Nutrimiromics: Role of microRNAs and Nutrition in Modulating Inflammation and Chronic Diseases.
Nutrimiromics studies the influence of the diet on the modification of gene expression due to epigenetic processes related to microRNAs (miRNAs), which may affect the risk for the development of chronic diseases. miRNAs are a class of non-coding endogenous RNA molecules that are usually involved in post-transcriptional gene silencing by inducing mRNA degradation or translational repression by binding to a target messenger RNA. They can be controlled by environmental and dietary factors, particularly by isolated nutrients or bioactive compounds, indicating that diet manipulation may hold promise as a therapeutic approach in modulating the risk of chronic diseases. This review summarizes the evidence regarding the influence of nutrients and bioactive compounds on the expression of miRNAs related to inflammation and chronic disease in several models (cell culture, animal models, and human trials).


Mucosal Abnormalities in Children With Congenital Chloride Diarrhea-An Underestimated Phenotypic Feature?
Objectives and Study: Congenital chloride diarrhea (CCD) is a rare, autosomal recessive disorder caused by mutations in the SLC26A3 gene encoding a transmembrane chloride/bicarbonate ion exchanger mainly expressed in the apical brush border of the ileal and colonic epithelium. Lifelong, secretory, chloride-rich diarrhea and hypochloremic, hypokalemic metabolic alkalosis are characteristic. Histological evidence of bowel inflammation is not typically described in CCD and has only been reported in a few patients. Methods: We report four cases of CCD who received adequate resuscitation with appropriate replacement of their fecal salt and water losses. Three had associated inflammatory bowel changes at endoscopy. The index case of CCD who developed frankly bloodstained diarrhea aged 7 months was found to have histologically confirmed colitis at endoscopy. An electronic search of the hospital database to identify all patients with confirmed CCD was performed. A further three children underwent de novo diagnostic evaluation and treatment. A retrospective case note review was undertaken to determine the incidence and subtype of inflammatory bowel disease (IBD) by clinical, endoscopic, and histological means. Results: Four children with genetically confirmed CCD were identified, two being female. The first girl had a granulomatous colitis with ulceration. She went into remission with a combination of steroids and azathioprine. Immunosuppression was subsequently discontinued without a further flare of colitis. A second girl was found to have patchy inflammatory changes in the small bowel and focal active colitis. A third patient, a boy, demonstrated mild inflammatory changes in the small bowel with apoptotic debris and mild inflammation in the colon. A fourth patient did not develop intestinal inflammation. Conclusion: Our case series highlights the potential association of CCD with panenteric inflammation. While our cohort was small, CCD is rare and three out of four children referred to our tertiary referral center were affected. While early diagnosis and adequate salt replacement therapy are crucial in CCD management, the clinician should also be aware of bowel inflammation as a potential cause of failure of CCD therapy to control bowel symptomatology. Further insight is needed to understand the underlying patho-mechanism giving rise to bowel inflammation in this group.


[The current evidence of S-1 and irinotecan hydrochloride combination chemotherapy with tri-weekly schedule].
A combination therapy of irinotecan hydrochloride (CPT-11) with continuous intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns on safety and convenience have prompted the development of new oral fluoropyrimidine derivatives which improved regimens. Yamada et al conducted a phase I study to assess the maximum tolerated dose and recommended dose of S-1 combined with CPT-11. The study recommended that 150 mg/m2 of CPT-11 be given on day 1 and 80 mg/m2 of S-1 daily on days 1 to 14 every 3 weeks. Recently, several phase I/II studies assessed the efficacy and safety of the combined therapy with S-1 and CPT-11 in patients with advanced colorectal cancer. Some of the studies which were ongoing assessed a tri-weekly schedule regimen. Our results showed that S-1 plus CPT-11 was very effective, with a response rate of 63% and PFS of 8 months. Toxicity was generally mild and manageable on an outpatient basis. The current evidence showed that a combination of S-1 and CPT-11 was more convenient and easier to administer than a combination of CPT-11 plus infusional 5-FU and LV. It will be essential to prove that the combination of S-1 plus CPT-11 can replace the combination of infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and toxicity.


Neighborhood Disadvantage, African Genetic Ancestry, Cancer Subtype, and Mortality Among Breast Cancer Survivors.
Racial disparities in breast cancer (BC) survival arise from multilevel causes, which may exert influence at different stages of BC progression. Clarifying the importance of genetic and social factors could help prioritize interventions. To jointly examine associations between African genetic ancestry, social environment, and mortality from any cause and BC in Black BC survivors. This population-based cohort study enrolled self-identified Black women aged 20 to 75 years with histologically confirmed BC from June 2005 to May 2019 and followed them up until death or censoring in September 2021. Participants lived in 10 New Jersey counties. Data were analyzed between December 2022 and April 2023. A neighborhood socioeconomic status (nSES) index composed of census tract measures (education, income, wealth, employment status, and occupation) was linked to residential addresses at diagnosis. Percentage African ancestry was estimated using the ADMIXTURE program. Sequentially adjusted (age adjusted: age and interview year; fully adjusted: age adjusted with individual SES, lifestyle factors, and comorbidities) logistic regression models were fit to estimate associations with tumor subtypes (estrogen receptor-negative [ER-] vs estrogen receptor-positive [ER+]; triple-negative breast cancer [TNBC] vs luminal A), and Cox models were fit for associations with all-cause mortality (ACM) and breast cancer-specific mortality (BCSM). Models for BCSM were fit using Fine-Gray competing risks models, and robust standard errors were used to account for census tract-level clustering. Among 1575 participants, median (IQR) African ancestry was 85% (76%-90%), and median (IQR) age was 55 (46-63) years. A 10-percentage point increase in African ancestry was associated with higher odds of ER- vs ER+ (adjusted odds ratio [aOR], 1.08; 95% CI, 0.98-1.18) and TNBC vs luminal (aOR, 1.15; 95% CI, 1.02-1.31) tumors, but not with ACM or BCSM. A 1-IQR increase in nSES was associated with lower ACM (adjusted hazard ratio [aHR], 0.76; 95% CI, 0.63-0.93), and the HR for BCSM was less than 1 but not statistically significant (aHR, 0.81; 95% CI, 0.62-1.04) in age-adjusted models, but associations attenuated following further adjustment for potential mediators (individual SES, lifestyles, comorbidities). In this cohort study of Black female BC survivors, higher African ancestry was associated with aggressive tumor subtypes. Compared with genetic ancestry, mediating pathways related to social environments may be more important for survival in these patients.


A Novel Fiber Optic Based Surveillance System for Prevention of Pipeline Integrity Threats.
This paper presents a novel surveillance system aimed at the detection and classification of threats in the vicinity of a long gas pipeline. The sensing system is based on phase-sensitive optical time domain reflectometry (ϕ-OTDR) technology for signal acquisition and pattern recognition strategies for threat identification. The proposal incorporates contextual information at the feature level and applies a system combination strategy for pattern classification. The contextual information at the feature level is based on the tandem approach (using feature representations produced by discriminatively-trained multi-layer perceptrons) by employing feature vectors that spread different temporal contexts. The system combination strategy is based on a posterior combination of likelihoods computed from different pattern classification processes. The system operates in two different modes: (1) machine + activity identification, which recognizes the activity being carried out by a certain machine, and (2) threat detection, aimed at detecting threats no matter what the real activity being conducted is. In comparison with a previous system based on the same rigorous experimental setup, the results show that the system combination from the contextual feature information improves the results for each individual class in both operational modes, as well as the overall classification accuracy, with statistically-significant improvements.


Fucoxanthin may inhibit cervical cancer cell proliferation via downregulation of HIST1H3D.
To investigate the role of fucoxanthin, reported to have significant anticancer effects, and histone Cluster 1 H3 Family Member D (HIST1H3D; implicated in tumorigenesis) in cervical cancer. The half maximal inhibitory concentration (IC50) of fucoxanthin against HeLa and SiHa cervical cancer cells was determined. Differentially expressed genes (DEGs) in SiHa cells treated with IC50 fucoxanthin were screened by high-throughput techniques and subjected to signal enrichment. Following identification of HIST1H3D as a candidate gene, HIST1H3D-knockdown models were created via transfection with a short hairpin HIST1H3D payload. Impacts on cell proliferation, cell-cycle distribution, colony formation, and apoptosis were studied. The fucoxanthin IC50 was 1 445 and 1 641 µM (Hela and SiHa cells, respectively). Chip results revealed 2 255 DEGs, including 943 upregulated and 1 312 downregulated genes, in fucoxanthin-treated versus untreated SiHa cells. Disease and function analysis indicated that these DEGs are primarily associated with cancer and organismal injuries and abnormalities, and online integrated pathway analysis showed that the DEGs were mainly enriched in p53 signalling. HIST1H3D was significantly downregulated in response to fucoxanthin. Inhibition of HIST1H3D mRNA significantly reduced cell proliferation and colony formation, significantly augmented the percentage of apoptotic HeLa and SiHa cells, and cells were arrested in G0/G1 cell cycle phase. The results suggest that HIST1H3D may be an oncogene in cervical carcinogenesis and a potential fucoxanthin target in treating cervical cancer.


Fundamentals of trapped ion mobility spectrometry.
Trapped ion mobility spectrometry (TIMS) is a relatively new gas-phase separation method that has been coupled to quadrupole orthogonal acceleration time-of-flight mass spectrometry. The TIMS analyzer is a segmented rf ion guide wherein ions are mobility-analyzed using an electric field that holds ions stationary against a moving gas, unlike conventional drift tube ion mobility spectrometry where the gas is stationary. Ions are initially trapped, and subsequently eluted from the TIMS analyzer over time according to their mobility (K). Though TIMS has achieved a high level of performance (R > 250) in a small device (<5 cm) using modest operating potentials (<300 V), a proper theory has yet to be produced. Here, we develop a quantitative theory for TIMS via mathematical derivation and simulations. A one-dimensional analytical model, used to predict the transit time and theoretical resolving power, is described. Theoretical trends are in agreement with experimental measurements performed as a function of K, pressure, and the axial electric field scan rate. The linear dependence of the transit time with 1/K provides a fundamental basis for determination of reduced mobility or collision cross section values by calibration. The quantitative description of TIMS provides an operational understanding of the analyzer, outlines the current performance capabilities, and provides insight into future avenues for improvement.


