Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line.
The doxorubicin-selected multidrug resistant small cell lung cancer cell line, H69AR, is cross-resistant to the Vinca alkaloids and epipodophyllotoxins, but does not overexpress P-glycoprotein, a 170 kDa plasma membrane efflux pump usually associated with this type of resistance. Monoclonal antibodies were raised against the H69AR cell line and one of these, MAb 3.186, recognises a peptide epitope on a 36 kDa phosphorylated protein that is membrane associated, but not presented on the external surface of H69AR cells (Mirski & Cole, 1991). In the present study, in vitro translation and molecular cloning techniques were used to determine the relative levels of mRNA corresponding to the 3.186 antigen. In addition, a cDNA clone containing an insert of approximately 1.4 kb was obtained by screening an H69AR cDNA library with 125I-MAb 3.186. Fragments of this cloned DNA hybridised to a single mRNA species of approximately 1.6 kb that was 5 to 6-fold elevated in H69AR cells. Partial DNA sequencing and restriction endonuclease mapping revealed identity of the cloned DNA with p36, a member of the annexin/lipocortin family of Ca2+ and phospholipid binding proteins.


Choline increases endogenous GABA release in rat hippocampus by a mechanism sensitive to hemicholinium-3.
The effects of choline (Ch) on the spontaneous release of endogenous gamma-aminobutyric acid (GABA) and of 3H-GABA were studied in superfused rat hippocampal synaptosomes. Choline enhanced in a concentration-dependent way the release of endogenous GABA but did not affect that of the radioactive aminoacid. The effect of Ch was not antagonized by atropine or mecamylamine; moreover, it was not mimicked by acetylcholine, oxotremorine or carbachol. The Ch-induced GABA release was counteracted by hemicholinium-3. Thus the release of endogenously synthesized GABA (but not that of the aminoacid taken up) may be regulated by Ch through a mechanism involving penetration into the releasing terminal through a Ch uptake system.


Identification of a Risk Predictive Signature Based on Genes Associated with Tumor Size and Lymph Node Involvement in Breast Cancer.
Background: Breast cancer is a heterogeneous disease. Small tumors with extensive lymph node involvement (STEL) in breast cancer often reflect a biologically aggressive phenotype and poor prognosis. The aim of this study was to identify key genes associated with STEL and investigate their prognostic values in breast cancer. Methods: RNA sequence data from breast cancer specimens were acquired from The Cancer Genome Atlas (TCGA) database for differential analysis. Weighted gene correlation network analyses (WGCNA) were performed to identify coexpressed gene modules associated with tumor size and lymph node metastases. Gene set enrichment analysis (GSEA) was employed to investigate the biological functions of the identified genes. A combination of LASSO and Cox regression analyses was conducted to establish a risk predictive signature, and time-dependent receiver operating characteristic (tdROC) and Kaplan-Meier analyses were used to evaluate its prediction precision. Quantitative RT-PCR was employed to validate the expression levels of the key genes from the signature set. Results: A total of 2777 genes from three coexpressed gene modules were identified by WGCNA, and 880 differentially expressed genes were identified by transcriptome analyses. The 63 overlapping genes identified by both methods were considered STEL-associated genes, and a 9-gene risk-predictive signature was established based on them, with AUCs at 3, 5, and 7 years reaching 0.810, 0.811, and 0.753, respectively. Conclusion: This study demonstrated the transcriptomic profile of STEL breast cancer and successfully established a risk predictive signature with satisfactory accuracy. These findings may provide insights in to the genetic etiology of breast cancer.


Angelman syndrome.
Angelman syndrome combines severe mental retardation, epilepsy, ataxia, speech impairment, and unique behavior with happy demeanor, laughing, short attention span, hyperactivity, and sleep disturbance. Occurrence has been calculated at 1:20000 to 1:12000 constituting about 6% of all children with severe mental retardation and epilepsy. The physical "prototype" includes microcephaly with flat neck, fair skin and hair, wide-spaced teeth, and open mouth with tongue protrusion. Epilepsy is characterized by atypical absences, erratic myoclonus, and occasional tonic-clonic seizures. EEG demonstrates high-amplitude 2-3Hz delta activity with spike and slow-wave discharges and sleep-activated generalized epileptiform discharges. Sodium valproate, benzodiazepines, and priacetam are frequently used and effective. Development is generally slow, the majority attaining independent walking in the first 2.5-6 years. Vocabulary is limited to a few single words with superior speech and object apprehension. The condition is due to a lack of expression of the UBE3A gene on chromosome 15q. Maternal deletions of 15q11-13 produce the most pronounced phenotype (65-70% of probands), uniparental disomy and imprinting center mutations (10%), and UBE3A point mutations (11%) produce milder phenotypes.


An Early Implementation Analysis of Syringe Services Programs in Kentucky: Barriers and Facilitators Identified by Program Operators and Local Officials.
Kentucky is one of ten states that require syringe services program (SSP) approval from local officials to operate legally. Public health leaders and local officials participated in semi-structured interviews in 2016 about the barriers and facilitators of SSP adoption and implementation (N = 22). Interviews were transcribed verbatim, and a thematic content analysis was conducted using Nvivo software. Political support, program champions who led education efforts, and access to resources and training facilitated SSP adoption. The most frequently reported barriers to adoption were often rooted in stigma and included the lack of political will to approve SSPs or lack of recognition of the need for a SSP. Requiring approval from local governing authorities could impose significant implementation delays, limits to the range of harm reduction services provided, and threaten harm reduction program sustainability. Removing barriers to the adoption and implementation of harm reduction programs is critical in order to effectively scale up harm reduction services to reduce the risks of infection and fatal overdose.


Asthma history influences gait performance and associated prefrontal cortex activation patterns in older adults.
Walking and cognition are interrelated due to dependence on shared brain regions that include the prefrontal cortex (PFC). Limited literature indicates that asthma is associated with poor mobility in older adults but the mechanisms underlying this relationship are unknown. Therefore, we tested the hypothesis that asthma history was associated with poor gait performance due to limited attention resources and neural inefficiency. Participants, older adults age ≥ 65 years reporting positive (n = 36) and negative (n = 36) history of asthma, walked under single and dual-task conditions with a functional near-infrared-spectroscopy (fNIRS) sensor placed on their forehead to assess task-related changes in PFC oxygenated hemoglobin (HbO2). Results showed that positive asthma history was associated with slower gait and higher fNIRS-derived HbO2 under dual-task walking. These findings suggest that limited attention resources and neural inefficiency underlie the association between asthma and poor walking performance in older adults.


Heat shock protein 70 could enhance porcine epidemic diarrhoea virus replication by interacting with membrane proteins.
In this study, we investigated the role of heat shock protein 70 (HSP70) in porcine epidemic diarrhoea virus (PEDV) replication. We found that PEDV infection induced strong HSP70 overexpression in the very early stage of infection. We also confirmed that HSP70 overexpression increased the speed of PEDV replication, resulting in the generation of more virions. In contrast, knockout of HSP70 in cells significantly downregulated PEDV protein expression, resulting in a significant reduction in PEDV replication. Most importantly, we confirmed that among the structural proteins of PEDV, membrane (M) proteins have this important role. We found that membrane proteins control cellular HSP70 expression in PEDV-infected cells. We confirmed HSP70/M complex formation by both immunoprecipitation and immunofluorescence assays. Additionally, PEDV M overexpression induced strong HSP70 expression. All our results clearly confirmed that in PEDV-infected cells, the M protein plays a very important role in PEDV replication in collaboration with HSP70.


Prevention and management of perioperative arrhythmias in the thoracic surgical population.
Although bradyarrhythmias or malignant ventricular tachyarrhythmias have been reported in less than 1% of patients following noncardiac surgery, rapid atrial arrhythmias more frequently affect the elderly who undergo thoracic operations. This article focuses on new issues leading to the improved understanding of the pathophysiology and mechanisms of postoperative atrial arrhythmias. It discusses new risk factors and a prediction rule for postthoracotomy atrial fibrillation (AF), reviews prophylaxis and acute therapeutic interventions for postthoracotomy AF, and highlights the most recent recommendations of the American Heart Association Task Force on the management of patients who have AF with emphasis on preventing thromboembolic events.


The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids.
Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. We studied 893 subjects from the Life-Lines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤ 25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins.


Retinal diseases linked with photoreceptor guanylate cyclase.
Inherited retinal dystrophies are the main causes of progressive visual impairment often leading to blindness. They represent a clinically and genetically heterogenous group of disorders. Continuously increasing body of evidence links retinal dystrophies to mutations in numerous genes. These genes code for retinal proteins of various function (phototransduction, visual cycle, transcription factors, structural and metabolic functions). Mutations in the gene coding for photoreceptor specific guanylate cyclase type 1, ROS-GC1, were found to be the cause for the type 1 Leber's congenital amaurosis (LCAI) and cone-rod dystrophy type 6 (CORD6). The LCA1-linked mutations are distributed over almost the entire ROS-GCI coding sequence but the CORD6-linked mutations are restricted to three positions, E786, R787 and T788, located within the putative ROS-GC1 dimerization domain. A linkage between the biochemical effect of the mutation and its phenotypic manifestation was provided for only one LCA1 mutation, F514S. This was followed by biochemical analyses of the consequences of the CORD6-causing mutations. Here, an overview on the existing results and a discussion of the possible physiological implications are presented.


Three fatalities in flash fire with variable dental charring.
The deaths of three teenagers in an automobile crash and flash fire are presented. The inability to draw valid conclusions about whether the victims were dead prior to the fire based on dental examination is discussed.


Postgastrectomy Syndromes and Nutritional Considerations Following Gastric Surgery.
Postgastrectomy syndromes result from altered form and function of the stomach. Gastrectomy disrupts reservoir capacity, mechanical digestion and gastric emptying. Early recognition of symptoms with prompt evaluation and treatment is essential. Many syndromes resolve with minimal intervention or dietary modifications. Re-operation is not common but often warranted for afferent and efferent loop syndromes and bile reflux gastritis. Preoperative nutritional assessment and treatment of common vitamin and mineral deficiencies after gastrectomy can reduce the incidence of chronic complications. An integrated team approach to risk assessment, patient education, and postoperative management is critical to optimal care of patients with gastric cancer.


