Biomonitoring of a Nile Delta Lake using benthic foraminifera.
Lake Edku, one of the northern Nile Delta lakes, is a shallow brackish coastal lake subjected to domestic and agricultural effluents via two main drains, El-Khairy and Barsik, in addition to the discharge water of hundreds of fish farms. This study measures the responses of the benthic foraminiferal assemblage to the environmental stressors in Lake Edku. Grain size, organic carbon, and seven potentially toxic elements (Cu, Pb, Zn, Cd, Cr, Ni, and As) were determined in nine short cores (25-35 cm depth). The lake was characterized by vertical increase in mud, organic matter, and concentrations of all metals, particularly in the eastern basin at the vicinity of the drain discharges. This trend coincides with a general decrease in species diversity and increase in deformed specimens. The foraminiferal assemblage was dominated by Ammonia tepida (Cushman), a pollution-tolerant and euryhaline species. This study demonstrates that benthic foraminiferal assemblages provide a reliable pollution proxy in the brackish environments of Nile Delta that can be used in the periodical monitoring of the coastal lakes.


Non-invasive measurement of respiratory mechanics in ICU patients.
Recent methods developed for non-invasive determination of the mechanical properties of the respiratory system have been reviewed. These methods can provide valuable on-line information in patients mechanically ventilated in the intensive care unit setting. More extensive use of such methods should help to provide a better understanding of the physiopathologic processes and adaptive mechanisms present in patients who require mechanical ventilation.


The DNA sequence of the sulfate activation locus from Escherichia coli K-12.
The DNA sequence of the sulfate activation locus from Escherichia coli K-12 has been determined. The sequence includes the structural genes encoding the enzymes ATP sulfurylase (cysD and cysN) and APS kinase (cysC) which catalyze the synthesis of activated sulfate. These are the only genes known to reside in the sulfate activation operon. Consensus elements of the operon promoter were identified, and the start codons and open reading frames of the Cys polypeptides were determined. During this work, another gene, iap, was partially sequenced and mapped. The activity of ATP sulfurylase is stimulated by an intrinsic GTPase. Comparison of the primary sequences of CysN and Ef-Tu revealed that CysN has conserved many of the residues integral to the three-dimensional structure important for guanine nucleotide binding in Ef-Tu and RAS. nodP and nodQ, from Rhizobium meliloti, are essential for nodulation in leguminous plants. The Cys and Nod proteins are remarkably similar. NodP appears to be the smaller subunit of ATP sulfurylase. NodQ encodes homologues of both CysN and CysC; thus, these enzymes may be covalently associated in R. meliloti. The consensus GTP-binding sequences of NodQ and CysN are identical suggesting that NodQ encodes a regulatory GTPase.


Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma.
We previously showed that the natural herb Coptidis rhizoma has an anticachectic effect in nude mice bearing human esophageal cancer cells. We further investigated this phenomenon by examining the anticachectic effect of C. rhizoma in syngeneic mice bearing colon 26/clone 20 carcinoma cells, which cause IL-6-related cachexia after cell injection. We evaluated nutritional parameters such as serum glucose level and wasting of adipose tissue and muscle in tumor-bearing and non-tumor-bearing mice treated with C. rhizoma (CR) supplement or a normal diet. IL-6 levels in those mice were quantified by ELISA and real-time RT-PCR. CR supplementation significantly attenuated weight loss in tumor-bearing mice without changing food intake or tumor growth. Furthermore, these mice maintained good nutritional status. IL-6 mRNA levels in tumors and spleens and IL-6 protein levels in tumors and sera were significantly lower in tumor-bearing mice treated with CR supplement than in those treated with a normal diet. CR supplementation did not affect food intake, body weight, nutritional parameters and IL-6 levels in non-tumor-bearing mice. An in vitro study showed that C. rhizoma and its major component, berberine, inhibited IL-1-induced IL-6 mRNA expression in a dose-dependent manner in colon 26/clone 20 cells. Our results showed that C. rhizoma exerts an anticachectic effect on colon 26/clone 20-transplanted mice and that its effect is associated with tumor IL-6 production. We also suggest that its effect might be due to berberine.


Human health risk-based Generic Assessment Criteria for agricultural soil in Jiangsu and Zhejiang provinces, China.
Agricultural soil pollution in China poses a major threat to human health and food safety. There are no agricultural soil environmental standards based on human health in China, which prevents effective screening and assessment of risks. Jiangsu (JS) and Zhejiang (ZJ) provinces, located in the Yangtze River Delta (YRD) core region, have obvious differences in agricultural land conditions, which will result in differences in Generic Assessment Criteria (GAC). In this study, we derived and compared human health risk-based GAC using the Contaminated Land Exposure Assessment (CLEA) model for agricultural land scenarios in these two provinces. We found differences in the GAC between JS and ZJ due to differences in parameters. These differences are greatest for benzene, and cadmium (Cd). For Cd, the contribution of oral intake exceeds 90 %, and the vegetable consumption rate and mean daily intake (MDI) may be key parameters affecting GAC. For the volatile organic compound benzene, the inhalation of indoor vapor accounts for about 30 %, and the key parameters affecting the GAC for benzene may be the attenuation factor and soil organic matte (SOM). The derived GAC are generally lager (i.e., less stringent) than the GB15618-2018 and UK Suitable 4 Use Levels (S4ULs); however, the derived GAC for JS and ZJ were lower than the soil screening values (SSV) for residential land in China. This may be related to methods, land use types, and critical receptors. This work will contribute to the development of regional soil environmental standards in China.


Lipid phosphatases as a possible therapeutic target in cases of type 2 diabetes and obesity.
Phosphatidyl inositol 3-kinase (PI3-kinase) functions as a lipid kinase to produce PI(3,4,5)P(3) from PI(4,5)P(2) in vivo. PI(3,4,5)P(3) is crucial as a lipid second messenger in various metabolic effects of insulin. Lipid phosphatases, src homology 2 domain containing inositol 5'-phosphatase 2 (SHIP2) and skeletal muscle and kidney-enriched inositol phosphatase (SKIP) hydrolyze PI(3,4,5)P(3) to PI(3,4)P(2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) hydrolyzes PI(3,4,5)P(3) to PI(4,5)P(2). SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity. Targeted disruption of the SHIP2 gene in mice resulted in increased insulin sensitivity and conferred protection from obesity induced by a high-fat diet. Polymorphisms in the human SHIP2 gene are associated, at least in part, with the insulin resistance of type 2 diabetes. Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice. Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells. Although a homozygous disruption of the PTEN gene in mice results in embryonic lethality, either skeletal muscle or adipose tissue-specific disruption of PTEN ameliorated glucose metabolism without formation of tumors in animal models of diabetes. The role of SKIP in glucose metabolism remains to be further clarified in vivo. Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity. Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.


The Feasibility and Acceptability of a Cognitive Behavioral Therapy-Based Intervention for Patients With Advanced Colorectal Cancer.
Advanced colorectal cancer and its treatment can bring about challenges associated with psychological distress. The primary aims of this study were to examine the feasibility and acceptability of a cognitive behavioral therapy (CBT)-based intervention to improve coping with the disease. The secondary aim is to evaluate preliminary intervention efficacy. Patients with advanced colorectal cancer in Singapore (N = 60) were randomized to either receive a four-session CBT intervention immediately or be waitlisted. Intervention feasibility (i.e., recruitment and intervention adherence) and acceptability (i.e., participant satisfaction and cultural sensitivity) were assessed. Changes in psychological distress and self-efficacy were examined. The study successfully recruited the intended sample (mean age 61; 62% men). A proportion (12%) reported Hospital Anxiety and Depression Scale scores indicative of distress at baseline. Most (88%) completed all sessions. Participants reported high rates of satisfaction (97%), helpfulness (96%), and cultural sensitivity (95%) of the intervention. The intervention group did not show decrease in psychological distress; however, self-efficacy in cancer-related coping (information seeking: effect size [ES] = 0.64; 95% CI = 0.17, 0.85; coping with side effects: ES = 0.69; 95% CI = 0.33, 0.82; and maintaining positive attitude: ES = 0.45; 95% CI = 0.19, 0.79) increased in the intervention group compared with the waitlisted group. The CBT-based intervention was feasible and acceptable to patients in Singapore. There is no sufficient evidence to warrant a larger trial in this sample with low baseline distress. Future work should identify and target those who are most in need of support.


Golgi study on brain of macular mutant mouse as a model of Menkes kinky hair disease.
This study was undertaken to elucidate, using the Golgi method, the neuropathological change in the brain of the macular mutant mouse, whose hemizygote (Ml/y) is considered to be a model of Menkes kinky hair disease (MKHD). The hemizygote mice gradually lost weight after 10 days of age and died with emaciation and seizure around day 15. The normal littermate (+/y) was well developed. In the cerebrum, the arborization of pyramidal neurons in the layer V of the Ml/y was the same as that in the +/y on day 10. However, development of arborization in the Ml/y was delayed in comparison with that in the +/y on days 12 and 14. Purkinje cells with several somal sprouts were observed in the cerebellum in both the Ml/y and +/y on day 7. The somal sprouts in the +/y had regressed gradually by day 12, while they were still in the anterior and middle lobes of the Ml/y on day 14. Additionally, the trunks of Ml/y stem dendrites became thicker and a cactus formation was recognized on the branching portion of the dendrites on day 14. Arborization of these abnormal Purkinje cells was distinctly poor compared with that in the +/y. These results suggest that the growth of the neurons is delayed in the Ml/y and simultaneously their cytoskeletal developments are disturbed, especially in the Purkinje cells. There is a close similarity in many respects to the neuropathological change in MKHD.


Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China.
Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.


Scintigraphic detection of vascular and urological complications in the transplanted kidney: 133 cases.
A total of 133 consecutive kidneys, grafted during the past 2 years, were followed by scintigraphy. Patterns of prerenal, renal, and postrenal complications were recognized. Vascular thrombosis diagnosed by photodeficiency of the transplanted kidney was diagnosed and confirmed in 10 patients. Fourteen patients having postrenal urological complications (12 leaks and 2 ureteral obstructions) were all recognized in the late phase of the scintigraphic study. The differentiation between the known parenchymatous causes of anuria was less satisfactory. As a whole, all cases were recognized in which the complication was due to causes that required surgical intervention.


