Laser-Fabricated Plasmonic Nanostructures for Surface-Enhanced Raman Spectroscopy of Bacteria Quorum Sensing Molecules.
We used a laser-directed fabrication to create silver nanostructures on glass cover slips via photo-reduction. The resulting silver films exhibited plasmonic properties which show promise in application towards surface enhanced Raman spectroscopy (SERS). The enhancement factor calculated for the deposits was approximately ~106 using the standard thiophenol, which is comparable to other SERS-active plasmonic nanostructures fabricated through more complex techniques, such as electron beam lithography. The silver nanostructures were then employed in the enhancement of Raman signals from N-butyryl-L-homoserine lactone, a signaling molecule relevant to bacteria quorum sensing. In particular, the work presented here shows that the laser-deposited plasmonic nanostructures are promising candidates for monitoring concentrations of signaling molecules within biofilms containing quorum sensing bacteria.


On the molecular weight of thiosulfate sulfurtransferase.
Bovine liver thiosulfate sulfurtransferase (rhodanese) (EC 188.8.131.52) HAS BEEN REPORTED TO EXIST IN SOLUTION IN A RAPID, PH-dependent equilibrium between monomeric and dimeric forms of molecular weights 18 500 and 37 000 (Volini, M., DeToma, F. and Westley, J. (1967), J. Biol. Chem. 242, 5220). We have reinvestigated the proposed dissociation using sodium dodecylsulfate-polyacrylamide gel electrophoresis. The smallest rhodanese species observed has a molecular weight around 35 000, which is not reduced by severe denaturing conditions, including alkylation in 8 M guanidine-HCl or dialysis against 2% sodium dodecylsulfate and 5% mercaptoethanol. After limited CNBr cleavage, intermediate products of greater than 18 500 molecular weight are formed. The apparent molecular weight of these intermediate fragments is not changed by addition of mercaptoethanol. The total apparent molecular weights of the CNBr fragments after exhaustive cleavage is approx. 45 000 plus or minus 15 000. These results are not consistent with a monomer molecular weight of approx. 18 500 for thiosulfate sulfurtransferase.


The effect of increasing concentrations ofFusarium toxins in the diets for piglets on histological parameters of the uterus.
The effects of feeding diets containing 0.01, 0.06, 0.15, 0.22 and 0.42 mg zearalenone and 0.2, 0.8, 1.0, 1.9 and 3.9 mg deoxynivalenol per kg, coming fromFusarium toxin contaminated maize, on the uterus of 50 prepubertal piglets were investigated. The mean weight of the uteri of the animals which received the most contaminated diet was significantly increased at the time of slaughtering. The histological investigation showed no marked differences between the feeding groups. Histometrical parameters of the surface epithelium of the uterus and of the uterine glands were not altered by the treatment.


Effects of Maternal Psychological Stress During Pregnancy on Offspring Brain Development: Considering the Role of Inflammation and Potential for Preventive Intervention.
Heightened psychological stress during pregnancy has repeatedly been associated with increased risk for development of behavior problems and psychiatric disorders in offspring. This review covers a rapidly growing body of research with the potential to advance a mechanistic understanding of these associations grounded in knowledge about maternal-placental-fetal stress biology and fetal brain development. Specifically, we highlight research employing magnetic resonance imaging to examine the infant brain soon after birth in relation to maternal psychological stress during pregnancy. This approach increases capacity to identify specific alterations in brain structure and function and to differentiate between effects of pre- versus postnatal exposures. We then focus on the extensive preclinical literature and emerging research in humans that have found that heightened maternal inflammation during pregnancy as a mechanism through which maternal stress influences the developing fetal brain. We place these findings in the context of recent work identifying psychotherapeutic interventions that have been found to be effective for reducing psychological stress among pregnant individuals and that also show promise for reducing inflammation. We argue that a focus on inflammation, among other mechanistic pathways, may lead to a productive and necessary integration of research focused on the effects of maternal psychological stress on offspring brain development and on prevention and intervention studies aimed at reducing maternal psychological stress during pregnancy. In addition to increasing capacity for common measurements and understanding potential mechanisms of action relevant to maternal mental health and fetal neurodevelopment, this focus may inform and broaden thinking about prevention and intervention strategies.


Connection between two peripherical markers in a group of asthmatic patients.
We have studied the goniometric value of the tda angle and the alpha 1 antitrypsin phenotypes in a group of thirty atopic patients with the following patterns: 1) they were affected with asthma, atopic dermatitis and rhinitis. 2) they presented positive prick skin tests for pneumo-allergens and had. 3) positive allergic antecedents. There exists a significant statistical value for the lower tda angle in the right hand, in the MZ phenotypes of alpha 1 antitrypsin bearers, with P less than 0.05 significance. In the left hand there are many individual values that are identical (62% of the total test effected) thus the statistical methods cannot be applied satisfactorily, bearing in mind the significant difference as the statistical group recognized. From this and other previous works, we can conclude that an individual whose right hand tda angle reaches values near 75%, and with a MZ phenotype of alpha 1 antitrypsin, has a greater possibility of pertaining to one of the groups of asthma, atopic dermatitis and rhinitis symptomatology.


Prospective associations between diet quality, dietary components, and risk of cardiometabolic multimorbidity in older British men.
Cardiometabolic multimorbidity (CMM) is a major public health challenge. This study investigated the prospective relationships between diet quality, dietary components, and risk of CMM in older British men. We used data from the British Regional Heart Study of 2873 men aged 60-79 free of myocardial infarction (MI), stroke, and type 2 diabetes (T2D) at baseline. CMM was defined as the coexistence of two or more cardiometabolic diseases, including MI, stroke, and T2D. Sourcing baseline food frequency questionnaire, the Elderly Dietary Index (EDI), which was a diet quality score based on Mediterranean diet and MyPyramid for Older Adults, was generated. Cox proportional hazards regression and multi-state model were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 19.3 years, 891 participants developed first cardiometabolic disease (FCMD), and 109 developed CMM. Cox regression analyses found no significant association between baseline EDI and risk of CMM. However, fish/seafood consumption, a dietary component of the EDI score, was inversely associated with risk of CMM, with HR 0.44 (95% CI 0.26, 0.73) for consuming fish/seafood 1-2 days/week compared to less than 1 day/week after adjustment. Further analyses with multi-state model showed that fish/seafood consumption played a protective role in the transition from FCMD to CMM. Our study did not find a significant association of baseline EDI with CMM but showed that consuming more fish/seafood per week was associated with a lower risk of transition from FCMD to CMM in older British men.


Human erythrocyte anion permeabilities measured under conditions of net charge transfer.
1. The permeability of the human erythrocyte to anions has been measured under conditions of net charge transfer: for Cl(-) and HCO(3) (-) ions, at 37 degrees C, this permeability is 5 orders of magnitude too small to account for the rate of the electroneutral anion exchange which is responsible for the chloride, or Hamburger, shift.2. The method is an indirect one in which the ionophore, valinomycin, is used to increase the erythrocyte K(+) permeability: in the absence of permeant cation externally, the rate of the resulting K(+) efflux may be limited by the slowness of the accompanying anion efflux, allowing the true anion permeability to be estimated.3. The average Cl(-) permeability estimated in ACD-stored erythrocytes (seven experiments) and erythrocytes from fresh blood (two experiments) was 2.1 x 10(-8) cm/sec at 37 degrees C and pH 7.4: this may also be expressed as a Cl(-) conductance of about 1.0 x 10(-5) Omega(-1) cm(-2). The apparent activation energy for net efflux of Cl(-) was found to be 3.9 kJ/mole (16.4 kcal/mole).4. In fresh cells, the ratios of Cl(-), HCO(3) (-), Br(-) and I(-) permeabilities (or conductances) were 1:0.8:1.5:5. The three halide ions follow Eisenman's Sequence I, representing a binding site of low field strength.


Women's voices: the lived experience of HIV-positive women in the postpartum period at the University of Gondar comprehensive specialized referral hospital, Ethiopia: a phenomenological study.
Pregnancy and the postpartum period are incredibly challenging for women living with the Human Immune Deficiency Virus (HIV) due to the multidimensional influence of HIV infection. These women experience the challenges of navigating pregnancy and motherhood while living with HIV. It is poorly understood how women living with HIV (WLWH) experience pregnancy and postpartum. Therefore, the current study aimed to explore the lived experience of pregnancy and postpartum among women living with HIV. A phenomenological qualitative study design was employed. A semi-structured, interview guide was used to conduct in-depth interviews with HIV-positive postpartum women from April to May 2022. All interviews were recorded using a voice recorder and note was taken. The collected data were transcribed and translated into English for analysis. Inductive thematic analysis was applied to analyze the data. Six main themes about the lived experience of women living with HIV were identified: (1) Fear and distress related to maternal and child Health, (2) HIV status self-disclosure dilemma, (3) Courage and commitment of HIV-positive women to prevent HIV, (4) Challenges faced and coping mechanisms used by HIV-positive women, (5) Health care providers and HIV-positive women interaction, and (6) Solution from their voices. HIV infection also has a multidimensional impact on women's life during pregnancy and postpartum. The findings of this study improve our understanding of the lived experience of HIV-positive women while pregnant and in the postpartum period. These women's descriptions showed that they have been experiencing various challenges that are not often addressed in antenatal clinics, such as distress and uncertainties related to vertical transmission of HIV. These women need specialized support and all-encompassing care to have a healthy pregnancy and postpartum period. Moreover, it is essential to understand the circumstances of women's lives, their relationships with others, and their decision-making processes. Healthcare professionals and other responsible bodies working with women living with HIV should encourage and support these mothers to appraise and maintain their commitment to protecting their children from acquiring HIV infection and maintaining their Health to the maximum to raise their children.


Administration of poly[di(sodium carboxylatoethylphenoxy)]phosphazene (PCEP) as adjuvant activated mixed Th1/Th2 immune responses in pigs.
The selection of an optimal adjuvant to enhance the potency and longevity of antigen specific immune responses has always been imperative for the development of more effective and safer vaccines. A balanced type of immune enhancing ability of a new adjuvant known as polyphosphazene (PCEP) has been demonstrated in mice. In the present study we have compared the humoral and cellular immune responses to vaccine formulations containing Actinobacillus pleuropneumoniae outer membrane antigen (OmlA) with PCEP or Emulsigen as adjuvants. Our data showed a significant improvement and a shift toward more balanced immune responses when OmlA antigen was formulated with PCEP and CpG ODN. Moreover, in contrast to Emulsigen, immunization with PCEP did not result in local injection site reactions highlighting its potential as a safe and effective adjuvant for pigs. Further, the ease of formulation, administration and relatively low per dose cost of PCEP make it a promising adjuvant for pigs.