Influence of buffering effects of dentifrices and fluoride gels on abrasion on eroded dentine.
Evaluation of abrasion resistance of eroded and non-eroded dentine brushed with experimental dentifrices and gels of varying buffering capacities. One hundred and twenty human dentine specimens were distributed among six groups (A-F) according to the different buffering capacities of experimental toothpastes and gels. The dentifrices (pH: 4.5) and gels (pH: 4.5) differed in fluoride content, RDA-value and buffer capacity (given as mg KOH needed for neutralisation): (A) 0.125%F, RDA: 77, 6mg KOH; (B) 0.125%F, RDA: 125, 24mg KOH; (C) 0.125%F, RDA: 129, 12mg KOH; (D) 0%F, RDA: 81, 1.55mg KOH; (E) 1.25%F, RDA: 21, 8.5mg KOH; (F) 0.125%F, RDA: 7, 3.11mg KOH. Ten specimens were cycled through three alternating demineralisations (1% citric acid, 5min) and remineralisations (artificial saliva, 1min) including brushing abrasion in an automatic brushing machine (2 x 2000 strokes). Ten samples of each group were not eroded, but only brushed. After three cycles, loss of dentine was determined by profilometry (mean +/- S.D. [microm]). Eroded samples: (A) 37.12+/-4.95; (B) 48.67+/-4.77; (C) 39.88+/-3.76; (D) 32.92+/-2.67; (E) 3.65+/-1.35; (F) 6.47+/-1.31. Uneroded samples: (A) 30.78+/-6.47; (B) 37.84+/-7.75; (C) 30.07+/-3.05; (D) 26.93+/-2.30; (E) 1.76+/-0.94; (F) 0.51+/-0.18. Analysis of variance revealed significantly higher abrasion values for the eroded compared to the non-eroded samples (P<or=0.05). Dentifrices with same pH-value, fluoride content and similar RDA-values but a higher buffering capacity exhibited significantly more abrasion than toothpastes with lower buffering capacity. Highly-concentrated fluoride gel with higher buffering capacity lead to less abrasion values compared to the gel with low fluoride concentration and low buffering capacity. Toothbrushing abrasion behaviour of eroded dentine may be influenced by the fluoride content, RDA-value and buffering capacity of the applied dentifrice or gel.


A pilot randomized controlled trial to assess the effect of Islamic spiritual intervention and of breathing technique with heart rate variability feedback on anxiety, depression and psycho-physiologic coherence in patients after coronary artery bypass surgery.
This study investigated the effects of Islamic religious and breathing techniques with heart rate variability (HRV) biofeedback therapies on HRV and psycho-physiologic coherence (resonance frequency), depression and anxiety in coronary artery bypass graft surgery (CABG) patients. Sixty CABG patients were chosen and randomly assigned to religious, breathing techniques and control groups. The experimental groups received 8 weeks of treatments; a 2-h session with home works in each week. The control group received only their normal hospital interventions. The groups' depression, anxiety, HRV and psycho-physiologic coherence levels were assessed before and after the interventions by DASS-21 for depression and anxiety, and em-wave desktop software for HRV and psycho-physiologic coherence. The data were analyzed using ANCOVA with Bonferroni Comparison test and descriptive tests in SPSS software. The findings showed that there were significant differences in psycho-physiologic coherence (HRV), depression and anxiety scores among the three groups in the post-tests. In fact, depression and anxiety were reduced more in the religious group, while psycho-physiologic coherence raised more in the breathing with the HRV feedback group. The results showed that both Islamic religious and breathing techniques with HRV biofeedback therapies can be used in rehabilitation programs for CABG patients in clinics and hospitals.


Postprandial lipemia, fenofibrate and coronary artery disease.
This report describes the response of patients with severe coronary artery disease to a dynamic fat load test and monitors the change induced by fenofibrate therapy. The presence of disease was associated with prolonged and exaggerated hypertriglyceridemia following the meal and with lower basal HDL cholesterol and HDL subfraction masses. A further indicator of risk was the persistence of increased amounts of retinyl palmitate in the plasma of severely affected individuals 24 h after its ingestion with the meal. These observations are consistent with the proposal that the clearance of chylomicrons and their remnants is impaired in coronary atherosclerosis. Fenofibrate reduced alimentary lipemia following the fat load in both normo- and hypercholesterolemic subjects. This was associated with a 10% rise in plasma HDL cholesterol levels. The improvement in chylomicron catabolism probably derived from a 37% increase (P less than 0.001) in lipoprotein lipase activity induced by fenofibrate. Hepatic lipase on the other had was only slightly affected by treatment.


Effects of perfusion flow rate, prostaglandin F2 alpha, phenylephrine, and serotonin on isolated, perfused brains of spontaneously hypertensive rats.
Effects of perfusion flow rate and three vasoconstrictors, phenylephrine, prostaglandin F2 alpha (PGF2 alpha) and serotonin, on isolated, perfused brain preparations of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY) were investigated. The basal perfusion pressure of the cerebral vascular beds at a flow rate of 2.5 ml/min was 48 +/- 3 mm Hg (n = 11) in SHR and 32 +/- 2 mm Hg (n = 12) in WKY (P less than 0.005). The perfusion pressures at all flow rates tested (2.5-6.5 ml/min) in SHR were significantly greater than those in WKY. Concentration-perfusion pressure curves for the vasoconstrictors showed that the brain vascular bed was much more reactive to serotonin compared with phenylephrine and PGF2 alpha. EC50 values (-logM) for serotonin in the perfused brains of SHR and WKY were 7.0 +/- 0.06 (n = 10) and 6.5 +/- 0.06 (n = 11), respectively (P less than 0.01). There were no differences in EC50 values for phenylephrine or PGF2 alpha between SHR and WKY. Exogenous serotonin and phenylephrine caused significantly greater maximal vasoconstrictor responses in SHR compared with WKY, while the pressor response to PGF2 alpha was very weak and no significant difference between SHR and WKY preparations was observed. These results indicate that cerebral vascular beds in SHR exhibit higher cerebrovascular resistance than those in WKY. and that reactivity and sensitivity to serotonin and reactivity to phenylephrine in SHR rats are enhanced to a greater extent compared to WKY.


Market opportunities seizing capability and fish farming firm performance: A dynamic managerial capability perspective.
The role that owner-managers' managerial capabilities play in agricultural firms' strategic change and performance is still unclear. A firm's market opportunities seizing capability (OSC) is a source of competitiveness and superior performance. The objective of this study is to establish how owner-manager's dynamic managerial capabilities (DMCs) including managerial human capital, managerial social capital and managerial cognition affect firm performance through the mediating effect of OSC, as well as the moderating effect of market dynamism in the relationship OSC and firm performance. 306 cross-sectional data collected at fish farming firms (FFF) level in southern Benin were used and partial least squares structural equation model was applied to test research hypotheses. The results of SmartPLS4 reveal that owner-managers' DMCs including business ties (BTs), political ties (PTs), and managerial cognition (MC) demonstrate a significant effect at improving FFF market OSC and performance. Finding also underline the significant contribution of market dynamism to FFF performance as well the mediating role of market OSC in the relationship between BTs, PTs, MC, and FFF performance. Findings suggest that FFF owner-managers can achieve superior performance by strengthening their DMCs while improving market OSC. The study provides useful insights to FFF owner-managers, agriculture policymakers and practitioners who are engaged in agriculture firms' strategic management and sustainable performance.


[Health, hospitality sector and tobacco industry].
To present the strategies used by the tobacco industry to meet government regulatory measures of its products. To demonstrate the relationship between tobacco industry and the hospitality sector. Note that the arguments and strategies used routinely by the hospitality industry have been previously provided by the tobacco industry. Location of key documents by meta-search, links to declassified documents, specific websites of the tobacco and hospitality industry, news sources and published articles in health journals. This review reveals the close relationship between tobacco industry and hospitality sector. It highlights the strategies carried out by the tobacco industry, including strategic hoarding of information, public relations, lobbying, consultation program, smoker defence groups, building partnerships, intimidation and patronage. The arguments and strategies used by the hospitality industry to match point by point that used by the tobacco industry. These arguments are refutable from the point of view of public health as it is scientifically proven that totally smoke-free environments are the only way to protect non-smokers from tobacco smoke exposure and its harmful effects on health.


Genetic traits for hematogeneous tumor cell dissemination in cancer patients.
Metastatic relapse in patients with solid tumors is the consequence of cancer cells that disseminated to distant sites, adapted to the new microenvironment, and escaped systemic adjuvant therapy. There is increasing evidence that hematogeneous dissemination starts at an early stage of cancer progression with single tumor cells or cell clusters leaving the primary site and entering the blood circulation. These circulating tumor cells (CTCs) can extravasate into secondary tissues where they become disseminated tumor cells (DTCs). Patients might relapse years after initial resection of the primary tumor when DTCs become overt metastases. Current diagnostic strategies for stratification of therapies against metastatic cells focus on the primary tumor tissue. This approach is based on the availability of stored primary tumors obtained at primary surgery, but it ignores that the DTCs might have evolved over years, which can affect the antimetastatic drug response. However, taking biopsies from metastatic tissues is an invasive procedure, and multiple metastases located at different sites in an individual patient show marked genomic heterogeneity. Thus, capturing CTCs from the peripheral blood as a "liquid biopsy" has obvious advantages in particular when repeated sampling is required for monitoring therapies in cancer patients. However, the biology behind tumor cell dissemination and its contribution to metastatic progression in cancer patients is still subject to controversial discussions. This manuscript reviews current theories on the genetic traits behind the spread of CTCs and progression of DTCs into overt metastases.


Imaging and histomorphometric evaluation of mandible and tibia of rats treated with bisphosphonates.
To evaluate the mandible and tibia of rats treated with bisphosphonates (BPs) by imaging and histomorphometric analysis. Thirty-four rat specimens (Rattus norvegicus, Wistar strain) were distributed into 3 groups: (1) 12 rats treated with zoledronic acid; (2) 12 rats treated with clodronate; and (3) the control group, containing 10 rats that received saline. All bones were exposed to cone beam computed tomography (CBCT). The images were analyzed to determine bone density (BD), using the software OsiriX 7.0. Histological slides were prepared from the specimens and the proportion of bone volume (BV) was quantified using the software Adobe Photoshop CC. There was no statistically significant difference in BD either between the drug groups or between mandible and tibia. BV between BPs and control group did not show a significant difference. However, comparing the two bones, the mandibles in the control group displayed higher BV than did the tibiae in the same group. According to our results, we conclude that (1) BD was not altered by bone type or by type of BP administered, and (2) treatment with zoledronic acid or clodronate did not affect BV in the mandible or tibia of test groups.