Better sleep quality and less daytime symptoms in patients on evening hemodialysis: a questionnaire-based study.
The aims of this study were to investigate the prevalence of sleep disorders in patients with end-stage renal disease (ESRD), and to assess the effect of dialysis schedule on sleep quality and the presence of daytime symptoms. We prospectively selected 150 long-term hemodialysis (HD) patients in three groups (morning, afternoon, and evening dialysis) and gave them a sleep questionnaire, the Epworth sleepiness scale and the Pittsburgh sleep quality index. Snoring was the most common complaint (56%), followed by insomnia (38%) and restless legs syndrome (22.7%). The evening dialysis group experienced more sleep time in bed (P = 0.02), required less hypnotic medication (P = 0.049), had fewer daytime symptoms (P < 0.01), and experienced less daytime sleepiness (P = 0.034). Our study confirms the high prevalence of sleep disorders in ESRD patients, and indicates a beneficial effect of evening HD on sleep quality and reduction of daytime symptoms.


Food-borne botulism in Canada, 1971-84.
Sixty-one outbreaks of food-borne botulism involving a total of 122 cases, of which 21 were fatal, were recorded from 1971 to 1984 in Canada. Most occurred in northern Quebec, the Northwest Territories or British Columbia. Of the 122 victims 113 were native people, mostly Inuit. Most of the outbreaks (59%) were caused by raw, parboiled or "fermented" meats from marine mammals; fermented salmon eggs or fish accounted for 23% of the outbreaks. Three outbreaks were attributed to home-preserved foods, and one outbreak was attributed to a commercial product. The causative Clostridium botulinum type was determined in 58 of the outbreaks: the predominant type was E (in 52 outbreaks), followed by B (in 4) and A (in 2). Renewed educational efforts combined with a comprehensive immunization program would significantly improve the control of botulism in high-risk populations.


[Imaging of endocrine tumours of the pancreas].
Islet cell tumors are rare pancreatic or peripancreatic neoplasms that produce and secrete hormones to a variable degree. Neuroendocrine tumors of the pancreas can occur sporadically or in association with multiple endocrine neoplasia type 1 (MEN I). Biologically active neuroendocrine tumors produce early symptoms and are often difficult to diagnose owing to their small dimensions, whereas biologically inactive forms are often large and sometimes found by chance. Imaging has a major role in the preoperative localization of the primary tumor and detection of metastases, providing an anatomic substrate whereas it plays a primary role in the regional staging of these neoplasm, for which surgery is the first and essential therapeutic approach. Several techniques are available including computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound, intraoperative ultrasound, somatostatin receptor scintigraphy, and arterial stimulation with venous sampling; each with unique advantages and certain limitations. Recent technical advances in Multidetector CT, and dynamic MRI using breath hold sequences have improved the sensitivity of these modalities markedly.


Therapeutic lung puncture for diffuse unilateral pulmonary interstitial emphysema in preterm infants.
Pulmonary interstitial emphysema (PIE) represents a severe complication of respiratory distress syndrome and can dramatically impair the ventilation of premature infants. We report three mechanically ventilated premature infants with severe diffuse, unilateral PIE not responding to conventional treatment, whose clinical condition improved dramatically following an ipsilateral pneumothorax. In the first two patients, the pneumothoraces occurred spontaneously. In the third patient, the ipsilateral lung was punctured with a pigtail catheter to create and - subsequently drain - a pneumothorax. Thereafter, mechanical ventilation could be discontinued within 3 days in all infants. Lung puncture with consecutive tension release of the overinflated lung by drainage is a therapeutic option for premature infants suffering from diffuse PIE in whom other conservative measures fail. It may be considered before proceeding to surgical measures in order to preserve potentially functional lung tissue.


Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer.
The role of platelets in tumor progression and metastasis has been recognized but the mechanism of their action remains unclear. Five human lung cancer cell lines (A549, CRL 2066, CRL 2062, HTB 183, HTB 177) and a murine Lewis lung carcinoma (LCC) cell line (for an in vivo model of metastasis) were used to investigate how platelet-derived microvesicles (PMV), which are circular fragments shed from the surface membranes of activated platelets, and exosomes released from platelet alpha-granules, could contribute to metastatic spread. We found that PMV transferred the platelet-derived integrin CD41 to most of the lung cancer cell lines tested and stimulated the phosphorylation of mitogen-activated protein kinase p42/44 and serine/threonine kinase as well as the expression of membrane type 1-matrix metalloproteinase (MT1-MMP). PMV chemoattracted 4 of the 5 cell lines, with the highly metastatic A549 cells exhibiting the strongest response. In A549 cells, PMV were shown to stimulate proliferation, upregulate cyclin D2 expression and increase trans-Matrigel chemoinvasion. Furthermore, in these cells, PMV stimulated mRNA expression for angiogenic factors such as MMP-9, vascular endothelial growth factor, interleukin-8 and hepatocyte growth factor, as well as adhesion to fibrinogen and human umbilical vein endothelial cells. Intravenous injection of murine PMV-covered LLC cells into syngeneic mice resulted in significantly more metastatic foci in their lungs and LLC cells in bone marrow than in control animals injected with LCC cells not covered with PMV. Based on these findings, we suggest that PMV play an important role in tumor progression/metastasis and angiogenesis in lung cancer.


Barriers Affecting the Oral Health of People Diagnosed with Depression: A Systematic Review.
The problems of oral health of people diagnosed with depression are not adequately recognized, either in developed or developing countries. Social stigma, lack of self-interest, or even inadequate approaches of dental doctors towards the unique situation of this group of people this lead to excessive oral health problems. The bibliographic database PubMed/Medline, Google Scholar, and Whiley online library were searched using the following text and MeSH as separate key terms and in combination: depression and oral health/dental caries/periodontal disease/tooth loss/utilization of oral health services/and barriers. The content of documents was analysed using qualitative methodology. Twenty-six original studies were included in the review. Level/severity of depression, medication and medical comorbidity are the most important medical barriers influencing the oral health of people diagnosed with depression. Dental fear and anxiety are mostly combined with low oral hygiene and bad oral health. Socioeconomic status, dental insurance, bad habits and education also have important roles in the oral health status of people diagnosed with depression. Including individuals with depression and oral health problems in national health programs, creating specific prevention programs, or subsidizing the cost of treatment are some of the recommendations suggested as solutions.


Urgency of reassessment of role of obesity indices for metabolic risks.
The definition of metabolic syndrome places emphasis on health care for persons at risk. However, whether an obesity index should be a mandatory component of the definition and whether obesity indices can identify metabolic risks satisfactorily require further exploration. Therefore, we investigated the effectiveness of various anthropometric obesity indices in identifying the clustering of 2 or more American Heart Association (AHA)/National Heart, Lung, and Blood Institute (NHLBI)/International Diabetes Federation (IDF)-defined metabolic risk factors (hypertension, hyperglycemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol) for metabolic syndrome and those of other metabolic risk factors (high low-density lipoprotein cholesterol, hyperuricemia, high gamma-glutamyltransferase, fatty liver) in 6141 men and 2137 women. The anthropometric indices were the following: (1) for both sexes--various levels of waist-to-height ratio (WHtR) including 0.5 and body mass index (BMI) of 23 and 25 kg/m(2); (2) for men and women individually--waist circumference (W) 90/80 cm (AHA/NHLBI/IDF for ethnic groups), W 85/90 cm (Japan Society for the Study of Obesity), and combined W and BMI: W 85/90 cm and/or BMI 25 kg/m(2) (Japanese government). The results showed the following: (1) The optimal value for WHtR was 0.5 for AHA/NHLBI/IDF-defined risk factors and approximately 0.5 for other risk factors in both sexes. (2) The sensitivities of various proposed obesity indices for identifying clustering of defined and other risk factors varied between 74.4% (WHtR 0.5) and 36.3% (BMI 25) and between 80.5% (WHtR 0.5) and 43.7% (BMI 25) in men, and varied between 65.6% (WHtR 0.5) and 16.8% (W 90 cm) and between 82.3% (WHtR 0.5) and 28.2% (W 90 cm) in women. Because the sensitivities of many anthropometric indices were very low, a reassessment of the effectiveness of obesity indices in evaluating metabolic risks and especially their suitability as a single mandatory component of metabolic syndrome is urgently needed. However, WHtR 0.5 provides a very useful algorithm for screening persons at risk.


The synaptonemal complex protein Zip1 promotes bi-orientation of centromeres at meiosis I.
In meiosis I, homologous chromosomes become paired and then separate from one another to opposite poles of the spindle. In humans, errors in this process are a leading cause of birth defects, mental retardation, and infertility. In most organisms, crossing-over, or exchange, between the homologous partners provides a link that promotes their proper, bipolar, attachment to the spindle. Attachment of both partners to the same pole can sometimes be corrected during a delay that is triggered by the spindle checkpoint. Studies of non-exchange chromosomes have shown that centromere pairing serves as an alternative to exchange by orienting the centromeres for proper microtubule attachment. Here, we demonstrate a new role for the synaptonemal complex protein Zip1. Zip1 localizes to the centromeres of non-exchange chromosomes in pachytene and mediates centromere pairing and segregation of the partners at meiosis I. Exchange chromosomes were also found to experience Zip1-dependent pairing at their centromeres. Zip1 was found to persist at centromeres, after synaptonemal complex disassembly, remaining there until microtubule attachment. Disruption of this centromere pairing, in spindle checkpoint mutants, randomized the segregation of exchange chromosomes. These results demonstrate that Zip1-mediated pairing of exchange chromosome centromeres promotes an initial, bipolar attachment of microtubules. This activity of Zip1 lessens the load on the spindle checkpoint, greatly reducing the chance that the cell will exit the checkpoint delay with an improperly oriented chromosome pair. Thus exchange, the spindle checkpoint, and centromere pairing are complementary mechanisms that ensure the proper segregation of homologous partners at meiosis I.


