Computer-aided diagnostic system for hypertensive retinopathy: A review.
Hypertensive Retinopathy (HR) is a retinal disease caused by elevated blood pressure for a prolonged period. There are no obvious signs in the early stages of high blood pressure, but it affects various body parts over time, including the eyes. HR is a biomarker for several illnesses, including retinal diseases, atherosclerosis, strokes, kidney disease, and cardiovascular risks. Early microcirculation abnormalities in chronic diseases can be diagnosed through retinal examination prior to the onset of major clinical consequences. Computer-aided diagnosis (CAD) plays a vital role in the early identification of HR with improved diagnostic accuracy, which is time-efficient and demands fewer resources. Recently, numerous studies have been reported on the automatic identification of HR. This paper provides a comprehensive review of the automated tasks of Artery-Vein (A/V) classification, Arteriovenous ratio (AVR) computation, HR detection (Binary classification), and HR severity grading. The review is conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The paper discusses the clinical features of HR, the availability of datasets, existing methods used for A/V classification, AVR computation, HR detection, and severity grading, and performance evaluation metrics. The reviewed articles are summarized with classifiers details, adoption of different kinds of methodologies, performance comparisons, datasets details, their pros and cons, and computational platform. For each task, a summary and critical in-depth analysis are provided, as well as common research issues and challenges in the existing studies. Finally, the paper proposes future research directions to overcome challenges associated with data set availability, HR detection, and severity grading.


Staging Melanoma: What's Old and New.
The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and III patients from the International Melanoma Database and Discovery Platform. Key changes in the eighth edition are regarding subcategorization of T1, M1, pathologic stage grouping of stage I and III, and refining the definitions and terminologies used in the staging system. As the knowledge of tumor biology improves, the staging of melanoma will continue to evolve to enable betterment of care.


Factors influencing participation in collective marketing through organic rice farmer groups in northeast Thailand.
Despite the significant roles of farmer groups in collective action for production and marketing of organic paddy, limited literature has studied the farmer-level determinants of participation in collective action in northeast Thailand. This study examined factors associated with participation in collective marketing for three organic rice farmer groups (Nam Om Community Enterprise Network, Na So Farmer Group, and Moral Rice Farmer Group) in Yasothon Province of Thailand, producing organic jasmine rice for export and domestic markets through contract farming. Primary data were collected from 335 farmers and analyzed by descriptive statistics and the two-limit tobit regression method. The descriptive results showed relatively high levels of social, economic, institutional, and environmental benefits arising from the participation in those groups. In particular, environmental benefits were higher than the other types of benefits. The regression analysis found that age and agricultural loan negatively influenced the extent of participation in collective marketing through farmer groups, whereas education, paddy cultivation area size, non-agricultural income, experience in rice farming, experience in organic rice farming, group membership duration, perceived economic benefits, and membership with Na So farmer group were positively associated with the extent of participation. The effect of experience with organic rice farming was relatively small in Na So Farmer Group. The findings suggest that economic benefits from participation in organic farmer groups should be enhanced in order to increase the collective marketing of organic rice produce. Moreover, the government should provide alternative employment opportunities, knowledge-based training, and low-interest credit to support production and collective marketing of organic rice.


Complete genome sequence of Paenibacillus beijingensis 7188(T) (=DSM 24997(T)), a novel rhizobacterium from jujube garden soil.
We present here the complete genome sequence of a novel species Paenibacillus beijingensis 7188(T) (=DSM 24997(T)) from jujube rhizosphere soil that consists of one circular chromosome of 5,749,967 bp with a GC content of 52.5%. On the significance of first genome information in this species, the genome sequence of strain 7188(T) will provide a better comprehension of Paenibacillus species for the practical uses as a biofertilizer in agriculture.


Studies on the calcium antagonistic action of tetrandrine: X VI. Hemodynamic effects of tetrandrine on conscious rats.
Hemodynamic study of tetrandrine (Tet) in conscious rats showed that 15 mg/kg i.v. lowered BP, LVSP, +/- dp/dtmax, and (dP/dt)P-1. The degree of diminutions was nearly equal to that of BP during the initial period, while the LVEDP was elevated. But all these parameters (except -dp/dtmax) recovered gradually and earlier than BP, and LVEDP decreased to a level slightly lower than that of control. These results indicate that the hypotensive action of Tet is mainly due to its inhibition of cardiac contractility at the early period, but due to vasodilatation in the later stage. The HR was slowed down abruptly followed by a reflex acceleration, and than a gradual but sustained decrease in HR supervened with i.v. Tet. When large dose (40 mg/kg) of Tet i.v. caused a cardiac standstill with the R wave of ECG persisting for a few minutes, it means that an excitation-contraction decoupling occurred as that found on isolated myocardial preparation treated with verapamil and Tet.


A reaction-diffusion framework for hydrolytic degradation of amorphous polymers based on a discrete chain scission model.
Hydrolytic degradation of polymers involves the scission of long chain molecules, leading to molecular weight reduction and mass loss. The precise degradation response however depends on the scission probability of individual bonds along the polymer backbone. In particular, bonds near the chain ends are considered to be more susceptible to hydrolysis than inner bonds. In this paper, we incorporate a discrete chain scission model that can handle arbitrary bond scission probabilities within a continuum reaction-diffusion framework. Overall hydrolysis kinetics (including autocatalysis) is described independently of the chain scission model. By decoupling the description of the chain scission mechanism from kinetics, our framework enables the identification of the chain scission mechanism from molecular weight reduction and mass loss curves commonly reported in experimental degradation studies. We further propose a reduced continuum model which is better suited for large-scale simulations while retaining the predictive capability of the full discrete-continuum model. The model capability is illustrated in representative case studies based on experimental data from the literature for different materials and geometries. STATEMENT OF SIGNIFICANCE: Many models have been proposed to predict the evolution of molecular weight and mass loss in biodegradable polymers undergoing hydrolytic degradation. However, existing models remain limited in their ability to describe the degradation mechanism, autocatalytic kinetics and short chains diffusion simultaneously. Moreover, existing models often rely on empirical relations and a large number of fitting parameters. Here, we propose a conceptually simple discrete-continuum mathematical framework with a small number of parameters which all have a clear physical meaning. Model calibration against experimental data is simplified, and further provides insights into the degradation mechanisms at play, namely random scission, chain-end scission, or a combination of both. The framework can serve as a basis for future generalisations, including a description of evolving crystallinity, or other degradation mechanisms, such as thermal oxidation or photo-degradation.


Reduced features set neural network approach based on high-resolution time-frequency images for cardiac abnormality detection.
A suitable temporal and spectral processing of the electrocardiogram (ECG) signals can facilitate the visual interpretation and discrimination between known patterns for classification. This paper proposes a non-invasive hybrid neural network and time-frequency (TF) based method to detect and classify commonly found cardiac abnormalities in ECG signals including congestive heart failure, ventricular tachyarrhythmia, intracardiac atrial fibrillation, arrhythmia, malignant ventricular ectopy, normal sinus rhythm, and postictal heart rate oscillations in partial epilepsy. Non-stationary raw ECG signals are collected from an online healthcare dataset source 'PhysioBank' that contains physiologic signals. These temporal signals are processed through Wigner-Ville distribution to produce high-resolution and concentrated TF images depicting specific visual patterns of cardiac abnormalities. The TF images are used to extract the abnormality parameters with the help of medical experts with good diagnostic accuracy. Principal component analysis (PCA) is employed for feature reduction and important features selection from the ECG signals. The selected features are used for training the multilayer feed-forward artificial neural network (ANN) for detection and classification while training parameters like the number of epochs, activation functions, and the learning rate is suitably selected with appropriate stopping criteria. Experimental results demonstrate the effectiveness of the hybrid neural-TF approach using PCA for abnormality detection and classification.


Non-viral microbial keratitis in children.
Microbial (non-viral) keratitis is a serious vision-threatening condition. The management of microbial keratitis in children is particularly complicated by the children's inability to cooperate during examinations and the lack of information prior to presentation. Predisposing factors vary according to geographical location and age. Corneal trauma is the leading cause for microbial keratitis in children, followed by systemic and ocular disease. Etiologic agents are most frequently Gram-positive and Gram-negative bacteria commonly found in contact lens-related microbial keratitis. Mycotic keratitis is a major risk factor in tropical weather conditions, particularly when associated with agricultural trauma. Early diagnosis, intensive drug treatment, and timely planned surgical intervention may effectively improve the outcome of pediatric microbial keratitis.


Workflow optimization of brachytherapy-based very accelerated partial breast irradiation.
For low-risk breast cancer, accelerated partial breast irradiation (APBI) is a level 1 evidence procedure. Brachytherapy based very APBI (vAPBI) makes it possible to perform adjuvant irradiation in 4 to 1 fraction. However, vAPBI organization is critical. The aim of this technical note is to report on its optimization. To offer to low-risk breast cancer patient an efficient, simple, rapid adjuvant irradiation with a reduced number of hospital visits, a new organization of vAPBI based on a single fraction was established, merging all the different steps (from first consultation to irradiation) into a 4-5-consecutive-hour period. This therapeutic program was developed in strong collaboration with radiation oncologists, medical physicists, radiation therapists, and the medical secretary. After the validation of adjuvant breast irradiation, the patient was offered a telemedicine consultation with the radiation oncologist. Then, the day of vAPBI, the patient arrived at the brachytherapy unit at 08:00 AM for an in-person consultation followed by a preimplant CT scan (defining catheter number and position). After breast local anesthesia, catheter placement was performed followed by a postimplant CT scan for planning purposes. A total dose of 16 Gy in 1 fraction was delivered before removing the catheters. The patient was discharged from the brachytherapy unit around 12:30 PM with an upcoming surveillance consultation date. VAPBI organization optimization makes it possible to propose a short 5-h procedure from medical consultation to treatment with only one round trip. Strict organization among staff is required.