N-Ethylmaleimide-Sensitive Factor b (nsfb) Is Required for Normal Pigmentation of the Zebrafish Retinal Pigment Epithelium.
Despite the number of albinism-causing mutations identified in human patients and animal models, there remain a significant number of cases for which no mutation has been identified, suggesting that our understanding of melanogenesis is incomplete. Previously, we identified two oculocutaneous albinism mutations in zebrafish, au13 and au18. Here, we sought to identify the mutated loci and determine how the affected proteins contribute to normal pigmentation of the retinal pigment epithelium (RPE). Complementation analyses revealed that au13 and au18 belonged to a single complementation group, suggesting that they affected the same locus. Whole-genome sequencing and single nucleotide polymorphism (SNP) analysis was performed to identify putative mutations, which were confirmed by cDNA sequencing and mRNA rescue. Transmission electron microscopy (TEM) and image quantification were used to identify the cellular basis of hypopigmentation. Whole-genome sequencing and SNP mapping identified a nonsense mutation in the N-ethylmaleimide-sensitive factor b (nsfb) gene in au18 mutants. Complementary DNA sequencing confirmed the presence of the mutation (C893T), which truncates the nsfb protein by roughly two-thirds (Y297X). No coding sequence mutations were identified in au13, but quantitative PCR revealed a significant decrease in nsfb expression, and nsfb mRNA injection rescued the hypopigmentation phenotype, suggesting a regulatory mutation. In situ hybridization revealed that nsfb is broadly expressed during embryonic development, including in the RPE. Transmission electron microscopy analyses indicated that average melanosome density and maturity were significantly decreased in nsfb mutants. au18 and au13 contain mutations in nsfb, which encodes a protein that is required for the maturation of melanosomes in zebrafish RPE.


MHC class I chain-related molecule A and B expression is upregulated by cisplatin and associated with good prognosis in patients with non-small cell lung cancer.
MHC class I chain-related molecule A and B (MICA/B) are NK group 2 member D (NKG2D) ligands, which are broadly expressed in transformed cells. Both DNA damage-induced ataxia-telangiectasia-mutated (ATM)- and ATM and Rad3-related protein kinases (ATM-ATR) signaling and oncogene-induced PI3K-AKT signaling regulate the expression of NKG2D ligands, which promote NK cell-mediated cytotoxicity via NKG2D-NKG2D ligand interactions. NKG2D ligand overexpression was recently reported to be correlated with good prognosis in several types of cancer. However, the prognostic significance of NKG2D ligands in non-small cell lung cancer (NSCLC) remains unclear. Here, MICA/B expression was evaluated based on immunohistochemistry of 91 NSCLC samples from patients following radical surgery. In addition, expression of MICA/B was assessed in NSCLC cell lines treated with cisplatin in order to evaluate the regulatory mechanisms of MICA/B expression. Overall, 28 out of 91 (30.8%) specimens showed high expression level of MICA/B, which was associated with low (18)F-fluorodeoxyglucose uptake and manifestation of adenocarcinoma. After a median follow-up of 48.2 months, high MICA/B expression was associated with good recurrence-free survival (p = 0.037). In vitro assays using cell lines revealed that MICA/B expression was upregulated by cisplatin via ATM-ATR signaling, resulting in enhanced NK cell-mediated cytotoxicity. Upregulated MICA/B expressions in patients with radically resected NSCLC are predictive of good disease prognosis. Cisplatin-induced MICA/B upregulation is possibly an indirect mechanism by which the innate immune system eliminates tumor cells. NKG2D-NKG2D ligand-targeting therapy is a promising avenue for future immune-chemotherapy development.


Does inpatient health services utilization vary by remoteness in the medical financial assistance population? Evidence from Shaanxi province, China.
Medical Financial Assistance (MFA) provides health insurance and financial support for millions of low income and disabled Chinese people, yet there has been little systematic analysis focused on this vulnerable population. This study aims to advance our understanding of MFA recipients' access to health care and whether their inpatient care use varies by remoteness. Data were collected from the Surveillance System of Civil Affairs of Shaanxi province in 2016. To better proxy remoteness (geographic access), drive time from the respondent's village to the nearest county-level or city-level hospital was obtained by a web crawler. Multilevel models were used to explore the impacts of remoteness on inpatient services utilization by MFA recipients. Furthermore, the potential moderating role of hospital grade (i.e. the grade of medical institution where recipient's latest inpatient care services were taken in the previous year) on the relationship between geographic access and inpatient care use was explored. The analytical sample consisted of 9516 inpatient claims within 73 counties of Shaanxi province in 2016. We find that drive time to the nearest hospital and hospital grade are salient predictors of inpatient care use and there is a significant moderation effect of hospital grade. Compared to those with shortest drive time to the nearest hospital, longer drive time is associated with a longer inpatient stay but fewer admissions and lower annual total and out-of-pocket (OOP) inpatient costs. In addition, these associations are lower when recipients are admitted to a tertiary hospital, for annual total and OOP inpatient expenditures, but higher for length of the most recent inpatient stay no matter what medical treatments are taken in secondary or tertiary hospitals for the most remote recipients. Our results suggest that remoteness has a significant and negative association with the frequency of inpatient care use. These findings advance our understanding of inpatient care use of the extremely poor and provide meaningful insights for further MFA program development as well as pro-poor health strategies.


Mortality and cancer incidence in women with extra X chromosomes: a cohort study in Britain.
About one woman in 1,000 has an extra X chromosome, but such women have no recognised characteristic somatic features and little is known about their long-term health and cancer risks. We conducted a cohort study of mortality and cancer incidence in 542 women diagnosed with X polysomy at 25 cytogenetic centres in Britain since 1959. Fifty-nine deaths occurred during follow-up to mid-2004. Mortality was significantly raised (standardised mortality ratio (SMR) = 2.5 (95% confidence interval (CI) 1.9-3.2)), with excess deaths due particularly to cardiovascular disease (SMR = 2.5 (95% CI 1.5-3.8)) and respiratory disease (SMR = 4.0 (95% CI 1.7-7.9)). Risks of cancer incidence and cancer mortality overall were not raised, but there was significantly raised mortality from non-Hodgkin's lymphoma (NHL) (SMR = 10.4 (95% CI 1.3-37.6); based on 2 cases). The data indicate that mortality in women diagnosed with X polysomy is considerably raised. The raised risk of NHL is seen also in males with more than one X chromosome, and hence although unexpected and based on small numbers, it might indicate the action of a gene on the X chromosome, possibly in the pseudoautosomal region, that escapes X-inactivation.


Biotinidase activity is affected by both seasonal temperature and filter collection cards.
This study set out to examine pre-analytical factors affecting the frequency of positive results in newborn screening for biotinidase deficiency. This investigation was prompted by an increase in the annual screen positive rate for biotinidase deficiency in Ontario from 2.65x10-4 in 2016 to 6.57x10-4 in 2017. Season and trend decomposition was used to separate seasonality from an underlying trend in the time series of biotindase activity measurements for the period 2014-01-12 to 2019-07-27 (n = 798,770). This analysis revealed a marked seasonal effect (winter = median + ⩽ 17 MRU, summer = mean - ⩽20 MRU) and a non-linear negative trend. Seasonal temperature was correlated with biotinidase results (Pearson's r = 0.79) but not with the observed negative trend (Pearson's r = 0.0025). Time series analysis of biotinidase results grouped by print lot of filter paper revealed that recently printed filter paper cards inhibit biotinidase and that this inhibition resolved over time. This study demonstrates that biotindase activity is inhibited by both increased seasonal temperature and collection on newly printed filter cards.


Synthesis of new pyrimidine-containing compounds: 5-(2-(alkylamino)-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-6-hydroxypyrimidine-2,4(1H,3H)-dione derivatives.
In this study, the one-pot reaction between primary amines, 1,1-bis-(methylthio)-2-nitroethene, ninhydrin, and barbituric acid as an enolizable C-H-activated compound provides a simple method for the preparation of 5-(2-(alkylamino)-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-6-hydroxypyrimidine-2,4(1H,3H)-dione derivatives with potential synthetic and pharmacological interest. This reaction shows attractive characteristics, such as substrate availability, good yields, existence of numerous hydrogen-bonding possibilities in product, and its mild conditions in ethanol media.


Computer processing of intracardiac electrograms for conduction studies.
Computer techniques developed to process intracardiac signals recorded in dogs are presented. The signals under measurement are the auricular and ventricular monophasic action potentials and the His bundle electrogram. Computerized measurement of significant timing parameters on simultaneous recordings of these signals can assess quite precisely changes in the normal conduction scheme of the heart provoked by different experimental protocols. Increased accuracy is mainly due to the objective way of defining wave onsets and the processing power of the system used. Signal recording, signal acquisition, automatic waveform measurements, interactive process and production of end result graphs by computer are all described.


A different response to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection in UK people with multiple sclerosis (PwMS) compared to controls.
The nature of past cytomegalovirus (CMV) infection in multiple sclerosis (MS) populations is relatively unexplored. Relationships between CMV infection markers and Epstein-Barr virus (EBV) infection markers in a UK resident population of people with MS (PwMS) and controls have been investigated. CMV and EBV nuclear antigen-1(EBNA-1)/virus capsid antigen (VCA) IgG levels were determined for 78 MS patients and anonymised controls by enzyme immunoassays. CMV IgG levels were expressed as Paul Ehrlich Institute (PEI) units/ml (U/ml) and EBNA-1/VCA IgG levels as enzyme units/ml. CMV IgG seroprevalence was lower (p = 0.0003) in PwMS (35.9% [95%CI: 25.2-46.5]) compared to controls (62.9% [95%CI:54.4-71.4). CMV IgG geometric mean levels in PwMS (353 PEI U/ml [95%CI:272-457]) were lower (p = 0.03) compared to the controls (492 PEI U/ml [95%CI:405-599]). EBNA-1 IgG levels were higher (p < 0.0001) in PwMS compared to the controls and were lower (p = 0.238) in CMV seropositive PwMS (49.4 units/ml [95%CI:32.2-75.6]) compared to CMV seronegative PwMS (65.4 units/ml [95%CI:53.4-80.1]). These effects were not apparent with EBV VCA IgG. Several aspects of CMV and EBV infection in PwMS appear to differ compared to controls. The potential immunomodulatory effect of CMV infection on MS disease and potential interactions with EBV require further investigation.


