Efficacy of shoulder arthroscopic surgery for the treatment of rotator cuff injury: A protocol of systematic review and meta-analysis.
This study will investigate the efficacy and safety of shoulder arthroscopic surgery (SAS) for patients with rotator cuff injury (RCI). We will systematically search for randomized controlled trials in the electronic databases of PUBMED, EMBASE, Cochrane Library, CINAHL, PsycINFO, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All above databases will be searched from their beginning to March 1, 2020 without language restrictions. Two reviewers will independently scan retrieved records, evaluate study quality and extract data. If possible, we will synthesize the data and conduct a meta-analysis by RevMan 5.3 software. This systematic review will summarize the most recent evidence to explore the efficacy and safety of SAS for patients with RCI. The findings of this study will help to provide a genuine understanding of perspective from a scientific basis on the efficacy and safety of SAS for patients with RCI. PROSPERO CRD42020170009.


Culture and Borderline Personality Disorder in India.
The present paper discusses how cultural context can be used as an essential tool in the diagnosis of mental disorders as well as in segregating individuals with normal or abnormal personality functioning. Further, such information about the culture can be used to diagnose individuals specifically with borderline personality disorder (BPD). BPD is a mental illness marked by impulsivity and instability in interpersonal relationships, moods, and self-image. We discuss how culture shapes patterns of behavior in the individual with BPD. An extensive review of manifestation of BPD in eastern countries suggests that culture and social norms are the two crucial factors, which can differentiate normal and abnormal behavioral patterns in BPD. For example, the social norms shape and give directions to our interpersonal functioning, emotions are experienced within the cultural context and expressed accordingly, and self is a reflection and representation of one's culture. Hence, these constructs of BPD (such as interpersonal functioning, emotions, and self) indicate that they are experienced differently in different cultures and vary on the continuum of normal to abnormal personality functioning. The cultural manifestation of BPD helps to understand the specific profile of the three constructs of BPD in an eastern culture like India. A synthesis of studies on prevalence, development, and symptom presentation of BPD in the Indian context is emphasized to support the personality functioning within the constructs of BPD. The literature review indicates that BPD research in India is based only on a few cases and a tiny sample of such patients. However, studies on BPD in the cultural context are minimal and incomprehensive. Hence, it suggests the importance of more empirical studies concerning the appropriate diagnosis of BPD within the cultural context of India.


Fully Automated Gross Tumor Volume Delineation From PET in Head and Neck Cancer Using Deep Learning Algorithms.
The availability of automated, accurate, and robust gross tumor volume (GTV) segmentation algorithms is critical for the management of head and neck cancer (HNC) patients. In this work, we evaluated 3 state-of-the-art deep learning algorithms combined with 8 different loss functions for PET image segmentation using a comprehensive training set and evaluated its performance on an external validation set of HNC patients. 18F-FDG PET/CT images of 470 patients presenting with HNC on which manually defined GTVs serving as standard of reference were used for training (340 patients), evaluation (30 patients), and testing (100 patients from different centers) of these algorithms. PET image intensity was converted to SUVs and normalized in the range (0-1) using the SUVmax of the whole data set. PET images were cropped to 12 × 12 × 12 cm3 subvolumes using isotropic voxel spacing of 3 × 3 × 3 mm3 containing the whole tumor and neighboring background including lymph nodes. We used different approaches for data augmentation, including rotation (-15 degrees, +15 degrees), scaling (-20%, 20%), random flipping (3 axes), and elastic deformation (sigma = 1 and proportion to deform = 0.7) to increase the number of training sets. Three state-of-the-art networks, including Dense-VNet, NN-UNet, and Res-Net, with 8 different loss functions, including Dice, generalized Wasserstein Dice loss, Dice plus XEnt loss, generalized Dice loss, cross-entropy, sensitivity-specificity, and Tversky, were used. Overall, 28 different networks were built. Standard image segmentation metrics, including Dice similarity, image-derived PET metrics, first-order, and shape radiomic features, were used for performance assessment of these algorithms. The best results in terms of Dice coefficient (mean ± SD) were achieved by cross-entropy for Res-Net (0.86 ± 0.05; 95% confidence interval [CI], 0.85-0.87), Dense-VNet (0.85 ± 0.058; 95% CI, 0.84-0.86), and Dice plus XEnt for NN-UNet (0.87 ± 0.05; 95% CI, 0.86-0.88). The difference between the 3 networks was not statistically significant (P > 0.05). The percent relative error (RE%) of SUVmax quantification was less than 5% in networks with a Dice coefficient more than 0.84, whereas a lower RE% (0.41%) was achieved by Res-Net with cross-entropy loss. For maximum 3-dimensional diameter and sphericity shape features, all networks achieved a RE ≤ 5% and ≤10%, respectively, reflecting a small variability. Deep learning algorithms exhibited promising performance for automated GTV delineation on HNC PET images. Different loss functions performed competitively when using different networks and cross-entropy for Res-Net, Dense-VNet, and Dice plus XEnt for NN-UNet emerged as reliable networks for GTV delineation. Caution should be exercised for clinical deployment owing to the occurrence of outliers in deep learning-based algorithms.


Parents' report of family life with a developmentally delayed child.
This study was undertaken to investigate how parents who have a child with some degree of handicap perceive the effect of the child on family life. Also, a measure of parental health was taken. The parents' response was compared with that of parents of age-matched children without any known developmental difficulties. The parents and children were grouped according to the manifested handicap of the child [Down's syndrome, developmental quotient (DQ) greater than 65, DQ less than 65 with/without limb dysfunction and normal controls]. The children's ages ranged from 4 to 126 months and they all had received the South Galmorgan Home Advisory Service (HAS) at some time. Sixty-one families completed a questionnaire concerning family life and activities and Rutter's Malaise Inventory (Rutter et al. 1971). Thirty-one control families also completed the questionnaire and Malaise Inventory. The findings showed very little difference between the control group and handicapped groups and suggested that the presence of a delayed child in the family unit does not appear to change the family routine to any large extent. Parents of handicapped children were not found to suffer from significantly greater ill health when compared with the parents of normal children. The implication of the results is that provision should be made available for both fathers and mothers to play an equal part in the support facilities and guidance offered.


First reports evaluating the effectiveness of strategies for preventing violence: early childhood home visitation. Findings from the Task Force on Community Preventive Services.
Early childhood home visitation programs are those in which parents and children are visited in their home during the child's first 2 years of life by trained personnel who provide some combination of the following: information, support, or training regarding child health, development, and care. Home visitation has been used for a wide range of objectives, including improvement of the home environment, family development, and prevention of child behavior problems. The Task Force on Community Preventive Services (the Task Force) conducted a systematic review of scientific evidence concerning the effectiveness of early childhood home visitation for preventing several forms of violence: violence by the visited child against self or others; violence against the child (i.e., maltreatment [abuse or neglect]); other violence by the visited parent; and intimate partner violence. On the basis of strong evidence of effectiveness, the Task Force recommends early childhood home visitation for the prevention of child abuse and neglect. The Task Force found insufficient evidence to determine the effectiveness of early childhood home visitation in preventing violence by visited children, violence by visited parents (other than child abuse and neglect), or intimate partner violence in visited families. (Note that insufficient evidence to determine effectiveness should not be interpreted as evidence of ineffectiveness.) No studies of home visitation evaluated suicide as an outcome. This report provides additional information regarding the findings, briefly describes how the reviews were conducted, and provides information that can help in applying the recommended intervention locally.


Ca(2+)-dependent K(+) currents and spike-frequency adaptation in medial entorhinal cortex layer II stellate cells.
The entorhinal cortex (EC), located in the medial temporal lobe (MTL) of the brain, plays an important functional role in the MTL memory circuit. Medial EC (MEC) Layer II stellate cells (SCs) serve as one of the most prominent target cell types within the EC for inputs arising from higher cortical areas, and these same cells provide most of the output from the EC to the hippocampal region. We used the whole-cell patch clamp technique in a rat in vitro slice preparation to test whether SCs express afterhyperpolarization (AHP) currents and if these currents can be modulated. Our results revealed that SCs contain medium (mI(K(Ca))) and slow (sI(AHP)) Ca(2+)-dependent K(+) currents. Furthermore, we determined that an apamin-sensitive current does not underlie the mAHP in SCs. Our studies also showed that a cAMP-dependent modulation process significantly reduces mI(K(Ca)), sI(AHP), and spike-frequency adaptation in MEC Layer II SCs. Modulation of the firing pattern of SCs resulting from this effect may play an important role in the encoding of information related to memory processes.


Slow digestion properties of rice different in resistant starch.
The hydrolysis of starch is a key factor for controlling the glycemic index (GI). Slow digestion properties of starch lead to slower glucose release and lower glycemic response. Food with high resistant starch (RS) possesses great value for controlling the GI. To elucidate the factors that play a role in slow digestibility, seven rice mutants different in RS contents were selected for comparative studies. The degree of hydrolysis showed highly significant correlation with RS, apparent amylose content (AAC), lipid content (LC), and other starch physiochemical properties in all these materials with different RS contents. The rate of in vitro digestible starch correlated positively with RS, whereas digestibility was affected mostly by lipid content for those mutants with similar RS. Starch-lipid complexes and short chains with degrees of polymerization (DP) of 8-12 strongly influenced starch digestion. The integrity of aggregated starch and the number of round starch granules might influence the digestibility of starch directly.


An Improved Label-Free Indirect Competitive SPR Immunosensor and Its Comparison with Conventional ELISA for Ractopamine Detection in Swine Urine.
Ractopamine (RCT) is banned for use in animals in many countries, and it is urgent to develop efficient methods for specific and sensitive RCT detection. A label-free indirect competitive surface plasmon resonance (SPR) immunosensor was first developed with a primary antibody herein and then improved by a secondary antibody for the detection of RCT residue in swine urine. Meanwhile, a pre-incubation process of RCT and the primary antibody was performed to further improve the sensitivity. With all the key parameters optimized, the improved immunosenor can attain a linear range of 0.3-32 ng/mL and a limit of detection (LOD) of 0.09 ng/mL for RCT detection with high specificity. Furthermore, the improved label-free SPR immunosenor was compared thoroughly with a conventional enzyme-linked immunosorbent assay (ELISA). The SPR immunosensor showed advantages over the ELISA in terms of LOD, reagent consumption, analysis time, experiment automation, and so on. The SPR immunosensor can be used as potential method for real-time monitoring and screening of RCT residue in swine urine or other samples. In addition, the design using antibody pairs for biosensor development can be further referred to for other small molecule detection.


