Identification and validation of miR-583 and mir-877-5p as biomarkers in patients with breast cancer: an integrated experimental and bioinformatics research.
Breast cancer (BC) is one of the most common cancers with a high mortality rate in women worldwide. The advantages of early cancer diagnosis are apparent, and it is a critical factor in increasing the patient's life and survival. According to mounting evidence, microRNAs (miRNAs) may be crucial regulators of critical biological processes. miRNA dysregulation has been linked to the beginning and progression of various human malignancies, including BC, and can operate as tumor suppressors or oncomiRs. This study aimed to identify novel miRNA biomarkers in BC tissues and non-tumor adjacent tissues of patients with BC. Microarray datasets GSE15852 and GSE42568 for differentially expressed genes (DEGs) and GSE45666, GSE57897, and GSE40525 for differentially expressed miRNAs (DEMs) retrieved from the Gene Expression Omnibus (GEO) database were analyzed using "R" software. A protein-protein interaction (PPI) network was created to identify the hub genes. MirNet, miRTarBase, and MirPathDB databases were used to predict DEMs targeted genes. Functional enrichment analysis was used to demonstrate the topmost classifications of molecular pathways. The prognostic capability of selected DEMs was evaluated through a Kaplan-Meier plot. Moreover, the specificity and sensitivity of detected miRNAs to discriminate BC from adjacent controls were assessed by area under the curve (AUC) using the ROC curve analysis. In the last phase of this study, gene expression on 100 BC tissues and 100 healthy adjacent tissues were analyzed and calculated by using the Real-Time PCR method. This study declared that miR-583 and miR-877-5p were downregulated in tumor samples in comparison to adjacent non-tumor samples (|logFC|< 0 and P ≤ 0.05). Accordingly, ROC curve analysis demonstrated the biomarker potential of miR-877-5p (AUC = 0.63) and miR-583 (AUC = 0.69). Our results showed that has-miR-583 and has-miR-877-5p could be potential biomarkers in BC.


Platelet membrane fluidity and Na+/K+ ATPase activity in acute stroke.
Stroke is a consequence of a reduction in cerebral blood flow but the mechanisms involved in the production of ischemic damage are complex and probably not fully known. It is hypothesized that alterations in platelet membrane fluidity are directly related to the severity of the stroke as measured by the National Institute of Health Stroke Scale (NIHSS). Thus, the aim of the present study was to investigate Na+/K+ ATPase activity and platelet membrane fluidity, measured by fluorescent probes TMA-DPH and DPH in patients affected by ischemic stroke and controls in order to identify, if any, chemical-physical and/or functional modifications associated with cerebral ischemic damage. Patients were divided into three groups according to the presence of vascular risk factors (Diabetes Mellitus, Hypertension and Smoking) in order to evaluate the possible influence of each risk factor on the NIHSS score and both Na+/K+ ATPase activity and platelet membrane fluidity. Data showed a significant decrease in both Na+/K+ ATPase activity and platelet fluidity values in patients compared to controls. Moreover, all three groups showed a negative significant correlation between NIHSS and Na+/K+ ATPase activity and a positive significant correlation between NIHSS, TMA-DPH and DPH. In conclusion, the present data point out that alterations in the platelet membrane's chemical-physical (decreased fluidity) and functional properties (reduced Na+/K+ ATPase activity) rose proportionally with NIHSS increase. These modifications and their interaction with some vascular risk factors might be involved in the pathogenesis of ischemic damage development.


Hirschsprung's disease: absence of serotonergic neurons in the aganglionic colon.
The distribution of enteric serotonergic neurons was studied in patients with Hirschsprung's disease. Specimens of bowel obtained at surgery were incubated in vitro with tritiated serotonin (3H-5-HT) in the presence of a high concentration of nonradioactive norepinephrine. Sites of high-affinity 3H-5-HT uptake were visualized by light-microscopic autoradiography. Specimens taken from ganglionic regions of the intestine (distal ileum or colon) showed intense labeling of the neuropil within the myenteric plexus. Silver grains were localized in a pericellular distribution around ganglion cells, but the ganglion cells themselves were relatively free of overlying silver grains. Corresponding regions of aganglionic colon or rectum demonstrated silver grain densities equivalent to background levels. Specific labeling was absent over the large nerve trunks in this region. These results suggest that 5-HT-containing neurons are present in the normal human intestine and that these neurons are absent in the aganglionic segment in Hirshsprung's disease.


Significance of changes in R wave amplitude during treadmill stress testing: angiographic correlation.
Coronary angiograms and treadmill stress tests were reviewed in 89 patients. Changes in R wave amplitude were measured in the control and immediate postexercise periods. Of 45 patients with normal coronary arteries, 41 (91 percent) had a decrease in R wave amplitude (P less than 0.01); 3 (7 percent) had an increase in amplitude, including 2 with abnormal left ventriculograms. The remaining patient (2 percent) had abnormal wall motion but no change in R wave amplitude. Among the 44 patients with significant coronary artery disease (70 percent or greater luminal narrowing in one or more vessels), R wave amplitude increased after exercise in 26 (59 percent) with more severe coronary artery disease. R wave amplitude decreased in 18 patients (41 percent) with normal or minimally abnormal resting ventriculograms and less severe coronary artery disease (P less than 0.01). Changes in R wave amplitude reflect ventricular function, an increase in R wave amplitude reflecting more severe dysfunction and severe coronary narrowing. A decreased R wave amplitude indicates normal or minimal dysfunction and is strongly associated with normal coronary angiograms.


General hospital admissions in young and middle-aged people who use psychoactive substances: Impact of Covid-19 lockdowns.
The Covid-19 pandemic offered a unique opportunity to investigate trends in hospitalizations related to psychoactive substance intoxication, since the usual health burden of social use at parties and gatherings was likely to be decreased during lockdowns and curfew periods. Since young adults are the main users of psychoactive substances for experimental and recreational purposes, this study identified and compared hospitalization trends in young adults and adults over 30 years old. This national cohort study was conducted using the French hospital discharge database. An interrupted time-series analysis for the period between 2014 and 2020 was performed in two groups: young (age 18-29) and other adults (30+) to ascertain the trends in the monthly incidence of hospitalization related to psychoactive substance intoxication (opiates, cocaine, benzodiazepines, psychostimulants, alcohol and cannabis). Hospitalization characteristics during the first and second lockdown and the period between them were compared to the reference period (from 01/01/2014 to 29/02/2020). Among 1,358,007 stays associated with psychoactive substance intoxication, 215,430 concerned young adults. Compared with adults 30+, hospitalization trends in young adults showed a greater decrease in the number of stays during lockdown, with a maximum decrease of -39% during the first lockdown (1,566 vs. 2,576; CI95%: 2,285-2,868) versus -20% (10,212 vs. 12,894; CI95%: 12,001-13,787) in the second lockdown. Presentations for alcohol intoxication decreased throughout the pandemic, particularly during the second lockdown, while admissions for benzodiazepine intoxication increased during both lockdowns. Admissions for cannabis intoxication increased throughout the entire period. Lockdowns were associated with fewer hospitalizations related to psychoactive substance intoxication in both age groups, especially among young adults, which might reflect a decrease in social use. Recreational use might therefore be an important target for prevention and risk minimization.


Handgrip Strength and Cognitive Function among Elderly Koreans: Insights from the Korean Longitudinal Study of Ageing.
This study aims to assess handgrip strength as a predictor of cognitive decline within men and women in Korea. A random-intercept logistic regression is fit to estimate the status changes in cognitive function throughout all rounds of the KLoSA, a nationally-representative survey of adults aged 45 years and older. Males in the highest quartile were 71.9% less likely to experience cognitive impairment than those in the lowest quartile. The odds of cognitive impairment for men in the third and second quartiles reduced by 62.6% and 60.4% respectively. Similarly, the odds of cognitive impairment for women declined as 72.7%, 63.0%, and 41.8% for fourth, third, and second quartile, respectively, compared with the lowest quartile. These results imply that assessing and monitoring handgrip strength may enable us to identify subgroups of the elderly with higher likelihood of cognitive impairment in Korea.


PRMT1 promotes the proliferation and metastasis of gastric cancer cells by recruiting MLXIP for the transcriptional activation of the β-catenin pathway.
Protein arginine methyltransferase 1 (PRMT1), a type I PRMT, is overexpressed in gastric cancer (GC) cells. To elucidate the function of PRMT1 in GC, PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hairpin RNA (shRNA) or inhibited by PRMT1 inhibitors (AMI-1 or DCLX069), which resulted in inhibition of GC cell proliferation, migration, invasion, and tumorigenesis in vitro and in vivo. MLX-interacting protein (MLXIP) and Kinectin 1 (KTN1) were identified as PRMT1-binding proteins. PRMT1 recruited MLXIP to the promoter of β-catenin, which induced β-catenin transcription and activated the β-catenin signaling pathway, promoting GC cell migration and metastasis. Furthermore, KTN1 inhibited the K48-linked ubiquitination of PRMT1 by decreasing the interaction between TRIM48 and PRMT1. Collectively, our findings reveal a mechanism by which PRMT1 promotes cell proliferation and metastasis mediated by the β-catenin signaling pathway.


Researches and Application of Ganoderma Spores Powder.
Ganoderma lucidum spores (GLS) are the mature germ cells of Ganoderma lucidum. They have all the genetic substances and similar active components of Ganoderma lucidum. Similar to the fruiting body of Ganoderma lucidum, ganoderma spores powder has the effect of regulating immunity, antitumor, antioxidation, and protecting cells and so on. In recent decades, with the development of the technology of breaking the wall of Ganoderma lucidum spores and the technology of extracting and preparing, the researches and application of Ganoderma lucidum spores powder have made great progress.


Iron intakes and serum ferritin levels in developmentally delayed children. An assessment of maternal knowledge and attitudes.
A survey conducted on a quota sample of 42 developmentally delayed children included assessment of maternal nutrition knowledge and attitudes. A 24-hour recall was combined with a two-day food record for calculation of dietary iron intakes of the children. Serum ferritin levels were used to assess subjects' iron stores. Maternal education was positively correlated with maternal nutrition knowledge, attitude toward meal planning, and stricter attitudes toward feeding children. Maternal nutrition knowledge and strictness attitudes significantly correlated with dietary iron intake. Relative feeding skills and age correlated with serum ferritin levels.