Papillary thyroid microcarcinoma: decision-making, extent of surgery, and outcomes.
The optimal extent of surgery for patients with papillary thyroid microcarcinoma (PTMC), tumors ≤1 cm, is controversial because survival is excellent regardless of approach. The objective of this study was to investigate patient and surgeon decision-making about the extent of surgery for PTMC. We conducted a retrospective review of thyroid cancer patients operated on at a single institution from 2008-2016. To examine decision-making about the extent of surgery, we performed a discourse analysis on all available documentation looking for patient or surgeon reasons. Of the 853 thyroid cancer patients, 125 (14.7%) had a PTMC as their largest tumor. Overall, 27.2% of the PTMC patients underwent a thyroid lobectomy, whereas 72.8% had a total thyroidectomy (TT). Of those patients diagnosed with PTMC preoperatively (19/125), a significantly higher proportion underwent a TT (94.7% versus 68.9%, P = 0.02). In all cases, documentation indicated that these preoperatively diagnosed patients followed the surgeon's recommendation regarding the extent of surgery. Reasons surgeons cited for recommending a TT included patient and disease factors (34.6%), belief that TT was the standard treatment (21.7%), ease of follow-up (8.7%), and referring provider preference (4.3%). Of the 19 patients diagnosed preoperatively, four (21.1%) patients had a complication, one (5.3%) of which was permanent and potentially avoidable with less extensive surgery. These data suggest that surgeons drive decision-making about the extent of thyroidectomy in patients with preoperatively diagnosed PTMC. With recent guidelines recommending thyroid lobectomy, closer examination of decision-making is needed to ensure that patients make well-informed, preference-based decisions.


A signal-amplified whole-cell biosensor for sensitive detection of Hg2+ based on Hg2+-enhanced reporter module.
A signal-amplified mercury sensing biosensor with desired sensitivity was developed through firstly using the GFP mutant with fluorescence increasing response towards Hg2+ as the reporter module. The developed biosensor showed response for Hg2+ in a relatively wide range of 1-10,000 nmol/L, and the detection limit was improved one or two orders of magnitude in comparison with most metal-sensing biosensors in similar constructs. In addition, the biosensor could distinguish Hg2+ easily from multiple metal ions and displayed strong adaptability to extensive pH conditions (pH 4.0-10.0). More importantly, the developed biosensor was able to provide an initial assessment of Hg2+ spiked in the environmental water with the recoveries between 85.70% and 112.50%. The signal-amplified strategy performed by the modified reporter module will be widely applicable to many other whole-cell biosensors, meeting the practical requirements with sufficient sensing performance.


The Flow brain stimulation headset for the treatment of depression: overview of its safety, efficacy and portable design.
Major depressive disorder (MDD) is a prevalent and debilitating condition. First-line treatments include antidepressants and cognitive-behavioral psychotherapy (CBT). However, several patients present treatment-resistance and/or adverse effects. Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique, is an effective alternative for MDD. We hereby review a portable tDCS device designed to be combined with a cognitive-behavioral intervention. This home-use device was developed by Flow Neuroscience™ and was recently approved in the UK and European Union. We discuss present evidence on tDCS efficacy and safety, both as a monotherapy and as a combined treatment. Moreover, we show a computer modeling tDCS procedure based on Flow parameters and montage. Electric field simulations revealed that Flow's tDCS device targets prefrontal cortical areas involved in MDD pathophysiology. In addition, the safety and efficacy profile revealed from prior tDCS studies support its use in depression. Finally, combining tDCS with cognitive-behavioral interventions might further enhance overall efficacy, although this aspect should be investigated in upcoming randomized, placebo-controlled trials.


Effect of astaxanthin rich red yeast (Phaffia rhodozyma) on oxidative stress in rainbow trout.
The antioxidative biological effect of dietary red yeast, Phaffia rhodozyma, which is rich in astaxanthin, on rainbow trout, Oncorhynchus mykiss, was examined. The levels of serum transaminase (glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase) activities and of lipid peroxides (LPO) of fish fed oxidized oil were significantly higher than those of the control fish fed non-oxidized oil. However, the supply of red yeast considerably decreased both enzyme activities and LPO level. Furthermore, the serum lipid (triglycerides, total cholesterol and phospholipids) concentrations were also significantly decreased. Especially, the serum triglyceride level of fish fed the red yeast was as low as that of the control. It was also observed that there were no significant differences in muscle LPO levels between the fish fed red yeast and the control. The present results suggest for the first time that dietary red yeast may effectively suppress the LPO generation of tissue and normalize liver function as well as improving muscle pigmentation of trout. Thus, red yeast should have a reducing effect on oxidized oil-induced oxidative stress in fish.


Inhibition of DNA methyltransferase activity upregulates Fyn tyrosine kinase expression in Hut-78 T-lymphoma cells.
Tyrosine kinase Fyn, the expression of which is epigenetically regulated, has been proposed to be a tumour suppressor gene. A frequent deletion at the 6q chromosomal region encoding the Fyn gene in lymphomas has been reported. Therefore, we assessed the impact of 5-Aza-2'-deoxycytidine (5-dAzaC), a DNA methyltransferase (DNMTs) inhibitor on Fyn expression in Hut-78 T-lymphoma cells. Using reverse transcription, real-time quantitative PCR (RQ-PCR), and western blot analyses, we found that 5-dAzaC significantly increased transcript and protein levels of Fyn in Hut-78 T-lymphoma cells. However, bisulfite sequencing revealed that Hut-78 T-lymphoma cells cultured in the absence of 5-dAzaC contained unmethylated cytosine in the cytosine-guanosine dinucleotide island of the Fyn promoter. Our results suggest that the DNMTs activity may have an indirect influence on the expression of Fyn without altering the methylation level of its promoter in Hut-78 T-lymphoma cells.


Myeloperoxidase as a biomarker for intestinal-brain axis dysfunction induced by malnutrition and Cryptosporidium infection in weanling mice.
Cryptosporidiosis is a waterborne protozoal infection that may cause life-threatening diarrhea in undernourished children living in unsanitary environments. The aim of this study is to identify new biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle, necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enteropathy that could drive gut-derived brain inflammation. We utilized a model of environmental enteropathy in C57BL/6 weanling mice challenged by Cryptosporidium and undernutrition. Mice were fed a 2%-Protein Diet (dPD) for eight days and orally infected with 107-C. parvum oocysts. C. parvum oocyst shedding was assessed from fecal and ileal-extracted genomic DNA by qRT-PCR. Ileal histopathology scores were assessed for intestinal inflammation. Prefrontal cortex samples were snap-frozen for MPO ELISA assay and NF-kb immunostaining. Blood samples were drawn by cardiac puncture after anesthesia and sera were obtained for serum amyloid A (SAA) and MPO analysis. Brain samples were also obtained for Iba-1 prefrontal cortex immunostaining. C. parvum-infected mice showed sustained stool oocyst shedding for six days post-infection and increased fecal MPO and inflammation scores. dPD and cryptosporidiosis led to impaired growth and weight gain. C. parvum-infected dPD mice showed increased serum MPO and serum amyloid A (SAA) levels, markers of systemic inflammation. dPD-infected mice showed greater MPO, NF-kB expression, and Iba-1 immunolabeling in the prefrontal cortex, an important brain region involved in executive function. Our findings suggest MPO as a potential biomarker for intestinal-brain axis dysfunction due to environmental enteropathy.


Report on the First Symposium on Invertebrate Neuroscience held on 13-17th August 2019 at the Balaton Limnological Institute, MTA Centre for Ecological Research, Tihany, Hungary.
This meeting report provides an overview of the oral and poster presentations at the first international symposium for invertebrate neuroscience. The contents reflect the contributions of invertebrate neuroscience in addressing fundamental and fascinating challenges in understanding the neural substrates of animal behaviour.


Long interpregnancy interval and mode of delivery.
WHO sets 24 months as the ideal minimum interpregnancy interval (IPI) to minimize maternal and perinatal adverse outcomes. Some studies suggest that an interval longer than 59 months may affect these outcomes, but little is known about its influence on labor. The primary objective of this study was to compare the cesarean delivery rate between primiparous women with a long IPI and, on the one hand, primiparous women with an ideal minimum IPI of 18-24 months and, on the other hand, with nulliparous women. This retrospective cohort study of 17 years included nulliparas and primiparas who gave birth to live singleton fetuses in cephalic presentation after 22 weeks of gestation. Women with an IPI < 18 months or from 24 to 59 months were excluded, as were women with planned cesarean. We analyzed three groups: primiparous women with a long IPI defined as > 59 months, primiparous women with an ideal minimum IPI (18-24 months), and nulliparous women. The study included 18,503 women: 1342 women in the "long IPI" group, 1388 in the "ideal minimum IPI" group, and 15,773 in the nulliparous women group. The cesarean delivery rate was significantly higher in the long compared to the ideal minimum IPI group [12.2% vs. 6.3%, respectively; aOR = 2.2 (95% CI 1.6-3.1)], but both groups had similar durations of labor, regardless of mode of delivery. Women in the long IPI group had significantly lower cesarean rates than nulliparous women [12.2% and 14.3%, respectively; aOR = 0.5 (95% CI 0.4-0.7)], and the nulliparous women had a significantly longer mean duration of labor. Primiparas with a long IPI, compared with ideal minimal IPI have a higher risk of cesarean delivery during labor. Compared with nulliparous women, primiparous women with a long IPI had a lower cesarean rate.