Complex regulatory pathways coordinate cell-cycle progression and development in Caulobacter crescentus.
Caulobacter crescentus has become the predominant bacterial model system to study the regulation of cell-cycle progression. Stage-specific processes such as chromosome replication and segregation, and cell division are coordinated with the development of four polar structures: the flagellum, pili, stalk, and holdfast. The production, activation, localization, and proteolysis of specific regulatory proteins at precise times during the cell cycle culminate in the ability of the cell to produce two physiologically distinct daughter cells. We examine the recent advances that have enhanced our understanding of the mechanisms of temporal and spatial regulation that occur during cell-cycle progression.


Associations of job satisfaction and burnout with psychological distress among Chinese nurses.
Nurses' mental health is related to the quality of medical care and the outcome of treatment, and has become an important issue in nursing management. However, the role of burnout in the relationship between job satisfaction and psychological distress have not been evaluated. This study aimed to examine the prevalence of psychological distress among Chinese nurses and explore the associations of job satisfaction and burnout with psychological distress. A cross-sectional survey of 866 nurses was conducted in Qiqihar City, Heilongjiang Province of China. Job satisfaction, burnout, and psychological distress were assessed via the single-item, the Maslach Burnout Inventory-Human Services Survey, and the 12-item General Health Questionnaire respectively, followed by a mediation analysis through the multiple regression analysis and a PROCESS macro method. The prevalence of psychological distress was 35.2% among the participants. After controlling the potential confounding factors, job satisfaction and burnout were found to be still associated with psychological distress (P < 0.001). Furthermore, psychological distress was negatively correlated with both job satisfaction (r = -0.312) and personal accomplishment (r = -0.422) but positively correlated with both emotional exhaustion (r = 0.491) and depersonalization (r = 0.449). Burnout may mediate the association between job satisfaction and psychological distress (B = 0.139, β = 0.440, P < 0.001 for emotional exhaustion; B = 0.226, β = 0.382, P < 0.001 for depersonalization; and B = -0.105, β = -0.368, P < 0.001 for personal accomplishment). The mental health status of Chinese nurses remains to be improved. Low job satisfaction and burnout could increase the risk of psychological distress among Chinese nurses. Moreover, job satisfaction may partially affect psychological distress among Chinese nurses through emotional exhaustion, personal accomplishment, and depersonalization. The online version contains supplementary material available at 10.1007/s12144-022-04006-w.


Rice availability and stability in Africa under future socio-economic development and climatic change.
As Africa is facing multiple challenges related to food security, frameworks integrating production and availability are urgent for policymaking. Attention should be given not only to gradual socio-economic and climatic changes but also to their temporal variability. Here we present an integrated framework that allows one to assess the impacts of socio-economic development, gradual climate change and climate anomalies. We apply this framework to rice production and consumption in Africa whereby we explicitly account for the continent's dependency on imported rice. We show that socio-economic development dictates rice availability, whereas climate change has only minor effects in the long term and is predicted not to amplify supply shocks. Still, rainfed-dominated or self-producing regions are sensitive to local climatic anomalies, while trade dominates stability in import-dependent regions. Our study suggests that facilitating agricultural development and limiting trade barriers are key in relieving future challenges to rice availability and stability.


Reduced interhemispheric resting-state functional connectivity in unmedicated bipolar II disorder.
Abnormalities in structural and functional brain connectivity have been increasingly reported in patients with bipolar disorder (BD) by recent neuroimaging studies. However, relatively little is known about the changes in functional interaction between the cerebral hemispheres in BD. The present study aimed to examine the interhemispheric functional connectivity of the whole brain in patients with BD II during resting state. Twenty-six patients with unmedicated BD II depression and 40 normal controls underwent the resting-state functional magnetic resonance imaging. The functional connectivity between any pair of symmetrical interhemispheric voxels (i.e., functional homotopy) was measured by voxel-mirrored homotopic connectivity (VMHC). The patients with BD II showed lower VMHC than normal controls in the medial prefrontal cortex and inferior temporal gyrus. No regions of increased VMHC were detected in patients. There were no significant correlations between the VMHC values in these regions and clinical severity of BD symptoms. These findings suggest substantial impairment of interhemispheric coordination in BD II.


2-Deoxy-2-fluoro-D-glycosyl fluorides. A new class of specific mechanism-based glycosidase inhibitors.
Mechanism-based glycosidase inhibitors are of considerable use in studies of enzyme mechanism, in studies of glycoprotein processing, and possibly therapeutically in control of sugar uptake. This paper describes a new general approach to mechanism-based inactivation of glycosidases which involves trapping a covalent glycosyl enzyme intermediate. This is achieved by use of 2-deoxy-2-fluoro-D-glycosyl fluorides, for which the rate of hydrolysis of the fluoroglycosyl enzyme intermediate is extremely slow, resulting in accumulation of the intermediate. Eleven different glycosidases were tested with their corresponding 2-deoxy-2-fluoro-D-glycosyl fluorides. Eight of the eleven were inactivated, four of them according to pseudo first-order kinetics and four according to a more complex kinetic scheme. The specificity of these inhibitors was investigated by assaying for inhibition of one enzyme with four different 2-deoxy-2-fluoro-D-glycosyl fluorides. Large differences in inactivation rate were observed which paralleled previously observed substrate specificities.


HDAC9, TWIST1 and FERD3L gene expression in asymptomatic stable and unstable carotid plaques.
A variant located at the end of HDAC9 gene within clusters of DNAse I sensitivity zones and histone modification hotspots has been associated with large vessel stroke and could be linked to plaque instability. The aim of the study is to define if an altered expression of HDAC9, TWIST1 and FERD3L genes could be involved in plaque vulnerability. Histological classification and gene expression analysis were performed in 6 stable and 16 unstable plaques obtained from asymptomatic patients undergoing endarterectomy. Gene expression was analysed by real-time PCR. TWIST1 gene expression resulted higher in stable plaques (P < 0.02). HDAC9 gene expression followed a similar trend (P = 0.11). These results highlighting the significant correlation between TWIST and HDAC9 gene expression suggest that both genes may contribute to plaque stability in a coordinated way.


Hyperintense putamen on T1-weighted MR images in a case of chorea with hyperglycemia.
A 77-year-old woman had an acute onset of chorea after hyperglycemic coma. She had no family history of neurologic disorders. Although brain CT showed no detectable lesions in the putamen, MR revealed a high intensity on T1-weighted images and a low intensity on T2-weighted images in both putamina.


A randomised single-centre trial of inhaled liposomal cyclosporine for bronchiolitis obliterans syndrome post-lung transplantation.
No proven treatments exist for bronchiolitis obliterans syndrome (BOS) following lung transplantation. Inhaled liposomal cyclosporine (L-CsA) may prevent BOS progression. A 48-week phase IIb randomised clinical trial was conducted in 21 lung transplant patients with BOS assigned to either L-CsA with standard-of-care (SOC) oral immunosuppression (L-CsA group) or SOC (SOC-alone group). Efficacy end-points were BOS progression-free survival (defined as absence of ≥20% decline in forced expiratory volume in 1 s (FEV1) from randomisation, re-transplantation or death) and BOS grade change. BOS progression-free survival was 82% for L-CsA versus 50% for SOC-alone (p=0.1) and BOS grade worsened in 18% for L-CsA versus 60% for SOC-alone (p=0.05). Mean changes in ΔFEV1 and forced vital capacity, respectively, stabilised with L-CsA: +0.005 (95% CI -0.004- +0.013) and -0.005 (95% CI -0.015- +0.006) L·month-1, but worsened with SOC-alone: -0.023 (95% CI -0.033- -0.013) and -0.026 (95% CI -0.039- -0.014) L·month-1 (p<0.0001 and p=0.009). Median survival (4.1 versus 2.9 years; p=0.03) and infection rate (45% versus 60%; p=0.7) improved with L-CsA versus SOC-alone; creatinine and tacrolimus levels were similar. L-CsA was well tolerated and stabilised lung function in lung transplant recipients affected by BOS without systemic toxicity, providing a basis for a global phase III trial using L-CsA.


Metabolism of selenocyanate in the rat.
Rats injected subcutaneously with 2 mg Se/kg body weight of [75Se]selenocyanate or [14C, 75Se]selenocyanate excreted dimethylselenide (DMSe) in the breath and trimethyl-selenonium ion (TMSe) in the urine. The 24-h respiratory DMSe and urinary TMSe excretions were 26.8 +/- 8.1 and 14.5 +/- 5.1% of the dose, respectively. Tissue concentrations of 75Se were highest in the kidneys (1.89 +/- 0.2% dose/g), liver (1.46 +/- 0.2% dose/g), and blood (0.50 +/- 0.05% dose/ml), and lower (greater than 0.3% dose/g) in the other tissues. Trimethyl-selenonium was the major form (61%) of selenium in urine. Approximately 2% of the dose of doubly labeled SeCN- was excreted unchanged in urine (about 12% of urinary Se). 14C from doubly labeled SeCN- was not present in the methylated selenium metabolites, but a major 14C urinary metabolite was identified as thiocyanate. These results indicate that a substantial part of selenocyanate in the body undergoes metabolism and Se is excreted in methylated forms following scission of the C-Se bond.


Assessment of Heterotrophic Growth Supported by Soluble Microbial Products in Anammox Biofilm using Multidimensional Modeling.
Anaerobic ammonium oxidation (anammox) is known to autotrophically convert ammonium to dinitrogen gas with nitrite as the electron acceptor, but little is known about their released microbial products and how these are relative to heterotrophic growth in anammox system. In this work, we applied a mathematical model to assess the heterotrophic growth supported by three key microbial products produced by bacteria in anammox biofilm (utilization associated products (UAP), biomass associated products (BAP), and decay released substrate). Both One-dimensional and two-dimensional numerical biofilm models were developed to describe the development of anammox biofilm as a function of the multiple bacteria-substrate interactions. Model simulations show that UAP of anammox is the main organic carbon source for heterotrophs. Heterotrophs are mainly dominant at the surface of the anammox biofilm with small fraction inside the biofilm. 1-D model is sufficient to describe the main substrate concentrations/fluxes within the anammox biofilm, while the 2-D model can give a more detailed biomass distribution. The heterotrophic growth on UAP is mainly present at the outside of anammox biofilm, their growth on BAP (HetB) are present throughout the biofilm, while the growth on decay released substrate (HetD) is mainly located in the inner layers of the biofilm.