Changes in the expression of HLA and beta 2-microglobulin by cultured lymphoid cells.
Changes in the expression of HLA and beta 2-microglobulin (beta 2-m) antigens by cultured human lymphoid cell lines were investigated. HLA expression was assayed by indirect trace binding radioimmunoassay (RIA) with monoclonal antibodies and by determining sensitivity to complement-dependent lysis by alloantisera. Lymphoid cells in culture were found to undergo changes in the expression of HLA and beta 2-m antigens characterized by decreased membrane expression of these antigens at high cell densities or after a prolonged period of cultivation. The decreased expression of HLA and beta 2-m antigens apparently is due neither to a masking phenomenon nor to a lack of nutrients or an accumulation of metabolites in the culture media but is perhaps mediated by a cell-to-cell contact mechanism. Human interferon was found to enhance the expression of HLA and beta 2-m, apparently overriding the effects on major histocompatibility complex (MHC) expression induced by cell density.


Characterization of spatiotemporal electroactive anodic biofilm activity distribution using 1D simulations.
Activity distribution limitation in electroactive biofilm remains an unclear phenomenon. Some observations using confocal microscopy have shown notable difference between activity close to the anode and activity at the liquid interface. A numerical model is developed in this work to describe biofilm growth and local biomass segregation in electroactive biofilm. Under our model hypothesis, metabolic activity distribution in the biofilm results from the competition between two limiting factors: acetate diffusion and electronic conduction in the biofilm. Influence of inactive biomass fraction (i.e. non-growing biomass fraction) properties (such as conductivity and density) is simulated to show variation in local biomass distribution. Introducing a dependence of effective diffusion to local density leads to a drastic biomass fraction segregation. Increasing density of inactive fraction reduces significantly acetate diffusion in biofilm, enhances biomass activity on the outer layer (liquid/biofilm interface) and maintains inner core largely inactive. High inactive fraction conductivity enhances biomass activity in the outer layer and enhances current production. Hence, investment in extracellular polymer substance (EPS), anchoring redox components, is benefit for biofilm electroactivity. However, under our model hypothesis it means that conductivity should be two order lower than biofilm conductivity reported in order to observe inner core active biomass segregation.


What do clinicians mean by epidemics' preparedness.
Infectious disease pandemics and epidemics pose significant global threats, and the risk of emerging infectious diseases has increased because of factors such as international connections, travel, and population density. Despite investments in global health surveillance, much of the world remains unprepared to manage infectious disease threats. This review article discusses the general considerations and lessons learned from the COVID-19 pandemic in terms of epidemic preparedness. Non-systematic search on PubMed, scientific society websites, and scientific newspapers (performed in April 2023). Key factors for preparedness include robust public health infrastructure, adequate allocation of resources, and effective communication between stakeholders. This narrative review emphasizes the need for timely and accurate dissemination of medical knowledge, as well as addressing the challenges of misinformation and infodemics. It also highlights the importance of quick availability of diagnostic tests and vaccines, ensuring equitable access to these technologies. The role of scientific coordination in developing treatment strategies and the safety and mental well-being of healthcare workers are discussed. Lastly, it should be emphasized the need for medical training, multidisciplinary teams, new technologies and artificial intelligence, and the active role of infectious disease physicians in epidemic preparedness efforts. From clinicians' perspective, healthcare authorities play a crucial role in epidemic preparedness even by providing resource management plans, ensuring availability of essential supplies and training, facilitating communication, and improving safe infection management.


Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. II. Structure elucidation.
The structures of new acetylcholinesterase inhibitors, arisugacins A and B, were elucidated by NMR study. Arisugacins have a (4aR,6aR,12aS,12bS)-4a,6,6a,12,12a, 12b-hexahydro-4a,12a-dihydroxy-4,4,6a,12b-tetramethyl-4H,11H -naphtho[2,1-b] pyrano[3,4-e]pyran-1,11(5H)-dione moiety in common and 3,4-dimethoxyphenyl or 4-methoxyphenyl residues are attached to C-9 of the moiety.


Neoadjuvant Chemotherapy Prior Fertility-Sparing Surgery in Women with FIGO 2018 Stage IB2 Cervical Cancer: A Systematic Review.
Nowadays, the optimal management of patients with cervical cancers measuring 2-4 cm desiring to maintain fertility is still uncertain. In this systematic review, we assessed the reliability of neoadjuvant chemotherapy (NACT) prior to fertility-sparing (FS) surgery in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer, in terms of pathologic response, oncological and obstetric outcomes. The review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, using MEDLINE and PubMed, were searched for from 1 January 2005 up to 1 December 2020. We identified 20 articles and 114 women with IB2 disease, possible candidates for NACT prior to FS surgery. However, uterine conservation was achieved only in 76.7% of them. Patients reached optimal pathological response to NACT in 60.9% of cases and a TIP (cisplatin, ifosfamide and paclitaxel) regime was related to the best response. Suboptimal response to NACT appeared to be an independent negative prognostic factor. Up to 9.2% of patients recurred with a median 7.4-months DFS, and 4.6% of patients died of disease. Fifty percent of women tried to conceive after treatment and NACT prior to conization appeared to be the most promising alternative to upfront radical trachelectomy in terms of obstetric outcomes. In conclusion, NACT prior to FS surgery is an option, but the literature about this issue is still weak and FS should be carefully discussed with patients.


Prognostic Value of SMAD4 in Pancreatic Cancer: A Meta-Analysis.
The prognostic value of SMAD4 in pancreatic cancer has been evaluated in several studies. However, the conclusions remain controversial. Therefore, we aimed to evaluate the association between SMAD4 expression and the outcome of pancreatic cancer patients by performing a meta-analysis. We systematically searched for relevant studies evaluating the relationship between SMAD4 expression and the outcome of pancreatic cancer patients until May 2015. A meta-analysis was performed using STATA 12.0, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 expression and the prognosis of pancreatic cancer patients. The analysis included 1762 patients from 14 studies, with 1401 patients from 11 studies and 927 patients from 8 studies included in the univariate and multivariate analyses, respectively. Loss of SMAD4 expression was found to be significantly correlated with poor overall survival, with the combined HR (95% CI) of 1.20 (1.03-1.40). After adjusting for potential confounders using the Cox regression model, the pooled HR (95% CI) was 1.88 (1.31-2.70). In subgroup analysis, study region, number of patients, follow-up duration, and cutoff value were found to affect the significance of the association between loss of SMAD4 expression and poor prognosis. In addition, there was no evidence of publication bias, as suggested by Begg's and Egger's test. Loss of SMAD4 was associated with poor survival and was a negative prognostic indicator in patients with pancreatic cancer.


In vitro investigations on induction and reversal of cisplatin resistance in a rat ovarian tumor cell line.
Resistance of a rat ovarian tumor cell line (O-342/DDP) to cisplatin was induced in vitro by stepwise increase of cisplatin concentrations. Both chemosensitive parental cells (O-342) and resistant O-342/DDP cells grow in a monolayer and enter log-phase growth about 24 h after seeding (cell population doubling time in log-phase growth is about 24 h). O-342/DDP cells show a 33-fold resistance to cisplatin as compared to O-342 cells (ID50 = 33 microM in O-342/DDP vs 1 microM in O-342 cells). The intracellular total glutathione (GSH + GSSG) of O-342/DDP cells was twice as high as that of O-342 cells (3.04 vs 1.37 nmol/10(6) cells), while the intracellular GSSG was increased by 26% in O-342/DDP cells compared to O-342 cells. DNA interstrand crosslinks were found to be 8.5 times higher in O-342 cells than in O-342/DDP cells (204 vs 24 rad equiv.), following cisplatin treatment. DNA single-strand breaks were approximately doubled in the sensitive line as compared to the resistant line following exposure to cisplatin. Chromosome analysis uncovered a change in the karyotype of O-342/DDP cell as compared to O-342 cells. In the sensitive line hyperploid (3n) clones, in the resistant line near-diploid clones predominated. Both DL-buthionine-(S,R)-sulfoximine and 3-aminobenzamide were able to sensitize the resistant line towards cisplatin. Thus, the present results suggest that mechanisms for cisplatin resistance in this tumor line apparently are multi-factorial, and include a higher intracellular GSH content and an increased repair activity.


Exploring hospital practice types and their impact on glomerular pathologic patterns: Insights from the largest kidney biopsy cohort in Thailand.
This study aims to investigate the influence of different kidney biopsy practices on the prevalence of glomerular pathologic patterns in the largest kidney biopsy registry in Thailand. We conducted a retrospective review of kidney biopsy records from the period between 2000 and 2014. The records were obtained from 2 major institutions: King Chulalongkorn Memorial Hospital, a large university-based hospital, and the Kidney Center Bangkok Hospital, which provides pathology services to hospitals throughout Thailand. The study included native kidney biopsies from all provinces in Thailand, excluding paediatric patients, kidney transplant recipients, and cases of inadequate and repeated biopsies. Patient demographics, indications for biopsy, and final glomerular diagnoses were compared across different hospital practice settings: university (UVH), private (PVH) and public (PBH). A total of 5893 eligible native kidney biopsies were identified from a pool of 7005 biopsies conducted over a 15-year period in 25 provinces throughout Thailand. The 3 most common indications for biopsy were suspected kidney involvement in systemic lupus erythematosus (SLE) (29%), nephrotic syndrome (NS) (29%), and acute glomerulonephritis (AGN)/rapidly progressive glomerulonephritis (RPGN) (13%). The leading indication for biopsy differed across practice types, with suspected kidney involvement in SLE being the primary indication in UVH, while NS took precedence in both PBH and PVH practices. Notably, UVH performed fewer kidney biopsies for asymptomatic urinary abnormalities and diabetes-related indications compared with PVH and PBH. The leading glomerular diagnoses correlated with the biopsy indications, with lupus nephritis (LN) being the most common diagnosis in UVH and PBH practices, whiles immunoglobulin A nephropathy was the predominant diagnosis in PVH practice. Hospital practice types significantly impact the prevalence of glomerular pathologic diagnosis patterns in kidney biopsy data, highlighting the importance of considering this influence in epidemiological comparisons.