Symbiosis maintenance in the facultative coral, Oculina arbuscula, relies on nitrogen cycling, cell cycle modulation, and immunity.
Symbiosis with unicellular algae in the family Symbiodiniaceae is common across tropical marine invertebrates. Reef-building corals offer a clear example of cellular dysfunction leading to a dysbiosis that disrupts entire ecosystems in a process termed coral bleaching. Due to their obligate symbiotic relationship, understanding the molecular underpinnings that sustain this symbiosis in tropical reef-building corals is challenging, as any aposymbiotic state is inherently coupled with severe physiological stress. Here, we leverage the subtropical, facultatively symbiotic and calcifying coral Oculina arbuscula to investigate gene expression differences between aposymbiotic and symbiotic branches within the same colonies under baseline conditions. We further compare gene ontology (GO) and KOG enrichment in gene expression patterns from O. arbuscula with prior work in the sea anemone Exaiptasia pallida (Aiptasia) and the salamander Ambystoma maculatum-both of which exhibit endophotosymbiosis with unicellular algae. We identify nitrogen cycling, cell cycle control, and immune responses as key pathways involved in the maintenance of symbiosis under baseline conditions. Understanding the mechanisms that sustain a healthy symbiosis between corals and Symbiodiniaceae algae is of urgent importance given the vulnerability of these partnerships to changing environmental conditions and their role in the continued functioning of critical and highly diverse marine ecosystems.


Feasibility of spiral fMRI based on an LTI gradient model.
Spiral imaging is very well suited for functional MRI, however its use has been limited by the fact that artifacts caused by gradient imperfections and B0 inhomogeneity are more difficult to correct compared to EPI. Effective correction requires accurate knowledge of the traversed k-space trajectory. With the goal of making spiral fMRI more accessible, we have evaluated image reconstruction using trajectories predicted by the gradient impulse response function (GIRF), which can be determined in a one-time calibration step. GIRF-predicted reconstruction was tested for high-resolution (0.8 mm) fMRI at 7T. Image quality and functional results of the reconstructions using GIRF-prediction were compared to reconstructions using the nominal trajectory and concurrent field monitoring. The reconstructions using nominal spiral trajectories contain substantial artifacts and the activation maps contain misplaced activation. Image artifacts are substantially reduced when using the GIRF-predicted reconstruction, and the activation maps for the GIRF-predicted and monitored reconstructions largely overlap. The GIRF reconstruction provides a large increase in the spatial specificity of the activation compared to the nominal reconstruction. The GIRF-reconstruction generates image quality and fMRI results similar to using a concurrently monitored trajectory. The presented approach does not prolong or complicate the fMRI acquisition. Using GIRF-predicted trajectories has the potential to enable high-quality spiral fMRI in situations where concurrent trajectory monitoring is not available.


Basic fibroblast growth factor (bFGF)-induced cell death is mediated through a caspase-dependent and p53-independent cell death receptor pathway.
The mechanism of bFGF-induced cell death in tumours of the Ewing's sarcoma family (ESFT) has been investigated. bFGF-induces phosphorylation of FGFr 1 and activation of Ras/ERK in ESFT cells that die when exposed to bFGF. Induction of cell death was associated with activation of both initiator (caspases-2, -8 and -10) and effector (caspases-3, -6 and -7) caspases. Moreover, the general caspase inhibitor Z-VAD-FMK protected cells from bFGF-induced cell death. After treatment with bFGF, a loss of mitochondrial transmembrane potential was accompanied by down-regulation of Bcl-2. However, the observed cell death was not associated with release of cytochrome c from the mitochondria. Furthermore, expression of wild-type p53 was not required for bFGF-induced cell death. These observations suggest that bFGF-induced cell death may be mediated through a cell death receptor mechanism, supported by up-regulation of the p75 neurotrophin receptor. bFGF-induced cell death was associated with up-regulation of p21 and p53, down-regulation of PCNA and cyclin A and a decrease in active pRb1, changes consistent with accumulation of cells in G1. These data demonstrate that bFGF-induced cell death is effected through a caspase-dependent and p53-independent mechanism, that may be mediated through a cell death receptor pathway.


Effects of defects in g-C3N4 on excited-state charge distribution and transfer: Potential for improved photocatalysis.
Graphite phase carbon nitride (g-C3N4) with triazine ring structures is a polymeric metal-free semiconductor with a medium bandgap and two-dimensional layered structure. g-C3N4 has attracted attention because of its photocatalytic applications, such as the photodegradation of pollution and hydrogen production via water splitting. Defective elements and sites are two essential factors in rationally designing highly-efficient photocatalysts based on g-C3N4 at the nanoscale. When the molecule absorbs energy and enters an excited state, electrons migrate and the charge distribution changes accordingly. The properties of the excited states of g-C3N4 are related to its defect elements and sites. Therefore, it is necessary to understand the effects of defects on excited states in the design of g-C3N4 catalysts. In this paper, the excited-state characteristics of intrinsic g-C3N4 and g-C3N4 with C- and N-atom defects are analyzed by density functional theory. We apply quantum chemistry and wave function analysis to determine the hole-electron distributions and charge transfer directions. To measure and discuss the characteristics of electron excitation using quantitative numerical methods, the D, Sr, H, and t indices are calculated. Our results promote a deeper understanding of the roles of defective elements and sites in photocatalysis by g-C3N4.


Synthesis and structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as non-peptide, small-molecule antagonists for interleukin-8 receptor.
Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.


Heart rate complexity: An early prognostic marker of patient outcome after cardiac arrest.
Early prognostication in comatose patients after cardiac arrest (CA) is difficult but essential to inform relatives and optimize treatment. Here we investigate the predictive value of heart-rate variability captured by multiscale entropy (MSE) for long-term outcomes in comatose patients during the first 24 hours after CA. In this retrospective analysis of prospective multi-centric cohort, we analyzed MSE of the heart rate in 79 comatose patients after CA while undergoing targeted temperature management and sedation during the first day of coma. From the MSE, two complexity indices were derived by summing values over short and long time scales (CIs and CIl). We splitted the data in training and test datasets for analysing the predictive value for patient outcomes (defined as best cerebral performance category within 3 months) of CIs and CIl. Across the whole dataset, CIl provided the best sensitivity, specificity, and accuracy (88%, 75%, and 82%, respectively). Positive and negative predictive power were 81% and 84%. Characterizing the complexity of the ECG in patients after CA provides an accurate prediction of both favorable and unfavorable outcomes. The analysis of heartrate variability by means of MSE provides accurate outcome prediction on the first day of coma.


Young's modulus of peritubular and intertubular human dentin by nano-indentation tests.
The local Young modulus of dry dentin viewed as a hierarchical composite was measured by nano-indentation using two types of experiments, both in a continuous stiffness measurement mode. First, tests were performed radially along straight lines running across highly mineralized peritubular dentin sections and through less mineralized intertubular dentin areas. These tests revealed a gradual decrease in Young's modulus from the bulk of the peritubular dentin region where modulus values of up to ∼40-42GPa were observed, down to approximately constant values of ∼17GPa in the intertubular dentin region. A second set of nano-indentation experiments was performed on the facets of an irregular polyhedron specimen cut from the intertubular dentin region, so as to probe the modulus of intertubular dentin specimens at different orientations relative to the tubular direction. The results demonstrated that the intertubular dentin region may be considered to be quasi-isotropic, with a slightly higher modulus value (∼22GPa) when the indenting tip axis is parallel to the tubular direction, compared to the values (∼18GPa) obtained when the indenting tip axis is perpendicular to the tubule direction.


{N'-[(2-Oxidonaphthalen-1-yl)methyl-idene]benzohydrazidato}(1,10-phenanthroline)copper(II) methanol monosolvate.
The title mononuclear complex, [Cu(C(18)H(12)N(2)O(2))(C(12)H(8)N(2))]·CH(3)OH, contains one N'-[(2-oxidonaphthalen-1-yl)methyl-idene]benzohydrazidate ligand (L(2-)), a Cu(2+) cation, one 1,10-phenanthroline ligand and a methanol solvent mol-ecule. The Cu(II) ion adopts a CuO(2)N(3) distorted square-pyramidal coordination. An O-H⋯O hydrogen bond is formed between the methanol solvent mol-ecule and the hydrazide O atom of the L(2-) ligand.


Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors.
Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis. Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels. Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed. In vitro biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC50 of 1.03 µM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation. Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.


Transport and distribution of biotherapeutics in different tissue layers after subcutaneous injection.
The subcutaneous injection is the main route of administration for monoclonal antibodies (mAbs) and several other biotherapeutics due to the patient comfort and cost-effectiveness. However, their transport and distribution after subcutaneous injection is poorly understood. Here, we exploit a three-dimensional poroelastic model to find the biomechanical response of the tissue, including interstitial pressure and tissue deformation during the injection. We quantify the drug concentration inside the tissue. We start with a single-layer model of the tissue. We show that during the injection, the difference between the permeability of the solvent and solute will result in a higher drug concentration proportional to the inverse permeability ratio. Then we study the role of tissue layered properties with primary layers, including epidermis, dermis, subcutaneous (SQ), and muscle layers, on tissue biomechanical response to injection and drug transport. We show that the drug will distribute mainly in the SQ layer due to its lower elastic moduli. Finally, we study the effect of secondary tissue elements like the deep fascia layer and the network of septa fibers inside the SQ tissue. We use the Voronoi tessellation algorithm to create random geometry of the septa network. We show how drugs accumulate around these tissue components as observed in the experimental SQ injection. Next, we study the effect of injection rate on drug concentration. We show how higher injection rates will slightly increase the drug concentration around septa fibers. Finally we demonstrate how the concentration dependent viscosity will increase the concentration of biotherapeutics in the direction of septa fibers.


Myolipoma of the round ligament of the liver: a diagnosis to be considered.
A 39-year-old patient consulted for an incidental finding of a mesenteric-epiploic mass measuring 11x6x9.5 cm. Laparoscopic excision of the lesion and cholecystectomy were indicated, revealing a myolipomatous mesenchymal neoplasm in the hepatic round ligament.


Retention deficits produced in monkeys with reversible cold lesions in the prestriate cortex.
Cryodes were implanted over the prelunate and fusiform gyri in 4 monkeys. The intention was to block the prestriate projection to the inferotemporal cortex (IT). Cooling this cortex produced deficits that were completely reversed by removing the cold. The deficits appeared in the recall of visual discriminations that were learned prior to the application of the cold, but new discriminations were learned during cooling at the same rate as in control animals. This closely resembles the results of ablation experiments in this same cortex. There was no deficit when cooling this area on a delayed match-to-sample (DMS) task that required the animals to hold visual information over delays of 10 or 45 s. However, performance was close to chance during cooling when the delays were 6 min. With this long delay, when cooling was done separately at sample when the stimulus is received, or at match when the information is recalled, a significant deficit occurred only at match. The results are consistent with the suggestion that this area is involved in retrieval of visual information from long-term memory.


