The influence of the ambient temperature on tumour growth, metastasis and survival in mice.
The effect of ambient temperature was analysed on the behaviour of MO4 cells which are malignant, invasive and metastasizing C3H mouse fibroblastic cells when implanted in the tail of the syngeneic animal. Raising the ambient temperature to 28 degrees C increases growth of the primary tumour, incidence of metastases and shortens survival. Lowering the ambient temperature to 13 degrees C prevents all these phenomena. Measurements at the implantation site show that the temperature of the tail remains in a range +/- 2-3 degrees C in accordance with the environment. From these results we conclude that room temperature may be important when experiments are performed in vivo.


Subarachnoid hemorrhage secondary to ruptured aneurysms in infants. Report of two cases.
Two infants with subarachnoid bleeding from middle cerebral artery aneurysms are presented, with detailed case histories.


Glutamate receptor-interacting protein 1 in D1- and D2-dopamine receptor-expressing medium spiny neurons differentially regulates cocaine acquisition, reinstatement, and associated spine plasticity.
The nucleus accumbens (NAc) is involved in the expression of cocaine addictive phenotypes, including acquisition, extinction, and reinstatement. In the NAc, D1-medium spiny neurons (MSNs) encode cocaine reward, whereas D2-MSNs encode aversive responses in drug addiction. Glutamate receptor-interacting protein 1 (GRIP1) is known to be associated with cocaine addiction, but the role of GRIP1 in D1-MSNs and D2-MSNs of the NAc in cocaine acquisition and reinstatement remains unknown. A conditioned place preference apparatus was used to establish cocaine acquisition, extinction, and reinstatement in mouse models. GRIP1 expression was evaluated using Western blotting. Furthermore, GRIP1-siRNA and GRIP1 overexpression lentivirus were used to interfere with GRIP1 in the NAc. After the behavioral test, green fluorescent protein immunostaining of brain slices was used to detect spine density. GRIP1 expression decreased during cocaine acquisition and reinstatement. GRIP1-siRNA enhanced cocaine-induced CPP behavior in acquisition and reinstatement and regulated associated spine plasticity. Importantly, the decreased GRIP1 expression that mediated cocaine acquisition and reinstatement was mainly driven by the interference of the GRIP1-GluA2 interaction in D1-MSNs and could be blocked by the interference of the GRIP1-GluA2 interaction in D2-MSNs. Interference with the GRIP1-GluA2 interaction in D1- and D2-MSNs decreased spine density in D1- and D2-MSNs, respectively. GRIP1 in D1- and D2-MSNs of the NAc differentially modulates cocaine acquisition and reinstatement. GRIP1 downregulation in D1-MSNs has a positive effect on cocaine acquisition and reinstatement, while GRIP1 downregulation in D2-MSNs has a negative effect. Additionally, GRIP1 downregulation in D1-MSNs plays a leading role in cocaine acquisition and reinstatement.


Development of green micellar HPLC-DAD method for simultaneous determination of some sulbactam combinations used in COVID-19 regimen.
In a new attempt to separate some sulbactam combinations by green chemical method we came up with this research in which an ecofriendly, green, sustainable and selective method was established for separation of four antibiotics, namely, cefoperazone (CFP), cefixime (CFX), ampicillin (AMP) and sulbactam (SLB). No organic solvents were used in the composition of the mobile phase as it was replaced by mixing two surfactants together, sodium dodecyl sulfate (SDS) and polyoxyethylene-23-lauryl ether (Brij-35). Effect of varying the concentrations of the two surfactants on chromatographic separation was studied. Optimum separation was maintained using a mobile phase consisting of 0.01 mol/L SDS, 0.03 mol/L Brij-35, 0.4% Tri-ethylamine (TEA) and pH of 2.8 adjusted by using 1 M ortho-phosphoric acid on reversed phase Isère C18 BDS column with temperature of 40 °C at flow rate 1 mL/min, wavelength 215 nm, and the total run time was 6 min. Validation of the proposed method has been made according International Conference of Harmonization (ICH) guidelines at linearity range of 10-200 µg mL-1 for all drugs under study, high accuracy results (recovery range 98.39-100.35%). and the variation coefficient (RSD) of the points on the calibration curve was ranged from (0.1-1.7%) indicating precise method. The LOQ was (6.09 μg mL-1) for CFP, (6.07 μg mL-1) for CFX, (3.85 μg mL-1) for AMP and (7.20 μg mL-1) for SLB. Successful applications were made on marketed dosage forms with recovery range of (100.16-102.25%) and RSD of (0.03-1.88%). The method was verified on the Green Analytical Procedure Index (GAPI) and Analytical Greenness metric approach (AGREE) and it was found to be an excellent green alternative method.


Association between the alanine aminotransferase/aspartate aminotransferase ratio and new-onset non-alcoholic fatty liver disease in a nonobese Chinese population: a population-based longitudinal study.
The alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio has been considered an alternative marker for hepatic steatosis. However, few studies have investigated the association of the ALT/AST ratio with non-alcoholic fatty liver disease (NAFLD) in nonobese people. A total of 12,127 nonobese participants who were free of NAFLD participated in this study. The participants were divided into quintiles of the ALT/AST ratio. Multiple Cox regression models were used to explore the association of the ALT/AST ratio with new-onset NAFLD. During the five-year follow-up period, 2147 individuals (17.7%) developed new-onset NAFLD. After adjusting for all non-collinear covariates, the multiple Cox regression analysis results showed that a higher ALT/AST ratio was independently associated with new-onset NAFLD in nonobese Chinese (adjusted hazard ratios [aHRs]: 2.10, 95% confidence intervals: 1.88, 2.36). The aHRs for NAFLD across increasing quintiles of the ALT/AST ratio were 1, 1.63 (1.30, 2.04), 2.07 (1.65, 2.60), 2.84 (2.33, 3.48) and 3.49 (2.78, 4.39) (P for trend< 0.001). The positive association was more significant among people with high blood pressure, high blood lipids and hyperglycaemia, as well as in men. Additionally, the regression spline showed that the saturation effect of the ALT/AST ratio on NAFLD risk was at 0.93 in this study population, which was 1.22 in males and 0.89 in females. In nonobese Chinese individuals without NAFLD at baseline, the increase in the ALT/AST ratio is closely associated with the risk of new-onset NAFLD.


Machine learning for prediction of septic shock at initial triage in emergency department.
We hypothesized utilizing machine learning (ML) algorithms for screening septic shock in ED would provide better accuracy than qSOFA or MEWS. The study population was adult (≥20 years) patients visiting ED for suspected infection. Target event was septic shock within 24 h after arrival. Demographics, vital signs, level of consciousness, chief complaints (CC) and initial blood test results were used as predictors. CC were embedded into 16-dimensional vector space using singular value decomposition. Six base learners including support vector machine, gradient-boosting machine, random forest, multivariate adaptive regression splines and least absolute shrinkage and selection operator and ridge regression and their ensembles were tested. We also trained and tested MLP networks with various setting. A total of 49,560 patients were included and 4817 (9.7%) had septic shock within 24 h. All ML classifiers significantly outperformed qSOFA score, MEWS and their age-sex adjusted versions with their AUROC ranging from 0.883 to 0.929. The ensembles of the base classifiers showed the best performance and addition of CC embedding was associated with statistically significant increases in performance. ML classifiers significantly outperforms clinical scores in screening septic shock at ED triage.


Absence of drug interaction between temafloxacin and low dose heparin.
An open 5-day study was conducted in 12 healthy male volunteers to determine the potential for drug interaction between low dose standard heparin and temafloxacin, a new fluorinated quinolone antibiotic. Heparin 5000IU was administered subcutaneously on the morning of the first and last study days and temafloxacin 600mg was administered twice daily for 4 days. The mean change in activated factor X (antifactor Xa) concentration relative to baseline 2h after coadministration was similar to that after heparin alone. Likewise, changes in activated partial prothrombin time, prothrombin time and thrombin time were similar after either heparin alone or concomitant temafloxacin administration, indicating the absence of interaction between temafloxacin and low dose standard heparin in healthy volunteers.


Combined beam hardening artifact correction and quantitative microanalysis of colloidal depositions in deep bed filtration experiments investigated by 3D X-ray computed microtomography.
In this study we present quantitative X-ray computed microtomography measurements (μCT) of retained sub-micron-sized particles in open porous media carried out in a laboratory μCT setup. Due to the polychromatic spectrum of the used X-rays, the tomograms are affected by various non-linear artifacts, which belong to the class of beam hardening artifacts. These artifacts become more dominant, when the amount of retained particles increases and can affect wide areas of the images, making a qualitative and quantitative analysis barely possible. Furthermore, the colloidal depositions show an inhomogeneous distribution inside the filter, making a reliable material discrimination between filter and particle material challenging. We introduce a calibration method, which is capable to sufficiently remove the majority of the artifacts by linearization of the projection data and thus enabling the precise material quantification of the retained colloids in the reconstructed tomograms. While most beam hardening correction routines are only applicable to homogeneous materials, our algorithm takes into account inhomogeneous material distributions and is adapted to multi-material systems. Moreover, the method includes a material discrimination of the colloids and the filter in the raw data domain. Thus, erroneous segmentations at the interfaces between different material fractions are avoided. As a result we present quantitative concentration maps of the particle distribution inside the porous media with a resolution of < 10μm. A series of validation samples was prepared, covering a wide range of different, representative filter loading stages. The accuracy of the particle quantification was evaluated from these samples and the relative deviation of the overall contained particle mass was less than 10% in all cases, partially even less than 1%. The overall image quality due to the artifact removal was significantly improved. The local variation of the particle concentration could be well assessed from the obtained concentration maps.


Development of dense microsatellite markers in the entire SLA region and evaluation of their polymorphisms in porcine breeds.
We developed 40 microsatellite markers in the entire swine leukocyte antigen (SLA) region, spanning over 2.35 Mb. The average span between markers was 59 kb, and the largest interval between markers was 127 kb. We also evaluated polymorphisms of length for the markers using 97 pigs derived from 12 breeds, including representative commercial breeds. All of the markers were successfully amplified in genomic DNA and shown to be polymorphic. These markers will provide an alternative method for determining the SLA haplotypes instead of direct typing of SLA genes per se. They will be valuable for transplantation studies and for association studies between immunological traits such as disease susceptibility and tumor rejection.