Parafollicular cells of rabbit thryoid store both calcitonin and somatostatin and resemble gut D cells ultrastructurally.
Both calcitonin and somatostatin have been detected immunohistochemically in rabbit parafollicular cells; only calcitonin has been found in the same cells of the dog, guinea-pig and man. Large amounts of a peptide radioimmunochemically identical with synthetic somatostatin have been detected in extracts of rabbit thyroid. The ultrastructural and staining features of rabbit parafollicular cells differ from those of parafollicular cells in other species, while resembling in part those of somatostatin D cells scattered in the rabbit stomach.


An analysis of a large multi-institutional database reveals important associations between treatment parameters and clinical outcomes for stereotactic body radiotherapy (SBRT) of oligometastatic colorectal cancer.
In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database. Patients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes. We identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression. This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED10 should be considered if feasible and safe.


The effect of glucocorticoids on corticosteroid binding globulin.
To evaluate the effect of glucocorticoids on corticosteroid binding globulin (CBG), we measured the binding capacity and binding affinity of cortisol for CBG in normal subjects, patients receiving glucocorticoids and patients with Cushing's syndrome. Normal subjects had a mean binding capacity of 3.8 (+/- SD 0.7) X 10(-7) mol/l and mean binding affinity of 1.96 +/- 0.48 X 10(-8) M. Patients with Cushing's syndrome had a 40% decrease in binding capacity (2.3 +/- 0.4 X 10(-7) mol/l) compared to control subjects and significantly lower mean binding capacity than patients receiving pharmacological (2.9 +/- 0.6 X 10(-7) mol/l) and physiological doses of glucocorticoids (3.4 +/- 0.6 X 10(-7) mol/l) (P = 0.05 one-way analysis of variance). Patients with endogenous cortisol excess also had significantly lower mean binding affinity (1.54 +/- 0.37 X 10(-8) M) than normal subjects and glucocorticoid treated subjects. These changes suggest that both endogenous and exogenous glucocorticoids can modulate circulating levels of CBG and may have important implications for patients receiving steroid therapy.


Targeting minor histocompatibility antigens in graft versus tumor or graft versus leukemia responses.
Allogeneic hematopoietic cell transplantation (alloHCT) represents the only curative therapy for several hematologic malignancies, and shows promise as a nascent treatment modality for select solid tumors. Although the original goal of alloHCT was hematopoietic reconstitution after sub-lethal chemoradiotherapy, recognition of a profound donor lymphocyte-mediated graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect has shifted the paradigm from pre-transplant cytoreduction to tumor control via donor lymphocytes. In human leukocyte antigen (HLA)-compatible alloHCT, GVL and GVT reactions are induced primarily by donor T-cell recognition of minor histocompatibility antigens (mHAgs). Here we review the literature regarding mHAg-specific T cells in GVL and GVT reactions, and discuss the prospects of exploiting mHAgs as immunotherapeutic targets.


Pharyngo-laryngeal histoplasmosis: one case in an immunocompetent child.
We report a very rare case of disseminated pharyngo-laryngeal histoplasmosis with systemic spread in a 10-year-old, immunocompetent child from Guyana. The main signs were a marked deterioration in his general condition, hepato-splenomegaly, multiple lymphadenopathy and ulcerated pharyngo-laryngeal lesions. The diagnosis was made from brushings of the ulcerative lesions, a lymph node biopsy and serological tests performed in the national reference center for histoplasmosis. The initial treatment was with amphotericin B, which was then replaced by oral itraconazole. We report here the main epidemiological, clinical and therapeutic characteristics.


Erratum: Are there a guidelines for implantable spinal cord stimulator therapy in patients using chronic anticoagulation therapy? - A review of decision-making in the high-risk patient.
[This corrects the article on p. 33 in vol. 7, PMID: 27127698.].


Nearly total unilateral buttock reconstruction with a proximally pedicled anterolateral thigh flap: a case report.
The anterolateral thigh flap has been used to reconstruct defects of lower trunk, perineum and upper thigh. We used a proximally based pedicled anterolateral thigh flap to repair an extensive gluteal defect ranging from the greater trochanter to the posterior midline and preserve the buttock contour. We conclude that the maximal lateral reach of the flap can extend to the posterior midline.


Applications of mental rotation figures of the Shepard and Metzler type and description of a mental rotation stimulus library.
The 3D cube figures used by Shepard and Metzler [Shepard, R. N., & Metzler, J. (1971). Mental rotation of three-dimensional objects. Science, 171, 701-703] have been applied in a broad range of studies on mental rotation. This note provides a brief background on these figures, their general use in cognitive psychology and their role in studying spatial behavior. In particular, it is pointed out that large sex differences with the 3D mental rotation figures tend to be observed only in particular tasks, such as the Vandenberg and Kuse test [Vandenberg, S. G., & Kuse, A. R. (1978). Mental rotations, a group test of three-dimensional spatial visualization. Perceptual and Motor Skills, 47, 599-604] that involve multiple figures within a single problem. In contrast, pairwise presentation of the same 3D figures yields either small or no significant sex differences. In the context of the very broad range of ongoing research done with 3D figures, and the desirability of uniformity in the stimulus material used, we introduce a library of 16 cube mental rotation figures, each presented in orientations ranging from 0 to 360 degr in 5 degr steps, and with its mirror image, for a total of 2336 figures. This library, freely available to researchers, will help in the creation of mental rotation tasks both for presentation on the computer screen and for pencil and paper applications.


gyrB mutations which confer coumarin resistance also affect DNA supercoiling and ATP hydrolysis by Escherichia coli DNA gyrase.
Coumarins are inhibitors of the ATP hydrolysis and DNA supercoiling reactions catalysed by DNA gyrase. Their target is the B subunit of gyrase (GyrB), encoded by the gyrB gene. The exact mode and site of action of the drugs is unknown. We have identified four mutations conferring coumarin resistance to Escherichia coli: Arg-136 to Cys, His or Ser and Gly-164 to Val. In vitro, the ATPase and supercoiling activities of the mutant GyrB proteins are reduced relative to the wild-type enzyme and show resistance to the coumarin antibiotics. Significant differences in the susceptibility of mutant GyrB proteins to inhibition by either chlorobiocin and novobiocin or coumermycin have been found, suggesting wider contacts between coumermycin and GyrB. We discuss the significance of Arg-136 and Gly-164 in relation to the notion that coumarin drugs act as competitive inhibitors of the ATPase reaction.


Experimental dermatophytoses produced by E. floccosum in guinea pigs.
Experimental dermatophytoses were tested in guinea pigs by 17 strains of genus Epidermophyton. Only three strains of E. floccosum produced lesions. These lesions were detected 5-7 d after inoculation, and no crust formation or alopecia was observed. These lesions were also studied using microbiological and histopathological techniques. No infection occurred after cutaneous application of E. floccosum var. nigricans and E. stockdaleae.


Cloning CD8⁺ cytolytic T lymphocytes.
CD8(+) T lymphocyte cloning has resulted in many fundamental advances: structural elucidation of peptide-MHC recognition, spatiotemporal dissection of the thymic positive and negative selection processes and is further expected, TCRs being the key molecules controlling T cell activation, to provide us with molecular tools of immuno-therapeutical interest for infectious, tumor, and autoimmune diseases. However, cloning CD8(+) T lymphocytes remains a relatively difficult enterprise. Cloning mouse CD8(+) T lymphocytes that will be first consider is to some extend facilitated by our complete control of the in vivo priming process and the unlimited access we usually have to perfectly suited (syngeneic) antigen presenting cells. Cloning human CD8(+) T lymphocytes is more difficult largely but not exclusively for ethical reasons.


Competition between ABO and Le gene specified enzymes. II. Quantitative analysis of A and B antigens in saliva of ABH nonsecretors.
One B- and two A-specific radioimmunoassays detected A and B antigenic determinants in saliva of ABH nonsecretors. The A or B antigens found in saliva of nonsecretors had lower efficiency and higher heterogeneity, in the inhibition of the A or B assays, as compared to A or B antigens in saliva of ABH secretors. In the 3 assays, samples of nonsecretor Lewis positive donors (Lea) had less A or B antigens than samples of nonsecretor Lewis negative donors (Lec), suggesting that there is a competition between A or B and Le gene-specified products.


Hypoplasia of the left lobe of the liver.
In a forensic autopsy, hypoplasia of the left lobe (lateral segment) of the liver was found. Although the cause was unknown, the morphologic anomaly observed in this case was regarded as congenital because there was no history of surgery. Moreover, the main vessels of the left lobe were present despite complete absence of the parenchyma.


Cross-sectional survey of hypertension management in clinical practice in Japan: the Kanagawa Hypertension Study 2021 conducted in collaboration with Japan Medical Association Database of Clinical Medicine.
We aim to assess the data of patients with hypertension in Kanagawa Prefecture, Japan, collected in 2021 that were provided by the Japan Medical Association Database of Clinical Medicine. Data collected in 2011 and 2014 by the Kanagawa Physicians Association were used for comparative analysis. The target blood pressure (BP) achievement rates for patients whose target office and home BP were <140/90 mmHg and <135/85 mmHg, respectively, were 72.5% and 75.8% in 2011, 66.0% and 68.5% in 2014, and 46.7% and 83.3% in 2021, respectively. The target office BP achievement rate in 2021 was significantly lower than those in 2011 and 2014 (p ≤ 0.009). In contrast, there was no significant difference and improvement of the achievement rates for patients whose target office and home BP were <130/80 mmHg and <125/75 mmHg, respectively, among the three surveys. After the Japanese Society of Hypertension 2019 Guidelines were released, the achievement rates for patients whose target BP was tightened were significantly lower than those for patients with unchanged target BP (office/home, p < 0.001/0.04). The proportion of the patients who achieved their office and home target BP using more than three drugs was 38.5% and 20.0%, respectively. In the present analysis, we unveiled the current problems encountered in the clinical management of hypertension in Japan. In particular, efforts should be focused on the management of patients that require strict BP control.