Labor induction after fetal death. A retrospective analysis.
To describe the delivery outcomes in patients with stillborn infants after labor induction versus spontaneous onset of labor. A retrospective chart review was performed of singleton pregnancies complicated by fetal death over a three-year period when awaiting spontaneous onset of labor was a common practice. Exclusion criteria were prior multiple cesarean deliveries, placenta previa, preeclampsia or suspected abruptio placentae. Outcome measures included time spent in the labor and delivery unit and rates of maternal hemorrhagic morbidity and endomyometritis. Two hundred eight patients, 100 patients undergoing labor induction and 108 with spontaneous onset of labor, met the study criteria. Patients delivering after induction spent a longer time in the labor and delivery unit (13.7 versus 4.4 hours). The endomyometritis rate was higher in the spontaneous labor group (6% versus 1%). There were no differences in the frequency of postpartum hemorrhage, retained placenta or need for blood transfusion. Induction following diagnosis of fetal death is safe and may reduce maternal infectious morbidity.


Clinical implications of Golgi protein 73 and granulocyte colony-stimulating factor and their related factors in children with bronchopneumonia.
To investigate the clinical implications of Golgi glycoprotein 73 (GP73) and granulocyte colony-stimulating factor (G-CSF) in children with bronchopneumonia (BP). Seventy-two children with BP (observation group) and 81 healthy children (control group) consecutively brought to the present study's hospital between June 2019 and October 2020 were enrolled. GP73 and G-CSF levels were determined to analyze their diagnostic value for pediatric BP. High-sensitivity C-reactive protein (hs-CRP) was also measured. The clinical implications of GP73 and G-CSF in pediatric BP complicated with respiratory failure and their connections with the inflammatory response were discussed. GP73 and G-CSF levels were remarkably higher in the observation group (p < 0.05). The sensitivity and specificity of combined detection (GP73+G-CSF) in predicting pediatric BP were 72.22% and 86.42%, respectively (p < 0.001). GP73 and G-CSF, which are closely related to X-ray classification and complications in the observation group, decreased after treatment and were positively correlated with hs-CRP (p < 0.05), especially in children complicated with respiratory failure. Regression analysis identified the independence of the course of the disease, hs-CRP, X-ray classification, GP73, and G-CSF as influencing factors of respiratory failure in children with BP (p < 0.05). GP73 and G-CSF, with elevated levels in children with BP, are strongly linked to disease progression and are independent influencing factors of respiratory failure, which may be the key to diagnosing and treating pediatric BP in the future.


Changing the Care Paradigm for Patients: Advanced Illness Beds Care Model.
Over 90 million Americans suffer from advanced illness (AI) and spend their last days of life in critical care units receiving costly, unwanted, aggressive medical care. Evaluate the impact of a specialized care model in medical/surgical units for hospitalized geriatric patients and patients with complex care requirements where designated AI beds align care with patient's wishes/goals, minimize aggressive interventions, and influence efficient resource utilization. US based multi-facility retrospective, longitudinal descriptive study of screened positive AI patients in AI Beds (N = 1,237) from 3 facilities from 2015 to 2017. Patient outcomes included 60% referrals to AI beds from ICU, a decrease of 39-49% in average ICU LOS, a 23% reduction of AI bed patient expirations, 9.0% referrals to hospice, and projected cost savings of $4,361.66/patient, US dollars. Allocating AI beds to deliver care to AI patients resulted in a decreased cost of care by reducing overall hospital LOS, mortality, and efficient use of both critical care and hospital resources.


Siglec-9 enhances IL-10 production in macrophages via tyrosine-based motifs.
We examined whether Siglec-9 modulates cytokine production in the macrophage cell line RAW264. Cells expressing Siglec-9 produced low levels of tumor necrosis factor (TNF)-alpha upon stimulation with lipopolysaccharide, peptidoglycan, unmethylated CpG DNA, and double-stranded RNA. On the other hand, interleukin (IL)-10 production was strongly enhanced in Siglec-9-expressing cells. Similar activities were also exhibited by Siglec-5. However, the up-regulation of IL-10 as well as the down-regulation of TNF-alpha was abrogated when two tyrosine residues in the cytoplasmic tail of Siglec-9 were mutated to phenylalanine. A membrane proximal ITIM mutant of Siglec-9 did not enhance IL-10 production but partly inhibited TNF-alpha production, indicating diverse regulation mechanisms of TNF-alpha and IL-10. Siglec-9 also enhanced the production of IL-10 in the human macrophage cell line THP-1. These results demonstrate that Siglec-9 enhances the production of the anti-inflammatory cytokine IL-10 in macrophages.


Reoperations after gastric banding: replacement or alternative procedures?
Laparoscopic gastric banding (LAGB) is the most popular surgical procedure for morbid obesity in Europe. Long-term complications like slippage of the band or pouch dilatation are well known and lead to reoperations in a substantial number of patients. In this study, results and follow-ups of patients with reoperations after gastric banding were analyzed. Between May 1997 and June 2006, 172 patients were treated with LAGB for morbid obesity. 41 of these patients underwent one or more band-related reoperations (female symbol = 32, male symbol = 9). Causes for and type of reoperation were analyzed. Weight loss and comorbidities were compared for different types of reoperations. There were no deaths following the reoperations. Band replacement (n = 18), band repositioning (n = 7), conversion to sleeve gastrectomy (SG, n = 2) and Roux-en-Y gastric bypass (RYGBP, n = 2) or band removal without any further substitution (n = 12) were performed as first reoperation. Seven patients had a second reoperation: RYGBP (n = 3), SG (n = 1), or band removal (n = 3). Median follow-up since reoperation was 56 months (range 7-113). Excess weight loss (EBWL%) of patients was 59.4% after RYGBP (n = 5), 45.1% after re-banding (n = 18), and 33.4% after SG (n = 2). Comorbidities were further reduced or even resolved after reoperation. Patients whose band was removed without subsequent bariatric procedures lost significantly less weight (n = 13, EBWL% 23.4) than patients with band replacement (n = 18, EBWL% 46.4, p = 0.04). Laparoscopic reoperation after LAGB is safe and feasible. Reoperation leads to further decrease of BMI and obesity-related comorbidities. Band replacement is a good option for patients with good weight loss after initial LAGB. Alternative procedures, preferably RYGBP, are required for cases of band failure. Overall, RYGBP appears to be the most effective option to induce further weight loss.


Programmed Cell Death Ligand 1 Expression in Primary Central Nervous System Lymphomas: A Clinicopathological Study.
Programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) have been shown to predict response to PD-L1/PD-1-targeted therapy. We analyzed PD-L1 expression in primary central nervous system lymphomas (PCNSLs). PD-L1 protein and mRNA expression were evaluated in 64 PCNSL tissue samples. IFN-γ, IL-10, CD4, and CD8 mRNA expression was also evaluated. PD-L1 protein was detected in tumor cells in 2 (4.1%) cases and in tumor microenvironments in 25 (52%) cases. PD-L1 mRNA positively correlated with IFN-γ (p=0.0024) and CD4 (p=0.0005) mRNA expression. IFN-γ mRNA positively correlated with CD8 mRNA expression (p=0.0001). Furthermore, tumor cell PD-L1 expression correlated positively with overall survival (p=0.0177), whereas microenvironmental PD-L1 expression exhibited an insignificant negative trend with overall survival (p=0.188). PD-L1 was expressed on both tumor and/or tumor-infiltrating immune cells in PCNSL. The biological roles of this marker warrant further investigation.


Biosensor-enabled pathway optimization in metabolic engineering.
Microbes can convert inexpensive renewable substrates to valuable metabolites by their natural metabolic pathways. To maximize the productivity, the pathways yet require further optimization, which remains challenging for our limited knowledge of complex biology. Genetically encoded biosensors are able to detect metabolite concentrations or environmental changes and transfer these inputs to measurable or actionable outputs, thus providing enabling regulation and monitoring tools for complicated pathway optimization. Here, we review recent advances in biosensor-mediated dynamic regulation and strain screening for the highest microbial production of diverse desirable products.


Further experience with chemotherapy in the Dunning prostatic adenocarcinoma.
A number of chemotherapeutic agents, including L-asparaginase, actinomycin D, chloroethylcyclohexy-nitrosourea, 5-flourouracil, cyclophosphamide, hydroxyurea, cis-platinum, adriamycin and methotrexate, alone and in combination and at variable dose levels, were applied against the Dunning R3327 rat prostatic adenocarcinoma-subline G. We found a continuing parallel between responses of the human and rat tumors and conclude that the usefulness of this animal model as a screening system for agents against the human tumor is further supported.


Stroke prevention in atrial fibrillation--an Asian stroke perspective.
Despite relatively lower prevalence of atrial fibrillation (AF) in Asians (~1%) than in Caucasians (~2%), Asia has a much higher overall disease burden because of its proportionally larger aged population. For example, on the basis of reported age-adjusted prevalence rates and projected population figures in China, there will be an estimated 5.2 million men and 3.1 million women with AF older than 60 years by year 2050. Stroke is a disabling complication of AF that is of increasing cause for concern in Asians patients. Implementing consensus expert recommendations for managing stroke risk in patients with AF can considerably reduce stroke rates. However, caution is necessary when aligning management of Asian patients with AF to that of their Caucasian counterparts. Current international guidelines and risk stratification tools for AF management are based on findings in predominantly Caucasian populations and may therefore have limited relevance, in certain respects, to Asian patients. Oral anticoagulants play an important role in preventing AF-related stroke. The vitamin K antagonist warfarin is recommended for reducing the risk of stroke and thromboembolism in high-risk patients with nonvalvular AF; however, warfarin interacts with many drugs and food ingredients, which may pose significant challenges in administration and monitoring among Asian patients. Further research is needed to inform specific guidance on the implications of different stroke and bleeding profiles in Asians vs Caucasians. Moreover, there is scope to improve physician perceptions and patient knowledge, as well as considering alternative new oral anticoagulants, for example, direct thrombin inhibitors or factor Xa inhibitors.


Integrated recognition and quantitative detection of starch in surimi by infrared spectroscopy and spectroscopic imaging.
Surimi products have become increasingly-consumed food with prominent characteristics of high nutrition and convenience and its supply falls short of demand. However, due to exhausted fishery resource in recent years, surimi adulteration, such as addition of plant proteins, starch and other animal origin meat, is becoming serious, so recognition of these exogenous substances has become an urgent issue. In this study, Fourier transform infrared spectroscopy (FT-IR) combined with infrared spectroscopic imaging could distinguish heterogeneity in surimi qualitatively and quantitatively and obtain integral chemical images so that spatial distribution of each component in surimi could be visually displayed, thus a rapid recognition method and a prediction model were developed. The different starch contents in surimi had been primarily identified through intensity change of infrared absorption peaks at 1045cm-1 and 988cm-1, specifically with peak shifts to 1041cm-1 and to 992cm-1, respectively. In infrared imaging analysis, principal components (PCs) were separated and one key PC was confirmed as starch by characteristic peaks comparison at 1147cm-1, 1075cm-1, 997cm-1 and 930cm-1. Meanwhile, an established statistic model could predict starch content in surimi correctly with a reliable correlation coefficient (R=0.9856) and root mean square error of prediction (RMSEP=5.64). Therefore, FT-IR combined with infrared spectroscopic imaging could be applicable to integrally recognize and quantitatively detect starch in surimi.