Cue validity modulates the neural correlates of covert endogenous orienting of attention in parietal and frontal cortex.
Parietal brain regions have been implicated in reorienting of visuospatial attention in location-cueing paradigms when misleading advance information is provided in form of a spatially invalid cue. The difference in reaction times to invalidly and validly cued targets is termed the "validity effect" and used as a behavioral measure for attentional reorienting. Behavioral studies suggest that the magnitude of the validity effect depends on the ratio of validly to invalidly cued targets (termed cue validity), i.e., on the amount of top-down information provided. Using fMRI, we investigated the effects of a cue validity manipulation upon the neural mechanisms underlying attentional reorienting using valid and invalid spatial cues in the context of 90% and 60% cue validity, respectively. We hypothesized that increased parietal activation would be elicited when subjects need to reorient their attention in a context of high cue validity. Behaviorally, subjects showed significantly higher validity effects in the high as compared to the low cue validity condition, indicating slower reorienting. The neuroimaging data revealed higher activation of right inferior parietal and right frontal cortex in the 90% than in the 60% cue validity condition. We conclude that the amount of top-down information provided by predictive cues influences the neural correlates of reorienting of visuospatial attention by modulating activation of a right fronto-parietal attentional network.


Mechanistic insights into CKD-MBD-related vascular calcification and its clinical implications.
Chronic Kidney Disease (CKD) is linked to a rising prevalence of morbidity and mortality primarily from cardiovascular complications and is considered a high or very high-risk associated cardiovascular state. These poor outcomes are associated with CKD-mineral and bone disorders (CKD-MBD) in CKD patients, which are manifested by vascular calcification. Patients with chronic renal illness have not only accelerated intimal and medial calcification, but heart valves, and possibly the myocardium get also calcified, as well as the uncommon state of calcific uremic arteriolopathy (calciphylaxis). So the CKD-MBD associated vascular calcification might be a key mediator for an array of cardiovascular sequelae. Various routes link vascular calcification with CKD including the involvement of non-traditional risk factors but still, mechanisms are incompletely understood, and focused treatments have been slow to emerge. Major events and factors in vascular calcification involve the conversion of vascular smooth muscles cells into chondrocyte-like cells. Further dysregulation of calcium, phosphate, parathyroid hormone (PTH), Vitamin D hormonal system, phosphorous, and imbalance of promoters and inhibitors (Fetuin-A and Vitamin K dependent matrix Gla protein) plays the important role in promoting CKD-MBD associated vascular calcification. Fibroblast growth factor-23 (FGF-23), Sclerostin, and Klotho are thought to be the emerging factors involved in the CKD-MBD leading to vascular calcification process and cardiovascular mortality. This review summarizes the brief pathological basis of vascular calcification in CKD, current and emerging approaches including the vast arrangement of contributors and inhibitors for the early identification and treatment.


Variation of POP concentrations in fresh-fallen snow and air on an Alpine glacier (Monte Rosa).
To understand better the mechanisms ruling the fate of POPs (persistent organic pollutants) in cold environments, a field campaign sampling fresh-fallen snow and air on an Alpine glacier was carried out during Summer 2003. The concentrations of all analyzed chemicals in fresh-fallen snow show a sharp decrease over time, particularly for the more volatile POPs, confirming the rather limited literature evidence of a rapid decline of such substances from the snowpack and/or ice. Even if the results presented here are preliminary and should be confirmed by further studies, some evidence of the influence of a night/day cycle of temperature on POP deposition and revolatilization mechanisms has been highlighted. Finally, the role of cold condensation and long-range atmospheric transport in the contamination of higher altitudes in this Alpine system has been substantiated, particularly for OC pesticides.


Long-term effectiveness of a school-based primary prevention program for anorexia nervosa: A 7-to 8-year follow-up.
This is the first study to evaluate the long-term effectiveness of a school-based prevention program in Germany. The aim is to determine the long-term effects of the primary prevention program PriMa (Primary prevention of anorexia nervosa in preadolescent girls) on disordered eating and body self-esteem from childhood to young adulthood. PriMa was conducted and successfully evaluated in a quasi-experimental pre-post design with a control group from 2007 to 2008 consisting of 11-13year old girls (N=1508) from Thuringian schools in Germany. Seven to eight years after the intervention, the same cohort (mean age 19.8years) was invited to complete an online survey. Disordered eating (EAT-26), body self-esteem (FBeK) and BMI were assessed via self-report. The response rate at seven-to-eight-year follow-up was very low (7%). Data of N=100 girls were analyzed. Concerning changes in disordered eating, results revealed no significant long-term effect of PriMa seven to eight years after the intervention. During this time, disordered eating remained stable without a significant increase or decrease. Regarding changes in body self-esteem, group courses differed significantly from each other. The results revealed a significant main effect of group, indicating significant differences in changes of body self-esteem between the intervention and the control group. Following the analysis of these changes of body self-esteem over time, it was found that the intervention group revealed an increase of body self-esteem after program participation and remained stable over time. By contrast, the control group revealed a decrease of body self-esteem over time. Long-term intervention effects of PriMa could be found for body self-esteem but not for disordered eating. The findings suggest that PriMa prevented a decrease of body self-esteem from childhood to young adulthood. For a broader dissemination it is necessary to implement prevention programs consistently in school settings. In order to maintain the prevention effects, it would be interesting to investigate the effects of booster sessions which refresh the programs content on a regular basis. Furthermore, the results of this study revealed the implementation difficulties of primary prevention programs especially concerning the retention of the sample size.


Suicide - a statistical analysis by age, sex and method.
A total of 115 suicide cases dealt with by St. Pancras Coroner's Court, London, UK were studied in order to determine what patterns exist regarding the age and gender of the victims and chosen method of suicide. The results were compared with those of a 1998 study of suicides in England and Wales commissioned by the UK Home Office. It was found that suicides in the male population are approximately twice as common as female victims of suicide. In terms of gross number of cases, the peak age group for both males and females resorting to suicide was found to be the 15-44 age group. When the results were standardised according to 2001 census data, however, the most vulnerable age group per head of population for both sexes was 75 and over. Good agreement was found between the results of this study and those of the Home Office Study.


Quantifying the dynamic density driven convection in high permeability packed beds.
The density driven convection phenomenon is expected to have a significant and positive role in CO2 geological storage capacity and safety. The onset and development of density-driven convective on the core scale is critical to understand the mass transfer mechanism. In this paper, laboratory experiments were conducted to investigate the density-driven convective in a vertical tube. The deuterium oxide (D2O)/manganese chloride (MnCl2) water solution in water or brine were as an analog for CO2-rich brine in original brine. Experiments are repeated with variations in permeability to vary the characteristic Rayleigh number. Based on the MRI technology, the intensity images showed the interface clearly, reflecting the transition from diffusion to convective. With the echo-multi-slice pulse sequence method, the intensity images can be obtained as 2min 8s. For the denser fluid pairs, fingers appeared, propagated, coalesced and multi-fingers formed. The finger growth rate of the convective was visualized as three distinct periods: rising, stable and declining. Detailed information regarding the wave number, wave length, onset time and mixing time as functions of Rayleigh number are developed.


Appraisal of hepatic resection in the treatment of hepatocellular carcinoma with severe thrombocytopenia.
Hepatic resection for hepatocellular carcinoma (HCC) patients with liver cirrhosis and severe hypersplenic thrombocytopenia is risky and controversial. From 1989 to 2005, 341 patients underwent hepatic resection for HCC in our hospital. Of these, 15 patients were concomitant with severe thrombocytopenia (platelet count, <or=5 x 10(4)/mm(3)), and their clinical outcomes were retrospectively reviewed. Among the 15 patients, 11 underwent hepatectomy alone and 4 underwent concomitant splenectomy. The mean preoperative platelet count was 4.2 +/- 0.8 x 10(4)/mm(3) (range, 1.9-5 x 10(4)/mm(3)). The surgical procedures performed were partial resection in five patients, subsegmentectomy in three, and segmentectomy in seven. A blood transfusion was required for 11 of 15 patients, and 8 of these received a platelet-rich plasma transfusion. With the exception of one patient who suffered from postoperative liver failure, all the patients had an uneventful postoperative course. The 3-year cumulative survival rate of these patients was comparable to those without thrombocytopenia. Severe thrombocytopenia alone is not a contraindication for hepatectomy in patients with HCC associated with liver cirrhosis. For these patients, hepatic resection-hepatectomy alone or concomitant splenectomy-should be considered as a treatment option.


Determination of pre-arthropathy scapular anatomy with a statistical shape model: part I-rotator cuff tear arthropathy.
Rotator cuff tear arthropathy (RCTA) is a pathology characterized by a massive rotator cuff tear combined with acromiohumeral and/or glenohumeral arthritis. The severity of RCTA can be staged according to the Hamada classification. Why RCTA develops in some patients is unknown. Furthermore, in RCTA patients, distinctly different articular damage patterns can develop on the glenoid side as categorized by the Sirveaux classification (glenoid erosion). The goal of this study was to determine whether an association exists between scapular anatomy and RCTA and different severity stages of RCTA, as well as the associated glenoid erosion types. A statistical shape model of the scapula was constructed from a data set of 110 computed tomography scans using principal component analysis. Sixty-six patients with degenerative rotator cuff pathology formed the control group. The computed tomography scan images of 89 patients with RCTA were included and grouped according to the Hamada and Sirveaux classifications. A complete 3-dimensional scapular bone model was created, and statistical shape model reconstruction was performed. Next, automated 3-dimensional measurements of glenoid version and inclination, scapular offset, the critical shoulder angle (CSA), the posterior acromial slope (PAS), and the lateral acromial angle (LAA) were performed. All measurements were then compared between controls and RCTA patients. The control group had a median of 7° of retroversion (variance, 16°), 8° of superior inclination (variance, 19°), and 106 mm of scapular offset (variance, 58 mm). The median CSA, PAS, and LAA were 30° (variance, 14°), 65° (variance, 60°), and 90° (variance, 17°), respectively. In terms of inclination, version, scapular offset, and the PAS, we found no statistically significant differences between the RCTA and control groups. For RCTA patients, the median CSA and median LAA were 32° (P ≤ .01) and 86° (P ≤ .01), respectively. For all investigated parameters, we did not find any significant difference between the different stages of RCTA. Patients with type E3 erosion had a different pre-arthropathy anatomy with increased retroversion (12°, P = .006), an increased CSA (40°, P ≤ .001), and a reduced LAA (79°, P ≤ .001). Our results seem to indicate that a 4° more inferiorly tilted and 2° more laterally extended acromion is associated with RCTA. RCTA patients in whom type E3 erosion develops have a distinct pre-arthropathy scapular anatomy with a more laterally extended and more inferiorly tilted acromion and a more retroverted glenoid in comparison with RCTA patients with no erosion. The pre-arthropathy scapular anatomy does not seem to differ between patients with different stages of RCTA.