Elevated serum Bcl-2 in children with temporal lobe epilepsy.
Intractable temporal lobe epilepsy (TLE) is associated with alterations in expression of apoptosis-associated signaling molecules in the temporal lobe. Bcl-2 is an anti-apoptotic molecule which has previously been reported to be raised in patient's brain and serum. In the present study we examined serum Bcl-2 protein levels as a surrogate marker of apoptosis-associated signaling in children with non lesional TLE. Serum Bcl-2 levels were found to be higher in patients with TLE than controls. The serum level correlated to seizure variables including, duration of disease, frequency of seizures, and disease severity. The impact of epilepsy on cognition was assessed using total score intelligence quotient (IQ). IQ was found to be lower than controls and negatively correlated to serum Bcl-2. These findings support serum Bcl-2 levels as a marker of seizure burden and cognition in children with epilepsy.


Negative parenting styles and social adjustment of university students: a moderated chain mediation model.
This study aimed to explore the relationship between parenting styles and the social adjustment of university students as well as the mediating effects of attachment avoidance and friendship quality. We further examined the moderating role of gender. This study used convenience sampling to recruit 501 Chinese university students to complete the Chinese version of the Negative Parenting subscale of EMBU, Attachment Avoidance Scale, Friendship Quality Questionnaire, and Social Adjustment Scale. SPSS 24.0 and the Process 3.5 macro program were used to carry out descriptive statistical and correlation analyses and mediating effect and moderated chain-mediating effect tests on the data. The analyses revealed that negative parenting styles significantly negatively predicted social adjustment in university students. Attachment avoidance mediated the relationship between negative parenting styles and social adjustment in university students, and friendship quality mediated the relationship between negative parenting styles and social adjustment in university students. Attachment avoidance and friendship quality played a chain-mediating role in the relationship between negative parenting styles and university students' social adjustment. Gender moderated the effect of negative parenting style on friendship quality among university students. These results show how negative parenting styles affect college students' social adjustment and its underlying mechanisms in the context of China's collectivist culture and high power distance and further reveal the gender differences involved, providing insights to better understand the factors influencing college students' social adjustment.


Identification of differentially expressed gene pathways between cytopathogenic and non-cytopathogenic BVDV-1 strains by analysis of the transcriptome of infected primary bovine cells.
The bovine viral diarrhea virus 1 (BVDV-1), belonging to the Pestivirus genus, is characterized by the presence of two biotypes, cytopathogenic (cp) or non-cytopathogenic (ncp). For a better understanding of the host pathogen interactions, we set out to identify transcriptomic signatures of bovine lung primary cells (BPCs) infected with a cp or a ncp strain. For this, we used both a targeted approach by reverse transcription droplet digital PCR and whole genome approach using RNAseq. Data analysis showed 3571 differentially expressed transcripts over time (Fold Change >2) and revealed that the most deregulated pathways for cp strain are signaling pathways involved in responses to viral infection such as inflammatory response or apoptosis pathways. Interestingly, our data analysis revealed a deregulation of Wnt signaling pathway, a pathway described in embryogenesis, that was specifically seen with the BVDV-1 cp but not the ncp suggesting a role of this pathway in viral replication.


Effect of pelvic floor dysfunction on sexual function and quality of life in Chinese women of different ages: An observational study.
The aim of the present study was to investigate the effect of female pelvic floor dysfunction on sexual function and quality of life among different age groups. An observational study was carried out on 648 patients with pelvic organ prolapse (POP) or/and stress urinary incontinence. We assessed female sexual function and quality of life through the Prolapse/Urinary Incontinence Sexual Questionnaire Short Form and Incontinence Quality of Life Scale before surgeries, respectively. Patients were assigned into different age groups. The mean age of all patients was 62.04 ± 9.39 years. A total of 436 patients had POP, 120 patients had stress urinary incontinence and the remaining patients had both. Although sexual frequency decreased with increasing age, 517 patients still remained sexually active. A total of 10.83% of the patients aged ≥70 years were still sexually active, and 8.51% of them had sex less than one time per month. The Prolapse/Urinary Incontinence Sexual Questionnaire Short Form score and sexual frequency decreased with increasing age. However, the Incontinence Quality of Life Scale score increased with increasing age. Patients with only POP and aged ≥70 years showed a higher Incontinence Quality of Life Scale score (P < 0.001). The present study showed that POP and stress urinary incontinence are common among older Chinese women, and re associated with decreased sexual satisfaction and quality of life in China. It suggests that the existing sexual requirement of these patients should also be reconsidered before surgical assessment. Doctors should take sexual satisfaction into consideration when choosing a personalized type of surgery to improve the patients' quality of life physiologically and psychologically. Geriatr Gerontol Int 2019; 19: 299-304.


Deficiency of exchange protein directly activated by cAMP (EPAC)-1 in mice augments glucose intolerance, inflammation, and gut dysbiosis associated with Western diet.
Gut microbiota (GM) dysregulation, known as dysbiosis, has been proposed as a crucial driver of obesity associated with "Western" diet (WD) consumption. Gut dysbiosis is associated with increased gut permeability, inflammation, and insulin resistance. However, host metabolic pathways implicated in the pathophysiology of gut dysbiosis are still elusive. Exchange protein directly activated by cAMP (Epac) plays a critical role in cell-cell junction formation and insulin secretion. Here, we used homozygous Epac1-knockout (Epac1-/-), Epac2-knockout (Epac2-/-), and wild-type (WT) mice to investigate the role of Epac proteins in mediating gut dysbiosis, gut permeability, and inflammation after WD feeding. The 16S rRNA gene sequencing of fecal DNA showed that the baseline GM of Epac2-/-, but not Epac1-/-, mice was represented by a significantly higher Firmicutes to Bacteroidetes ratio and significant alterations in several taxa compared to WT mice, suggesting that Epac2-/- mice had gut dysbiosis under physiological conditions. However, an 8-week WD led to a similar gut microbiome imbalance in mice regardless of genotype. While Epac1 deficiency modestly exacerbated the WD-induced GM dysbiosis, the WD-fed Epac2-/- mice had a more significant increase in gut permeability than corresponding WT mice. After WD feeding, Epac1-/-, but not Epac2-/-, mice had significantly higher mRNA levels of tumor necrosis factor-alpha (TNF-α) and F4/80 in the epididymal white adipose tissue (EWAT), increased circulating lipocalin-2 protein and more severe glucose intolerance, suggesting greater inflammation and insulin resistance in WD-fed Epac1-/- mice than corresponding WT mice. Consistently, Epac1 protein expression was significantly reduced in the EWAT of WD-fed WT and Epac2-/- mice. Despite significantly dysregulated baseline GM and a more pronounced increase in gut permeability upon WD feeding, WD-fed Epac2-/- mice did not exhibit more severe inflammation and glucose intolerance than corresponding WT mice. These findings suggest that the role of gut dysbiosis in mediating WD-associated obesity may be context-dependent. On the contrary, we demonstrate that deficiency of host signaling protein, Epac1, drives inflammation and glucose intolerance which are the hallmarks of WD-induced obesity. Video abstract.


A new strategy for treatment of liver fibrosis: letting MicroRNAs do the job.
MicroRNAs (miRNAs) are short, endogenous, noncoding RNA molecules that regulate gene expression at a post-translational level. MiRNAs have been recognized in the regulation of physiological conditions. Moreover, awareness of the association between dysregulated miRNAs and human diseases is increasing, which consequently brings miRNAs to the frontline in the development of novel therapeutic strategies. We review the latest advances in our knowledge of the involvement of miRNAs in fibrosis with particular emphasis on hepatic fibrosis and the possibilities in the near future for miRNA-based therapy for targeted treatment of liver fibrosis. With recent advances in our understanding of the important role of senescence in the resolution of activated hepatic stellate cells (HSCs), we suggested the therapeutic potential of inducing activated HSCs into senescence by an miRNA-based strategy.


Carotenoid and Apocarotenoid Analysis by SFE-SFC-QqQ/MS.
Carotenoids and carotenoids oxidative and enzymatic cleavage products called apocarotenoids are very important bioactive molecules in plants and humans, with different biological functions. Both central and noncentral carotenoid cleavage products have been reported to occur in food and in humans, where they may act as bioactive molecules with functions that were previously attributed to the parent carotenoid. However, relatively few studies are available in the literature on the apocarotenoid occurrence in food and biological fluids which were mainly based on liquid chromatographic separation approaches and even fewer reports are available on the carotenoid and apocarotenoid separation by a direct online supercritical fluid extraction-supercritical fluid chromatography with triple-quadrupole mass spectrometry detection (SFE-SFC-QqQ/MS) methodology. In comparison with offline approaches the online nature of the system drastically reduces the extraction time required in traditional solid/liquid extraction, which may require a few hours. Moreover, it reduces the analysis run time, as well as the risks of sample contamination and the possible occurrence of operator errors, improves run-to-run precision, and enables the setting of batch-type applications. The purpose of this contribution was to provide an updated description of the SFE-SFC-QqQ/MS methodology applied to carotenoid and apocarotenoid analysis in various matrices, although with a particular focus on the apocarotenoid applications.


British Association of MR Radiographers (BAMRR) safety survey 2005: potential impact of European Union (EU) Physical Agents Directive (PAD) on electromagnetic fields (EMF).
To measure the potential impact on clinical MRI practice in the UK of the European Union (EU) Physical Agents Directive (PAD) on electromagnetic fields (EMF). There is evidence that the exposure limit values contained in the PAD will make it impossible for members of staff to stand close to the magnet during scanning; currently this is common practice in order to provide care and support for vulnerable patients. Interventional MR procedures will also be impossible. Members of the British Association of MR Radiographers (BAMRR) were sent a questionnaire to assess the impact of the PAD and related safety issues. A total of 25% of responding sites have at least one sedation/general anesthesia (GA) session per week, while only 3% reported any interventional practice. A total of 29% of respondents reported that operators give a bolus injection by hand during contrast-enhanced magnetic resonance angiography (CE-MRA) scans. Overall it is estimated that 3% of all MR examinations in the UK are performed with a staff member in the magnet room. Some of these examinations would be impossible without staff in the room and it would be necessary for patients to have computed tomography (CT) instead of MRI. The additional radiation dose of substituting CT for MRI is estimated at 224 man-sievert per year. While the financial costs of implementing the PAD (EMF) are relatively low, the social costs are difficult to quantify but potentially more alarming.


