Scheimpflug analysis of corneal power changes after myopic excimer laser surgery.
To assess the ability of corneal power measurements by a rotating Scheimpflug camera to measure the refractive change induced by myopic excimer laser surgery. G.B. Bietti Foundation-IRCCS, Rome, Italy. Evaluation of diagnostic test. The following corneal power measurements by the Pentacam Scheimpflug camera were analyzed: average keratometry (K), true net power (calculated by Gaussian optics formula), and total corneal refractive power (TCRP) at 2.0 mm, 3.0 mm, and 4.0 mm, calculated by ray tracing on a ring and as the average of the zone inside the ring. The difference between the preoperative and postoperative values was compared with the subjective surgically induced refractive change (SIRC) and with the difference between the preoperative and the postoperative anterior corneal power measured by Placido corneal topography (Keratron). In 36 consecutive eyes, the average K significantly underestimated the SIRC as determined by subjective refraction (-4.47 diopters [D] ± 1.81 [SD]) and corneal topography (-4.38 ± 1.81 D). The 3.0 mm and 4.0 mm ring total corneal refractive power significantly overestimated the SIRC. The remaining values did not show statistically significant differences with respect to the SIRC. The 3.0 mm zone TCRP and the 2.0 mm ring TCRP provided the lowest median difference compared with the SIRC (-0.07 D and -0.17 D, respectively) and the closest agreement. The corneal power values provided by the Scheimpflug camera accurately reflected the SIRC after myopic excimer laser surgery. The best options seem to be the 3.0 mm zone TCRP and the 2.0 mm ring TCRP.


Historical record of lead accumulation and source in the tidal flat of Haizhou Bay, Yellow Sea: Insights from lead isotopes.
In order to investigate the historical records of lead contamination and source in coastal region of Haizhou Bay, Yellow Sea, a sediment core was collected from tidal flat, dated by (210)Pb and (137)Cs. Lead and its stable isotopic ratios were determined. The profiles of enrichment factor (EF) and Pb isotope ratios showed increasing trend upward throughout the core, correlating closely with the experience of a rapid economic and industrial development of the catchment. According to Pb isotopic ratios, coal combustion emission mainly contributed to the Pb burden in sediments. Based on end-member model, coal combustion emission dominated anthropogenic Pb sources in recent decades contributing from 48% to 67% in sediment. And the contribution of leaded gasoline was lower than 20%. A stable increase of coal combustion source was found in sediment core, while the contribution of leaded gasoline had declined recently, with the phase-out of leaded gasoline in China.


Is normal pregnancy cholestatic?
Fasting and 2-h postprandial concentrations of conjugated cholate and conjugated chenodeoxycholate in plasma were measured sequentially through normal pregnancy in a consecutive series of 26 women. Fasting concentrations of cholate significantly increased by 34 weeks and remained so up to 6 weeks post partum. No significant changes were found in fasting or 2-h postprandial concentrations of chenodeoxycholate. Postprandial concentrations of cholate were significantly higher post partum than at 22 weeks of pregnancy. The ratio of fasting cholate: chenodeoxycholate rose from 1.1 : 1.0 at 20 weeks to 1.9 : 1.0 at 38 weeks. In the third trimester, concentrations of conjugated cholate were elevated above the laboratory reference range in 5 of these 26 normal pregnancies. It is concluded that normal pregnancy is associated with mild sub-clinical cholestasis.


Louse-borne relapsing fever: I. A clinical and laboratory study of 363 cases in the Sudan.
Louse-borne relapsing fever seems to have become endemic in the southern Sudan. The epidemic history of the disease in the Sudan is reviewed. We have studied 363 Sudanese patients involved in an outbreak of louse-borne relapsing fever in Khartoum (Sudan) between January and June 1974. 318 of the 363 patients were new immigrants from the soughern Sudan to Khartoum. The clinical presentation varied. The common clinical fetures of the disease were: fever (94%), headache (85%), hepatosplenomegaly (74%), body and joint pains (66%), abdominal pain and tenderness (63%), jaundice (46%) and epistaxis (40%). Thrombocytopenia was common. Biochemical evidence of hepatocellular and renal damage was present in most patients. The mortality rate was 5-5% with treatment. Post-mortem examination was performed on six cases. The organs predominantly involved were the liver, spleen, brain and lungs. The common causes of death were severe hepatic damage, lobar pneumonia, subarachnoid haemorrhage and splenic rupture.


Conditions when statistical tests for model discrimination have high power. Some examples from pharmacokinetics, ligand binding, transient and steady-state enzyme kinetics.
The situation where data pairs xi, yi are actually generated by a true model, f(delta, x), but erroneously fitted by a deficient model, g(phi, x), is explored. A function, Q(delta), is described which is the average squared distance between f(delta, x) and the best-fit false model, g(phi, x). For a range of x covering 5-95% 'saturation' of f(delta, x), Q(delta) is calculated numerically for sums of exponentials, binding functions and rational functions. In each case, the region of delta when the second model in the series can be reliably differentiated from the first by statistical tests is described.


Shaky drawing: what is the rate of decline during prospective follow-up of essential tremor?
Few studies have attempted to estimate the rate of decline over time in essential tremor (ET). The study objectives were to: (1) measure change, deriving a single summary measure for the entire group, and relate it to a commonly used clinical rating scale (ie, yearly change in points on that scale); (2) to assess change as a function of baseline clinical characteristics and (3) to answer the basic clinical question-is change perceptible/obvious during the follow-up of ET cases? Prospective collection of longitudinal data on ET cases enrolled in a study of the environmental epidemiology of ET at Columbia University Medical Center (2000-2008). 116 unselected ET cases. Each case underwent the same evaluation at baseline and during one follow-up visit (mean follow-up interval (range)=5.8 (1.4-12.4) years). We assessed tremor during a commonly affected daily activity-drawing (ie, spirography), quantifying tremor using a simple, standardised 10-point rating scale developed by Bain and Findley. The Bain and Findley spiral score increased at an average rate of 0.12±0.23 points per year (maximum=1 point/year). In cases who had been followed for ≥5 years, the change was obvious-a blinded neurologist was able to correctly order their spirals (baseline vs follow-up) in three-fourth of cases. The rate of change was higher in cases with versus without familial ET (p=0.01). Tremor in ET is slowly progressive; yet in the majority of cases, a clear difference in handwritten spirals was visible with a follow-up interval of five or more years. There may be differences between familial and non-familial ET in the rate of progression. These clinical data are intended to aid in the prognostic discussions that treating physicians have with their patients with ET.


Curcumin-based nanotechnology approaches and therapeutics in restoration of autoimmune diseases.
Autoimmune diseases usually arise as a result of an aberrant immune system attack on normal tissues of the body, which leads to a cascade of inflammatory reactions. The immune system employs different types of protective and anti-inflammatory cells for the regulation of this process. Curcumin is a known natural anti-inflammatory agent that inhibits pathological autoimmune processes by regulating inflammatory cytokines and their associated signaling pathways in immune cells. Due to the unstable nature of curcumin and its susceptibility to either degradation, or metabolism into other chemical entities (i.e., metabolites), encapsulation of this agent into various nanocarriers would appear to be an appropriate strategy for attaining greater beneficial effects from curcumin as it pertains to immunomodulation. Many studies have focused on the design and development of curcumin nanodelivery systems (micelles, dendrimers, and diverse nanocarriers) and are summarized in this review in order to obtain greater insight into novel drug delivery systems for curcumin and their suitability for the management of autoimmune diseases.


Erratum to: Cytokine and human leukocyte antigen (HLA) profile for graft-versus-host disease (GVHD) after organ transplantation.
Following publication of the original article [1], the authors requested a correction in the presentation of their institutions as they appear on the Web of Science. Specifically, it should be emphasized that the institutions belong to Zhejiang University. The correct presentation of affiliations is given in this erratum.


Sulf2 gene is alternatively spliced in mammalian developing and tumour tissues with functional implications.
SULF2 enzyme regulates the activities of a number of signalling pathways that in many tissues are up-regulated during development and disease. As we recently showed for avian Sulf1, the present study demonstrates that mammalian Sulf2 gene can also generate functionally distinct splice variants that would regulate normal development and tumour growth differentially. It is thus important to distinguish SULF1/SULF2 isoforms in mammalian tissues to understand their functional and clinical relevance to disease. This study demonstrates that unlike normal adult lung with little or no SULF2 expression, this enzyme is expressed at high levels in most lung tumours showing differential cellular distribution of full length and shorter SULF2 variants in such tumours. Furthermore, we show that the short SULF2 splice variants are associated with those signalling pathways that are inhibited by full length SULF1/SULF2 variants and therefore could promote growth in such lung tumours.


Perturbations in gut microbiota composition in patients with polycystic ovary syndrome: a systematic review and meta-analysis.
The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women. Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I2) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed. Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria. Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk. PROSPERO registration: CRD42021285206, May 22, 2023.


Mapping of early development of electrical activity in the embryonic chick heart using multiple-site optical recording.
1. Using a multiple-site optical recording method with a 100-element photodiode array and a voltage-sensitive merocyanine-rhodanine dye, we have been able to monitor, for the first time, spontaneous electrical activity in pre-fused cardiac primordia in the 6- and 7-somite chick embryos. 2. To study the regional development of spontaneous electrical activity in the early embryonic pre-contractile chick heart at the later 7-9-somite stages, we have also recorded optically action potentials simultaneously from the entire heart, and constructed maps of the early development of electrical activity. 3. The data show that during the 6-9-somite stages, the size of the active area gradually increases, and that the development of electrical activity was spatially non-uniform: two peaks of activity were found in the right and left sides of the cono-ventricular region at the 7-8-somite stages. As development proceeded to the 9-somite stage, several peak areas of activity appeared. 4. The results are discussed in relation to the spatial pattern of proliferation of electrically active cells in the early phases of cardiogenesis.


Evaluation of the surface characteristics of used and new ProTaper Instruments: an atomic force microscopy study.
The purpose of this study was to evaluate the topography of new and used ProTaper rotary nickel-titanium (NiTi) instruments by using atomic force microscope. Four new and four used size S1, S2, F1, and F2 instruments were selected for this study. New and used instruments were analyzed on 11 points along a 3-mm section at the tip of the instrument. Quantitative measurements according to the topographic deviations (root mean square) were recorded. Data were analyzed by paired samples t test. Mean root mean square values for used ProTaper instruments were higher than the new ones, and the difference between them was statistically significant. The results of this study showed that used ProTaper instruments demonstrated more surface deformation and wear.