Characterizing tumors using metabolic imaging: PET imaging of cellular proliferation and steroid receptors.
Treatment decisions in oncology are increasingly guided by information on the biologic characteristics of tumors. Currently, patient-specific information on tumor biology is obtained from the analysis of biopsy material. Positron emission tomography (PET) provides quantitative estimates of regional biochemistry and receptor status and can overcome the sampling error and difficulty in performing serial studies inherent with biopsy. Imaging using the glucose metabolism tracer, 2 -deoxy-2- fluoro-D-glucose (FDG), has demonstrated PET's ability to guide therapy in clinical oncology. In this review, we highlight PET approaches to imaging two other aspects of tumor biology: cellular proliferation and tumor steroid receptors. We review the biochemical and biologic processes underlying the imaging, positron-emitting radiopharmaceuticals that have been developed, quantitative image-analysis considerations, and clinical studies to date. This provides a basis for evaluating future developments in these promising applications of PET metabolic imaging.


Should routine pyeloureterostomy be advocated in adult kidney transplantation? A prospective study of 283 recipients.
Ureteroneocystostomy surgical techniques have been repeatedly debated in the medical literature, in contrast to pyeloureterostomy, which is merely considered a salvage procedure. We assessed urological complications and their management after routine pyeloureterostomy in adult kidney transplantation cases. We performed a 2-center, uncontrolled, prospective study from January to December 2007. We compared results in 151 consecutive kidney transplantations with routine pyeloureterostomy (group 1) and in 129 procedures with extravesical anti-reflux ureteroneocystostomy (group 2). Perioperative ureteral stenting was done on demand in each group. Major complications included complex leakage, stenosis and surgical revision. Transient leakage or obstruction less than 15 days in duration were considered minor complications. Recipients in group 1 were more likely to undergo ureteral stenting on demand than those in group 2 (68.9% vs 21.7%). The incidence of overall complications was similar in groups 1 and 2 (9.3% and 13.2%, respectively, p = 0.15), although the major complication rate was higher in group 2. Group 1 recipients had a tendency to require long-term ureteral stenting more often. The only recipient with ureteral necrosis in group 1 was treated with surgical resection and repeat end-to-end ureteroureterostomy. In each group no graft was lost due to urological complications or their management. Routine pyeloureterostomy is a safe technique that may be a valuable alternative to ureteroneocystostomy for adult renal transplantation. It does not preclude further open re-intervention. Its main advantages include a significant decrease in the risk of surgical re-intervention, the opportunity to perform further endourological procedures on the allograft urinary system and the avoidance of vesicoureteral reflux.


Population-based reference values for the 1-min sit-to-stand test.
To determine reference values for the 1-min sit-to-stand (STS) test in an adult population. Cross-sectional study nested within a nationwide health promotion campaign in Switzerland. Adults performed the STS test and completed questions on demographics and health behavior. 6,926 out of 7,753 (89.3 %) adults were able to complete the STS test. The median number of repetitions ranged from 50/min (25-75th percentile 41-57/min) in young men and 47/min (39-55/min) in young women aged 20-24 years to 30/min (25-37/min) in older men and 27/min (22-30/min) in older women aged 75-79 years. The reference values support the interpretation of 1-min STS test performance and identification of subjects with decreased lower body muscular strength and endurance.


Motivation, blood donor satisfaction and intention to return during the COVID-19 pandemic.
This study aimed to describe motives as well as donation experiences and the intention to return for further donations of German whole blood donors who donated at the beginning of the COVID-19 pandemic. To describe motives and donor experiences, a retrospective survey was conducted among whole blood donors that had a donation appointment at the German Red Cross Blood Donation Service in the first 4 weeks of the pandemic. A donor questionnaire including 17 retrospective questions was sent to 7500 donors. Donor motivation and donor experiences were compared for different donor groups using chi-square statistics. Finally, in an ordinal logistic regression model predictors for the intention to return were identified. More than half of the participating donors (56.9%) wanted to contribute to the fight against the pandemic by donating blood. Most of the donors were satisfied with their last donation experience and felt safe during the blood donor appointment. However, some donors would have liked more information on how to deal with the pandemic (20.3%). Intention to return for further donations was strongly associated with overall satisfaction (OR: 1.67, CI: 1.47-1.90) and the feeling of being safe during blood donation (OR: 1.33, CI: 1.05-1.68). Donor satisfaction with the last donation was high and the vast majority of donors felt very safe. However, those donors who felt unsafe expressed a low intention to return and blood donation services should therefore carefully monitor donor satisfaction.


Restrained drinking: risk factor for problems with alcohol?
A seven-item Drinking Restraint Scale (DRS) has been developed which indicates that a style of alcohol consumption, equivalent in a number of ways to the style of food consumption termed eating restraint, may exist. Several hypothesized relationships between DRS scores and other drinking-related measures were confirmed. A restrained drinking style was associated with: more extreme patterns of alcohol consumption; a higher proportion of drinking occasions that result in intoxication; more external styles of alcohol consumption control; and more alcohol-related negative consequences. The latter three relationships were found even when heavy drinkers were excluded from the analysis, which suggests that these relationships are not dependent on a heavy drinking pattern. These findings encourage continued investigation of drinking restraint as a risk factor for developing problems with alcohol.


High density lipoprotein metabolism in normolipidemic and cholesterol-fed rabbits.
New Zealand white rabbits were used to determine the compositional and metabolic changes induced in high density lipoproteins (HDL, rho = 1.063--1.21 g/ml) in response to cholesterol feeding. There was no change in total HDL cholesterol in plasma due to cholesterol feeding (12 weeks), but the triglyceride level was decreased to 29% of pretreatment values. Total protein content of HDL was decreased in response to cholesterol feeding, resulting in a significant increase in the cholesterol/protein ratio. There was a decrease in some isomer of the major apolipoproteins (A-I2) of HDL. The decay of radioactivity in HDL or its apolipoproteins was biphasic in both normolipidemic and hypercholesterolemic rabbits. The first phase was much more rapid than the second. The decay rates for the radioactivity in HDL depended upon the dietary status of the recipient animal.


Visualization of NO3⁻/NO2⁻ Dynamics in Living Cells by Fluorescence Resonance Energy Transfer (FRET) Imaging Employing a Rhizobial Two-component Regulatory System.
Nitrate (NO3(-)) and nitrite (NO2(-)) are the physiological sources of nitric oxide (NO), a key biological messenger molecule. NO3(-)/NO2(-) exerts a beneficial impact on NO homeostasis and its related cardiovascular functions. To visualize the physiological dynamics of NO3(-)/NO2(-) for assessing the precise roles of these anions, we developed a genetically encoded intermolecular fluorescence resonance energy transfer (FRET)-based indicator, named sNOOOpy (sensor for NO3(-)/NO2(-) in physiology), by employing NO3(-)/NO2(-)-induced dissociation of NasST involved in the denitrification system of rhizobia. The in vitro use of sNOOOpy shows high specificity for NO3(-) and NO2(-), and its FRET signal is changed in response to NO3(-)/NO2(-) in the micromolar range. Furthermore, both an increase and decrease in cellular NO3(-) concentration can be detected. sNOOOpy is very simple and potentially applicable to a wide variety of living cells and is expected to provide insights into NO3(-)/NO2(-) dynamics in various organisms, including plants and animals.


Vulvar intra-epithelial neoplasia associated with other genital tract neoplasia. Four case reports and discussion.
It is recognised that a significant number of patients who develop vulvar intra-epithelial neoplasia (VIN), will have had previous genital tract neoplasia. This has resulted in speculation that there may be a common aetiology and, in particular, on the possibility of an infective element. Four such cases from the Vulva Clinic at the Western Infirmary, Glasgow are presented for discussion.


Inorganic nanoparticle-integrated mesenchymal stem cells: A potential biological agent for multifaceted applications.
Mesenchymal stem cell (MSC)-based therapies are flourishing. MSCs could be used as potential therapeutic agents for regenerative medicine due to their own repair function. Meanwhile, the natural predisposition toward inflammation or injury sites makes them promising carriers for targeted drug delivery. Inorganic nanoparticles (INPs) are greatly favored for their unique properties and potential applications in biomedical fields. Current research has integrated INPs with MSCs to enhance their regenerative or antitumor functions. This model also allows the in vivo fate tracking of MSCs in multiple imaging modalities, as many INPs are also excellent contrast agents. Thus, INP-integrated MSCs would be a multifunctional biologic agent with great potential. In this review, the current roles performed by the integration of INPs with MSCs, including (i) enhancing their repair and regeneration capacity via the improvement of migration, survival, paracrine, or differentiation properties, (ii) empowering tumor-killing ability through agent loaded or hyperthermia, and (iii) conferring traceability are summarized. An introduction of INP-integrated MSCs for simultaneous treatment and tracking is also included. The promising applications of INP-integrated MSCs in future treatments are emphasized and the challenges to their clinical translation are discussed.