Microalgae-based bioplastics: Future solution towards mitigation of plastic wastes.
Global demand for plastic materials has severely harm the environment and marine sea life. Therefore, bioplastics have emerged as an environmentally friendly alternative due to sustainability, minimal carbon footprint, less toxicity and high degradability. This review highlights the sustainable and environmentally friendly approach towards bioplastic production by utilizing microalgae as a feed source in several ways. First, the microalgae biomass obtained through the biorefinery approach can be processed into PHA under certain nutrient limitations. Additionally, microalgae biomass can act as potential filler and reinforcement towards the enhancement of bioplastic either blending with conventional bioplastic or synthetic polymer. The downstream processing of microalgae via suitable extraction and pre-treatment of bioactive compounds such as lipids and cellulose are found to be promising for the production of bioplastics. Moving on, the intermediate processing of bioplastic via lactic acid synthesized from microalgae has favoured the microwave-assisted synthesis of polylactic acid due to cost efficiency, minimum solvent usage, low energy consumption, and fast rate of reaction. Moreover, the reliability and effectiveness of microalgae-based bioplastics are further evaluated in terms of techno-economic analysis and degradation mechanism. Future improvement and recommendations are listed towards proper genetic modification of algae strains, large-scale biofilm technology, low-cost cultivation medium, and novel avocado seed-microalgae bioplastic blend.


Resistance training changes LDL metabolism in normolipidemic subjects: a study with a nanoemulsion mimetic of LDL.
To evaluate the effects of resistance training (RT) on the metabolism of an LDL-like nanoemulsion and on lipid transfer to HDL, an important step of HDL metabolism. LDL-like nanoemulsion plasma kinetics was studied in 15 healthy men under regular RT for 1-4 years (age = 25 ± 5 years, VO(2)peak = 50 ± 6 mL/kg/min) and in 15 healthy sedentary men (28 ± 7 years, VO(2)peak = 35 ± 9 mL/kg/min). LDL-like nanoemulsion labeled with (14)C-cholesteryl-ester and (3)H-free-cholesterol was injected intravenously, plasma samples were collected over 24-h to determine decay curves and fractional clearance rates (FCR). Lipid transfer to HDL was determined in vitro by incubating of plasma samples with nanoemulsions (lipid donors) labeled with radioactive free-cholesterol, cholesteryl-ester, triacylglycerols and phospholipids. HDL size, paraoxonase-1 activity and oxidized LDL levels were also determined. The two groups showed similar LDL and HDL-cholesterol and triacylglycerols, but oxidized LDL was lower in RT (30 ± 9 vs. 61 ± 19 U/L, p = 0.0005). In RT, the nanoemulsion (14)C-cholesteryl-ester was removed twice as fast than in sedentary individuals (FCR: 0.068 ± 0.023 vs. 0.037 ± 0.028, p = 0.002), as well as (3)H-free-cholesterol (0.041 ± 0.025 vs. 0.022 ± 0.023, p = 0.04). While both nanoemulsion labels were removed at the same rate in sedentary individuals, RT (3)H-free-cholesterol was removed slower than (14)C-cholesteryl-ester (p = 0.005). HDL size, paraoxonase 1 and the transfer rates to HDL of the four lipids were the same in both groups. RT accelerated the clearance of LDL-like nanoemulsion, which probably accounts for the oxidized LDL levels reduction in RT. RT also changed the balance of free and esterified cholesterol FCR's. However, RT had no effect on HDL metabolism related parameters.


Clostridium subterminale septicemia in a patient with esophageal cancer.
Clostridium subterminale (C. subterminale) is a pathogenic species of Clostridium that has been infrequently isolated. We report a case of C. subterminale bacteremia causing sepsis in a patient with metastatic gastrointestinal malignancy.


Infective endocarditis in adults in Glasgow, 1976-81.
Seventy-one cases of endocarditis in adults, defined on strict clinical criteria over a period of 5 years were studied. The demographic profile was similar to other published studies except that no bimodal peak in age distribution was detected. The major presenting features were infection, cardiac failure and embolism. Rheumatic valvular disease (44%) was the most common predisposing condition. Twenty percent of our patients developed endocarditis on an apparently normal valve and 28% presented with prosthetic valve infection. M-mode echocardiography was carried out in only 44% of cases and with a low rate of detection of vegetations. Streptococcus viridans was the most common causal organism. The mortality for the total series (45%) was considerably greater than that in other recent reports. Our study confirmed that failure to show early response to appropriate antimicrobial therapy was an indication to consider immediate valve replacement.


Differential Wnt-β- catenin pathway activation in HPV positive and negative oral epithelium is transmitted during head and neck tumorigenesis: clinical implications.
The aim of this study is to understand the association of HPV infection and wnt-β-catenin self-renewal pathway in development of head and neck squamous cell carcinoma (HNSCC). For this reason, the molecular profiles (methylation/deletion/expression) of antagonists (SFRP1/2 and DKK1), agonists (FZD7 and LRP6) and effector protein β-catenin of the pathway were analyzed in HPV positive/negative oral epithelium at first, followed by its changes during development of the tumor along with correlations with different clinico-pathological parameters. HPV infection alone or in combination with tobacco habit could activate p- β-catenin expression in basal/parabasal layers of oral epithelium through high expression of FZD7 and significant down regulation of SFRP1/2 through promoter hypermethylation due to over expression of DNMT1 with ubiquitous down regulation of DKK1 and up-regulation of LRP6. This phenomenon has been seen in respective HPV positive and negative HNSCC tumors with additional deletion/microsatellite size alterations in the antagonists. Overall alterations (methylation/deletion) of SFRP1/2, DKK1 gradually increased from Group I (HPV-/Tobacco-) to Group IV(HPV+/Tobacco+) tumors, leading to the worst prognosis of the patients. Thus, the transmission of differentially activated wnt-β-catenin pathway from HPV positive/negative basal/parabasal layers of oral epithelium to HNSCC tumors determines differences in molecular pathogenesis of the disease.


Surgical knot integrity: effect of suture type and caliber, and level of residency training.
To evaluate if suture type and caliber or level of residency training affects strength and mode of failure of surgical knots. All residents in an obstetrics and gynecology training program were invited to tie knots on a bench model using 2 calibers (0 and 3-0) of 2 types of surgical suture (polyglactin 910 and polydioxanone). The failure load, mode of failure, and loop lengths of the knots were determined. University of Texas Southwestern Medical Center, Dallas, Texas. Physicians enrolled in the University of Texas Southwestern Medical Center Obstetrics and Gynecology residency training program. Seventy-one of 73 residents participated. Knots tied with 0-caliber sutures had a higher mean failure load than those tied with 3-0 caliber sutures. For each type and caliber of suture, there were no differences in failure load between each level of residency training. However, senior residents tied knots with shorter loop lengths and had a lower proportion of knots that unraveled or slipped. Even though there were no differences in failure loads, senior residents tied tighter and more secure knots than their junior counterparts.


A clinically "silent" pheochromocytoma with spontaneous hemorrhage.
We report a case of an abdominal mass that had hemorrhaged spontaneously into the retroperitoneal space and presented as an acute abdominal catastrophe. The pathological diagnosis was pheochromocytoma, although the patient had no suggestive symptoms preoperatively. The management of this silent pheochromocytoma and its atypical presentation are discussed.


Percutaneous lateral ligament reconstruction with allograft for chronic lateral ankle instability.
The majority of lateral ankle instability can be treated successfully with conservative method. However, if such treatments fail, surgical treatment should be considered. A wide variety of procedures have been introduced to treat chronic lateral ankle instability. The percutaneous method avoids dissection which is associated with open surgery and can lead to excessive morbidity. The purpose of this study was to evaluate the clinical and radiological outcomes of percutaneous lateral ligament reconstruction with an allograft in the treatment of chronic lateral ankle instability. Between October 2006 and April 2009, percutaneous lateral ligament reconstruction using an allograft was performed on 15 ankles in 13 patients for chronic lateral ankle instability. The patients included in this study satisfied at least one of the following criteria: a previously failed reconstruction of the ligament, severe ankle instability (more than 15 degrees of talar tilt, more than 10 mm of anterior drawer), general laxity of ligaments, body mass index (BMI) higher than 25. The mean followup period was 18.1 (range, 12 to 40) months. The grafted tendon was secured by double tenodeses at both the talus and calcaneus or triple tenodeses which included a fibular tenodesis. The clinical outcomes were evaluated with Visual Analogue Scale (VAS) for pain, Karlsson-Peterson ankle score, and patients' subjective satisfaction. The radiological results were evaluated using the varus tilting angle and the anterior displacement distance. The VAS improved from preoperative 3.7 ±2.2 to 1.6 ±1.3 at the last followup (p = 0.002). The Karlsson-Peterson ankle score increased from 54.2 ±8.8 to 80.9 ±7.2 (p = 0.001). Patients were satisfied in 13 cases (86.7%) with excellent or good results. Radiologically, the mean varus tilting angle was 15.5 ±4.4 degrees preoperatively and 7.3 ±3.6 at the last followup (p = 0.001). The anterior drawer distance was 10.1 ±3.3 mm preoperatively and 7.2 ±2.7 mm at last followup (p = 0.001). We believe percutaneous lateral ligament reconstruction with allograft to be a useful method as a salvage procedure for the treatment of severe and complicated types of chronic lateral ankle instability. Furthermore, the minimal invasiveness of this technique provides a good cosmetic outcome and we found it to be a technically easy and fast procedure.


A Case of Thrombotic Microangiopathy and Acute Sarcoidosis.
Although sarcoidosis is an established cause of multiorgan dysfunction, acute presentation with thrombotic microangiopathy resulting in severe renal and hematological sequelae has not been reported. We describe the case of a patient presenting with hypercalcemia, pancreatitis, and acute renal failure, followed by microangiopathic hemolytic anemia. Although there were no significant respiratory symptoms, thoracic radiology and mediastinal lymph node biopsy results were in keeping with sarcoidosis as the underlying cause of this multisystem presentation. Corticosteroids were commenced with clinical and biochemical improvement. This novel case highlights the need to consider sarcoidosis as part of the differential diagnosis for unusual multiorgan presentations and for early multidisciplinary involvement in such cases to permit optimal treatment.