Use of interleukin 12 to enhance the cellular immune response of swine to an inactivated herpesvirus vaccine.
Vaccination is the single most successful medical measure against infectious disease. However, the major barrier for achieving the full protective effect or immunization is how to render attenuated, killed, or subunit vaccines as immunogenic as the fully infectious versions of these microbes (Hughes and Babiuk, 1995; Rabinovich et al., 1994). In the case of PrV, infection with wild-type virus induces an immune response superior to vaccination with a live modified vaccine. After primary intranasal infection with wild-type PrV, the replication of a homologous secondary virus challenge is completely inhibited, and the much sought "sterile immunity" is generated (Kimman et al., 1994). In contrast, the immune response of pigs similarly exposed to PrV mutants, which have been attenuated by removal of the thymidine kinase (TK) and the envelope glycoprotein gE gene (McGregor et al., 1985; Zuckermann et al., 1988), is insufficient for preventing the replication of a homologous wild-type virus challenge (Kimman et al., 1994). Furthermore, inactivated PrV vaccines are even less effective at inducing protective immunity than are live modified PrV vaccines (de Leeuw and Van Orischot, 1985; Stellman et al., 1989; Vannier, 1985). The importance of inactivated and subunit vaccines resides in their stability and safety, since no infectious microbe is being introduced into the animal. However, because of the recognized lower effectiveness of inactivated vaccine types, they usually fall in disfavor when a modified live vaccine alternative is available. There is a critical need to develop strategies to enhance the immunogenicity of live, inactivated, and sub-unit vaccines for human and veterinary use (Hughes and Babiuk, 1995; Rabinovich et al., 1994). Although the inoculation of an animal with a virulent microbe is obviously not the desired method to produce sterile immunity, the immune response generated to infection with wild-type PrV clearly demonstrates that this type of immunity is possible. Research directed at devising strategies to increase the immunogenicity of different types of vaccines is necessary. Because of the wealth of information available on PrV immunity (reviewed by Chinsakchai and Molitor, 1994; Nauwynck, 1997), on PrV vaccines (Kimman et al., 1992, 1994; Mettenleiter, 1991; Scherba and Zuckermann, 1996) and increasingly on the porcine immune system (Lunney, 1993; Lunney et al., 1996; Saalmüller, 1995), the swine herpesvirus model is ideal for investigating the development of vaccine formulations with enhanced immunogenicity. Among the strategies currently being examined for the enhancement of the immunogenicity of inactivated and subunit vaccines is the use of recombinant cytokines administered together with antigen (Hughes and Babiuk, 1995; Rabinovich et al., 1994). The ability to regulate the development of an immune response by cytokines such as IL-12 provides the theoretical basis to use these cytokines as adjuvants to immunopotentiate the response to an inactivated vaccine. More importantly, it provides a model to investigate the mechanisms behind the induction of protective immunity and the components of a vaccine necessary for stimulating such a response. By providing cytokines such as IL-12 or IFN-gamma in combination with the vaccine inoculum, it is reasonable to expect that they will be able to direct the differentiation of T cells during the primary immune response. Modulation, in a predictable and desired manner of the quality and quantity of the induced protective immunity, should be achievable. The ability to manipulate a vaccine-induced immune response in the direction of a predominantly cellular response (Th1-like) instead of a predominantly humoral one (Th2-like) is perhaps best illustrated by the need to develop an effective vaccine against the porcine reproductive and respiratory syndrome (PRRS) virus, whose infectivity can be significantly enhanced in vitro and in vivo by antibody induced by vaccination


Relationship of C-reactive protein with components of the metabolic syndrome in normal-weight and overweight elderly.
C-reactive protein (CRP) is known to be elevated in the metabolic syndrome. We aimed to explore in more detail the relationship between CRP and other components of the metabolic syndrome in a general population of 605 Dutch elderly individuals aged 65-84 years. Data were collected on body mass index (BMI), plasma CRP, plasma plasminogen activator inhibitor 1 (PAI-1), serum insulin, serum lipids, blood pressure, lifestyle and medical history. CRP was log-transformed (ln-CRP) to improve normality. Associations of ln-CRP with components of the metabolic syndrome were studied by multivariate linear regression analysis, in strata of gender and overweight status, with adjustment for age, physical activity, and smoking habits. A total of 322 subjects (53%) were overweight (BMI > or =25 kg/m2). In normal-weight women, ln-CRP was significantly associated with BMI, PAI-1, serum insulin, and HDL-cholesterol. In overweight women, however, these relationships were weak and not statistically significant. Findings were similar in men, although less pronounced than in women. Our data suggest that the role of CRP in the metabolic syndrome is modified by the amount of body fat.


Strong ground motion data of the 2015 Gorkha Nepal earthquake sequence in the Kathmandu Valley.
Strong-motion records of earthquakes are used not only to evaluate the source rupture process, seismic wave propagation and strong ground motion characteristics, but also to provide valuable data for earthquake disaster mitigation. The Kathmandu Valley, Nepal, which is characterised by having soft sediments that have been deposited in an earthquake-prone zone, has experienced numerous earthquakes. We have operated four strong-motion stations in the Kathmandu Valley since 2011. These stations recorded the 2015 magnitude 7.8 Gorkha Nepal earthquake that occurred in the Himalayan continental collision zone. For several months after the mainshock, we deployed four additional temporary stations. Here, we describe the seismic data for 18 earthquakes over magnitude 5.0 collected by this array, including the 2015 magnitude 7.3 Dolakha earthquake of maximum aftershock and three large aftershocks of magnitude 6-class. These data are essential for validating the sedimentary structure of the basin and for evaluating the hazard and risk of future earthquakes in the Kathmandu Valley.


Hereditary Vitamin D-Resistant Rickets (HVDRR) associated SNP variants of vitamin D receptor exhibit malfunctioning at multiple levels.
Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily. It is a primary regulator of calcium and phosphate homeostasis required for skeleton and bone mineralization. Vitamin D in active form 1α,25 dihydroxyvitamin-D3 mediates its cellular functions by binding to VDR. Active VDR forms heterodimers with partner RXR (retinoid X receptor) to execute its physiological actions. HVDRR (Hereditary Vitamin D-Resistant Rickets) is a rare genetic disorder that occurs because of generalized resistance to the 1α,25(OH)2D3. HVDRR is caused by the polymorphic variations in VDR gene leading to defective intestinal calcium absorption and mineralization of newly forming bones. Using point and deletion SNPs of VDR we have studied several HVDRR-associated SNP variants for their subcellular dynamics, transcriptional functions, 'genome bookmarking', heterodimeric interactions with RXR, and receptor stability. We previously reported that VDR is a 'mitotic bookmarking factor' that remains constitutively associated with the mitotic chromatin to inherit 'transcriptional memory', however the mechanistic details remained unclear. We document that 'genome bookmarking' property by VDR is critically impaired by naturally occurring HVDRR-associated point and deletion variants found in patients. Furthermore, these HVDRR-associated SNP variants of VDR were found to be compromised in transcriptional function, nuclear translocation, protein stability and intermolecular interactions with its heterodimeric partner RXR. Intriguingly, majority of these disease-allied functional defects failed to be rescued by RXR. Our findings suggest that the HVDRR-associated SNP variations influence the normal functioning of the receptor, and this derived understanding may help in the management of disease with precisely designed small molecule modulators.


Predictors of employment after liver transplantation.
Employment after orthotopic liver transplantation (OLT) indicates recipients' physical/psychosocial adjustment. Our aim was to determine clinical, socioeconomic and health-related quality of life parameters influencing employment after OLT. Questionnaire on demographics, medical conditions, alcohol and drug use before/after OLT, and a validated 12-Item Short Form Health Survey (SF-12) were mailed to 126 adult OLT patients. Stepwise logistic regression was conducted to identify best predictors of post-OLT employment. Among non-retirees, 49% were employed after OLT. The predictors of employment were: employment status, income, disability status before OLT and Model of End Stage Liver Disease score. These variables had prediction rate of 82%. Individuals working during the five yr prior to OLT were likely to return to work (p<0.0001), particularly those who held a job for >6 months prior to OLT (p<0.0001), income>$80 000 before OLT compared with <$30 000 (p=0.036). Patients receiving Social Security Insurance (SSI) payment for >or=6 months prior to OLT, were less likely to work (p=0.0005). Severity/duration of liver dysfunction prior to OLT did not correlate with employment. Sense of physical health was poorer in those employed after OLT than in unemployed (p=0.0003). Socioeconomic factors were the most important predictors of post-OLT employment.


spinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content.
Droplet microfluidic methods have massively increased the throughput of single-cell sequencing campaigns. The benefit of scale-up is, however, accompanied by increased background noise when processing challenging samples and the overall RNA capture efficiency is lower. These drawbacks stem from the lack of strategies to enrich for high-quality material or specific cell types at the moment of cell encapsulation and the absence of implementable multi-step enzymatic processes that increase capture. Here we alleviate both bottlenecks using fluorescence-activated droplet sorting to enrich for droplets that contain single viable cells, intact nuclei, fixed cells or target cell types and use reagent addition to droplets by picoinjection to perform multi-step lysis and reverse transcription. Our methodology increases gene detection rates fivefold, while reducing background noise by up to half. We harness these properties to deliver a high-quality molecular atlas of mouse brain development, despite starting with highly damaged input material, and provide an atlas of nascent RNA transcription during mouse organogenesis. Our method is broadly applicable to other droplet-based workflows to deliver sensitive and accurate single-cell profiling at a reduced cost.