Conversion of E4 (E4 =P4 , As4 , AsP3 ) by Ni(0) and Ni(I) Synthons - A Comparative Study.
The reactivity of white phosphorus and yellow arsenic towards two different nickel nacnac complexes is investigated. The nickel complexes [(L1 Ni)2 tol] (1, L1 =[{N(C6 H3 i Pr2 -2,6)C(Me)}2 CH]- ) and [K2 ][(L1 Ni)2 (μ,η1 : 1 -N2 )] (6) were reacted with P4 , As4 and the interpnictogen compound AsP3 , respectively, yielding the homobimetallic complexes [(L1 Ni)2 (μ-η2 ,κ1 :η2 ,κ1 -E4 )] (E=P (2 a), As (2 b), AsP3 (2 c)), [(L1 Ni)2 (μ,η3 : 3 -E3 )] (E=P (3 a), As (3 b)) and [K@18-c-6(thf)2 ][L1 Ni(η1 : 1 -E4 )] (E=P (7 a), As (7 b)), respectively. Heating of 2 a, 2 b or 2 c also leads to the formation of 3 a or 3 b. Furthermore, the reactivity of these compounds towards reduction agents was investigated, leading to [K2 ][(L1 Ni)2 (μ,η2 : 2 -P4 )] (4) and [K@18-c-6(thf)3 ][(L1 Ni)2 (μ,η3 : 3 -E3 )] (E=P (5 a), As (5 b)), respectively. Compound 4 shows an unusual planarization of the initial Ni2 P4 -prism. All products were comprehensively characterized by crystallographic and spectroscopic methods.


Carbon dots, cellulose nanofiber, and essential oil nanoemulsion from Torreya grandis aril added to fish scale gelatin film for tomato preservation.
In this study, carbon dots (CDs), cellulose nanofibers (CNF) and essential oil nanoemulsion (EON) were extracted from the aril waste of Torreya grandis following nuts production. These three nanomaterials were formulated for the preparation of a composite film to be employed for postharvest tomato storage. Visual, microscopical and physicochemical properties of the prepared nanocomposite films were analyzed at different levels of CDs and CNF for optimization purposes. The UV absorption and antioxidant capacity of gelatin film with 10 % CDs (G/10CD) were enhanced compared with gelatin (G) film, concurrent with a reduction in water barrier capacity, water contact angle (WCA) and tensile strength (TS). Compared with G/10CD film, the WCA of G film after incorporation of 10 % CDs and 3 wt% CNF (G/10CD/3CNF) was significantly increased by 14.5°at 55 s. In contrast, TS increased by 1.26 MPa, as well as the significant enhancement in water barrier capacity. The above composite film mixed with EON (G/10CD/3CNF/EON) exerted further antimicrobial effects against Escherichia coli. G/10CD/3CNF/EON coating effectively extended tomato shelf life compared with the control group. Therefore, this new eco-friendly film presents several advantages of biodegradability, sustainability as well as multifunctional properties posing it as potential packaging material for food applications.


Comprehensive characterization of the in vitro and in vivo metabolites of ziyuglycoside I in rat microsome, intestinal flora, excretion specimen and fresh tissues based on LC-Q-TOF/MS.
Ziyuglycoside I is one of the major active ingredients in Sanguisorba officinalis, a popular medicinal plant in China. In the present study, the metabolites of ziyuglycoside I in rat liver microsome and intestinal flora were identified and structurally characterized, and the metabolic rules were summed based on the LC-Q-TOF/MS system. Then, the metabolites in rat excreta samples were rapidly screened and identified according to the in vitro metabolic rules. Finally, ziyuglycoside I was incubated with fresh liver/lung/kidney/stomach homogenates to further explore the source of the metabolites and reveal the possible metabolic organs involved. Four metabolites in liver microsome were identified as M0-Glu, M0-CH2OH, M0-Glu+CH3, M0-Glu-Ara+CH3. In intestinal flora incubation system, 6 degradation products including M0-Glu-Ara+O, M0-Ara, M0-Glu-COOH, M0-Glu, M0-Glu-Ara+O and M0-Ara+H2O were tentatively identified by interpretation of their accurate MS(1) and MS(2) data. Fifteen metabolites in rat urine and feces were identified, and most of the metabolites were attributed to the transformation in liver microsome and intestinal flora. Specifically, more than a dozen of new metabolites were identified in rat fresh tissues, and ziyuglycoside II was confirmed as the major metabolite in rats.


Complete Rupture of the Pregnant Uterus: A 10-year Retrospective Descriptive Study.
The goal of this work is to analyze the incidence, etiology, clinical characteristics, maternal and neonatal outcomes of complete uterine rupture during pregnancy. The information of complete uterine rupture between June 2010 and May 2020 was investigated retrospectively at a tertiary center, and included demographic data, delivery characteristics, intraoperative findings, and maternal and neonatal outcomes. The prevalence rate of uterine rupture in the early group (hospitalized from June 2010 to May 2015) and late group (June 2015 to May 2020) was compared and analyzed. There were 37 (0.056%) cases of complete uterine rupture in 66 092 births, including 27 (0.041%) of scar uterus and 10 (0.015%) of non-scarred uterus. High-risk factors for scarred uterine rupture included: previous cesarean section (13, 48.1%), myomectomy (8, 29.6%), corneal pregnancy resection (6, 22.2%), history of uterine rupture (1, 3.7%), and uterus perforation during abortion (1, 3.7%). Compared to the early group, the number of uterine ruptures caused by previous cesarean section was significantly reduced in the late group. Of the 10 patients with non-scarred uterine rupture, 3 (30%) occurred during delivery and 7 (70%) were spontaneous. Among the 37 complete rupture patients, 3 (8.1%) died of uterine scar rupture, 19 (51.3%) cases were reported with fetal/newborn deaths, 5 (13.5%) cases underwent hysterectomy and the rest were treated with uterine repair. Complete uterine rupture often has catastrophic effect on pregnancy outcomes. Obstetrics doctors should be vigilant to identify the risk factors and clinical presentations of uterine rupture during pregnancy. Strict prenatal management is beneficial to improve pregnancy outcomes.


Specificity of word meaning and use of sentence context by hearing-impaired adults.
The effects of a semantic aspect of sentence context, general versus specific words, on word identification by hearing-impaired adults was examined. In Experiment 1, subjects heard incomplete sentences over headsets and attempted to identify the omitted test word. These sentences varied the number of contextual words with general or specific meanings. As predicted, listeners identified more test words when the sentences contained specific contextual words. In Experiment 2, listeners attempted recall of test words that were included in the sentence presentation. Listeners were required to recall the entire sentence in order to direct attention to the context. Again, recall of the test word occurred more frequently when sentences contained specific words. Implications of the findings for aural rehabilitation are discussed.


Esophageal replacement with whole stomach in infants and children.
This is a report of ten patients in whom the esophagus is replaced by the whole stomach brought through the chest. It was used for children with long gap or previously failed esophageal atresia repair. It documents complications (anastomotic leak and stricture) and morbidity, and highlights precautions that must be taken.


Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease.
Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies.


Bone mineral density and circulating cytokines in patients with acromegaly.
Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p < 0.01), but not at femoral neck level or at Ward's triangle level (0.92 + 0.15 g/cm2 vs 0.97 + 0.11 g/cm2, p = NS; and 0.74 +/- 0.16 g/cm2 vs 0.85 +/- 0.1 g/cm2, p = NS) when compared to controls. Baseline serum levels of TNF-alpha and IL-1 were in the normal range both in patients and controls. After acute octreotide administration, no differences in circulating TNF-alpha and IL-1 levels were found. In conclusion, acromegalic patients present a reduced BMD at lumbar spine but not at femoral neck level and Ward's triangle. Circulating cytokines such as TNF-alpha and IL-1 are in the normal range. These data suggest that cytokines are not involved in the pathogenesis of GH-excess induced osteoporosis. The possibility that the GH excess might affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.


Bela Julesz in Depth.
A brief tribute to Bela Julesz (1928-2003) is made in words and images. In addition to a conventional stereophotographic portrait, his major contributions to vision research are commemorated by two 'perceptual portraits', which try to capture the spirit of his main accomplishments in stereopsis and the perception of texture.


Surgical and non-surgical management of thoracic and cervical paraganglioma.
Thoracic and cervical paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest progenitors located outside the adrenal gland. We describe our current protocol as a multidisciplinary team for the management of cervical and thoracic PGLs. Surgery is generally considered the treatment of choice as it offers the best chance for cure. For resection of thoracic PGLs, video-assisted thoracoscopic surgery (VATS) is the main surgical approach, while open thoracotomy is preferred in case of tumors > 6cm, lacking confirmation of a plane of separation with adjacent structures, or with technical difficulties during VATS. In cervical PGLs, the surgical approach should be individualized according to location, mainly based on the Glasscock-Jackson and the Fisch-Mattox classifications. Surgery is the treatment of choice for most cervical and thoracic PGLs, but radiotherapy or observation could be more suitable options in unresectable cervical and thoracic PGLs or when resection has been incomplete.


Communities of ammonia oxidizers at different stages of Spartina alterniflora invasion in salt marshes of Yangtze River estuary.
Spartina alterniflora, an aggressive invasive plant species at the estuarine wetlands of China's coasts, has become a major threat to the natural ecosystems. To understand its potential influence on nitrification processes, the community structures and abundance of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were investigated using 454-pyrosequencing and quantitative real-time PCR (qPCR) in S. alterniflora invading salt marsh sediments at the Yangtze River estuary in Chongming island, Shanghai, China. Copy numbers of archaeal and bacterial ammonia monooxygenase subunit A (amoA) genes did not show accordant shifts with S. alterniflora invasion in the two sampling sites. However, the copy numbers of archaeal amoA gene were higher in summer than in spring. Phylogenetic analysis indicated that more than 90% of the archaeal and 92% of the bacterial amoA gene sequences were closely related to marine group I.1a and the clusters 13 and 15 in Nitrosospira lineage, respectively. The effect of different seasons (spring and summer) was important for the abundance variation of AOA, while different stages of S. alterniflora invasion did not show significant effect for both AOA and AOB. Variation of AOA community was significantly related to total carbon (TC) and sulfate concentration (P < 0.05), whereas the AOB community was significantly related to sulfate concentration, total nitrogen (TN), TC and pH (P < 0.05). In conclusion, the abundance and diversity of ammonia oxidizing microbial communities were not strongly affected by S. alterniflora invasion.