Update: influenza activity--United States, 1993-94 season.
From mid-November through December 1993, influenza activity in the United States increased. This report summarizes surveillance information regarding influenza activity in the United States from October 3, 1993, through January 1, 1994.


Blood compatibility of methyl, methyl vinyl, methyl phenyl, and trifluoropropylmethylvinyl silicone rubber without silica fillers in the spiral-coiled membrane lung.
Spiral-coiled membrane lungs of 0.6 m2 surface area were fabricated from silicone rubber membranes coated with four types of commercially available pure-gum polysiloxane rubber: 1) polytrifluoropropylmethylvinylsiloxane, 2) polymethylphenylsiloxane, 3) polymethylvinylsiloxane, and 4) polydimethylsiloxane. Membranes lungs were tested in an arteriovenous shunt without added heparin after bypass was begun. All group 4 had major rise in resistance to blood flow or clotting in over 33% of the membrane lungs studied, after 6 hr of bypass. Membrane lungs with polydimethylsiloxane (group 4) had no rise in resistance to blood flow during 24 hr of bypass and had the least amount of changes in blood platelet count.


Conformations and molecular interactions of poly-γ-glutamic acid as a soluble microbial product in aqueous solutions.
Soluble microbial products (SMPs) are of significant concern in the natural environment and in engineered systems. In this work, poly-γ-glutamic acid (γ-PGA), which is predominantly produced by Bacillus sp., was investigated in terms of pH-induced conformational changes and molecular interactions in aqueous solutions; accordingly, its sedimentation coefficient distribution and viscosity were also elucidated. Experimental results indicate that pH has a significant impact on the structure and molecular interactions of γ-PGA. The conformation of the γ-PGA acid form (γ-PGA-H) is rod-like while that of the γ-PGA sodium form (γ-PGA-Na) is sphere-like. The transformation from α-helix to random coil in the γ-PGA secondary structure is primarily responsible for this shape variation. The intramolecular hydrogen bonds in the γ-PGA-H structure decrease and intramolecular electrostatic repulsion increases as pH increases; however, the sedimentation coefficient distributions of γ-PGA are dependent on intermolecular interactions rather than intramolecular interactions. Concentration has a more substantial effect on intermolecular electrostatic repulsion and chain entanglement at higher pH values. Consequently, the sedimentation coefficient distributions of γ-PGA shift significantly at pH 8.9 from 0.1 to 1.0 g/L, and the viscosity of γ-PGA (5% w/v) significantly increases as pH increases from 2.3 to 6.0.


Parental Psychological Control and Children's Relational Aggression: Examining the Roles of Gender and Normative Beliefs about Relational Aggression.
Drawing on the information processing model for the development of aggression, children's acquisition of aggressive responses could be associated with parenting that communicated norms favoring aggression. Extending this view, the present study examined the mediating role of children's normative beliefs about relational aggression (NBRA) on the association between psychologically controlling parenting and children's relational aggression (RA), and further explored whether this possible indirect effect would be contingent on the child's gender. 341 upper elementary school students (174 boys and 166 girls) reported perceived paternal psychological control (PPC) and maternal psychological control (MPC) during their fifth-grade fall semester, rated their NBRA during their sixth-grade fall semester, and assessed RA through a peer-nomination procedure during their sixth-grade spring semester. Results demonstrated that the indirect effects of perceived PPC and MPC on children's RA via their NBRA were both significant among the entire sample. However, by means of conditional process analysis, we found that whereas perceived PPC positively predicted boys' and girls' NBRA, perceived MPC positively predicted boys' but not girls' NBRA. In addition, children's NBRA was only positively predictive of RA for girls. As such, the indirect effect was exclusively significant for perceived PPC among girls.


DIADEM--a system for the interactive data acquisition and processing in an analytical laboratory.
A conversational program for the acquisition of experimental data in a multi-user, multi-instrument computer system is described. It assists the researcher when recording on-time data. Due to the simple structure of the dialogue, no special knowledge of computer handling is required by the experimenter. Whereas the experimental methods are versatile, a uniform concept of the dialogue and the file structure is realized.


Quality control of retinoids in commercial cosmetic products.
Retinoids are widely used in different cosmetic products because of general improvement of skin appearance. However, retinoid concentration in cosmetics is restricted, and one particular form-retinoic acid, is banned in cosmetics due to safety reasons. Within this study, we aimed to examine the quality of a considerable number of commercial retinoid cosmetic products in terms of their content and labeling, including also screening for the presence of retinoic acid. An appropriate analytical methodology, based on HPLC-UV for the simultaneous determination of common retinoids, along with a screening method for retinoic acid, was developed and validated. Structural identity confirmation of the newer retinoid-hydroxypinacolone retinoate, was performed by LC-MS. Retinol and retinyl palmitate were most often found, in concentrations mostly below 0.3%, and up to 1.3% retinol equivalents. Determined contents deviated significantly from the quantitatively declared ones in seven products (0%-130%). In more than half of the tested products, inconsistencies between the contained and labeled retinoid were noticed. These products, as well as 14 additional anti-age cosmetics, were screened for retinoic acid, which was detected in two products. The obtained results from retinoids assay in commercial cosmetic products confirmed that the proposed method is appropriate for their routine analysis. The presence of retinoic acid in two products and determined retinoid contents above the Scientific Committee on Consumer Safety recommendations in 20% of the tested cosmetics reveal the need for their more strict regulation and quality control to ensure their efficacy and safety.


Molecular immunological heterogeneity of the Salmonella zuerich [1, 9, 12, (46), 27] cell-wall polysaccharides.
Extraction of O specific polysaccharide from S. zuerich leads to three fractions (ZA, ZB, ZC). Polysaccharide ZB carries specificities 1, 27, and 46, present on the Salmonella cells. It exhibits a factor 27 that is very similar to that present on the S. typhi T2 1-minus 27-+ polysaccharide, a factor 1 that is close to that present on S. senftenberg polysaccharide, and a factor 46 that gives a very weak cross-reaction with anti-46 antibodies. Polysaccharides ZA and ZB are immunologically different and ZB contains two distinct fractions: ZB 1-minus devoid of Ofactor 1 and carrying the specificities 46 and 27 mostly, of not completely, on the same molecule (46, 27); and ZB1-+ carrying O factors 1, (46), 27. ZB 1-+ is composed of at least two different molecules: [1,(46)] precipitable with anti-1 antibodies but only coprecipitable with anti-46 antibodies; and (1, 27) precipitable with both anti-1 and anti-27 antibodies. Molecules [1, (46)] precipitate only part of the anti-1 antibodies precipitable by (1, 27). The smaller precipitation of anti-27 antibodies (when factor 27 is present together with factor 1 on the same molecule) and the coprecipitation, instead of precipitation, of anti-46 antibodies (when factors 46 and 1 are present on the same molecule) may be explained by a sterical hindrance between O-factors 1 and 27, and 1 and 46. The molecular, immunological heterogeneity of the polysaccharides extracted from S. zuerich would result from the presence on the cells of two kinds of O polysaccharides: one with, the other without O factor1, which is related to the presence of a side-chain of an alpha-D-glucosyl residue. A structure for S. zuerich polysaccharide is proposed.


Comparison of the Haemodynamic Performance of Various Treatment Options for Aorto-Iliac Occlusive Disease.
Several surgical and endovascular techniques are used during the treatment of aorto-iliac occlusive disease. Aortobifemoral bypass (AoBFB) is the standard of care, but other options such as axillobifemoral (AxBFB) bypass, aorto-iliac kissing stents (KS), and covered endovascular reconstruction of aortic bifurcation (CERAB) are also available. This study aimed to perform a computational comparison of these four modalities to investigate their haemodynamic performance. Eight patient specific anatomies were analysed, with each of the abovementioned techniques used to treat two anatomies. The CT angiograms were segmented from the renal (or axillary) to common femoral arteries and the 3D geometries were exported. A commercial finite volume solver was implemented for numerical simulations. Outcomes that were assessed were pressure drop (ΔP) between the inlet and the outlet for every configuration and haemodynamic indices of Time Average Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), and Relative Residence Time (RRT) as markers of a thrombogenic environment. The results indicate that maximum ΔP was observed at peak systole for all models, with values ranging between 12 mmHg and 21 mmHg for the AoBFB, 64 mmHg and 96 mmHg for the AxBFB, 31 mmHg and 46 mmHg for the KS, and 43 mmHg and 46 mmHg for the CERAB configuration. TAWSS, OSI, and RRT varied among different configurations, mostly presenting values well above thrombogenic thresholds. Regarding RRT, the percentage of total surface area presenting such values is 2.5%, 3.2%, 2%, and 4.3% for the AoBFB, AxBFB, KS, and CERAB configurations, respectively. Computational modelling indicates a favourable haemodynamic performance of AoBFB compared with the other configurations. This leads to a smaller pressure drop and sconsequently a higher pressure in the outlet of the conduit, which is the perfusion pressure of the limb. Notably, lower patency rates of the latter modalities cannot be explained based on haemodynamic indices.


Effects of respiratory gas composition on transthoracic impedance.
The transthoracic current generated during defibrillation comprises a cardiac and extracardiac component. Changes in impedance of transthoracic pathways will alter the transmyocardial current and may thus affect the outcome from defibrillation. The lungs comprise a large component of extracardiac tissue but the effects of different respiratory gases on transthoracic impedance has not been documented. We therefore measured transthoracic impedance (TTI) using different respiratory gas mixtures. TTI across self-adhesive defibrillation pads placed in the antero-apical position was measured at end-expiration using a 30 kHz low amplitude AC current. Ten healthy subjects aged 22-34 years (eight male) were studied whilst breathing alternate mixtures of air, 100% oxygen. 70% helium in 30% oxygen, and 70% nitrous oxide in 30% oxygen administered in a random sequence. There was no significant difference in TTI between any of the four respiratory gases. Therefore transthoracic current during defibrillation is unlikely to be affected by different respiratory gases. This is the first study to document that these respiratory gases do not change the impedance of transthoracic pathways.