Update on cardiopulmonary resuscitation and emergency cardiovascular care guidelines.
The key changes included in the 2005 cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC) guidelines are reviewed. Advances since publication of the current guidelines are also discussed. The 2005 CPR and ECC guidelines include several key changes from the previous version published in 2000. The new guidelines place an increased emphasis on chest compressions and recommend a compression:ventilation (C:V) ratio of 30:2. Current knowledge on defibrillation has also been incorporated by recommending that Emergency Medical Service (EMS) rescuers give two minutes of CPR before defibrillation when the response interval is greater than four to five minutes and EMS responders did not witness the arrest. Another major change is the recommendation for a single shock to be administered followed immediately by CPR with no check of the cardiac rhythm until two minutes of CPR has been performed postdefibrillation. The 2005 guidelines recommend that an automated external defibrillator should be implemented in public locations where there is a relatively high likelihood of witnessed cardiac arrest. In addition, the most recent guidelines highlight the shift from primary-rhythm-based therapies and resuscitation to a focus on neurologic outcomes. Several evidence-based changes were included in the 2005 CPR and ECC guidelines, including a C:V ratio of 30:2 and mitigation of hands-off time, early defibrillation, administration of a single shock versus a three-shock sequence, use of public-access defibrillators, and a shift from primary-rhythm-based therapies to a focus on neurologic outcomes.


Fine-grained features characterize hippocampal and amygdaloid change pattern in Parkinson's disease and discriminate cognitive-deficit subtype.
To extract vertex-wise features of the hippocampus and amygdala in Parkinson's disease (PD) with mild cognitive impairment (MCI) and normal cognition (NC) and further evaluate their discriminatory efficacy. High-resolution 3D-T1 data were collected from 68 PD-MCI, 211 PD-NC, and 100 matched healthy controls (HC). Surface geometric features were captured using surface conformal representation, and surfaces were registered to a common template using fluid registration. The statistical tests were performed to detect differences between groups. The disease-discriminatory ability of features was also tested in the ensemble classifiers. The amygdala, not the hippocampus, showed significant overall differences among the groups. Compared with PD-NC, the right amygdala in MCI patients showed expansion (anterior cortical, anterior amygdaloid, and accessory basal areas) and atrophy (basolateral ventromedial area) subregions. There was notable atrophy in the right CA1 and hippocampal subiculum of PD-MCI. The accuracy of classifiers with multivariate morphometry statistics as features exceeded 85%. PD-MCI is associated with multiscale morphological changes in the amygdala, as well as subtle atrophy in the hippocampus. These novel metrics demonstrated the potential to serve as biomarkers for PD-MCI diagnosis. Overall, these findings from this study help understand the role of subcortical structures in the neuropathological mechanisms of PD cognitive impairment.


Accurate Identification of Antioxidant Proteins Based on a Combination of Machine Learning Techniques and Hidden Markov Model Profiles.
Antioxidant proteins (AOPs) play important roles in the management and prevention of several human diseases due to their ability to neutralize excess free radicals. However, the identification of AOPs by using wet-lab experimental techniques is often time-consuming and expensive. In this study, we proposed an accurate computational model, called AOP-HMM, to predict AOPs by extracting discriminatory evolutionary features from hidden Markov model (HMM) profiles. First, auto cross-covariance (ACC) variables were applied to transform the HMM profiles into fixed-length feature vectors. Then, we performed the analysis of variance (ANOVA) method to reduce the dimensionality of the raw feature space. Finally, a support vector machine (SVM) classifier was adopted to conduct the prediction of AOPs. To comprehensively evaluate the performance of the proposed AOP-HMM model, the 10-fold cross-validation (CV), the jackknife CV, and the independent test were carried out on two widely used benchmark datasets. The experimental results demonstrated that AOP-HMM outperformed most of the existing methods and could be used to quickly annotate AOPs and guide the experimental process.


Long duration and high potency of antiexudative effects of formoterol in guinea-pig tracheobronchial airways.
Inflammatory stimulus-induced luminal exudation of plasma proteins is potentially pathogenic in asthma. This study of plasma exudation into tracheobronchial airways examines antiexudative effects (potency and duration of action) of two beta 2-agonists in anesthetized guinea pigs. The exudative response to airway provocations with bradykinin 1.25 x 10(-4) M (5 nmol) was determined in different groups of animals 10, 300, 450, and 600 min, respectively, after the mucosa had been treated topically with salbutamol 10(-6) to 10(-4) M (0.1 to 10 nmol), formoterol 10(-9) to 10(-7) M (0.1 to 10 pmol), or saline (control). Exuded plasma in tracheal lavage liquids was calculated from their contents of the plasma tracer, 125I-albumin, given intravenously 10 min before provocation with bradykinin. Salbutamol (1 and 10 nmol) and formoterol (1 and 10 pmol) promptly inhibited the mucosal exudation (p less than 0.001). Propranolol, 0.1 nmol, reduced (p less than 0.01) the antiexudative effects of both drugs. Only formoterol (1 and 10 pmol) maintained its effect at 300 min, abating gradually at 450 and 600 min. In a group of sensitized guinea pigs, formoterol (1 and 10 pmol) was demonstrated to inhibit also allergen-induced luminal exudation of plasma (p less than 0.001). It is suggested that an antiexudative action may contribute to the long duration of formoterol's antiasthma effect.


Recent progress in bio-mediated synthesis and applications of engineered nanomaterials for sustainable agriculture.
The ever-increasing demand for agricultural food products, medicine, and other commercial sectors requires new technologies for agricultural practices and promoting the optimum utilization of natural resources. The application of engineered nanomaterials (ENMs) enhance the biomass production and yield of food crop while resisting harmful environmental stresses. Bio-mediated synthesis of ENMs are time-efficient, low-cost, environmentally friendly, green technology. The precedence of using a bio-mediated route over conventional precursors for ENM synthesis is non-toxic and readily available. It possesses many active agents that can facilitate the reduction and stabilization processes during nanoparticle formation. This review presents recent developments in bio-mediated ENMs and green synthesis techniques using plants, algae, fungi, and bacteria, including significant contributions to identifying major ENM applications in agriculture with potential impacts on sustainability, such as the role of different ENMs in agriculture and their impact on different plant species. The review also covers the advantages and disadvantages of different ENMs and potential future research in this field.


Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy.
Adeno-associated virus (AAV)-based vectors are promising tools for gene therapeutic applications, in part because AAVs are nonpathogenic viruses, and vectors derived from them can drive long-term transgene expression without integration of the vector DNA into the host genome. AAVs are not strongly immunogenic, but they can, nonetheless, give rise to both a cellular and humoral immune response. As a result, a significant fraction of potential patients for AAV-based gene therapy harbors pre-existing antibodies against AAV. Because even very low levels of antibodies can prevent successful transduction, antecedent anti-AAV antibodies pose a serious obstacle to the universal application of AAV gene therapy. In this review, we discuss the current knowledge of the role of anti-AAV antibodies in AAV-based gene therapy with a particular emphasis on approaches to overcome the hurdle that they pose.


Clinical photography of skin lesions: Professional and legal considerations in primary care.
Clinical photography is a fundamental component of visually oriented medical fields. The ubiquity of digital technology has brought the capacity to capture clinical photographs to the palm of a practitioner's hand. It is important for general practitioners (GPs) who take clinical photographs of skin lesions to be aware of the associated legal and ethical obligations. The aim of this article is to explore and explain current professional and legal considerations related to the use of clinical photography in general practice. Ensuring compliance with professional and legal standards when using clinical photography in general practice requires a firm grasp of the obligations associated with image capture, use, sharing, storage and security. GPs should ensure that before employing clinical photography, they have adequate consent-obtaining practices, regular habits of uploading images to the patient record, and sufficient device security. This will help to ensure that patient images are protected from being compromised.


Platelet microRNA-15b protects against high platelet reactivity in patients undergoing percutaneous coronary intervention through Bcl-2-mediated platelet apoptosis.
High platelet reactivity (HPR) and low platelet reactivity (LPR) are associated with an increased risk of ischemic/bleeding events in patients undergoing percutaneous coronary intervention (PCI). The role platelet miRNAs carry out in platelet reactivity regulation is largely unknown. In this study, we profiled the expression pattern of platelet miRNA in patients undergoing PCI with HPR (n=4) and LPR (n=4) by miRNA microarray screening. The candidate miRNAs were further validated in a larger sample of 17 LPR and 22 HPR patients by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), and miR-15b was found differentially expressed. MiR-15b mimic and inhibitor were transfected into MEG-01 cells, then Bcl-2 protein expression and cell apoptosis were assessed. The relationship between platelet reactivity and platelet apoptosis was further evaluated. ABT-737, a Bcl-2 inhibitor was used to induce platelet apoptosis in PCI patients in vitro, and the influence of enhanced platelet apoptosis on platelet reactivity was explored. Two miRNAs were found to be differentially expressed in patients with LPR and HPR using microarray system. Furthermore, the expression of miR-15b, a miRNA known to induce cell apoptosis via targeting of Bcl-2, was confirmed by RT-qPCR (P=0.020) to be 1.4× higher in the platelets of LPR patients than in those of HPR patients. Overexpression of miR-15b was demonstrated to suppress Bcl-2 protein expression and enhance cell apoptosis in a megakaryocyte cell line (MEG-01). The platelets of LPR patients expressed lower levels of Bcl-2 protein than those of HPR patients, and an inverse relationship between platelet reactivity and platelet apoptosis was observed among 44 patients who underwent PCI. Inducing platelet apoptosis in PCI patients in vitro, we observed that their platelet reactivity was decreased in a dose-dependent manner. Through the promotion of platelet apoptosis, platelet miR-15b negatively regulates platelet reactivity in patients undergoing PCI. Platelet apoptosis may represent a novel antiplatelet target for overcoming HPR in PCI treatment.