The novel oral gonadotropin-releasing hormone receptor antagonist relugolix is a new option for controlled ovarian stimulation cycles.
Relugolix is an oral gonadotropin-releasing hormone antagonist (GnRHant), which was first introduced in 2019. This study investigated the effects of the conventional injectable GnRHant formulation and this new oral GnRHant formulation on controlled ovarian stimulation (COS) cycles. Relugolix was administered in 126 cycles and conventional GnRHant injection was administered in 658 cycles (controls). The follicle stimulation was performed by an antagonist method, and for final oocyte maturation, recombinant human chorionic gonadotropin (rHCG), or gonadotropin-releasing hormone agonist (GnRHa), or both (dual trigger) were selected. The number of retrieved oocytes was counted and then they were evaluated for subsequent development up to cleavage stage. The number of retrieved oocytes which was the primary outcome of this research was affected by the combination of GnRHant type and the final oocyte maturation agent. The combination of relugolix and a GnRHa trigger showed a significantly lower number of retrieved oocytes (p < 0.001) than the other combinations. Relugolix is a new option for COS cycles, but should be carefully combined with the final maturation agent. This study was conducted after approval by the Medical Corporation Sankeikai Institutional Ethics Committee (approval number: 2019-34).


Analgesia, development of tolerance, and 5-hydroxytryptamine turnover in the rat after cerebral and systemic administration of morphine.
Morphine HCl (10 micrograms/0.5 microliter) was injected into the right striatum, the caudal aqueduct and the region of the nucleus raphe magnus of the rat. Turnover of 5-hydroxytryptamine (5-HT) in the brain was assessed by fluorimetric estimation of 5-hydroxyindol-3-ylacetic acid following the administration of probenecid. Injection into the right striatum (a region containing 5-HT terminals) increased 5-HT turnover in the right, but not in the left striatum or in the anterior medulla. The pain threshold was unaltered. Injection into the aqueduct accelerated 5-HT turnover in the anterior medulla, but the striata and spinal cord showed no such change. Analgesia was pronounced. Injection of morphine into the region of the nucleus raphe magnus analgesia and increased 5-HT turnover in the posterior medulla and the spinal cord. The action on the cord must have been the result of the stimulation of cells in the raphe. The effects of the local injections of morphine on 5-HT turnover were antagonized by systemic naloxone (1-2 mg/kg) in all the regions studied. When morphine was administered subcutaneously three times a day for five days, tolerance developed to the analgesic effect of morphine (7mg/kg). However, tolerance to its acceleration of 5-HT turnover was only seen in the spinal cord, not in striatum or anterior and posterior medulla. When morphine was withdrawn, its effects on analgesia and 5-HT turnover in the spinal cord recovered simultaneously. The results emphasize the likely part played by the descending serotoninergic pathway in the analgesic effect of morphine.


Personality traits and long-term health status. The influence of neuroticism and conscientiousness on renal deterioration in type-1 diabetes.
Stringent long-term control of blood glucose concentration in patients with insulin-dependent diabetes mellitus (IDDM) can decrease albuminuria, presumably forestalling development of renal insufficiency. Personality characteristics may influence a diabetic patient's ability and willingness to follow a prescribed regimen to achieve glycemic control. This study investigated the relationship of 2 personality factors to renal deterioration time (from initiation of insulin therapy to renal failure) in 85 patients with IDDM and end-stage renal disease. Persons moderate in the personality trait of neuroticism and high in conscientiousness had renal deterioration times that were 12 years longer than persons with either high or low neuroticism and low conscientiousness, presumably because of better self-care. The implications of this study's findings are discussed.


Safety and efficacy of a new modified intravenous recombinant tissue plasminogen activator (rt-PA) regimen in Chinese patients with acute ischemic stroke: A descriptive retrospective cohort study with subgroup-analysis of different rt-PA dose.
Evidence for effects of the dose of recombinant tissue plasminogen activator(rt-PA) in Asian populations is inconclusive. The standard dose may cause drug waste and increase economic burden in developing country. Therefore, we preliminarily describe the safety and efficacy of a new modified dose of rt-PA regimen(0.6 or 0.9 mg/kg, with a maximum dose of 50 mg) in real world settings. 265 consecutive patients with ischemic stroke were treated with intravenous(IV) rt-PA alone from all the 323 consecutive patients treated with reperfusion therapy between January 1, 2017 and March 31, 2020. Safety and Efficacy was assessed by early neurological improvement(ENI), early neurological deterioration(END), symptomatic intracranial hemorrhage(sICH) and 90-day outcome defined by modified Rankin scale(mRS). Subgroup analysis was conducted to draw comparisons between different dose groups ([0.5,0.6)mg/kg, [0.6,0.7)mg/kg, [0.7,0.8)mg/kg, [0.8,0.9]mg/kg). Among the 265 patients, 150(56.60%) had a favorable outcome at 3 months(3 M); Mortality occurred in 17(6.40%) in 3 M; sICH in 12(4.50%); ENI in 70(26.40%); END2 in 29(10.90%) and END4 in 18(6.80%). In subgroup analysis, there was a significant difference in sICH that more patients developed sICH in [0.8-0.9]mg/kg group(P = 0.044) in univariate analysis of different dose. After adjusting, there was no significant difference between 4 dosage groups. Significant differences were seen in gender, atrial fibrillation and baseline NIHSS in the multivariable model of favorable outcome at 3 M. Our study preliminarily shows a good safety and efficacy of our modified rt-PA regimen, indicating that this regimen should be worthy of further study especially in developing country to reduce the financial burden of patients and avoid drug waste.


Three-dimensional hierarchical architectures constructed by graphene/MoS2 nanoflake arrays and their rapid charging/discharging properties as lithium-ion battery anodes.
Charged up: Three-dimensional architectures constructed from graphene/MoS2 nanoflake arrays have been successfully fabricated by a one-step hydrothermal method. MoS2 nanoflakes with thicknesses less than 13 nm grow vertically on both sides of graphene sheets (see figure), which allows the architectures to be more stable during charging and discharging. Even at a high current density of 8000 mA g(-1), their discharge capacity is still up to 516 mA h g(-1).


Excited-State Dynamics of a meta-Dimethylamino Locked GFP Chromophore as a Fluorescence Turn-on Water Sensor.
Strategic incorporation of a meta-dimethylamino (-NMe2 ) group on the conformationally locked green fluorescent protein (GFP) model chromophore (m-NMe2 -LpHBDI) has drastically altered molecular electronic properties, counterintuitively enhancing fluorescence of only the neutral and cationic chromophores in aqueous solution. A ~200-fold decrease in fluorescence quantum yield of m-NMe2 -LpHBDI in alcohols (e.g., MeOH, EtOH and 2-PrOH) supports this GFP-derived compound as a fluorescence turn-on water sensor, with large fluorescence intensity differences between H2 O and ROH emissions in various H2 O/ROH binary mixtures. A combination of steady-state electronic spectroscopy, femtosecond transient absorption, ground-state femtosecond stimulated Raman spectroscopy (FSRS) and quantum calculations elucidates an intermolecular hydrogen-bonding chain between a solvent -OH group and the chromophore phenolic ring -NMe2 and -OH functional groups, wherein fluorescence differences arise from an extended hydrogen-bonding network beyond the first solvation shell, as opposed to fluorescence quenching via a dark twisted intramolecular charge-transfer state. The absence of a meta-NMe2 group twisting coordinate upon electronic excitation was corroborated by experiments on control samples without the meta-NMe2 group or with both meta-NMe2 and para-OH groups locked in a six-membered ring. These deep mechanistic insights stemming from GFP chromophore scaffold will enable rational design of organic, compact and environmentally friendly water sensors.


Melnick-Needles osteodysplasia associated with pulmonary hypertension, obstructive uropathy and marrow hypoplasia.
A three and one half-year-old female with Melnick-Needles osteodysplasia is presented. In addition to the characteristic bone roengenograms and obstructive uropathy, the patient had inadequate formation of bone marrow elements and pulmonary arter hypertension.


Synthesis of spiro[2.5]octa-4,7-dien-6-one with consecutive quaternary centers via 1,6-conjugate addition induced dearomatization of para-quinone methides.
An efficient one-pot approach for the synthesis of spiro[2.5]octa-4,7-dien-6-ones by employing para-quinone methides has been developed. The reaction proceeded smoothly in high yields under mild conditions without the use of metals. Moreover, all products obtained herein contained two or three consecutive quaternary centers.


Oenological potential and health benefits of Chinese non-Vitis vinifera species: An opportunity to the revalorization and to breed new varieties.
The wine industry is focused on the producing wine mostly from European grapevine varieties (Vitis vinifera L.). China has experienced a significant growth of the vineyard surface, based on the cultivation of these grapevine varieties. Currently, China has become one of the countries with the largest surface of planted vineyards in the world. In the last years, there has been a trend to oenologically and viticulturally revalorize certain autochthonous grapevine species. China holds a great diversity of Vitis species, which are being the focus of study. This could be an important alternative for the diversification of wine production, providing new products with a strong identity. Additionally, the varietal homogenization has increased the vineyard genetic vulnerability in relation to the emergence of grapevine diseases and their resistance to chemical fungicides. In this way, non-Vitis vinifera species are characterized by having a high resistance to a wide range of biotic and abiotic factors, which can bring an opportunity to breed new varieties. However, there is little available information about the oenological potential of these species, which makes it a current interesting topic. Therefore, this review aims to summarize the oenological potential of non-Vitis vinifera species found in China, discussing their potential effects on human health and thus, to propose some Chinese wild grapes for their use in breeding programs.


Early lung cancer diagnostic biomarker discovery by machine learning methods.
Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients' plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer.