Predictors of body image dissatisfaction in elementary-age school girls.
Concerns about weight, shape, body image, dieting, and eating are evident among elementary-age school girls [Int. J. Eating Disord. 10 (1991) 199; J. Adolesc. Health 12 (1991) 307; Pediatrics 84 (1989) 482; J. Clin. Psychol. 21 (1992) 41; Addict. Behav. (2000).]. Body image dissatisfaction, found to predict the formation of eating disturbances in longitudinal studies [Eating Disord.: J. Treat. Prev. 2 (1994) 114; Int. J. Eating Disord. 18 (1995) 221.], is likely a necessary precursor of eating disturbance development [J. Abnorm. Psychol. 102 (1993) 438.]. Turning back the etiological clock, this study examines the association between body image dissatisfaction and four potential areas of influence, including peer relationships, family characteristics, personality features, and body mass index, among girls in grades three, four, and five. Each conceptual area significantly contributed to the prediction of body image dissatisfaction. The combination of statistically significant variables, including teasing, peer modeling of weight and shape concerns, daughters' perceptions of parental influence to lose or control weight, appearance comparison, sensitivity, and body mass index, accounted for 50% of the variance in general body image dissatisfaction and 45% in weight and shape dissatisfaction. Implications for prevention, treatment, and future research are discussed.


Mechanism-based criteria to improve therapeutic outcomes in progressive multiple sclerosis.
In contrast to the multiple disease-modifying therapies that are available for relapsing-remitting multiple sclerosis (MS), the therapeutic options for progressive MS (PMS) are limited. Recent advances in our understanding of the neuroimmunology of PMS, including the mechanisms that drive slowly expanding lesions, have fuelled optimism for improved treatment of this condition. In this Review, we highlight the commonly observed neuropathology of PMS and discuss the associated mechanisms of CNS injury. We then apply this knowledge to formulate criteria for therapeutic efficacy in PMS, beginning with the need for early treatment owing to the substantial neuropathology that is already present at the initial clinical presentation. Other requirements include: antagonism of neuroaxonal injury mediators such as pro-inflammatory microglia and lymphocytes; remediation of oxidative stress resulting from iron deposition and mitochondrial dysfunction; and promotion of neuroprotection through remyelination. We consider whether current disease-modifying therapies for relapsing-remitting MS meet the criteria for successful therapeutics in PMS and suggest that the evidence favours the early introduction of sphingosine 1-phosphate receptor modulators. Finally, we weigh up emerging medications, including repurposed generic medications and Bruton's tyrosine kinase inhibitors, against these fundamental criteria. In this new therapeutic era in PMS, success depends collectively on understanding disease mechanisms, drug characteristics (including brain penetration) and rational use.


Levels of tetrabromobisphenol A, hexabromocyclododecanes and polybrominated diphenyl ethers in human milk from the general population in Beijing, China.
Three brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs), were measured in 103 human milk samples collected from Beijing in 2011. The donors' personal information, such as dietary habit and socioeconomic and lifestyle factors, was obtained by questionnaires. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) analysis indicated that the levels of TBBPA ranged from <LOD to 12.46 ng g(-1) lipid weight (lw), with a median value of 0.10 ng g(-1) lw. Three HBCD diastereoisomers (α-, β- and γ-HBCD) were also measured using UPLC-MS/MS. The levels of ΣHBCDs ranged from <LOD to 78.28 ng g(-1) lw, with a median value of 2.40 ng g(-1) lw. α-HBCD was generally the most abundant of the three isomers. Eight PBDE congeners, BDE-28, 47, 99, 100, 153, 154, 183 and 209, were measured using gas chromatography coupled with a mass spectrometry (GC/MS). The concentrations of ΣPBDEs ranged from 0.22 to 135.41 ng g(-1) lw, with a median value of 3.24 ng g(-1) lw. BDE-209 dominated the PBDE profile in the majority of the human milk samples. The mean estimated daily intakes (EDIs) of TBBPA, ΣHBCDs and ΣPBDEs by breast-fed infants were 2.34, 24.89 and 71.27 ng kg(-1) bw day(-1), respectively. No significant correlation was found between the BFR levels in milk and the mother's diet, place of residence, smoking habit, nursing duration or computer use habit. In contrast, the mother's age, body mass index (BMI), education level and number of computers in the home were related to the levels of some types of BFRs. More research is needed to further investigate the major source(s) of exposure, the effect of each potential factor and the possible toxicological impact of high daily BFR intake on infants.


Serial scanning with technetium pyrophosphate (99mTc-PYP) in advanced ATTR cardiac amyloidosis.
Development of noninvasive imaging modalities to quantify amyloid burden over time is an unmet clinical need. Technetium pyrophosphate (99mTc-PYP) scintigraphy is a simple and widely available radiotracer useful to differentiate transthyretin from light-chain amyloidosis in patients with advanced cardiac amyloidosis. We examined the utility of serial 99mTc-PYP scanning to quantify amyloid burden over time in TTR cardiac amyloidosis (ATTR-CA). Twenty subjects with ATTR-CA (10 wild type, 10 mutant) underwent serial 99mTc-PYP planar cardiac imaging. Cardiac retention was assessed both semiquantitatively (visual score 0, no uptake to 3, uptake greater than bone) and quantitatively (region of interest drawn over the heart, copied, and mirrored over the contralateral chest) to calculate a heart-to-contralateral (H/CL) ratio. Index scan mean visual score and H/CL were 3.0 ± 0.2 and 1.79 ± 0.2, respectively, and after an average 1.5 ± 0.5 years follow-up, did not differ, 3.0 ± 0.2, P = .33 and 1.76 ± 0.2, P = .44. H/CL change was minimal, 0.03 ± 0.17, did not correlate with time between scans, r = 0.19, P = .43, and was observed despite obvious clinical progression (increase in troponin ≥ 0.1 ng/mL, BNP ≥ 400 pg/mL, NYHA class, and/or death). Serial 99mTc-PYP scanning in subjects with advanced ATTR-CA does not show significant changes over an average 1.5 years of follow-up despite obvious clinical progression.


Antigenic variation of wild and vaccine rabies strains of Egypt.
Nineteen street rabies virus strains, isolated in Egypt from humans (two), dogs (nine), cats (two), farm animals (two), gerbils (three), and a jackal were antigenically analyzed. The Pasteur strain used for the preparation of human rabies vaccine, the Flury high and low egg passage stains (HEP, LEP) used for animal vaccines, and the challenge virus standard (CVS) strain were also assayed. All were examined by the indirect fluorescent antibody test, using a panel of 20 monoclonal antibodies against the nucleocapsid of rabies and rabies-related viruses. The rabies isolates demonstrated patterns of reactivity with the antinucleocapsid panel different from those of the Pasteur, HEP, and CVS strains. Representative human, dog, and rodent isolates were analyzed by neutralization tests in mice, with a second panel of 19 monoclonal antibodies against rabies and Mokola envelope glycoproteins. With this panel, the isolates demonstrated patterns of reactivity different from the vaccine strains. These data indicate antigenic variation between wild virus and vaccine strains.


Infrared optical properties and AFM of spin-cast chitosan films chemically modified with 1,2 Epoxy-3-phenoxy-propane.
Chemical modification of spin-cast chitosan films has been performed. This modification involves the attachment of 1,2 Epoxy-3-phenoxy-propane, commonly known as glycidyl phenyl ether (GPE), to the amine group of the chitosan molecule. Optical properties of modified films have been determined in the infrared region of the spectrum using spectroscopic ellipsometry, and are reported in this paper. Special attention is paid to the infrared region where the index of refraction and extinction coefficients from 750 to 4000 cm(-1) were determined. Difference plots of IR optical data before and after chemical modification were generated to confirm that modification had occurred. Optical modeling of infrared spectroscopic ellipsometry (IRSE) data with respect to chemical bond vibrations has also been performed. This modeling involved curve fitting of resonant chemical bond absorptions using Lorentz oscillators. These oscillator models allow for comparison of modified chitosan to unmodified chitosan. The purpose of this research was to determine infrared optical constants of chemically modified chitosan films This work shows that surface chemistry of biomaterials can be studied quite sensitively with spectroscopy ellipsometry, detecting as little as 100 ng/cm(2) of GPE.


Label-Free Proteomics of a Defined, Binary Co-culture Reveals Diversity of Competitive Responses Between Members of a Model Soil Microbial System.
Interactions among members of microbial consortia drive the complex dynamics in soil, gut, and biotechnology microbiomes. Proteomic analysis of defined co-cultures of well-characterized species provides valuable information about microbial interactions. We used a label-free approach to quantify the responses to co-culture of two model bacterial species relevant to soil and rhizosphere ecology, Bacillus atrophaeus and Pseudomonas putida. Experiments determined the ratio of species in co-culture that would result in the greatest number of high-confidence protein identifications for both species. The 281 and 256 proteins with significant shifts in abundance for B. atrophaeus and P. putida, respectively, indicated responses to co-culture in overall metabolism, cell motility, and response to antagonistic compounds. Proteins associated with a virulent phenotype during surface-associated growth were significantly more abundant for P. putida in co-culture. Co-culture on agar plates triggered a filamentous phenotype in P. putida and avoidance of P. putida by B. atrophaeus colonies, corroborating antagonistic interactions between these species. Additional experiments showing increased relative abundance of P. putida under conditions of iron or zinc limitation and increased relative abundance of B. atrophaeus under magnesium limitation were consistent with patterns of changes in abundance of metal-binding proteins during co-culture. These results provide details on the nature of interactions between two species with antagonistic capabilities. Significant challenges remaining for the development of proteomics as a tool in microbial ecology include accurate quantification of low-abundance peptides, especially from rare species present at low relative abundance in a consortium.