Long-term stroke prognosis in relation to medical prevention and lifestyle factors. A prospective population-based study.
Few studies have focused on the quality of secondary prevention among long-term stroke survivors. This study explores the intensity of medical intervention and the impact of lifestyle and other risk factors on the long-term stroke prognosis in a population-based setting of Swedish individuals with a history of stroke. A population-based cohort (n = 28,449) in Malmo, Sweden, was recruited during 1991-1996. Of them, 394 had a history of stroke, according to self-reported physician diagnosis and record linkage with the Stroke Register in Malmo. Information on medical intervention and lifestyle factors was collected from the questionnaire. The incidence of a cardiac event (CE) or recurrent stroke was followed for 7.5 years after the baseline examination. The prevalence of hypertension was 79.4% in patients with a history of stroke. Only half of them received blood-pressure (BP)-lowering medication, and 11.5% of them achieved a BP <140/90 mm Hg. Most patients with hypercholesterolemia did not receive lipid-lowering medication. Antithrombotic agents were used by 38%. Nearly one third were still smoking, and two thirds were overweight or obese. Compared to subjects without a history of stroke, the risk of cardiovascular disease (CVD, i.e. CE or recurrent stroke) was significantly higher in stroke survivors. The increased CVD risk was significantly associated with elevated BP levels. No significant relationship was found between CVD risk and lifestyle risk factors reported at the time of baseline examination. There was a large gap between recommended secondary preventive measures and their implementation in subjects with a history of stroke. Achieving recommended hypertension control may prevent a substantial proportion of the CE and recurrent strokes in this group.


The ecological significance of burrowing behaviour in the toad (Bufo viridis).
The burrowing behaviour of the toad Bufo viridis was studied in the laboratory on soil containing 11-13% moisture. These toads usually excavate shallow, temporary burrows from which they emerge intermittently. Time spent subsurface increases with rising ambient temperature in the range of 18-30° C. In these conditions, water loss is effectively reduced and a new water balance is achieved. On return to water access, after two months on soil, the toads rapidly regain only that amount of water lost previously. It is concluded that this temperature-sensitive burrowing behaviour is an important factor in these animals' successful survival in semi-arid conditions.


Clinical significance of postradiotherapy [18F]-fluorodeoxyglucose positron emission tomography imaging in management of head-and-neck cancer-a long-term outcome report.
To determine the accuracy and prognostic significance of post-treatment [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in head-and-neck squamous cell carcinoma after radiotherapy (RT). This was a retrospective study of 188 patients with head-and-neck squamous cell carcinoma who had undergone FDG-PET within 12 months after completing RT. All living patients had >/=1 year of follow-up after FDG-PET. All patients had undergone intensity-modulated RT, 128 with definitive and 60 with postoperative intensity-modulated RT. For all patients, the median follow-up after RT completion was 32.6 months and after FDG-PET was 29.2 months. For the neck, 171 patients had negative FDG-PET findings. Of these results, two were falsely negative. Seventeen patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the neck was 86%, 97%, 71%, and 99%, respectively. For the primary site, 151 patients had negative FDG-PET findings, of which two were falsely negative. Thirty-seven patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the primary site was 86%, 86%, 32.4%, and 98.7%, respectively. Patients with positive post-RT PET findings had significantly worse 3-year overall survival and disease-free survival. The results of our study have shown that the findings of post-RT FDG-PET have a high negative predictive value and are a significant prognostic factor. It can provide guidance for the management of head-and-neck cancer after definitive treatment.


Modulation of carbon tetrachloride-induced oxidative stress by dietary fat in rats(open star).
Oxidative stress is believed to be involved in the pathophysiology of a number of chronic diseases including atherosclerosis, diabetes, and cataracts and to accelerate the aging process. The aim of this study was to elucidate the role of various dietary fats in the in vivo modulation of CCl(4) induced oxidative stress using rat as a model. Rats were raised on diets enriched with saturated (Beef Tallow), n-9 (Sunola oil), n-6 (Safflower oil) or n-3 (Flaxseed oil) fatty acids and exposed to elevated oxidative stress by administration of CCl(4.) Plasma concentration of 8-iso-PGF(2alpha), antioxidant micronutrients and antioxidant enzymes were measured to examine changes to oxidative stress subsequent to the administration of CCl(4). The fatty acid profiles of plasma and RBC membranes reflected the fats fed in the different diets. CCl(4) administration had no significant effect on fatty acid composition of plasma or RBC lipids. Plasma 8-iso-PGF(2alpha) concentrations were elevated by CCl(4) administration regardless of the dietary fat fed. Within the induced oxidative groups the 8-iso-PGF(2alpha) concentrations were highest in Safflower oil followed by Sunola oil, Tallow and finally Flaxseed oil. Induction of oxidative stress by CCl(4) administration was associated with a significant reduction in Vitamin A content reaching a significantly lower concentration (P <0.05) in the Tallow and Flaxseed oil groups. Vitamin E concentrations were significantly lower (p = 0.01) in the Safflower oil and the Flaxseed oil than in the Tallow diet group following CCl(4) administration. Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSHPx) activities were not affected by dietary fat manipulation. The results of this study indicate that dietary fat can modulate lipid peroxidation and antioxidant defenses when exposed to a pro-oxidant challenge.


Use of anti-CMV immunoglobulins in lung transplant recipients: The French experience.
Pending the authorization of new anti-CMV drugs with fewer adverse effects, exploring the possibilities offered by CMV immunoglobulins (CMVIG) seems necessary. In France, access to CMVIG requires official authorization by the national Health authority and is restricted to second line rescue therapy for CMV infection/disease. The aim of this multicenter retrospective study is to describe the indications and clinical situations that justified its use in France. A multicenter retrospective study included 22 lung transplant patients over a 3-year period. Data on clinical indication, tolerance and efficacy were collected. The main indication for CMVIG initiation, which was documented in 17 of them (82%) was complex clinical situations resulting from side effects to antiviral drug. CMVIG indication was documented as treatment for 15 patients (68%) and as a secondary prophylaxis for 7 patients (32%). Only one side effect (pruritus during infusion with no anaphylactic symptoms) attributable to CMVIG was reported. After CMVIG initiation, no recurrence of infection or disease was observed during a median follow-up of 174 (12-682) days after treatment initiation for respectively 68% and 66% of the patients. This study describes an unusual indication of CMVIG use as a last resort treatment in complex situations, based on clinical needs. CMVIG could be useful to change the course of CMV infection with minimal adverse effects or comorbidity.


Knocking down schistosomes - promise for lentiviral transduction in parasites.
Underpinned by major advances in our understanding of the genomes of schistosomes, progress in the development of functional genomic tools is providing unique prospects to gain insights into the intricacies of the biology of these blood flukes, their host relationships, and the diseases that they cause. This article reviews some key applications of double-stranded RNA interference (RNAi) in Schistosoma mansoni, appraises delivery systems for transgenesis and stable gene silencing, considers ways of increasing efficiency and specificity of gene silencing, and discusses the prospects of using a lentivirus delivery system for future functional genomic-phenomic explorations of schistosomes and other parasites. The ability to achieve effective and stable gene perturbation in parasites has major biological implications and could facilitate the development of new interventions.


COVID-19 mRNA vaccine in pregnancy: Results of the Swiss COVI-PREG registry, an observational prospective cohort study.
Pregnant individuals with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease, prematurity, and stillbirth. In March 2021, vaccination for at risk pregnant women was recommended in Switzerland, expanding this to all pregnant women in May 2021. Our aim was to assess the safety of mRNA COVID-19 vaccines in pregnancy. This multicentre prospective cohort study describes early adverse events and perinatal outcomes in pregnant women who received at least one dose of mRNA vaccine between March 1st and December 27th, 2021 in Switzerland, using the COVI-PREG registry. Early adverse events were collected at least one month following vaccine administration. Pregnancy and neonatal outcomes were extracted from medical records using the maternity discharge letters providing follow-up information up to 5 days after birth. Of 1012 vaccinated women, 894 (88·3%) received both injections during pregnancy, with BNT162b2 (n = 271) or mRNA-1273 (n = 623) vaccines. Local events (mainly local pain) were reported in 81·3% and 80·5% after the first and second doses. Rates of systemic reactions (mainly fatigue and headache) were similar after the first dose and most frequent after the second dose of mRNA-1273. Of the 1012 women, four (0·4%; 95%CI [0·1-1·0]) severe early adverse events occurred: pulmonary embolism, preterm premature rupture of membranes, isolated fever with hospitalisation, and herpes zoster. Of 107 patients vaccinated before 14 weeks, one (0·9%; 95%CI [0·0-5·1]) early spontaneous abortions was reported (8 weeks). Of 228 vaccinated before 20 weeks one (0·4%; 95%CI [0·0-2·4]) late spontaneous abortion was reported (16 weeks). Of 513 women exposed before 37 weeks, 33 (6·4%; 95%CI [4·5-8·9]) delivered preterm. Among 530 patients exposed in pregnancy, no stillbirth was reported and 25 (4·7%; 95%CI [3·0-6·8]) neonates were admitted to intensive care unit. Frequent local and systemic effects were described after exposure to mRNA COVID-19 vaccines during pregnancy but severe events were rare. Women vaccinated during pregnancy did not experience higher adverse pregnancy or neonatal outcomes when compared to historical data on background risks in the obstetric population. This research was funded by a grant from the Swiss Federal Office of Public Health and the CHUV Foundation.