Serum and urinary amylase levels following pulsatile and continuous cardiopulmonary bypass.
The incidence of elevated serum and urine amylase values was examined in a prospective clinical study of patients subjected to either continuous or pulsatile extracorporeal perfusion. Mean postoperative values for urine and serum amylase were higher in the continuous group, and the incidence of abnormal values was also greater in the continuous group (70 percent versus 32 percent, p less than 0.01). Clinical pancreatitis was absent in both groups. This study documents a high incidence of elevated amylase values following bypass with either modality and provides evidence for possible improved visceral circulation with pulsatile extracorporeal bypass during routine cardiac operations.


Ultrasound-guided percutaneous cholecystostomy as bridging or definitive treatment in patients with acute cholecystitis grade II or III.
We aimed to investigate the extent to which ultrasound (US)-guided percutaneous cholecystostomy (PC) is used as a bridging or definitive therapy for grade II and III acute cholecystitis and whether this treatment causes significant changes in C-reactive protein (CRP) and direct bilirubin (DB) levels in the first 72 h and the first three weeks. We included 145 consecutive patients who underwent PC over 17 years. No patient had cirrhosis. PC was performed in the interventional radiology department under US guidance. US-guided PC was the definitive treatment for more than half of the patients (51.7%) and decreased DB levels significantly more than CRP levels. No statistically significant correlation between those whose CRP and DB levels normalized within three weeks and those who did not and required a second invasive procedure. Nevertheless, the bridging treatment group was significantly older than the definitive treatment group.


Anastomotic leak and recurrent fistula following operation of oesophageal atresia.
Experiences from 14 disruptions of oesophageal sutures and with 8 cases of recurrent fistula from 1973 to 1982 are described. Healing of an early oesophageal insufficiency could be achieved by conservative means in 3 newborns. Conservative therapy seems to be possible if life-threatening clinical conditions are reduced effectively. 6 oesophago-pulmonary and recurrent oesophago-tracheal fistulas were closed operatively, two cases closed spontaneously.


Behavior genetic research on gambling and problem gambling: a preliminary meta-analysis of available data.
A meta-analysis of family and twin studies on gambling and problem gambling was initiated in an effort to determine the probable role of genetic factors in high risk wagering. Two twin studies and 17 investigations employing the family history or family study method were included in this meta-analysis. A summation of the 19 studies produced a small but significant overall effect size (weighted phi = .10, unweighted phi = .13), with both family (weighted phi = .12, unweighted phi = .14) and twin (weighted phi = .06, unweighted phi = .05) studies achieving significant individual mean effects. Given the paucity of twin data, further analysis was confined to family studies and revealed a stronger familial effect for the sons of problem gambling fathers than for the daughters of problem gambling mothers and for more severe forms of problem gambling than for less severe forms of problem wagering, and was strongest for high severity problem gambling in males. The implications of these results are discussed.


Toward the design of an optimal filter for enhancement of dichromat monocular chromatic discrimination.
Based on Farnsworth's theories of color confusion and discrimination, "rose-colored" or "pink" filters such as the X-Chrom material of 0.16 mm in thickness or the Kodak Wratten no. 30 filter act as monocular chromatic enhancers for red/green color deficients by virtue of colorimetrically lengthening color space in a direction perpendicular to the dichromatic axis of color confusion. Using derived formulas for dichromat colorimetry, a set of representative isoluminant-isochroma spectral hues, and interactive computer graphic colorimetric tools, it is possible to determine an optimum spectrophotometric filter curve. Such a filter has minimal middle wavelength transmission and is optimal in terms of providing maximal monocular chromatic clues for discriminative tasks involving confused colors.


Synovial fluid characteristics and the lupus erythematosus cell phenomenon in drug-induced lupus. Findings in three patients and review of pertinent literature.
The characteristics of synovial fluid obtained from 3 patients with drug-induced lupus erythematosus are described. Two patients had "inflammatory" counts of synovial leukocytes, in the range of 2,500-39,000/mm3, with mononuclear predominance in 1 patient and neutrophil predominance in the other. The third patient had "noninflammatory" fluid, with mononuclear predominance. Lupus erythematosus cells formed in vivo were observed in the synovial fluid of 2 of the patients. Biopsy of the synovium of 1 patient showed nonspecific chronic inflammatory changes. Our findings in these patients with drug-induced lupus are indistinguishable from those previously described in patients with idiopathic lupus erythematosus.


Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic ELevated prolactin).
Prolactin elevations occur in people treated with antipsychotic medications and are often much higher in women than in men. Hyperprolactinemia is known to cause amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also associated with sexual dysfunction and bone loss. These side effects increase risk of antipsychotic nonadherence and suicide and pose significant problems in the long term management of women with schizophrenia. In this manuscript, we review the literature on prolactin; its physiology, plasma levels, side effects and strategies for treatment. We also present the rationale and protocol for an ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal women with schizophrenia. More attention and focus are needed to address these significant side effects and help the field better personalize the treatment of women with schizophrenia.


An in-vitro evaluation of silicone elastomer latex for topical drug delivery.
A silicone elastomer latex was evaluated as a topical drug-delivery system. With the addition of a fumed silica and the removal of water, the latex produced elastomeric solid films. The water vapour permeability of the solid film was found to be a function of the film composition. An increase in silica content and the incorporation of a water-soluble component, PEG 3350, rendered the silicone elastomer-free film even more permeable to water vapour. The release of hydrocortisone from the elastomer film can be described by a matrix-diffusion-controlled mechanism. Drug diffusion is thought to occur through the hydrophobic silicone polymer network and the hydrated hydrophilic silica region in the film matrix. Silicone elastomer film with a higher silica content exhibited a faster drug-release rate. The addition of PEG 3350 to the film further enhanced the drug-release rate.


Chloramphenicol: magic bullet or double-edge sword?
The genetic and genotoxic potentials of chloramphenicol are reviewed and analyzed. Although this widely used antimicrobial agent appears to cause chromosomal effects in somatic cells, in view of the consistent absence of other genetic effects, these cytogenetic abnormalities are ascribed to non-genotoxic causes. It is pointed out that despite its widespread use in human medicine, chloramphenicol has not been systematically tested for genotoxicity.


Multiple Infection and Human Immunodeficiency Virus Superinfection Among Persons who Inject Drugs in Indonesia and Ukraine.
The HIV Prevention Trials Network (HPTN) 074 study evaluated an integrated human immunodeficiency virus (HIV) treatment and prevention strategy among persons who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. We previously detected multiple HIV infection in 3 of 7 (43%) of seroconverters with 3-8 HIV strains per person. In this report, we analyzed multiple HIV infection and HIV superinfection (SI) in the HPTN 074 cohort. We analyzed samples from 70 participants in Indonesia and Ukraine who had viral load >400 copies/mL at enrollment and the final study visit (median follow-up, 2.5 years). HIV was characterized with Sanger sequencing, next-generation sequencing, and phylogenetic analysis. Additional methods were used to characterize a rare case of triple-variant SI. At enrollment, multiple infection was detected in only 3 of 58 (5.2%) participants with env sequence data. SI was detected in only 1 of 70 participants over 172.3 person-years of follow-up (SI incidence, 0.58/100 person-years [95% confidence interval, .015-3.2]). The SI case involved acquisition of 3 HIV strains with rapid selection of a strain with a single pol region cluster. These data from a large cohort of PWID suggest that intrahost viral selection and other factors may lead to underestimation of the frequency of multiple HIV infection and SI events.


A novel Cry1A resistance allele of fall armyworm in the new invaded region.
The fall armyworm, Spodoptera frugiperda, is a devastating pest in its native range Western Hemisphere and has become a major invasive pest around the globe. Transgenic crops producing Bt toxins have been widely used to control S. frugiperda. However, the evolution of resistance threatens the sustainability of Bt crops. Field-evolved S. frugiperda resistance to Bt crops was observed in America, whereas, no case of field-resistance was reported in its newly invaded East Hemisphere. Here we investigated the molecular mechanism of a Cry1Ab-resistant LZ-R strain of S. frugiperda, which selected 27-generations using Cry1Ab after being collected in corn fields from China. Complementation tests between LZ-R strain and SfABCC2-KO strain, which have been knockout SfABCC2 gene and confer 174-fold resistance to Cry1Ab, showed a similar level of resistance in the F1-progeny as their parent stains, indicating that a common locus of SfABCC2 mutation in LZ-R stain. Sequencing of the full length of SfABCC2 cDNA from LZ-R strain, we characterize a novel mutation allele of SfABCC2. Cross-resistance results showed that Cry1Ab-resistance strain also confers >260-fold resistance to Cry1F, with no cross-resistance to Vip3A. These results provided evidence of a novel SfABCC2 mutation allele in the newly invaded East Hemisphere of S. frugiperda.


Combining the use of two non-invasive instruments to confirm that a formula can improve skin luminance while respecting constitutive melanogenesis.
Skin radiance products achieve perceivable benefits with different sort of mechanism of action. To use two non-invasive instrumental devices to evaluate the effectiveness of a cosmetic formula designed to improve skin reflectance while respecting skin integrity. Subjects (N = 43) aged 18-50 years old had healthy skin of phototype V-VI and Individual Typology Angle between -10° and -50°. The treatment was applied twice weekly for 4 weeks on a delineated area of the back, and an adjacent area was left untreated. Instrumental and clinical scoring assessments of treated and untreated skin were performed at baseline and Day 26. Between baseline and Day 26, reflectance (Delta L*) increased by 1.27 points and was considered as clinically relevant. Dermatologist clinical scoring of radiance significantly improved from 2.6 to 3.6 after 4 weeks of treatment and the Skin Color Chart Clarity level significantly decreased from a score of 15.5 to 14.3, representing a skin reflectance improvement. Conversely, the change between baseline and Day 26 in Mexameter Melanin Density was not clinically different for treated skin versus untreated skin (difference of 2.54). At Day 26, changes from baseline for Mexameter Melanin Density and Delta L* parameters appeared to be uncorrelated (r = -0.036). This combination of two non-invasive devices can be useful to confirm that a product can modulate skin reflectance without modifying constitutive pigmentation. The formula tested in this study did not interfere with constitutive melanogenesis.