[Reasons for allergology consultations prior to COVID-19 vaccination and their outcomes : Two-year experience of an allergy center in North Rhine-Westphalia].
To counteract the coronavirus disease 2019 (COVID-19) pandemic, several severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines have been licensed since December 2020. Shortly after the start of the vaccination campaigns, occasional allergic reactions related to vaccines were described, thus, leading to concerns in many patients with a history of allergies. The aim of this work was to evaluate which anamnestic events represented a reason for an allergology work-up before COVID-19 vaccination. Furthermore, the results of the allergology diagnostics are described. We performed a retrospective data analysis of all patients who presented at the Center for Dermatology, Allergology and Dermatosurgery of the Helios University Hospital Wuppertal during the years 2021 and 2022 for allergology work-up prior to COVID-19 vaccination. Demographic data, allergological history, reason for the consultation in the clinic and results of allergology diagnostic tests including reactions after vaccination were included. A total of 93 patients presented for allergology work-up with COVID-19 vaccines. In about half of the cases, the reasons for the presentation to the clinic were doubts and concerns about allergic reactions and side effects. In all, 26.9% (25/93) of the presented patients had not previously received a COVID-19 vaccine yet and 23.7% (22/93) of patients developed non-allergic reactions after prior COVID-19 vaccine (e.g., headache, chills, fever, malaise). Of the patients, 46.2% (43/93) were successfully vaccinated in the clinic due to a complex allergological history, while the remaining 53.8% (50/93) were subjected to outpatient vaccination in the vaccination practice. Only one patient with known chronic spontaneous urticaria developed a mild angioedema of the lips a few hours after vaccination; however, we do not consider this episode an allergic reaction to the vaccine due to the time delay. Allergic reactions after COVID-19 vaccines are rare, but many patients with a positive medical history of allergies are concerned about allergic reactions after COVID-19 vaccination. Thus, public work by practicing allergologists is important during vaccination campaigns to meet the concerns and fears of the population, especially of patients with allergies in their medical history.


Management of post-cervical laminectomy fusion pain syndrome with a successful trial of spinal cord stimulation.
Spinal cord stimulation has been shown to be beneficial in various postsurgical neuropathic pain syndromes, but the already small cervical epidural space due to epidural fibrosis makes cervical spinal cord stimulator placement very difficult. We present a case of successful cervical cord stimulator implantation in a patient with a history of anterior cervical discectomy and fusion, posterior cervical fusion, and significant epidural fibrosis. A 48-year-old woman with a history of type 2 diabetes, nonalcoholic steatohepatitis, and fibromyalgia presented with trauma-induced cervicalgia and bilateral upper extremity radiculopathy. In a 4-day trial of stimulation, she reported an 80% reduction of her pain and significant improvement in her quality of life. Although anecdotal evidence and case series have shown spinal cord stimulation to be successful in cervical failed back surgery syndrome, we are the first to discuss the technical challenges and complications associated with epidural fibrosis.


Long term parenteral therapy by percutaneous tunneled silicone central venous catheter--a follow-up of 300 catheters.
We have developed a technique for the management of central venous catheters which incorporates percutaneous insertion and daily care for routine use in different wards. A follow-up of the first 300 catheters is presented. When intravenous therapy was planned for more than two weeks, a silicone rubber catheter was introduced percutaneously with a skin tunnel and the position of the tip in the lower superior vena cava checked by venous pressure measurement. The metal hub of the catheter was disinfected daily by heating with a modified soldering iron which has been proved to be effective by in vitro testing with different microorganisms. The external jugular vein was used in 164 cases (55 per cent) the internal jugular vein in 115 (38 per cent) and the remaining catheters were inserted by the subclavian or antecubital route. Correct positioning was obtained in 96 per cent and serious early or late complications were rare there being only one case of septicaemia in a total treatment period of 270 months. One patient developed a lung infarct, but no case of pneumothorax has been seen. The mean duration of the catheters was 27 days (range 1-239) and the common reasons for termination were cessation of need in 84 per cent, mechanical obstruction in 6 per cent and inadvertent removal in 6 per cent. The described method has proved to be safe and to function well on ordinary wards.


Annual Trends and Geographic Variation in the Utilization of Imaging in Pediatric Patients with Low Back Pain in the United States.
Low back pain (LBP) is increasing in the pediatric population. Advanced imaging, such as computed tomography and magnetic resonance imaging, performed for LBP imposes significant costs with little benefit. We investigated annual trends and demographic and geographic variation in spinal imaging for first-time pediatric presenters with LBP in primary care clinics. We queried a private administrative claims database for patients presenting with LBP who underwent plain radiography, computed tomography, and magnetic resonance imaging from 2011 to 2017. We used a Cochrane Armitage test of trend to determine significant annual variation in diagnostic imaging utilization during the study period. The χ2 test was used to determine demographic and geographic variation. The study included 67,423 patients with mean age 15.2 ± 3 years. There was no significant change in radiography (34.8% in 2011 vs. 35.5% in 2017, P = 0.795) or computed tomography (1.6% in 2011 vs. 1.1% in 2017, P = 0.073), but there was a significant increase in magnetic resonance imaging (3.3% in 2011 vs. 4.5% in 2017, P = 0.017). Overall, there was no significant change in total imaging use (P = 0.895). Boys had higher rates of imaging compared with girls (40.2% vs. 35.6%, P < 0.001). Imaging rates significantly varied between regions across the United States (P < 0.001). The Midwest had the highest imaging rates (41%), while the Northeast had the lowest rates (31%). There was significant demographic and geographic variation but no significant annual change in total diagnostic spinal imaging for pediatric patients with LBP between 2011 and 2017, with rates of advanced imaging remaining relatively low.


Artificial liver support system in pediatric acute liver failure due to mushroom poisoning: Case series.
Pediatric acute liver failure (PALF) due to mushroom poisoning is a rare and life-threatening disease. There is no specific treatment. Plasma exchange (PE) is often used as a bridge to the regeneration of the liver or transplantation. However, PE is limited due to an inadequate plasma supply and transfusion-related risks. The double plasma molecular adsorption system (DPMAS) can adsorb toxins, including bilirubin and inflammatory mediators. However, the DPMAS cannot improve coagulation disorders. Combining PE and the DPMAS could compensate for the shortcomings of the two techniques. A previous study showed that the combination might be more effective than using PE or the DPMAS alone in patients with mild acute-on-chronic liver failure. To the best of our knowledge, few studies combined PE and the DPMAS for the treatment of PALF due to mushroom poisoning. Here, we specifically describe our experience with PE and the DPMAS in PALF. In conclusion, our study shows that the DPMAS and PE are safe and effective in reducing the bilirubin level and improving blood coagulation in PALF due to mushroom poisoning as a bridge to transplantation or recovery.


Objectives to direct the training of emergency medicine residents on off-service rotations: emergency medical services.
Emergency Medical Services are an area of special interest in emergency medicine. Many emergency physicians are called upon to direct, train, or manage emergency medical services. Residents training in emergency medicine have a need for a defined curriculum in emergency medical services. Residency training should provide a basic foundation in EMS including on- and off-line medical control, medicolegal aspects, communications, disaster management, and EMS history, structure, and function. The resident must gain experience through on-scene observation, EMT/Paramedic education, medical direction, and quality assurance activities. This paper is one in a continuing series of goals and objectives to direct resident training in off-service rotations. Specific resources, learning objectives, and experiences are suggested.


Investigating the site selective binding of busulfan to human serum albumin: Biophysical and molecular docking approaches.
We have studied the binding of busulfan (BN) to human serum albumin (HSA) at physiological pH 7.4 by using fluorescence, UV-vis and circular dichroism (CD) spectroscopic tools, as well as dynamic light scattering (DLS) measurements and molecular simulation approaches. HSA fluorescence quenching experiments showed that BN reduces the HSA native fluorescence intensity through the static mechanism. In addition, a single binding site on the HSA is occupied by BN with a binding constant at 298K of 1.84×103M-1. The enthalpy change (ΔH) and entropy change (ΔS) of BN-HSA interaction were calculated as -1.40kcalmol-1 and +10.14calmol-1K-1 respectively, which suggest the possible interaction mode as hydrophobic and hydrogen bonding. Moreover, the secondary structure alteration of HSA following its complexation with BN was studied and showed that α-helical content of HSA gets increased on interacting with BN. Ligand binding site to HSA was further investigated by site-specific markers in fluorescence measurements as well molecular modeling approach which indicated that BN bind to the nearby sudlow site II of HSA through hydrophobic as well as hydrogen bonding interaction. The present study will be helpful for understanding the binding mechanism of BN to human serum albumin.


'You have to use everything and come to some equilibrium': a qualitative study on hypoglycemia self-management in users of continuous glucose monitor with diverse hypoglycemia experiences.
Although continuous glucose monitoring systems (CGMs) can help reduce hypoglycemia, about one-quarter of people with type 1 diabetes (T1D) who use CGMs still either spend at least 1% of the time with dangerously low blood glucose or develop severe hypoglycemia. This study explored experiences around hypoglycemia self-management in people who are living with T1D and using CGMs to identify factors contributing to hypoglycemia development. Purposive sampling and semistructured interviews with 28 respondents with T1D and using CGMs were conducted to explore experiences around hypoglycemic episodes and hypoglycemia self-management during CGM use. Open coding and thematic analysis were employed to identify emergent themes related to hypoglycemia experiences. About one-third of respondents each respectively spent 0%, 0.1%-0.9% and ≥1% of time in level 2 hypoglycemia; 39% had impaired awareness of hypoglycemia and 32% had severe hypoglycemia in the past 6 months. Four themes were generated: (1) prioritizing symptoms over CGM data (subthemes: hypoglycemia symptoms for confirming hypoglycemia and prompting management actions; minimal management actions without hypoglycemia symptoms); (2) distraction from the demands of daily life; (3) concerns about hypoglycemia management choices (subthemes: fear of rebound hyperglycemia; other health consequences related to sugary food consumption; aversions to treatment foods and treatment food consumption); and (4) social influences on management choices (subthemes: positively perceived social support and inclusion; unwanted attention to oneself or concerns about inconveniencing others; social stigma and criticism related to hypoglycemia and CGM use). Despite using CGMs, people with T1D can face a complex biopsychosocial process of managing hypoglycemia. Interventions for addressing psychosocial and behavioral barriers are needed to improve hypoglycemia self-management in those who continue to face challenges in minimizing hypoglycemia while using CGMs.