Identification of co-occurring diseases using ontological data mining techniques.
In this work we investigate the identification of co-occurring diseases in a patient database using two ontological data mining techniques: fuzzy clustering and fuzzy co-clustering. We present preliminary results on a pilot data set of 107 patients.


Heterotrimeric Gq proteins act as a switch for GRK5/6 selectivity underlying β-arrestin transducer bias.
Signaling-biased ligands acting on G-protein-coupled receptors (GPCRs) differentially activate heterotrimeric G proteins and β-arrestins. Although a wealth of structural knowledge about signaling bias at the GPCR level exists (preferential engagement of a specific transducer), little is known about the bias at the transducer level (different functions mediated by a single transducer), partly due to a poor understanding of GPCR kinase (GRK)-mediated GPCR phosphorylation. Here, we reveal a unique role of the Gq heterotrimer as a determinant for GRK-subtype selectivity that regulates subsequent β-arrestin conformation and function. Using the angiotensin II (Ang II) type-1 receptor (AT1R), we show that β-arrestin recruitment depends on both GRK2/3 and GRK5/6 upon binding of Ang II, but solely on GRK5/6 upon binding of the β-arrestin-biased ligand TRV027. With pharmacological inhibition or genetic loss of Gq, GRK-subtype selectivity and β-arrestin functionality by Ang II is shifted to those of TRV027. Single-molecule imaging identifies relocation of AT1R and GRK5, but not GRK2, to an immobile phase under the Gq-inactive, AT1R-stimulated conditions. These findings uncover a previously unappreciated Gq-regulated mechanism that encodes GRK-subtype selectivity and imparts distinct phosphorylation-barcodes directing downstream β-arrestin functions.


Bone metastases from differentiated thyroid carcinoma: heterogenous tumor response to radioactive Iodine therapy and overall survival.
Bone metastases (BM) from differentiated thyroid carcinoma (DTC) impact negatively the quality of life and the life expectancy of patients. The aim of the study was (a) to evaluate the overall survival (OS) and prognostic factors of OS and (b) to assess predictive factors of complete BM response (C-BM-R) using radioiodine treatment (RAI) either alone or in association with focal treatment modalities. A total of 178 consecutive DTC patients harbouring BM, treated between 1989 and 2015, were enrolled in this retrospective study conducted in two tertiary referral centers. OS analysis was performed for the whole cohort, and only the 145 considered non-RAI refractory patients at BM diagnosis were evaluated for C-BM-R following RAI. The median OS from BM diagnosis was 57 months (IQR: 24-93). In multivariate analysis, OS was significantly reduced in the case of T4 stage, 18FDG uptake by the BM and RAI refractory status. Among the 145 DTC considered non-RAI refractory patients at BM diagnosis, 46 patients (31.7%) achieved a C-BM-R following RAI treatment, either alone in 32 (18%) patients or in association with focal BM treatment modalities in 14. The absence of extra-skeletal distant metastasis and of 18FDG uptake in BM were predictive for C-BM-R. In nearly one-third of DTC patients with RAI avid BM, RAI alone or in combination with BM focal treatment can induce C-BM-R. The presence of 18FDG uptake in BM is associated with an absence of C-BM-R and with a poor OS. 18FDG PET-CT should be performed when BM is suspected.


To Compare the Maternal and Fetal Outcomes of COVID-19-Affected Expectant Mothers During the First and Second COVID-19 Waves: Data From a Tertiary Care Referral Hospital in Punjab.
Coronavirus 2019 (COVID-19) infection, declared pandemic in March 2020 by the World Health Organization, paved the way for newer research in the field of medicine. The second wave, beginning in March 2021, appeared to be more devastating. The purpose of this study is to evaluate the clinical characteristics, effects of COVID-19 infection in pregnancy, and obstetric and perinatal outcomes in the first and second waves. This study was conducted from January 2020 to August 2021 at the Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab. The patients were enrolled immediately after each infected woman was identified as per the inclusion and exclusion criteria. Demographic details of the patients, associated comorbid conditions, intensive care unit (ICU) admission, and treatment details were noted. Neonatal outcomes were recorded. The testing of pregnant women was done as per the Indian Council of Medical Research (ICMR) guidelines. There were 3421 obstetric admissions and 2132 deliveries during this period. Group 1 had 123 COVID-19-positive admissions, while group 2 had 101 admissions. The incidence of COVID-19 infection in pregnancy was 6.54%. In both groups, the majority of patients were between the ages of 21 and 30. About 80(66%) of the admissions in group 1 and 46(46%) in group 2 were in the gestational age of 29-36 weeks. Multiparity was more common in both groups, with 58% of cases in group 1 and 79% of cases in group 2. Obstetric comorbidities were common in both groups, seen in 46% of cases in group 1 and 78% of cases in group 2. The majority of patients were asymptomatic in group 1, with an 89% incidence, whereas only 33% of patients in group 2 were without symptoms. In biological data, D-dimers, prothrombin time, and platelet count were altered in 11%, 14%, and 17% of cases, respectively, in group 2, with almost normal data in group 1. Most cases in group 2 (52%) were critical cases in the moderate and severe categories requiring intensive care unit (ICU) treatment, whereas there was only single ICU admission in group 1. The overall case fatality rate (CFR) in group 2 was found to be 19.8(20/101). Delivery by cesarean section was done in 38.2% of cases in group 1, while in 33% of cases in group 2, with a significant p-value of 0.001. About 29% of cases in group 1 and 34% of cases in group 2 underwent vaginal delivery. The rate of abortion was almost similar in both groups. Only two cases in group 1 and nine cases in group 2 had intrauterine fetal death. Observations of neonatal outcomes suggested that five cases in group 2 and two cases in group 1 had severe birth asphyxia. Only one case in group 1 and four cases in group 2 had positive COVID-19 status. Maternal mortality was significantly higher in group 2 with 20 cases, while only one case was in group 1. Anemia and pregnancy-induced hypertension were the chief comorbidities in this group. COVID-19 infection during pregnancy may be associated with maternal mortality while having a minimal effect on neonatal morbidity and mortality. The possibility of maternal-fetal transmission cannot be ruled out completely. The severity and characteristics of COVID-19 may vary in each wave, and we need to modify treatment strategies. More studies or meta-analyses reports are required to authenticate this transmission.


Genome-Wide Identification, Characterization and Expression Analysis of Soybean CHYR Gene Family.
The CHYR (CHY ZINC-FINGER AND RING FINGER PROTEIN) proteins have been functionally characterized in iron regulation and stress response in Arabidopsis, rice and Populus. However, their roles in soybean have not yet been systematically investigated. Here, in this study, 16 GmCHYR genes with conserved Zinc_ribbon, CHY zinc finger and Ring finger domains were obtained and divided into three groups. Moreover, additional 2-3 hemerythrin domains could be found in the N terminus of Group III. Phylogenetic and homology analysis of CHYRs in green plants indicated that three groups might originate from different ancestors. Expectedly, GmCHYR genes shared similar conserved domains/motifs distribution within the same group. Gene expression analysis uncovered their special expression patterns in different soybean tissues/organs and under various abiotic stresses. Group I and II members were mainly involved in salt and alkaline stresses. The expression of Group III members was induced/repressed by dehydration, salt and alkaline stresses, indicating their diverse roles in response to abiotic stress. In conclusion, our work will benefit for further revealing the biological roles of GmCHYRs.


Individual effects of dietary EPA and DHA on the functioning of the isolated working rat heart.
The aim of this study was to evaluate the effects of dietary pure eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the physiology of the heart in normoxic conditions and during postischemic reperfusion. These effects were compared with those of dietary n-6 polyunsaturated fatty acids (PUFA). Rats were fed a diet containing either sunflower seed oil (75 g x kg(-1), SSO group), or a mixture of EPA (20:5 n-3) ethyl ester and SSO (10:90, EPA group), or a mixture of DHA (22:6 n-3) ethyl ester and SSO (10:90, DHA group), or a mixture of EPA + DHA ethyl esters and SSO (4.2:5.8:90, e+D group) for 6 weeks. The hearts were then perfused according to the working mode. The perfusion was maintained either in normoxic conditions or stopped for 17 min (global zero-flow ischemia) and restored for 33 min (reperfusion). The aortic and coronary flows, aortic developed pressure, and electrocardiogram were continuously monitored. When rats were fed a diet containing either EPA and (or) DHA, the n-6/n-3 PUFA ratio of cardiac phospholipids decreased. The proportion of arachidonic acid was reduced more with DHA than dietary EPA. In the EPA group, the percentage of DHA was lower than in the DHA group, but the percentage of EPA and docosapentaenoic acid (22:5 n-3) was higher. These changes in membrane fatty acid composition altered the cardiac function. In normoxic conditions, the coronary flow was higher in the SSO group than in the DHA and EPA groups. The heart rate was lower in the DHA and e+D groups than in the EPA and SSO groups. The aortic flow, cardiac output, and aortic developed pressure were not affected. During postischemic reperfusion, the recovery of aortic flow, coronary flow, and aortic developed pressure was similar in the four groups. A slightly improved recovery of cardiac function was noticed in the EPA group, but the difference was not significant. Feeding rats 5% fish oil + 5% SSO instead of 10% SSO for 8 weeks increased the incorporation of EPA in cardiac phospholipids and favored the recovery (+120%) of aortic flow during postischemic reperfusion. In conclusion, the beneficial effect of dietary fish oil on the recovery of cardiac pump activity during reperfusion was not observed with DHA or EPA alone. It appears to be positively related to the accumulation of EPA in membrane phospholipids. The dietary conditions favouring EPA accumulation remain to be determined.