Temporal and spatial analysis of cartilage proteoglycan core protein gene expression during limb development by in situ hybridization.
As limb mesenchymal cells differentiate into chondrocytes they initiate the synthesis of a cartilage-specific sulfated proteoglycan, cartilage-characteristic type II collagen, and other cartilage-specific proteins. In the present study, in situ hybridization with a 32P-labeled cloned cDNA probe complementary to mRNA encoding the core protein of cartilage proteoglycan has been used to visualize and localize the accumulation of cartilage proteoglycan core protein mRNA sequences during development of the chick limb bud in vivo. When the probe was hybridized to sections through 7-day (stage 32) limbs, an intense hybridization signal was observed over the well-differentiated cartilage rudiments of the limb, while no signal above background was observed over nonchondrogenic tissues including muscle, loose connective tissue, and epidermis. At early stages of limb development, an accumulation of silver grains representing hybridizable core protein mRNA first became detectable in the proximal central core of the limb where the prechondrogenic condensation of mesenchymal cells that characterizes the onset of cartilage differentiation was occurring. In fact, the pattern of silver grain accumulation closely followed the pattern of mesenchymal cell condensation, and no hybridizable core protein mRNA sequences were detectable in the limb bud prior to condensation. Cartilage-characteristic type II collagen mRNA was colocalized with core protein mRNA in the condensing central core of the limb suggesting that the genes for these two major constituents of cartilage matrix are coordinately regulated at the onset of chondrogenesis. Furthermore, the appearance of hybridizable core protein mRNA was closely followed by the appearance of the protein for which it codes as detected by immunohistochemical staining with monospecific antibody. These observations support the hypothesis that at the initial stages of limb chondrogenesis core protein gene expression is controlled primarily at the transcriptional level.


Separation of disaccharides by affinity capillary electrophoresis in lectin-containing electrophoretic solutions.
Separation of the 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives of simple disaccharides (maltose, cellobiose, gentiobiose, lactose, and melibiose) by affinity capillary electrophoresis was investigated using lectin-containing neutral phosphate buffers, filled in a linear polyacrylamide-coated capillary. When Lens culinaris agglutinin (LCA) was added, the derivatives of glucobioses were retarded with varying magnitudes depending on the amount of LCA and were well separated from each other and from galactosyl glucose under optimized conditions. Addition of Ricinus communis 60 kDa agglutinin (RCA60) to the phosphate buffer gave a different migration profile, in which the derivatives of galactosyl glucoses were more retarded than those of glucobioses. However, addition of either lectin did not accomplish complete separation of the derivatives of all these disaccharides even under optimum conditions. The addition of two kinds of lectins in appropriate proportions improved separation. Thus, the binary system composed of LCA and RCA60, as well as LCA and soybean agglutinin from Glycine max (SBA), gave better separation of these derivatives, giving peak tops for all derivatives.


Tumorigenic mechanisms of estrogen and Helicobacter pylori cytotoxin-associated gene A in estrogen receptor α-positive diffuse-type gastric adenocarcinoma.
Diffuse-type gastric cancer (DGC), for which Helicobacter pylori infection is a causal factor, is associated with poor prognosis among young women, possibly due to female hormones such as estrogen. We aimed to identify the carcinogenesis induced by estrogen and H. pylori in DGC. We screened and selected estrogen receptor alpha (ERα)-positive (MKN45) and ERα-negative (SNU5) DGC cell lines. H. pylori strain 60190 and its isogenic mutant strain lacking cytotoxin-associated gene A (60190ΔCagA) were used to infect MKN45 cells. And the cytotoxin-related gene A (CagA) cDNA which was cloned into pSP65-SR-HA (cagA-pSP65SRa) vector was used to transfect MKN45 cells. Tumor samples were used for DGC organoid culture. In MKN45 cells, we found that estradiol promotes epithelial-mesenchymal transition (EMT) and stemness phenotypes via HOTAIR expression. These effects were further enhanced by the addition of CagA secreted by H. pylori but were reversed by co-treatment with fulvestrant (ICI 182,780), a selective ER degrader. We also validated the effect of estrogen on DGC organoids. ERα expression was associated with tumor invasion and HOTAIR expression in DGC patients with overt H. pylori infection. These findings may explain the rapid DGC progression in young women with physiologically high levels of estrogen and suggest that fulvestrant with ovarian function suppression could serve as a tumor-suppressive agent in premenopausal patients with DGC.


Magnetic resonance imaging of parotid gland tumors: a pictorial essay.
Imaging of parotid gland tumors is challenging due to the wide variety of differential diagnoses. Malignant parotid tumors can have very similar features to benign ones, such as slow growth and displacement instead of infiltration of neighboring structures. Malignant and benign tumors may therefore not be clinically distinguishable. Correct characterization of parotid tumors (i.e., benign or malignant) determines preoperative treatment planning and is important in optimizing the individualized surgical plan. Magnetic resonance imaging (MRI) is the imaging modality of choice for evaluation of suspected parotid gland lesions and differentiation between benign and malignant lesions. Certain conventional MRI features can suggest whether a mass is more likely to be a benign or low-grade malignancy or a high-grade malignancy and adding diffusion-weighted imaging or advanced MRI techniques like perfusion can aid in this distinction. Morphological features seen on MRI, such as low signal on T2-w, infiltrative changes or ill-defined margins, change over time and diffusion restriction can point to the malignant nature of the lesion. MRI is useful for detection and localization of the lesion(s), and associated findings like perineural spread of tumor, lymph node involvement and infiltrative changes of the surrounding tissues. In this pictorial essay, we present selected images of a variety of benign and malignant parotid tumors and emphasize the MRI features that may be useful in their characterization.


Germling fusion via conidial anastomosis tubes in the grey mould Botrytis cinerea requires NADPH oxidase activity.
In many filamentous ascomycete species, the early steps of colony development include fusion between germinating vegetative spores (conidial germlings). Often these fusion events are mediated by specialized hyphal structures, so-called conidial anastomosis tubes (CATs). Here, we show that germling fusion in the grey mould Botrytis cinerea is mediated by hyphal structures possessing the typical features of CATs. Formation of these structures is delayed when spores are germinating on complex media compared to growth on poor substrates. Fusion frequency is also influenced by the growth conditions of the precultures from which spores were obtained. During germination on hydrophobic plant surfaces, which induce pathogenic development, CAT formation is significantly suppressed. Screening of existing B. cinerea gene knockout mutants identified strains lacking the NADPH oxidase BcNoxA or the potential Nox regulator BcNoxR as fusion deficient, suggesting a potential role of reactive oxygen species (ROS) signalling in CAT formation and fusion.


Viral hepatitis prevention education: what do people and providers need to know?
Although hepatitis has been on the decline overall, tens of thousands of new infections are still projected for the coming years. Few studies have investigated the basic (core) educational concepts that are essential to understanding viral hepatitis. This study surveyed three categories of people: (hepatitis 'experts', healthcare providers, and patients) to gather ideas for core concepts for two populations (healthcare providers and patients). The first round of data collection generated ideas for concepts and the second round provided rank orderings. Statistical analyses standardized the suggestions, and provided a numerical system of inclusion and exclusion of concepts. From this process, four lists of core concepts were compiled: hepatitis A, B, and C (individually) for healthcare providers, and hepatitis A, B, and C (combined) for patients. These concepts are useful for educators, nurses and trainers in designing hepatitis prevention materials, counseling patients about hepatitis prevention, and teaching healthcare providers about hepatitis prevention.


2-5A-dependent endoribonuclease activity and effects of A2'p5'A2'p5'A (2-5A core) in mouse pancreatic islets.
Glucose-stimulated (pro)insulin biosynthesis is markedly inhibited is mouse pancreatic islets incubated with micromolar concentrations of 2-5A 'core', (A2'p5'A2'p5'A). Total protein synthesis was also reduced, but to a lesser extent, while insulin release and total insulin content of the islets was untouched by 2-5A 'core'. Evidence is given for the presence of a 2-5A-dependent endoribonuclease which mediates these effects.


Diastereoselective Intramolecular Hydride Transfer Triggered by Electrophilic Halogenation of Aryl Alkenes.
Diastereoselective hydride transfer could be triggered by electrophilic halogenation (bromination or fluorination) of homoallylic alcohol O-Bn ethers. The resulting diastereomerically enriched haloalkyl alcohols underwent subsequent intramolecular nucleophilic substitution to afford the corresponding tetrahydrofurans.


A vented laryngeal stent with phonatory and pressure relief capability.
This prototype vented laryngeal stent incorporates a dome-shaped, one-way valve that allows articulation of transmitted vibrations to produce speech, while preventing aspiration and not interfering with deglutition. The stent is placed endoscopically and is used in conjunction with a T-tube or a tracheostomy tube. The stent has been placed in seven patients for chronic aspiration, after partial laryngectomy, and with laryngotracheal reconstruction for stenosis. Aspiration pneumonia has not been seen in any patient after placement of the appropriate stent, with follow-up of 2 to 6 months. One patient's swallowing improved and none deteriorated. All patients were able to phonate with the stent in place. No significant long-term sequelae are apparent in three patients whose stents were removed after resolution of their primary diseases.