Carbonyl heterocycle modified mesoporous carbon nitride in photocatalytic peroxydisulfate activation for enhanced ciprofloxacin removal: Performance and mechanism.
Polymer carbon nitride is considered to be a promising photocatalyst with broad application prospects in water treatment. However, the defects of pristine polymer carbon nitride (PCN), such as small specific surface area, fast photogenerated electron-hole recombination, and low mass transfer efficiency, limit its photocatalytic activity. In this work, by introducing 2-thiouracil into the precursor, a carbonyl heterocycle-containing mesoporous carbon nitride photocatalyst (TCN) was successfully obtained with significantly enhanced peroxydisulfate (PDS) photocatalytic activity. In this study, the modulation mechanism of carbonyl heterocycle introduction on surface electronic structure and the band structure were fully discussed by means of a combination of experiments and theoretical calculations. The carbonyl and vicinal carbon-modified heterocycles dominated the electrons, while the adjacent heptazine ring dominated the holes. The photogenerated electron-hole pair recombination efficiency and the electron transition energy barrier were greatly reduced. According to the findings of density functional theory (DFT) calculations, the introduction of carbonyl and vicinal C modulated the electronic structure of catalyst, enhanced the adsorption of PDS at the carbonyl ortho N site, which promoted the electronic interaction between TCN and PDS molecules. Experiments showed that the free radical pathway and non-radical pathway coexisted in TCN/PDS/Vis system. The reactive oxygen species were mainly derived from PDS molecules. DFT calculations provided a more comprehensive theoretical basis for the experimental results. This study provided a fresh perspective on the rational design of carbon nitride-based catalysts and the reaction mechanism of persulfate advanced oxidation systems.


Immunotherapy for the treatment of perineural spread in cutaneous head and neck squamous cell carcinoma: Time to rethink treatment paradigms.
Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited. Retrospective review of 13 patients with PNS receiving anti-PD-1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi-Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET). Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8-2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3-4 treatment related adverse events. This case series supports developing evidence for anti-PD-1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population.


Creation of a histone deacetylase 6 inhibitor and its biological effects [corrected].
We report the development of a potent, selective histone deacetylase 6 (HDAC6) inhibitor. This HDAC6 inhibitor blocks growth of normal and transformed cells but does not induce death of normal cells. The HDAC6 inhibitor alone is as effective as paclitaxel in anticancer activity in tumor-bearing mice.


Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non-B, non-C outcomes.
Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.


Calibration and validation of 6 DOFs instrumented spatial linkage for biomechanical applications. A practical approach.
A method for both calibration and validation of a 6 DOF electrogoniometer is presented. A 6 Revolute Instrumented Spatial Linkage (6R-ISL) and a three-dimensional digitizer (3DD) were used simultaneously to collect both static and continuous poses of unconstrained or constrained motions. Validation occurred using a calibrated ball-and-socket joint. A parametrical model of the 6R-ISL (i.e. Virtual Goniometer or VG) was designed using a standard multibody system geometry. Two approaches were used to adjust the VG parameters: a parametrical adjustment of the VG linkage geometry, and a functional adjustment of the potentiometer calibration curves (angle-voltage) in a predefined range of motion. After calibration, 6R-ISL accuracy was better than 1 mm and 1 degrees for translation and orientation, respectively. The functional method presented in this paper can be suggested as a practical approach, which allows on-line checking and calibration of 6R-ISL within the specific range of interest of a particular anatomical joint. In addition, improving the potentiometer calibration curves was less time consuming than the parametrical adjustment.


Glucose uptake in dilated small intestine.
The development of dilated small intestine in patients with short bowel syndrome results in increased mucosal surface area. This study examines whether the incremental increase in surface area leads to a proportional increase in absorptive function of the small intestine. Partial obstruction of the small intestine was created in rats by placing an intussusception valve in the proximal jejunum. Rats that underwent sham operations served as controls. One week postoperatively, the small intestine proximal and distal to the valve was removed. The intestinal diameter proximal and distal to the obstruction was measured. The rate of glucose uptake was measured by the everted sleeve technique. The results were analyzed by analysis of variance (ANOVA). The intestine proximal to the valve was significantly dilated and thickened when compared with the intestine distal to the valve. The wet mass per centimeter of the dilated segment was 2.5 times that of the control group (P<.001). The glucose uptake capacity of the dilated segment was slightly higher than that of the control group (540 v 420 nmol/min/cm, P<.05). However, the specific glucose uptake rate was reduced significantly in the intestine proximal to the valve (247 v 335 nmol/min/cm2, P<.01). Although the partial obstruction of small intestine resulted in a substantial increase in the intestinal surface area, the absorptive capacity of the dilated intestine per unit surface area was decreased significantly. This translated ultimately into a slight increase in the overall functional absorptive capacity of glucose in the small intestine. These results suggest that dilated small intestine may not enhance mucosal absorption.


An ELISA for the detection of anti-acetylcholine receptor antibodies using biotinylated alpha-bungarotoxin.
An antibody-capture enzyme immunoassay has been developed for the detection of anti-acetylcholine receptor (AChR) antibodies in tissue culture supernatants using biotinylated alpha-bungarotoxin (B alpha BGT). Immunoglobulins in culture supernatants were bound indirectly to microtitre plates via an anti-globulin antibody already coupled to polyvinyl plates. Anti-AChR antibodies were then detected by incubation with AChR crude extract. Bound AChR was revealed by incubation with B alpha BGT followed by horseradish peroxidase-conjugated avidin. This assay is specific, more sensitive than the commonly used double antibody radioimmunoassay, avoids the use of radioactive material, is practical for large numbers of samples and is particularly suitable for detecting anti-AChR antibodies in tissue culture supernatants.


Subcellular expression pattern and clinical significance of CBX2 and CBX7 in breast cancer subtypes.
Chromobox (CBX)2 and CBX7, members of CBX family protein, show diverse expression patterns and contrasting roles in certain cancers. We aimed to investigate the subcellular expression patterns and clinical significances of CBXs in breast cancer (BC) subtypes, which have heterogeneous clinical course and therapeutic responses. Among the subtypes, the triple-negative BC (TNBC) is a heterogeneous group that lacks specific markers. We categorized TNBC into quadruple-negative BC (QNBC) and TNBC, based on androgen receptor (AR) status, to make the groups more homogeneous. Immunohistochemistry for CBX proteins was performed on 323 primary invasive BC tissues and their clinical significances were analyzed. Cytoplasmic CBX2 (CBX2-c) was linked to adverse clinicopathological factors and TNBC and QNBC subtypes. In contrast, nuclear CBX7 (CBX7-n) was associated with favorable parameters and luminal A subtype. CBX2-c expression increased progressively from that in benign lesions to that in in situ carcinomas and invasive cancers, whereas CBX7-n and AR expressions showed sequential downregulation. AR was lower in metastatic tissues compared to matched primary cancer tissues. We speculate that the upregulation of CBX2-c and downregulation of CBX7-n could play a role in breast oncogenesis and an adverse clinical course, suggesting them as potential prognostic markers and therapeutic targets in invasive BCs.


The Role of Redox Dysregulation in the Inflammatory Response to Acute Myocardial Ischaemia-reperfusion Injury - Adding Fuel to the Fire.
The inflammatory response to acute myocardial ischaemia/ reperfusion injury (IRI) plays a critical role in determining myocardial infarct (MI) size, and subsequent post-MI left ventricular (LV) remodelling, making it a potential therapeutic target for improving clinical outcomes in patients presenting with an acute myocardial infarction (AMI). Recent experimental studies using advanced imaging and molecular techniques, have yielded new insights into the mechanisms through which reactive oxygen species (ROS) contribute to the inflammatory response induced by acute myocardial IRI - "adding fuel to the fire". The infiltration of inflammatory cells into the MI zone, leads to elevated myocardial concentrations of ROS, cytokine release, and activation of apoptotic and necrotic death pathways. Anti-oxidant and anti-inflammatory therapies have failed to protect the heart against acute myocardial IRI. This may be, in part, due to a lack of understanding of the time course, nature and mechanisms of the inflammation and redox dysregulation, which occur in the setting of acute myocardial IRI. In this article, we examine the inflammatory response and redox dysregulation induced by acute myocardial IRI, and highlight potential therapeutic options for targeting redox dysregulation, in order to attenuate the detrimental effects of the inflammatory response following an AMI, so as to reduce MI size and prevent heart failure.


Effects of thalamic parafascicular stimulation on the periaqueductal gray and adjacent reticular formation neurons. A possible contribution to pain control mechanisms.
To investigate the mechanism of analgesic effect of electrical stimulation of the thalamic parafascicular nucleus (Pf), we studied modulations of neuronal activities in the periaqueductal gray (PAG) and the adjacent reticular formation (RF) in response to Pf electrical and peripheral noxious stimulations in the rat. Extracellular single unit activities were recorded from 129 neurons in the PAG and adjacent RF under light halothane anesthesia. Pf stimulation caused neuronal responses in approximately 80% of the PAG and adjacent RF neurons, and noxious stimulation in 75%, with predominant excitatory responses to either stimulation. When the responses to the two stimuli were tested in the same neurons (n = 69), 91% responding to noxious stimuli also responded to Pf stimuli, again with predominant excitatory responses to either stimulation. The PAG and adjacent RF neurons that were verified antidromically to project to the nucleus raphe magnus (NRM), showed a similar pattern of response (n = 20). These results suggest that a sizeable population of neurons in the PAG and adjacent RF receives excitatory effects from the Pf and noxious afferents, and that part of these neurons projects to the NRM, which inhibits the dorsal horn cells of the spinal cord (the descending pain suppression system). Thus, part of the mechanism of the analgesic effects of Pf stimulation is due to activation of the descending pain suppression system by exciting the PAG and adjacent RF neurons. A possible role of noxious afferents on the negative feedback to pain mediation through this descending system also has to be considered.


Multiple biological activities for two peptides derived from the nerve growth factor precursor.
ProNGF can be cleaved proteolytically at dibasic residues and liberates two other peptides beside NGF, LIP1 a 29 amino acid (aa) peptide and LIP2 a 38 aa peptide. These peptides were found present in the rat intestine and shown to induce rapid phosphorylation of the Trk receptor in cell lines. The present study describes several novel biological properties for these peptides. They exert an anti-proliferative effect on the mitogenic activity of estrogen and IGF in MCF-7 cells. They protect against in vivo induction of excitotoxic lesions by the glutamatergic analogue ibotenate injected into the developing mouse brain and against in vitro NMDA-induced cell death in primary neuronal cultures. They bind to murine microglial cells and induce phosphorylation of Akt. These results suggest a role for LIP1 and LIP2 in cell survival.