The interaction of fungi with dendritic cells: implications for Th immunity and vaccination.
Human beings are continuously exposed to fungi, yet they rarely get fungal diseases. The delicate balance between the host and these otherwise harmless pathogens may turn into a parasitic relationship, resulting in the development of severe infections. The ability to reversibly switch between unicellular and filamentous forms, all of which can be found in infected tissues, is thought to be important for virulence. Efficient responses to the different forms of fungi require different mechanisms of immunity. Dendritic cells (DC) are uniquely able at decoding the fungus-associated information and translating it in qualitatively different T helper (Th) immune responses, in vitro and in vivo. Myeloid DC phagocytosed yeasts and hyphae of Candida albicans and conidia and hyphae of Aspergillus fumigatus, both in vitro and in vivo. Phagocytosis occurred through distinct phagocytic morphologies, involving the engagement and cooperativity of distinct recognition receptors. However, receptor engagement and cooperativity were greatly modified by opsonization. The engagement of distinct receptors translated into disparate downstream signaling events, ultimately affecting cytokine production and costimulation. In vivo studies confirmed that the choice of receptor and mode of entry of fungi into DC was responsible for Th polarization and patterns of susceptibility or resistance to infection. Adoptive transfer of different types of DC activated protective, nonprotective and regulatory T cells, ultimately affecting the outcome of infection. The conclusions are that the selective exploitation of receptors and mode of entry into DC may determine the full range of host's immune relationships with fungi and have important implications in the design of vaccine-based strategies.


Suspected extragonadal germ-cell cancer syndrome presenting with an orbital mass and elevation of serum CEA, CA 19-9 and CA50 levels.
Patients with extragonadal germ-cell cancer syndrome (EGCCS) represent a subgroup of patients with poorly differentiated carcinoma or adenocarcinoma of an unknown primary site for whom potentially curative therapy is available. We report the case of a young man presenting an orbital tumor and high serum levels of CEA, CA 19-9 and CA50 for whom an initial diagnosis of metastatic poorly differentiated carcinoma was made. Suspecting EGCCS, he was treated as for a germ-cell tumor. While in treatment, he underwent residual orbital mass resection, and the histologic diagnosis was embryonal carcinoma based on alpha-fetoprotein immunoperoxidase staining. We discuss the rare location at diagnosis, the impressive increase in the commonly considered gastrointestinal markers that he showed, and the potential utility of these markers for such patients.


Autonomic neuropathy in non-insulin-dependent diabetic patients: correlation with age, sex, duration and metabolic control of diabetes.
The aim of this study has been to assess the prevalence of autonomic neuropathy among non-insulin dependent diabetic patients, and to determine whether a correlation could be found between autonomic impairment and the following: age, sex, duration of diabetes, body mass and metabolic control. Two hundred and twenty one non-insulin dependent patients were submitted to four cardiovascular tests: heart rate response to deep breathing and to standing up; blood pressure response to handgrip and to standing up. Sixty six percent of patients showed at least one abnormal cardiovascular response. The prevalence of autonomic impairment was higher in non-insulin dependent than in insulin-dependent diabetics. Patients were grouped according to the extent of autonomic impairment: absent (33.5%), early (27.6%), definite (3.6%), severe (4.5%). An atypical pattern (abnormality of blood pressure responses in absence of a definite abnormality of heart rate responses) was found in 30.8% of patients. Heart rate responses correlated significantly with age (p less than 0.001). No correlation between test results and duration was found in the multivariate analysis. The tests' results did not correlate with metabolic control or body mass index. Patients with symptoms of autonomic neuropathy had values for heart rate response to deep breathing and to standing significantly lower than those without (p less than 0.05).


The time window for the reversal of depigmentation from aggravation to recovery in a non-small-cell lung cancer patient with pre-existing vitiligo using anti-programmed cell death-1 therapy: A case report.
Immune checkpoint inhibitors have made remarkable breakthroughs in the treatment of lung cancer, bringing significant survival benefits to the patients. A number of adverse events aggravated by immunotherapy in patients with pre-existing autoimmune diseases have been reported in the past, especially skin toxicity, such as rash, pruritus, erythema, and vitiligo. However, whether the exacerbated autoimmune disease is reversible and when it will return to its original state after immunotherapy discontinuation is still inconclusive. In our report, we described a patient diagnosed with non-small cell lung cancer whose vitiligo was stable for about 10 years. We followed up and observed the patient's skin depigmentation for the complete time window, from aggravation of application anti-programmed cell death-1 receptor antibody (anti-PD-1 antibody) to recovery after the withdrawal. We presented the objective images at particular time points using reflectance confocal microscopy and wood's light. We found that the use of anti-PD-1 antibody aggravated in skin toxicity, but it was reversible, the time window from the beginning to recovery status was approximately 9 months. We used this real case scenario to explain the relationships between immunotherapy and autoimmune diseases.


Ultrasound-guided percutaneous radiofrequency ablation of small renal tumors: Clinical results and radiological evolution during follow-up.
Treatment of small renal masses with percutaneous radiofrequency ablation (RFA) is under development. Data are limited regarding the oncologic efficacy and complication rates of ultrasound (US)-guided RFA. To retrospectively analyze results and factors predictive of incomplete ablation and local recurrence in patients treated for small renal tumors with US-guided percutaneous RFA. Forty-one consecutive patients (27 males), mean 70 (40-86) years, with 44 tumors were included. Core biopsies were obtained before treatment. Follow-up was performed with CT or MRI. Tumor diameter, tumor volume, volume of the ablation zone, necrosis index, tumor location, distance from tumor to skin, and BMI were analyzed. Biopsies showed malignancy in 72%, 10% were benign, and 18% were inconclusive. Thirty-six tumors (82%) were completely ablated after first RFA and 40 tumors (91%) after a second treatment. Mean follow-up was 27 months. Nine completely ablated tumors (23%) showed local recurrence during follow-up, six of them were retreated. Tumor size was significantly larger and mean necrosis index lower in tumors with incomplete ablation compared with those completely ablated initially. In tumors <30 mm, the initial complete ablation rate was 93% and the local recurrence rate during follow-up was 16% (4/25). US guidance is feasible for RFA of small renal tumors. However, thorough long-term follow-up appears mandatory, as a substantial proportion of the patients will develop late local recurrence and will need more than one RFA treatment session. Large tumor diameter and volume and a low necrosis index were predictive indicators of incomplete ablation after the first treatment.


Water temperature, voluntary drinking and fluid balance in dehydrated taekwondo athletes.
Voluntary drinking is one of the major determiners of rehydration, especially as regards exercise or workout in the heat. The present study undertakes to search for the effect of voluntary intake of water with different temperatures on fluid balance in Taekwondo athletes. Six young healthy male Taekwondo athletes were dehydrated by moderate exercise in a chamber with ambient temperature at 38-40°C and relative humidity between 20-30%. On four separate days they were allowed to drink ad libitum plane water with the four temperatures of 5, 16, 26, and 58°C, after dehydration. The volume of voluntary drinking and weight change was measured; then the primary percentage of dehydration, sweat loss, fluid deficit and involuntary dehydration were calculated. Voluntary drinking of water proved to be statistically different in the presented temperatures. Water at 16°C involved the greatest intake, while fluid deficit and involuntary dehydration were the lowest. Intake of water in the 5°C trial significantly correlated with the subject's plasma osmolality change after dehydration, yet it showed no significant correlation with weight loss. In conclusion, by way of achieving more voluntary intake of water and better fluid state, recommending cool water (~16°C) for athletes is in order. Unlike the publicly held view, drinking cold water (~5°C) does not improve voluntary drinking and hydration status. Key pointsFor athletes dehydrated in hot environments, maximum voluntary drinking and best hydration state occurs with 16°C water.Provision of fluid needs and thermal needs could be balanced using 16°C water.Drinking 16°C water (nearly the temperature of cool tap water) could be recommended for exercise in the heat.


Models of cervical screening in the era of human papillomavirus vaccination.
Epidemiologic and economic evaluation using simulation modelling can support complex policy decisions, and is an important tool in predicting the future interaction between human papillomavirus vaccination and cervical screening. Several categories of screening program evaluation are of interest, including: (1) changes to screening considered over the short term, over which the effects of vaccination should be confined to the youngest age groups (<30 years old); (2) the medium and long-term effect of vaccination on the screening program; and (3) changes to screening in context of vaccination. This review considers some of the policy questions in each category and discusses the modelling implications, with particular focus on the Australian context.


Developing performance-appraisal systems.
The development and applications of performance-appraisal systems for hospital pharmacy personnel are discussed. The need for a performance-appraisal system is explained from the perspectives of the employee, the manager, and the hospital. Ethical standards that should be considered by managers during the appraisal process are listed. Performance standards are a key component of a performance-appraisal system and should be developed jointly by management and staff. Types of appraisal methods, personnel who should conduct appraisals, and the frequency at which appraisals should be conducted are discussed. Potential biases in appraisal methods and the preparation for and conduct of employee appraisals are discussed. A performance-appraisal system should be designed to meet the needs of employees, managers, and the hospital. Such a system will be more effective if it ensures the regular, frequent flow of data on employee performance, the systematic comparison of these data with previously agreed-upon expectations, and the frequent reporting of the results of these comparisons to both employees and managers.


Differentiation-inducing factor for a human leukemic cell line produced by colony-stimulating factor producing human lung cancer tissue.
We have found that medium conditioned by a colony-stimulating factor producing tumor derived from a granulocytosis case with lung cancer contained a factor to differentiate a human promyelocytic leukemic cell line (HL-60) to macrophage-like cells that were butyrate esterase-positive and had phagocytosing activity and membrane Fc receptors. This differentiation-inducing factor was not active for a human myeloblastic cell line (KG-1), and was separated from a colony-stimulating factor by its molecular weight and isoelectric point. The conditioned medium did not contain a detectable amount of gamma interferon when tested by bioassay as well as by radioimmunoassay. This is the first report that a human lung cancer tissue produces not only a colony-stimulating factor, but also a differentiation-inducing factor. The conditioned medium is considered to be a good source of differentiation-inducing factor.


