozapine challenge showed increased sensitivity in groups previously exposed to repeated PD149163 treatment. Our findings suggest that repeated exposure to NTS1 receptor agonists can induce a dose-dependent tolerance and cross-tolerance to clozapine to some of its behavioral effects but not others.


First-in-human trial of SAR107375E, a novel small molecule anticoagulant with dual inhibition of factor Xa and factor IIa.
SAR107375E is a direct dual inhibitor of both Factor Xa and Factor IIa and has shown potent anticoagulation activity in vitro and animals. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending intravenous doses of SAR107375E in healthy Chinese adult subjects. In this randomized, double-blind, placebo-controlled trial, 60 healthy Chinese adult subjects were administered intravenously single ascending doses (0.5, 1.5, 3.0, 5.0, 7.5, 10.0, 15.0, or 20.0 mg) of SAR107375E (N = 44) or placebo (N = 16). Plasma and urine concentrations of SAR107375E were measured and used to calculate pharmacokinetic parameters. Coagulation functions were measured and compared with baseline values. Treatment-emergent adverse events were recorded to evaluate safety. In plasma, from the 0.5 to 20.0 mg dose group, t1/2 is 1.51-4.00 h, Cmax is 59.05-1360 ug/L, and AUC0-t is 25.01-528.45 h*ug/L. And it shows dose proportionality in the 5.0-20.0 mg range. Activated partial thromboplastin time and Ecarin clotting time correlated linearly with drug plasma concentration. No serious adverse events were reported during the study. SAR107375E exhibits good safety and tolerability, predictable pharmacokinetics and pharmacodynamics. www.chinadrugtrials.org.cn, identifier is CTR20211082.


Gait initiation is affected during emotional conflict.
The present study examined whether emotion eliciting images affected motor output when a whole body movement was concerned: gait initiation. From a standing posture, 15 young adults were instructed to initiate gait (several steps) towards pleasant or unpleasant images corresponding to a congruent (CO) or an incongruent (IC) task. The movement was performed as soon as possible after the onset of images, using a paradigm of go/nogo. Because an emotional conflict had to be overcome in IC trials, we hypothesized that the longest reaction times and lowest amplitude of early postural adjustments were found during IC trials, as compared to CO trials. We also anticipated that conflict resolution would be improved if the previous trial was IC rather than CO, as previously reported in a typical press button task. Results demonstrated longer reaction times in IC than CO trials revealing that emotional conflict resolution interfered with cognitive resources involved in motor planning. Although the peak of forward velocity reached by the centre of body mass at the end of the first step and length of this step were similar between CO and IC trials, the amplitude of early postural modifications was reduced in IC trials. All together, these findings provided supporting evidence that a defensive response, possibly a freezing-like behaviour, was implemented during IC trials, but in a transient manner. Furthermore, conflict resolution was improved when the previous trial was IC rather than CO in terms of amplitude of early postural response, but not reaction time.


CTLA-4 expression in T cells of patients with atopic dermatitis.
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is a surface molecule of activated T cells with sequence homologous to CD28, and may act as a negative regulator of T-cell activation. In murine animal models, cross-linkage of CTLA-4 molecules on the cell surface results in decreased T-cell proliferation, accompanied by increased interleukin (IL)-2 production and apoptosis. To clarify the activation of peripheral blood T cells, we studied the CTLA-4 expression in 32 patients with atopic dermatitis who visited our institution, and 19 normal children who visited for pre-operative laboratory examination were used as normal controls. Whole blood was obtained from all subjects and stained with anti-CD3, anti-CD4, anti-CD8 monoclonal antibodies (mAb). After erythrocyte lysis with lysing solution, the cells were stained with anti-CTLA-4 mAb, and stained cells were analysed by fluorescence-activated cell sorter (FACScan) flow cytometer. Intracellular expression of CTLA-4 was significantly upregulated in peripheral blood CD3+ T cells (36.8%), CD4+ T cells (21.7%) and CD8+ T cells (18.7%) of patients with atopic dermatitis, compared with normal control (18.3%, 9.7%, 9.8%; respectively). Furthermore, CTLA-4-positive CD3+ T cells in patients with severe atopic dermatitis were significantly higher compared with milder group (42.8% vs. 32.2%). However, no significant difference was obtained in CD4+ and CD8+ T cells. Mean percentage of T cells expressing CTLA-4 in patients with atopic dermatitis was higher than the control group. These observations suggest the possibility that the disease activity can be correlated with the CTLA-4 level.