Transient outward current in adult rat supraoptic neurones with slice patch-clamp technique: inhibition by angiotensin II.
1. Outward potassium currents were recorded from microscopically identified supraoptic neurones of adult Wistar male rats using the whole-cell patch-clamp technique in thin-slice preparations. The basic characteristics of transient outward current (IA or A-current) and the effects of angiotensin II (AII) on the currents were studied. 2. IA was isolated by subtracting outward currents elicited by stepping from two different holding potentials to a test potential or by applying 4-aminopyridine (4-AP) at 5 mM. The isolated IA had a threshold for activation between -55 and -65 mV and was characterized by fast activation and inactivation. Values of the time to peak and the inactivation time constants for current decay at different test potentials were voltage dependent. 3. Normalized currents for activation and steady-state inactivation of IA were fitted to the Boltzmann function. The mid-points and the slope factors were, respectively, -35.0 and -14.3 +/- 0.40 mV (n = 5) for the activation curve, and -72.0 and 7.0 +/- 0.68 mV (n = 5) for the inactivation curve. 4. The time course of recovery from inactivation was best fitted to a single exponential function with the time constant of 37.8 +/- 6.6 ms (n = 6). 5. The effects of AII on IA and delayed rectifier current (IK) were investigated. According to their responses to AII, cells were classified into two groups, sensitive and low-sensitive. Bolus injection of AII (10 microM, 100 microliters) decreased the IA amplitude by 25.1 +/- 2.4% in seven (53.8%) of the thirteen neurones tested (sensitive group), whereas the other six neurones (low-sensitive group) changed by only 2.2 +/- 0.8%. Perfusion of AII (0.1 microM) decreased the IA amplitude by 21.3 +/- 3.1% in six (54.5%) of eleven neurones tested (sensitive group), whereas the other five neurones (low-sensitive group) changed only by 1.7 +/- 0.8%. Bolus injection of AII (10 microM, 100 microliters) decreased the IK amplitude 9.6 +/-1.6% mV in five (45.5%) of the eleven neurones tested (sensitive group), whereas the other six neurones (low-sensitive group) changed only by 0.46 +/- 0.27%. In the sensitive groups, the reduction of IA by AII was significantly larger than that of IK (P < 0.05). 6. Application of saralasin at 1 microM, an AII antagonist, blocked the effects of AII on IA. 7. These results suggest that the excitatory action of AII on supraoptic neurosecretory cells is mediated at least in part through suppression of IA.


Formalin instillation for refractory radiation-induced hemorrhagic proctitis.
Radiation proctitis is a common complication after pelvic irradiation. One to five percent of these patients will develop intractable or massive hemorrhagic radiation proctitis that will require repeated hospital admissions and blood transfusions. We evaluated the benefits of instillation of 4% formalin in the management of refractory hemorrhagic radiation-induced proctitis. From January 1998 to May 1999, 20 female patients who failed with administration of topical steroids and/or mesalazine were treated with 500 ml of 4% formalin instilled into the rectum in 50-ml aliquots. Median age was 58 years. Eighteen patients had cervical cancer and two, endometrial cancer. These patients received a mean of 7,500 rads to the pelvis. The symptoms began at a mean of 8 months after termination of radiotherapy. Median time of symptomatic rectal hemorrhage was 8 months. Median of blood units previously transfused was six (range: 2-11). Hemorrhage immediately ceased after the 4% formalin instillation in 17 patients. Three patients required formalin instillation repetition with success in one. Overall success was 90%. Median follow-up was 20 months. Five patients had moderate pelvic pain after instillation and one developed rectosigmoideal necrosis that required resection plus Hartmann procedure. Two patients developed rectovaginal fistula and required colostomy, and one thereafter, required abdominoperineal resection en bloc with the posterior wall of the vagina due to pelvis sepsis. Rectal instillation of 4% formalin is a simple, inexpensive, and efficient treatment for refractory hemorrhagic radiation proctitis.


Production of xylanase and β-xylosidase from autohydrolysis liquor of corncob using two fungal strains.
Agroindustrial residues are materials often rich in cellulose and hemicellulose. The use of these substrates for the microbial production of enzymes of industrial interest is mainly due to their high availability associated with their low cost. In this work, corncob (CCs) particles decomposed to soluble compounds (liquor) were incorporated in the microbial growth medium through autohydrolysis, as a strategy to increase and undervalue xylanase and β-xylosidase production by Aspergillus terricola and Aspergillus ochraceus. The CCs autohydrolysis liquor produced at 200 °C for 5, 15, 30 or 50 min was used as the sole carbon source or associated with untreated CC. The best condition for enzyme synthesis was observed with CCs submitted to 30 min of autohydrolysis. The enzymatic production with untreated CCs plus CC liquor was higher than with birchwood xylan for both microorganisms. A. terricola produced 750 total U of xylanase (144 h cultivation) and 30 total U of β-xylosidase (96-168 h) with 0.75% untreated CCs and 6% CCs liquor, against 650 total U of xylanase and 2 total U of β-xylosidase in xylan; A. ochraceus produced 605 total U of xylanase and 56 total U of β-xylosidase (168 h cultivation) with 1% untreated CCs and 10% CCs liquor against 400 total U of xylanase and 38 total U of β-xylosidase in xylan. These results indicate that the treatment of agroindustrial wastes through autohydrolysis can be a viable strategy in the production of high levels of xylanolytic enzymes.


Identification and removal of nitroxide spin label contaminant: impact on PRE studies of α-helical membrane proteins in detergent.
NMR paramagnetic relaxation enhancement (PRE) provides long-range distance constraints (~15-25 Å) that can be critical to determining overall protein topology, especially where long-range NOE information is unavailable such as in the case of larger proteins that require deuteration. However, several challenges currently limit the use of NMR PRE for α-helical membrane proteins. One challenge is the nonspecific association of the nitroxide spin label to the protein-detergent complex that can result in spurious PRE derived distance restraints. The effect of the nitroxide spin label contaminant is evaluated and quantified and a robust method for the removal of the contaminant is provided to advance the application of PRE restraints to membrane protein NMR structure determination.


[The Observatory of Spirituality, an organization serving citizens].
Since 2007, the Observatoire de la Laïcité has been helping the French Government in its actions aimed at ensuring compliance with the principle of "laïcité"--the French concept of secularity--in the country. Implementation of its missions enable it to measure how the concept of "laïcité" is understood and applied today.


Etiologic agents of otitis media in Benin city, Nigeria.
Otitis Media continues to be a major presentation in the ear, nose and throat clinic. This study aimed to isolate, characterize and identify the bacteriological and mycological etiologic agents of otitis media in Benin city. Ear discharge from 569 (299 males and 270 females) patients diagnosed clinically of otitis media between August 2009 and August 2010 were processed to recover the bacterial and fungal etiologic agents. Susceptibility test was performed on all bacterial isolate. Pseudomonas aeruginosa (28.3%) was the predominant bacteria isolate causing otitis media followed by Staphylococcus aureus (21.0%), Klebsiella sp (8.9%), Proteus sp (8.2%), Alkaligenes spp (4.3%), Streptococcus pneumoniae (3.9%), Escherichia coli (3.0%) and Citrobacter freundi (1.7%). Fungi isolated were Aspergillus niger (9.2%), Candida albicans (5.4%), Candida tropicalis (3.0%), Aspergillus flavus (2.1%) and Candida parasilopsis (1.5%). 413 had a single organism isolated from the middle ear culture while twenty (3.51%) patients had mixed organisms isolated. Infection was highest among 0 - 5 years, and lowest among aged 18 - 23. All bacterial isolates were poorly susceptible to the antibacterial agents. The study uncovers a high frequency of bacteria associated otitis media with the finding of fungi too as a significant etiologic agent.


The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner.
The HIV-1 Nef virulence factor interacts with multiple host cell-signaling proteins. Nef binds to the Src homology 3 domains of Src family kinases, resulting in kinase activation important for viral infectivity, replication, and MHC-I down-regulation. Itk and other Tec family kinases are also present in HIV target cells, and Itk has been linked to HIV-1 infectivity and replication. However, the molecular mechanism linking Itk to HIV-1 is unknown. In this study, we explored the interaction of Nef with Tec family kinases using a cell-based bimolecular fluorescence complementation assay. In this approach, interaction of Nef with a partner kinase juxtaposes nonfluorescent YFP fragments fused to the C terminus of each protein, resulting in YFP complementation and a bright fluorescent signal. Using bimolecular fluorescence complementation, we observed that Nef interacts with the Tec family members Bmx, Btk, and Itk but not Tec or Txk. Interaction with Nef occurs through the kinase Src homology 3 domains and localizes to the plasma membrane. Allelic variants of Nef from all major HIV-1 subtypes interacted strongly with Itk in this assay, demonstrating the highly conserved nature of this interaction. A selective small molecule inhibitor of Itk kinase activity (BMS-509744) potently blocked wild-type HIV-1 infectivity and replication, but not that of a Nef-defective mutant. Nef induced constitutive Itk activation in transfected cells that was sensitive to inhibitor treatment. Taken together, these results provide the first evidence that Nef interacts with cytoplasmic tyrosine kinases of the Tec family and suggest that Nef provides a mechanistic link between HIV-1 and Itk signaling in the viral life cycle.


The bisexual branching process with population-size dependent mating as a mathematical model to describe phenomena concerning to inhabit or re-inhabit environments with animal species.
We consider the bisexual Galton-Watson branching process with population-size dependent mating as a mathematical model adequate for the description of some natural phenomena. More specifically we are interested in studying some questions about the problem of populating an environmental with new animal species or re-populating it with species which have previously disappeared.