Surgery Versus Transcatheter Interventions for Significant Paravalvular Prosthetic Leaks.
This study sought to assess the relative merit of surgical correction (SC) versus transcatheter reduction on long-term outcomes in patients with significant paravalvular leak (PVL) refractory to medical therapy. PVL is the most frequent dysfunction following prosthetic valve replacement. Although repeat surgery is the gold standard, transcatheter reduction (TR) of PVL has been associated with reduced mortality. From 1994 to 2014, 231 patients underwent SC (n = 151) or TR (n = 80) PVL correction. Propensity matching and Cox proportional hazards regression models were used to assess the effect of either intervention on long-term rates of all-cause death or hospitalization for heart failure. Survival after TR and SC were further compared with the survival in a matched general population and to matched patients undergoing their first surgical valve replacement. Over a median follow-up of 3.5 years, SC was associated with an important reduction in all-cause death or hospitalization for heart failure compared with TR (hazard ratio: 0.28; 95% confidence interval: 0.18 to 0.44; p < 0.001). There was a trend towards reduced all-cause death following SC versus TR (hazard ratio: 0.61; 95% confidence interval: 0.37 to 1.02; p = 0.06). Neither intervention normalized survival when compared with a general population or patients undergoing their first surgical valve replacement. In patients with significant prosthetic PVL, surgery is associated with better long-term outcomes compared with transcatheter intervention, but results in important perioperative mortality and morbidity. Future studies are needed in the face of increasing implementation of transcatheter PVL interventions across the world.


Lipid biosynthesis perturbation impairs endoplasmic reticulum-associated degradation.
The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation. INO4 encodes one subunit of the Ino2/Ino4 heterodimeric transcription factor, which regulates expression of genes required for lipid biosynthesis. Deg1-Sec62 degradation was also impaired by mutation of genes encoding several enzymes mediating phospholipid and sterol biosynthesis. The degradation defect in ino4Δ yeast was rescued by supplementation with metabolites whose synthesis and uptake are mediated by Ino2/Ino4 targets. Stabilization of a panel of substrates of the Hrd1 and Doa10 ER ubiquitin ligases by INO4 deletion indicates ER protein quality control is generally sensitive to perturbed lipid homeostasis. Loss of INO4 sensitized yeast to proteotoxic stress, suggesting a broad requirement for lipid homeostasis in maintaining proteostasis. A better understanding of the dynamic relationship between lipid homeostasis and proteostasis may lead to improved understanding and treatment of several human diseases associated with altered lipid biosynthesis.


Safety and efficacy of cryoablation of accessory pathways adjacent to the normal conduction system.
Cryoablation of Septal Accessory Pathways. Catheter ablation has become a routine treatment for patients with Wolff-Parkinson-White syndrome because of its low risk and high efficacy; however, radiofrequency ablation in the septum close to the AV node or His bundle still carries a definite risk for AV block. Cryoenergy catheter ablation has recently become available. This technique has specific features, such as the ability to create reversible loss of function to predict the effects of ablation (ice mapping) and the adherence of the catheter tip to the endocardium with freezing, which avoids the risk for dislodgment. Both of these characteristics may minimize the risk of complications. The aim of this study was to analyze the effectiveness and safety of catheter cryoablation in 20 patients with para-Hisian or midseptal accessory pathways (AP). Eleven patients with para-Hisian and 9 patients with midseptal AP underwent catheter cryoablation. Ice mapping at -30 degrees C was performed to ascertain the disappearance of AP conduction and the absence of impairment of AV nodal conduction. If the expected result was obtained, cryoablation was performed by lowering the temperature to -75 degrees C for 4 minutes in order to create a permanent lesion. Cryoablation was successful in all patients using a mean of 1.2 +/- 0.4 applications. Recurrences occurred in 4 patients (20%) who underwent a second successful cryoablation session. No complications were observed. Cryoablation appears to be a safe and effective technique for ablation of APs close to the AV node or His bundle because of the ability to predict the acute effects of ablation with ice mapping before creation of an irreversible lesion.


Willingness to receive an annual COVID-19 booster vaccine in the German-speaking D-A-CH region in Europe: A cross-sectional study.
Emergence of new coronavirus variants and waning immunity may necessitate regular COVID-19 vaccine boosters, but empirical data on population willingness for regular vaccination are limited. In August 2021, we surveyed 3,067 quota-sampled German-speaking adults residing in the D-A-CH region (Germany, Austria, Switzerland). Using multivariable adjusted ordered logistic regression models we calculated odds ratios (OR) and 95% confidence intervals (95% CIs) to assess factors associated with willingness to vaccinate annually against COVID-19. Among 2,480 participants vaccinated or planning to get vaccinated, 82·4% indicated willingness to receive annual COVID-19 boosters. This willingness was higher in Austria (OR=1·47, 95% CI, 1·19-1·82; p < 0·001) and Germany (OR=1·98, 95% CI, 1·60-2·45; p < 0·001) versus Switzerland and increased with age. Having voted in the last national election (ORopposition party voters=1·51, 95% CI=1·18-1·92; p = 0·001 and ORgoverning party voters=1·57, 95% CI=1·28-1·93; p < 0·001, versus non-voters) and not regularly participating in religious meetings (OR=1·37, 95% CI=1·08-1·73; p = 0·009, versus participation at least monthly) were significantly associated with willingness to vaccinate, as was partial (OR=1·97, 95% CI=1·43-2·72; p < 0·001) or total (OR=5·20, 95% CI=3·76-7·19; p < 0·001) approval of COVID-19 mitigation measures (versus non-approval). By country, Austrians showed the strongest association of voting behavior and mitigation measure approval with willingness to vaccinate. Targeted promotion programs informed by political and religious engagement and mitigation measure approval are needed to increase willingness to receive regular COVID-19 boosters. Medical University of Vienna, Department of Epidemiology, Danube University Krems, Department for Knowledge and Communication Management; Austrian Society of Epidemiology.


Realizing the promise of EMRs. How a group of physicians in Texas moved forward on EMR and HIE at the same time.
North Texas Specialty Physicians (NTSP), an independent practice association based in Forth Worth, has been working with healthcare organizations across North Texas to build an HIE known as SandlotConnect. NTSP Executive Director Karen Van Wagner, Ph.D. lays out four key strategies that appear to have been successful in winning broad and sustained acceptance by clinicians.


Activity of pure streptovaricins and fractionated streptovaricin complex against Friend virus.
Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures.


Homeostatic Expansion of CD4+ T Cells Promotes Cortical and Trabecular Bone Loss, Whereas CD8+ T Cells Induce Trabecular Bone Loss Only.
Bone loss occurs in human immunodeficiency virus (HIV) infection but paradoxically is intensified by HIV-associated antiretroviral therapy (ART), resulting in an increased fracture incidence that is largely independent of ART regimen. Inflammation in the bone microenvironment associated with T-cell repopulation following ART initiation may explain ART-induced bone loss. Indeed, we have reported that reconstitution of CD3+ T cells in immunodeficient mice mimics ART-induced bone loss observed in humans. In this study, we quantified the relative effects of CD4+ and CD8+ T-cell subsets on bone. T-cell subsets in T-cell receptor β knockout mice were reconstituted by adoptive transfer with CD4+ or CD8+ T-cells subsets were reconstituted in T-cell receptor β knockout mice by adoptive transfer, and bone turnover, bone mineral density, and indices of bone structure and turnover were quantified. Repopulating CD4+ but not CD8+ T cells significantly diminished bone mineral density. However, micro-computed tomography revealed robust deterioration of trabecular bone volume by both subsets, while CD4+ T cells additionally induced cortical bone loss. CD4+ T-cell reconstitution, a key function of ART, causes significant cortical and trabecular bone loss. CD8+ T cells may further contribute to trabecular bone loss in some patients with advanced AIDS, in whom CD8+ T cells may also be depleted. Our data suggest that bone densitometry used for assessment of the condition of bone in humans may significantly underestimate trabecular bone damage sustained by ART.


Urea-formaldehyde resin monolith as a new packing material for affinity chromatography.
A urea-formaldehyde resin (UF) continuous bed has been prepared through in-situ condensation polymerization in a confined tube. The monolith is an agglomerate of 2-microm irregular particles. Nitrogen adsorption shows that the monolith has a bimodal pore size distribution. It has low resistance to flow. A dyed monolith is obtained through modification of the UF monolith with Cibacron blue F3GA. Although its dye concentration and dynamic capacity are low compared to Sepharose type affinity media, the dyed monolith can separate some proteins in the affinity mode of liquid chromatography.


Impacts of CR1 genetic variants on cerebrospinal fluid and neuroimaging biomarkers in alzheimer's disease.
The complement component (3b/4b) receptor 1 gene (CR1) gene has been proved to affect the susceptibility of Alzheimer's disease (AD) in different ethnic and districts groups. However, the effect of CR1 genetic variants on amyloid β (Aβ) metabolism of AD human is still unclear. Hence, the aim of this study was to investigate genetic influences of CR1 gene on Aβ metabolism. All data of AD patients and normal controls (NC) were obtained from alzheimer's disease neuroimaging initiative database (ADNI) database. In order to assess the effect of each single nucleotide polymorphism (SNP) of CR1 on Aβ metabolism, the PLINK software was used to conduct the quality control procedures to enroll appropriate SNPs. Moreover, the correlation between CR1 genotypes and Aβ metabolism in all participants were estimated with multiple linear regression models. After quality control procedures, a total of 329 samples and 83 SNPs were enrolled in our study. Moreover, our results identified five SNPs (rs10494884, rs11118322, rs1323721, rs17259045 and rs41308433), which were linked to Aβ accumulation in brain. In further analyses, rs17259045 was found to decrease Aβ accumulation among AD patients. Additionally, our study revealed the genetic variants in rs12567945 could increase CSF Aβ42 in NC population. Our study had revealed several novel SNPs in CR1 genes which might be involved in the progression of AD via regulating Aβ accumulation. These findings will provide a new basis for the diagnosis and treatment AD.


[Prognosis of cognitive deficit progression in aged patients with mild cognitive impairment under prolonged therapy (a three year observation)].
The aim of the study was to predict treatment efficacy in patients with mild cognitive impairment (MCI) and to find the most reliable clinical tests for the prediction of dementia. Patients with amnestic MCI (n=53) were treated with cerebrolysin for three years and underwent regularly neurocognitive and clinical psychiatric tests. The data were analyzed using non-parametric statistics, cluster analysis, and linear discriminate analysis. The combination of statistical methods has enabled to predict the degree of cognitive impairment as well as the development of dementia. A "dementia risk group" with fast cognitive decline (i.e. the low efficacy of the treatment) was identified. The tests are ranked according to their predictive values.