Pull Incentives for Antibacterial Drug Development: An Analysis by the Transatlantic Task Force on Antimicrobial Resistance.
New alternative market models are needed to incentivize companies to invest in developing new antibacterial drugs. In a previous publication, the Transatlantic Task Force on Antimicrobial Resistance (TATFAR) summarized the key areas of consensus for economic incentives for antibacterial drug development. That work determined that there was substantial agreement on the need for a mixture of push and pull incentives and particularly those that served to delink the revenues from the volumes sold. Pull incentives reward successful development by increasing or ensuring future revenue. Several pull incentives have been proposed that could substantially reward the development of new antibacterial drugs. In this second article authored by representatives of TATFAR, we examine the advantages and disadvantages of different pull incentives for antibacterial drug development. It is TATFAR's hope that this analysis, combined with other related analyses, will provide actionable information that will shape policy makers' thinking on this important issue.


Anti-miR-21 oligonucleotide enhances chemosensitivity of leukemic HL60 cells to arabinosylcytosine by inducing apoptosis.
Drug insensitivity or resistance is a major obstacle for successful treatment of acute myeloid leukemia. MicroRNAs (miRNAs) are small non-coding RNA molecules. Increasing evidence suggests that miRNAs modulate cellular sensitivity to anticancer drugs. We used a specific anti-miR-21 oligonucleotide (AMO-miR-21) to sensitize leukemic HL60 cells to arabinosylcytosine (Ara-C) by down-regulating miR-21. AMO-miR-21 alone effectively inhibited HL60 cell viability as measured by MTT assays and induced apoptosis as evaluated by flow cytometry, whereas AMO-miR-21 in combination with Ara-C enhanced HL60 cells to Ara-C-sensitivity and promoted Ara-C-induced apoptosis. Levels of miR-21 and its target PDCD4, quantified by real-time PCR, showed that expression of miR-21 was significantly decreased after AMO-miR-21 treatment. PDCD4 as a direct target of miR-21 in leukemic HL60 cells was confirmed by the dual-luciferase reporter assay. Our study suggests that AMO-miR-21 significantly sensitizes HL60 cells to Ara-C by inducing apoptosis and these effects of AMO-miR-21 may be partially due to its up-regulation of PDCD4. Therefore, exploiting synergistic effects between AMO-miR-21 and Ara-C might be an effective clinical strategy for leukemia chemotherapy.


Effects of subtoxic concentrations of benzoyl peroxide on cell lipid metabolism.
Benzoyl peroxide (BP), a tumor promoter, has been shown to cause free-radical-induced lipid peroxidation and membrane damage at toxic concentrations. However, its effects on lipid metabolism at concentrations that were not overtly toxic have not been investigated. The purpose of the current study was to examine the effects of BP and its final degradation product, benzoic acid (BA), on lipid metabolism. Two cell lines, hamster cheek pouch (HCP) and human monocytes (THP-1), were used to determine the effects of BP, BA, and BP combined with FeCl2 on cell lipid metabolism. Cells were exposed to BP and 14C acetate for 24 h, or cells with prelabeled lipids were harvested, and the lipids were extracted and separated with the use of thin-layer chromatography. Lipid metabolism of some neutral lipids such as triglycerides was altered for both cell types in response to BP. Also, cholesterol content was reduced in THP-1 cells and a phospholipid, phosphatidylethanolamine (PE), was reduced in HCP cells. The final degradation product of BP, BA, failed to elicit any response in lipid metabolism. Subtoxic concentrations of BP induced changes in neutral lipids such as triglycerides and cholesterol. The metabolism of major phospholipids except PE remained unchanged. The effects were related to BP and its degradation and varied with the cell type.


The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue.
Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a broad spectrum of symptoms, including headache. A simple, yet powerful tool - the pain drawing identifies essential aspects such as pain distribution. The aim with this study was to 1) evaluate the significance of pain drawing as a screening tool for cervicogenic headache using a predefined C2 pain pattern, 2) assess whether there was an association between dizziness/imbalance and a C2 pain pattern, and 3) compare subgroups according to the pain drawing with respect to pain characteristics and quality of life. Pain drawings and clinical data from 275 patients investigated for ME/CFS were stratified into: 1) cervicogenic headache as determined by a C2 pain pattern, 2) headache with no C2 pain pattern, and 3) no headache. For inference logistic regression presented with odds ratios (OR) and 95% confidence intervals (95% CI) and Kruskal-Wallis test were applied. One hundred sixteen participants (42%) were stratified to the group for which the pain drawing corresponded to the C2 pain pattern, thus indicating putative cervicogenic origin of the headache. Dizziness/imbalance was strongly associated with a C2 pain pattern; OR 6.50 ([95% CI 2.42-17.40] p ˂ 0.00), whereas this association was non-significant for patients with headache and no C2 pain pattern. Those demonstrating a C2 pain pattern reported significantly higher pain intensity (p = 0.00) and greater pain extent (p = 0.00) than the other groups, and lower health-related quality of life (p = 0.00) than the group with no headache. For patients with chronic fatigue who present with a C2 pain pattern (interpreted as cervicogenic headache) the pain drawing seems applicable as a screening tool for signs associated with neuropathic and more severe pain, dizziness and reduced quality of life as detection of these symptoms is essential for targeted treatment.


[Interpretation of QFT results in several contact investigations].
QuantiFERON TB-2G (QFT-2G) is now widely used for contact investigations, as QFT-2G is not affected by BCG vaccination, whereas the conventional tuberculin skin test (TST) is confounded by BCG vaccination. We applied the QFT-2G tests to numerous contact investigations and found that the majority of contacts who had been supposed to be infected with M. tuberculosis (Mtb) based on TST were negative in the QFT-2G tests, strongly suggesting the possibility that the unnecessary preventive chemotheraphy was indicated for many TST positive contacts due to BCG vaccination in conventional contact investigations. Although QFT-2G positive results implicate that Mtb in certain active phases presents in the body, when Mtb had been infected cannot be decided by QFT-2G. Therefore, QFT-2G results should be carefully interpreted, especially in elder persons who had been exposed to Mtb in the past in Japan. Furthermore, since there were some active TB cases in QFT-2G negative contacts, attention must be paid for QFT-2G negative contacts in highly exposed groups. In this paper, I will discuss about current usages of QFT-2G based on our experiences of contact investigations.


Short communication: Effect of age at group housing on behavior, cortisol, health, and leukocyte differential counts of neonatal bull dairy calves.
To determine the effect of age at grouping on behavior, health, and production of dairy bull calves, 90 Holstein-Friesian bull calves were housed in individual pens until moved to 1 of 3 treatments. Calves were housed in groups of 3 calves at 3 d old (GH3), 7 d old (GH7), or 14 d old (GH14) until 7 wk of age. Ten groups of 3 calves for each treatment were used, with 5 pens/treatment in each of 2 replications (10 pens/treatment, 3 treatments, 3 calves/treatment; 90 calves total). Direct behavioral observations using instantaneous scan sampling every 10 min were conducted twice per week for 7 wk. At the same times, video data were recorded for continuous observations at feeding time to observe the overall activity of group-housed calves. Hip height, heart girth, and health scores were recorded weekly and body weight was recorded at the start and end of the study. Calves in GH3 spent more time playing and but more time cross-sucking and displacing other calves from milk bottles. Calves engaged in social interaction as early as 3 d of age, and social interactions between 3 to 6 wk of age increased markedly. Calves housed in GH14 vocalized more than did calves in GH7 and GH3. No difference was found between treatments in growth performance. Calf fecal, cough, and nasal and ocular discharge scores, differential leukocyte counts, and plasma cortisol concentrations were not affected by age at grouping. However, during the first week of grouping, when calves were moved from individual pens to group pens, some calves were unable to find their milk bottles and required guidance. In conclusion, these data show no adverse effects on health or performance and some benefits on social behavior for early (d 3) grouping of calves.


Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells.
The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation. To further eliminate contaminating cells, the capillary fragments were cultured with puromycin-containing medium. When 60-95% confluent, pBECs growing from the capillary fragments were passaged to permeable membrane filter inserts and established in the models. To increase barrier tightness and BBB characteristic phenotype of pBECs, the cells were treated with the following differentiation factors: membrane permeant 8-CPT-cAMP (here abbreviated cAMP), hydrocortisone, and a phosphodiesterase inhibitor, RO-20-1724 (RO). The procedure was carried out over a period of 9-11 days, and when establishing the NCC model, the astrocytes were cultured 2-8 weeks in advance. Adherence to the described procedures in the protocol has allowed the establishment of endothelial layers with highly restricted paracellular permeability, with the NCC model showing an average transendothelial electrical resistance (TEER) of 1249 ± 80 Ω cm2, and paracellular permeability (Papp) for Lucifer Yellow of 0.90 10-6 ± 0.13 10-6 cm sec-1 (mean ± SEM, n=55). Further evaluation of this pBEC phenotype showed good expression of the tight junctional proteins claudin 5, ZO-1, occludin and adherens junction protein p120 catenin. The model presented can be used for a range of studies of the BBB in health and disease and, with the highly restrictive paracellular permeability, this model is suitable for studies of transport and intracellular trafficking.


Almotriptan, a new anti-migraine agent: a review.
Almotriptan is a new anti-migraine agent with nanomolar affinity for human 5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors, weak affinity for 5-HT(1A) and 5-HT(7) receptors and no significant affinity for more than 20 other pharmacological receptors. Almotriptan was effective in animal models predictive of anti-migraine activity in humans and had a good safety profile in animal studies. From the toxicological point of view, almotriptan has a profile similar to that of other marketed triptans. In animal studies, at levels substantially higher than required for therapeutic activity in humans, almotriptan was devoid of any oncogenic, genotoxic or teratogenic effects. Almotriptan is well absorbed orally; its absolute bioavailability in humans is 70%. Its peak plasma levels are reached at 1 to 3 h after its administration; its elimination half-life is 3 to 4 h. Almotriptan is metabolized by monoamine oxidase-mediated oxidative deamination and cytochrome P450-mediated oxidation as the major metabolic route and by flavin monooxygenase as the minor route. No dose adjustment is required for gender or age, and only in the case of severe renal impairment the dose should not exceed 12.5 mg over a 24-h period. There was no significant interaction between a single dose of almotriptan and propranolol, fluoxetine or verapamil, at multiple doses. The efficacy of almotriptan in the treatment of acute migraine was demonstrated in clinical trials on more than 3000 patients with migraine. At two h after oral administration of almotriptan, 12.5 mg, the percentages of patients showing pain relief and a pain-free score were 64 and 36%, respectively. The effects of almotriptan were significantly better than those of placebo. When almotriptan was administered in the early phase of migraine, the percentage of pain-free patients at 2 h rose to 84%. In a phase III, double-blind and placebo-controlled study, the incidence of adverse events with almotriptan was not statistically different from that of placebo. Based on the available data, it appears that almotriptan is the triptan of choice when good efficacy and high tolerability are desired.