Comparison of culture and rapid enzyme immunoassay for the detection of group B streptococcus in high-risk pregnancies.
The purpose of this study was to evaluate the Equate Strep B(R) test for clinical use in patients at high risk for complications from group B streptococcus (GBS) disease. Vaginoperineal swabs were obtained from patients with preterm premature rupture of the membranes and/or preterm labor and semiquantitative GBS cultures and Equate(R) assay were performed. From May 14, 1990, to April 30, 1992, 650 patients were enrolled; 626 had both culture and Equate(R) results available, of whom 24% were colonized with GBS. The sensitivity, specificity, positive predictive value, and negative predictive value of the rapid assay were 28%, 84%, 35%, and 79%, respectively. Although the prevalence of GBS was higher in patients with ruptured membranes compared with those with intact membranes, rupture of membranes did not affect test sensitivity or specificity. We conclude that the Equate(R) rapid assay is not a sensitive method of GBS detection in high-risk patients.


Hepatic Sarcoidosis: Clinico-pathological characterization of symptomatic cases.
The aim of this study was to investigate the clinical and pathological features of hepatic sarcoidosis in symptomatic cases. Twenty-two symptomatic hepatic sarcoidosis cases were included in the study. Hepatic sarcoidosis was determined by typical imaging, histopathology, and high angiotensin-converting enzyme levels. Demographic data, laboratory data, imaging findings, liver biopsies, and clinical findings were analyzed. Portal hypertension (PH) was defined by the presence of ascites and/or varices; imaging findings suggestive of PH-splenomegaly (> 12 cm on longest axis); portal vein dilation (> 13 mm); collateral vessel formation; and hepatic venous pressure gradient ≥ 6 mmHg. Mean age was 49.63 ± 10.7 years. Liver tests showed elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase levels (95%). Serum albumin levels were low (< 3 g/dl) in 32% of the patients. Histologically, hepatic granulomas were located in the portal/periportal areas, with or without parenchymal involvement (77%). Duct damage (27%), absent portal veins (32%), and hepatomegaly (41%) were also observed. Clinically, chronic cholestatic symptoms and PH features were observed in 41% and 50% of the patients, respectively. Three-quarters of patients with PH features were non-cirrhotic. Cirrhosis and bleeding varices were observed in 14%. Hepatic sarcoidosis overlaps with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) was observed in two cases. Sarcoidosis causes significant hepatic disease. PH and jaundice are main clinical presentations in liver sarcoidosis patients. Imaging findings of PH should be carefully reviewed, as it can occur even before the establishment of cirrhosis. Hepatic sarcoidosis mimics and overlaps with PBC and PSC.


Effect of acetone on VLDL secretion by the isolated rat liver.
High acetone levels occur in uncontrolled diabetes and after isopropanol administration to rats. In both conditions, very low density lipoproteins (VLDL) secretion is depressed. Acetone, hoever, failed to affect the VLDL secretion rate by the isolated perfused rat liver, suggesting that this metabolite is not involved in impaired VLDL production in diabetes and after isopropanol administration.


Risk factors affecting asthma prevalence in adolescents living in Istanbul, Turkey.
Asthma is one of the most important diseases of childhood. The aim of this study was to evaluate the prevalence of asthma symptoms and risk factors affecting asthma. In a cross-sectional study design, 9991 children, aged 13-14 years in 61 primary schools in 32 districts of Istanbul were evaluated. Asthma prevalence among the children was assessed using the ISAAC protocol. In our study, a total of 10,894 questionnaires were distributed to 13-14 years old children, and of these 9991 questionnaires were suitable for analysis with an overall response rate of 91.7%. The rates of wheeze ever, wheezing in last 12 months and lifetime doctor diagnosed asthma prevalence were 17.4%, 9.0%, and 11.8%, respectively. There were 4746 boys (47.9%) and 5166 girls (52.1%) with M/F ratio of 0.92. Atopic family history, fewer than three siblings living at home, tonsillectomy or adenoidectomy history, consumption of fermented foods, mixed pickles, margarine and meat were found to be associated with an increased asthma risk. Use of paracetamol in the last 12 months, consumption of fruit and animal fats acted as a protective factor against asthma. The Mediterranean-style diet was not associated with the prevalence of asthma. Lifetime doctor diagnosed asthma prevalence was found to be 11.8% in 13-14 year olds. History of tonsillectomy and/or adenoidectomy and consumption of fermented foods, mixed pickles, margarine and meat may increase the symptoms of asthma. Usage of paracetamol and consumption of animal fats may be investigated as a protective factor against asthma.


Which dietary and lifestyle behaviours may be important in the aetiology (and prevention) of stroke?
Prevention of stroke requires optimal control of causal risk factors. However, only three-quarters of all strokes can be attributable to known causal risk factors. We aimed to identify novel risk factors for acute stroke in 48 patients with acute (<1 week) stroke admitted to Royal Perth Hospital Stroke Unit and 47 controls matched for age and sex from the northeast Perth metropolitan area. Patients and controls were interviewed, and had physical measurements and blood taken. Multiple odds ratios (OR) for risk factors, with 95% confidence intervals (CI), were calculated by unconditional multiple logistic regression. Mediterranean diet (OR: 0.1; 95% CI, 0.02-0.4), increased waist-to-hip ratio (OR 4.0, 95% CI, 1.5-11), physical activity during leisure time (OR 0.2; 95% CI, 0.1-0.9), periodontal disease (OR 6.4; 95% CI, 1.5-27), and acute febrile illness (OR 14; 95% CI, 1.5-127) were associated significantly and independently with ischaemic stroke. These preliminary data suggest that certain dietary and lifestyle behaviours may play as important a role in the aetiology (and prevention) of stroke as other conventional causal risk factors for stroke. However, these associations need confirmation from larger randomised trials given the small sample size of the current study.


Detection of metastatic parathyroid carcinoma with Tc-99m sestamibi imaging.
To assess the use of Tc-99m sestamibi to localize recurrent and metastatic parathyroid carcinoma. A patient with a history of parathyroid carcinoma that was resected 6 months before had high serum calcium and high serum parathyroid hormone levels. Tc-99m sestamibi imaging was performed to localize the recurrence. Tc-99 sestamibi imaging detected the recurrence and the metastatic lymph nodes. These findings were confirmed surgically and pathologically. Tc-99m sestamibi can be useful in diagnosing and localizing metastatic parathyroid carcinoma.


Chat GPT in Tailoring Individualized Lifestyle-Modification Programs in Metabolic Syndrome: Potentials and Difficulties?
Worldwide metabolic syndrome (MeTS) rates have been alarmingly increased in the last decades. The use of Chat GPT technology allows for the provision of individualized guidance on MeTS-related health issues like dietary restriction programs, nutritional plans, and exercise regimens/protocols. The use of Chat GPT technology in providing MeTS patients with health advices may be limited by continuous need for high-speed internet sources or advanced/sophisticated computing technologies, providing incorrect/harmful medical/lifestyle advice to patients, and concerns around the security/privacy of MeTS patients' information.


Acute diverticulitis of the left colon: value of the initial CT and timing of elective colectomy.
Computed Tomography is undeniably the most useful tool to confirm the suspected diagnosis of acute left-colonic diverticulitis and to objectively grade its severity into moderate diverticulitis (no signs of colonic perforation) and severe diverticulitis (signs of colonic perforation). Indeed, the severity of acute diverticulitis is statistically predictive of the risk both to need surgical treatment of the first episode of acute diverticulitis, and to follow a complicated evolution after successful conservative treatment of the acute phase. Consequently, CT brings a major contribution to define the place of surgery during the acute phase of diverticulitis, and, later on, inside the long-term evolution of the disease after initial successful conservative treatment.


A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis.
IgG4-related disease is a newly defined disease characterized by elevated serum IgG4 levels and infiltration of affected organs by IgG4-positive plasma cells. Recently, increased IgG4 levels were reported to be closely related with malignancy. To assess the relationship between IgG4 and the progression of gastric cancer, we immunohistochemically stained in this study gastric cancer tissue samples for IgG4-positive cells using an anti-IgG4 antibody. In addition, pre- and postoperative serum concentrations of IgG4 were measured, using an enzyme-linked immunosorbent assay. In gastric cancer samples, the number of CD138-positive plasma cells was significantly lower and the number of IgG4-positive cells significantly higher than in non-cancerous gastric mucosa. The number of IgG4-positive cells was significantly correlated with gross tumor appearance, tumor depth, lymph node metastasis, venous invasion, and lymphatic invasion. Prognosis was significantly poorer in patients with a high number of IgG4-positive cells than in those with a low number. Multivariate analysis indicated that both the number of IgG4-positive cells and the depth of tumor invasion were independently prognostic of survival. In conclusion, in gastric cancer, the number of IgG4-positive cells is increased and this is closely associated with gastric cancer progression.


[Childcare problems in mothers with twins as compared with children born singly].
The purpose of this survey was to study childcare problems in the families with twins as compared with singletons. The subjects were 234 mothers of twins and 200 mothers of singletons, all born after 1994. 1. Mothers of twins showed significantly higher anxiety during pregnancy compared with those having singletons. There was no significant difference in prevalence of anxiety for infant health between the two groups, but the mothers of twins showed significant higher rate for childcare after delivery, economy, or childcare of other brothers and sisters. 2. Mothers who felt shortage of time for childcare were more frequent in the twin group than in the singleton group. 3. Mothers of twins showed significant more severe fatigue (physical and mental) as compared with those having singletons. They also reported significantly poorer sleeping conditions. In particular, the average sleeping time for mothers of twins was 6.54 hours a day, while for those of singletons, it was 7.32 hours. 4. Mothers of twins who did not receive assistance from fathers for childcare reported more severe physical and mental fatigue than those of twins who were given such help. This study indicated a tendency for mothers of twins to show more severe fatigue, poorer sleeping condition and a greater shortage of time for childcare as compared with those having singletons.