A characteristic dissection microscopy appearance of a renal biopsy of a Fabry heterozygote.
We report a 15-year-old Fabry heterozygote presenting to us with asymptomatic proteinuria. During the dissection-microscopic examination, the glomeruli exhibited a characteristic swollen, glistening and white appearance. They were swollen and bulged out from the surface of the renal core. The glomerular tufts appeared to be filled with opaque and whitish material giving them a pale white discoloration. This appearance is due to the accumulation of glycosphingolipids in visceral epithelial cells of the kidney. This feature is important for the investigation of female patients with asymptomatic proteinuria, as in two thirds of Fabry heterozygotes the characteristic skin lesions are absent, and thus heterozygous Fabry disease may not be considered. We suggest that this easily demonstrable appearance can be the first evidence for the disease and pathologists should be aware of it in future.


Hearing results in tympanoplasty.
Recent reports from Scandinavian authors have put forth the concept that hearing improvement following tympanoplasty is seldom satisfactory and difficult to obtain. This view is contradictory to the experience of most American authors. A study, therefore, was undertaken to evaluate the hearing results obtained by this author through the use of homograft material in middle ear and mastoid reconstruction. These hearing results are categorized according to time periods, types of reconstruction, and materials used. The hearing statistics are all taken from audiograms obtained one year or more postoperatively. These correspond with the type of reconstruction employed such as an intact ossicular chain, absence of the malleus, absence of the superstructure of the stapes, or both. Other categories include tympanoplasty with mastoidectomy or reconstruction of the posterior canal wall with homograft knee cartilage. The surgical techniques are not discussed in this article because they have been detailed in previous publications.


Neurokinin-1 receptor in peripheral nerve terminals mediates thermal hyperalgesia.
Neurokinin-1 receptor (NK-1) plays an important role in nociception. The present study was to explore whether activation of peripheral NK-1 receptor, especially expressed on primary sensory afferents, could induce hyperalgesia and sensitize C-type sensory afferents. (1) Intraplantar administration of NK-1 agonist [Sar9, Met(O2)11]SP (Sar-SP, 0.2, 1 nmol, 20 microl) produced significant thermal hyperalgesia and edema, which was blocked by co-injection of NK-1 antagonist WIN51,708 (10 nmol). But in the rats with compound 48/80 treatment for mast cell depletion, the Sar-SP-induced edema, but not hyperalgesia, was attenuated. (2) Close-arterial injection of Sar-SP (1 nmol, 0.1 ml) excited and sensitized sensory C afferents of the sural nerve to heat stimuli. The results suggest involvement of NK-1 receptors expressed on the peripheral afferent terminals in thermal hyperalgesia mediated by directly sensitizing C-type sensory afferents.


DNP and PhD scholarship: Making the case for collaboration.
The Institute of Medicine calls for meaningful collaboration between doctor of nursing practice (DNP)- and doctor of philosophy (PhD)-prepared nurses to improve health outcomes. The purpose of this paper is to answer the questions: 1) how do Colleges of Nursing influence DNP and PhD collaboration for faculty and students? 2) how does DNP and PhD collaboration in an academic setting impact health care practices and patient outcomes? Two examples of DNP and PhD collaboration (one faculty and one student) are presented. Shared faculty responsibilities and a supportive organizational culture influenced collaboration between faculty and students. Research and practice roles can complement and strengthen each other while improving health outcomes. Colleges of Nursing should build processes and culture that encourage faculty and students to collaborate across doctoral programs. Successful intraprofessional collaboration has the potential to positively impact healthcare quality, and outcomes, while advancing the nursing profession.


Fine structure and composition of the zoogloeal matrix surrounding Zoogloea ramigera.
The fingerlike projections, which have been considered to be characteristic of the genus Zoogloea, appear to consist of generally globular packets of cells, each surrounded by capsular matrix. The individual packets which surround Z. ramigera 115 cells appear to adhere one to another by intermeshed fibrils that measure 2 to 5 nm in diameter. The fibril polymer appears to be polyglucose that is susceptible to cellulase. The polymer resembles cellulose in several respects, with the exception that it is soluble in 1 n NaOH. Although Z. ramigera I-16-M does not possess an observable zoogloeal matrix when viewed under a light microscope, chemical data indicate that it does produce cellulase-susceptible polymer. Fibrils can be observed under the electron microscope, which are resistant to 1 n NaOH and may be cellulose. Less polymer fibrils are observed around isolate I-16-M cells than around isolate 115 cells; the inability to observe the I-16-M material as a zoogloeal matrix under light microscopy may be due to lack of sufficient amount of polymer.