Pet-keeping in early childhood and airway, nose and skin symptoms later in life.
It is discussed whether exposure to pets during childhood is a risk or a protective factor for sensitization and allergic symptoms. The aim of this study was to investigate the association between pet-keeping at time of birth and allergic symptoms in airways, nose and skin among young children in Sweden. A questionnaire was sent to the parents of 14 077 children (1-6 years), the focus being on allergic symptoms, home environment and other background factors including pet-keeping and avoidance behaviour. The response rate was 79%. Almost one-tenth of the population had got rid of pets because of allergy in the family, and 27.3% reported "avoidance" behaviour towards pets. In a cross-sectional analysis current pet-keeping was "protective", but this may be due to the fact that people avoid exposing their child to something that they believe is a risk factor for allergies. Pet-keeping at the time of birth was associated with "wheezing", "asthma" and "rhinitis on pet-exposure" later in life for children from families with an "avoidance" behaviour, and was not "protective" for other children. There was also an indication of a dose-response relationship between the number of types of furred pets at time of birth and later symptoms in analyses adjusted for avoidance behaviour or current pet-keeping. The distribution of pet-keeping in the population is largely explained by avoidance behaviour, meaning that those who have pets mainly are those who can stand them, indicating a "healthy pet-keeping effect".


Novel approach for synthesis of boehmite nanostructures and their conversion to aluminum oxide nanostructures for remove Congo red.
A phase transfer method was developed to prepare boehmite (γ-AlOOH) nanostructures with various morphologies including nanofragments, nanorods, nanoflakes and multiply stacked nanostructures. The effect of the reaction temperature on the morphology of the as-prepared γ-AlOOH was investigated systematically. After calcination, the corresponding aluminum oxide (γ-Al2O3) nanostructures were obtained from the as-prepared γ-AlOOH products and preserving the same morphology. The obtained samples were characterized by several techniques, such as X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and N2 adsorption-desorption technique. The possible formation mechanism of the boehmites has also been proposed. Adsorption experiments indicated that γ-Al2O3 nanorods exhibited better adsorption capacity for Congo red (CR) in contrast to other as-prepared γ-Al2O3 nanostructures and commercial alumina (Al2O3), and the adsorption obeyed well to Langmuir isotherm model. Besides, the adsorption kinetics followed pseudo-second-order rate equation.


Transumbilical laparoscopic appendectomy for acute appendicitis: a reliable one-port procedure.
Emergency surgical procedures frequently must be performed at times when availability of adequately trained personnel is problematic yet the requirements for maintaining surgical quality and patient safety remain unchanged. This report aims to describe a safe, effective, transumbilical, one-port laparoscopic technique for appendectomy that can be performed by one surgeon. Between January 2006 and December 2008, transumbilical one-port laparoscopic appendectomy (TOPLA) was used by two pediatric surgeons in the authors' department to treat 152 consecutive patients presenting with simple and complicated appendicitis. With the patient placed in the Trendelenburg position and rotated to the left, a single surgeon was easily able to perform the procedure using a 10-mm 0° operative laparoscope (Karl Storz) with a 5-mm working channel. The appendix was lifted with transabdominal suspensory sutures to facilitate its removal. The results were compared with those for 112 patients receiving open appendectomy (OA) during the same period. The operative time was significantly shortened using TOPLA (mean, 61.5 min) compared with using OA (mean, 118.3 min) (p = 0.000). Despite significantly higher numbers of patients with complicated appendicitis enrolled in the TOPLA arm of the study, the rate of wound infection was significantly lower after TOPLA (0%, 0/152) than after OA (9.8%, 11/112) (p = 0.000). The number of patients requesting intramuscular or intravenous analgesics for pain relief was significantly lower after TOPLA than after OA. The overall results for TOPLA were comparable with those for the more common three-port laparoscopic procedure, but it offers the alternative of having an inconspicuous scar hidden within the umbilicus. This report describes a simple and safe laparoscopic procedure that offers an effective way for one surgeon to treat simple and complicated appendicitis through a single port with satisfactory cosmetic outcomes.


Light-scattering studies of fractionated ovine submaxillary mucins.
Static and dynamic light-scattering studies of solutions of ovine submaxillary mucin (OSM) glycoproteins, fractionated by exclusion chromatography on Sephacryl S-1000, are reported. These experiments yielded information regarding the structure and conformation of the glycoprotein chain, in the form of weight-average molecular weights, Mw, z-average radius of gyration, Rg,z, and z-average of the inverse hydrodynamic radius, (Rh-1)z. The values of (Rh-1)z are found to correlate very well with the S-1000 elution volume characteristics for four OSM fractions of different molecular weights. The structural parameters for these OSM fractions are, within experimental error, similar to those deduced for porcine submaxillary mucins (PSM) in earlier studies. The results suggest that, like PSM, the glycoprotein structure of OSM consists of linear chains constructed by covalently linking two or more elementary subunits together via disulfide bonds. In addition, the rigidity of the protein core of OSM is substantially greater than that observed for non-glycosylated-polypeptide random coils. Because (Rh-1)z, and hence, elution volume depends only on the molecular weight of the mucin protein core, the Mw calibration obtained for OSM should be applicable to the chromatography of other mucin glycoproteins.


[Hemoglobin abnormalities and glucose 6 phosphate dehydrogenase deficiency (G6PD) in 101 refugees from southeast Asia].
Hematological studies were performed systematically in 101 refugees from South-Eastern Asia living in the Grenoble area at the present time. We found: --4 haemoglobin E homozygosity, --29 haemoglobin E heterozygosity, --2 beta-thalassemia heterozygosity, --4 alpha-thalassemia heterozygosity, --14 glucose 6 phosphate dehydrogenase deficiencies.


Water extracts of Helicobacter pylori delay healing of chronic gastric ulcers in rats: role of cytokines and gastrin-somatostatin link.
Helicobacter pylori (Hp) is considered as a major risk factor of peptic ulcer, but the pathogenic mechanism of its action has not been fully explained. This study was designed: (1) to compare the ulcer healing effects of water extract (WE) obtained from type-I cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) expressing Hp and from type-II CagA- and VacA-negative Hp strain with those of vehicle (saline), and (2) to determine the alterations in gastric secretion, gastric blood flow (GBF) and expression of Hp-related cytokines during the ulcer healing in rats treated with toxigenic (type-I) and non-toxigenic (type-II) Hp-derived WE. Gastric ulcers were produced by serosal application of acetic acid in rats with or without gastric fistula treated with vehicle (saline) or WE originating from type-I or type-II Hp administered intragastrically on days 1, 3, 5 and 7 upon ulcer induction. On days 3, 9 and 15, animals were lightly anesthetized with ether, the abdomen was opened and the GBF was measured by the H2-gas clearance technique in the ulcer area and non-ulcerated mucosa. Venous blood was withdrawn for the measurement of plasma cytokine (IL-1beta and TNFalpha) levels and plasma and gastric contents were also collected for gastrin and somatostatin determination by specific radioimmunoassay. Gastric ulcers healed gradually in vehicle-treated controls and the ulcer area on days 3, 9 and 15 was reduced by 12, 43 and 92%, respectively. In rats treated with WE of type-I Hp, ulcer healing was significantly delayed, and gastritis and infiltration of ulcerated gastric mucosa with inflammatory cells were observed histologically. The prolongation of ulcer healing by WE of both Hp strains was accompanied by a marked fall in the GBF at the ulcer margin and transient hyposecretion especially in rats given WE of type-I Hp strain. On day 15 of ulcer healing, the plasma concentration of IL-1beta and TNFalpha was negligible in vehicle control rats, but it was significantly elevated particularly in rats treated with WE of type-I Hp. RT-PCR analysis revealed that mucosal expression of IL-1beta and TNFalpha mRNA was significantly upregulated in the gastric mucosa of rats treated with either toxigenic or non-toxigenic Hp WE. The plasma gastrin level was significantly higher and the luminal concentration of somatostatin was significantly lower in rats treated with Hp-WE than in vehicle-treated controls and these alterations were more pronounced in rats treated with WE type-I than type-II Hp. WE of toxigenic Hp strain delays ulcer healing due to the reduction in the gastric microcirculation at the ulcer margin, the overexpression of inflammatory cytokines and the impairment of the gastrin-somatostatin link.


Editing of polymer backbones.
Polymers are at the epicentre of modern technological progress and the associated environmental pollution. Considerations of both polymer functionality and lifecycle are crucial in these contexts, and the polymer backbone - the core of a polymer - is at the root of these considerations. Just as the meaning of a sentence can be altered by editing its words, the function and sustainability of a polymer can also be transformed via the chemical modification of its backbone. Yet, polymer modification has primarily been focused on the polymer periphery. In this Review, we focus on the transformations of the polymer backbone by defining some concepts fundamental to this topic (for example, 'polymer backbone' and 'backbone editing') and by collecting and categorizing examples of backbone editing scattered throughout a century's worth of chemical literature, and outline critical directions for further research. In so doing, we lay the foundation for the field of polymer backbone editing and hope to accelerate its development.


Bora-alkenes: Metal Coordination and Reactions with BH-boranes.
The neutral N-heterocyclic carbene stabilized bora-alkene 1, conveniently prepared by a BH borenium/hydroboration route, forms stable copper, gold or palladium π-complexes. The polar bora-alkene B=C system undergoes regioselective hydroboration reactions with the (C6 F5 )2 BH or C6 F5 BH2 ⋅ SMe2 boranes. The latter reaction involves a subsequent rearrangement that leads to internal hydride vs. isothiocyanate substituent exchange at the borane pair.


Thymectomy in myasthenia gravis: comparison of outcome in Santiago, Cuba and Nottingham, UK.
We compared the outcome of thymectomy for myasthenia gravis (MG) in two healthcare systems. In Nottingham, UK, thymectomy is performed for thymic enlargement and considered in acetylcholine receptor (AchR) antibody positive patients. In Santiago, Cuba, thymectomy is considered in all generalised MG patients irrespective of their radiological findings or AchR antibodies. 22 MG patients in Nottingham and 75 in Santiago who had a thymectomy were identified and their notes reviewed. We compared the median age, stage of disease, thymic histology and clinical outcome at two years post-thymectomy. The median ages for the Cuban and Nottingham patients were 25 and 35 years respectively. The median stage of disease was IIa by Osserman's classification in both. In Nottingham, 59% (13/22) showed an improvement compared with 88 % (66/75) in Santiago (p < 0.01). There were significantly more cases of thymoma in Nottingham whereas thymic hyperplasia and atrophy were a more frequent finding in Cuban patients. The majority of cases who improved post-thymectomy had thymic hyperplasia on histology in both Nottingham (46%) and Cuban (61%) patients. Selecting MG patients based on thymic enlargement alone or AchR antibody positivity may be inadequate and thymectomy should perhaps be considered in all patients with generalised myasthenia.