Risk of pneumonia among patients with splenectomy: a retrospective population-based cohort study.
People without a spleen are particularly susceptible to various overwhelming infections including pneumonia. Although the association between splenectomy and pneumonia has been previously studied, there has been no study using the national claims data. The aim of the study was to investigate the association between splenectomy and pneumonia. A retrospective population-based cohort analysis. Database of the Taiwan National Health Insurance Program. Persons newly diagnosed with splenectomy from 2000 to 2010 were compared with randomly selected subjects without splenectomy. The groups were matched by sex, age, comorbidities, and the year of index date and analyzed by multivariate methods. The difference in incidence of pneumonia at the end of 2011. In 12 757 individuals aged 20-84 years with splenectomy, the overall incidence of pneumonia was 1.86-fold higher than in the 51 019 individuals without splenectomy (25.0 vs. 13.4 per 1000 person-years, 95% CI 1.78, 1.95). After multivariate analysis, the adjusted hazard ratio for pneumonia was 2.2 for subjects with splenectomy (95%CI 2.07, 2.34). In further analysis, in the absence of any comorbidity, the adjusted HR for pneumonia was 3.03 for those with splenectomy alone (95% CI 2.76, 3.33) and 5.28 (95% CI 4.82, 5.78) for splenectomy and any comorbidity. Although not a novel finding, we confirmed that splenectomy increases the relative risk for developing pneumonia in a large study population. Even in the absence of any comorbidity, the risk remains high. Patients with splenectomy should receive preventive interventions for pneumonia, such as vaccination. ICD-9 codes do not differentiate if pneumonia is caused by a viral, a bacterial or unspecified organisms, and some behavioral factors like smoking could not be ascertained directly.


Segregational drift hinders the evolution of antibiotic resistance on polyploid replicons.
The emergence of antibiotic resistance under treatment depends on the availability of resistance alleles and their establishment in the population. Novel resistance alleles are encoded either in chromosomal or extrachromosomal genetic elements; both types may be present in multiple copies within the cell. However, the effect of polyploidy on the emergence of antibiotic resistance remains understudied. Here we show that the establishment of resistance alleles in microbial populations depends on the ploidy level. Evolving bacterial populations under selection for antibiotic resistance, we demonstrate that resistance alleles in polyploid elements are lost frequently in comparison to alleles in monoploid elements due to segregational drift. Integrating the experiments with a mathematical model, we find a remarkable agreement between the theoretical and empirical results, confirming our understanding of the allele segregation process. Using the mathematical model, we further show that the effect of polyploidy on the establishment probability of beneficial alleles is strongest for low replicon copy numbers and plateaus for high replicon copy numbers. Our results suggest that the distribution of fitness effects for mutations that are eventually fixed in a population depends on the replicon ploidy level. Our study indicates that the emergence of antibiotic resistance in bacterial pathogens depends on the pathogen ploidy level.


Association of Chorioamnionitis With Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review, Meta-analysis, and Metaregression.
Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, remains one of the major and most common complications of very preterm birth. Insight into factors associated with the pathogenesis of BPD is key to improving its prevention and treatment. To perform a systematic review, meta-analysis, and metaregression of clinical studies exploring the association between chorioamnionitis (CA) and BPD in preterm infants. PubMed and Embase were searched without language restriction (last search, October 1, 2018). Key search terms included bronchopulmonary dysplasia, chorioamnionitis, and risk factors. Included studies were peer-reviewed studies examining preterm (<37 weeks' gestation) or very low-birth-weight (<1500 g) infants and reporting primary data that could be used to measure the association between exposure to CA and the development of BPD. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. Data were independently extracted by 2 researchers. A random-effects model was used to calculate odds ratios (ORs) and 95% CIs. Heterogeneity in effect size across studies was studied using multivariate, random-effects metaregression analysis. The primary outcome was BPD, defined as supplemental oxygen requirement on postnatal day 28 (BPD28) or at the postmenstrual age of 36 weeks (BPD36). Covariates considered as potential confounders included differences between CA-exposed and CA-unexposed infants in gestational age, rates of respiratory distress syndrome (RDS), exposure to antenatal corticosteroids, and rates of early- and late-onset sepsis. A total of 3170 potentially relevant studies were found, of which 158 met the inclusion criteria (244 096 preterm infants, 20 971 CA cases, and 24 335 BPD cases). Meta-analysis showed that CA exposure was significantly associated with BPD28 (65 studies; OR, 2.32; 95% CI, 1.88-2.86; P < .001; heterogeneity: I2 = 84%; P < .001) and BPD36 (108 studies; OR, 1.29; 95% CI, 1.17-1.42; P < .001; heterogeneity: I2 = 63%; P < .001). The association between CA and BPD remained significant for both clinical and histologic CA. In addition, significant differences were found between CA-exposed and CA-unexposed infants in gestational age, birth weight, odds of being small for gestational age, exposure to antenatal corticosteroids, and early- and late-onset sepsis. Chorioamnionitis was not significantly associated with RDS (48 studies; OR, 1.10; 95% CI, 0.92-1.34; P = .24; heterogeneity: I2 = 90%; P < .001), but multivariate metaregression analysis with backward elimination revealed that a model combining the difference in gestational age and the odds of RDS was associated with 64% of the variance in the association between CA and BPD36 across studies. The results of this study confirm that among preterm infants, exposure to CA is associated with a higher risk of developing BPD, but this association may be modulated by gestational age and risk of RDS.


In vitro reconstitution of rotavirus transcriptional activity using viral cores and recombinant baculovirus expressed VP6.
Purified baculovirus-expressed group A rotavirus VP6 polypeptide was shown to be active in the recovery of the transcriptase activity associated with the reconstitution of the single-shelled rotavirus particle. Recombinant VP6 polypeptide was able to restore the transcriptional activity in purified viral cores from both SA-11 and RF rotavirus strains. Recombinant group C VP 6 (Cowden strain) is capable of binding as a trimer to group A viral core particles but unable to restore the transcriptase activity, suggesting that the binding of the polypeptide to cores is not the only requirement to restore the transcriptase activity. The VP 6 group A polypeptide was shown to bind as a monomer to viral cores, indicating that trimerization of VP 6 may be not required for reconstitution of the polymerase activity.


Designing drugs when there is low data availability: one-shot learning and other approaches to face the issues of a long-term concern.
Modern drug discovery is generally accessed by useful information from previous large databases or uncovering novel data. The lack of biological and/or chemical data tends to slow the development of scientific research and innovation. Here, approaches that may help provide solutions to generate or obtain enough relevant data or improve/accelerate existing methods within the last five years were reviewed. One-shot learning (OSL) approaches, structural modeling, molecular docking, scoring function space (SFS), molecular dynamics (MD), and quantum mechanics (QM) may be used to amplify the amount of available data to drug design and discovery campaigns, presenting methods, their perspectives, and discussions to be employed in the near future. Recent works have successfully used these techniques to solve a range of issues in the face of data scarcity, including complex problems such as the challenging scenario of drug design aimed at intrinsically disordered proteins and the evaluation of potential adverse effects in a clinical scenario. These examples show that it is possible to improve and kickstart research from scarce available data to design and discover new potential drugs.


Correlation between the effects of salbutamol on contractions and cyclic AMP content of isolated fast-and slow-contracting muscles of the guinea pig.
The effects of isoprenaline and salbutamol on incomplete tetanic contractions of the isolated soleus (slow contracting) and extensor digitorum longus (EDL-fast-contracting) muscles of the guinea pig were studied and an attempt made to correlate these effects on contractility with changes in cyclic AMP concentrations. Salbutamol was 10-12 times less potent than (+/-)isoprenaline in decreasing the force of subtetanic contractions in the soleus and between 5-6 times less potent in increasing the force of subtetanic contractions in the EDL. This observation plus the lack of activity of both the selective beta1-adrenoceptor antagonist (atenolol) and the selective beta1 agonist (H 133/22) in the EDL implies involvement of beta2-adrenoceptors in these responses of the muscles to isoprenaline and salbutamol. The soleus muscle was about 6-12 times more sensitive to effects of beta-adrenoceptor agonists than the EDL. In concentrations which produced effects on muscle contractility, salbutamol significantly elevated cyclic AMP concentrations in both types of muscle. These effects were antagonised by propranolol. It seems clear that the contrasting effects of sympathomimetic amines on slow-and fast contracting muscle are mediated through a common mechanism-elevation of cyclic AMP. Possible explanations of this apparent paradox are discussed.


The limitation of staged repair in the surgical management of congenital complex heart anomalies with aortic arch obstruction.
Severe aortic arch obstruction including an interrupted aortic arch in congenital complex heart anomalies remains a challenge in surgical management. Treatment and outcomes in 75 consecutive patients who underwent an aortic arch repair as the first step of the staged repair protocol between 1975 and 2000 were reviewed. Their ages at repair ranged from 1 day to 8.5 months. Cross-sectional postoperative follow-up data were available in all the patients. The follow-up period ranged from 0 to 27.6 years (mean: 7.3 +/- 7.3 years). There were 20 postoperative hospital deaths (27%) and 7 late deaths. The Kaplan-Meier estimate of survival was 81.3% +/- 4.5% at 1 month, 68.0% +/- 5.4% at 1 year, 65.0% +/- 5.5% at 5 years, 63.1% +/- 5.7% at 10 years, 63.1% +/- 5.7% at 20 years. By Cox regression analysis, body weight of 2.5 kg or less is the only independent determinant of postoperative mortality (p = 0.04, multivariable odds ratio: 2.50, [95% confidence interval: 1.02-6.1]). The aortic arch morphology, the primary cardiac lesion, or date of operation did not reach a statistically significant level to show correlation with mortality. Reintervention to reconstruct the aortic arch was performed at 9 occasions in 8 of the 55 patients who survived the primary operation (14.5%). The Kaplan-Meier estimate of the reintervention-free rate was 91.3% +/- 4.2% at 5 years, 85.5% +/- 5.6% at 10 years, 75.6% +/- 8.2% at 20 years. Using multivariable Cox regression analysis, interrupted aortic arch (versus aortic coarctation) was the only independent predictor of a shorter time to reintervention (p = 0.001, multivariable odds ratio: 16.1, [95% confidence interval: 3.2-80.2]). The staged repair protocol was associated with significant limitations in patient survival and with the development of recurrent aortic arch obstruction. Thus, a primary repair protocol may serve as an alternate approach, especially in patients with low weight or with an interrupted aortic arch.