The prognostic nutritional index, an independent predictor of overall survival for newly diagnosed follicular lymphoma in China.
The prognostic nutritional index (PNI) is an important prognostic factor for survival outcomes in various hematological malignancies. The current study focused on exploring the predictive value of the PNI in newly diagnosed follicular lymphoma (FL) in China. The clinical indicators and follow-up data of 176 patients who received chemotherapy or immunotherapy combined with chemotherapy with FL in our hospital from January 2016 to March 2022 were retrospectively analyzed. Cox proportional hazard model was used for univariate and multivariate analyses. Kaplan-Meier curves were used to calculate survival rates and draw survival curves. The log-rank test was applied to compare differences between groups. The optimal cut-off value of PNI was 44.3. All patients were divided into a high PNI group (>44.3) and a low PNI group (≤44.3). The low PNI group had a low CR rate and a high risk of death, with a tendency toward POD24, and Both OS and PFS were worse than those in the high PNI group. PNI was able to predict OS and PFS in FL patients and was the only independent predictor of OS (P = 0.014 HR 5.024; 95%CI 1.388∼18.178) in multivariate analysis. PNI could re-stratify patients into groups of high FLIPI score, high FLIPI2 score, no POD24, and rituximab combined with chemotherapy. Moreover, integrating PNI into the FLIPI and FLIPI2 models improved the area under the curve (AUC) for more accurate survival prediction and prognosis. PNI is a significant prognostic indicator for newly diagnosed FL in China that can early identify patients with poor prognosis and guide clinical treatment decisions.


[Experimental studies on the role of GATA4 in the endocardial cushions development].
To investigate the role of GATA4 gene in the endocardial cushions development. Target gene eukaryote expression vectors were constructed by pcDNA3.1(-) vector plasmid, and were identified by DNA sequence analysis. Recombinant plasmids were transfected into Hela cells with lipofectamine 2000, meanwhile Hela cells transfected with empty vector or those without transfection served as transfection control group and blank control group, respectively. Real-time PCR and Western blot were performed to detect the relative expression of mRNA and protein of transcription factors GATA4, Sox9, Scleraxis and ECM proteins Aggrecan, Tenascin in each group. The relative mRNA expression of GATA4 in experimental group was significantly higher than in transfection control group and blank control group. GATA4 mRNA expression in Hela(GATA4), Hela(H436Y), Hela(Null) and Hela group was 310.83 ± 2.39, 146.35 ± 1.74, 0.94 ± 0.32, 1.00 ± 0.28, respectively (F = 72.508, P < 0.05). Western blot results were consistent with the results obtained by qRT-PCR. The relative mRNA and protein expressions of Sox9, Scleraxis, Aggrecan and Tenascin in both experimental groups were significantly higher than that in transfection control group and blank control group (P < 0.05), and above gene expressions were significantly downregulated in GATA4(H436Y) group, while they were similar between transfection control group and blank control group (all P > 0.05). GATA4 H436Y mutation reduces it's transcriptional activation, which might serve as a theoretical framework to demonstrate the roles of GATA4 gene in endocardial cushion development.


Dosage-dependent dominance over wild-type p53 of a mutant p53 isolated from nasopharyngeal carcinoma.
Mutational inactivation of p53, a tumor suppressor gene, is the most common genetic alteration found in human cancer. Most mutated p53s either lose tumor suppressor function or gain oncogenic activity. We recently reported the detection of a heterozygous point mutation of p53 at codon 280 in nasopharyngeal carcinoma (NPC) (1), a high-incidence malignancy in southern China and southeast Asia. Given its heterozygous state, in which both wild-type and mutated p53 gene were expressed, p53-thr280 should function dominantly in the presence of the wild-type form if it is to play a role in nasopharynx carcinogenesis. We tested this dominance hypothesis in the cells of two model systems: 1) human Saos-2 cells lacking endogenous p53, and 2) mouse JB6 tumor promotion-resistant cells (P-) expressing endogenous wild-type p53. The results showed dosage-dependent dominance of p53-thr280 in controlling WT p53-driven transcriptional activity; in governing cell growth; and in progressing P- phenotype to tumor promotion-sensitive (P+) phenotype. This dominant negative effect was seen at a 1:1 (WT:MU) ratio and was more striking at a ratio of 1:3. A model is proposed to explain the dominant negative effect of mutant p53. We conclude from this study that p53-thr280 is likely to be dominant in the heterozygous state found in NPC and that this dominant-negative mutated p53 may contribute to the genesis of NPC or of other carcinomas in which both mutant and wild-type p53 are expressed.


Subarachnoid anaesthesia: comparison of hyperbaric solutions of bupivacaine and amethocaine.
Hyperbaric solutions of 0.5% bupivacaine and 0.5% amethocaine (2 and 3 ml) were compared in a double-blind study of 40 patients receiving subarachnoid anaesthesia for urological surgery. The drugs produced similar and satisfactory analgesia in the tested concentrations and volumes. Motor blockade was more profound and longer lasting with amethocaine.


Gene expression profiling of epothilone A-resistant cells.
In the current study, we isolated sublines of the human breast adenocarcinoma cell line MDA 435 that exhibited increasing resistance to epothilone A, a microtubule-stabilizing cytotoxic agent. The resistant cells did not express P glycoprotein or multidrug resistance-associated protein (MRP) which are known mediators of multidrug resistance (MDR). Two groups of epothilone A-resistant cells were selected: cells which exhibited low resistance to both epothilone A and Taxol, and cells which exhibit low resistance to Taxol but high resistance to epothilone A. cDNA microarrays of epothilone A-resistant and Taxol-resistant cells were utilized to further characterize epothilone A resistance. Hierarchical clustering of genes according to their levels of expression indicated that the majority of genes which were highly expressed in epothilone A-resistant cells but not in taxol-resistant MDR cells encode known interferon-inducible proteins. Genes whose expression increased with increasing epothilone A resistance include microtubule-associated GTPases, cytoskeletal proteins, cell signalling proteins and a drug metabolising enzyme. The majority of the genes that were repressed in both epothilone A- and Taxol-resistant cells encode proteins regulating cellular growth signalling mechanisms.


Ninjurin 1 asp110ala single nucleotide polymorphism is associated with protection in leprosy nerve damage.
Leprosy is the major cause of non-traumatic neuropathy. Herein, we investigated the role of ninjurin 1, an adhesion molecule involved in nerve regeneration in leprosy. Our results demonstrated that M. leprae stimulates in vitro up-regulation of ninjurin mRNA in cultured Schwann and blood cells as well as in vivo mRNA and protein expression in leprosy nerve biopsies. A polymorphism (asp110ala) was investigated in a case-control study (1123 individuals) and no association was found with leprosy per se or with disseminated forms. Nevertheless, ala110 was associated with functional nerve impairment (OR=2.42; p=0.02 for ala/ala) and with lower mRNA levels. Our data suggests that asp110ala could be a valuable genetic marker of nerve damage in leprosy.


Enrichment of phosphorylated proteins and peptides from complex mixtures using metal oxide/hydroxide affinity chromatography (MOAC).
A novel method termed metal oxide affinity chromatography (MOAC) of enriching for phosphorylated proteins and peptides based on the affinity of the phosphate group for Al(OH)(3) is presented here. When compared to commercial phosphoprotein-enrichment kits, this method is more selective, more cost effective and easily applicable to method optimization. The use of glutamic and aspartic acid in the loading buffer significantly enhances selectivity. Standard protein mixtures and complex Arabidopsis thaliana leaf protein extracts were tested for efficacy of enrichment. The method can be applied to proteins extracted using either mild or denaturing conditions. The same Al(OH)(3) material is suitable for the enrichment of phosphopeptides out of a tryptic digest of alpha-casein. Peptide phosphorylation was revealed by beta-elimination of phosphate groups. Enrichment and in vivo phosphorylation of A. thaliana leaf proteins were confirmed with Pro-Q diamond stain. Several of the phosphoprotein candidates that were identified by MS are known to be phosphorylated in vivo in other plant species.


Cloud Based AI-Driven Video Analytics (CAVs) in Laparoscopic Surgery: A Step Closer to a Virtual Portfolio.
To outline the use of cloud-based artificial intelligence (AI)-driven video analytics (CAVs) in minimally invasive surgery and to propose their potential as a virtual portfolio for trainee and established surgeons. Methods: An independent online demonstration was requested from three platforms, namely Theator (Palo Alto, California, USA), Touch Surgery™ (Medtronic, London, England, UK), and C-SATS® (Seattle, Washington, USA). The assessed domains were online and app-based accessibility, the ability for timely trainee feedback, and AI integration for operation-specific steps and critical views. The CAVs enable users to record surgeries with the advantage of limitless video storage through clouding and smart integration into theatre settings. This can be used to view surgeries and review trainee videos through a medium of communication and sharing with the ability to provide feedback. Theator and C-SATS® provide their users with surgical skills scoring systems with customizable options that can be used to provide structured feedback to trainees. Additionally, AI plays an important role in all three platforms by providing time-based analysis of steps and highlighting critical milestones. Conclusion: Cloud-based AI-driven video analytics is an emerging new technology that enables users to store, analyze, and review videos. This technology has the potential to improve training, governance, and standardization procedures. Moreover, with the future adaptation of the technology, CAVs can be integrated into the trainees' portfolios as part of their virtual curriculum. This can enable a structured assessment of a surgeon's progression and degree of experience throughout their surgical career.