Radiographic assessment of the sinuses in patients treated for nasopharyngeal carcinoma.
Patients undergoing therapy for nasopharyngeal carcinoma (NPC) often experience dysfunction of the sinonasal mucosa as a side effect of radiotherapy and chemotherapy. Sinonasal mucosal changes may vary throughout the treatment and posttreatment periods, but little objective data exist characterizing such changes. We evaluated serial radiologic changes of the paranasal sinus mucosa in patients with NPC undergoing treatment. Medical and radiographic records were reviewed for all patients treated for NPC between 2004 and 2006 at Stanford University Medical Center. Pretreatment computed tomography (CT) images served as the baseline images for comparison, and posttreatment CT and magnetic resonance imaging (MRI) images were categorized temporally into 3-month intervals, up to 25 months after initiation of treatment. Images were scored in a blinded fashion using the Lund-Mackay (LM) staging system. Thirty-five patients received treatment for NPC during the study period, of whom 27 had adequate data for analysis and inclusion in the study. The mean pretreatment LM score was 1.41, and a statistically significant increase in LM score was observed at 3, 6, 9, 12, 15, and 18, 22, and 28 months. There was continued progression of radiologic sinus opacification over the first 30 months after treatment. The treatment of NPC with radiotherapy and chemotherapy is associated with radiologic evidence of sinus mucosal thickening. The extent of mucosal thickening can be expected to progress after treatment for up to 30 months. Patients undergoing treatment for NPC should be monitored carefully throughout the posttreatment period for clinical manifestations of dysfunctional sinonasal mucosa.


Recent trends in term trial of labor after cesarean by number of prior cesarean deliveries.
Cesarean delivery is a major source of maternal morbidity, and repeat cesarean delivery accounts for 40% of cesarean delivery, but recent data on the trial of labor after cesarean and vaginal birth after cesarean are limited. This study aimed to report the national rates of trial of labor after cesarean and vaginal birth after cesarean by number of previous cesarean deliveries and examine the effect of demographic and clinical characteristics on these rates. This was a population-based cohort study using the US natality data files. The study sample was restricted to 4,135,247 nonanomalous singleton, cephalic deliveries between 37 and 42 weeks of gestation, with a history of previous cesarean delivery and delivered in a hospital between 2010 and 2019. Deliveries were grouped by number of previous cesarean deliveries (1, 2, or ≥3). The trial of labor after cesarean (deliveries with labor among deliveries with previous cesarean delivery) and vaginal birth after cesarean (vaginal deliveries among trial of labor after cesarean) rates were computed for each year. The rates were further subgrouped by history of previous vaginal delivery. Year of delivery, number of previous cesarean deliveries, history of previous cesarean delivery, age, race and ethnicity, maternal education, obesity, diabetes mellitus, hypertension, inadequate prenatal care, Medicaid payer, and gestational age were examined concerning the trial of labor after cesarean and vaginal birth after cesarean using multiple logistic regression. SAS software (version 9.4) was used for all analyses. The trial of labor after cesarean rates increased from 14.4% in 2010 to 19.6% in 2019 (P<.001). This trend was seen in all categories of number of previous cesarean deliveries. Moreover, vaginal birth after cesarean rates increased from 68.5% in 2010 to 74.3% in 2019. The trial of labor after cesarean and vaginal birth after cesarean rates were the highest for deliveries with a history of both 1 previous cesarean delivery and a vaginal delivery (28.9% and 79.7%, respectively) and the lowest for those with a history of ≥3 previous cesarean deliveries and no history of vaginal delivery (4.5% and 46.9%, respectively). Factors associated with the trial of labor after cesarean and vaginal birth after cesarean rates are similar, but several factors have different directions of effect, such as non-White race and ethnicity, which is associated with a higher likelihood of trial of labor after cesarean but a lower likelihood of successful vaginal birth after cesarean. More than 80% of patients with a history of previous cesarean delivery deliver by repeat scheduled cesarean delivery. With vaginal birth after cesarean rates increasing among those who attempt a trial of labor after cesarean, emphasis should be put on safely increasing the trial of labor after cesarean rates.


Application of non-parametric regression to quantitative structure-activity relationships.
Several non-parametric regressors have been applied to modelling quantitative structure-activity relationship (QSAR) data. Performances were benchmarked against multilinear regression and the nonlinear method of smoothing splines. Variable selection was explored through systematic combinations of different variables and combinations of principal components. For the training set examined--539 inhibitors of the tyrosine kinase, Syk--the best two-descriptor model had a 5-fold cross-validated q2 of 0.43. This was generated by a multi-variate Nadaraya-Watson kernel estimator. A subsequent, independent, test set of 371 similar chemical entities showed the model had some predictive power. Other approaches did not perform as well. A modest increase in predictive ability can be achieved with three descriptors, but the resulting model is less easy to visualise. We conclude that non-parametric regression offers a potentially powerful approach to identifying predictive, low-dimensional QSARs.


Gold nanoparticles-based biosensing of single nucleotide DNA mutations.
Detection of DNA mutations is critical for scientific research and diagnostic procedures. Here, we propose a novel interdisciplinary method for rapid and simple detection of DNA mutations. We show that heating a solution containing DNA and gold nanoparticles results in degradation of the DNA. Surprisingly, we found that the DNA can be protected against degradation, if an oligonucleotide that matches the DNA is added to the solution. Moreover, the level of degradation indicates the presence of mutations in the DNA. The method is sensitive enough to indicate even a single nucleotide difference, and has the potential to ultimately replace initial medical genetic tests. As proof of concept, we demonstrate a clear detection of two of the most common mutations leading to Cystic Fibrosis.


Decreased accuracy of protein synthesis in extracts from aging human diploid fibroblasts.
The accuracy of protein synthesis has been measured in extracts from human diploid fibroblasts of different ages. Extracts were supplied with purified mRNA for the coat protein of the cowpea variant of tobacco mosaic virus (CcTMV), which lacks codons for cysteine and methionine. The presence of 35S-cysteine in CcTMV coat protein synthesized during translation reactions therefore represents translational error. Translation reactions were performed with extracts from young fibroblasts (less than 50% of life span completed) and old fibroblasts (more than 90% of life span completed), and the translation products were purified by immunoprecipitation and analyzed by polyacrylamide gel electrophoresis. The error frequency increased from 4.2 x 10(-5) cysteines/amino acid in young cell extracts to 2.9 x 10(-4) cysteines/amino acid in old cell extracts. Cysteine incorporation was not due to nonspecific binding, and could be increased approximately sixfold by the addition of the misreading antibiotic, paromomycin. It is concluded that translational accuracy is not stable during aging in vitro, and it is proposed that this decrease in the fidelity of information transfer could be responsible for the variety of changes observed in aging cultured human cells.


Ablation of stage T1/T2 prostate cancer with permanent interstitial temperature self-regulating rods.
To determine if stage T(1)/T(2) prostate cancer can be treated safely and effectively with interstitial thermal ablation. Twenty patients with biopsy-confirmed prostate cancer were enrolled in the protocol. The average age was 71.0 years, and the pretreatment prostate specific antigen (PSA) concentration ranged from 2.5 to 10.7 ng/mL and the Gleason sum from 3 to 7. An array of small biocompatible magnetic alloy rods was placed in the patients percutaneously in a procedure analogous to the placement of brachytherapy seeds. Rods were placed end-to-end and no further than 1 cm apart; rods extended to the capsule and were placed at the capsule in the rectal grove. The rods are temperature self-regulating and heat to 70 degrees C when placed in an alternating magnetic field. Each patient was treated in a coil system that supplies a uniform magnetic field throughout the patient's pelvis for a single 60-minute session. Urethral cooling and rectal temperature monitoring was performed. Serial PSA was followed, and biopsy was performed 1 year post-treatment. Immediately after treatment, most PSA values increased dramatically but then fell to <1.0 ng/mL within 8 weeks. After 1 year, five patients had positive biopsies; these patients had significantly lower rodimplant densities. Eight patients reported erectile dysfunction, but none reported incontinence. Other complications were minor. The data suggest that this technique is well tolerated and safe and may be useful in certain patients with T(1)/T(2) prostate cancer.


Association of mannose binding lectin with chronic obstructive pulmonary disease susceptibility and its clinical outcomes.
The physiological interactions of MBL suggest its contribution towards the pathogenesis of COPD. The present case-control study was undertaken to elucidate the role of MBL with COPD risk and clinical outcomes in north Indian cohort. Patients were enrolled as per GOLD criteria. MBL2 variants were selected based on the literature and their putative functional significance. Genotyping of six single nucleotide polymorphisms of MBL2 comprising of two coding (rs1800450, rs1800451) and four non-coding variants (rs11003125, rs7096206, rs11003123 and rs7095891) was done by using PCR-RFLP and ARMS-PCR. Serum MBL levels were analysed by sandwich ELISA. Overall findings of the molecular genetic analysis of MBL2 indicated significant difference in frequency of three of the six studied variants, between patients and controls or among different disease severity stages. Heterozygous genotype of rs7095891 showed significant protective association towards severity of disease. Linkage disequilibrium (LD) analysis indicated a strong LD between rs1800450 and rs7095891 while intermediate LD was observed for rs11003123/rs11003125 and rs7096206/rs11003125. Haplotype analysis revealed 17.14-fold risk of developing exacerbations conferred by GGGTGG haplotype. Significantly low serum MBL levels observed in COPD patients as compared to controls. Significant difference in MBL deficiency levels were also observed for homozygous wild and variant genotypes of rs11003125 and rs7096206 respectively, as well as for all genotypes of rs11003123 than respective controls. The present study reinforces the role played by MBL in the susceptibility, protection and clinical outcomes of COPD. Therefore, including the reported associations at diagnostic, prognostic and therapeutic interventions may prove helpful.


Effect of detergents on the physicochemical properties of skin stratum corneum: a two-photon excitation fluorescence microscopy study.
Understanding the structural and dynamical features of skin is critical for advancing innovation in personal care and drug discovery. Synthetic detergent mixtures used in commercially available body wash products are thought to be less aggressive towards the skin barrier when compared to conventional detergents. The aim of this work is to comparatively characterize the effect of a mild synthetic cleanser mixture (SCM) and sodium dodecyl sulphate (SDS) on the hydration state of the intercellular lipid matrix and on proton activity of excised skin stratum corneum (SC). Experiments were performed using two-photon excitation fluorescence microscopy. Fluorescent images of fluorescence reporters sensitive to proton activity and hydration of SC were obtained in excised skin and examined in the presence and absence of SCM and SDS detergents. Hydration of the intercellular lipid matrix to a depth of 10 μm into the SC was increased upon treatment with SCM, whereas SDS shows this effect only at the very surface of SC. The proton activity of SC remained unaffected by treatment with either detergent. While our study indicates that the SC is very resistant to external stimuli, it also shows that, in contrast to the response to SDS, SCM to some extent modulates the in-depth hydration properties of the intercellular lipid matrix within excised skin SC.