Cheek Tooth Extraction Via a Minimally Invasive Transbuccal Approach and Intradental Screw Placement in 54 Equids.
To describe (1) preoperative findings and surgical technique, (2) intraoperative difficulties, and (3) postoperative complications and long-term outcome of equine cheek tooth extraction using a minimally invasive transbuccal screw extraction (MITSE) technique. Retrospective case series. Fifty-four equids; 50 horses, 3 ponies, and 1 mule. Fifty-eight MITSE procedures were performed to extract cheek teeth in 54 equids. Peri- and intraoperative difficulties, as well as short- (<1 month) and long-term (>6 months) postoperative complications were recorded. Followup information was obtained through telephone interviews, making specific inquiries about nasal discharge, facial asymmetry, and findings consistent with surgical site infection. Preoperative findings that prompted exodontia included 50 cheek teeth with apical infections, 48 fractures, 4 neoplasia, 2 displacements, and 1 supernumerary tooth. Previous oral extraction was attempted but had failed in 55/58 (95%) animals because of cheek tooth fracture in 28, or insufficient clinical crown for extraction with forceps in 27. MITSE was successful in removing the entire targeted dental structure in 47/58 (81%) procedures. However, MITSE failed to remove the entire targeted dental structure in 11/58 (19%) procedures and was followed by repulsion in 10/11 (91%). Short-term postoperative complications included bleeding (4/58 procedures, 7%) and transient facial nerve paralysis (4/58 procedures, 7%). Owners were satisfied with the functional and cosmetic outcome for 40/41 (98%) animals with followup. MITSE offers an alternate for cheek tooth extraction in equids, where conventional oral extraction is not possible or has failed. Overall, there was low morbidity, which compares favorably with invasive buccotomy or repulsion techniques.


Comparison of gastric peristalsis inhibition by scopolamine butylbromide and glucagon: evaluation by electrogastrography and analysis of heart rate variability.
Activation of glucagon receptors of the smooth muscle membrane suppresses gastric peristalsis. We evaluated autonomic nervous activity by two methods, electrogastrography (EGG) and analysis of heart rate variability, to compare the inhibiting effects of glucagon and scopolamine butylbromide on gastric peristalsis. Heart rate variability, EGG, and blood catecholamine levels were measured before and after administration of glucagon (G group), scopolamine butylbromide (SB group), or physiological saline (C group). Autonomic nervous function was evaluated using spectral analysis of heart rate variability, and low frequency (LF) and high frequency (HF) power; the LF/HF ratios were also determined. After administration of scopolamine butylbromide, HF power, an index of parasympathetic nervous activity, decreased; and the LF/HF ratio, an index of sympathetic nervous activity, increased. In contrast, no significant change was observed in autonomic nervous activity after administration of glucagon. The peak power amplitudes of the EGG decreased significantly in the G and SB groups after intramuscular injection, but the difference between the groups was not significant. Furthermore, the dominant frequency increased significantly in the G and SB groups after injection. Serum catecholamine levels showed no significant changes after administration of scopolamine butylbromide or glucagon. Inhibition of gastric peristalsis by glucagon via glucagon receptors on smooth muscles did not influence autonomic nervous activity, unlike the results obtained after administration of scopolamine butylbromide. Therefore, glucagon may be safe for use with elderly patients and those with cardiopulmonary complications.


Modus operandi of the bacterial RNA polymerase containing the sigma54 promoter-specificity factor.
Bacterial sigma (sigma) factors confer gene specificity upon the RNA polymerase, the central enzyme that catalyses gene transcription. The binding of the alternative sigma factor sigma(54) confers upon the RNA polymerase special functional and regulatory properties, making it suited for control of several major adaptive responses. Here, we summarize our current understanding of the interactions the sigma(54) factor makes with the bacterial transcription machinery.


In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells.
Early dissemination of treatment-resistant tumor cells remains the major cause of metastatic recurrence and death in breast cancer patients. Dendritic cells (DCs) are the most powerful antigen-presenting cells, and recently DC-based vaccination has shown great promise for the treatment of human malignancies by immunological intervention. CD8+ T lymphocytes derived from peripheral blood mononuclear cells stimulated in vitro with autologous breast tumor antigen-pulsed DCs were tested for their ability to induce a HLA class I restricted cytotoxic T lymphocyte (CTL) response against autologous tumor cells. To correlate cytotoxic activity by CTL with T cell phenotype, two-color flow cytometric analysis of surface markers and intracellular cytokine expression was performed. DC pulsed with breast tumor extracts consistently elicited a tumor-specific HLA class I restricted CTL response in vitro in three consecutive patients harboring locally advanced breast cancer. CTL expressed strong cytolytic activity against autologous tumor cells but did not lyse autologous Epstein Barr virus-transformed lymphoblastoid cell lines and showed variable cytotoxicity against the natural killer-sensitive cell line K-562. In all patients, two color flow cytometric analysis of surface markers and intracellular cytokine expression demonstrated that tumor-specific CTL exhibited an heterogeneous CD8+/CD56+ expression and a striking Th1 cytokine bias (IFNgamma(high)/IL-4 (low)). Tumor lysate-pulsed DCs can consistently stimulate specific CD8+ CTLs able to kill autologous tumor cells in patients with locally advanced breast cancer in vitro. Tumor antigen-pulsed DC-based vaccinations may be appropriate for the treatment of residual and/or chemotherapy-resistant breast cancer refractory to standard salvage treatment modalities.


Diffusion-relaxation correlation spectrum imaging for predicting tumor consistency and gross total resection in patients with pituitary adenomas: a preliminary study.
To evaluate the ability of diffusion-relaxation correlation spectrum imaging (DR-CSI) to predict the consistency and extent of resection (EOR) of pituitary adenomas (PAs). Forty-four patients with PAs were prospectively enrolled. Tumor consistency was evaluated at surgery as either soft or hard, followed by histological assessment. In vivo DR-CSI was performed and spectra were segmented following to a peak-based strategy into four compartments, designated A (low ADC), B (mediate ADC, short T2), C (mediate ADC, long T2), and D (high ADC). The corresponding volume fractions ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) along with the ADC and T2 values were calculated and assessed using univariable analysis for discrimination between hard and soft PAs. Predictors of EOR > 95% were analyzed using logistic regression model and receiver-operating-characteristic analysis. Tumor consistency was classified as soft (n = 28) or hard (n = 16). Hard PAs presented higher [Formula: see text] (p = 0.001) and lower [Formula: see text] (p = 0.013) than soft PAs, while no significant difference was found in other parameters. [Formula: see text] significantly correlated with the level of collagen content (r = 0.448, p = 0.002). Knosp grade (odds ratio [OR], 0.299; 95% confidence interval [CI], 0.124-0.716; p = 0.007) and [Formula: see text] (OR, 0.834, per 1% increase; 95% CI, 0.731-0.951; p = 0.007) were independently associated with EOR > 95%. A prediction model based on these variables yielded an AUC of 0.934 (sensitivity, 90.9%; specificity, 90.9%), outperforming the Knosp grade alone (AUC, 0.785; p < 0.05). DR-CSI may serve as a promising tool to predict the consistency and EOR of PAs. DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs and may serve as a promising tool to predict the tumor consistency and extent of resection in patients with PAs. • DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs by visualizing the volume fraction and corresponding spatial distribution of four compartments ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). • [Formula: see text] correlated with the level of collagen content and may be the best DR-CSI parameter for discrimination between hard and soft PAs. • The combination of Knosp grade and [Formula: see text] achieved an AUC of 0.934 for predicting the total or near-total resection, outperforming the Knosp grade alone (AUC, 0.785).


Patient profile in a bone health and osteoporosis prevention service in Ireland.
To (1) characterise a cohort of patients attending a major osteoporosis clinic in Ireland and (2) examine the prescribing of preventative therapies amongst these patients. Data were taken from 2006-2007 on patients attending the Osteoporosis Clinic at St. James's Hospital, Dublin. Information gathered included age, gender, fracture history, past medical and surgical history, co-morbidities, the results of the first DXA scans, anti-resorptive therapies along with other medications prescribed. Of all patients 87.6% were female and the mean age was 68 years (SD = 14.31). In total 166 (74%) patients had osteoporosis, 40 (17.8%) had osteopenia and 18 patients (8%) had normal T-score values, 163 (72.7%) had a history of a fracture. Only 13.7% of the patients did not have a documented history of other co-morbidities. Comprehensive services such as the Osteoporosis Clinic at St. James's Hospital can provide the necessary screening, monitoring and prescribing of appropriate osteoporosis medications with additional follow-up if required to this at risk group reducing the unnecessarily traumatic effects of the disease on patients.


Hyperbaric oxygen improves engraftment of ex-vivo expanded and gene transduced human CD34⁺ cells in a murine model of umbilical cord blood transplantation.
Delayed engraftment and graft failure represent major obstacles to successful umbilical cord blood (UCB) transplantation. Herein, we evaluated the use of hyperbaric oxygen (HBO) therapy as an intervention to improve human UCB stem/progenitor cell engraftment in an immune deficient mouse model. Six- to eight-week old NSG mice were sublethally irradiated 24 hours prior to CD34⁺ UCB cell transplant. Irradiated mice were separated into a non-HBO group (where mice remained under normoxic conditions) and the HBO group (where mice received 2 hours of HBO therapy; 100% oxygen at 2.5 atmospheres absolute). Four hours after completing HBO therapy, both groups intravenously received CD34⁺ UCB cells that were transduced with a lentivirus carrying luciferase gene and expanded for in vivo imaging. Mice were imaged and then sacrificed at one of 10 times up to 4.5 months post-transplant. HBO treated mice demonstrated significantly improved bone marrow, peripheral blood, and spleen retention and subsequent engraftment. In addition, HBO significantly improved peripheral, spleen and bone marrow engraftment of human myeloid and B-cell subsets. In vivo imaging demonstrated that HBO mice had significantly higher ventral and dorsal bioluminescence values. These studies suggest that HBO treatment of NSG mice prior to UCB CD34⁺ cell infusion significantly improves engraftment.