[Association between number of lymphadenectomy and postoperative complication in surgery for esophageal carcinoma].
To investigate the association between the number of lymph nodes retrieval and the incidence of postoperative complications in patients with esophageal carcinoma. From January 2008 to December 2009, 794 patients with esophageal carcinoma underwent esophagectomy and lymphadenectomy in the Department of Thoracic Surgery at the West China Hospital of Sichuan University. The clinical data, surgeons, the extent of lymphadenectomy and its association with operative morbidity were retrospectively analyzed. There was no operative death. A total of 84 patients with complication(10.6%) were documented. There were 11,770 lymph nodes harvested in total with an average of 14.8. Multivariate logistic regression showed that gender, number of metastatic lymph nodes, level of anastomosis, and surgeons' experience were risk factors associated with postoperative complications (all P<0.05), while the number and group of lymph node resection were not(all P>0.05). Within a rational range of lymphadenectomy(<50) following esophagectomy, the postoperative complications are significantly associated with the gender, extent of regional lymph nodes metastasis, site of anastomosis and the expertise of the surgeons, but not associated with the number and group of lymph nodes resection.


Quality of life in cancer rehabilitation: the role of life goal adjustment.
A cancer diagnosis affects patients' quality of life (QOL) as well as their pursuit of life goals. However, numerous studies have shown surprisingly stable QOL measures in cancer patients over time. We propose that life goal adjustment can act as the missing link in explaining this response shift. Thus, the aim of this study was to examine associations between life goal adjustment and patients' QOL at baseline and over the course of 20 months. Eighty-six cancer patients were recruited during rehabilitation and reassessed at follow-up 20 months later. Life goals were measured using the Life Goals Questionnaire and analyzed in relation to global QOL as assessed with the World Health Organization Quality of Life Questionnaire - Short Form. The overall attainment of life goals was associated with QOL. Moreover, over a period of 20 months, perceived QOL and goal attainment remained stable, whereas importance of life goals decreased. Lesser importance and improved goal attainment were predictors of increases in QOL. Results suggest that downgrading unattainable goals and making more progress in accomplishing attainable goals may be possible mechanisms of response shift as an adaption to illness. Thus, integrating life goal adjustment into rehabilitation services for cancer patients seems to be worthwhile to enhance an adaptive self-regulation and QOL.


Mutational and comparative analysis of streptolysin O, an oxygen-labile streptococcal hemolysin.
The structural gene of streptolysin O was cloned from Streptococcus pyogenes strain Sa and S. equisimilis H46A, and the nucleotide sequences were compared with those of strain Richards. To obtain the minimal active fragment of the toxin and to elucidate structure-function relationships in hemolytic function, streptolysin O mutants deleted in N- and C-terminal regions were constructed. Internal amino acid residues were also replaced by introduction of point mutations. Analyses of these mutants showed that considerable activity was retained even after deletion of the N-terminal 107 residues, but genetic removal of the ultimate C-terminal residue resulted in a marked decrease in hemolytic function. By removal in succession, hemolytic activity declined exponentially, and only 0.002% of the activity remained after deletion of the C-terminal four residues. Nucleotide replacement experiments indicated pivotal roles of I202, V217, D324-L325, V339, and H469 residues in hemolysis.


Genetic and epigenetic contributions to the cortical phenotype in mammals.
One aspect of cortical organization, cortical field size, is variable both within and across species. The observed variability arises from a variety of sources, including genes intrinsic to the neocortex and a number of extrinsic and epigenetic factors. Genes intrinsic to the cortex are directly involved in the development and specification of cortical fields and are regulated from both signaling centers located outside of the neocortex, which secrete diffusible molecules, and the expression of transcription factors within the neocortex. In addition, extrinsic factors such as the type, location and density of sensory receptor arrays and how these receptor arrays are utilized, are also strongly related to cortical field size. Epigenetic factors including the relative activity patterns generated by the different types of physical stimuli in a given environment also contribute to differences in cortical organization, including cortical field size. Since both genetic and epigenetic factors contribute to cortical organization, some aspects of the cortical phenotype evolve, while other aspects of the cortical phenotype persist only if the environment in which an individual develops is relatively stable.


Immunohistochemistry of tryptophan hydroxylase in the rat brain.
An antiserum raised against tryptophan tetrahydropterine oxygen oxidoreductase was used to examine in rat brain the immunohistochemical localization of this rate-limiting enzyme catalysing the biosynthesis of serotonin. Tryptophan tetrahydropterine oxygen oxidoreductase was detected in numerous nerve cell bodies, proximal dendrites and axon varicosities or terminals corresponding to those of serotonin neurons as judged by their anatomical distribution and concomitant immunoreactivity to an antiserum against serotonin. In hypothalamus, a serotonin-containing nerve cell group previously visualized in the pars ventralis of the nucleus dorsomedialis by radioautography after serotonin uptake, and by serotonin immunohistochemistry after tryptamine loading, remained tryptophan tetrahydropterine oxygen oxidoreductase-unreactive even in rats treated with colchicine. On the other hand, a small group of tryptophan tetrahydropterine oxygen oxidoreductase-positive cells was identified in the rostrolateral portion of nucleus dorsomedialis, which could play a part in the intrinsic serotonin innervation of hypothalamus. There was no overlap between tryptophan tetrahydropterine oxygen oxidoreductase immunostaining and the cellular distribution of N-acetyl serotonin as reported in earlier studies. It is therefore likely that the synthesis of N-acetyl serotonin from tryptophan does not take place in N-acetyl serotonin-containing neurons.


Predicting exposure-response associations of ambient particulate matter with mortality in 73 Chinese cities.
Estimating the burden of mortality associated with particulates requires knowledge of exposure-response associations. However, the evidence on exposure-response associations is limited in many cities, especially in developing countries. In this study, we predicted associations of particulates smaller than 10 μm in aerodynamic diameter (PM10) with mortality in 73 Chinese cities. The meta-regression model was used to test and quantify which city-specific characteristics contributed significantly to the heterogeneity of PM10-mortality associations for 16 Chinese cities. Then, those city-specific characteristics with statistically significant regression coefficients were treated as independent variables to build multivariate meta-regression models. The model with the best fitness was used to predict PM10-mortality associations in 73 Chinese cities in 2010. Mean temperature, PM10 concentration and green space per capita could best explain the heterogeneity in PM10-mortality associations. Based on city-specific characteristics, we were able to develop multivariate meta-regression models to predict associations between air pollutants and health outcomes reasonably well.


Validation of the German version of the short form of the dysfunctional beliefs and attitudes about sleep scale (DBAS-16).
Research shows that dysfunctional sleep-related cognitions play an important role in the development, maintenance and exacerbation of insomnia. This study examines the factorial validity, psychometric properties and both concurrent and predictive validity of the German version of the 16-item DBAS (dysfunctional beliefs and attitudes about sleep) scale. Data was collected in 864 vocational students from the German-speaking part of Switzerland (43% females, M age = 17.9 years). Data collection took place twice within a 10-month interval. The students completed a German translation of the DBAS-16, the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), and provided information about their psychological functioning. Descriptive statistics, factorial validity, internal consistency, gender differences, concurrent, and predictive validity were examined. Confirmatory factor analysis supported the 4-factor structure of the DBAS-16. All factors (consequences, worry/helplessness, expectations, medication) were positively correlated and had acceptable psychometric properties. Females reported higher scores across all DBAS measures. Weak-to-moderate correlations were found between dysfunctional sleep-related beliefs, insomnia and poor sleep quality. Dysfunctional sleep-related beliefs were also associated with decreased psychological functioning, and consistently predicted insomnia and poor psychological functioning at follow-up, even after controlling for socio-demographic background and baseline levels. The present study provides support for the validity and psychometric properties of the German version of the DBAS-16. Most importantly, it corroborates the relevance of cognitive-emotional factors in the onset and maintenance of insomnia and psychological symptoms among young people.


A Seaway Acoustic Observatory in Action: The St. Lawrence Seaway.
A setup for measuring spectral source levels (SSLs) of ships transiting along a seaway, the traffic density and shipping noise, is presented. The results feed shipping-noise modeling that reproduces the actual in situ observations to map shipping-noise variability over space and time for investigating its effects on aquatic organisms. The ship's SSL databank allows sorting the different contributors to total shipping noise for assisting in exploring mitigation approaches (e.g., fleet composition, rerouting). Such an acoustic observatory was deployed since November 2012 for a complete annual cycle of measurements in the deep downstream part of the St. Lawrence Seaway.


[Arterial hypertension in patients with obesity. Role of hyperinsulinism and insulin resistance].
The association between arterial hypertension and obesity has been known for many years and demonstrated by epidemiological studies. The physiopathological mechanisms involved consist of increased extracellular volumes, hyperactivity of the sympathetic nervous system and the renin-angiotensin-aldosterone system, and abnormal ion exchanges between extra- and intracellular compartments. Recent studies have demonstrated an association between arterial hypertension and insulin resistance. Insulin resistance may well be the most important aetiological factor in this type of arterial hypertension as it stimulates both renal sodium reabsorption and sympathetic nervous system activity and reduces vascular Na-K-ATPase activity.


Clinical applications of transpulmonary contrast echocardiography.
The recent development of new fluorocarbon-based echocardiographic contrast agents that are capable of opacification of the left-sided cardiac chambers after intravenous injection is a major new advance in diagnostic cardiac imaging. This is a review article focusing on these novel contrast agents, new echocardiographic imaging techniques to optimize their efficacy, and their clinical applications. Specific clinical applications of these agents are (1) enhancement of endocardial border definition to improve assessment of regional and global left ventricular function, (2) myocardial perfusion imaging by intravenous contrast echocardiography, (3) augmentation of spectral and color flow Doppler images, and (4) tissue-specific targeting of microbubbles for delivery of therapeutic agents. New intravenous contrast agents offer the possibility to assess myocardial perfusion echocardiographically. It is also possible to use these agents for delivery of therapeutic agents, including gene therapy.