[The effects of spinal fusion on respiratory function and quality of life in Duchenne muscular dystrophy].
We studied the functional outcome of spinal fusion for the surgical treatment of scoliosis in 8 patients with Duchenne muscular dystrophy (DMD). The mean age of DMD patients at the time of the surgery and the mean follow-up duration was 13.8 (12.3 to 15.4) and 3.9 (1.5 to 6.8) years, respectively. The average spinal angle (Cobb angle) was corrected from 58.8 to 28.6 degrees with the mean corrective rate of 51.3% by the surgical intervention. The correction rate was higher and the corrected Cobb angle remained unchanged during follow-up period in mildly scoliotic patients. Forced vital capacity (FVC) increased post-operatively in 3 patients with moderate scoliosis (Cobb angle: 50 to 80 degrees), indicating that the correction of spinal alignment is effective for the treatment of decreased thoracic volume in DMD. On the other hand, two cases with low % FVC (16.9% and 30.4%, respectively) had poor prognosis in respiratory status. Namely, one died of pneumonia at 17 months after the surgery and the other required mechanical ventilation via nasal mask at 3 years post surgery. Sitting balance improved in all patients, which resulted in more functional use of their upper extremities. During the follow-up period, all patients except one patient who died of pneumonia could maintain sitting balance without support. Moreover these included 2 patients over 20 year old. No complications related to spinal deformities have been found in these patients. Previous study in our hospital showed that 7 of 48 (14.6%) of DMD patients spent all their lives without apparent scoliosis (Cobb angle less than 30 degrees). These suggest that spinal fusion could be recommended for patients with Cobb angle more than 30 degrees and with % FVC more than 35%. Although the impact of spinal fusion upon the life expectancy remains unclear, favorable effect on respiratory function and quality of life can be expected for carefully selected patients with DMD.


Gallium-67-citrate imaging in extragonadal and gonadal seminomas: relationship to radiologic findings.
The results and analysis of baseline and follow-up 67Ga imaging in three patients with extragonadal seminoma were compared to those of nine patients with primary and metastatic gonadal seminomas. Gallium-67 tumor avidity was scored (0-6) relative to accumulation in the sternum and the liver. Response time to systemic therapy for 67Ga imaging compared to other radiological examinations was also measured. Prior to therapy, 67Ga scan sensitivity was 100%, (3/3) in patients with extragonadal seminomas and 90%, (9/10) for primary and radiologically evident metastatic sites in patients with gonadal seminomas. The combined sensitivity was 92%, (12/13) with the smallest 67Ga scan detecting a mass 1.5 cm in diameter. There was no significant difference in 67Ga avidity or sensitivity between extragonadal and gonadal sites. Following chemotherapy, CT scanning demonstrated residual radiologic abnormalities in all three extragonadal seminoma tumor sites and 5/8 metastatic gonadal seminoma tumor sites. However, the 67Ga scan was normal in 10/11 sites at the first radionuclide examination after systemic therapy, indicating no active tumor, an observation supported by clinical follow-up from 6 to 72 mo. Gallium-67 scanning appears useful in the management of patients with both extragonadal and gonadal seminoma and may be useful in differentiating active disease from fibrosis in the treated patient with a post-therapy residual radiologic mass.


Amino acid substitutions in CPC-LIKE MYB reveal residues important for protein stability in Arabidopsis roots.
TRYPTICHON (TRY) and ENHANCER OF TRY AND CPC2 (ETC2) encode R3-type MYB transcription factors that are involved in epidermal cell differentiation in Arabidopsis thaliana. TRY and ETC2 belong to the CPC-like MYB gene family, which includes seven homolog genes. Previously, we showed that among the CPC family members, TRY and ETC2 are characterized by rapid proteolysis compared with that of other members, and we demonstrated that this proteolysis is mediated by the proteasome-dependent pathway. In this study, we compared the functions of the wild-type TRY and ETC2 proteins and their amino acid-substituted versions. Our results showed that the substitution of amino acids in the C-terminal of TRY and ETC2 conferred them the ability to induce root hair formation. Furthermore, we confirmed that these mutations enhanced the stability of the TRY and ETC2 proteins. These results revealed that the amino acids, which are important for the functions of TRY and ETC2, mediate morphological pattern formation and can be useful in understanding the pathway determining the fate of root hair cells.


COVID-19 lockdown and natural resources: a global assessment on the challenges, opportunities, and the way forward.
The Coronavirus (COVID-19) is a global pandemic caused by SARS-CoV-2, which has an enormous effect on human lives and the global environment. This review aimed to assess the global scientific evidence on the impact of COVID-19 lockdown on natural resources using international databases and search engines. Thus, the unprecedented anthropause due to COVID-19 has positive and negative effects on natural resources. This review showed that the unprecedented pandemic lockdown events brought a negative impact on the physical environment, including pollution associated with a drastic increase in person protective equipment, deforestation, illegal poaching and logging, overfishing, disruption of the conservation program and projects. It is noted that the spread of pandemic diseases could be aggravated by environmental pollution and a rapid increase in the global population. Despite these negative impacts of COVID-19, the anthropause appear to have also several positive effects on natural resources such as short term reduction of indoor and outdoor environmental pollutants (PM2.5, PM10, NO2, SO2, CO, and CO2), reduction in noise pollutions from ships, boats, vehicles, and planes which have positive effects on aquatic ecosystems, water quality, birds behaviour, wildlife biodiversity, and ecosystem restoration. Therefore, governments and scientific communities across the globe have called for a green recovery to COVID-19 and implement multi-actor interventions and environmentally friendly technologies to improve and safeguard sustainable environmental and biodiversity management and halt the next pandemic.


The distribution in the cat brain stem of neurones activated by vagal nonmyelinated fibres from the heart and lungs.
In anaesthetized cats, right cardiac vagal branches were electrically stimulated and recordings of evoked 'slow wave' and single neurone activity were made in the brain stem. Short-latency 'slow wave' and multi-neuronal activity evoked by excitation of myelinated vagal afferent fibres were recorded in the medial and lateral subnuclei of the nucleus tractus solitarius, the area postrema, the dorsal vagal motor nucleus, the lateral reticular formation and the nucleus ambiguus. Long-latency responses evoked by vagal non-myelinated fibres were recorded in the medial subnucleus of the nucleus tractus solitarius, the area postrema, dorsal vagal motor nucleus, the parahypoglossal area and the lateral reticular formation dorsal to the nucleus ambiguus. A specific study was made of seventy-two single neurones activated by non-myelinated afferent fibres in the cardiac branch. Thirty-four were shown to be synaptically activated, twenty-one were activated nonsynaptically and seventeen could not be classified. One neurone was also activated by myelinated cardiac afferent fibres, and two by thoracic vagal (including pulmonary) afferent fibres. Neurones were not spontaneously active. Indirect evidence suggests that the majority of the recordings of nonsynaptically activated neurones were likely to be from cell bodies. Neurones were located from the level of the obex to 3.0 mm rostral to it in the medial subnucleus of the nucleus tractus solitarius (45), and in the lateral subnucleus (2), the area postrema and its border with the medial subnucleus of the nucleus tractus solitarius (13), the dorsal vagal motor nucleus (9), the parahypoglossal area (1) and the lateral reticular formation dorsal to nucleus ambiguus (2). Recordings were made from fifteen neurones activated by myelinated fibres in the cardiac vagal branches, and twelve were excited synaptically. The neurones were located in the medial (8) and lateral (3) subnuclei of the nucleus tractus solitarius, the dorsal vagal motor nucleus (1) and the lateral reticular formation (1). Four neurones were also excited by vagal afferent fibres in the thoracic vagal nerve immediately caudal to the caudal cardiac branch.


Uterine artery and umbilical vein blood flow are unaffected by moderate habitual physical activity during pregnancy.
This study aims to noninvasively quantify blood flow in the uterine arteries (UTAs) and umbilical vein (UV) using phase-contrast magnetic resonance imaging (PC-MRI) and test whether these correlate with maternal fitness parameters. Resting UTA and UV flows were measured in 23 healthy 30 ± 3-year-old women who engaged in moderate-intensity physical activity during pregnancy. Participant fitness was characterized in the second and third trimesters using the submaximal oxygen uptake (VO2 ) test measuring heart rate (HR), VO2 , ventilation (ventilatory equivalent [VE]/VO2 ), and the Borg rating of perceived exertion (respiratory quotient [RQ]). Linear regression models were used to determine the associations between blood flow and maternal fitness measures. Blood flows in the UTA (957 ± 241 mL/min) and UV (132 ± 38 mL/min/kg) were successfully measured in 20 (87%) participants. Neither was associated with any physical fitness parameters (HR, VO2 , VE/VO2 , and RQ) nor with any second-to-third trimester change in these parameters. PC-MRI can be used to noninvasively measure blood flow in the UTA and UV. Neither resting UTA nor UV flow is associated with maternal fitness parameters. This is the first MRI-based study to provide novel hemodynamic data suggesting decoupling between maternal moderate fitness level and the maternal-placental-fetal hemodynamic system in healthy, normal body mass index (BMI) pregnancies.


Pulmonary function parameters in workers of woolen industry.
There is an increase in proportion of workers suffering from occupational diseases. In occupational respiratory diseases, pulmonary function tests are the most important and widely used diagnostic tool. Limited studies have been conducted to evaluate the effect of wool dust on pulmonary function parameters. Hence, the present study was undertaken to evaluate the pulmonary function parameters in workers of woolen industry. This study was done on 150 subjects of either gender who were divided into two groups of 75 each. Group I comprised of healthy subjects who served as controls and group II included workers of woolen industry. The values of lung function parameters i.e. volumes and flow rates in these workers were found to be lower than the healthy controls. The significant reduction in percentage predicted values of FEV1 (82 vs 59), FVC (79 vs 63) and MVV (77 vs 64) in workers as compared to healthy controls indicates obstructive pattern of respiratory abnormality. In male workers, percentage predicted FEV1% was significantly lower. The values of all other parameters were lower in female workers. There was a significant decrease in FEV and FVC with increase in age in group I and this negative correlation was statistically significant. The decrease in respiratory volumes and flow rates was more with increase in duration of exposure to wool dust. It can be concluded that wool dust present in environment of woolen industry affected the pulmonary function parameters of the workers leading to obstructive pattern of respiratory changes.


Vasodilatation augments the blood-brain barrier lesions induced by an acute rise in intracarotid pressure.
The vessel wall tension is the product of pressure and internal radius divided by the vessel wall thickness. Hence, dilated vessels will be exposed to higher tension at a given intraluminal pressure. Provided the rise in cerebrovascular intraluminal pressure is sufficiently prominent, transient opening of the morphologic blood-brain barrier will occur. In the present study pressure increase, not sufficient in itself to cause barrier opening, was induced. However, at concomitant dilatation of the vessels--as induced by CO2 or papaverine--under otherwise identical pressure conditions a barrier opening was obtained. Hence, vasodilatation of cerebral vessels will increase their vulnerability to hypertension.