An assemblage of divergent variants of a novel putative closterovirus from American persimmon.
Deep-sequencing analysis of nucleic acids extracted from leaf tissue of an American persimmon (Diospyros virginiana L.) and subsequent-sequencing analyses uncovered at least four distinct closterovirus-like molecules. Two complete genomes of 18,569 and 18,030 nucleotides (nt) and partial genomes of 4,899 and 9,019 nt were determined. The two complete genomes encoded 11 potential open reading frames and the characteristic organization of closteroviruses. Among the four genomes, the putative heat shock protein 70 homolog (HSP70h), RNA-dependent RNA polymerase, and coat protein showed 82-85, 72-91, and 84-87 % amino acid sequence identities, respectively. These results suggested that the four identified viruses could be divergent variants in a single host plant. The phylogenetic tree based on HSP70h showed that their closest relative, although distant, is Olive leaf yellowing-associated virus, a putative unassigned member of the family Closteroviridae. The name Persimmon virus B was proposed for this new virus, representing another unassigned member of the family.


Peripheral blood catalase in patients undergoing renal transplantation.
Oxygen free radicals are mediators of tissue injury and catalase is an enzyme which is involved in limiting this process. We examined peripheral blood catalase activity (PBCA) to assess its value as a marker in detecting tissue injury related to renal allograft rejection. Thirty-one consecutive recipients of kidney (n = 29) or simultaneous kidney/pancreas (n = 2) transplants and 10 normal volunteers were studied. Catalase activity, measured by the disk-flotation method, was expressed as Sigma units X 10(-3)/ml (SU/ml) of whole blood. Normal PBCA was determined to be greater than 76 SU/ml. Twenty-nine episodes of renal allograft rejection (diagnosed by clinical criteria +/- biopsy [79%]) were observed in 26 patients. PBCA (mean +/- SEM) was found to be low (64 +/- 1 SU/ml) in 28/29 episodes (chi 2 = 46.3, P less than 0.001), and the decrease (at least two consecutive daily catalase values less than 76 SU/ml) occurred 2 days prior to the clinical/biopsy diagnosis of rejection in 26/28 episodes. The sensitivity of PBCA as a discriminant of rejection was 97%, specificity was 96%, and test accuracy was 96%. PBCA less than 50 SU/ml on two or more occasions occurred in five cases and transplant nephrectomy was required in four of these because of uncontrollable rejection. Nine episodes of cyclosporine nephrotoxicity occurred in 7 patients and none of these episodes was associated with a decreased PBCA. Our data suggest that decreased PBCA is a sensitive and specific indicator of renal allograft rejection. PBCA remains normal during episodes of cyclosporine nephrotoxicity and therefore provides a rapid and inexpensive discriminant from allograft rejection.


Condensing water vapor to droplets generates hydrogen peroxide.
It was previously shown [J. K. Lee et al., Proc. Natl. Acad. Sci. U.S.A, 116, 19294-19298 (2019)] that hydrogen peroxide (H2O2) is spontaneously produced in micrometer-sized water droplets (microdroplets), which are generated by atomizing bulk water using nebulization without the application of an external electric field. Here we report that H2O2 is spontaneously produced in water microdroplets formed by dropwise condensation of water vapor on low-temperature substrates. Because peroxide formation is induced by a strong electric field formed at the water-air interface of microdroplets, no catalysts or external electrical bias, as well as precursor chemicals, are necessary. Time-course observations of the H2O2 production in condensate microdroplets showed that H2O2 was generated from microdroplets with sizes typically less than ∼10 µm. The spontaneous production of H2O2 was commonly observed on various different substrates, including silicon, plastic, glass, and metal. Studies with substrates with different surface conditions showed that the nucleation and the growth processes of condensate water microdroplets govern H2O2 generation. We also found that the H2O2 production yield strongly depends on environmental conditions, including relative humidity and substrate temperature. These results show that the production of H2O2 occurs in water microdroplets formed by not only atomizing bulk water but also condensing water vapor, suggesting that spontaneous water oxidation to form H2O2 from water microdroplets is a general phenomenon. These findings provide innovative opportunities for green chemistry at heterogeneous interfaces, self-cleaning of surfaces, and safe and effective disinfection. They also may have important implications for prebiotic chemistry.


Introducing novice therapists to "go-between" techniques of family therapy.
The training of family therapists requires that learning objectives and expectations be specified in empirical terms so that the trainer and trainee can achieve clear goals, identify areas of progress, and meet the special needs of the trainee. This paper articulates the competencies, objectives, and criteria for evaluation used during a time-limited training program for therapists involved in family therapy research conducted at Centennial School of Lehigh University.


Evaluation of the EQ-5D-5L, EQ-VAS stand-alone component and Oxford knee score in the Australian knee arthroplasty population utilising minimally important difference, concurrent validity, predictive validity and responsiveness.
To evaluate the Oxford Knee Score (OKS), EQ-5D-5L utility index and EQ-5D visual analogue scale (EQ-VAS) for health-related quality of life outcome measurement in patients undergoing elective total knee arthroplasty (TKA) surgery. In this prospective multi-centre study, the OKS and EQ-5D-5L index scores were collected preoperatively, six weeks (6w) and six months (6 m) following TKA. The OKS, EQ-VAS and EQ-5D-5L index were evaluated for minimally important difference (MID), concurrent validity, predictive validity (Spearman's Rho of predicted and observed values from a generalised linear regression model (GLM)), responsiveness (effect size (ES) and standard response mean (SRM)). The MID for the individual patient was determined utilising two approaches; distribution-based and anchor-based. 533 patients were analysed. The EQ-5D-5L utility index showed good concurrent validity with the OKS (r = 0.72 preoperatively, 0.65 at 6w and 0.69 at 6 m). Predictive validity for the EQ-5D-5L index was lower than OKS when regressed. Responsiveness was large for all fields at 6w for the EQ-5D-5L and OKS (EQ-5D-5L ES 0.87, SRM 0.84; OKS ES 1.35, SRM 1.05) and 6 m (EQ-5D-5L index ES 1.31, SRM 0.95; OKS ES 1.69, SRM 1.59). The EQ-VAS returned poorer results, at 6w an ES of 0.37 (small) and SRM of 0.36 (small). At 6 m, the EQ-VAS had an ES of 0.59 (moderate) and SRM of 0.47 (small). It, however, had similar predictive validity to the OKS, and better than the EQ-5D-5L index. MID determined using anchor approach, was shown that for OKS at 6 weeks it was 8.84 ± 9.28 and at 6 months 13.37 ± 9.89. For the EQ-5D-5L index at 6 weeks MID was 0.23 ± 0.39, and at 6 months 0.26 ± 0.36. The EQ-5D-5L index score and the OKS demonstrate good concurrent validity. The EQ-5D-5L index demonstrated lower predictive validity at 6w, and 6 m than the OKS, and both PROMs had adequate responsiveness. The EQ-VAS had poorer responsiveness but better predictive validity than the EQ-5D-5L index. This article includes MID estimates for the Australian knee arthroplasty population.


A gastrointestinal stromal tumor with mesenteric and retroperitoneal invasion.
Gastrointestinal stromal tumors are rare visceral sarcomas arising in the gastrointestinal tract wall. In this report we present a case of gastrointestinal stromal tumors with mesenteric and retroperitoneal invasion, describe and discuss its computed tomography findings. A 57-years-old male patient has been complaining of abdominal distention, weight lose, and hematuria. During physical examination, significant distention and multiple palpable tumor masses were identified on the abdomen. Abdominal computed tomography showed multiple, well-defined, soft tissue masses with homogenous and heterogeneous pattern, in the mesenteric and retroperitoneal areas. Unlike specific features of gastrointestinal stromal tumor, renal obstruction and atypical central calcification without chemotherapy that has not been yet described were seen in this case. Computed tomography did not reveal liver metastases and/or the lymph nodes with pathological size. Ultrasonography-guided true-cut biopsy was made, histopathologic and immunohistochemical analyses demonstrated stromal tumor which, C-KIT (+). The patient underwent left ureterectomy, left nephrectomy and total colectomy. Postoperative histopathological analyses revealed lower grade malignant GISTs. As of 17 months after the surgery, he is alive and free of recurrence. When intraabdominal, multiple, large (>5 cm), well-circumscribed, homogenous or heterogeneous mass lesions without ascites, omental caking and lymph nodes metastases were seen, gastrointestinal stromal tumors should be considered in the differential diagnosis.


Mid-term efficacy and safety of Escherichia coli-derived rhBMP-2/hydroxyapatite carrier in lumbar posterolateral fusion: a randomized, multicenter study.
This study aimed to evaluate the mid-term efficacy and safety of Escherichia coli-derived bone morphogenetic protein-2 (E.BMP-2)/hydroxyapatite (HA) in lumbar posterolateral fusion (PLF). This multicenter, evaluator-blinded, observational study utilized prospectively collected clinical data. We enrolled 74 patients who underwent lumbar PLF and had previously participated in the BA06-CP01 clinical study, which compared the short-term outcomes of E.BMP-2 with an auto-iliac bone graft (AIBG). Radiographs and CT scans were analyzed to evaluate fusion grade at 12, 24, and 36 months. Visual analog scale (VAS), Oswestry disability index (ODI), and Short Form-36 (SF-36) scores were measured preoperatively and at 36 months after surgery. All adverse events in this study were assessed for its relationship with E.BMP-2. The fusion grade of the E.BMP-2 group (4.91 ± 0.41) was superior to that of the AIBG group (4.25 ± 1.26) in CT scans at 36 months after surgery (p = 0.007). Non-union cases were 4.3% in the E.BMP-2 and 16.7% in the AIBG. Both groups showed improvement in pain VAS, ODI, and SF-36 scores when compared to the baseline values, and there were no statistically significant differences between the two groups. No treatment-related serious adverse reactions were observed in either group. No neoplasm-related adverse events occurred in the E.BMP-2 group. The fusion quality of E.BMP-2/HA was superior to that of AIBG. E.BMP-2/HA showed comparable mid-term outcomes to that of AIBG in terms of efficacy and safety in one-level lumbar PLF surgery.


Effects of celecoxib on cycle kinetics of gastric cancer cells and protein expression of cytochrome C and caspase-9.
This investigation aimed to determine effects of celecoxib on the cell cycle kinetics of the gastric cancer cell line MGC803 and the mechanisms involved by assessing expression of cytochrome C and caspase-9 at the protein level. Cell proliferation of MGC803 was determined by MTT assay after treatment with celecoxib. Apoptosis was assessed using fluorescence staining and cell cycle kinetics by flow cytometry. Western blotting was used to detect the expression of caspase-9 protein and of cytochrome C protein in cell cytosol and mitochondria. Celecoxib was able to restrain proliferation and induce apoptosis in a dose- and time- dependent manner, inducing G0/G1 cell cycle arrest, release of cytochrome C into the cytosol, and cleavage of pro-caspase-9 into its active form. Celecoxib can induce apoptosis in MGC803 cells through a mechanism involving cell cycle arrest, mitochondrial cytochrome C release and caspase activation.