Time from dosing to sexual intercourse attempts in men taking tadalafil in clinical trials.
To determine whether patients with erectile dysfunction (ED) and treated with tadalafil use the 36-h duration of effect of the drug, and to discern if the timing of intercourse attempts is influenced by patient age, baseline severity of ED, or previous experience with sildenafil citrate. In 11 multicentre, double-blind, placebo-controlled studies, 2102 patients with ED were randomized to a maximum of one dose per day of tadalafil 10 or 20 mg (1464 men), or placebo (638 men) with no time restrictions before attempting sexual activity after the dose. A post hoc analysis was used to determine the proportion of men with ED who attempted sexual intercourse during various intervals (>0 to < or = 1, >1 to < or = 4, and >4 to < or = 36, including >12 to < or = 36 h) after dosing with tadalafil or placebo over a 12-week period. Patients were stratified by age, baseline severity of ED, and previous history of sildenafil use. Of patients in different age groups and various ED severity, > or = 79% and > or = 53% chose to attempt sexual intercourse at least once during the 12-week treatment period at 4-36 and 12-36 h, respectively, after taking tadalafil. Regardless of previous experience with sildenafil, about a third of patients using tadalafil attempted intercourse a mean of at least once per week at 4-36 h after the dose over 12 weeks. Furthermore, 58% of patients attempted intercourse at least once during two intervals (>1 to < or = 4 h and >12 to < or = 36 h) after separate doses of tadalafil. Regardless of age, ED severity, or previous experience with sildenafil, most patients attempted sexual intercourse at least once at 12-36 h after one dose of tadalafil over a 12-week treatment period. Furthermore, by engaging in sexual intercourse at both earlier and later intervals after separate doses, most patients on treatment did not adhere to a fixed schedule of intimacy and thus took advantage of the 36-h duration.


Non Familial Cherubism: A Case Report.
Cherubism might occur in solitary cases or in several members of the family, often in many generations. Treatment depends on the clinical course of the disease. The reported case is an example of solitary sporadic occurrence within a family, which is a less documented condition in the literature.


Kickstand Rod With Asymmetric Pedicle Subtraction Osteotomy for Treatment of Adult Kyphoscoliosis With Severe Coronal Imbalance.
The kickstand rod has been described for the treatment of severe coronal imbalance. We present a modified description that combines an asymmetric pedicle subtraction osteotomy (PSO) for correction of severe kyphoscoliosis. To describe the use of a temporary kickstand rod. Type 1 osteotomies were performed across the main and fractional curves. An asymmetric PSO was performed at the apex of the main curve, and a kickstand rod placed on the concavity anchored from the ilium to a temporary connector above the main curve. Distraction was applied across the kickstand rod because the PSO was closed on the convexity. A permanent rod was placed contralateral to the kickstand, followed by replacement of the kickstand with a permanent rod and bilateral accessory rods. A 66-year-old man presented with kyphoscoliosis causing severe coronal and sagittal imbalance. He underwent L4-S1 anterior lumbar interbody fusion followed by T4-pelvis instrumented fusion the following day. Type 1 osteotomies were performed from T6-T12 to L3-S1 and an asymmetric PSO at L2. A temporary kickstand rod was used to distract across the concavity because the PSO was closed on the convexity. The patient achieved excellent clinical and radiographical results. When used in conjunction with appropriate osteotomies, the kickstand rod can aid in correction of severe coronal imbalance. Use of a temporary kickstand rod is technically easier and allows for correction of the main and fractional curves when used with an asymmetric PSO.


A new era for schizophrenia drug development - Lessons for the future.
For many patients and their treating clinicians, the pharmacological management of psychotic symptoms centres on trying to find a regime that balances efficacy and quality of life-impairing side effects associated with dopamine antagonism. Recent reports of a positive Phase III study from Karuna Therapeutics indicate that the first primarily non-dopamine-based treatment for schizophrenia may come to market soon with the potential for substantially reduced or differentiated side effects. Against a background of repeated failures, Karuna's success promises a desperately needed new treatment option for patients. It also reflects some hard-won lessons about the methodology for schizophrenia drug development.


Eosinophilia and acquisition of resistance to Nematospiroides dubius in mice sensitized with adult worms.
BALB/c mice develop resistance to challenge with N. dubius third stage infective larvae (L3) 2-3 weeks after the administration of N. dubius worms. In contrast, CBA/H mice fail to develop resistance. Experiments were performed to test the hypothesis that the reason for the different behaviour of these mice was a difference in their eosinophil response. BALB/c mice and BALB/c leads to (BALB/c x CBA/H)F1 bone marrow chimaeras but not CBA/H mice or CBA/H leads to (BALB/c x CBA/H)F1 chimaeras mounted strong eosinophilia after N. dubius sensitization and the eosinophil response was associated with resistance to L3 infection in these mice. Induction of a mild eosinophilia in CBA/H mice by non-parasite antigen keyhole limpet haemocyanin (KLH) in complete Freund's adjuvant (CFA) following cyclophosphamide (CY) treatment was associated with the acquisition of a degree of resistance to L3 infection. In BALB/c mice, increase in eosinophilia induced by CY and KLH-CFA was not associated with a further reduction in worm numbers. These experiments support the hypothesis that eosinophilia is an important component of host protective immunity in vivo, and suggest a new basis for the heterogeneity of the outcome of some parasite infestations.


Intermediate filaments in the retinal Müller cells as natural light energy guides.
In the current study, we investigated transmission spectrum of the intermediate filaments (IFs) extracted from porcine retinal Müller cells (MC). The recorded transmission spectrum is quite similar to that of the entire guinea pig retina, providing direct proof that the quantum mechanism (QM) of light energy transmission through the inverted retina is in fact the main mechanism determining the high-contrast vision of the vertebrate eyes. The recorded transmission spectrum of the IFs was deconvoluted into four bands, which we assign to different types of IFs. We interpret the differences in the transmission band shape and maxima as differences in the effective electron mass, dependent on the IF structure and composition of its constituting proteins. We analyzed model systems containing IFs and dye molecules, and IFs bridging two adjacent cobalt nanofilms on a substrate. The respective results demonstrate that IFs function as waveguides transferring energy from an energy donor and to an energy acceptor, by way of the exchange mechanism. The presently reported results provide direct experimental confirmation of the earlier proposed quantum mechanism for the high-contrast vision of vertebrate eyes. The mechanism proposed in the current study may be generalized, providing a consistent alternative to Davydov's theory of vibrational solitons in enzymes.


Involvement of the lysosome in the catabolism of intracellular lysophosphatidylcholine and evidence for distinct pools of lysophosphatidylcholine.
The role of the lysosome in the metabolism of lysophosphatidylcholine was investigated in isolated rat hepatocytes. Chloroquine, primaquine, and ammonium chloride caused a 2.5-fold increase in radioactive lysophosphatidylcholine in [methyl-3H]choline-labeled cells. This effect was confirmed by a 1.7-fold increase in lysophosphatidylcholine mass in chloroquine-treated hepatocytes. Chloroquine caused a 2.7-fold increase in radioactive lysophosphatidylethanolamine in [1-3H]ethanolamine-labeled cells and a 2.3-fold increase in radioactive lysophosphatidylcholine in [methyl-3H]methionine-labeled cells. Chloroquine did not affect formation of choline-containing aqueous metabolites or the level of radioactivity in phosphatidylcholine (PC). The effect of chloroquine on radioactive lysophosphatidylcholine accumulation was concentration-dependent and occurred within 10 min, consistent with rapid inhibition of lysosomal function. As there was no observed decrease in the 3H in PC, the accumulation of lysophosphatidylcholine was likely due to the inhibition of acid lysophospholipase activity in chloroquine-treated cells. The accumulation of lysophosphatidylcholine in the presence of chloroquine was observed in both short-term- (30 min) and equilibrium-(24 h) [methyl-3H]choline-labeled cells. Simultaneous incubation of hepatocytes with both albumin and chloroquine increased the radioactivity in lysophosphatidylcholine in the medium independently of the accumulation of radioactive lysophosphatidylcholine in the cells. The results suggest that there are separate pools of lysophosphatidylcholine in the hepatocyte and that the pool donated to an extracellular acceptor is different from the lysosomal pool.(ABSTRACT TRUNCATED AT 250 WORDS)


Antitumor effects and chemical compositions of Eupolyphaga sinensis Walker ethanol extract.
Eupolyphaga sinensis Walker popularly known as "preferred drug to regulate blood flow" are traditionally used in folk medicine in the treatment of ecchymoma, posttraumatic wound, hepatic fibrosis and tumor. To characterize chemical compositions and to evaluate the antitumor and immunomodulatory of Eupolyphaga sinensis Walker ethanol extract (ESEE) in hepatocarcinoma H(22) bearing mice. ESEE was obtained by ethanol reflux extraction and analyzed by gas chromatography-mass spectrometry (GC-MS) after methylation. ICR mice were treated with ESEE for 14 consecutive days at doses of 31mg/kg (low-dose), 62mg/kg (mid-dose) and 124mg/kg (high-dose) after H(22) tumor cells were implanted. At the end of the experiments, the tumor weight of each mouse was measured. Levels of serum TNF-α and IFN-γ was assayed by ELISA. Protein expressions of Bax, Bcl-2 and caspases-3 were detected by immunohistochemistry. Chemical analysis revealed the presence of 6 components that account for 97.55% of fatty acids, indicating the occurrence of saturated and polyunsaturated fatty acids. Oral administration of ESEE could inhibit tumor growth, promote Th1 type cytokine productions (TNF-α and IFN-γ) and induce apoptosis of hepatocarcinoma via increase of Bax/Bcl-2 ratio and activation of caspases-3. Oral administration of ESEE in a dosage of 6.2g/kg did not lead to toxic effects in mice. ESEE was effective in inhibiting tumor growth in vivo and could also serve as immunoadjuvant for tumor therapy.


A plasma clot lysis assay based on the release of fibrin degradation products: application to the diagnosis of hypofibrinolytic states.
Using a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombophlebitis, 3 arterial occlusions of lower limbs). tPA and PAI-1 concentrations were determined using ELISA assays; the post-occlusion values were corrected for haemoconcentration. The increase in tPA during VO was correlated with haemoconcentration (r = 0.74), but 3 patients had ineffective VO (less than 2% increase in proteins). The fibrinolytic response to VO was evaluated using the shortening of the time necessary for the release of 200 micrograms of fibrin degradation products per mg of fibrinogen (delta T 200). Two among the 27 patients with effective VO were bad responders with a delta T 200 less than 3 h (whereas all the others had delta T 200 greater than 10 h). These patients had respectively a deficient tPA release (delta tPA = 1 ng/ml) and an elevated PAI-1 level at rest (33 ng/ml). Several other patients were bad responders in terms of tPA release or of shortening of the euglobulin clot lysis time but they had a normal delta T 200. This plasma clot test reflects the ability of free tPA to bind to fibrin (the amount of which depends on the level of tPA and PAI-1), and may be useful in the diagnosis of a hypofibrinolytic state.