Kynurenine pathway and its role in neurologic, psychiatric, and inflammatory bowel diseases.
Tryptophan metabolism along the kynurenine pathway is of central importance for the immune function. It prevents hyperinflammation and induces long-term immune tolerance. Accumulating evidence also demonstrates cytoprotective and immunomodulatory properties of kynurenine pathway in conditions affecting either central or peripheral nervous system as well as other conditions such as inflammatory bowel disease (IBD). Although multilevel association exists between the inflammatory bowel disease (IBD) and various neurologic (e.g., neurodegenerative) disorders, it is believed that the kynurenine pathway plays a pivotal role in the development of both IBD and neurodegenerative disorders. In this setting, there is strong evidence linking the gut-brain axis with intestinal dysfunctions including IBD which is consistent with the fact that the risk of neurodegenerative diseases is higher in IBD patients. This review aims to highlight the role of kynurenine metabolic pathway in various neurologic and psychiatric diseases as well as relationship between IBD and neurodegenerative disorders in the light of the kynurenine metabolic pathway.


Enhancing the genome editing toolbox: genome wide CRISPR arrayed libraries.
CRISPR-Cas9 technology has accelerated biological research becoming routine for many laboratories. It is rapidly replacing conventional gene editing techniques and has high utility for both genome-wide and gene-focussed applications. Here we present the first individually cloned CRISPR-Cas9 genome wide arrayed sgRNA libraries covering 17,166 human and 20,430 mouse genes at a complexity of 34,332 sgRNAs for human and 40,860 sgRNAs for the mouse genome. For flexibility in generating stable cell lines the sgRNAs have been cloned in a lentivirus backbone containing PiggyBac transposase recognition elements together with fluorescent and drug selection markers. Over 95% of tested sgRNA induced specific DNA cleavage as measured by CEL-1 assays. Furthermore, sgRNA targeting GPI anchor protein pathway genes induced loss of function mutations in human and mouse cell lines measured by FLAER labelling. These arrayed libraries offer the prospect for performing screens on individual genes, combinations as well as larger gene sets. They also facilitate rapid deconvolution of signals from genome-wide screens. This set of vectors provide an organized comprehensive gene editing toolbox of considerable scientific value.


[Aprotinin-ACD-blood: I. Experimental studies on the effect of aprotinin on the plasmatic and thrombocytic coagulation (author's transl)].
Aprotinin interrupts the spontaneous formation of microaggregates in stored blood. The analysis of the aprotinin-induced effects on the plasmatic and thrombocytic clotting systems showed a correlation between concentration and inhibitory effects of aprotinin on clotting factor VIII, IX, XI, XII as well as on the enzyme-induced second phase aggregation of the platelets. The effect of aprotinin on inhibition of platelet aggregation is probably due to binding of enzymes located in the membrane. The membrane stabilizing effect of aprotinin is discussed. Also in different experimental models using enzyme kinetic designs under maximal aprotinin inhibition a normalization of platelet functions could be immediately reached under transfusion analogous conditions. It is therefore, assumed that transfusion of aprotinin-ACD-Blood does not alter the coagulation mechanism of the patient.


Increases in fruit intakes in older low consumers of fruit following two community-based repeated exposure interventions.
The present study investigated the value of two repeated exposure interventions for increasing intakes of fruit in older people. A total of ninety-five participants (aged 65 years and over) were randomised to receive either one (E1), five (E5) or five plus (E5+) exposures to fruit over a 5-week period. Fruit exposures occurred in community-based church and social groups, through fruit-tasting sessions involving familiar fruits and novel fruit products and dishes (E1, E5, E5+), and through fruit provision (E5+). Daily intakes of fruit and vegetables were assessed before and after all interventions. Liking for all fruits was also measured during repeated exposure (E5, E5+). In low consumers of fruit (one portion/d or less), fruit intakes increased significantly in the repeated exposure groups (E5, E5+) (t(30) = 5·79, P< 0·01), but did not change in the E1 group (t(16) = 0·29, P= 0·78). No differences were found between E5 and E5+ groups (F(3,87) = 1·22, P= 0·31). Similar effects were also found in fruit and vegetable intakes. No effects were found in other participants. Also, no changes in liking were found. These findings suggest that compared to single exposure, repeated exposure to fruit via fruit-tasting sessions once per week for 5 weeks in a community setting significantly improved fruit intakes, and fruit and vegetable intakes in older low consumers of fruit, although no benefits of additional fruit provision were found. Repeated exposure was also easy to implement, of low cost and enjoyable.


[Sexuality in the aged--problems and results].
The study deals with historical, theoretical and practical aspects of sexuality at advanced age, including the effects of pathological disturbances and vocational stress, reference also being made to the international literature on the subject. Questions of sexuality at advanced age were not investigated until fairly recently. The author considers this to be due mainly to social and ideological barriers and recommends that gerosexual knowledge be propagated.


alpha-Tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy.
Intracortical injection of iron ions has been used to model post-traumatic epilepsy. The results obtained using these models suggest that oxidation of neural membranes by active oxygen free radicals may be involved in the etiology of post-traumatic epilepsy. This is a study of the effects of alpha-tocopheryl-L-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), known as a hydroxyl radical scavenger, on the peroxidation of neural membranes by FeCl(3) in vitro and on the occurrence of epileptic discharges in the FeCl(3) injected post-traumatic epilepsy model rats. EPC-K1 dose-dependently inhibited the production of thiobarbituric acid reactive substances (TBARS) and protein carbonyl (P-Carb), both indices of biogenic macromolecular peroxidation. In vivo studies, sporadic spike discharges and/or epileptiform activities were observed in electrocorticograms (ECoG) of male Sprague-Dawley rat 15-90 min after 500 nmol of FeCl(3) was injected into the motor cortex. On the other hand, when 200 mg/kg of EPC-K1 was injected intraperitoneally 60 min prior to the injection of FeCl(3), the occurrence of epileptic discharges was prevented or delayed. When EPC-K1 (2.5-5 nmol) was injected along with the ferric ions, the occurrence of epileptiform activities was also prevented or delayed. EPC-K1 prevented the induction of early convulsion, the major risk factor of post-traumatic epilepsy. Rats in the Fe+EPC group were injected with 500 nmol of FeCl(3) into the left motor cortex and were given an EPC-K1-diet (CE-2 chow contained 0.2% of EPC-K1, and daily EPC-K1 intake was about 80 mg/kg/day). In the Fe+EPC group rats, the percent induction of epileptic discharges in ECoGs was significantly lower than that in the Fe+CE group rats, which were fed CE-2 after FeCl(3) injection. In the homotropic contra lateral cortex, TBARS and P-Carb content did not show any changes. However, the relative TBARS content in the focal area significantly increased in the Fe+CE and Fe+EPC group rats 3 h after the injection. It became normal 3 days after in the Fe+EPC group. The relative P-Carb content in the focal area significantly increased in the Fe+CE and Fe+EPC group rats 3 h after the injection. However, it became normal after 3 days. In the present study, EPC-K1, which consists of vitamins E and C connected by a phosphate, protected the oxidation of neural membranes and prevented the occurrence of ferric ion-induced epileptic discharges by its radical scavenger activity. These data suggest that EPC-K1 may be clinically useful in not only preventing the focus formation of post-traumatic epilepsy, but also in treating and attenuating the progression of free radical-induced degenerative disorders.


Treadmill exercise and wheel exercise improve motor function by suppressing apoptotic neuronal cell death in brain inflammation rats.
Brain inflammation is involved in many brain disorders, such as brain ischemic injury, Alzheimer diseases, and Parkinson disease. Physical exercise has been recommended for the prevention and treatment of many brain inflammatory diseases. In the present study, the effects of exercise on motor function in relation with apoptotic neuronal cell death following neuroinflammation were investigated. Moreover, we compared the effect of forced exercise with voluntary exercise on neuroinflammation-induced motor malfunction. For this study, rota-rod test, vertical pole test, foot fault test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, immunohistochemistry for caspase-3, and western blot for Bcl-2 and Bax were performed. Lipopolysaccharide was intraventricular infused for induction of brain inflammation. Treadmill exercise and wheel exercise were conducted during 6 weeks. In the present results, Treadmill exercise and wheel exercise alleviated brain inflammation-induced motor impairments by suppressing apoptotic neuronal cell death in the motor cortex. These effects of treadmill exercise and wheel exercise were similarly appeared.


Prognostic values of proliferative markers ki-67 and repp86 in breast cancer.
Breast cancer is the leading cause of carcinoma death in women. Proper treatment depends on the consideration of molecular biology status of tumor cells, which may determine the patient's treatment and prognosis. To determine the prognostic models for this disease, we evaluated the role of cell proliferation-related antigens including ki-67 (a nuclear antigen, expressed in G1, G2, and M phases of cell cycle) and repp86 (an 86-kDa nuclear protein expressed in S, G2, and M phases of cell cycle) for detection of biologic behavior of breast cancer. We studied 60 women with grade I and II lymph node-negative and 27 with grade III lymph node-positive breast cancers. The mean follow-up periods for these two groups were 60 and 72 months, respectively. Tumor cell proliferation was measured by immunohistochemical methods with monoclonal antibodies directed against the nuclear antigens ki-67 and repp86. The ki-67, repp86 labeling indices (percentage of antibody-stained tumor cell nuclei) were not statistically different between the cases and controls of lymph node-negative patients (ki-67 with P = 0.33; repp86 with P = 0.40). The odds ratio (the mean chance of ki-67 labeling index > 10%, repp86 labeling index >10%) in patients with recurrence was 4 (CI = 0.2 - 76.5) for ki-67 and 3.6 (CI = 0.4 - 32.5) for repp86. Both indices were statistically different in lymph node-positive cases and controls (P < 0.0001). The odds ratio in patients with recurrence was 87 (CI = 4 - 18.71) for ki-67 and 71.5 (CI = 5.7 - 899.2) for repp86. The present study confirms the importance of cell proliferation as a determinant of biologic behavior of breast cancer. Measurement of ki-67 and repp86 labeling indices may be very helpful for physicians to detect high-risk patients and to adopt appropriate procedure such as adjuvant therapy.