Evaluation of the Oesophagogastric Cancer-Associated Microbiome: A Systematic Review and Quality Assessment.
Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. The role of bacteria in the pathogenesis of oesophagogastric cancer remains poorly understood. A systematic search identified studies assessing the oesophagogastric cancer microbiome. The primary outcome was to identify bacterial enrichment specific to oesophagogastric cancer. Secondary outcomes included appraisal of the methodology, diagnostic performance of cancer bacteria and the relationship between oral and tissue microbiome. A total of 9295 articles were identified, and 87 studies were selected for analysis. Five genera were enriched in gastric cancer: Lactobacillus, Streptococcus, Prevotella, Fusobacterium and Veillonella. No clear trends were observed in oesophageal adenocarcinoma. Streptococcus, Prevotella and Fusobacterium were abundant in oesophageal squamous cell carcinoma. Functional analysis supports the role of immune cells, localised inflammation and cancer-specific pathways mediating carcinogenesis. STORMS reporting assessment identified experimental deficiencies, considering batch effects and sources of contamination prevalent in low-biomass samples. Functional analysis of cancer pathways can infer tumorigenesis within the cancer-microbe-immune axis. There is evidence that study design, experimental protocols and analytical techniques could be improved to achieve more accurate and representative results. Whole-genome sequencing is recommended to identify key metabolic and functional capabilities of candidate bacteria biomarkers.


How should we measure global and regional left ventricular systolic function?
The assessment of left ventricular (LV) systolic function is frequently the most important task during the echocardiography examination. LV ejection fraction (EF) is the most commonly used measure to assess LV systolic function. EF is well established, with strong prognostic and therapeutic implications, but, nevertheless, it may not always be satisfactory in all patients. Other measures of myocardial contractility can provide valuable additive information in some patients. This is particularly true in patients with suspected heart failure but normal EF. The measurement of longitudinal function using M-mode and/or deformation analysis from tissue Doppler data or speckle tracking algorithms can be useful in this respect. Regional LV dysfunction can be difficult to detect using visual semi-quantitative assessment of regional wall motion. Contrast echocardiography can be most helpful in delineating the LV endocardial border and, thus, increasing sensitivity for detecting wall motion abnormalities. Deformation analysis can also be helpful for detecting subtle wall motion abnormalities, but these methods should be used with caution due to measurement variability and image quality dependence.


Heterozygote advantage and the maintenance of polymorphism for multilocus traits.
Explaining how polymorphism is maintained in the face of selection remains a puzzle since selection tends to erode genetic variation. Provided an infinitely large unsubdivided population and no frequency-dependance of selective values, heterozygote advantage is the text book explanation for the maintenance of polymorphism when selection acts at a diallelic locus. Here, we investigate whether this remains true when selection acts at multiple diallelic loci. We use five different definitions of heterozygote advantage that largely cover this concept for multiple loci. Using extensive numerical simulations, we found no clear associations between the presence of any of the five definitions of heterozygote advantage and the maintenance of polymorphism at all loci. The strength of the association decreases as the number of loci increases or as recombination decreases. We conclude that heterozygote advantage cannot be a general mechanism for the maintenance of genetic polymorphism at multiple loci. These findings suggest that a correlation between the number of heterozygote loci and fitness is not warranted on theoretical ground.


Issues in designing sequential stopping rules for monitoring side effects in clinical trials.
In a clinical trial of a new treatment, severe side effects may be a problem, and the trial may have to be stopped if the incidence is too high. We need to anticipate the need for such a decision to halt the trial early, and possibly design formal stopping rules for an excess of untoward events. The work presented here discusses the issues involved in such monitoring in comparison with more conventional analysis of the outcome variable. Stopping rules are derived by application of the sequential probability ratio test (SPRT), followed by computation of the exact size and power and adjustments of the consequent rules to achieve chosen operating characteristics appropriate to a monitoring situation. Rules are also derived from a Bayesian approach. These rules are applied to an illustrative trial and compared to the actual conditions that lead to the closing the trial.


Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.
Implantable silicon microelectrode array technology is a useful technique for obtaining high-density, high-spatial resolution sampling of neuronal activity within the brain and holds promise for a wide range of neuroprosthetic applications. One of the limitations of the current technology is inconsistent performance in long-term applications. Although the brain tissue response is believed to be a major cause of performance degradation, the precise mechanisms that lead to failure of recordings are unknown. We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays. Persistent ED1 up-regulation and neuronal loss was not observed in microelectrode stab controls indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response. In addition, we found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-alpha under serum-free conditions in vitro. Our findings suggest a potential new mechanism for chronic recording failure that involves neuronal cell loss, which we speculate is caused by chronic inflammation at the microelectrode brain tissue interface.


"What ELSE about this job?" Teaching Job Decision-Making to College Students With Intellectual and Developmental Disabilities.
Decision-making is the central element of self-determination, requiring targeted, systematic instruction to learn. In this study, researchers developed a multicomponent intervention, "What ELSE about this job?", to teach job decision-making skills to college students with intellectual and developmental disabilities. The intervention coupled remote audio coaching (RAC) with a mnemonic device, 'ELSE', to guide students to make decisions about whether certain jobs would be a good fit for them. The study aimed to investigate the effectiveness of the intervention and determine whether the skills would maintain once the intervention was removed. All students who received the intervention substantially increased their ability to make job decisions. Additionally, all participants maintained the skills upon removal of the intervention, and showed signs of generalizing their skills to novel job coaches and web-based job search apps. Implications and future research are discussed.


The effect of a natural high-fiber diet on serum lipids, fecal lipids, and colonic function.
In a cross-over experiment, 46 young healthy volunteers consumed in succession a high-fiber and a low-fiber diet for 3 weeks at two levels of dietary cholesterol. Half of the dietary fiber came from fruits and vegetables, and the rest from bread and other cereal products. On the high-fiber diet, concentrations of serum cholesterol decreased on average by 0.44 mmole/liter with high-cholesterol and 0.31 mmole/liter with low-cholesterol regimes; high density lipoprotein-cholesterole decreased by 0.1 mmole/liter; on average fecal weight increased by 115 g/day and mean transit time through the gut was decreased by 18 hr. Only part of the decrease in serum cholesterole may be due directly to the high intake of dietary fiber components. The remainder is due to differences in fat intake: during the high-fiber period subjects consumed less fat and cholesterol than had been planned.


Comparing the Diagnostic Value of Four Dementia Tests in the Amnestic and Healthy Elderly.
This study aimed to compare the diagnostic value of four questionnaires for the diagnosis of neurocognitive disorders (NCDs) in the elderly. In this project, people older than 60 years who lived in Tehran were investigated. A total of 99 literate cases were enrolled in the study, and four questionnaires, including functional assessment staging tool (FAST), abbreviated mental test score (AMTS), mini-mental state examination (MMSE), and modified Persian test of elderly for assessment of cognition and executive function (PEACE) were completed for them. They were then referred to a neuropsychiatrist, and the status of their cognition and neurobehavior was determined. The specialists were blinded to the results of the tests. Of the 99 participants studied, 39 cases were healthy, eight cases had mild Alzheimer's disease, 38 had amnesic MCI, five cases had secondary dementia, and nine cases had mixed vascular dementia and Alzheimer's disease. The area under the ROC curve for distinguishing the healthy group from the rest of the population was 0.692, 0.629, 0.734, and 0.751 for the FAST, AMTS, MMSE, and NBCSS questionnaires, respectively. MMSE and NBCSS tests had better diagnostic power than the other two tests to distinguish the healthy group from the rest of the population.


Fertility and pregnancy in chronic myeloid leukemia: real-world experience from an Indian tertiary care institution.
Chronic myeloid leukemia (CML) management during pregnancy is challenging. In this retrospective study, hospital records of CML patients treated between 2000 and 2021 were screened to identify patients who tried to conceive/got pregnant (planned and unplanned) on TKIs (tyrosine kinase inhibitors)/were pregnant at CML onset/fathered a child. We found ninety-three pregnancies involving thirty-three women and thirty-eight men, and they were analyzed for the pregnancy outcomes and the strategies utilized for CML management during pregnancy and the pre-conception period. There were two women and four men with primary infertility and five women with secondary infertility. TKIs were discontinued before conception in four planned pregnancies and at the time of recognition of pregnancy in unplanned pregnancies (n = 21). Unplanned pregnancy outcomes were two miscarriages, eight elective terminations, and eleven live births. Planned pregnancies led to four healthy babies. Outcomes of pregnancies at CML onset (n = 17) were six live births, one stillbirth, five elective terminations, and five abortions. Except for one child with congenital micro-ophthalmia, no other child born to the women on TKI had any malformations. Thirty-eight men fathered 51 healthy children. All but two patients (one planned and one unplanned pregnancy) lost their hematological responses during pregnancy and gained their previous best response after restarting TKI. In women who were pregnant at CML onset, complete cytological remission (CCYR) was achieved between 7 and 24 months (median:14 months) after starting TKI. During pregnancy, intermittent hydroxyurea ± TKI (in the second and third trimesters) was used to keep WBCs less than 30,000/mm3. Outcomes of pregnancies in CML patients can be optimized with our approach. TKIs (Imatinib and Nilotinib) can be safely used in the second and third trimesters. Delayed initiation or interruption of TKI during pregnancy does not negatively affect response to TKIs.