Biodegradation of nicotine by a novel nicotine-degrading bacterium, Pseudomonas plecoglossicida TND35 and its new biotransformation intermediates.
Tobacco wastes that contain nicotine alkaloids are harmful to human health and the environment. In the investigation, a novel nicotine-biodegrading bacterium TND35 was isolated and identified as Pseudomonas plecoglossicida on the basis of phenotypic, biochemical characteristics and 16S rRNA sequence homology. We have studied the nicotine biodegradation potential of strain TND35 by detecting the intermediate metabolites using an array of approaches such as HPLC, GC-MS, NMR and FT-IR. Biotransformation metabolites, N-methylmyosmine, 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and other three new intermediate metabolites namely, 3,5-bis (1-methylpyrrolidin-2-yl) pyridine, 2,3-dihydro-1-methyl-5-(pyridin-3-yl)-1H-pyrrol-2-ol and 5-(pyridin-3-yl)-1H-pyrrol-2(3H)-one have been identified. Interestingly, these intermediate metabolites suggest that the strain TND35 employs a novel nicotine biodegradation pathway, which is different from the reported pathways of Aspergillus oryzae 112822, Arthrobacter nicotinovorans pAO1, Agrobacterium tumefaciens S33 and other species of Pseudomonas. The metabolite, HPB reported in this study can also be used as biochemical marker for tobacco related cancer studies.


Seedless fruit in Annona squamosa L. is monogenic and conferred by INO locus deletion in multiple accessions.
Inheritance of the presence/absence of seeds in Annona squamosa is mediated by a single fully recessive gene and is caused by a deletion of the INNER NO OUTER (INO) locus. For some fruits, seedless varieties are desirable for consumption and processing. In the sugar apple tree (Annona squamosa L.), the seedless trait in the Thai seedless (Ts) and Brazilian seedless (Bs) accessions was associated with defective ovules and an apparent deletion of the INNER NO OUTER (INO) ovule development gene locus. Segregation analysis of F2 and backcross descendants of crosses of Bs to fertile wild-type varieties in this species with a multi-year generation time showed that seedlessness was recessive and controlled by a single locus. Comparison of whole genome sequence of a wild-type plant and a third accession, Hawaiian seedless (Hs), identified a 16 kilobase deletion including INO in this line. Ts and Bs lines were shown to have an identical deletion, indicating a common origin from a single deletion event. Analysis of microsatellite markers could not preclude the possibility that all three seedless accessions are vegetatively propagated clones. The sequence of the deletion site enabled a codominant assay for the wild-type and mutant genes allowing observation of complete cosegregation of the seedless/defective ovule phenotype with the INO deletion, showing maximal separation of less than 3.5 cM. The observed deletion is the only significant difference between the wild-type and Hs line over 587 kilobases, likely encompassing much more than 3.5 cM, showing that the deletion is the cause of seedless trait. The codominant markers and obtained progenies will be useful for introgression of the seedless trait into elite sugar apple lines and into other Annonas through interspecific crossings.


Synthesis in vitro of glycoprotein in regenerating rat liver.
The metabolism of glucosamine in regenerating rat liver was studied in liver slices. [1-14C] Glucosamine was incorporated into acid-soluble fraction, rapidly converted to UDP-N-acetylhexosamine and transferred to acid-insoluble fraction. Electrophoretic analysis revealed that most of the radioactive macromolecules released from the slices to the incubation medium were plasma glycoproteins. The incorporation of [1-14C] glucosamine into UDP-N-acetylhexosamine significantly increased from 6 h to 48 h after partial hepatectomy. On the contrary, the incorporation into acid-insoluble fractions of slice and medium decreased to about 50% of the control values. The rate of transfer of N-acetylhexosamine from UDP-N-acetylhexosamine to acid-soluble fractions also decreased at 12 h and 48 h respectively. This indicates that the transfer of N-acetylhexosamine to glycoproteins decreases during 48 h of liver regeneration. The enhancement of [1-14C] glucosamine incorporation into UDP-N-acetylhexosamine is due to an accumulation of the label in the larger pool of this compound. Evidently, some control mechanism may operate on the transfer of N-acetylhexosamine to glycoproteins in regenerating rat liver.


[Positron emission tomography in oncology].
Positron emission tomography (PET) is a highly sensitive imaging tool that noninvasively characterizes metabolic processes and molecular targets. PET has become an integral part of oncological diagnostics and an increasingly important tool for oncological therapy management. PET assessment, for example, directly influences treatment escalation or de-escalation in context of Hodgkin lymphomas or is, in case of lung cancer, able to reduce unnecessary surgeries. Hence, molecular PET imaging represents an indispensable tool in the development of personalized treatments. Furthermore, the development of new radiotracers for specific cell surface structures offers a promising potential for diagnostics and-combined with therapeutic nuclides-also for therapies. One recent example are radioligands targeting prostate-specific membrane antigen, which are relevant in prostate cancer.


Successful interventional treatment of post-biopsy renal artery pseudoaneurysm in pediatric patients.
With an incidence ranging from 0.01% to 1.0%, renal artery pseudoaneurysm (RAP) is a rare complication after renal biopsy, percutaneous renal surgery, penetrating trauma, and rarely blunt renal trauma. Percutaneous renal biopsy (PRB) of native kidneys was performed in 1,500 pediatric patients under real-time ultrasonographic guidance at our institution from July 1999 to January 2011. A retrospective review of these cases revealed that 2 patients developed a post-biopsy RAP. The diagnosis of RAP was established using color duplex ultrasonography (US), contrast-enhanced computed tomography (CT) and digital substraction angiography (DSA). Two patients developed RAP after 1,500 PRBs were performed (0.13% incidence). In the presented cases, immediate post-bioptic ultrasound showed no abnormalities. A high index of suspicion for RAP was prompted when complications such as unexplained gross hematuria and anemia occurred and the arterial phase of CT showed a well-circumscribed hyperdense area with a contrast enhancement similar to the adjacent arterial vessels. The diagnosis was confirmed by DSA and then the feeding artery of RAP was successfully occluded. After the procedure, the patients recovered and were discharged shortly. RAP is a rare, but potentially life-threatening complication after PRB and can be treated successfully with superselective arterial embolization.


Psychological distress related to COVID-19 - The contribution of continuous traumatic stress.
The novel coronavirus (COVID-19) is a substantial stressor that could eventuate in psychological distress. Evidence suggests that individuals previously exposed to traumatic events, and particularly to continuous traumatic stress (CTS), might be more vulnerable to distress when facing additional stressors. This study aimed to investigate these suppositions in the context of the ongoing shelling of Israel from the Israel-Gaza border, which continues even amidst the COVID-19 crisis. An online survey was conducted among Israel's general population. The sample included 976 participants. Seven-hundred-and-ninety-three participants had been exposed to traumatic events, with 255 participants reporting CTS. Trauma exposure, COVID-19-related stressors, and psychological distress related to COVID-19 (anxiety, depression, and peritraumatic stress symptoms) were assessed. Most participants reported experiencing at least one psychiatric symptom related to COVID-19. Being younger, female, not in a relationship, having a below-average income, being diagnosed with the disease, living alone during the outbreak, having a close other in a high-risk group, and negatively self-rating one's health status were associated with elevated distress. Individuals who had been exposed to trauma, and to CTS in particular, had elevated anxiety, depression, and peritraumatic stress symptoms compared to individuals without such a history or to survivors of non-ongoing traumatic events. CTS moderated the relations between PTSD symptoms, anxiety symptoms, and peritraumatic stress symptoms, with significantly stronger relations found among individuals exposed to CTS. This study relied on convenience sampling. Trauma survivors, and particularly traumatized individuals exposed to CTS, seem at risk for psychological distress related to COVID-19.


Distribution of K vitamins (phylloquinone and menaquinones) in human placenta and maternal and umbilical cord plasma.
It is a well-known fact that neonatal and infantile vitamin K deficiencies cause melena neonatorum and intracranial hemorrhagic disorders. These disorders occur more frequently in breast-fed babies than in bottle-fed babies, for reasons that are still obscure. Endogenous concentrations of K vitamins (phylloquinone and menaquinones) in human placentas and in paired specimens of maternal and umbilical cord plasma were detected by high-performance liquid chromatography with fluorometric detection and postcolumn reduction. Phylloquinone (K1) and menaquinones (MK-4, MK-6, and MK-7) were found in placentas and maternal plasma. K1 and MK-4 were found in umbilical cord plasma. The experimental subjects were 13 pregnant women with normal diets (group A) and two pregnant women with diets supplemented with fermented soybeans (group B), in which MK-7 is abundant. Samples from their placentas and maternal and umbilical cord plasma were collected just after delivery. The placentas and maternal plasma of group B contained higher concentrations of MK-7 (placentas = 10.82 ng/gm and maternal plasma = 3.55 ng/ml) than did group A (placentas = 1.08 ng/gm, maternal plasma = 0.70 ng/ml). However, MK-7 was not found in umbilical cord plasma of any of the subjects. The mean K1 values of all 15 patients in placentas and maternal and umbilical cord plasma were 1.28 ng/gm, 1.54 ng/ml, and 0.11 ng/ml, respectively; mean MK-4 values were 1.18 ng/gm, 0.05 ng/ml, and 0.04 ng/ml, respectively. A high concentration of MK-4 was detected in placentas.