Contextual interference effects in sequence learning for young and older adults.
Practice of different tasks in a random order induces better retention than practicing them in a blocked order, a phenomenon known as the contextual interference (CI) effect. Our purpose was to investigate whether the CI effect exists in sequence learning, such that practicing different sequences in a random order will result in better learning of sequences than practicing them in blocks, and whether this effect is affected by aging. Subjects practiced a serial reaction time task where a set of three 4-element sequences were arranged in blocks or in a random order on 2 successive days. Subjects were divided into 4 groups based on a 2-GROUP (young or old) by 2-ORDER (random or blocked practice) between-subject design. Three days after practice (Day 5), subjects were tested with practiced and novel sequences to evaluate sequence-specific learning. The results replicate the CI effect in sequence learning in both young and older adults. Older adults retained sequences better when trained in a random condition than in a blocked condition, although the random condition incurs greater task switching costs in older adults during practice. Our study underscores the distinction between age-related effects on learning vs. performance, and offers practical implications for enhancing skill learning in older adults.


Photosynthetic enhancement studied in intact spinach chloroplasts.
The Emerson enhancement effect was evaluated in the intact spinach (Spinacia oleracea var. Long Standing Bloomsdale) chloroplast by monitoring the uptake of (14)CO(2) during illumination by 640 nm and 720 nm lights. Low levels (about 10 mum) of fructose 1,6-diphosphate, ribose 5-phosphate, and glycerate 3-phosphate stimulated the rate of photosynthesis and abolished enhancement values observed in their absence. Concentrations of the two sugar phosphates at levels of 1 mm responded similarly. In contrast, 1 mm glycerate 3-phosphate inhibited the rate of photosynthesis and increased enhancement. The exchange of glycerate 3-phosphate for glyceraldehyde 3-phosphate was speculated to be a factor underlying the decrease in photosynthesis and the increase in enhancement. Glucose 6-phosphate, NADPH, and l-malate did not influence photosynthesis or enhancement.The uncoupler, p-trifluoromethoxyphenylhydrazone, decreased the rate of photosynthesis but did not change the enhancement values. ATP (0.2 to 1 mm) had an occasional stimulating effect on CO(2) fixation but no effect on enhancement. Magnesium ions inhibited photosynthesis and decreased the enhancement values. It was concluded that the enhancement phenomenon reflects events of the photosynthetic carbon reduction cycle as well as the photochemical act.


[The complexity of the implementation of an observation and tracking chart for critical illness].
Critically ill patients on wards are identified too late. At Aarhus University Hospital, Aarhus Sygehus, staff did not act appropriate to unacceptable values. The solution presented is development and implementation of a Track and Trigger System: a standardised observation chart encompassing frequency of vital signs measurement combined with a decision algorithm based on scores dictating skill level of decision-making. Educational programmes and specialist function for ward staff as well as action cards containing identification, situation, background, analysis, and advice and an airway, breathing, circulation, disability and environment approach to support clinical decision-making are introduced.


Competing for foreign aid for health development.
Health ministries in low-income countries faced with the problem of decreasing financial support from traditional external sources are taking steps to become more competitive in the "market" for foreign aid. This article describes some strategies that have enabled ministries to obtain external financing for their health development priorities, thereby improving the quality and increasing the quantity of aid they receive.


Validation of the Shedler-Westen Assessment Procedure Insight Scale.
In this cross-sectional study, we compare the Shedler-Westen Assessment Procedure (SWAP) Insight Scale scores in three groups of psychoanalytic patients. Psychoanalysts completed the SWAP to describe a real patient at the beginning of analysis, a real patient at the end of analysis, or a hypothetical ideal patient at the end of a successful analysis. The SWAP Insight Scale scores were lowest for the patients at the beginning of analysis and highest for the hypothetical patients at the ideal end of analysis. Further, the correlations between the SWAP Insight Scale and Global Assessment of Functioning scores were not significant at the beginning of analysis and were significant at the end of analysis. The data provide support for the known groups and convergent validity of the SWAP Insight Scale.


Dissecting the indirect effects caused by vaccines into the basic elements.
Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes.


Singlet nuclear magnetic resonance.
Nuclear singlet states may have lifetimes that are much longer than the conventional relaxation time of nuclear spin magnetization. This review covers how these states may be generated, observed, and exploited in solution nuclear magnetic resonance (NMR). Potential applications include the study of slow molecular processes, the elucidation of molecular geometry, and the transport of hyperpolarized nuclear spin order.


[Neuropathological aspects of normal and abnormal aging].
Several senile changes in the central nervous system in cadavers were examined. The pattern of extension of Alzheimer's neurofibrillary tangles (NFT) and senile plaques (SP) in the olfactory bulbs of 100 specimens was examined during routine autopsy by immunohistochemical staining. NFT were first observed in the anterior olfactory nucleus after the age of 60, and incidence rose with increasing age. Senile plaques were found in the nucleus when there were many SP in the cerebral cortex. Of 25 non-demented amyotrophic lateral sclerosis patients, SP were found in the cerebral cortices of 10, and 9 of 10 were over 60 years old. NFT were observed in almost all patients over 60 years of age, but the incidence was low. Many ubiquitin-positive small-sized granules were observed in the second and third layer of the parahippocampal gyrus of aged patients, and the incidence rose with increasing age. On the other hand, few of these granules were in patients with Alzheimer's type dementia. Granulovacuolar degeneration was examined. Many centrally-located granules were positive for ubiquitin. Based on electron microscopic observation of these granules at several stages, the granules were thought to be a type of autophagosome. During the first stage of granulovacuolar degeneration, electron-dense materials appeared in the cytoplasm, following which they were surrounded by smooth endoplasmic reticulum. Analytical electron microscopy disclosed that the granules contained some aluminium.


Electric modulation of conduction in multiferroic Ca-doped BiFeO3 films.
Many interesting materials phenomena such as the emergence of high-Tc superconductivity in the cuprates and colossal magnetoresistance in the manganites arise out of a doping-driven competition between energetically similar ground states. Doped multiferroics present a tantalizing evolution of this generic concept of phase competition. Here, we present the observation of an electronic conductor-insulator transition by control of band-filling in the model antiferromagnetic ferroelectric BiFeO3 through Ca doping. Application of electric field enables us to control and manipulate this electronic transition to the extent that a p-n junction can be created, erased and inverted in this material. A 'dome-like' feature in the doping dependence of the ferroelectric transition is observed around a Ca concentration of approximately 1/8, where a new pseudo-tetragonal phase appears and the electric modulation of conduction is optimized. Possible mechanisms for the observed effects are discussed on the basis of the interplay of ionic and electronic conduction. This observation opens the door to merging magnetoelectrics and magnetoelectronics at room temperature by combining electronic conduction with electric and magnetic degrees of freedom already present in the multiferroic BiFeO3.


A 31-bp indel in the 5' UTR region of GNB1L is significantly associated with chicken body weight and carcass traits.
G-protein subunit beta 1 like (GNB1L) encodes a G-protein beta-subunit-like polypeptide. Chicken GNB1L is upregulated in the breast muscle of high feed efficiency chickens, and its expression is 1.52-fold that in low feed efficiency chickens. However, no report has described the effects of GNB1L indels on the chicken carcass and growth traits. This study identified a 31-bp indel in the 5' untranslated region (UTR) of GNB1L and elucidated the effect of this gene mutation on the carcass and growth traits in chickens. The 31-bp indel showed a highly significant association with the body weight at 8 different stages and was significantly correlated with daily gains at 0 to 4 weeks and 4 to 8 weeks. Similarly, the mutation was significantly associated with small intestine length, breast width, breast depth and breast muscle weight. Moreover, DD and ID were superior genotypes for chicken growth and carcass traits. These results show that the 31-bp indel of GNB1L significantly affects chicken body weight and carcass traits and can serve as a candidate molecular marker for chicken genetics and breeding programs.


Analytical condition setting a crucial step in the quantification of unstable polyphenols in acidic conditions: analyzing prenylflavanoids in biological samples by liquid chromatography-electrospray ionization triple quadruple mass spectrometry.
The interest in studying hops and beer prenylflavanoids, isoxanthohumol, xanthohumol, and 8-prenylnaringenin, has increased in recent years due to their biological activity as strong phytoestrogens and potent cancer chemopreventive agents. However, prenylflavanoids behave differently from most polyphenols, since they are unstable at acidic pH. To our knowledge, no published studies to date have considered the degradation of these compounds during analytical processes. In the present work, a new sensitive and specific method based on solid phase extraction and liquid chromatography coupled to electrospray ionization triple quadruple mass spectrometry (LC-ESI-MS/MS) was developed and validated. The new method was optimized to avoid degradation of the selected analytes, isoxanthohumol, xanthohumol, and 8-prenylnaringenin, throughout the analytical process and to reduce the urine matrix effect in LC-ESI-MS/MS assays. It was concluded that a neutral pH (pH 7.0) is necessary for the analysis of prenylflavanoids, in order to maintain the stability of compounds for at least 24 h. The addition of ascorbic acid to the media improved stability, calibration curves, coefficients of correlation, accuracy, and precision parameters. Mix-mode cation exchange sorbent yielded the best matrix effect factors and recoveries. Method validation results showed appropriate intraday and interday accuracy and precision (<15%). Recovery of isoxanthohumol, xanthohumol, and 8-prenylnaringenin was 97.1% ± 0.03, 105.8% ± 0.05, and 105.4% ± 0.04, respectively, and matrix effect factors were nearly 100%. The stability assay showed that analytes were stable for at least 24 h. The method was applied to quantify 10 human samples of urine and was able to quantify prenylflavanoids in urine after the consumption of a single dose of beer (330 mL).