Evaluation of genotoxic and cytotoxic effects of ethyl acetate extract of Aspergillus flavus on Spodoptera litura.
Recent concerns about the possible adverse effects of agricultural chemicals on health and environment have generated a considerable interest in biological alternatives. This study aimed to test the insecticidal potential of fungus Aspergillus flavus and revealed its genotoxic and cytotoxic effects using Spodoptera litura (Fabricius) as a model. The fungus was isolated from the surface of the dead insect and investigated for its insecticidal potential against S. litura by bioassay studies. Significant increase in mortality, prolonged development period and reduced adult emergence in S. litura were observed in larva fed on diet supplemented with fungal extract. In addition, fungus was also found to cause oxidative stress, DNA damage and cell death. Significantly higher percentages of necrotic cells and DNA damage were observed in larvae treated with fungal extract. Furthermore, DNA repair studies predicted the longevity of toxic effects induced by fungus. Phytochemical and ultra-high performance liquid chromatography studies revealed the presence of phenolic compounds in the extract and liquid chromatography-mass spectrometry indicated it to be a non-aflatoxin strain of A. flavus. Fungal extract was less toxic to mammalian cell lines as compared to cytotoxic drug doxorubicin (DOX) in the MTT assay. The study highlights the insecticidal potential of A. flavus by revealing its genotoxicity and cytotoxicity causing potential. This is the first report showing the genotoxic and cytotoxic effects of the fungus A. flavus on S. litura. The study provides a useful insight to explore microbial agents as biopesticides in order to reduce various environmental as well as human health problems due to synthetic pesticides.


Development of PTH eluting microspheres for the treatment of hypoparathyroidism.
Parathyroid hormone (PTH) replacement has been demonstrated to be superior to conventional treatment with calcium supplementation and vitamin D analogs for the treatment of hypoparathyroidism. In this investigation we evaluated the feasibility of using PTH microsphere encapsulation as a potential delivery system for PTH. Using the spontaneous emulsion technique, PTH microspheres were created by encapsulating PTH (1-34) in a copolymer of polyglycolic and polylactic acid (PLGA). Additional microspheres were constructed by coencapsulating calmodulin with PTH (1-34) in the PLGA microspheres. Microsphere production was confirmed using electron microscopy. PTH release was measured in vitro using an enzyme-linked immunosorbent assay. The bioactivity of PTH released from the microspheres was confirmed in vivo using a hypoparathyroid rat model by measuring serum calcium concentrations before and 3 h after subcutaneous injection of PTH microspheres. PTH microsphere and PTH/calmodulin microspheres could be created using the spontaneous emulsion technique. Physiologically significant PTH release was measured in vitro for 20 days. PTH release was calcium sensitive and exhibited negative feedback. This effect was augmented by coencapsulation with calmodulin. PTH released from the microspheres caused a significant rise in serum calcium levels from an average of 6.35 (6.19-6.48 mg/dL) to 8.55 mg/dL (8.22-8.73). PTH released from the PTH/calmodulin microspheres resulted in an increase in serum calcium from a mean of 6.8 (6.7-6.9 mg/dL) to 8.1 mg/dL (7.8-8.2). The PLGA microspheres can be used to provide calcium sensitive controlled release of biologically active PTH and offer a potential mean of providing biomimetic hormone replacement therapy.


Factors influencing employment after minor stroke and NSTEMI.
To study the effect of cognitive function, fatigue and emotional symptoms on employment after a minor ischemic stroke compared to non-ST-elevation myocardial infarction (NSTEMI). We included 217 patients with minor ischemic stroke and 133 NSTEMI patients employed at baseline aged 18-70 years. Minor stroke was defined as modified Rankin scale (mRS) 0-2 at day seven or at discharge if before. Included NSTEMI patients had the same functional mRS. We applied a selection of cognitive tests and the patients completed questionnaires measuring symptoms of anxiety, depression and fatigue at follow up. Stroke patients were tested at three and 12 months and NSTEMI at 12 months. The patients still employed at 12 monthswere significantly younger than the unemployed patients and the NSTEMI patients employed were significantly older than the stroke patients (59 vs 55 years, p < .001). In total, 82 % of stroke patients and 90 % of the NSTEMI patients employed at baseline were still employed at 12 months (p = 06). Stroke patients at work after 12 months had higher education than unemployed patients. There were no difference between employed and unemployed patients in risk factors or location of cerebral ischemic lesions. Cognitive function did not change significantly in the stroke patients from three to 12 months. For stroke patients, we found a significant association between HADS-depression and unemployment at 12 months (p = 04), although this association was not present at three months. Lower age and higher educational level were associated with employment at 12 months for all patients. Age and education are the main factors influencing the ability to stay in work after a minor stroke. Employed stroke patients were younger than the NSTEMI patients, but there was no difference in the frequencies in remaining employed. The employment rate at 12 months was high despite the relatively high prevalence of cognitive impairment in both groups.


Antibiotic use in children before, during and after hospitalisation.
To investigate ambulatory antibiotic use in children during 1 year before and 1 year after in-hospital antibiotic exposure compared to children from the general population that had not received antibiotics in-hospital. Explorative data-linkage cohort study from Norway of children aged 3 months to 17 years. One group had received antibiotics in-Hospital (H+), and one group had not received antibiotics in-hospital (H-). The H+ group was recruited during admission in 2017. Using the Norwegian Population Registry, 10 children from the H- group were matched with one child from the H+ group according to county of residence, age and sex. We used the Norwegian Prescription Database to register antibiotic use 1 year before and 1 year after the month of hospitalisation. Of 187 children in the H+ group, 83 (44%) received antibiotics before hospitalisation compared to 288/1870 (15%) in the H- group, relative risk (RR) 2.88 (95% confidence interval 2.38-3.49). After hospitalisation, 86 (46%) received antibiotics in the H+ group compared to 311 (17%) in the H- group, RR 2.77 (2.30-3.33). Comorbidity-adjusted RR was 2.30 (1.84-2.86) before and 2.25 (1.81-2.79) after hospitalisation. RR after hospitalisation was 2.55 (1.99-3.26) in children 3 months-2 years, 4.03 (2.84-5.71) in children 3-12 years and 2.07 (1.33-3.20) in children 13-17 years. Children exposed to antibiotics in-hospital had two to three times higher risk of receiving antibiotics in ambulatory care both before and after hospitalisation. The link between in-hospital and ambulatory antibiotic exposure should be emphasised in future antibiotic stewardship programs.


Cluster analysis and its application to healthcare claims data: a study of end-stage renal disease patients who initiated hemodialysis.
Cluster analysis (CA) is a frequently used applied statistical technique that helps to reveal hidden structures and "clusters" found in large data sets. However, this method has not been widely used in large healthcare claims databases where the distribution of expenditure data is commonly severely skewed. The purpose of this study was to identify cost change patterns of patients with end-stage renal disease (ESRD) who initiated hemodialysis (HD) by applying different clustering methods. A retrospective, cross-sectional, observational study was conducted using the Truven Health MarketScan® Research Databases. Patients aged ≥18 years with ≥2 ESRD diagnoses who initiated HD between 2008 and 2010 were included. The K-means CA method and hierarchical CA with various linkage methods were applied to all-cause costs within baseline (12-months pre-HD) and follow-up periods (12-months post-HD) to identify clusters. Demographic, clinical, and cost information was extracted from both periods, and then examined by cluster. A total of 18,380 patients were identified. Meaningful all-cause cost clusters were generated using K-means CA and hierarchical CA with either flexible beta or Ward's methods. Based on cluster sample sizes and change of cost patterns, the K-means CA method and 4 clusters were selected: Cluster 1: Average to High (n = 113); Cluster 2: Very High to High (n = 89); Cluster 3: Average to Average (n = 16,624); or Cluster 4: Increasing Costs, High at Both Points (n = 1554). Median cost changes in the 12-month pre-HD and post-HD periods increased from $185,070 to $884,605 for Cluster 1 (Average to High), decreased from $910,930 to $157,997 for Cluster 2 (Very High to High), were relatively stable and remained low from $15,168 to $13,026 for Cluster 3 (Average to Average), and increased from $57,909 to $193,140 for Cluster 4 (Increasing Costs, High at Both Points). Relatively stable costs after starting HD were associated with more stable scores on comorbidity index scores from the pre-and post-HD periods, while increasing costs were associated with more sharply increasing comorbidity scores. The K-means CA method appeared to be the most appropriate in healthcare claims data with highly skewed cost information when taking into account both change of cost patterns and sample size in the smallest cluster.


Concentration effects on biotic and abiotic processes in the removal of 1,1,2-trichloroethane and vinyl chloride using carbon-amended ZVI.
A permeable reactive barrier, consisting of both zero valent iron (ZVI) and a biodegradable organic carbon, was evaluated for the remediation of 1,1,2-trichloroethane (1,1,2-TCA) contaminated groundwater. During an 888 day laboratory column study, degradation rates initially stabilized with a degradation half-life of 4.4±0.4 days. Based on the accumulation of vinyl chloride (VC) and limited production of 1,1-dichloroethene (1,1-DCE) and 1,2-dichloroethane (1,2-DCA), the dominant degradation pathway was likely abiotic dichloroelimination to form VC. Degradation of VC was not observed based on the accumulation of VC and limited ethene production. After a step reduction in the influent concentration of 1,1,2-TCA from 170±20 mg L(-1) to 39±11 mg L(-1), the degradation half-life decreased 5-fold to 0.83±0.17 days. The isotopic enrichment factor of 1,1,2-TCA also changed after the step reduction from -14.6±0.7‰ to -0.72±0.12‰, suggesting a possible change in the degradation mechanism from abiotic reductive degradation to biodegradation. Microbiological data suggested a co-culture of Desulfitobacterium and Dehalococcoides was responsible for the biodegradation of 1,1,2-TCA to ethene.


A strategy for the rapid discovery and validation of active diterpenoids as quality markers in different habitats of Langdu using ultrahigh-performance liquid chromatography-tandem mass spectrometry with multivariate statistical analysis.
Langdu, known as a traditional Chinese medicine, was identified as the roots of species of Euphorbia ebracteolata Hayata and Euphorbia fischeriana Steud, displaying anti-tuberculosis activity. To clarify the potent quality markers of Langdu, this research first developed a fast and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry method for the quantification of 13 diterpenoids in Langdu. The developed method was further applied in the analyses of 12 authentic E. ebracteolata and E. fischeriana samples collected in northern and southeastern China. Then, the anti-tuberculosis evaluation of 12 batches of Langdu samples was performed in vitro. Finally, partial least squares discrimination analysis was used in the discrimination of E. ebracteolata and E. fischeriana from different origins and processing methods. Jolkinolide A (1), jolkinolide E (3), yuexiandajisu D (6), and ebractenone A (11) were identified as key, potent diterpenoids for the quality control of E. ebracteolata Hayata and E. fischeriana Steud. The present study established a qualitative chemical analysis method for Langdu (E. ebracteolata and E. fischeriana) and suggested the key bioactive components that will improve qualitative control methodology for this important medicine.