Elevated serotonin alters whole-blood expression of serotonin receptor and metabolism genes in the lactating dairy cow.
Serotonin's role as a hormone has been demonstrated through modulating calcium metabolism, energy homeostasis, and immune function in the preweaned and lactating bovine. Recently, manipulation of the serotonergic axis in calves via administration of 5-hydroxy-l-tryptophan (5-HTP), the serotonin precursor, elicited immunomodulatory effects and regulated serotonin transport and metabolism genes in leukocytes. However, serotonin's ability to modulate whole-blood gene expression in lactating dairy cows is unknown. Our objective was to explore the effect of infusing 5-HTP on whole-blood expression of genes regulating serotonin transport (reuptake transporter), signaling (receptors), metabolism (synthesis and degradation), and cytokines in dairy cows. Twelve lactating multiparous Holstein dairy cows were blocked by parity, milk production, and days in milk in a randomized complete block design and randomly assigned to intravenous infusion of either 1 L of 1.5 mg/kg 5-HTP dissolved in saline (n = 6) or 1 L of saline solution (n = 6) for 3 consecutive days. Whole blood was collected at 48, 56, and 72 h relative to termination of first infusion to analyze whole-blood gene expression. Infusion of 5-HTP increased whole-blood mRNA expression of monoamine oxidase-A and serotonin receptor 7 across the experimental period. Forty-eight hours from termination of first infusion, the mRNA of monoamine oxidase-A, serotonin reuptake transporter, and serotonin receptor 7 were increased in blood relative to the control. Interleukin-8 concentrations and mRNA were unchanged in response to 5-HTP infusion. Collectively, these data suggest that infusion of 5-HTP may alter mRNA of serotonin metabolism, transport, and signaling genes in whole blood of lactating dairy cows.


Retardation of cell cycle progression of macrophages from G1 to S phase by ICAM-L from Leishmania.
Leishmania, an obligate intracellular parasite of host macrophages, infects the macrophage through receptor-mediated phagocytosis that either activates or deactivates macrophages to eliminate the parasite or allow the parasite to grow intracellularly. ICAM-L, an intercellular adhesion molecule from L. amazonensis, results in lower MTT tests and proliferative responses of macrophages when incubated in vitro. The inhibition of cell proliferation, however, results from temporary retardation of the cell cycle progression at the G1 to S phase transition rather than cell death. The retardation is due to the upregulation of two CKI proteins, p21 and p27, in a p53-independent manner which, control the G(1) to S phase transition checkpoint.


Identifying Patients at High Risk of Chronic Pain After Video-Assisted Thoracoscopic Surgery Using Thermal Quantitative Sensory Testing.
To examine whether perioperative thermal quantitative sensory testing could be used to identify patients at high risk of chronic pain after video-assisted thoracoscopic surgery (VATS). A single-center, prospective, observational study. At the Peking University People's Hospital. A total of 111 patients scheduled to undergo VATS were enrolled. Quantitative sensory testing was conducted at the anterior intercostal incision prior to surgery and after chest tube removal. The patient's chronic pain was assessed at 3 months after surgery using a questionnaire. The incidence of chronic pain was 35 out of 107 evaluable patients (32.7%). Among the 35 patients with chronic pain, 26 had features characteristic of neuropathic pain (74.3%). Compared to the patients without chronic pain, subjects with chronic pain had a significantly greater perioperative change in cold pain threshold (CPT; p = 0.032), but not cold detection threshold, warm detection threshold, and hot pain threshold . In the multivariate regression, perioperative CPT change was associated with chronic pain after VATS (odds ratio = 1.043, p = 0.026). Chronic pain after VATS is typically neuropathic. The change in perioperative CPT at the incision site may help to identify patients at higher risk of chronic pain after VATS.


Factor VIII inhibitors in mild and moderate-severity haemophilia A.
Inhibitors are an uncommon complication of mild haemophilia, occurring in 3-13% of patients and usually arising during adulthood. The risk of inhibitor development in this group appears to be associated with relatively few high-risk factor VIII genotypes clustered in the A2 and C2 domains, especially the Arg593-Cys and the Trp2229-Cys mutations. Kindreds with these mutations have an inhibitor incidence of up to 40%. These mutations may induce a stable conformational change in the factor VIII molecule rendering it antigenically distinct from wild-type factor VIII. Inhibitors in mild haemophilia usually cross-react with endogenous factor VIII reducing the basal VIIIC to < 0.01 IU/ml, and causing spontaneous bleeding. This bleeding is sometimes severe and life-threatening, two-thirds of patients developing a pattern of soft tissue, gastrointestinal (GI) and urinogenital bleeding reminiscent of acquired haemophilia. Bleeding has been treated with human and porcine factor VIII, bypass therapy and DDAVP. Recombinant factor VIIa and DDAVP have the advantage that they do not induce an anamnestic rise in inhibitor titre. About 60% of these inhibitors disappear in the remainder over a median of 9 months. Few of these inhibitors recur, suggesting that most such patients have become tolerant. The inhibitors persist long-term and remain troublesome in about 40% of patients. The limited data available on immune tolerance induction in this group indicate a generally poor response to this approach. Two of nine achieved tolerance, with a partial response in a further four. Inhibitors are an uncommon but life-threatening complication of haemophilia. This complication should be considered when selecting the treatment modality for patients with a family history of inhibitors, and DDAVP used whenever possible.


Linear accelerator utilization: Concept and tool to aid the scheduling of patients for radiotherapy.
Resources in radiotherapy (RT) need to be used effectively to meet the current clinical demand. The aim of this data-driven study is to identify temporal trends in the scheduling of patients for RT and to develop a tool for a visual overview of future scheduling levels. Scheduling data at an eight-linac modern RT department in Sweden were collected twice daily for planned and observed linac use in 2018-2020. Information was retrieved each day for the present (Day 0) and the forthcoming 100 weekdays with total linac utilization rates (LURs) calculated for two activity categories: treatment and non-treatment. An in-house tool based on the LUR concept, database queries from the oncology information system (OIS)/automatic calculations was developed and evaluated by RT managers and scheduling staff (n = 10). Overall median LURs were 87%/89% (planned/observed; p < 0.01) with more frequent and larger daily increase for non-treatment activities compared with treatment activities. LUR increased with shorter planning horizons and reached 100% for fully-operating linacs ≈3 weeks before Day 0. The tool was reported by 88% to ease the work and to contribute towards an even scheduling of patients (responses: 8/10). Alterations from a planned RT schedule occurs frequently. Having a tool that helps to reduce the abundance of booking information into clinically relevant overviews promise to increase the understanding of present and future scheduling levels. Our proposed concept and tool suggest that this is a feasible approach to schedule patients for RT more evenly.


Quantification of carbamazepine and its active metabolite by direct injection of human milk serum using liquid chromatography tandem ion trap mass spectrometry.
This work reports the use of a liquid chromatography ion trap tandem mass spectrometry (LC-IT-MS/MS) system for quantification in human milk samples of both carbamazepine (CBZ) and its active metabolite, carbamazepine 10,11-epoxide (CBZE). An octadecyl restricted-access media bovine serum albumin column (RAM-BSA C(18)) was used in single-column mode. Selectivity, extraction efficiency, accuracy and precision were achieved employing 100 μL of the sample, without preparation, with detection limits of 20.0 ng/mL for CBZ and 40.0 ng/mL for CBZE. The matrix effect was investigated for the compounds by post-column infusion (qualitative) and by on-line extraction (quantitative). It was observed suppression effect for CBZ and CBZE by post-column infusion, ion suppression of 0.80 for CBZ, and enhancement of 1.28 for CBZE by on-line extraction. The developed method was validated and applied to analyze breast milk samples from one nursing mother. CBZ and CBZE were quantified in the concentrations of 2.26 μg/mL and 1.54 μg/mL, respectively. To our knowledge, this is the first report on the simultaneous determination of CBZ and its active metabolite by direct injection of human milk serum.


EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.
EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which along with other PRC2 components mediates gene expression suppression via the methylation of Histone H3 at lysine 27. Recent studies have revealed a dichotomous role of EZH2 in physiology and in the pathogenesis of cancer. While it plays an essential role in the development of the lymphoid system, its deregulation, whether due to genetic or non-genetic causes, promotes B cell- and T cell-related lymphoma or leukemia. These findings triggered a boom in the development of therapeutic EZH2 inhibitors in recent years. Here, we discuss physiologic and pathogenic function of EZH2 in lymphoid context, various internal causes of EZH2 aberrance and how EZH2 modulates lymphomagenesis through epigenetic silencing, post-translational modifications (PTMs), orchestrating with surrounding tumor micro-environment and associating with RNA or viral partners. We also summarize different strategies to directly inhibit PRC2-EZH2 or to intervene EZH2 upstream signaling.


Zuclopenthixol Induced Ischemic Priapism: Case Report and Review of Literature.
Present a case of zuclopenthixol associated priapism, literature review and focus on the stuttering priapism entity as a potential serious complication as well as providing information about possible preventive treatments. A 44 year-old male patient with history of cocaine abuse with associated priapism presents with acute painful erection after starting zuclopenthixol for treatment of a psychotic episode. This episode was later followed by many other similar episodes defined as stuttering priapism. Acute ischemic priapism is a potential serious side effect of antipsychotics that physicians especially psychiatrists needs to be aware of especially if the patient has previous episodes in order to prevent reoccurrence.


Slow negative evoked potentials in the rhesus monkey (Macaca mulatta): myogenic versus neurogenic influences.
The influence of myogenic activity on the generation of slow negative evoked potentials (SN10) to octave, toneburst stimuli (0.5-2 Hz) was investigated in 5 rhesus monkeys (M. mulatta) by comparing responses obtained prior to and during total paralysis induced with curare. The SN10 could be easily elicited during paralysis, regardless of stimulus intensity, rate, or frequency. During paralysis, there were no systematic changes in either response latency or amplitude; variability in latency was less than 10% and changes in response amplitude were within 30%. These findings suggest that the myogenic contribution to the SN10 response is negligible and that this response is of neurogenic origin in the rhesus monkey.


Fabrication of nanofibers through a unique morphological transformation of poly(lactic acid) particles in water.
Poly(lactic acid) (PLA) particles dispersed in water were transformed into nanofibers by simply heating above the glass transition temperatures of the hydrated PLAs.


Lack of association between anti-V3 loop antibody and perinatal HIV-1 transmission in Kinshasa, Zaire, despite use of assays based on local HIV-1 strains.
Maternal antibodies against the V3 loop principal neutralizing domain (PND) have been reported to protect against perinatal HIV-1 transmission. To study this association in an African city with a long-standing HIV epidemic and no established "consensus sequence" for the V3 loop region of gp120, we determined the DNA sequence for the V3 region of HIV-1 from 13 HIV-1-infected residents of Kinshasa, Zaire, and developed peptide enzyme immunoassays (EIAs) reflecting the V3 loop PND for those HIV-1 strains. Using the most broadly reactive locally derived V3 loop peptide in a limited-antigen EIA, there was no significant difference in the perinatal HIV-1 transmission risk between 64 women with anti-V3 loop antibody (transmission risk, 30%) and 104 women without anti-V3 loop antibody (transmission risk, 25%; p = 0.5); this finding was unchanged after we controlled for maternal AIDS and low birth weight. Although we used assays for V3 loop antibody based on local HIV-1 strains and evaluated a large number of mother-child pairs, we found no evidence that maternal anti-V3 loop PND antibody protects against perinatal HIV-1 transmission.