Imaging in Endoscopic Cranial Skull Base and Pituitary Surgery.
Endoscopic endonasal approaches have widely accepted techniques for managing benign and malignant processes along the entire ventral skull base with similar or better results compared with open procedures, but with lower rates of complication. Managing pathology affecting the skull base can be challenging because of complex anatomy and the proximity of critical neurovascular structures. Postoperative imaging can be challenging, because of surgical alterations of normal anatomy and the now common use of complex reconstruction techniques. Understanding the normal imaging appearance of skull base reconstruction is important for accurate postoperative interpretation and delineation between normal reconstructive tissue and recurrent neoplasm.


Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia.
Pneumonia remains the leading cause of death from infection in the US, yet fundamentally new conceptual models underlying its pathogenesis have not emerged. We show that humans and mice with bacterial pneumonia have markedly elevated amounts of cardiolipin, a rare, mitochondrial-specific phospholipid, in lung fluid and find that it potently disrupts surfactant function. Intratracheal cardiolipin administration in mice recapitulates the clinical phenotype of pneumonia, including impaired lung mechanics, modulation of cell survival and cytokine networks and lung consolidation. We have identified and characterized the activity of a unique cardiolipin transporter, the P-type ATPase transmembrane lipid pump Atp8b1, a mutant version of which is associated with severe pneumonia in humans and mice. Atp8b1 bound and internalized cardiolipin from extracellular fluid via a basic residue-enriched motif. Administration of a peptide encompassing the cardiolipin binding motif or Atp8b1 gene transfer in mice lessened bacteria-induced lung injury and improved survival. The results unveil a new paradigm whereby Atp8b1 is a cardiolipin importer whose capacity to remove cardiolipin from lung fluid is exceeded during inflammation or when Atp8b1 is defective. This discovery opens the door for new therapeutic strategies directed at modulating the abundance or molecular interactions of cardiolipin in pneumonia.


Georgia: anti-drug law violates human rights.
At a time when the Georgian government should be protecting the human rights of people who use drugs, Parliament enacted a law that specifically aims to increase stigma against drug users by imposing a range of administrative sanctions against them, Nina Kiknadze and David Otiashvili write.


A century of Dutch neurology.
The Netherlands Society of Neurology evolved from the Society of Psychiatry founded in 1871. The name was changed into Netherlands Society of Psychiatry and Neurology (NSPN) in 1897. In the same year, the word neurology was also added to the name of the journal. The Society steadily blossomed, but in 1909 the first signs of dissatisfaction occurred: the Amsterdam Neurologists Society was founded. A few split-offs would follow. The number of members of the NSPN increased from 205 in 1920 to 585 in 1960. In the early 1960s, the Society was reorganised and would consist of two sections, one for psychiatry and one for neurology. However, this would not last, as a full separation was established in 1974. For several reasons, the name of the journal was changed four times until it assumed its present name in 1974. The 100th volume of CNN was not published, as expected. in 1996, but in 1998, because of two skipped publication years, one during WWII and another in the 1970s. During the last decades of the nineteenth century, teaching of neurology was mostly given within the frame of psychiatry, following the German tradition of 'brainpsychiatry' (organic or biologic psychiatry). The first official chair of psychiatry was founded at Utrecht, 1893 (Winkler). In Amsterdam, private teachers such as Delprat taught 'electro-therapy and nervous diseases' since the 1880s. The first extraordinary chair of neurology and electrotherapy was founded for his successor, Wertheim Salomonson in 1899. The first university clinic for psychiatry and neurology started at the Amsterdam Municipal University, when Winkler became professor of psychiatry and neurology in Amsterdam in 1896. Around the turn of the century, chairs of psychiatry and neurology were also founded in Groningen and Leiden. Separate chairs for neurology and psychiatry appeared in Amsterdam in 1923 and in Utrecht in 1936. Following an initiative of Brouwer, the first neurological university clinic opened its doors in Amsterdam in 1929. In the 20th century, a number specialised peripheral neurological clinics and epilepsy institutes were founded. In 1909, the the Central Institute for Brain Research was established in Amsterdam.


Ligand binding studies in the mouse olfactory bulb: identification and characterization of a L-[3H]carnosine binding site.
Binding sites for the dipeptide L-carnosine (beta-alanyl-L-histidine) have been detected in membranes prepared from mouse olfactory bulbs. The binding of L-[3H]-carnosine was saturable, reversible and stereospecific and had a Kd of about 770 nM. The stereospecific binding of L-carnosine represented about 30% of the total binding at pH 6.8, and decreased markedly with increasing pH. Binding was stimulated by calcium, unaffected by zinc, magnesium or manganese and inhibited by sodium and potassium. Carnosine binding was sensitive to trypsin and phospholipases A and C, but not to neuraminidase. Nystatin and filipin, which interact with membrane lipids, also interferred with binding. Some peptide analogues of carnosine were potent inhibitors of binding, but a variety of drugs serving as potent inhibitors in other binding systems had no effect on carnosine binding. Carnosine binding to mouse olfactory bulb membranes was 15-fold higher than that seen in membranes prepared from cerebral hemispheres, 5-fold higher than that seen in membranes prepared from cerebral hemispheres, 5-fold higher than in cerebellum membranes and 3-fold higher than in membranes from spinal medulla and the olfactory tubercle-lateral olfactory tract area. Binding sites for 6 other radiolabeled receptor ligands were also detected in bulb membranes. Peripheral deafferentation of the olfactory bulbs by intranasal irrigation with ZnSO4 led to a loss greater than 90% of the L-[3H]carnosine binding in 4--5 days with much smaller losses in binding of the other 6 ligands over a 180-day observation period. This initial loss of carnosine binding after denervation was due to a loss of binding site stereo-specificity followed by a loss of binding sites. The characteristics of the carnosine binding site in olfactory bulb fulfil 6 of the 7 criteria considered relevant for a functional receptor.


Analysis of the structure and luminescence properties of Zn2 GeO4 :Eu3+ according to Judd-Ofelt theory.
The preparation and characteristic of nanorod-like Zn2 GeO4 doped with Eu3+ or zinc germanate (ZGO):xEu3+ (x = 0 ÷ 0.05), which was synthesized using the hydrothermal method, are described. The influence of Eu3+ -doping ions on the structure and the optical properties of ZGO was also investigated. According to the photoluminescence spectra, ZGO:xEu3+ nanophosphors gave a red emission due to the 5 D0 →7 F2 emission of Eu3+ ions. In accordance with Judd-Ofelt theory, the intensity parameters for f-f transitions from the emission and absorption spectrum were determined. At the 5 D0 excited state of Eu3+ , total spontaneous emission probabilities (AR ), lifetimes (τR ), branching ratios (βR ), and quantum efficiency (η) were calculated. The ZGO:xEu3+ (x = 0.02, 0.03, 0.04) phosphor showed the branch ratio β (5 D0 →7 F2 ) > 60%, indicating that the phosphors prepared here have a promising potential as laser light. The sample with a concentration of 0.04Eu3+ achieved the highest quantum efficiency of 84%, suggesting that it has potential light-emitting diode applications.


Colorectal cancer incidence trends by tumour location among adults of screening-age in England: a population-based study.
Proximal and distal colorectal cancers (CRCs) exhibit different clinical, molecular and biological patterns. The aim of this study was to determine temporal trends in the age-standardized incidence rates (ASIRs) of proximal and distal CRC following the introduction of the English Bowel Cancer Screening Programme (BCSP) in 2006. The National Cancer Registration and Analysis Service database was used to identify incident cases of CRC among adults of screening age (60-74 years) between 2001 and 2017. ASIRs were calculated using the European Standard Population 2013 and incidence trends analysed by anatomical subsite (proximal, caecum to descending colon; distal, sigmoid to rectum), sex and Index of Multiple Deprivation (IMD) quintile using Joinpoint regression software. Between 2001 and 2017, 541 515 incident cases of CRC were diagnosed [236 167 proximal (43.6%) and 305 348 distal (56.4%)]. A marginal reduction in the proximal ASIR was noted from 2008 [annual percentage change (APC) -1.4% (95% CI -2.0% to -0.9%)] compared with a greater reduction in distal ASIR from 2011 to 2014 [APC -6.6% (95% CI -11.5% to -1.5%)] which plateaued thereafter [APC -0.5% (95% CI -3.2% to 2.2%)]. Incidence rates decreased more rapidly in men than women. Adults in IMD quintiles 4-5 experienced the greatest reduction in distal tumours [APC -3.5% (95% CI -4.3% to -2.7%)]. Following the introduction of the English BCSP, the incidence of CRC has subsequently reduced among adults of screening age, with this trend being most pronounced in distal tumours and in men. There is also evidence of a reduction in the deprivation gap for distal tumour incidence. Strategies to improve the detection of proximal tumours are warranted.


Looking at a blinking quantum emitter through time slots: the effect of blind times.
Most experimental observations of physical processes are naturally accompanied by "blind" ("dead") times, which in principle can distort the result of measurements. Here we analyze how the presence of blind times in measurements changes the measured statistics of blinking fluorescence of single quantum dots. We show that information can be extracted even for blinking processes with characteristic times longer than both blind times and time slots between them.


Obesity-related indices and its association with kidney stone disease: a cross-sectional and longitudinal cohort study.
Obesity increases the risk of several diseases, including kidney stone disease (KSD). The study aimed to explore the relationship between KSD and various obesity-related indices. A total of 121,605 participants in the Taiwan Biobank from December 2008 to February 2020 were analyzed. The association between self-reported history of KSD and eight obesity-related indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), abdominal volume index (AVI), body roundness index (BRI), conicity index, and triglyceride glucose index was examined in cross-sectional analysis; additionally, the risk of developing kidney stones was analyzed in a longitudinal cohort of 25,268 participants without KSD at baseline, which was a subset of the main cohort. Of all participants, 77,904 (64.1%) were female. Overall, 10.7% of males and 4.0% of females had KSD. Multivariate-adjusted logistic regression showed that all obesity-related indices were significantly associated with KSD. During a mean follow-up of 47 months, kidney stones occurred in 642 (2.5%) participants, and after adjusting for confounders, the risk of developing kidney stones was higher in participants with higher BMI, WC, WHtR, WHR, AVI and BRI. BMI, WC, WHtR, WHR, AVI, and BRI were found to be associated with a higher prevalence of kidney stones as well as development of incident kidney stones, which could be used as predictive factors for development of KSD in clinical practice.