The Effectiveness and Safety of Selective Lumbar Decompression in Diagnostic Doubt Patients: A Retrospective Control Study.
Our previous study demonstrated that selective nerve root block (SNRB) can influence decision-making in lumbar surgery by guiding the selection of nerve roots targeted for decompression in diagnostic doubt patients (DDPs). However, further studies were needed to determine whether this selective decompression (SD) procedure would result in similar clinical outcomes and reduce the perioperative parameters and postoperative complications as compared to the non-selective decompression (NSD) procedure. The specific goal of this study is to compare clinical outcomes, perioperative parameters, and complications between SD and NSD procedures in DDPs. A retrospective control study. Gaozhou People's Hospital. From January 2009 to January 2011, 57 lumbar surgery patients with diagnostic doubt were retrospectively reviewed. Basic patient parameters, as well as perioperative and postoperative data were compared between the selective and non-selective decompression groups. Clinical outcomes were evaluated using the visual analog scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, and JOA recovery rates. Both groups showed significant improvement in VAS, ODI, and JOA scores between preoperative and postoperative measurements. The differences in VAS and ODI scores between groups were not significant at 3 and 60 months postoperatively (both P > 0.05). In addition, there was no significant difference in JOA recovery rate (P = 0.659) and survival rate (P = 0.586) during the 60 months following surgery. However, distinctly superior perioperative parameters (operation time and hospital stay, blood loss and drainage volume, laminectomy numbers, and fusion segment numbers) were observed in the SD group (P < 0.001 for each score). Moreover, the SD-treated group experienced significantly fewer adverse events postoperatively (P = 0.036). The limitations of this study lie in the size of the study and selection of patients and in the fact that it was not feasible to include all cases of diagnostic doubt. On the basis of the 5-year follow-up data, we suggest that the SD procedure guided by SNRB is an effective and safe method for the surgical treatment of DDPs. This procedure produces superior perioperative parameters when compared with the conventional NSD procedure, but has a comparable clinical outcome. Moreover, the benefits of SD surgery include fewer perioperative and postoperative complications.


Reactive oxygen species do not cause arsine-induced hemoglobin damage.
Previous work suggested that arsine- (AsH3-) induced hemoglobin (HbO2) damage may lead to hemolysis (Hatlelid et al., 1996). The purpose of the work presented here was to determine whether reactive oxygen species are formed by AsH3 in solution, in hemoglobin solutions, or in intact red blood cells, and, if so, to determine whether these species are responsible for the observed hemoglobin damage. Hydrogen peroxide (H2O2) was detected in aqueous solutions containing AsH3 and HbO2 or AsH3 alone but not in intact red blood cells or lysates. Additionally, high-activity catalase (19,200 U/ml) or glutathione peroxidase (68 U/ml) added to solutions of HbO2 and AsH3 had only a minor protective effect against AsH3-induced damage. Further, the differences between the visible spectra of AsH3-treated HbO2 and H2O2-treated HbO2 indicate that two different degradative processes occur. The presence of superoxide anion (O2-) was measured by O2(-)-dependent reduction of nitro blue tetrazolium (NBT). The results were negative for O2-. Exogenous superoxide dismutase (100 micrograms/ml) did not affect AsH3-induced HbO2 spectral changes, nor did the hydroxyl radical scavengers, mannitol, and DMSO (20 mM each). The general antioxidants ascorbate (< or = 10 mM) and glutathione (< or = 1 mM) also had no effect. These results indicate that the superoxide anion and the hydroxyl radical (OH) are not involved in the mechanism of AsH3-induced HbO2 damage. The results also indicate that although AsH3 contributes to H2O2 production in vitro, cellular defenses are adequate to detoxify the amount formed. An alternative mechanism by which an arsenic species is the hemolytic agent is proposed.


Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer: a meta-analysis.
To investigate the effectiveness of 5-flurouracil-based neoadjuvant chemotherapy (NAC) for gastroesophageal and gastric cancer by meta-analysis. MEDLINE and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the flurouracil-based NAC for gastroesophageal and gastric cancer, and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery. Studies that included patients with metastases at enrollment were excluded. Primary endpoint was the odds ratio (OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer. Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gastroesophageal and gastric cancer. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as the treatment group (NAC plus surgery) vs control group (surgery alone) and was presented as a point estimate with 95% confidence intervals (CI). All calculations and statistical tests were performed using RevMan 5.1 software. Seven RCTs were included for the analysis. A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group (n = 620) and control group (n = 629). The quality scores of the RCTs were assessed according to the method of Jadad. The RCT quality scores ranged from 2 to 7 (5-point scale), with a mean of 3.75. The median follow-up time in these studies was over 3 years. The meta-analysis showed that NAC improved the overall survival rate (OR 1.40, 95%CI 1.11-1.76; P = 0.005), which was statistically significant. The 3-year progression-free survival rate was significantly higher in treatment group than in control group (37.7% vs 27.3%) (OR 1.62, 95%CI 1.21-2.15; P = 0.001). The tumor down-stage rate was higher in treatment group than in control group (55.76% vs 41.38%) (OR 1.77, 95%CI 1.27-2.49; P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group (75.11% vs 68.56%) (OR 1.38, 95%CI 1.03-1.85; P = 0.03), with significant differences. No obvious safety concerns about mortality and complications were raised in these trials. There were no statistically significant differences in perioperative mortality (5.08% vs 4.86%) (OR 1.05, 95%CI 0.57-1.94; P = 0.87 fixed-effect model) and in the complication rate between the two groups (13.25% vs 9.66%) (OR 1.40, 95%CI 0.91-2.14; P = 0.12 fixed-effect model). Trials showed that patients from Western countries favored NAC compared with those from Asian countries (OR 1.40, 95%CI 1.07-1.83). Monotherapy was inferior to multiple chemotherapy (OR 1.40, 95%CI 1.07-1.83). Intravenous administration of NAC was more advantageous than oral route (OR 1.41, 95%CI 1.09-1.81). Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer. Additionally, NAC can down the tumor stage and improve R0 resection.


Fitness to Drive: A Smartphone Application for Doctors, Patients and the Driver Licensing Authority.
Medical fitness to drive in Victoria is currently governed by the Austroads Fitness to Drive Guidelines. Doctors are expected to review the 188-page document and advise patients in relation to their unique medical condition. Patients must then report themselves to the driver licensing authority if they are unfit to drive. Despite multiple recommendations from coroners, there is no mandatory reporting system in Victoria, as mandatory reporting is disliked by both doctors and patients. Research has shown that binary decision trees are more accurate than doctors in determining fitness to drive. This article proposes a phone application implementing yes-no decision trees for each condition in the guidelines to increase accuracy and documentation rates and protect doctors from liability.


Clinical characteristics and successful treatment outcomes of children and adolescents with Kaposi sarcoma in Southwestern Tanzania.
The HIV/AIDS epidemic has driven the rise in cases of Kaposi sarcoma (KS) among children and adolescents living with HIV in countries with high Human gammaherpesvirus 8 (HHV-8) seroprevalence, such as Tanzania, where specialized oncology programs are sparse. Consequently, descriptions of successful treatment of KS in children and adolescents by general pediatricians are important. A retrospective analysis was performed of children and adolescents diagnosed with KS and treated with chemotherapy and combination antiretroviral therapy (cART) at the Baylor College of Medicine Children's Foundation Tanzania Center of Excellence - Mbeya between 2011 and 2017. Sixty-one patients were diagnosed with KS with a median age of 12.6 years (interquartile range (IQR) 9.4 - 15.5). Diagnosis was confirmed by histopathology in 36% (22/61). Among HIV positive patients (59/61), 78% (46/59) were on cART at KS diagnosis. Severe immunosuppression was present in 63% (35/56) of those with CD4 data and 44% (27/61) had SAM. Advanced-stage T1 disease was present in 64% (39/61), including 28% (17/61) with visceral/disseminated KS. Two-year estimated overall survival (OS) was 72% (95% Confidence Interval (CI): 58%-82%) and median follow up for survivors was 25.7 months (IQR 14.2-53.8). No patients were lost to follow up. Two-year OS was 63% (95% CI: 44%-77%) in patients with severe immune suppression and 60% (95% CI: 37%-76%) in patients with SAM. Among patients with visceral/disseminated KS, 53% (9/17) survived. This retrospective analysis demonstrated favorable outcomes in a complex cohort of children and adolescents with KS treated with chemotherapy by general pediatricians in Tanzania.


Accumulation of boron compounds to tumor with polyethylene-glycol binding liposome by using neutron capture autoradiography.
The cytotoxic effect of boron neutron capture therapy (BNCT) is due to a nuclear reaction between 10B and thermal neutrons. It is necessary to accumulate the 10B atoms to the tumor cells selectively for effective BNCT. In order to achieve an accurate measurement of 10B concentrations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of the sliced whole-body samples of tumor bearing mice using CR-39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University and thermal neutron facility of Paul Scherer Institute(PSI). We obtained NCAR images for mice injected intravenously by 10B-PEG liposome, 10B-transferrin-PEG liposome, or 10B-bare liposome. The 10B concentrations in the tumor tissue of mice were estimated by means of alpha-track density measurements. In this study, we can increase the accumulation of 10B atoms in the tumor tissues by binding polyethylene-glycol chains to the surface of liposome, which increase the retention in the blood flow and escape the phagocytosis by reticulo-endothelial systems. Therefore, we will be able to apply NCAR technique for selection of effective 10B carrier in BNCT for cancer.