Acamprosate suppresses ethanol-induced place preference in mice with ethanol physical dependence.
The present study investigated the effect of acamprosate on ethanol (EtOH)-induced place preference in mice with EtOH physical dependence. The expression of EtOH (2 g/kg, intraperitoneally)-induced place preference in mice without EtOH treatment before the experiment was dose-dependently suppressed by acamprosate. The levels of protein kinase A (PKA) and phospho-cAMP response element binding protein (p-CREB) in the limbic forebrain after EtOH-conditioning in naïve mice was unchanged. Furthermore, mice on the 4th day of withdrawal from continuous EtOH vapor inhalation for 9 days showed transient and significant enhancement of EtOH (1 g/kg, intraperitoneally)-induced place preference, which was significantly suppressed by acamprosate (300 mg/kg, oral administration; p.o., once a day) administered daily for 3 days after withdrawal from EtOH inhalation and during EtOH-conditioning. PKA and p-CREB proteins in the limbic forebrain of EtOH-conditioned mice on 4th day of withdrawal from continuous EtOH inhalation for 9 days significantly increased, which were completely abolished by acamprosate. These findings suggest that the signal transduction pathway via the PKA-p-CREB pathway in the limbic forebrain may be functionally related to the development of sensitization of EtOH-induced place preference and provide a possible molecular basis for the pharmacological effect of acamprosate to prevent or reduce the relapse of alcohol dependence.


[Comparison of endoscopic aspects and cytohistological patterns in primary lung neoplasia].
Four-hundred and thirty-six patients recognized affected by primitive lung neoplasia have been examined to prove possible correlation between the endoscopic aspects, histologic type and central or peripheral localization of the neoplasia. The diagnostic sensibility of the different cytohistological techniques used in fiberoptic bronchoscopy have been valued too. For the peripheral localizations the diagnosis has been obtained in most cases by using fine needle percutaneous aspiration.


Pancreatic secretory trypsin inhibitor stimulates the growth of rat pancreatic carcinoma cells.
Pancreatic secretory trypsin inhibitor was examined for growth-promoting activity on five cell lines using standard cell culture techniques. One cell line, AR4-2J, derived from a rat pancreatic acinar cell carcinoma, responded with significantly increased incorporation of [3H]thymidine and colony formation. Pancreatic secretory trypsin inhibitor stimulated the incorporation of [3H]thymidine in liquid culture; the maximal increase was 61 +/- 10% above control (P less than 0.001) and was seen at a concentration of 10(-9) mol/L. Using a soft agarose clonogenic assay, pancreatic secretory trypsin inhibitor also consistently stimulated (3 assays) colony formation: the peak activity occurred at a concentration of 10(-10) mol/L which caused a 150 +/- 55% (mean +/- SE, P less than 0.05) increase above control. Aprotinin had no effect on the growth of AR4-2J cells and pancreatic secretory trypsin inhibitor did not bind to the epidermal growth factor receptor. AR4-2J cells were shown to produce pancreatic secretory trypsin inhibitor. The study raises the possibility that pancreatic secretory trypsin inhibitor provides autocrine stimulation of tumor cell growth.


Next-generation epidemiology: the role of high-resolution molecular phenotyping in diabetes research.
Epidemiologists have for many decades reported on the patterns and distributions of diabetes within and between populations and have helped to elucidate the aetiology of the disease. This has helped raise awareness of the tremendous burden the disease places on individuals and societies; it has also identified key risk factors that have become the focus of diabetes prevention trials and helped shape public health recommendations. Recent developments in affordable high-throughput genetic and molecular phenotyping technologies have driven the emergence of a new type of epidemiology with a more mechanistic focus than ever before. Studies employing these technologies have identified gene variants or causal loci, and linked these to other omics data that help define the molecular processes mediating the effects of genetic variation in the expression of clinical phenotypes. The scale of these epidemiological studies is rapidly growing; a trend that is set to continue as the public and private sectors invest heavily in omics data generation. Many are banking on this massive volume of diverse molecular data for breakthroughs in drug discovery and predicting sensitivity to risk factors, response to therapies and susceptibility to diabetes complications, as well as the development of disease-monitoring tools and surrogate outcomes. To realise these possibilities, it is essential that omics technologies are applied to well-designed epidemiological studies and that the emerging data are carefully analysed and interpreted. One might view this as next-generation epidemiology, where complex high-dimensionality data analysis approaches will need to be blended with many of the core principles of epidemiological research. In this article, we review the literature on omics in diabetes epidemiology and discuss how this field is evolving. Graphical abstract.


Effect of Frying Process on Nutritional Property, Physicochemical Quality, and in vitro Digestibility of Commercial Instant Noodles.
The effects of frying process on the nutritional property, physicochemical quality, and in vitro digestibility of instant noodle products are investigated in this study. Scanning electron microscope (SEM) and Fourier transform infrared spectrometer (FT-IR) were also used to explore the changes in the microstructure and protein transformation. Noodles, after the frying process, showed a lower proportion of carbohydrate, protein, fiber, and also total starch and digestible starch, but higher content of fat and resistant starch in the proximate analysis. The frying process was also considered to improve the texture, surface color, and sensory properties of instant noodle products, accompanied by better cooking quality, including shorter cooking time and lower cooking loss during the rehydration. The honeycomb-like, porous, and less uniformed structure, and also the higher levels of β-sheets and β-turns, and the lower proportion of α-helixes of protein structure from fried instant noodle was also observed. The in vitro digestibility of starch and protein were downregulated in the fried group (81.96% and 81.31, respectively, on average) compared with the non-fried group (97.58% and 88.78, respectively, on average). Thus, the frying process lowered the glycemic index and regulated protein secondary structure by inhibiting continuous digesting enzyme activity, generating starch-lipid complexes, and changing the levels of protein transformation. In conclusion, our findings will provide an innovative evaluation of the frying process on instant noodles and even other various starch-based prepared food products.


Viruses and oral cancer.
Oral cancer is a disease with a complex etiology. There is evidence for important roles of smoking, drinking, and genetic susceptibility, as well as strong indications that DNA viruses could be involved. The herpes simplex virus type 1 has been associated with oral cancer by serological studies, and animal models and in vitro systems have demonstrated that it is capable of inducing oral cancer. Papillomaviruses are found in many oral cancers and are also capable of transforming cells to a malignant phenotype. However, both virus groups depend on co-factors for their carcinogenic effects. Future research on viruses and oral cancer is expected to clarify the role of these viruses, and this will lead to improvements in diagnosis and treatment of the disease.


[Effects of diphenyliodonium on the degree of conversion and the compressive strength of composite resin].
The degree of conversion (DC) and the compressive strength (CS) are important indexes of composite resin. This study is aimed to investigate the effects of diphenyliodonium on the DC and the CS of the light-curing composite resin. Different amount of diphenyliodonium hexaflourophosphate was added to the light-curing composite resin; the concentrations of diphenyliodonium hexaflourophosphate were 0 wt%, 0.5 wt%, 1.0 wt%, 2.0 wt%, 3.0 wt% and 4.0 wt% of the reisin matrix (containing BisS-GMA and TEGDMA) respectively. The DC and the CS of the six aforementioned groups of the composite resin were measured by the Fourier transform infrared spectroscopy and the tensile strength of machine, respectively. Diphenyliodonium hexaflourophosphate can improve the DC and CS of the light-curing composite resin. When the concentration is 2.0 wt%, the DC and CS can achieve better performance.


Combination of density gradient centrifugation and swim-up methods effectively decreases morphologically abnormal sperms.
Density gradient centrifugation (DGC) and swim-up techniques have been reported for semen preparation in assisted reproductive techniques in humans. We investigated whether semen preparation using a combination of DGC and swim-up techniques could effectively decrease morphologically abnormal human sperms at the ultrastructural level. Semen samples were obtained from 16 infertile males and fractionated by swim-up following DGC. Ultrastructural abnormalities of sperms obtained from original semen, lower layer of swim-up following DGC, and upper layer of swim-up following DGC were analyzed by transmission electron microscopy. The correlation among ultrastructural head abnormality in sperms from the upper layer of swim-up, fertilization in in vitro fertilization, and pregnancy after embryo transfer was also investigated. Furthermore, sperms with DNA fragmentation in the samples processed via a combination of DGC and swim-up was assessed in a sperm chromatin structure assay. Ultrastructural abnormalities in sperm heads and tails in the upper layer after swim-up following DGC was the lowest among the three groups. Sperms with nuclear vacuoles were the most difficult to eliminate using a combination of DGC and swim-up in all types of head abnormalities. A negative correlation was confirmed between the fertilization rates of intracytoplasmic sperm injection and head abnormality of sperms obtained from the upper layer of the swim-up following DGC. Sperms with DNA fragmentation were effectively decreased using the combination of two techniques. In conclusion, the combination of DGC and swim-up effectively decreased the number of sperms with ultrastructural abnormalities both in the head and in the tail. However, sperms with ultrastructural abnormalities that cannot be completely decreased using a combination of DGC and swim-up may impair fertilization in some cases of intracytoplasmic sperm injection.


Epigenetic mechanisms linking diabetes and synaptic impairments.
Diabetes is one of the major risk factors for dementia. However, the molecular mechanism underlying the risk of diabetes for dementia is largely unknown. Recent studies revealed that epigenetic modifications may play a role in the pathogenesis of diabetes. We hypothesized that diabetes may cause epigenetic changes in the brain that may adversely affect synaptic function. We found significant elevation in the expression of histone deacetylases (HDACs) class IIa in the brains of diabetic subjects compared with control subjects, and these changes coincide with altered expression of synaptic proteins. In a mouse model of diet-induced type 2 diabetes (T2D), we found that, similar to humans, T2D mice also showed increased expression of HDAC IIa in the brain, and these alterations were associated with increased susceptibility to oligomeric Aβ-induced synaptic impairments in the hippocampal formation and eventually led to synaptic dysfunction. Pharmacological inhibition of HDAC IIa restored synaptic plasticity. Our study demonstrates that diabetes may induce epigenetic modifications affecting neuropathological mechanisms in the brain leading to increased susceptibility to insults associated with neurodegenerative or vascular impairments. Our study provides, for the first time, an epigenetic explanation for the increased risk of diabetic patients developing dementia.