Combination therapy of leflunomide and glucocorticoids for the maintenance of remission in patients with IgG4-related disease: a retrospective study and literature review.
Although glucocorticoids are effective in IgG4-related disease (IgG4-RD), patients may relapse during or after glucocorticoid tapering. Immunosuppressive agents, including leflunomide (LEF), are regarded as steroid-sparing agents in other autoimmune disorders and need to be discussed in the management of IgG4-RD. To identify the efficacy and safety of combination therapy of LEF and glucocorticoids in IgG4-RD. We retrospectively summarised data of patients diagnosed with IgG4-RD between November 2012 and November 2015. Only patients treated with LEF plus glucocorticoids and had been followed up for more than three visits and 6 months were analysed with clinical symptoms, laboratory and imaging findings, treatment protocol, LEF-related adverse events and disease activity reflected by IgG4-RD Responder Index (IgG4-RD RI). A total of 18 patients, including 14 untreated patients and 4 relapsing patients, was included. The mean (SD) onset age was 54.0 (9.6) years. The mean (SD) follow-up period was 12.1 (7.4) months. All patients had active disease with mean (SD) IgG4-RD RI of 15.0 (5.6) at baseline and experienced improvements at 1 month. At the last follow up, the mean (SD) IgG4-RD Responder Index declined to 3.1 (1.7) in all patients and to 2.5 (1.2) in patients without relapse. The mean (SD) dose of GC declined to 6.9 (2.7) mg/day. A total of 12 (66.7%) and 11 (61.1%) patients were in remission at 6 months and the last follow up respectively. Three (16.7%) patients relapsed in clinical course. Two reversible adverse events were observed. The combination therapy of LEF and glucocoticoids is effective and safe in IgG4-RD.


Arthroscopic Lysis of Adhesions With Manipulation for Management of Late-Presenting Stiffness After Total Knee Arthroplasty.
Arthrofibrosis is a known complication of total knee arthroplasty (TKA). Closed manipulation is the treatment of choice for arthrofibrosis within 90 days of TKA. Treatment for arthrofibrosis that has failed prior interventions remains controversial, and the role for arthroscopic lysis of adhesions has not been examined for late-presenting arthrofibrosis. A retrospective analysis of patients who underwent arthroscopic lysis of adhesions (LOAs) with manipulation for post-TKA arthrofibrosis was performed. Chart review included patient characteristics, time from TKA, prior interventions, and range of motion (ROM) data. Knee extension, flexion, and total ROM were recorded preoperatively, intraoperatively, and throughout follow-up. Knee ROM was compared at the different time intervals using Wilcoxon signed-rank tests. A total of 13 patients (6 male and 7 female) with a mean age of 66.3 years were included. Average time since index TKA was 57.2 months (3.7-209.5). Ten of 13 patients had undergone prior interventions for arthrofibrosis, which included closed manipulation under anesthesia, open LOA, and revision arthroplasty. The mean preoperative knee flexion and extension values for the cohort were 76.5 ± 17.4 and -4.6 ± 6.1 degrees, respectively. Postoperative improvements in knee ROM were significant at all time points, with mean improvements of 17.2 ± 16.3 degrees at 1 week (P = .022), 17.2 ± 13.2 degrees at 4 weeks (P = .001), 19.2 ± 16.0 degrees at 8 weeks (P = .004), and 25.2 ± 13.1 degrees at 12 weeks (P = .005). No complications were recorded. Arthroscopic LOAs with manipulation achieves significant improvements in knee ROM for late-presenting arthrofibrosis after TKA.


Quantification of mitral valve anatomy by three-dimensional transesophageal echocardiography in mitral valve prolapse predicts surgical anatomy and the complexity of mitral valve repair.
Three-dimensional (3D) transesophageal echocardiography (TEE) is more accurate than two-dimensional (2D) TEE in the qualitative assessment of mitral valve (MV) prolapse (MVP). However, the accuracy of 3D TEE in quantifying MV anatomy is less well studied, and its clinical relevance for MV repair is unknown. The number of prolapsed segments, leaflet heights, and annular dimensions were assessed using 2D and 3D TEE and compared with surgical measurements in 50 patients (mean age, 61 ± 11 years) who underwent MV repair for mainly advanced MVP. Three-dimensional TEE was more accurate (92%-100%) than 2D TEE (80%-96%) in identifying prolapsed segments. Three-dimensional TEE and intraoperative measurements of leaflet height did not differ significantly, while 2D TEE significantly overestimated the height of the posterior segment P1 and the anterior segment A2. Three-dimensional TEE quantitative MV measurements were related to surgical technique: patients with more complex MVP (one vs two to four vs five or more prolapsed segments) showed progressive enlargement of annular anteroposterior (31 ± 5 vs 34 ± 4 vs 37 ± 6 mm, respectively, P = .02) and commissural diameters (40 ± 6 vs 44 ± 5 vs 50 ± 10 mm, respectively, P = .04) and needed increasingly complex MV repair with larger annuloplasty bands (60 ± 13 vs 67 ± 9 vs 72 ± 10 mm, P = .02) and more neochordae (7 ± 3 vs 12 ± 5 vs 26 ± 6, P < .01). Measurements of MV anatomy on 3D TEE are accurate compared with surgical measurements. Quantitative MV characteristics, as assessed by 3D TEE, determined the complexity of MV repair.


Demodex folliculorum hominis (Simon): incidence in a normomaterial and in patients under systemic treatment with erythromycin or glucocorticoid.
A study was made of 20 cilia and sebum from 20 nasal follicles from each of 86 persons. In a normomaterial aged 20-30 years. Demodex folliculorum was present in the nasal follicles in 25% and in the cilia in 29% of the subjects. This is consistent with the very high incidence we found 10 years ago. Systemic erythromycin treatment did not erradicate the mite, but the incidence decreased in both regions. Systemic glucocorticoid treatment lowered the incidence in the nasal region, whereas the incidence increased in the ciliary region.


Priapism in sickle cell disease.
An 18-year-old black man with known history of homozygous (SS) sickle cell disease presented with sudden onset of priapism awakening him from sleep. Priapism as an isolated manifestation, without other signs or symptoms of sickle cell crisis, is thought to be more prevalent than previously reported. The patient was taken to surgery, where 14-gauge intercaths were used to aspirate blood from his corpora cavernosa bilaterally. Complete detumescence was achieved. At a five-month follow-up visit, normal erectile capacity was reported.


Stimulation of GluN receptors decreases the surface density of GluN1/GluN2B subunits in cultured neocortical interneurons.
Changes in the density of NMDA (GluN) receptors in the neuronal membrane are critical for plasticity, whereas malfunction of precisely regulated GluN receptor activity may be involved in neurotoxicity. In cultured rat neocortical interneurons, we have studied the regulation of the surface density of GluN1, GluN2A and GluN2B subunits. Application of 5 μMol NMDA for 24 h followed by a washout period of 24 h decreased the response of GluN receptors for at least 2 days. The reduction was caused by a decrease in the surface density of GluN1/GluN2B subunits, whereas GluN2A subunits remained unaffected. Our data indicate that long but reversible low level activation of GluN receptors can cause long-term changes in their subunit composition in cultured interneurons.


Resident-teaching of ethics in undergraduate medical education: a grounded theory analysis.
In graduate medical education, teaching is a required subcompetency largely fulfilled via clinical teaching, journal clubs, and grand rounds. Evidence shows that when moving to undergraduate teaching, residents often face a steep learning curve. We aimed to assess residents' perspective of the experience of teaching medical students. Psychiatry residents taught small group sections of bioethics to first- and second-year medical students in December 2018. We conducted two 1-hour focus group interviews with four residents on their perspectives on the teaching experience. Resident-teachers described receiving certain benefits from teaching, such as meeting their altruistic desire to give back to the profession. Nonetheless, some participants felt frustrated by students' varying engagement and respect, while also feeling insecure and intimidated. Resident-teachers experienced some of the medical students as disrespectful and limited in their appreciation for diversity and the profession of medicine and perceived the students' disengagement and lessened professionalism. As residency programs seek to implement initiatives to improve teaching skills of residents, resident experiences should be considered when implementing these initiatives.


Neurite outgrowth assessment using high content analysis methodology.
High content analysis of neurite outgrowth enables the rapid and comprehensive phenotypic assessment of individual neurons in a multiwell format amenable to high throughput assays. The resulting data are considered "high content" because multiple measurements of neuronal outgrowth and morphometric data are calculated from hundreds of individual cells within each image. This approach has been widely adopted by the pharmaceutical industry to accelerate neurological drug discovery and in vitro safety assessment. High content technology utilizes automated fluorescent and/or brightfield microscopy for image acquisition. The acquired images are then quantified using mathematical algorithms to measure pertinent neurobiological morphometric information, including neurite length, count, and extent of branching for each cell within the images. Furthermore, evaluation of the individual cell-level measurements enables the detection of subpopulations of cellular responders not apparent when examining well-level averages. Using this technology, neurite outgrowth can be quantified in each well, derived from hundreds of cell measurements in a 96-well microplate in approximately 30 min.


Bacteriophage T4 regA protein. Purification of a translational repressor.
The bacteriophage T4 regA protein translationally regulates its own synthesis and the synthesis of several other T4 early proteins. In order to study the mechanism of translational regulation, we have purified the regA protein. Initially a mutant protein, incapable of autogenous repression, was placed under lambda PL transcriptional control and amplified to approximately 10% of total cell protein. The membrane-associated mutant protein was extracted with organic solvent mixtures and purified by reverse phase-high performance liquid chromatography. Polyclonal antibodies prepared against the mutant protein were used in Western blot assays to monitor purification of the wild-type protein from T4-infected cells. Phosphocellulose and poly(U)-agarose chromatography were important steps in its purification. The binding properties of regA protein to polyribonucleotides are discussed in relation to the mechanism by which the protein recognizes its mRNA targets.