The daily stress and coping process and alcohol use among college students.
To examine whether students drink more alcohol on higher-stress days than on lower-stress days; whether daily coping strategies and affective states mediate the within-person relationship between stress and drinking; and whether the daily stress-drinking process varies as a function of previously identified between-person risk factors (sex, family history, coping motives, sensation seeking, neuroticism). College students (N = 137) completed daily surveys for 28 consecutive days. With daily coping, affect and weekly trends in drinking controlled for, students consumed more alcohol on days that had events perceived as relatively more stressful. Students also drank more on days characterized by relatively lower problem-focused coping and relatively higher positive and negative affect. Contrary to predictions, the effect of stress on drinking was not fully mediated by coping and affect. Findings also revealed individual differences in several links in the daily stress coping-drinking process. The daily stress coping-drinking process is complex, and it appears that there are both positive and negative affective pathways underlying daily alcohol consumption.


The ratio of choline lysine ionic liquid determines the structure and digestion of starch-oleic acid complex.
Fully green choline lysine ([Cho][Lys]) ionic liquid (IL) was explored as the solvent to prepare starch-fatty acid complex, and the regulation of water: [Cho][Lys] (W:IL) ratio on the structure and digestion of starch-oleic acid (OA) complex was illuminated. Compared with pure water (W:IL-10:0), high (W:IL-0:10) or low concentration (W:IL-8:2, 6:4) of [Cho][Lys] IL would inhibit the disaggregation behaviors of starch. This inhibition led to the preservation of more original ordered multi-structures of starch (indicated as more double helix, type A crystalline structures, denser aggregate structure and ΔH values of gelatinization peak) and less complexion of starch with OA (indicated as less single helix, type V crystalline structures). While in W:IL-4:6, 2:8 mixtures, the disaggregation behaviors of starch were much promoted, and the original multi-structures of starch were much destroyed, which would enhance the complexion of starch with OA to form higher contents of single helix and type II V crystalline structures. As results, the anti-digestibility of starch-OA complexes prepared in W:IL-4:6, 2:8 mixtures were much improved in paste form. These results provide a new way of using [Cho][Lys] solvents to improve the complexion of starch with fatty acid and to create starch-based functional foods.


Requirements for the translational repression of ferritin transcripts in wheat germ extracts by a 90-kDa protein from rabbit liver.
A specific repressor of ferritin mRNA translation originally detected in rabbit reticulocyte lysates has now been purified to homogeneity from rabbit liver, as described in a companion paper (Walden, W. E., Patino, M. M., and Gaffield, L. (1989) J. Biol. Chem. 264, 13765-13769). This repressor is a 90-kDa protein that binds to a sequence in the 5'-untranslated region of ferritin mRNA. In this communication we describe the molecular features of a ferritin light chain transcript that are required for the repression of its translation by this protein. Addition of small amounts of the 90-kDa ferritin repressor protein (FRP) completely inhibited translation of ferritin transcripts in a wheat germ system. This repression did not require mRNA sequences contained in the 3'-untranslated region or in the majority of the ferritin coding region. In contrast, the first 130 nucleotides of the 5'-untranslated region, which contains the 28-nucleotide "iron responsive element" (IRE), was required for the repressive effect. Moreover, repression of full length transcripts was relieved by addition of a molar excess of a 92-nucleotide transcript of the 5'-untranslated region which also contained the IRE. These results suggest that no sequence information other than a portion of the 5'-untranslated region containing the IRE sequence is required for action of the 90-kDa FRP. In addition, a quantitative comparison of the repression of transcript with that of poly(A+) RNAs indicates that no post-transcriptional modifications of the latter (other than cap addition) are involved in the action of the 90-kDa FRP.


The mechanism of electrodiffusive K+ transport in leaky epithelia and some of its consequences for anion transport.
The ventricular membrane of the epithelium from the choroid plexus of Necturus maculosus was probed with double-barrelled ion-selective microelectrodes while the ventricular bathing solution was changed abruptly. The transient states induced by increasing the external concentration of K+ or by the application of ouabain showed that the passive movements of K+ across the ventricular membrane were electro-diffusive and could be described by the Goldmann equation and one constant permeability (PK) of 24 X 10(-6) cm s-1. The passive efflux was balanced by a ouabain-sensitive influx. PK was different in different steady states; when the cell was acidified by half a pH unit by increasing CO2 in the bathing solutions from 1 to 5%, then PK decreased to 13 X 10(-6) cm s-1. Removal of Cl- from the bathing solution increased PK by 50% and reduction of Cl- transport by furosemide did not alter PK, consequently major movements of K+ were independent of Cl- movements. Depolarizations of the cell caused an increase in the cellular HCO-3 concentration due to an electrodiffusive permeability (PHCO3), the value of which was estimated to 17 X 10(-6) cm s-1.


[Respiratory failure due to acid maltase deficiency].
Acid maltase deficiency (AMD) is a metabolic myopathy which may be revealed at adulthood by respiratory muscle weakness, resulting in reduced vital capacity, alveolar hypoventilation and sleep apnoea. We observed two men, 39 and 42 years old respectively, suffering from asthenia and exertional dyspnoea for several months. After a stay in the intensive care unit, as a result of respiratory failure associated with pneumonia, these patients were referred to the respiratory medicine unit on account of persistent hypercapnia during the day and a fall in oxygen saturation at night. The investigations revealed proximal muscle weakness, a reduced vital capacity, alveolar hypoventilation (PaCO2: 67 and 49 mmHg), reduced maximum static inspiratory and expiratory pressures, carbon dioxide hyporesponsiveness and sleep apnoea on overnight polysomnography. Electromyography showed a myopathic pattern. Muscle biopsy confirmed the diagnosis of AMD. Non-invasive ventilation overnight partially corrected the clinical symptoms and the resting hypercapnia in both patients. The adulthood form of AMD is a rare disease that should be considered in a large number of clinical situations, particularly in unexplained respiratory failure. Our observations suggest that non invasive ventilation together with enzyme supplementation (Myozyme®) is effective in correcting alveolar hypoventilation.


Malignant meningeal melanoma.
We report the case of an isolated pigmented lesion of the cerebellar tentorium which was initially interpreted as meningeal melanocytoma. The immunohistochemical study required as a result of a subsequent post-surgical recurrence prompted us to reconsider the early diagnosis in favour of malignant meningeal melanoma. On the basis of data in the literature, the possibility that the lesion may have been a dural melanoma is discussed.


Outcomes after thumb carpometacarpal joint stabilization with an abductor pollicis longus tendon strip for the treatment of chronic instability.
Instabilities of the thumb carpometacarpal (CMC) joint, caused by idiopathic ligamentous hyperlaxity, trauma or other conditions may lead to pain, functional impairment and eventually osteoarthritis. Several techniques have been described to enhance stability of the CMC 1. The aim of this study was to evaluate postoperative outcomes after CMC 1 joint stabilization using a soft-tissue procedure in patients with chronic instability. This study was designed as a retrospective study with a single follow-up visit after a minimum of 1 year postoperatively. All patients who underwent stabilization of the CMC 1 with an abductor pollicis longus (APL) tendon strip for chronic, habitual instability were re-assessed using clinical examination, dedicated outcome scores [Visual Analogue Scale (VAS); The Disability of the Arm, Shoulder and Hand (DASH) score; Nelson score; Kapandji opposition score], grip and pinch strength measurements, and radiographic examination. 12 patients (15 operated thumbs) with a mean age at surgery of 23.2 (± 9.3) years were included after a mean follow-up period of 3.5 (± 1.3) years. The postoperative outcomes indicated excellent results, with a mean DASH score of 13.3 (± 11.3), VAS 1.1 at rest (and 2.8 during stress) and Nelson score of 87.7 (± 11.3). Postoperative grip, pinch strength and passive stability were not significantly different between operated and non-operated sides (p = 0.852; p = 0.923 and p = 0.428, respectively). We observed one case of recurrent instability besides no other complications. However, patients with trapezium hypoplasia (5 of 12) were more prone to signs of radiographic instability during stress testing. Thumb carpometacarpal stabilization with an APL tendon strip yielded excellent clinical outcomes and low morbidity in the mid-term. However, long-term follow-up is needed to assess specifically whether patients with trapezium hypoplasia may be more prone to clinical symptom recurrence than those with normal anatomy. Level IV.


Genetically predicted osteoprotegerin levels and the risk of cardiovascular diseases: A Mendelian randomization study.
The relationship between circulating osteoprotegerin (OPG) levels and the risk of cardiovascular diseases (CVDs) has been the subject of conflicting results in previous observational and experimental studies. To assess the causal effect of genetically predicted OPG levels on the risk of a wide range of CVDs, we used the Mendelian randomization design. We initially extracted information of genetic variants on OPG levels and their corresponding effect values from the summary data based on the European ancestry genome-wide association study. Subsequently, we performed two-sample Mendelian randomization analyses to assess the causal effect of genetically predicted OPG levels on CVDs by using inverse variance weighting (IVW), MR-Egger, weighted median, and MR-PRESSO methods. We also conducted sensitivity analyzes as well as complementary analyses with a more relaxed threshold for the exposure genetic instrumental variable (P < 5 × 10-6) to test the robustness of our results. Our results indicated that genetically predicted OPG levels causally reduce the risk of atrial fibrillation (IVW OR = 0.84; 95% CI = 0.72-0.98; P = 0.0241), myocardial infarction(IVW OR = 0.89; 95% CI = 0.80-0.98; P = 0.0173) and coronary heart disease (IVW: OR = 0.90; 95% CI = 0.82-0.99; P = 0.0286). Further complementary analyses also confirmed the above results remain robust and we also identified a potential causal association of OPG levels with a reduced risk of hypertensive diseases(IVW OR = 0.94;95% CI = 0.88-1.00; P = 0.0394). This study provides compelling evidence for a causal relationship between genetically predicted OPG levels and risk reduction of coronary heart disease, myocardial infarction, and atrial fibrillation, indicating that OPG could potentially serve as a cardiovascular risk marker in clinical practice.