[Kanji-predominant alexia with agraphia in opticospinal multiple sclerosis].
Alexia with agraphia is very rare symptom in multiple sclerosis. We present a patient of opticospinal multiple sclerosis with kanji-predominant alexia with agraphia. A 55-year-old, right-handed man was admitted to our hospital because of difficulty in reading and writing in August 2001. The patient had been diagnosed as having relapsing-remitting opticospinal multiple sclerosis eight years prior to admission. Language examination showed alexia with agraphia predominantly affecting kanji and also mild naming difficulties, but a good comprehension and a normal repetition. T2-weighted MRI demonstrated hyperintensity area in the left temporo-parietal lobe, involving the white matter beneath the postero-inferior temporal lobe and inferior parietal lobule. On brain SPECT, low blood perfusion was observed in the left temporo-parietal regions. Although agraphia for kana and alexia for both kana and kanji improved after steroid therapy, agraphia for kanji did not improve. After the treatment, high intensity area of inferior parietal lobule was disappeared on MRI, and the hypoperfusion of inferior parietal lobule on brain SPECT was also improved, but the lesion of left postero-inferior temporal lobe did not show any remarkable changes. We considered that the kanji-predominant alexia with agraphia was due to the lesions of left inferior parietal lobule and postero-inferior temporal lobe, and agraphia for kanji was due to the lesion of left postero-inferior temporal lobe.


Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping.
Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus) is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs) associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS) and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs), and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM) on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs) in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD) and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS) of A. flavus resistance and a characterisation of the causal gene.


[Demographic and ideational change in the European Community].
"It is argued in this article that family formation is conditioned not only by economic factors (more particularly changes in opportunity structures for the two sexes), but also by ideational trends. The economic factors could be seen as responsible for period fluctuations that are superimposed on a long term ideationally driven trend with marked cohort contrasts. Value orientations are explored and compared across countries and age groups using the international data set of the European Values Studies. The analysis identifies a scale for the degree of tolerance towards non-conformism (e.g. divorce, abortion, one-parent family, rejection of marriage as an institution...) and the meaning of parenthood. Both are related to a set of other scales (religiosity, morality, leftism, nationalism, materialism, etc.). Theoretical links are also established with the theories of, respectively, Easterlin and Simons concerning the reasons for the recent fertility decline in the West." (SUMMARY IN ENG AND FRE)


Development of a DNA microarray for the simultaneous detection and genotyping of noroviruses.
Current methods for detecting and genotyping noroviruses focus on the use of reverse transcriptase (RT)-mediated PCR. A major drawback of this approach is that short target RT-PCR products do not always encompass sequences that can be compared among research laboratories, resulting in difficulties for molecular epidemiology. We describe the use of a microarray-based system for simultaneous detection and molecular characterization of noroviruses. The protocol generates a 917-bp RT-PCR product that encompasses two major regions currently used for detection and analysis of norovirus genomes. The PCR products are then hybridized to an oligonucleotide array (NoroChip) based on 50-mer features, which allows for both confirmation of reaction specificity and molecular characterization of the amplified genome. Parallel sequence analyses of amplicons revealed that our microarray data were robust in separating genogroups I and II, and further subtyping to the cluster level was possible. This approach, combining detection and characterization, overcomes the need for expensive and time-consuming sequence analysis of amplified genome targets for molecular epidemiology.


[Social Inequalities and COVID-19: Social-Epidemiological Perspectives on the Pandemic].
The new Coronavirus Disease (COVID-19) hits specific population groups harder than others. However, social-epidemiological patterns of the pandemic which go beyond differences by age and gender have hardly been addressed in Germany. First reports from other western industrialised countries indicate that people living in socioeconomically deprived areas and people of color have an increased risk of severe COVID-19 progression and mortality. Social inequalities in the risk of infection due to different living and working conditions, and social inequalities in the susceptibility and risk factors for severe COVID-19, particularly in pre-existing medical conditions, might play an important role in explaining those findings. Such inequalities are well established for Germany, as well. It can therefore be assumed that also in Germany people with a lower socioeconomic status might be more affected during the further course of the pandemic. In addition, the interventions to contain the pandemic might have unequal social, economic and psychological impacts on different social groups. Hence, the COVID-19 pandemic has the overall potential to increase social and health inequalities. Social-epidemiological research into COVID-19 is therefore needed to advance measures of health protection and infection control in an evidence-based, targeted and socially equitable manner.


Dihydroxyacetone variants in the organocatalytic construction of carbohydrates: mimicking tagatose and fuculose aldolases.
Dihydroxyacetone variants have been explored as donors in organocatalytic aldol reactions with various aldehyde and ketone acceptors. The protected form of dihydroxyacetone that was chosen for in-depth study was 2,2-dimethyl-1,3-dioxan-5-one, 1. Among the catalysts surveyed here, proline proved to be superior in terms of yield and stereoselectivities in the construction of various carbohydrate scaffolds. In a fashion analogous to aldolase enzymes, the de novo preparation of L-ribulose, L-lyxose, D-ribose, D-tagatose, 1-amino-1-deoxy-D-lyxitol, and other carbohydrates was accomplished via the use of 1 and proline. In reactions using 2,2-dimethyl-1,3-dioxan-5-one 1 as a donor, (S)-proline can be used as a functional mimic of tagatose aldolase, whereas (R)-proline can be regarded as an organocatalytic mimic of fuculose aldolase.


Motivated closing of the mind: "seizing" and "freezing".
A theoretical framework is outlined in which the key construct is the need for (nonspecific) cognitive closure. The need for closure is a desire for definite knowledge on some issue. It represents a dimension of stable individual differences as well as a situationally evocable state. The need for closure has widely ramifying consequences for social-cognitive phenomena at the intrapersonal, interpersonal, and group levels of analysis. Those consequences derive from 2 general tendencies, those of urgency and performance. The urgency tendency represents an individual's inclination to attain closure as soon as possible, and the permanence tendency represents an individual's inclination to maintain it for as long as possible. Empirical evidence for present theory attests to diverse need for closure effects on fundamental social psychological phenomena, including impression formation, stereotyping, attribution, persuasion, group decision making, and language use in intergroup contexts.


[The effects of fibrin glue on acute complete transection spinal cord injury].
To investigate the effects of fibrin glue on repair and regeneration of acute complete spinal cord injury. Acute complete transaction spinal cord injury model were made in 10 adult healthy SD rats (female, weighing 250-300 g), randomized grouping: treated group (n=5) and control group (n=5). In the treated group, fibrin glue was implanted covering on the injury site and filling the lesion gap. In the control group, no treatment was given. At 4 weeks, the locomotor functions of the rats were detected by basso, beattie and bresnahan (BBB) score, then the means of immunohistochemistry were used to observe neurofilament(NF) and glial fibrillary acidic protein(GFAP). And image analysis was used to measure the quantify of the nerve fiber and the fibers area ratio of astrocyte. The BBB scores were 2.40 +/- 0.51 in control group, 3.00 +/- 0.45 in treated group, showing no significant difference (P > 0.05). By immunohistochemistry: a little positive NF cells and GFAP frame were found in control group; more positive NF cells and GFAP frame were found in treated group, the cells and frame grew toward the center but did not arrive at the center. Image analysis showed the amount of never fibers in treated group (rostral region: 113.10 +/- 20.75, caudal region: 73.60 +/- 33.61) was more than that in control group (rostral region: 45.50 +/- 17.18, caudal region 23.50 +/- 8.20), showing significant difference. The fibers area ratio of astrocyte in treated group (rostral region: 33.75% +/- 11.06%, caudal region: 27.75% +/- 7.15%) was more than that in control group(rostral region: 23.78% +/- 5.76%, caudal region: 19.78% +/- 5.17%), showing significant difference (P < 0.05). Fibrin glue can promote repair and regeneration of acute spinal cord injury.


Naltrexone-induced pruritus in a dog with tail-chasing behavior.
Naltrexone, an opioid antagonist recently advocated for the control of stereotypic behavioral patterns in horses and dogs, induced an intense dose-related pruritic reaction in a dog with tail-chasing and self-mutilating behavior. Used in human beings primarily as an adjunct in the treatment of opioid abusers, naltrexone's adverse effects include dermatologic signs, such as alopecia and pruritus, observed in < 1% of human patients. In contrast to previously reported findings, naltrexone treatment was of limited benefit to the dog of this report. During administration of the drug, stereotypic patterns were reduced but did not disappear. Although naltrexone may be effective in controlling certain obsessive-compulsive disorders, its inconsistent therapeutic value, prohibitive cost to pet owners, and side effects such as the pruritus observed in the dog of this report may restrict use of this drug.


Monitoring of leukemia growth in a rat model using a highly sensitive assay for the detection of LacZ marked leukemic cells.
A very sensitive assay for the detection of LacZ marked cells of an in vitro growing subline of the brown Norway rat myelocytic leukemia (BNML) model was developed. By combining cytochemical X-gal staining with D-galactose mediated suppression of endogenous background beta-galactose activity, a detection sensitivity of one leukemic cell per 10(8) normal bone marrow cells could be achieved. A detailed analysis of the in vivo growth pattern and kinetics of this cell line is presented. Also, it is shown that after cyclophosphamide treatment of leukemic rats no leukemic colonies are formed in an agar-colony assay, whereas the leukemic cells remain detectable in the bone marrow for a considerable time period. Eventually, however, all leukemic cells disappear from the marrow. These findings are discussed in the light of prolonged detection of rare leukemic cells in patients in continuing remission.