Processing technologies and cell wall degrading enzymes to improve nutritional value of dried distillers grain with solubles for animal feed: an in vitro digestion study.
Currently, the use of maize dried distillers grain with solubles (DDGS) as protein source in animal feed is limited by the inferior protein quality and high levels of non-starch polysaccharides (NSP). Processing technologies and enzymes that increase NSP degradability might improve digestive utilization of DDGS, enhancing its potential as a source of nutrients for animals. The effects of various combinations of processing technologies and commercial enzyme mixtures on in vitro digestion and subsequent fermentation of DDGS were tested. Wet-milling, extrusion, and mild hydrothermal acid treatment increased in vitro protein digestion but had no effect on NSP. Severe hydrothermal acid treatments, however, effectively solubilized NSP (48-78%). Addition of enzymes did not affect NSP solubilization in unprocessed or processed DDGS. Although the cell wall structure of DDGS seems to be resistant to most milder processing technologies, in vitro digestion of DDGS can be effectively increased by severe hydrothermal acid treatments.


Immunohistochemical localization of desmin in the quail ovary. Demonstration of a suspensory apparatus.
We have localized desmin in the quail ovary, by the unlabelled antibody peroxidase-antiperoxidase technique, using two monoclonal and one polyclonal antisera. Special attention has been paid to the influence of fixation and of proteolytic pretreatment of sections. It appeared that the immunostaining of desmin largely depends on the nature of the fixative. Carnoy fluid, Bouin's fixative, and a paraformaldehyde-acetic acid fixative preserved the histological structure very efficiently. However, trypsin pretreatment proved to be necessary to unmask the antigenic sites in the ovaries fixed in Bouin's fixative and the paraformaldehyde-acetic acid fixative. Desmin immunoreactivity was detected in the tunica albuginea and the chordae, a number of which surrounding the blood vessels, from the hilus to the thecal surface of the follicles. Small branches of chordae connected them with the tunica albuginea, forming a suspensory apparatus. Desmin was also localized in the smooth-muscle cells of the blood vessels. In the theca, immunoreactivity was detected in the wall of arterioles, of venules, and of capillaries. Further experimental and immunohistochemical research have to be performed to establish if the suspensory apparatus is a myoid tissue.


Improving the discrimination of hand motor imagery via virtual reality based visual guidance.
While research on the brain-computer interface (BCI) has been active in recent years, how to get high-quality electrical brain signals to accurately recognize human intentions for reliable communication and interaction is still a challenging task. The evidence has shown that visually guided motor imagery (MI) can modulate sensorimotor electroencephalographic (EEG) rhythms in humans, but how to design and implement efficient visual guidance during MI in order to produce better event-related desynchronization (ERD) patterns is still unclear. The aim of this paper is to investigate the effect of using object-oriented movements in a virtual environment as visual guidance on the modulation of sensorimotor EEG rhythms generated by hand MI. To improve the classification accuracy on MI, we further propose an algorithm to automatically extract subject-specific optimal frequency and time bands for the discrimination of ERD patterns produced by left and right hand MI. The experimental results show that the average classification accuracy of object-directed scenarios is much better than that of non-object-directed scenarios (76.87% vs. 69.66%). The result of the t-test measuring the difference between them is statistically significant (p = 0.0207). When compared to algorithms based on fixed frequency and time bands, contralateral dominant ERD patterns can be enhanced by using the subject-specific optimal frequency and the time bands obtained by our proposed algorithm. These findings have the potential to improve the efficacy and robustness of MI-based BCI applications.


Characterization of airway nitric oxide in allergic rhinitis: the effect of intranasal administration of L-NAME.
Several studies have attempted to assess nasal nitric oxide (NO) levels in allergic rhinitis (AR). However, there seem to be differences in the results obtained. We therefore wanted to investigate this further by studying airway NO in AR and controls at several modalities, and also the effect of intranasal administration of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine-methyl ester.HCl (L-NAME). Airway NO was determined through repeated measurements at three flow rates of air (0.5, 3, and 9 l/min), using a single-breath method and a method of nasal aspiration, in 18 patients with birch pollen AR during season and in 18 controls. Patients with AR were characterized by no difference in nasal but higher orally exhaled NO and a larger interindividual spread in nasal and orally exhaled NO compared to controls. We also found a greater reduction in nasal NO after L-NAME in patients compared to controls. These results indicate that several factors determine the levels of nasal NO in rhinitis. NO production in the nasal mucosa of patients with AR may be upregulated. On the other hand, this increase could be counteracted by swelling of the mucosa and secretions resulting in impaired NO diffusion from, for example, the paranasal sinuses, where particularly high levels of NO have been found. Also, the high background levels of NO from constitutive sources in the nose may blunt smaller increases in mucosal NO output. It seems that the methods for measurement of nasal NO need to be improved and standardized before we can consider to use this test in monitoring inflammation in AR.


Race, Ethnicity, and Clinical Features of Alcohol Use Disorder Among US Military Veterans: Results From the National Health and Resilience in Veterans Study.
Alcohol use disorder (AUD) is highly prevalent in US military veterans, though little is known about whether the psychiatric comorbidities and functional outcomes (ie, clinical features) of AUD differ across race/ethnic groups. We aimed to identify differences in the clinical features of veterans with AUD by race/ethnicity. In a sample of veterans with AUD (n = 1212) from the nationally representative National Health and Resilience in Veterans Study, we compared the clinical features associated with AUD across racial/ethnic groups using analysis of covariance and logistic regression. Black veterans (n = 60, 34.0%) were less likely to screen positive for lifetime AUD compared with white (n = 1099, 42.7%) and Hispanic (n = 53, 41.5%) veterans. Among those with lifetime AUD, Hispanic veterans were more likely than white veterans to have lifetime and current mood or anxiety disorders (adjusted odds ratio range [AORR] = 2.21-2.52, P < .05). Black veterans were more likely than white veterans to have current mood and anxiety disorders (AORR = 2.01-3.07, P < .05). Hispanic veterans reported poorer functioning and quality of life than white and black veterans (Cohen's d range = 0.12-0.37, P < .05). Black and Hispanic veterans with lifetime AUD may experience a higher disease burden relative to white veterans. Results underscore the importance of race/ethnicity-sensitive assessment, monitoring, and treatment of AUD for veterans. This is the first known study to examine differences by race/ethnicity in the clinical features of Veterans with AUD in a nationally representative sample. Findings suggest higher disease burden for racial/ethnic minority veterans. (Am J Addict 2021;30:26-33).


Identification and validation of risk factors for antisocial behaviour involving police.
Adult antisocial behaviour has precursors in childhood and adolescence and is most successfully treated using childhood interventions. The aim of this study was to identify and validate robust risk factors for antisocial behaviour involving police contact in a data-driven, hypothesis-free framework. Antisocial behavior involving police contact (20/25% incidence) as well as 554 other behavioural and environmental measures were assessed in the longitudinal general population Estonian Children Personality Behaviour and Health Study sample (n=872). The strongest risk factors for antisocial behaviour included past substance use disorder, gender, aggressive mode of action upon provocation, and concentration difficulties and physical fighting in school at age 15 years. Prediction using the selected variables for both methods in the other, unseen cohort resulted in an area under the receiver operating characteristics curve of 0.78-0.84. Our work confirms known risk factors for antisocial behaviour as well as identifies novel specific risk factors. Together, these provide good predictive power in an unseen cohort. Our identification and validation of risk factors for antisocial behaviour can aid early intervention for at-risk individuals.


Comparing the welfare effects of public and private health care subsidies in the United Kingdom.
We use a calibrated analytical model to compare the welfare costs (gross of externalities) of increasing subsidies for public and private health care in the UK. The model incorporates wait costs for rationed public care, burdens that subsidies impose on the tax system, and distributional weights for different households. Welfare costs are significantly higher for expanding public health care over a range of parameter scenarios. Both policies reduce average wait times, but for public health care this is offset by new waiting costs incurred on extra treatments. And the burden on the tax system is much larger for expanding public health care.


The Internet and the paediatric surgeon.
The Internet, which has truly united the world, is an extensive network of inter-linked computers storing immense bytes of information that can be accessed by anyone, transcending all barriers. The paediatric surgery Internet consists of exponentially growing material that deals with information specifically for paediatric surgeons and patients of the paediatric age group. We reviewed the methods available to take advantage of this network to enable busy paediatric surgeons to accrue the benefits easily and efficiently rather than be lost in the information ocean by surfing individually. By getting connected to the Internet, the paediatric surgeon gains enormous information that can be useful for patient care. The Internet has revolutionised scientific publications by virtue of its fast and accurate transmission of manuscripts. Paediatric surgeons can send manuscripts by this channel and also access journals, obviating the inherent lag period of communication by post.


[Cytogenetic activity of the butylcaptax defoliant transformation product].
Cytogenetical activity of the product of metabolitic butylcaptax transformations in cells of cotton plants G. barbadense has been studied. It is shown that butylcaptax, with a significant mutagenicity, looses its mutagenic activity, metabolizing in low mutagenic 2-oxyamylthiobenzthiazole. Low water solubility prevents its concentration to exceed 0.005% in tissue liquids and to exert a mutagenic action on cotton plants.


Integrated Analysis of DNA Methylation, Hydroxymethylation, and Gene Expression Data Using ME-Class2.
There is increasing interest in understanding the pathological role of DNA methylation changes in disease by profiling genome-wide methylation changes. This includes both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The typical profiling study is designed to measure 5mC and/or 5hmC levels alongside gene expression in a set of samples and controls to determine a list of candidate genes whose 5mC and/or 5hmC changes are associated with expression changes. We recently showed that ME-Class2 substantially outperforms other bioinformatic approaches at accurately identify genes with highly associated methylation and expression changes. ME-Class2 further illuminated how synergistic changes in 5mC and 5hmC potentially contribute to gene silencing and activation. Here we present a detailed protocol for using ME-Class2 to analyze genome-wide methylation (5mC and/or 5hmC) and expression data. Further, we provide advice about extending ME-Class2 to study the relationships between other epigenetic marks.