[Words that speak well to pains].
Cross-cultural consultation often uses metaphors. These promote narration, facilitate the therapeutic alliance, and allow psychic elaborations that release our patients' pains. The terms and conditions of their use, as well as their purposes, are more and more determined. They draw from imagination and therapists' lived experiences, in classical stories, in tales and fables from various cultures. This gives them real therapeutic potential, which must be learned to use.


Selective detection of fenaminosulf via a molecularly imprinted fluorescence switch and silver nano-film amplification.
A novel fluorescence switch sensor was constructed for detecting the fungicide fenaminosulf (FM), based on a dye-doped molecularly imprinted polymer (MIP) and silver nanofilm amplification. The MIP was prepared by electropolymerization of hydroquinone doped with neutral red on the silver nanofilm modified electrode. A fluorescence signal was produced by the neutral red and the fluorescence intensity was diminished by the ion pair that formed via electrostatic forces between FM and the dye. Therefore, elution and adsorption of FM by the MIP acted as a switch to control the fluorescence intensity, which was effectively amplified by the silver nanofilm. The decrease in fluorescence intensity was linear with the FM concentration, establishing a new method for FM detection. Under optimal conditions, good linear correlation was obtained for FM concentrations over the range from 2.0 × 10(-10) to 4.0 × 10(-8)mol/L, with a detection limit of 1.6 × 10(-11)mol/L. This method was utilized to determine residual FM in vegetable samples, and recoveries ranging from 92.0% to 110% were obtained.


Oral administration of guanosine impairs inhibitory avoidance performance in rats and mice.
Extracellular guanine-based purines, mainly the nucleoside guanosine, have recently been shown to exert neuroprotective effects, which seem to be related to antagonism of the glutamatergic system. In this study, we investigated the effects of acute oral administration of guanosine on inhibitory avoidance task in rats and mice. We also studied its effects on locomotor activity, anxiety-related behaviors and mechanisms of action involving the purinergic system. Guanosine (2.0 and 7.5mg/kg, per os), administered 75min pretraining, dose-dependently impaired retention of the inhibitory avoidance task in rats and mice, an effect not prevented by the adenosine receptor antagonist caffeine. Guanosine presented no effects on locomotor activity and anxiety-related behaviors. This amnesic effect of guanosine may be compatible with inhibition of glutamatergic system and seems to be not mediated by adenosine.


Real-World Outcomes Among Crizotinib-Treated Patients with ROS1-Positive Advanced Non-Small-Cell Lung Cancer: A Community Oncology-Based Observational Study.
Crizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC). Data to support long-term clinical benefit in a real-world setting are limited. This study aimed to assess real-world clinical outcomes among patients with ROS1-positive advanced NSCLC treated with crizotinib in the US community oncology setting. We conducted a retrospective cohort study using iKnowMed electronic health record data to identify adult patients with ROS1-positive advanced NSCLC who initiated crizotinib between 17 January 2013 (time of the addition of crizotinib for ROS1-positive NSCLC to National Comprehensive Cancer Network (NCCN) treatment guidelines) and 1 June 2019 with a potential follow-up period through 1 December 2019. Patient characteristics were assessed descriptively. Kaplan-Meier analyses were used to evaluate time to treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS). A Cox proportional hazards model was conducted to determine factors associated with OS. The study cohort included 38 ROS1-positive patients treated with crizotinib. The median age was 68 years (interquartile range 60.0-73.0) and 65.8% were female. Over 50% were current/former smokers, and 18.4% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Overall, 21 (55.3%) patients remained on crizotinib, 10 (26.3%) had evidence of subsequent treatment, and 16 (42.1%) died. The median TTD, TTNT, and OS were 25.2 months [95% confidence interval (CI): 5.2-not reached (NR)], 25.0 months (95% CI 5.2-61.0), and 36.2 months (95% CI 15.9-NR), respectively. In a multivariate Cox regression model, ECOG performance status of 2 was associated with a 4.9-fold higher risk of death (hazard ratio = 4.9; 95% CI 1.1-21.4) compared to ECOG performance status of 0 or 1. This ROS1-positive NSCLC real-world population was older and had a higher proportion of smokers and of patients with poorer ECOG performance status than those investigated in clinical trials. Nevertheless, our findings support the clinical benefit of crizotinib in this patient population with ROS1-positive advanced NSCLC.


Entropy Stabilization Strategy for Enhancing the Local Structural Adaptability of Li-Rich Cathode Materials.
Layered Li-rich cathode materials with high reversible energy densities are becoming prevalent. However, owing to the activation of low-potential redox couples and the progressively irreversible structural transformation caused by the local adjustment of transition-metal ions in the intra/interlayer driven by anionic redox, continuous capacity degradation, and voltage decay emerge, thus greatly reducing the energy density and increasing the difficulty of battery system management. Herein, layered Li-rich cathode materials with higher intralayer configuration entropy have more local structural diversity and higher distortion energy, resulting in superior local structural adaptability with no drastic redox couple evolution, major local structural adjustment, or obvious layered-to-spinel phase transition. Consequently, the energy retention of the entropy-stabilization-strategy-enhanced Li-rich cathode materials is almost twice that of a typical Li-rich cathode material (Li1.20 Mn0.54 Ni0.13 Co0.13 O2 , T-LRM) after 3 months of cyclic testing. Moreover, when cycled at 1 C, the voltage degradation per cycle is less than 0.02%, that is, it results in a voltage loss of only 0.8 mV per cycle, which is excellent performance. This study paves the way for the development of Li-rich cathode materials with stabilized intralayer atomic arrangements and high local structural adaptability.


Pulmonary metastasis: rationale for local treatments and techniques.
The indication for pulmonary metastasectomy has been postulated based on nonrandomized clinical experiences. The postoperative survival rate of selected patients with pulmonary metastasis is acceptable; nevertheless, pulmonary metastasectomy might cure patients if the neoplastic cells are located only in the lung parenchyma. Computed tomography has been the most reliable preoperative diagnostic methods for identifying pulmonary metastasis. However, it has the limitations that small nodules often cannot be detected, or they are overestimated. Through thoracoscopy, which has largely been applied for metastasectomy in Japan, bimanual palpation during surgery cannot be performed. Considering the fact that the survival rate of the patients undergoing thoracoscopy is not significantly different from that of the patients undergoing conventional thoracotomy, pulmonary metastasectomy is a suboptimal method for eradicating the disease. Less invasive local therapy may be promising for repeat local intervention.


[The "Hilfsverein für Nerven- und Gemütskranke in Württemberg" - On Post-Discharge Community Care for Psychiatric Patients, 1895-1975].
This article on the history of psychiatry provides an introductory overview of the development of psychiatric Hilfsvereine in Germany and for the first time describes the history of the Hilfsverein in the former kingdom of Württemberg - from its foundation until 1975, exploring various archival sources including this society's own archives. Since its foundation, the Hilfsverein had played a central role in the post-discharge care and support of mentally ill people in Württemberg. Until the years of National Socialism, the focus was on individual cases and family support, with a sharp ideological cut in this era. With the expansion of the social-psychiatric care structures, beginning in the late 1960 s, the focus of the society's work clearly shifted towards the support of projects for out-patients. The history of the Hilfsverein shows evidence of various breaks, as well as adjustments to political change and changes due to the development of the psychiatric care system.


Microglia dynamics in aging-related neurobehavioral and neuroinflammatory diseases.
Microglia represent the first line of immune feedback in the brain. Beyond immune surveillance, they are essential for maintaining brain homeostasis. Recent research has revealed the microglial cells' spatiotemporal heterogeneity based on their local and time-based functions in brain trauma or disease when homeostasis is disrupted. Distinct "microglial signatures" have been recorded in physiological states and brain injuries, with discrete or sometimes overlapping pro- and anti-inflammatory functions. Microglia are involved in the neurological repair processes, such as neurovascular unit restoration and synaptic plasticity, and manage the extent of the damage due to their phenotype switching. The versatility of cellular phenotypes beyond the classical M1/M2 classification, as well as the double-edge actions of microglia in neurodegeneration, indicate the need for further exploration of microglial cell dynamics and their contribution to neurodegenerative processes. This review discusses the homeostatic functions of different microglial subsets focusing on neuropathological conditions. Also, we address the feasibility of targeting microglia as a therapeutic strategy in neurodegenerative diseases.


Meta-analysis of the correlation between CT-based features and invasive properties of pure ground-glass nodules.
Several studies have revealed that computed tomography (CT) features can make a distinction in the invasive properties of pure ground-glass nodules (pGGNs). However, imaging parameters related to the invasive properties of pGGNs are unclear. This meta-analysis was designed to decipher the correlation between the invasiveness of pGGNs and CT-based features, and ultimately to be conducive to making rational clinical decisions. We searched a series of databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, wanfang, CNKI, VIP, as well as CBM databases, until September 20, 2022, for the eligible publications only in Chinese or English. This meta-analysis was implemented with the Stata 16.0 software. Ultimately, 17 studies published between 2017 and 2022 were included. According to the meta-analysis, we observed a larger maximum size of lesions in invasive adenocarcinoma (IAC) versus that in preinvasive lesions (PIL) [SMD = 1.37, 95% CI (1.07-1.68), P < 0.05]. Meanwhile, there were also increased mean CT values of IAC [SMD = 0.71, 95% CI (0.35, 1.07), P < 0.05], the incidence of pleural traction sign [OR = 1.94, 95% CI (1.24, 3.03), P < 0.05], the incidence of IAC spiculation [OR = 1.55, 95% CI (1.05, 2.29), P < 0.05] in comparison to those of PIL. Nevertheless, IAC and PIL exhibited no significant differences in vacuole sign, air bronchogram, regular shape, lobulation and vascular convergence sign (all P > 0.05). Therefore, IAC and PIL manifested different CT features of pGGNs. The maximum diameter of lesions, mean CT value, pleural traction sign and spiculation are important indicators to distinguish IAC and PIL. Reasonable use of these features can be helpful to the treatment of pGGNs.