Elaeagnus angustifolia can improve salt-alkali soil and the health level of soil: Emphasizing the driving role of core microbial communities.
Saline-alkali environments are widely distributed in China and significantly hinder the development of agriculture. This study characterizes the long-term effects of planting Elaeagnus angustifolia (E. angustifolia) on the physical and chemical properties, enzyme activities and microbial community characteristics of saline-alkali soil in the Songnen Plain (1, 2 and 3 years). The results showed that planting E. angustifolia reduced soil pH and electrical conductivity (EC) and increased soil total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (Nni), total potassium (TK), dissolved organic C (DOC), dissolved organic matter (DOM) and available potassium (AK) content and catalase, urease, polyphenol oxidase, phosphatase, sucrase and cellulase enzyme activities, and the results peaked in the 3 year. High-throughput sequencing showed that the bacterial abundance and diversity were as follows (from high to low) y3 > y2 > y1 > CK. E. angustifolia resulted in an increase in the relative abundance of the dominant bacteria. Proteobacteria and Pseudomonas were the major phylum and genus, respectively. Redundancy analysis showed that changes in the soil microbial community significantly affect the physical and chemical properties of the soil, with Proteobacteria members being the key microorganisms that reduce soil salinity. Network analysis showed that Pseudomonas (Proteobacteria) participated in the synthesis of key soil enzymes. 16S rRNA sequencing predicted that the expression of genes related to carbon (rbcL, acsA, acsB, Pcc and accA) and nitrogen (amoA/B, nxrA, hao, gdh, ureC and nosZ) transformation increased, and Pseudomonas members were key regulators of carbon and nitrogen dynamics. In conclusion, the planting of E. angustifolia could improve the physical and chemical properties of the soil by releasing root exudates into the soil and increasing the diversity and richness of soil microbial communities to improve saline-alkali soil, providing a theoretical basis for improving saline-alkali soil and promoting the sustainable development of modern agriculture.


Can medical algorithms be fair? Three ethical quandaries and one dilemma.
To demonstrate what it takes to reconcile the idea of fairness in medical algorithms and machine learning (ML) with the broader discourse of fairness and health equality in health research. The methodological approach used in this paper is theoretical and ethical analysis. We show that the question of ensuring comprehensive ML fairness is interrelated to three quandaries and one dilemma. As fairness in ML depends on a nexus of inherent justice and fairness concerns embedded in health research, a comprehensive conceptualisation is called for to make the notion useful. This paper demonstrates that more analytical work is needed to conceptualise fairness in ML so it adequately reflects the complexity of justice and fairness concerns within the field of health research.


Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol.
Licorice (Glycyrrhiza glabra, GG) is one of the most frequently used herbal medicines worldwide, and its various biological activities have been widely studied. GG is reported to have neurological properties such as antidepressant, anxiolytic, and anticonvulsant effects. However, its hypnotic effects and the mechanism of GG and its active compounds have not yet been demonstrated. In this study, GG ethanol extract (GGE) dose-dependently potentiated pentobarbital-induced sleep and increased the amount of non-rapid eye movement sleep in mice without decreasing delta activity. The hypnotic effect of GGE was completely inhibited by flumazenil, which is a well-known γ-aminobutyric acid type A-benzodiazepine (GABA(A)-BZD) receptor antagonist, similar to other GABA(A)-BZD receptor agonists (e.g., diazepam and zolpidem). The major flavonoid glabrol was isolated from the flavonoid-rich fraction of GGE; it inhibited [(3)H] flumazenil binding to the GABA(A)-BZD receptors in rat cerebral cortex membrane with a binding affinity (K(i)) of 1.63 μM. The molecular structure and pharmacophore model of glabrol and liquiritigenin indicate that the isoprenyl groups of glabrol may play a key role in binding to GABA(A)-BZD receptors. Glabrol increased sleep duration and decreased sleep latency in a dose-dependent manner (5, 10, 25, and 50mg/kg); its hypnotic effect was also blocked by flumazenil. The results imply that GGE and its flavonoid glabrol induce sleep via a positive allosteric modulation of GABA(A)-BZD receptors.


Distinct and overlapping binding sites for IKP104 and vinblastine on tubulin.
IKP104 is one of a group of tubulin-binding drugs whose interaction with tubulin suggests that it may bind to the protein at or close to the region where vinblastine binds. By itself IKP104 is a potent enhancer of tubulin decay as evidenced by the fact that it induces the exposure of the sulfhydryl groups and hydrophobic areas on tubulin. In this respect, IKP104 differs from vinblastine and other drugs such as phomopsin A, dolastatin 10, rhizoxin, and maytansine which are competitive or noncompetitive inhibitors of vinblastine binding. In contrast, however, in the presence of colchicine, IKP104 behaves differently and strongly stabilizes tubulin, to an extent much greater than does colchicine alone. IKP104 appears to have two classes of binding site on tubulin, differing in affinity; the acceleration of decay appears to be mediated by the low-affinity site (Chaudhuri et al., 1998, J. Protein Chem., in press). We investigated the relationship of the binding of IKP104 and vinblastine. We found that the high-affinity site or sites of IKP104 overlap with or interact with the vinblastine-binding sites, but that the low-affinity site is distinctly different.


Methods and evidence on volume-targeted ventilation in preterm infants.
Several modalities of volume-targeted ventilation have been developed for the premature infant or were adopted from those used in older populations. The article describes these modalities, their clinical application in preterm infants and reviews the evidence for the possible beneficial effects in this population. Evidence from physiologic studies indicates increased stability of tidal volume and gas exchange while requiring less ventilatory support. Randomized trials of volume-targeted ventilation indicate faster weaning and shorter duration of mechanical ventilation, but this has not resulted in better respiratory outcome. The proposed benefits of volume-targeted ventilation on respiratory outcome have not been fully confirmed by the existing data. Some trends suggest possible benefits, but these need to be further explored. The efficacy of volume-targeted ventilation may be method dependent and may also be influenced by the magnitude of the volume targeted.


Characterization and functional studies of the murine T-lymphocyte response to Mycobacterium leprae antigen.
Mice were immunized with Mycobacterium leprae in incomplete Freund's adjuvant, and sensitized lymphocytes were obtained from draining lymph nodes. The lymphocytes thus obtained proliferated specifically in vitro in the presence of M. leprae antigen, and this response was shown to be both T-cell and macrophage dependent. T-cell blasts generated in vitro in response to M. leprae antigen were grown in the presence of interleukin-2 (IL-2). The proliferative response of these blasts to M. leprae antigen was strictly dependent on the presence of syngeneic spleen cells as antigen-presenting cells. M. leprae-immune F1 blasts responding to the antigen in the context of either parental H-2 haplotype-bearing accessory cell could be obtained by positive selection from an F1 hybrid-responding cell population. By means of flow microfluorometry the T-cell phenotype of the M. leprae-specific T-cell blasts was found to be Thy-1+ and to be composed of Lyt-1+ and Lyt-2+ subpopulations. Functionally, the blasts were shown to transfer delayed-type hypersensitivity locally to non-immunized recipients and to have cytolytic activity. Limiting dilution analysis showed the frequency of M. leprae-responding cells from blasts grown in IL-2 to be approximately 1/333.


The Early Memories of Warmth and Safeness Scale: Dimensionality and Measurement Invariance.
Research has shown that rearing styles and early emotional memories, especially those related to feelings of threat or safeness, play a key role in subsequent emotional and social adjustment throughout the lifespan. Several authors have argued for the study of early memories of warmth and safeness rather than rearing styles. The Early Memories of Warmth and Safeness Scale (EMWSS) has proven to be a valid instrument to do so. This study adds to previous research about the EMWSS by investigating its dimensionality throughout confirmatory analysis procedures and its measurement invariance between male and females in an adult sample. A sample of 502 adults (51.2% female, Mean age = 36.46 years, SD = 13.79) recruited from a community sample in Portugal was collected. In addition to the EMWSS, participants completed measures of recall of parental rearing behavior, attachment, self-criticism, self-reassuring, self-compassion and psychopathology. A one-factor measurement model revealed a good fit to the data and the instrument showed excellent internal consistency, with a Cronbach alpha of .96. The EMWSS also proved to be gender invariant. Regarding construct validity, the EMWSS was found to be associated with external variables in the expected direction. The convenience sample used might be not representative of the general population. This work highlights the relevance of the EMWSS in helping to advance knowledge on how early memories of warmth and safeness impact on psychopathological outcomes, and of making it available for use in research and clinical settings.


Contribution of metabolic reprogramming to macrophage plasticity and function.
Macrophages display a spectrum of functional activation phenotypes depending on the composition of the microenvironment they reside in, including type of tissue/organ and character of injurious challenge they are exposed to. Our understanding of how macrophage plasticity is regulated by the local microenvironment is still limited. Here we review and discuss the recent literature regarding the contribution of cellular metabolic pathways to the ability of the macrophage to sense the microenvironment and to alter its function. We propose that distinct alterations in the microenvironment induce a spectrum of inducible and reversible metabolic programs that might form the basis of the inducible and reversible spectrum of functional macrophage activation/polarization phenotypes. We highlight that metabolic pathways in the bidirectional communication between macrophages and stromals cells are an important component of chronic inflammatory conditions. Recent work demonstrates that inflammatory macrophage activation is tightly associated with metabolic reprogramming to aerobic glycolysis, an altered TCA cycle, and reduced mitochondrial respiration. We review cytosolic and mitochondrial mechanisms that promote initiation and maintenance of macrophage activation as they relate to increased aerobic glycolysis and highlight potential pathways through which anti-inflammatory IL-10 could promote macrophage deactivation. Finally, we propose that in addition to their role in energy generation and regulation of apoptosis, mitochondria reprogram their metabolism to also participate in regulating macrophage activation and plasticity.