Choanal atresia - a recurrent feature of foetal carbimazole syndrome.
Choanal atresia is described as a feature of several congenital anomaly phenotypes. Most cases of choanal atresia arises as an isolated clinical finding. In utero exposure to carbimazole for maternal hyperthyroidism has been reported in five cases of choanal atresia. We report another instance of this teratogenic cause of choanal atresia. Maternal drug history is an important aspect of assessment in cases of choanal atresia.


[Surgery of the tip of nose. Which approach to choose?].
The indications of the different surgical approaches of the alar cartilages for a rational nasal tip correction are given on the basis of their respective advantages and disadvantages.


Synthesis of C4-modified acanthoic acid analogs and their biological evaluation as nitric oxide inhibitors.
Synthesis and biological evaluation of a series of C4-modified acanthoic acid analogs are reported. Among them, the analog 7 and 10 exhibit potent cellular inhibitory activity in NO inhibition assay.


The influence of acute smoking on leucocytes, platelets and the endothelium.
Cigarette smoking is a risk factor for the development of atherosclerosis. Possible mechanisms for this include leucocytes and platelet activation, and/or damage to the endothelium, any of which may contribute to changes in thrombosis and haemostasis. We examined the acute effects of smoking on these systems by obtaining blood before, immediately after, and at 10 and 30 min after the rapid smoking of two cigarettes in sequence by 20 smokers. Blood samples taken at the same time points from ten non-smokers acted as control material. In the smokers there was a transient rise in leucocyte count and neutrophil activation, but von Willebrand factor (VWF--marking endothelial damage) increased steadily at each time point (P <0.05). There were no changes in neutrophil elastase, soluble intercellular adhesion molecule-1 (sICAM-1 normally increased in smokers), fibrinogen, platelet count or soluble P-selectin (marking platelet activation, also normally increased in smokers). We conclude that the acute smoking of two cigarettes in succession will activate leucocytes and cause endothelial cell damage, but will not immediately influence platelet activity.


Application of Tranexamic Acid in Trauma and Orthopedic Surgery.
Tranexamic acid has gained recent interest in orthopedics and trauma surgery because of its demonstrated benefit in several clinical trials. It is inexpensive and effective at reducing blood loss and blood transfusion requirements without a significant increase in morbidity or mortality. The optimal timing, dosing, and route of administration in orthopedics are yet to be elucidated. Significant investigation of tranexamic acid use in joint replacement and spine surgery has promoted its incorporation into the everyday practice of many of these surgeons. The paucity of studies regarding its use in orthopedic trauma has limited its integration into a field that may stand to benefit most from the drug.


Biomechanical simulations of scoliotic spine correction due to prone position and anaesthesia prior to surgical instrumentation.
The positioning of patients during scoliosis surgery has been shown to affect the scoliosis curve, yet positioning has not been exploited to help improve surgical outcome from a biomechanics point of view. Biomechanical models have been used to study other aspects of scoliosis. The goal of this study is to simulate the specific influence of the prone operative position and anaesthesia using a finite element model with patient personalized material properties. A finite element model of the spine, ribcage and pelvis was created from the 3D standing geometry of two patients. To this model various positions were simulated. Initially the left and right supine pre-operative bending were simulated. Using a Box-Benkin experimental design the material properties of the intervertebral disks were personalized so that the bending simulations best matched the bending X-rays. The prone position was then simulated by applying the appropriate boundary conditions and gravity loads and the 3D geometry was compared to the X-rays taken intra-operatively. Finally an anaesthesia factor was added to the model to relax all the soft tissues. The behaviour of the model improved for all three positions once the material properties were personalized. By incorporating an anaesthesia factor the results of the prone intra-operative simulation better matched the prone intra-operative X-ray. However, the anaesthesia factor was different for both patients. For the prone position simulation with anaesthesia patient 1 corrected from 62 degrees to 47 degrees and 43 degrees to 31 degrees. Patient 2 corrected from 70 degrees to 55 degrees and 40 degrees to 32 degrees for the thoracic and lumbar curves respectively. Positioning of the patient, as well as anaesthesia, provide significant correction of the spinal deformity even before surgical instrumentation is fixed to the vertebra. The biomechanical effect of positioning should be taken into consideration by surgeons and possibly modify the support cushions accordingly to maximise 3D curve correction. The positioning is an important step that should not be overlooked by when simulating surgical correction and biomechanical models could be used to help determine optimal cushion placement.


Intestinal very-low-density lipoprotein secretion in the genetically obese Zucker rat.
The objectives of this study were to measure intestinal very-low-density lipoprotein (VLDL) production in obese Zucker rats and to assess an eventual effect of a high-fat diet. VLDL secretion was specifically inhibited by orotic acid, and intestinal VLDL output was measured following the Triton WR-1339 method. After a control diet, total VLDL secretion (without orotic acid) was 4.8 +/- 0.3 and 1.4 +/- 0.1 mg triacylglycerol/ml in obese and lean rats, respectively, decreasing by 30% in obese rats after fat-feeding. Intestinal VLDL production was similar in obese and lean rats fed the control diet (0.32 +/- 0.05 and 0.27 +/- 0.05 mg triacylglycerol/ml, respectively), increasing 2.5-fold after fat-feeding in both genotypes. Thus, intestine contributed 21 and 60% of total VLDL in lean but only 7 and 24% in obese rats with the control and high-fat diets, respectively. These results show that the intestine of obese Zucker rats does not contribute to their hypertriglyceridemia, suggesting that it originates solely from liver. Moreover, their intestinal VLDL production was stimulated by fat-feeding to the same extent as in lean animals.


Alternatives to pristane priming for ascitic fluid and monoclonal antibody production.
A variety of agents were compared to pristane for priming mice prior to ascitic fluid production. Incomplete Freund's adjuvant was found to be as good as or better than pristane for priming before hybridoma cell inoculation. Complete adjuvant was also useful while priming with proteose-peptone; thioglycollate, corn oil or mineral oil elicited only minimum amounts of ascitic fluid after hybridoma injection.


Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production.
Monocytes/macrophages play an important role in rheumatoid arthritis (RA) pathogenesis. They can activate fibroblasts through many molecules, including IL-1 and tumor necrosis factor-alpha, but there have been very few reports on the role of CD147 in RA. In our study, the results of flow cytometry reveal that the mean fluorescence intensity (MFI) of CD147 expression on CD14+ monocytes of peripheral blood from RA patients was higher than that in normal control and ankylosing spondylitis (AS) patients. The MFI of CD147 expression on the CD14+ monocytes in RA synovial fluid was higher than that in RA peripheral blood. Immunohistochemical staining shows that CD147 expression in RA synovium correlated with matrix metalloproteinase (MMP)-1 expression. A double immunofluorescent assay shows that CD147 was expressed on CD68+ cells in RA synovium. The potential role of CD147 in cyclophilin A (CyPA)-mediated cell migration was studied using a chemotaxis assay in vitro and it was found that the addition of anti-CD147 antibody or a CD147 antagonistic peptide significantly decreased the chemotactic index of the mononuclear cells. The role of CD147 in MMP production and cell invasion in vitro were studied through the co-culture of human CD14+ monocytes or monocytic line THP-1 cells and human fibroblasts, as well as by gel zymography and an invasion assay. Significantly elevated release and activation of MMP-9 and/or MMP-2 were seen in the co-culture of human monocytes/THP-1 cells and fibroblasts compared with cultures of the cells alone. An increased number of cells invading through the filters in the invasion assays was also observed in the co-cultured cells. The addition of CD147 antagonistic peptide had some inhibitory effect, not only on MMP production but also on cell invasion in the co-culture. Our study demonstrates that the increased expression of CD147 on monocytes/macrophages in RA may be responsible for elevated MMP secretion, cell invasion and CyPA-mediated cell migration into the joints, all of which may contribute to the cartilage and bone destruction of RA. These findings, together with a better understanding of CD147, CyPA and RA, will help in the development of innovative therapeutic interventions for RA.


Renal adenocarcinoma in benign hyperdense mass.
We report a case of a renal adenocarcinoma presenting as a benign hyperdense mass. The etiology and radiologic diagnosis of hyperdense renal masses are presented.


[Experimental changes of the pH in the middle ear and its effect on the internal ear (author's transl)].
Irrespective of their highly differing pH-value many pharmaca are nowadays applied to the middle ear. Animal experiments are to answer the question, weather changes in the pH-value of the middle ear may cause internal ear damages, With local application of different buffers (2.3-9.1 pH) into the tympanic cavity, the membrane of the round window was examined by means of the surface preparation technique, the pH-value of the perilymph was measured and the hair cells of the organ of corti were counted and histologically evaluated. With the reduction of the pH-value in the middle ear from 4.0 to 2.3 an increasing damage of the round window membrane could be detected. The pH-value of the perilymph, however, showed only a slight statistical variation, which cannot be guaranteed. After multiple applications of extremely acid buffers into the tympanic cavity directly before the round window membrane, a small but statistically significant reduction in the pH-value of the perilymph could be noticed. Hair cell damages at the organ of corti could in no case be observed.


Drug-cue conditioning to external stimulus conditions.
Rats were trained to discriminate 0.04 mg/kg fentanyl from saline in a 2-lever procedure, and to discriminate 10 mg/kg pentobarbital from saline in a maze procedure. Stimulus generalization experiments in rats trained in this double discrimination indicate that the internal cues produced by these training drugs can be conditioned to the external stimulus conditions associated with the different discrimination procedures.


Scale development: perceived barriers to public use of school recreational facilities.
To test an original scale assessing perceived barriers among school administrators to allowing community use of school recreational facilities outside of regular school hours. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Using EFA and CFA, we found that a model including factors of legal/security, resources, and social support demonstrated the best relative fit for our data. The Perceived Barriers to Community Use (PBCU) Scale is psychometrically sound and provides a framework to guide the design of future research and discussion of perceived barriers that school administrators have about opening their school recreational facilities outside of regular school hours.


Three-dimensional, time-resolved (4D) relative pressure mapping using magnetic resonance imaging.
We describe here a method for generating relative pressure maps from magnetic resonance velocity data in three spatial and one temporal dimension (4D). The relative pressure map calculated for pulsatile flow in a compliant phantom was shown to be consistent with independent pressure transducer measurements. The feasibility of performing 4D pressure mapping in vivo is also demonstrated.