Improved water quality monitoring indicators may increase carbon storage in the oceans.
Indicators related to organic matter are important when assessing aquatic environment quality. The chemical oxygen demand (COD) is widely used as a water quality reference. However, oxidizing agents used to determine the COD can oxidize refractory organic matter that is not pollutant and can persist in the ocean for thousands of years. This means the COD can misrepresent the water quality. The actual water quality can be indicated better by the biochemical oxygen demand (BOD) than the COD, but determining the BOD is time-consuming and gives variable results. In this study, the optical properties of dissolved organic matter in water samples from the Chinese coast that had been incubated for a long time or directly oxidized using COD oxidant were analyzed. The results indicated that the oxidizing agent rapidly oxidized 22.93% ± 4.96% of refractory dissolved organic matter (RDOM) that was resistant to microbial degradation, implying that RDOM made a marked contribution to the COD. Meanwhile, size-fractional fluorescence spectroscopy and COD measurements indicated that the COD of the >0.7 μm fraction and the fluorescence intensity of the protein-like component significantly positively correlated with the BOD of the bulk sample. This indicated that, for monitoring organic pollutants in coastal waters, the COD of the >0.7 μm fraction could be used as a proxy for the standard COD and that the fluorescence intensity of the protein-like component could be used as a convenient proxy for the BOD. The method can help retain recalcitrant organic matter in seawater to act as a carbon sink.


Use of 16S rRNA sequencing for identification of Actinobacillus ureae isolated from a cerebrospinal fluid sample.
Actinobacillus ureae, previously Pasteurella ureae, has on rare occasions been described as a cause of human infection. Owing to its rarity, it may not be easily identified in clinical microbiology laboratories by standard tests. This report describes a patient with acute bacterial meningitis due to A. ureae. The identity of the isolate was determined by means of DNA sequence analysis of a portion of the 16S rRNA gene.


[Treatment methods of body surface hemangioma].
To discuss the methods selection on treatment of body surface hemangioma. From February 1983 to March 2001, 265 patients with different types of body surface hemangioma were treated with prednisone in 94 cases, laser in 102 cases, and plastic surgery operation in 69 cases respectively. Followed up 6 months to 15 years, 70 cases with prednisone treatment were cured (74.5%), which meaned the hemangioma was totally removed and no recurrence in 6 months follow-up, 51 cases with laser treatment were cured (50%), while in the plastic surgery operation group, the cure rate was 98.6% (68 cases). Treatment with prednisone, laser or plastic surgery operation are all effective to body surface hemangioma and proper treatment method should be selected according to different period and different type of hemangioma to improve the therapeutic effectiveness.


UTX inhibition as selective epigenetic therapy against TAL1-driven T-cell acute lymphoblastic leukemia.
T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A. Specifically, we identify UTX as a coactivator of TAL1 and show that it acts as a major regulator of the TAL1 leukemic gene expression program. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a pro-oncogenic cofactor essential for leukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we propose a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that efficiently kills TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients.


DEAD box RNA helicases protect Antarctic Pseudomonas syringae Lz4W against oxidative stress.
DEAD box RNA helicases are involved in important cellular processes like RNA metabolism (Processing and Degradation), ribosome biogenesis and translation. Besides being crucial to the formation of cold adapted degradosomes, RNA helicases have been implicated in structural rearrangement of RNA, implying a role in alleviation of RNA secondary structure stabilization at low temperature. This study depicts the results of experiments on protective role played by DEAD box RNA helicases against nucleic acid damaging agents. RNA helicase mutants ΔrhlE, ΔsrmB, ΔcsdA, ΔdbpA and ΔrhlB cells were exposed to various DNA damaging agents (UV, Paraquat, Mitomycin C, Hydroxyurea and Hydrogen peroxide) and assessed for sensitivity to them. Our results illustrate that ∆csdA displayed sensitivity to paraquat (that causes oxidative damage) and UV radiation induced DNA damage. On the other hand, ∆srmB displays sensitivity to hydroxyurea that causes damage to the replication forks (RFs) by inhibiting ribonucleotide reductase and depleting the dNTP pool of cells. However, all five RNA helicase mutants were resistant to H2O2 mediated oxidative stress and mitomycin C induced DNA cross-links.


Expression of MAPK1 in cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition, invasion and metastasis.
To discuss the expression of mitogen-activated protein kinase 1 (MAPK1) in the cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition and invasion and metastasis. Immunohistochemistry, western blot and RT-PCR method were employed to detect the expression of MAPK1 protein and mRNA in cervical cancer tissue and adjacent normal tissue. The constructed siRNA-MAPK1 was transferred into human cervical cancer HeLa cells using Lipofectamine™2000. MTT method was used to detect the cell vitality, transwell method to detect the cell invasion, and western blot to detect the expression of matrix metalloproteinases (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, zinc finger transcription factor (Snail), epithelial-mesenchymal transition related protein (EMT) E-cadherin and vimentin in cells. The expression of MAPK1 protein and mRNA in the cervical cancer tissue was significantly higher than the one in the adjacent normal tissue (P < 0.01); after transfecting the siRNA-MAPK1 into the human cervical cancer HeLa cells through liposome, compared with the control group, its cell vitality was significantly decreased (P < 0.01), cell invasion was significantly decreased (P < 0.01); expressed of MMP-2, MMP-9, Snail and vimentin was significantly decreased (P < 0.01), and expression of TIMP-1, TIMP-2 and E-cadherin was significantly increased (P < 0.01). Because of the high expression of MAPK1 in the cervical cancer tissue, the interference in the expression of MAPK1 can significantly inhibit the invasion and metastasis of cervical cancer HeLa cells, which is related to the interference in the expression of MMPs/TIMP and Snail-mediated generation of EMT.


Aphasia following a right thalamic hemorrhage.
A left-handed patient with a right thalamic hemorrhage and disordered speech is described. Sequential examinations and aphasia testing were done during a 1-year follow-up period and the results are reported. This case supports those authors who have described characteristics they feel are helpful in diagnosing disordered speech associated with thalamic lesions. Paucity of speech, reduced voice volume, anomia, some paraphasia, and severe dysgraphia were present, but comprehension and repetition were relatively preserved. She showed modest improvement with time. This case also confirms that thalamic involvement in speech is a dominant, rather than a specifically left hemispheric function.


Spatial relationship between ambulatory surgery centers and colorectal cancer mortality within Pennsylvania, United States.
The objective of this study was to evaluate the spatial relationship between colorectal cancer (CRC) mortality and ambulatory surgery center (ASC) density in Pennsylvania's 67 counties. This was an ecological study. Age-adjusted CRC mortality rates were linked to ASC densities per 1,000 people. The data set was analyzed using global, local, and regional Moran's I, to test for randomness in CRC mortality and ASC density. CRC mortality rates (median: 15.30 per 100,000 of the US 2000 standard million population) exhibited hot spots in rural Pennsylvania counties. ASC densities (median: 0.35 providers/km2 per 1,000 people) showed hot spots in urban southeastern Pennsylvania and cold spots in northern Pennsylvania. CRC mortality rates tended to cluster in rural northern Pennsylvania counties; ASC density tended to cluster in urban southeastern counties, indicating a spatial disparity between needed and provided healthcare resources. There is a need for public health and health system changes to increase the availability of CRC services to rural communities.


Association of Gestational Weight Gain With Infant Morbidity and Mortality in the United States.
The associations of gestational weight gain (GWG) with infant morbidity and mortality are unclear, and the existing recommendations for GWG have not been stratified by the severity of obesity. To identify optimal GWG ranges associated with reduced risks of infant morbidity and mortality across maternal body mass index (BMI) categories. This retrospective cohort study used US nationwide, linked birth and infant death data between 2011 and 2015 to assess the associations of GWG in 2.0-kg groups with infant morbidity and mortality and identified optimal GWG ranges associated with reduced risks of both outcomes, using multivariable logistic regression models. Statistical analysis was performed from February 11 to October 14, 2021. Gestational weight gain equivalent to 40 weeks. The 2 main outcomes were (1) significant morbidity of the newborn infant, defined as any presence of assisted ventilation, admission to the neonatal intensive care unit, surfactant therapy, antibiotic therapy, or seizures; and (2) infant mortality younger than 1 year of age (<1 hour, 1-23 hours, 1-6 days, 7-27 days, or 28-365 days after birth). In this study of 15 759 945 mother-infant dyads, the mean (SD) age of the women was 28.1 (5.9) years. Women gained a mean (SD) of 14.1 (7.3) kg during pregnancy, and the mean (SD) GWG decreased with BMI categories (underweight, 15.7 [6.4] kg; normal weight, 15.4 [6.2] kg; overweight, 14.2 [7.4] kg; obesity class 1, 12.2 [8.0] kg; obesity class 2, 10.3 [8.4] kg; obesity class 3, 8.2 [9.2] kg; P < .001). A total of 8.8% of the newborns experienced significant morbidity, with the lowest prevalence among infants delivered by women in the normal weight BMI class (8.0%) and the highest among infants delivered by women with class 3 obesity (12.4%); 0.34% of infants died within 1 year of birth, with the lowest prevalence among infants delivered by women in the normal weight BMI class (0.28%) and the highest among infants delivered by women with class 3 obesity (0.58%). Optimal GWG ranges were 12.0 to less than 24.0 kg for underweight and normal weight women, 10.0 to less than 20.0 kg for overweight women, 8.0 to less than 16.0 kg for women with class 1 obesity, 6.0 to less than 16.0 kg for class 2 obesity, and 6.0 to less than 10.0 kg for class 3 obesity. The lower bounds of the optimal GWG ranges appeared to be higher than the existing recommendations for overweight women (10.0 vs 7.0 kg) and for those with class 1 (8.0 vs 5.0 kg), class 2 (6.0 vs 5.0 kg), and class 3 (6.0 vs 5.0 kg) obesity. This study analyzed the associations of GWG with infant morbidity and mortality across BMI categories and found that inadequate GWG was associated with increased risks of adverse infant outcomes even for women with obesity. The results suggested that weight maintenance or weight loss should not be used as routine guidelines.