Allergic reactions associated with airborne fish particles in IgE-mediated fish hypersensitive patients.
We evaluated the clinical characteristics found in 21 children who showed allergic reactions upon incidental inhalation of fish odors or fumes, from 197 diagnosed with IgE-mediated fish hypersensitivity. Allergic reactions to fish via ingestion began in most patients (86%) within the first 24 months of life. The vast majority (19/21) of patients showed cutaneous symptoms, either alone or, less frequently, associated with other clinical manifestations. Hake and flounder were the species of fish most frequently implicated in eliciting clinical manifestations upon ingestion. After diagnosis, all these patients were placed on a strict fish-avoidance diet. During this period of avoidance, patients reported allergic reactions (mean age 7 years) after incidental exposure to airborne fish odors or fumes. Clinical manifestations through inhalation were respiratory (mainly wheezing) in 12 patients and cutaneous (mainly urticaria) in nine patients. Nineteen of 21 patients reported three or more episodes upon exposure to fish aerosols; in most cases, these episodes occurred at home when other people were eating fish. In conclusion, incidental inhalation of fish odors or fumes could play an important role in accidental and unknown encounters with fish in children on fish-avoidance diets for fish IgE-mediated hypersensitivity. Such exposures could elicit clinical symptoms and could have some effect in delaying the development of tolerance.


Ultrasensitive detection of UO2 2+ based on dopamine-functionalized MoOx quantum dots.
Uranium is an important nuclear fuel and the risk of human exposure to uranium increases as increasing amounts of uranium-containing waste enter the environment due to the rapid growth of nuclear power. Therefore, rapid, sensitive, and portable uranium detection is a promising approach to effectively control and monitor uranium contamination. To achieve this goal, abundant oxygen- and nitrogen-containing groups were introduced to molybdenum oxide quantum dot (MoOx QDs) surfaces with dopamine (DA) modification. Due to the excellent coordination ability of oxygen- and nitrogen-containing groups with uranium, the obtained DA-functionalized MoOx QDs (DA-MoOx QDs) showed a strong binding affinity for uranium and sensitivity was increased nearly 1000-fold compared with MoOx QDs alone. The limit of detection was 3.85 nM, which is higher than most of the reported nanomaterials. Moreover, the DA-MoOx QD-based method showed high selectivity and uranium could be clearly detected under masking with ethylenediaminetetraacetic acid even when the concentration of other metal ions was 100-fold higher than that of uranium, showing a very promising method for uranium contamination control and monitoring.


Establishment of a methodology for identifying Paeoniae Radix based on metallomic analysis.
We aimed to establish a methodology for identifying Paeonia samples based on metallomic analysis. We prepared 66 batches of samples (16 batches of crude drugs and 50 batches of cultivars, comprising 64 batches of Paeonia lactiflora and 2 batches of P. veitchii) collected from Japan and China (Inner Mongolia and elsewhere) between 1996 and 2008. P. lactiflora samples were genetically classified into white peony root (WPR) type and red peony root (RPR) type. Up to 47 elements were measured by inductively coupled plasma-mass spectrometry, and RPR type crude drug samples contained up to five times as much calcium as the others. Principal component analysis (PCA) of the multi-element fingerprints obtained suggested that P. veitchii, which grows wild, were distinguishable from the other cultivated P. lactiflora samples. This was confirmed perfectly by soft independent modeling of class analogy (SIMCA). The PCA of the fingerprints of P. lactiflora crude drug samples also suggested that it was possible to classify them by production area (Japan, Inner Mongolia, and China excluding Inner Mongolia) and genetic type (RPR and WPR types). They were also classified 100 % to the predicted class by SIMCA in both cases. These analyses were successful among the samples whose collection dates varied. This simple metallomic method is an efficient approach for verifying the complex origin of Paeoniae Radix.


Niche changes between parasite populations: An example from ticks on reptiles.
Two Australian tick species Aponomma hydrosauri and Amblyomma albolimbatum have the same major host species, the lizard Trachydosaurus rugosus. While females of Amb. albolimbatum are most often attached in the ears and on the neck of their hosts, Ap. hydrosauri females prefer to attach further back, under the forearms and on the back. Males show the same interspecific difference but there is also a difference between populations. Ap. hydrosauri males from populations in contact with Amb. albolimbatum attach more often in posterior positions than Ap. hydrosauri males from populations isolated from Amb. albolimbatum. These differences were found in both field populations and laboratory reared ticks. Phylogenetic evidence suggests that the change in male attachment site between Ap. hydrosauri populations followed the colonization of T. rugosus. We propose that the most likely reason for the change of attachment sites has been interspecific interactions with Amb. albolimbatum and that competition has been for space for efficient reception of female signals.


Candida albicans ventriculoperitoneal shunt infection in an infant: A case report and review of the literature.
Ventriculoperitoneal shunt malfunction is commonly seen with infection. Fungal cases are rare. We report the case of an infant with a ventriculoperitoneal shunt infection who presented with accelerated head growth. Cerebrospinal fluid cultures demonstrated Candida albicans. She was successfully treated with device removal and 3 weeks of intravenous antifungal therapy. This case highlights challenges with the diagnosis and treatment of fungal shunt infections.


Multicomponent water proton transverse relaxation and T2-discriminated water diffusion in myelinated and nonmyelinated nerve.
The influence of compartmental boundaries on water proton transverse relaxation and diffusion measurements was investigated in three distinct excised nerves, namely, the non-myelinated olfactory nerve, the Schwann cell myelinated trigeminal nerve, and the oligodendrocyte myelinated optic nerve of the garfish. The transverse relaxation decay curves were multiexponential and their decomposition yielded three primary components with T2 values approximately 30-50, 150, and 500 ms, which were subsequently assigned to water protons in the myelin, axoplasm, and interaxonal compartments. The short T2 component was absent in the non-myelinated olfactory nerve, but present in both myelinated nerves and thus provides supporting evidence for the use of quantitative T2 measurements to measure the degree of myelination. The signal contribution of each T2 component to the apparent diffusion coefficient measurements was varied by incrementing the spin-echo time with a preparatory CPMG train of radiofrequency pulses. The apparent diffusion coefficient and its anisotropy were shown to be independent of the spin-echo time over the range of 70 to 450 ms.


Endodermal sinus tumor of the vagina.
Malignant germ cell tumors of the vagina represent a critical site for local treatment. We report on our experience with two vaginal endodermal sinus tumors. Treatment with PEB regimen induced both tumor regression and alpha fetoprotein normalization. One patient had a residual lesion that was biopsied twice and no viable tumor cells were ever found. Both patients remained alive and disease-free, without having had surgical procedures except for biopsies. Platinum-based chemotherapy is able to achieve complete remissions and should be considered for vaginal endodermal sinus tumors.


Magnetic resonance imaging for prospective assessment of local recurrence of non-small cell lung cancer after stereotactic body radiation therapy.
To evaluate multi-parametric MRI for distinguishing stereotactic body radiation therapy (SBRT) induced pulmonary fibrosis from local recurrence (LR). SBRT treated non-small cell lung cancer (NSCLC) patients suspected of LR by conventional imaging underwent MRI: T2 weighted, diffusion weighted imaging, dynamic contrast enhancement (DCE) with a 5-minute delayed sequence. MRI was reported as high or low suspicion of LR. Follow-up imaging ≥12 months or biopsy defined LR status as proven LR, no-LR or not-verified. MRI was performed between 10/2017 and 12/2021, at a median interval of 22.5 (interquartile range 10.5-32.75) months after SBRT. Of the 20 lesions in 18 patients: 4 had proven LR, 10 did not have LR and 6 were not verified for LR due to subsequent additional local and/or systemic therapy. MRI correctly identified as high suspicion LR in all proven LR lesions and low suspicion LR in all confirmed no-LR lesions. All proven LR lesions (4/4) showed heterogeneous enhancement and heterogeneous T2 signal, as compared to the proven no-LR lesions in which 7/10 had homogeneous enhancement and homogeneous T2 signal. DCE kinetic curves could not predict LR status. Although lower apparent diffusion coefficient (ADC) values were seen in proven LR lesions, no absolute cut-off ADC value could determine LR status. In this pilot study of NSCLC patients after SBRT, multi-parametric chest MRI was able to correctly determine LR status, with no single parameter being diagnostic by itself. Further studies are warranted.


Extended operation for invasive thymoma with intracaval and intracardiac extension.
Two cases of invasive thymoma with intracaval and intracardiac extension into the right atrium are reported. Radical excisions and reconstructions of the superior vena cava (SVC) requiring extracorporeal circulation were performed. Invasive thymoma with this growth pattern is extremely rare, and patients with SVC obstruction should be evaluated for the resection of tumors and reconstruction of the SVC.


Refining interpretation of transcutaneous bilirubin measurement in newborns born late preterm.
Transcutaneous bilirubin (TCB) monitoring is widely used for jaundice screening in the newborn period. Limited data exists on adjusting TCB for bias in late preterm infants. The objective of this study was to determine the median bias between transcutaneous bilirubin and total serum bilirubin levels in newborns born at 35-36 weeks' gestation. This was a retrospective cohort study of late preterm infants born at 35-0/7 to 36-6/7 weeks' gestation who were admitted to a level III neonatal intensive care unit from May 2018 to February 2020. Transcutaneous and total serum bilirubin levels were assessed within 2 h of each other during the first 60 h of life. Bland-Altman plots were used to evaluate transcutaneous bilirubin bias. Bilirubin risk stratification based on age (in hours) was done using an adaptation of the Bhutani nomogram for transcutaneous, adjusted transcutaneous, and total serum bilirubin measurements. The median bias between transcutaneous and total serum bilirubin bias was 2.4 mg/dL (IQR 1.7-3.4, 95% CI 2.2-2.7). The kappa statistic demonstrated slight agreement between the unadjusted transcutaneous bilirubin and total serum bilirubin (k = 0.033, p = 0.194. The kappa statistic demonstrated fair agreement between an adjusted transcutaneous bilirubin (subtract 1 mg/dL) and total serum bilirubin (k = 0.298, p < 0.0001) and moderate agreement between another adjusted transcutaneous bilirubin (subtract 2 mg/dL) and total serum bilirubin (k = 0.430, p < 0.0001). In a single center study of late preterm infants, transcutaneous bilirubin systematically overestimated the total serum bilirubin level. Subtracting 1 mg/dL from the transcutaneous bilirubin identified infants with total serum bilirubin levels in the high or high intermediate risk range. Adjusting the transcutaneous bilirubin prior to risk stratification may reduce unnecessary blood draws for total serum bilirubin. Studies of racially and ethnically diverse newborns using various transcutaneous bilirubin meters are needed prior to broad application of the adjusted transcutaneous bilirubin approach.