Starting the process of mother-infant bonding.
Establishing a bond between a mother and her newborn is essential for the infant to grow and thrive in the mother's care. Hospital staff can promote the creation of this bond by providing continuous support during labor, by placing the newborn skin-to-skin on the mothers chest immediately after delivery until the infant latches on for the first feeding, by encouraging continued breast feeding and by keeping her mother and infant always together in the first hours and days after delivery. Even in case where the mother initially rejects her infant, sensitive medical personnel can provide an environment which allows the bond between mother and infant to begin.


Paediatric blepharoptosis: a 10-year review.
To examine the characteristics of blepharoptosis and the success of surgical intervention in a large group of children presenting to a specialist at paediatric ophthalmology center. Ten-year retrospective case notes review of patients presenting to the Birmingham Children's Hospital for blepharoptosis surgery. Resultant database was interrogated for aetiology of ptosis; severity; surgical correction; outcome; complications and need for reoperation. One hundred and fifty five children (186 eyes) underwent blepharoptosis surgery. Hundred and ten patients (71%) were treated with a levator resection procedure, 28 (18%) underwent a brow suspension using Mersilene mesh, 15 (10%) with Fasanella Servat procedure and 2 (1%) with La Mange procedure. The mean post-operative follow-up was 30.82 months with 84 children completing a minimum of 12 months follow-up. Overall, 70.97% lids were successfully corrected with a single operation. In 9.14% lids, the results were fair but no further surgery was carried out. Reoperation was required in 19.89% of lids with the mean time to second surgery being 32.69 months. Amblyopia was found in 26.45% (41 children); in 3 patients, their amblyopia became manifest after the ptosis surgery. A concomitant squint was present in 14.19%, and 18.70% had a significant refractive error requiring spectacles prescription, with anisometropia present in more than 72% of these patients. Early referral to an ophthalmologist is necessary even though surgical correction may be delayed. Children with congenital ptosis need to be monitored for amblyopia both pre- and post-operatively, as the incidence of strabismus and refractive errors is much higher than the general population and these may develop even after ptosis surgery.


Enhanced and prolonged efficacy of superantigen-induced cytotoxic T lymphocyte activity by interleukin-2 in vivo.
The bacterial superantigen, staphylococcal enterotoxin A (SEA) activates T cells with high frequency and directs them to lyse MHC-class-II-expressing cells in superantigen-dependent cell-mediated cytotoxicity (SDCC). Treatment of mice with SEA induced strong CD8+ T-cell(CTL)-mediated SDCC, as well as abundant cytokine production from CD4+ and CD8+ T cells. However, both cytotoxicity and cytokine release were transient. In contrast, combined treatment with SEA and recombinant interleukin-2 (rIL-2) increased peak levels and maintained CTL activity. These effects were concomitant with an increased number of SEA-reactive V beta 11+ T cells. Both the CD4+ and CD8+ populations contained higher frequencies of cells expressing IL-2 receptor (IL-2R) alpha beta, which suggests that continuous IL-2R signaling preserves its high expression and subsequently prevents loss of growth factor signals necessary for expansion of T cells. Although IL-2R expression was increased among both CD4+ and CD8+ cells, only the cytotoxic function of CTL, but not cytokine production from either CD4 or CD8, was augmented. These findings demonstrate that treatment with rIL-2 potentiates superantigen-induced cytotoxicity and maintains high CTL activity. rIL-2 might therefore be useful in improving superantigen-based tumor therapy.


Heuristics reasoning in diagnostic judgment.
Heuristics inquiry is an exciting new approach to understanding diagnostic reasoning. Heuristics are short-cut mental strategies that streamline information. Although heuristics allow for faster processing of information than analytic methods, they can lead to errors because not all information is considered. This article describes three heuristics particularly relevant to diagnostic reasoning: accessibility, similarity, and anchoring and adjustment. Specific factors thought to influence heuristic reasoning are reviewed and analyzed. Last, interventions to be tested for both practice and education are presented.


In vivo metabolism of 3-deoxy-3-fluoro-D-glucose.
Recent studies have demonstrated that 3-deoxy-3-fluoro-D-glucose (3-FG) is metabolized to 3-deoxy-3-fluoro-D-sorbitol (3-FS), via aldose reductase, and 3-deoxy-3-fluoro-D-fructose (3-FF), via the sorbitol dehydrogenase reaction with 3-FS, in rat cerebral tissue (Kwee, I. L., Nakada, T., and Card, P. J. (1987) J. Neurochem. 49, 428-433). However, the biochemistry of 3-FG in other mammalian organs has not been investigated making the application of 3-FG as a metabolic tracer uncertain. To address this issue we investigated 3-FG metabolism and distribution in isolated cell lines and in rabbit tissues in vivo with 19F NMR and gas chromatography-mass spectrometry. In general, the production of 3-FS is well correlated with the known distribution of aldose reductase in all the systems studied. Further metabolism of 3-FS to 3-FF was verified to occur in cerebral tissue. Surprisingly, two new fluorinated compounds were found in the liver and kidney cortex. These compounds are identified as 3-deoxy-3-fluoro-D-gluconic acid, which is produced via glucose dehydrogenase activity on 3-FG, and 3-deoxy-3-fluoro-D-gluconate-6-phosphate. Based on enzyme studies, it is argued that the 3-deoxy-3-fluoro-D-gluconate-6-phosphate is derived directly from 3-deoxy-3-fluoro-D-gluconic acid and not as a product of pentose phosphate activity. Direct oxidation and reduction are the major metabolic routes of 3-FG, not metabolism through glycolysis or the pentose phosphate shunt. Thus, 3-FG metabolism coupled with 19F NMR appears to be very useful for monitoring aldose reductase and glucose dehydrogenase activity in vivo.


[Experience with the use of methods of improving the healing of surgical wounds in children].
To improve healing of the operative wounds in children, a complex of measures is suggested, which stipulates the reduction of patient's stay in the hospital before the operation, the use of transverse skin incision, atraumaticity of the operation, meticulous layer-by-layer suturing of the skin wound, free of dressings management of the operative wounds, early removal of skin sutures. As a result, the duration of hospitalization reduced, bed turnover increased, a high cost effectiveness was achieved.


Inhibition of BMP signaling reduces MMP-2 and MMP-9 expression and obstructs wound healing in regenerating fin of teleost fish Poecilia latipinna.
The tail fin of teleost fish responds to amputation by expressing few putative factors that promote scar-free wound healing, which paves the way for restoration of the lost part. Among the factors playing a role in this initial response, bone morphogenetic proteins (BMPs) are crucial. In the current study, we have analyzed the effect of BMP inhibition on wound healing in sailfin molly Poecilia latipinna. The study involved histological assessment of wound epithelium formation, an expression profile of proteins, and gelatinase activity as well as expression in response to BMP signal inhibition. LDN193189, a pharmacological inhibitor of BMP receptor, was administered to experimental fish. Our observations include incomplete wound healing and a significant reduction in the expression of a number of proteins as a result of LDN treatment at 24 h post-amputation. A pronounced effect was also seen on the gelatinases MMP-9 and MMP-2, which showed significantly reduced activities on a zymogram. Reduced expression of these MMPs after inhibitor treatment was also confirmed by western blot and real-time PCR analyses. In view of these results, we confirm that BMP signaling has a definitive role in the early stages of fin regeneration in P. latipinna. The effect of BMP inhibition is especially seen on the expression of MMP-9 and MMP-2, which are very important effectors of tissue remodeling immediately following amputation.


Changes in the rRNA levels of specific microbial groups in activated sludge during sample handling and storage.
To quantitatively analyse the changes in group-specific rRNA levels in activated sludge as a function of sample handling and storage procedure. Quantitative membrane hybridizations with (32)P-labelled oligonucleotide probes were used to analyse the effects of different sample handling and storage conditions on the relative rRNA levels of the alpha, beta, and gamma-Proteobacteria, the Cytophaga-Flavobacteria group, and the mycolic acid-containing actinomycetes in activated sludge. Group-specific rRNA levels, expressed as percentages of total 16S rRNA detected with a universal probe, in samples maintained at room temperature significantly changed after 48 h. Group-specific rRNA levels in samples treated with chloramphenicol showed significant change after 72 h. Sample storage at room temperature is a viable option if freezing or analysis can be performed within 24 h, while treatment with chlorampenicol can extend that time to at least 48 h. Handling, shipping, and storage of environmental samples under several conditions may result in inaccurate determination of the microbial populations in microbial ecology studies.


Developmental Skills Moderate the Association Between Core Autism Features and Adaptive Behaviour in Early Childhood.
While research indicates that both the core features of autism and associated developmental skills influence adaptive behaviour outcomes, results to date suggest greater influence of the latter than the former, and little attention has been given to how the interaction of both together might impact functional disability. Seeking to expand understanding of associations between young children's core social autism features, developmental skills, and functional ability/disability, we specifically tested whether early developmental skills might have a moderating effect on the association between early social features and subsequent functional disability. Data from 162 preschool children were available for this study. These included time-1 measures of social autism features (ADOS-Social Affect score) and developmental skills (MSEL-Developmental Quotient; DQ), and a measure of functional ability/disability (VABS-Adaptive Behaviour Composite; ABC) available at follow-up 1-year later (time-2). Time-1 ADOS-SA and MSEL-DQ scores were concurrently associated with one another, and both prospectively associated with time-2 VABS-ABC scores. Examination of partial correlations (i.e., controlling for MSEL-DQ) demonstrated that the association of time-1 ADOS-SA and time-2 VABS-ABC was accounted for by shared variance with DQ. Formal moderation analysis returned a non-significant overall interaction term, but showed a lower-bound region of significance whereby the association of time-1 ADOS-SA with time-2 VABS-ABC was significant for children with baseline DQ ≤ 48.33. Our results add to a body of empirical evidence consistent with an understanding of the needs of and resources available to autistic people through a 'cognitive compensation' lens.