Examination of a brief anxiety sensitivity cognitive concerns intervention on suicidality among individuals with obsessive-compulsive symptoms.
A growing body of research has demonstrated elevated rates of suicidality among individuals with obsessive-compulsive disorder (OCD). Recently, it has been proposed that the cognitive concerns component of anxiety sensitivity (AS) may be one factor contributing to this association. AS cognitive concerns, which reflect fears of mental incapacitation, has been found to be associated with OCD and increased suicidality in a number of populations. However, questions remain as to whether reductions in AS cognitive concerns will lead to subsequent reductions in suicidality among individuals with OCD symptoms. In the current study, the sample (N=54) was comprised of individuals with elevated OCD symptoms recruited from the community who were participating in a larger randomized clinical trial. Individuals were randomly assigned to a one-session AS cognitive concerns intervention or a health information control intervention and assessed at post-treatment and one-month follow-up. Results indicated that the active intervention produced significantly greater reductions in AS cognitive concerns immediately post-intervention. Moreover, changes in AS cognitive concerns following the intervention mediated changes in suicidality at one-month follow-up. Findings are discussed in regard to adjunct interventions for OCD.


Early amantadine treatment reduces the risk of death in patients with large hemisphere infarctions:a Chinese hospital-based study.
Amantadine hydrochloride is one of the most frequently prescribed drugs for patients with severe traumatic brain injury in restoring consciousness and accelerating the pace of functional recovery. However, there is a paucity of studies on the effectiveness of amantadine in patients with severe stroke especially large hemisphere infarction (LHI). The present study aimed to investigate whether amantadine treatment is associated with better clinical outcomes in conservatively treated LHI patients. We retrospectively collected conservatively treated LHI patients according to inclusion/exclusion criteria. The patients were divided into two groups based on the treatment regimen, whether they did receive amantadine hydrochloride in addition to standard therapy (ST) or not. The primary outcomes were in-hospital death, 3-month mortality, and unfavorable outcome (defined as modified Rankin Scale score of 4 to 6). All outcomes were compared between the two groups before and after propensity score matching (PSM). Multivariate logistic regression was performed to identify the association between early amantadine hydrochloride treatment and clinical outcomes in LHI patients. Thirty-one LHI patients treated with amantadine combined with ST and 127 patients treated with ST were enrolled. Amantadine group had a shorter prehospital delay (median: 2 vs. 10 h), a higher baseline NIHSS score (21.71 ± 4.76 vs. 17.49 ± 5.84), and a higher rate of dominant hemisphere involvement (67.74% vs. 45.67%). After PSM, amantadine treatment significantly reduced the risk of in-hospital death (7.41% vs. 31.11%, p=0.019) and 3-month mortality (25.93% vs. 55.56%, p=0.008). Amantadine treatment yielded a significant decrease in death in-hospital (before PSM: OR 0.143, 95% CI 0.034 to 0.605; after PSM: OR 0.113, 95% CI 0.020 to 0.635) and 3-month mortality (before PSM: OR 0.214, 95% CI 0.077 to 0.598; after PSM: OR 0.176, 95% CI 0.053 to 0.586) in unmatched and matched multivariate analyses. The results of our study provide initial evidence that early amantadine treatment was associated with a decrease in death in conservatively treated LHI patients. Considering the limitations of observational study, randomized controlled trials with a large sample size may help provide a clearer picture of the utility of amantadine in LHI patients.


Immunoglobulin A deficiency in children, an undervalued clinical issue.
Immunoglobulin A (IgA) is the principal antibody in secretions that bathe the gastrointestinal and respiratory mucosal surfaces and acts as an important first line of defense against invasion of pathogenic micro-organisms. The reported prevalence rate of complete IgA deficiency in healthy children ranges from 1:170 to 1:400, and as a solitary condition, it is often considered of limited clinical importance. However, patients with IgA deficiency can develop recurrent respiratory and gastrointestinal infections, as well as allergic and autoimmune diseases. In children referred for recurrent respiratory tract infections, the observed prevalence rate increases more than tenfold. This review discusses several aspects of IgA deficiency in children, including immunologic and microbiome changes in early childhood and the potential consequences of this condition in later life. It illustrates the importance of early identification of children with impaired IgA production who deserve appropriate clinical care and follow-up.


The effects of different electrode materials on seed germination of Solanum nigrum L. and its Cd accumulation in soil.
The effects of different electrode on Solanum nigrum L. seed germination were determined. The result showed that germination percentage (GP) of seeds in treatment T2 (titanium electrode) was 26.6% higher than in control (CK, without electric field). High potassium and calcium concentrations were beneficial for seed enzymatic activity in treatment T2, which could partly explain the increase in GP. Cd accumulation (μg/pot) in S. nigrum treated with any electric field was significantly higher (p<0.05) than in CK without electric field. Specifically, Cd accumulation under the treatment T3 (stainless steel electrode) was the highest both in roots and shoots; this accumulation in shoots and roots were 74.7 % and 67.4 % higher for stainless steel than in CK. This increase must have been associated with a higher Cd concentration in plants and did not exert a significant effect on the biomass. In particular, Cd concentrations in roots and shoots under stainless steel treatment were both significantly higher than in CK (p<0.05), which had to be related to the higher available Cd concentration in the soil in the middle region. Furthermore, it could be attributed to altered soil pH and other soil properties. Moreover, none of the biomasses were significantly affected (p<0.05) by different electrode materials compared to CK.


Determination of self-absorption corrections for gamma analysis of environmental samples: comparing gamma-absorption curves and spiked matrix-matched samples.
Accurate determination of the massic activity of gamma-emitting radionuclides in environmental samples, particularly sediments and soils, cannot be achieved without taking into account sample self-absorption. The extent of self-absorption in the sample will depend on a number of factors including sample composition, density, sample size and gamma-ray energy. The preferred method for correcting for this effect is to use spiked or natural matrix reference materials that match each sample type to be analysed. However, for laboratories that must measure a wide variety of sample matrices this method is too costly and time-consuming. Another technique commonly used is to make direct gamma-ray transmission measurements for each sample. This method, while more practical, still requires a minimum of three measurements to be made for each sample analysed. A more convenient method is to prepare sets of gamma-absorption curves. This approach involves making a series of direct transmission measurements for samples of varying densities but similar type. Sets of matching samples, both spiked and unspiked, were prepared and density correction factors determined using the direct transmission method and the spiked sample approach. It was found that, for soil and sediment samples, these two methods typically differed by 5-9% for higher energy gamma rays and by 12-15% for the 59.54 keV 241Am peak. Gamma-absorption curves were also derived and, for the admittedly limited dataset, 95% confidence intervals of +/-7% for the curve generated using the spiked samples method were obtained.


Cytotoxic activity of peripheral blood and cerebrospinal fluid lymphocytes from patients with multiple sclerosis and other neurological diseases: analysis at the single cell level of the relationship of cytotoxic effectors and interferon-producing cells.
The production of interferon (IFN alpha) in relationship to NK and ADCC activity of peripheral blood and cerebrospinal lymphocytes was examined at the single cell level in patients with multiple sclerosis (MS) and other neurological diseases (OND) compared with age- and sex-matched controls. IFN-producing cells were assessed by indirect immunofluorescent scoring of cytoplasmic IFN+ cells. Peak production of cytoplasmic IFN alpha in nylon wool-passed ( NWP ) cells occurred between 5 and 17 hr in vitro under the inductive stimulus of MOLT 4, K562, or antibody-coated Chang liver cells. The proportion of K562- and MOLT 4-induced IFN alpha-positive cells in the total lymphocyte and target-binding cell (TBC) population was significantly lower in MS NWP -peripheral blood lymphocytes (PBL) than in OND and normal controls; this was in direct relationship to a decreased percentage of NK cells in MS PBL. In contrast MS cells responded the same as controls (total IFN+ cells) or higher than controls (IFN+-TBC) after IFN alpha induction by antibody-coated Chang, the ADCC target, in parallel with elevated ADCC activity by MS PBL. MS CSF contained a higher proportion of total IFN+ cells but a similar proportion of IFN+-TBC as their homologous NWP PBL population. In OND CSF, both the percentage of total IFN+ and the percentage of IFN+-TBC were higher than in OND blood and higher than their respective MS CSF populations. The relationship of IFN-producing cells in the central nervous system (CNS) to putative cytotoxic cells is discussed.


Triiodothyronine (T3) concentration and therapy in autistic children.
The clinical and biochemical status of thyroid function of patients with an autistic syndrome was investigated. The study consisted of 13 patients between the ages of 7 and 21 years. There was no clinical evidence for hypothyroidism in any patient, and T3, T4, and TSH concentrations were within the normal range. Two patients who had retarded bone ages were treated with triiodothyronine for 6 months. Hyperthyroidism developed when T3 levels exceeded physiologic concentrations in these patients. The concept that the clinical response to triiodothyronine in autistic patients results from correction of thyroid dysfunction is not supported by these findings.


Auxin effects on Pb phytoextraction from polluted soils by Tegetes minuta L. and Bidens pilosa L.: Extractive power of their root exudates.
The principal impediment for Pb uptake by plants is the Casparian strip in roots. It prevents metals reaching the xylem, thereby hampering translocation to the aerial organs. In the root apices, young root cells have thin cell walls and the Casparian strip is not completely developed, which could facilitate Pb uptake by roots at these vulnerable points. However, as the phytotoxic effects of Pb reduce root growth and enhance suberization, entry of Pb into the plant is avoided. We propose that the application of root growth promotors could be an important complement in the phytoextraction of Pb from polluted soils, due to their effects on produced biomass, Pb toxicity, and root exudate production. A greenhouse experiment was carried on to evaluate the auxin application effect on the Pb uptake of Bidens pilosa and Tagetes minuta. These species were sensitive to auxins, but the phytotoxic effect of Pb was not reversed by this treatment. Root exudates capable of extracting Pb were produced only when the species were grown in highly polluted soils, indicating a behavioral response to Pb exposure which is desirable for phytoremediation.