Growth of the conceptus from day 33 to 45 of pregnancy is minimally associated with concurrent hormonal or metabolic status in postpartum dairy cows.
A hypothetical explanation for pregnancy loss in postpartum dairy cows is that the metabolic environment of the cow inhibits the growth of the conceptus and places the pregnancy at risk for loss. The objective of the current study, therefore, was to model the association between cow-level metabolic indicators and conceptus growth during early pregnancy (day 33-45 after AI) and to determine if an association (if present) is large enough to cause pregnancy loss. Metabolic indicators included milk production, changes in body weight and body condition score, parity, and concentrations of circulating hormones and metabolites (glucose, non-esterified fatty acids, growth hormone, IGF1, progesterone, and pregnancy-associated glycoproteins). One-hundred cows were enrolled. Cows that became pregnant with single conceptus pregnancies (n=53) weighed more (P<0.007) and had fewer uterine polymorphonuclear neutrophils (uterine health indicator; P<0.051) compared with cows that failed to become pregnant. The embryo and amniotic vesicle were measured by using ultrasound on day 33, 35, 38, 40, 42, and 45 of pregnancy. Most of the cow-level indicators that were included in the model of conceptus growth failed to achieve statistical significance. Day of pregnancy had the largest effect on conceptus growth (size and cross-sectional area of the embryo and amniotic vesicle; P<0.001). There were effects of sex of fetus (male fetuses larger than female), insulin (negative association), and body weigh change (positive association) on embryo length and cross-sectional area but these effects were small when compared with the range in conceptus length or area that we observed. The conclusion was that the capacity of the cow to become pregnant was associated with body weight and uterine health but we failed to find a large association with metabolic status on conceptus growth from day 33 to 45 of pregnancy in lactating dairy cows.


Carotid ultrasonography for detection of vascular abnormalities in hypertensive children.
To determine whether hypertension and overweight status are associated with increased carotid intimal-medial thickness (cIMT) in children, vascular ultrasonography was performed in newly diagnosed hypertensive patients ( n=53) and normotensive controls ( n=33). Hypertensive subjects were identified either by referral or by systematic school-based hypertension screening. Hypertension was defined as blood pressure above the 95th percentile based on current Task Force criteria, and overweight was defined as body mass index (BMI) >25 kg/m(2). cIMT was assessed by high-resolution vascular ultrasonography of the distal common carotid artery. Hypertensive subjects had a higher cIMT than normotensive subjects (0.62 vs. 0.53 mm, P<0.00001). This difference remained significant after controlling for the effects of gender, race, age, height, weight, and BMI. Similarly, overweight subjects had a higher cIMT than normal-weight subjects (0.63 vs. 0.54 mm, P<0.0001). Subjects with both systolic and diastolic hypertension had higher cIMT than those with isolated systolic hypertension (0.67 vs. 0.60, P<0.05). cIMT showed significant positive pairwise correlation with age, height, weight, BMI, and systolic blood pressure. Among all clinical variables analyzed, cIMT was most strongly correlated with BMI ( r=0.53, P<0.001). These results provide further evidence that vasculopathy occurs in association with known cardiovascular risk factors such as hypertension and obesity during childhood.


Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.
Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the luteal phase before a microdose GnRH agonist flare protocol for in vitro fertilization did not improve outcomes in "poor responder" patients.


[Characteristics of the response of sensomotor cortex neurons of the cat during performance of rapid purposeful movements].
Neuronal activity of cat sensorimotor cortical area was studied during performance of movements of grasping a visual goal appearing for a short time. Characteristics and the pattern of neuronal discharge became stabilized in the process of animal training and did not depend on the time of goal presentation, absence or presence of the reinforcement under preservation of animal's motor reaction. Changes in responses were observed in situations of uncertainty: at 50% of reinforcement probability and (or) at successful performance of the motor reaction in half of cases.


Ras Homolog Family Member F, Filopodia Associated Promotes Hepatocellular Carcinoma Metastasis by Altering the Metabolic Status of Cancer Cells Through RAB3D.
The mechanism by which tumor cells resist metabolic stress remains unclear, but many oncogenes are known to regulate this process. Accordingly, metabolic stress is closely associated with tumor metastasis. In this study, gene chip technology showed that Ras homolog family member F, filopodia associated (RHOF), a member of the Rho guanosine triphosphatase family, is an oncogene that is significantly related to hepatocellular carcinoma (HCC) metastasis; however, it has rarely been reported in tumors. Our aim was to determine the clinicopathological significance and role of RHOF in HCC progression and investigate the associated mechanisms. The results showed that compared to expression in adjacent noncancerous tissues, RHOF was frequently up-regulated in HCC tumor samples and elevated under conditions of glucose deprivation. RHOF expression was associated with tumor-node-metastasis stage, T grade, metastasis status, recurrence, and survival in HCC. RHOF also affected cell morphology and promoted migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cell lines. Analysis of the underlying mechanism showed that RHOF promoted the Warburg effect by up-regulating the expression and function of several glycolytic enzymes in HCC cells. This metabolic shift enhanced HCC cell migration and invasion. Specifically, RHOF exerted a tumor-promoting effect by directly interacting with AMP-activated protein kinase (AMPK) and increasing the phosphorylation of AMPK. This subsequently affected RAB3D mRNA stability and led to elevated RAB3D expression, thereby amplifying the Warburg effect and malignant biological behaviors of HCC cells. RHOF helps tumor cells resist metabolic stress through modulating the Warburg effect and plays a critical role in promoting HCC cell migration, invasion, and EMT, highlighting its important role in remodeling the metastatic microenvironment and regulating tumor metastasis. RHOF shows potential as a therapeutic target and prognostic biomarker for HCC.


Evidence for the role of higher order reasoning processes in cue competition and other learning phenomena.
When people judge the contingency between atarget cue and an outcome, they also take into account the contingency between the outcome and other cues with which the target cue co-occurred. Several authors have argued that such cue competition effects are due to higher order reasoning processes. We review the evidence that supports this hypothesis and discuss whether higher order reasoning might also play a role in other learning phenomena.


Effects of oximes on muscle force and acetylcholinesterase activity in isolated mouse hemidiaphragms exposed to paraoxon.
Toxicity of organophosphates (OP) is caused by inhibition of acetylcholinesterase (AChE), resulting in accumulation of acetylcholine. While cholinolytics such as atropine are able to counteract muscarinic symptoms, they are unable to restore the impaired neuromuscular transmission (NMT). Here, oximes as potential reactivators of inhibited AChE may be effective. Until now, no unequivocal relation between oxime-induced increase in muscle force and reactivation has been demonstrated. To address this issue the isolated circumfused mouse hemidiaphragm was used as an experimental model. The muscle force generation upon tetanic stimuli was recorded during AChE inhibition by 1 microM paraoxon and after a wash-out period in the presence of obidoxime, pralidoxime and the experimental oximes HI 6, and HLö 7, 10 microM each. At the end of the experiments AChE activity was determined in the diaphragm homogenates by a radiometric assay. At 50-Hz stimulation, recovery was complete with obidoxime, nearly complete with HLö 7 but incomplete with HI 6 and pralidoxime. Only with obidoxime a significant increase in AChE activity was found. An increase of AChE to 10% of normal was sufficient to allow normal muscle force generation. When paraoxon was still present, obidoxime and HLö 7 were effective at 0.1 microM paraoxon, but failed so at paraoxon >1 microM. The data show different effectiveness of the oximes investigated in reactivation of muscle AChE and recovery of NMT after inhibition by paraoxon. Although an increase in muscle force by the oximes was accompanied by a measurable increase in AChE activity only in the case of obidoxime, the plot of muscle force against AChE activity as well as lacking evidence for a direct effect and adaptive processes indicate that reactivation of the enzyme is the main mechanism of NMT recovery. In agreement, in presence of AChE inhibitory concentrations of paraoxon during reactivation a reduced effectiveness of oximes was found.


Radiomics analysis of CT imaging improves preoperative prediction of cervical lymph node metastasis in laryngeal squamous cell carcinoma.
To investigate the role of CT radiomics for preoperative prediction of lymph node metastasis (LNM) in laryngeal squamous cell carcinoma (LSCC). LSCC patients who received open surgery and lymphadenectomy were enrolled and randomized into primary and validation cohorts at a ratio of 7:3 (325 vs. 139). In the primary cohort, we extracted radiomics features from whole intratumoral regions on venous-phase CT images and constructed a radiomics signature by least absolute shrinkage and selection operator (LASSO) regression. A radiomics model incorporating the radiomic signature and independent clinical factors was established via multivariable logistic regression and presented as a nomogram. Nomogram performance was compared with a clinical model and traditional CT report with respect to its discrimination and clinical usefulness. The radiomics nomogram was internally tested in an independent validation cohort. The radiomics signature, composed of 9 stable features, was associated with LNM in both the primary and validation cohorts (both p < .001). A radiomics model incorporating independent predictors of LNM (the radiomics signature, tumor subsite, and CT report) showed significantly better discrimination of nodal status than either the clinical model or the CT report in the primary cohort (AUC 0.91 vs. 0.84 vs. 0.68) and validation cohort (AUC 0.89 vs. 0.83 vs. 0.70). Decision curve analysis confirmed that the radiomics nomogram was superior to the clinical model and traditional CT report. The CT-based radiomics nomogram may improve preoperative identification of nodal status and help in clinical decision-making in LSCC. • The radiomics model showed favorable performance for predicting LN metastasis in LSCC patients. • The radiomics model may help in clinical decision-making and define patient subsets benefiting most from neck treatment.


The metabolites of the mangrove fungus Verruculina enalia No. 2606 from a salt lake in the Bahamas.
Two metabolites enalin A (1) and B (2), together with hydroxymethyl furfural (3) and three cyclodipeptides (4, 5 and 6), were isolated from the mangrove fungus Verruculina enaria from a salt lake in the Bahamas. Their structures were determined by spectroscopic methods, mainly by 2D NMR spectroscopic analyses. A possible biosynthetic scheme to 1 and 2 is presented.