Osteocalcin: A Protein Hormone Connecting Metabolism, Bone and Testis Function.
During the last decade, the disclosure of systemic effects of osteocalcin (OCN) in its undercarboxylated form contributed to switch the concept of bone from a merely structural apparatus to a fully endocrine organ involved in the regulation of systemic functions. Since that time, the role of OCN as osteokine has been more and more widened appreciated and detailed by the major use of animal models, starting from the original function in the bone extracellular matrix as Gla-protein and spanning from the protective effects towards weight gain, insulin sensitivity and glucose homeostasis, to the anabolic and metabolic roles in skeletal muscle, to the stimulating effects on the testis endocrine function and male fertility, to the most recent preservation from anxious and depressive states through a direct activity on the central nervous system. In this review, experimental data supporting the inter-organ communication roles of this protein are discussed, together with the available data supporting the consistency between experimental data obtained in animals and those reported in humans. In addition, a specific session has been devoted to the possible significance the OCN as a template agonist on its receptor GPRC6A, for the development of novel therapeutic and pharmacological approaches for the treatment of dismetabolic states and male infertility.


BRAF in malignant melanoma progression and metastasis: potentials and challenges.
Recent advances in gene sequencing have shown that activated BRAF mutations are present in more than 50% of malignant melanomas and contribute to constitutive signals in the MAPK pathway. Besides the importance of its mutations in cell proliferation, BRAF is associated with lymph node, brain and liver metastasis, along with the loss of PTEN expression and ATG5. Knowledge of this genetic alteration has led to the development of personalized and targeted therapy strategies which block different pathways driving melanoma pathogenesis. Several targeted therapy agents such as vemurafenib, dabrafenib and encorafenib have been approved by the FDA as BRAF inhibitors, as well as other immunotherapies such as anti-CTLA-4 (ipilimumab). However, one of the main challenges is acquired resistance via reactivation of MAPK via CRAF/COT overexpression. Resistance to current BRAF inhibitors is a clinical challenge and one of the strategies to overcome this phenomenon is combination treatment, with the most recently approved combination being BRAF/MEK inhibitors (dabrafenib and trametinib) and BRAF or MEK inhibitors with immunocheckpoint blockers. This review delineates the current role of BRAF in melanoma progression and metastasis. It discusses targeted therapies and resistance mechanisms to BRAF inhibitors, and illustrates strategies to overcome this mechanism with recently approved agents.


Gene expression in cells infected with gammaherpesvirus saimiri: properties of transcripts from two immediate-early genes.
During productive infections of cells with the gammaherpesvirus, herpesvirus saimiri (HVS), a polyadenylated RNA of 2.2-2.4 kb accumulates to form a large fraction of virus-specified RNA. This transcript is from the virus thymidylate synthase (TS) gene and its synthesis, like that of late mRNAs encoding the virus structural proteins, is sensitive to an inhibitor of virus DNA synthesis (phosphonoacetic acid, PAA). Transcription which is insensitive to PAA occurs from many parts of the HVS genome, including the EcoRI-D, EcoRI-E, EcoRI-I, and HindIII-G fragments. A 1.6-kb RNA from EcoRI-I/E and a 1.3-kb RNA from HindIII-G accumulate in HVS-infected cells incubated in the continuous presence of cycloheximide, and thus represent immediate-early (IE) class transcripts. The 1.3-kb message from HindIII-G is the predominant stable RNA under these conditions; accumulation of the 1.6-kb transcript from EcoRI-I/E (which encodes the previously characterized 52-kDa IE phosphoprotein) is markedly more dependent on the multiplicity of infection. The sequence of a 2.5-kbp region of the HindIII-G fragment has been determined and a single major open reading frame is present within the boundaries of the 1.3-kb IE RNA. Comparison of the amino acid sequence of the encoded protein (IE-G) with current databases of protein sequences failed to demonstrate significant similarities with herpesvirus proteins, but did detect a significant similarity with a region of the protein specified by an open reading frame in the LTR of mouse mammary tumor virus. The function of the IE gene in HindIII-G and the basis for the distinctive multiplicity dependence of IE transcription from the 52-kDa gene remain to be established.


[Combined non-biological artificial liver in treatment of late stage chronic severe hepatitis].
To explore the clinical effects of combined non-biological artificial liver in the treatment of late stage chronic severe hepatitis and especially to observe their effects on hepatic encephalopathy, hepatorenal syndrome and disturbance of electrolytes. 103 chronic severe hepatitis patients were treated with the same medical measures, including plasma exchange. Among them, 63 patients were also treated with combinations of non-biological artificial liver (treatment group), and the other 40 patients served as controls (control group). The efficacy of the treatments and survival rates of the two groups were compared. In the treatment group, the rate of regaining normal consciousness was 72.7%, the rate of electrolyte disorder being rectified was 89.5%, the rate of restoring renal function was 66.7% and the total survival rate was 47.6%. In comparison, in the control group the rate of regaining normal consciousness was 16.7%, the rate of electrolyte disorder being rectified was 42.3%, none of their renal functions were restored and the total survival rate was 22.5%. The differences between the two groups were significant (chi2=6.56, P less than 0.05). With other medical treatment, combined non-biological artificial liver can improve the survival rate of severe hepatitis patients.


Individual differences in frequency and impact of daily memory lapses: results from a national lifespan sample.
Everyday memory problems are believed to increase with age, leading many researchers to focus on older ages when examining reports of memory lapses. However, real world memory lapses are ubiquitous across the adult lifespan, though less is known about the types of problems and their impacts at younger ages. The current study examined occurrence and impacts of memory lapses using daily diaries in a broad age range and whether characteristics of lapses varied across age, gender, or education level. Using an 8-day daily diary protocol, 2,018 individuals (ages 25-91) provided reports of their experiences of two types of daily memory lapses (retrospective and prospective) as well as the impact those lapses had on their emotional and functional well-being that day. Using multilevel modeling, we examined the likelihood of reporting memory lapses and their impacts on daily life and whether these depended on age, gender, or education level. Participants reported lapses on approximately 40% of days; retrospective memory lapses were significantly more likely than prospective lapses. Older ages and higher education level were related to greater likelihood of reporting retrospective lapses. Women (compared to men) were more likely to report prospective memory lapses. Women also tended to report greater impacts of their memory lapses. Lower education levels were related to greater impacts of memory lapses compared to higher education levels. Interestingly, age was not related to impacts of lapses. Our results indicate that memory lapses are common across the lifespan and that those individuals more likely to report lapses are not necessarily those that experience the greatest impacts of those lapses on daily life. Additional work is needed to understand the daily experience of memory lapses and how they differentially affect individuals regardless of age, gender, and education. Memory lapses are an important aspect of daily life across the lifespan and require measurement in an individual's real-world environments. Better measurement of these experiences will allow the development of more sensitive measures of changes in cognitive functioning that may impact an individual's ability to live independently.


Osteoblastic differentiation.
The fully differentiated osteoblast may be easily recognized in bone tissue. Its cuboidal shape, its position directly opposed to the bone surface and its capacity to produce calcified bone matrix are characteristic. Three other differentiation stages are also reasonably well defined--the preosteoblast, the osteocyte and the lining cell. These differentiation stages are preceded by an unknown number of precursor, progenitor and stem cell stages. Little is known about the regulation of the transitions between the various osteogenic phenotypes and their reversibility or irreversibility. One of the reasons for this is the lack of adequate tools with which to recognize the various differentiation stages. We have developed a number of monoclonal antibodies (in bone) specifically directed against osteocytes, osteoblasts and as yet unidentified cells in the periosteum. The anti-osteocyte monoclonals were used to recognize osteocytes in bone cell cultures and we obtained purified osteocyte populations for metabolic studies. Osteocytes were shown to have binding sites for parathyroid hormone. The antibodies directed against osteoblasts showed that at present our culture conditions are inadequate to allow osteoblast differentiation in vitro.


[Changes in lipid metabolism which accompany thioacetamide-induced cirrhosis].
Intraperitoneally-administered thioacetamide to rats produces the incorporation of 3H2O into the liver lipids during eight days, diminishing thereafter together with a decrease in 32P incorporation to phosphatidyl choline. Contrarily, the sphingomyelin incorporated 32P increases by the effect of the toxic action of the drug, while the 3H binding decreases. The cirrhosis-inducing agent possibly produces a shunt of the common CDP-choline precursor to the biosynthesis of sphingomyelin with detriment to the synthesis of phosphatidyl choline. The role of the unsaturation of fatty acids by thioacetamide is considered.


The effect of socio-economic status and ethnicity on the comparative oral health of Asian and White Caucasian 12-year-old children.
To investigate the oral health of 12-year-old children of different deprivation but similar fluoridation status from South Asian and White Caucasian ethnic groups. An epidemiological survey of 12-year-old children using BASCD criteria, with additional tooth erosion, ethnic classification and postcode data. Examinations were completed in schools in Leicestershire and Rutland, England, UK. Participants A random sample of 1,753 12-year-old children from all schools in the study area. Caries experience was measured using the DMFT index diagnosed at the caries into dentine (D3) threshold, and tooth erosion using the index employed in the Children's Dental Health UK study reported in 1993. The overall prevalence of caries was greater in White than Asian children, but varied at different levels of deprivation and amongst different Asian religious groups. There was a significant positive association between caries and deprivation for White children, but the reverse was true for non-Muslim Asians. White Low Deprivation children had significantly less tooth erosion, but erosion experience increased with decreasing deprivation in non-Muslim Asians. Oral health is associated with ethnicity and linked to deprivation on an ethnic basis. The intra-Asian dental health disadvantage found in the primary dentition of Muslim children is perpetuated into the permanent dentition.


Strong Electron-Phonon Coupling in the Excitonic Insulator Ta2NiSe5.
An excitonic insulating (EI) state is a fantastic correlated electron phase in condensed matter physics, driven by screened electron-hole interaction. Ta2NiSe5 is an excitonic insulator with a critical temperature (TC) of 328 K. In the current study, temperature-dependent Raman spectroscopy is used to investigate the phonon vibrations in Ta2NiSe5. The following observations were made: (1) an abnormal blue shift around TC is observed, which originates from the monoclinic to orthorhombic structural phase transition; (2) the splitting of a mode and two new Raman modes at 147 and 235 cm-1 have been observed with the formation of an EI state. With the help of first-principles calculations and temperature-dependent X-ray diffraction (XRD) experiments, it is found that the TaSe6 octahedra are "frozen" and the NiSe4 tetrahedra are greatly distorted below TC. Thus, it seems that the distortion of NiSe4 tetrahedra plays an important role in the strong electron-phonon coupling (EPC) in Ta2NiSe5, while the strong EPC, coupled with electron-hole interaction, opens the energy gap to form the EI state in Ta2NiSe5.