Deep transcriptomic study reveals the role of cell wall biosynthesis and organization networks in the developing shell of peanut pod.
Peanut (Arachis hypogaea L.) belongs to an exceptional group of legume plants, wherein the flowers are produced aerially, but the pods develop under the ground. In such a unique environment, the pod's outer shell plays a vital role as a barrier against mechanical damage and soilborne pathogens. Recent studies have reported the uniqueness and importance of gene expression patterns that accompany peanut pods' biogenesis. These studies focused on biogenesis and pod development during the early stages, but the late developmental stages and disease resistance aspects still have gaps. To extend this information, we analyzed the transcriptome generated from four pod developmental stages of two genotypes, Hanoch (Virginia-type) and IGC53 (Peruvian-type), which differs significantly in their pod shell characteristics and pathogen resistance. The transcriptome study revealed a significant reprogramming of the number and nature of differentially expressed (DE) genes during shell development. Generally, the numbers of DE genes were higher in IGC53 than in Hanoch, and the R5-R6 transition was the most dynamic in terms of transcriptomic changes. Genes related to cell wall biosynthesis, modification and transcription factors (TFs) dominated these changes therefore, we focused on their differential, temporal and spatial expression patterns. Analysis of the cellulose synthase superfamily identified specific Cellulose synthase (CesAs) and Cellulose synthase-like (Csl) genes and their coordinated interplay with other cell wall-related genes during the peanut shell development was demonstrated. TFs were also identified as being involved in the shell development process, and their pattern of expression differed in the two peanut genotypes. The shell component analysis showed that overall crude fiber, cellulose, lignin, hemicelluloses and dry matter increased with shell development, whereas K, N, protein, and ash content decreased. Genotype IGC53 contained a higher level of crude fiber, cellulose, NDF, ADF, K, ash, and dry matter percentage, while Hanoch had higher protein and nitrogen content. The comparative transcriptome analysis identified differentially expressed genes, enriched processes, and molecular processes like cell wall biosynthesis/modifications, carbohydrate metabolic process, signaling, transcription factors, transport, stress, and lignin biosynthesis during the peanut shell development between two contrasting genotypes. TFs and other genes like chitinases were also enriched in peanut shells known for pathogen resistance against soilborne major pathogens causing pod wart disease and pod damages. This study will shed new light on the biological processes involved with underground pod development in an important legume crop.


Five homologous repeats of the protein G-related protein MIG cooperate in binding to goat immunoglobulin G.
Protein MIG, from Streptococcus dysgalactiae, binds alpha2-macroglobulin and immunoglobulin G (IgG). MIG-derived fusion proteins with one to five IgG-binding repeats differed up to 72,000- fold in avidity for goat IgG, indicating a considerable cooperativity of the repeats. Significant sequence variation in the IgG-binding repeats was recognized. Protein MIG interacted with goat IgG1 via both the Fc and Fab parts.


Kinetics of mezlocillin and carbenicillin.
The kinetics of mezlocillin, a semisynthetic acylureido penicillin, more active than carbenicillin against many gram-negative bacteria, were compared with those of carbenicillin. Following an intravenous infusion of 4 gm in 5 min to 8 normal men there was an average serum level of 294 microgram/ml for mezlocillin and 365 microgram/ml for carbenicillin. The t1/2 for mezlocillin was 47 min and that for carbencillin was 70 min. The apparent volume of distribution was 13.4 L for mezlocillin and 14.4 L for carbenicillin. The mean urinary recovery of mezlocillin was 72% and that for carbenicillin was 92%. Constant infusion of 5 mg of mezlocillin over 2 hr gave steady-state levels of 234 microgram/ml. Half-life, apparent volume of distribution, and serum and renal clearance of mezlocillin after constant infusion were in the same range as those after rapid infusion.


Rapid increase in diabetes incidence among Chinese Canadians between 1996 and 2005.
To examine trends in diabetes incidence among Ontario residents with Chinese and European origins. Respondents to population-based health surveys in 1996, 2001, 2003, and 2005 who were aged≥30 years, who did not have diabetes, and who self-identified as having European (n=76,285) or Chinese (n=1,041) origins were followed for diabetes incidence through a validated administrative data-derived diabetes registry. Age- and sex-standardized diabetes incidence increased from 1.3 to 19.6 per 1,000 person-years in the Chinese population and from 7.8 to 10.0 in the European population. Relative to the 1996 European population, the adjusted hazard ratio for diabetes was 4.50 (95% CI 1.89-7.49) for the 2005 Chinese population and 1.22 (1.05-1.39) for the 2005 European population. Diabetes incidence increased much more rapidly between 1996 and 2005 in the Chinese population than in the European population, independent of age, obesity, and other risk factors.


Is cystectomy a safe procedure in elderly patients with carcinoma of the bladder?
Often total cystectomy is not advocated in elderly patients for the treatment of carcinoma of the bladder. A group of 25 patients more than 70 years old were reviewed to determine if cystectomy is a reasonable therapeutic alternative in elderly individuals. Since there was satisfactory survival and no immediate operative mortalities elderly patients should not be denied this form of therapy on the basis of age alone. A higher incidence of postoperative complications was noted in the patients treated previously with radiation therapy.


Cannabinoid Type 1 Receptors in the Basolateral Amygdala Regulate ACPA-Induced Place Preference and Anxiolytic-Like Behaviors.
The number of cannabis users is increasing in the world. However, the mechanisms involved in the psychiatric effects and addiction formation remain unclear. Medical treatments against cannabis addiction have not yet been established. Δ9-Tetrahydrocannabinol (THC), the main active substance in cannabis, binds and affects cannabinoid type 1 receptors (CB1R) in the brain. The mice were intraperitoneally (i.p.) administered arachidonylcyclopropylamide (ACPA), a CB1R-selective agonist, and then two behavioral experiments on anxiety and addiction were performed. Administration of ACPA caused anxiolytic-like behavior in the elevated plus maze test. In addition, ACPA increased place preference in a conditioned place preference (CPP) test. The basolateral amygdala (BLA), which is the focus of this study, is involved in anxiety-like behavior and reward and is reported to express high levels of CB1R. We aimed to reveal the role of CB1R in BLA for ACPA-induced behavior. AM251, a CB1R selective antagonist, was administered intra-BLA before i.p. administration of ACPA. Intra-BLA administration of AM251 inhibited ACPA-induced anxiolytic-like behavior and place preference. These results suggest that CB1R in the BLA contributes to behavior disorders caused by the acute or chronic use of cannabis.


Objective evaluation of allergic conjunctival disease (with a focus on the application of artificial intelligence technology).
We have summarized the past efforts and results of objective measurement methods for conjunctival hyperemia classification. Severity classification using conjunctival blood vessel occupancy rate, ocular surface temperature analysis, and artificial intelligence have been reported to be clinically useful, as they have been found to correlate with the severity of conjunctival hyperemia by doctors. The AI method using slit lamp microscope images, whose main purpose is to be widely used in daily clinical practice, can be spread all over the world. As a result, it may lay the foundation for clinical research using large amounts of clinical data collected on the same basis without human bias.


Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin (IL)-4 and IL-13 after segmental allergen challenge and their effects on alpha-smooth muscle actin and collagen III synthesis by primary human lung fibroblasts.
Asthmatic airway remodelling is characterized by myofibroblast hyperplasia and subbasement membrane collagen deposition. We hypothesized that cytokines and growth factors implicated in asthmatic airway remodelling are increased in bronchoalveolar lavage (BAL) fluid of asthmatics after segmental allergen challenge (SAC), and that these growth factors and cytokines increase alpha-smooth muscle actin (alpha-SMA) and collagen III synthesis by human lung fibroblasts (HLFs). Transforming growth factor (TGF)-beta1, TGF-beta2, IL-4 and IL-13 levels were measured in BAL fluid from 10 asthmatics and 9 non-asthmatic controls at baseline and then 1 day, 1 week and 2 weeks after SAC. Confluent cultures of HLFs were stimulated by exogenous addition of TGF-beta1, TGF-beta2, IL-4 or IL-13 (concentration range 0.01-10 ng/mL) over 48 h. Collagen III was measured in culture supernates and alpha-SMA in cell lysates by Western blot. At baseline, there was no difference in BAL fluid concentrations of TGF-beta1, IL-4 and IL-13 between asthmatics and controls; however, non-asthmatics had higher concentrations of total TGF-beta2. In asthmatics, BAL fluid concentrations of all four factors increased significantly 1 day after SAC. TGF-beta1, TGF-beta2 and IL-13 concentrations returned to baseline by 1 week after SAC, but BAL fluid IL-4 concentration remained elevated for at least 2 weeks. TGF-beta1, TGF-beta2 and IL-4 significantly increased alpha-SMA in fibroblasts, but only IL-4 caused corresponding increases in collagen III synthesis. IL-13 had no direct effects on collagen III synthesis and alpha-SMA expression. Because IL-4 caused a dose-dependent increase in alpha-SMA and collagen III synthesis, it may be an important cytokine mediating asthmatic airway remodelling. TGF-beta1 and TGF-beta2 may also play a role in airway remodelling by stimulating phenotypic change of fibroblasts to myofibroblasts. Additionally, collagen III synthesis appears to be independent of myofibroblast phenotype and is apparently regulated by different growth factors and cytokines.


Water sorption behaviour of commercial furcellaran.
Water sorption isotherms are important tool for designing the technological processes and predicting stability and shelf life of food. The aim of the work was to determine the water sorption isotherms of commercial furcellaran at different temperatures (20, 35 and 50 °C) using a gravimetric method under different levels of relative humidity (19-95%). The experimental data obtained have been interpreted in the terms of various isotherm models and it was found that the best results were obtained with the Peleg model (P < 2.1%; RSME <0.01; R2 = 1.00). The obtained isotherms followed the type II pattern and, in all cases, the sorption capacity increased with increasing water activity and decreased with increasing temperature. The maximum net isosteric heat for adsorption and desorption was 938.9 and 988.6 J g -1, respectively, at an equilibrium moisture content of 0.05 gw gdb -1. The net isosteric heat of sorption decreased exponentially with increasing moisture content and approached zero at 0.26 gw gdb -1 for adsorption and 0.32 gw gdb -1 for desorption. The developed mathematical relationships can be used to optimize the drying processes and storage conditions of furcellaran.