Mastectomy scar histopathology of limited clinical value.
This study assesses whether the routine submission of mastectomy scars for histologic examination at the time of delayed breast reconstruction is useful. A retrospective review was performed of all delayed breast reconstructions for breast cancer performed by a single surgeon over a 5-year period from January 2000 to December 2004. One hundred eighty-eight patients underwent delayed breast reconstruction during this period, and of these, 133 scars (1 patient had bilateral scars excised) were submitted for histology where the reconstruction was performed by either transversus rectus abdominus muscle flap (TRAM) or latissimus dorsi myocutaneous flap (LDF) +/- implant. Fifty-six patients had reconstruction performed by tissue expander through the inframammary crease where the original mastectomy scar was not excised and were excluded from the study. One mastectomy scar specimen showed a 2-mm suspicious area of invasive ductal carcinoma consistent with same histopathology at the time of mastectomy. This study corroborates evidence that it is questionable whether routine histopathology of mastectomy scar at the time of delayed breast reconstruction should not be a standard practice.


Effects of nucleoside transport inhibitors and adenine/ribose supply on ATP concentration and adenosine production in cardiac myocytes.
Adenosine plays an important role in protection of the heart before, during and after ischemia. Nucleoside transport inhibitors (NTI) increase adenosine concentration without inducing ischemia by preventing its uptake and metabolism in cardiac cells. However, prolonged effects of nucleoside transport inhibitors on adenosine and nucleotide metabolism and its combined effect with nucleotide precursors has not been established in cardiomyocytes. The aim of this study was to investigate the effect of two nucleoside transport inhibitors, dipyridamole (DIPY) and nitrobenzylthioinosine (NBTI) alone or combined with adenine and ribose on adenosine production and ATP content in cardiomyocytes. Rat cardiomyocytes were isolated using collagenase perfusion technique. Isolated cell suspensions were incubated for up to 480 min with different substrates and inhibitors as follows: (1) control; (2) 100 microM adenine and 2.5 mM ribose; (3) 10 microM DIPY; (4) 1 microM NBTI; (5) DIPY, adenine and ribose and (6) NBTI, adenine and ribose. Five microM EHNA (erythro-9(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase) was added to all incubations. After incubation, extracts of myocyte suspension were analysed by HPLC for adenine nucleotides and metabolite concentrations. ATP content decreased in cardiomyocytes after 8 h of incubation with DIPY, while no change was observed with NBTI or without inhibitors. Adenosine concentration increased with both DIPY and NBTI. In the presence of adenine and ribose an elevation in ATP concentration was observed, but no significant change in adenosine content. In the presence of DIPY or NBTI together with adenine and ribose, an enhancement in cardiomyocyte ATP concentration was observed together with an increase in adenosine content. This increase in adenosine production was especially prominent with DIPY. In conclusion, dipyridamole causes a decrease in ATP concentration in isolated cardiomyocytes by mechanisms other than nucleoside transport inhibition. Addition of adenine/ribose with dipyridamole prevents the depletion of ATP. Combination of adenine/ribose with nucleoside transport inhibitors may also further enhance adenosine concentration and thus, could be more effective as pharmacological agents for treatment.


Use of a fluorescence assay to monitor the kinetics of fusion between erythrocyte ghosts, as induced by Sendai virus.
The kinetics of the fusion process between erythrocyte ghosts, as induced by Sendai virus, were readily revealed by a simple fluorescence procedure previously employed to characterize the fusion of viruses with biological membranes. The method relies on the relief of fluorescence selfquenching of the membrane-inserted probe octadecyl Rhodamine B chloride (R18) as occurs when labeled membranes fuse with unlabeled counterparts. The kinetics of R18 insertion into ghost membranes, the non-exchangeable properties of the fluorophore and the kinetics, and some characteristics of Sendai virus-induced fusion of ghosts, are described. We propose that the experimental approach may be particularly advantageous to obtain insight into the efficiency and mechanism of a wide range of fusogens, capable of inducing fusion of erythrocyte membranes.


A Prospective Cohort Study on the Respiratory Effect on Modified Mallampati Scoring.
Mallampati scoring is a common exam method for evaluating the oropharynx as a part of the airway assessment and for anticipation of difficult intubation. It partitions the oropharynx into 4 categories with scores of 1, 2, 3, and 4. Even though its reliability is known to be limited by confounding factors such as patient positioning, patient phonation, tongue protrusion, and examiner variability, the effect of respiration, i.e., inspiration and expiration, has not yet been formally studied. Mallampati scores were collected from 100 surgical patients during both inspiration and expiration and later compared to the score obtained in the medical record, determined by a board certified anesthesiologist. Score deviations from the medical record reference were compared for both inspiration and expiration showing that respiration affects Mallampati scores; for some patients, the scores improved (i.e., decreased), while in others they worsened (i.e., increased). The respiratory change effect was quantified and visualized by plotting the area under the curve of the histogram of the deviations. 42% of the patients had a worsening of scores by 1 or 2 points with inspiration while 36% of the patients had a worsening of scores by 1 or 2 points with expiration. Mallampati scoring is commonly used in evaluating the oropharynx as a part of the airway assessment and as a screening tool for difficult intubations. However, as this study points out, the respiratory cycle substantially affects the Mallampati scoring system, with significant deviations of 1 or 2 points. In a scoring system of 4 score categories, these deviations are remarkable.


EEG coherences in patients with brain lesions.
EEG coherence between all pairwise combinations of the 10/20 system was studied in two groups: control subjects and patients with space-occupying brain lesions. Coherence was separately computed for the delta, theta, alpha and beta bands. Comparisons between both groups showed highly significant differences in all bands. In the patients with lower coherence values, these differences were mainly in the alpha band. When intra-hemispheric coherences between controls and patients with left hemispheric lesions were compared, significant differences were observed only in the left hemisphere. Comparisons between controls and patients with lesions in the right hemisphere also showed significant differences only in the injured hemisphere. In patients, paired t tests between the values of the intra-hemispheric coherence in the left hemisphere and the corresponding values in the right hemisphere demonstrated that lower coherences were confined to the damaged hemisphere. Our conclusion is that in the presence of lesions disrupting cortex and adjacent white matter the coherence between this area and the remaining cortical areas is lower than normal due to impairment of the fibers that connect the damaged area with the rest of the brain.


What's in a look?
The most common behavioral technique used to study infant perception, cognition, language, and social development is some variant of looking time. Since its inception as a reliable method in the late 1950s, a tremendous increase in knowledge about infant competencies has been gained by inferences made from measures of looking time. Here we examine the logic, utility, and future prospects for further gains in our understanding of infant cognition from the use of looking time measures.


Your mother was right: Eat your vegetables.
A lower risk of cancer at many different sites is seen in association with higher intakes of vegetables and fruit. There are many biologically plausible reasons for this potentially protective association. It is argued that increasing intake of plant foods to 400-800 g/day is a public health strategy of considerable importance for individuals and communities worldwide.


Size of endotracheal tube and neonatal acquired subglottic stenosis. Study Group for Neonatology and Pediatric Emergencies in the Parisian Area.
Risk factors for acquired laryngotracheal stenosis in newborn infants are poorly known. The extreme scarcity of acquired laryngotracheal stenosis in young infants in France, compared with the published rate in the English literature, suggested that these patients may be treated in a different way in France. A prospective study was performed to analyze local features. Six-month multicenter inception cohort study. Seven neonatal intensive care units of referral centers in the area of Paris, France. A total of 247 intubated surviving neonates in a consecutive sample during 6 months. A file was completed with sex, birth weight, gestational age, underlying disease, and every feature concerning the intubation period and the outcome. All the collected data were compared with those available from previous studies in the English literature. After extubation, respiratory outcome was uncomplicated in 242 cases. The five patients with dyspnea were treated medically and recovered. A much higher rate of extubation difficulties was reported in the English literature. The rate of stenosis in this series was significantly lower than in previously reported studies. The differences between this and other series seem to be higher birth weights, shorter duration of intubation, and, most important, a smaller tube size (2.5 mm in neonates weighing less than 2500 g and 3.0 mm in those weighing 2500 g or more). Although this is a limited series and many unknown variables can differ from those in previous studies, the size of the endotracheal tube appears to be a major risk factor for acquired laryngotracheal stenosis in the neonate. Further studies seem necessary to point out additional factors.


Fifty novel HLA-DPB1 alleles identified in a UK cohort of unrelated hematopoietic cell donors and recipients.
HLA-DPB1 is the classical HLA class II genes with the least recorded variation on the IPD-IMGT/HLA Database, suggesting the full extent of its diversity is perhaps yet to be characterized. Here, a full-gene typing strategy was employed to genotype a UK cohort of 1470 HCT recipients (n = 744) and donors (n = 726). In total, 2940 full-length HLA-DPB1 sequences were generated, comprising 193 distinct alleles. Of these, 107 sequences contained novel variation, totaling 49 unique intronic HLA-DPB1 alleles, and one coding variant (HLA-DPB1*1188:01). Full-gene sequencing resulted in zygosity changes for 129 individuals by identifying two distinct intronic variants of the same coding allele. We verified the existence of nine unconfirmed alleles and extended the sequence of two existing alleles on the IPD-IMGT/HLA Database.


The macroconidial septum of some dermatophyton species.
The septum of the macroconidium (MC) of dermatophytes was examined by light microscopy. Significant taxonomical differences between species have not been found. The septa seem to be three-layered, but only the middle layer can be considered a septum in the wall substance of two neighbouring chambers, impressed and completed by the septum. The septum verum originates from the middle layer of the three-layered MC wall or from its surface adjacent to the chamber wall. This type of septum is different from that described in Ascomycetes and other species. Light microscopic findings are insufficient to characterize the nature of the septal pore. The microscopic observation of the layers of the MC wall and of the septum may be disturbed by misleading optical phenomena.


Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA.
Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.