A novel system for continuous, real-time monitoring of heart motion signals.
Understanding cardiac mechanics is important for developing cardiac therapies. Current modalities for assessing cardiac mechanics sample patient's heart at specific heart rate, contractility, preload, and afterload. The objective of this study was to test the feasibility of a novel system composed of intra-cardiac leads equipped with an inertial module chip (3D accelerometers and 3D gyroscopes) in monitoring continuous heart motion. In this descriptive study, four healthy pigs were anesthetized and instrumented with motion-sensitive intra-cardiac leads; the temporal correlation between signals from motion sensors and tissue Doppler from the chest wall were studied; changes in real-time heart accelerations (ACC) and angular velocity (ANGV) were reported as percentages of change from baseline. Heart motion signals were sensed continuously from the right ventricular apex (RVa) and coronary sinus (CS). Volume expansion did not produce significant changes in the ACC and ANGV signals. Increasing heart rate increased the peak systolic ACC signal recorded from RVa and CS by 94 and 76%, respectively, and increased both peak systolic (61% RVa and 27% CS) and diastolic ANGV (200% CS vs. 31% RVa). Epinephrine administration increased peak systolic ACC signals at both sites (246% RVa; 331% CS). Peak systolic and diastolic ANGV increased in response to epinephrine (systolic: 198% RVa and 175% CS; diastolic: 723% CS and 89% RVa) (p = 0.125 for all changes expressed in percent). Temporal correlation between the ANGV signal and tissue Doppler signal was detected throughout all interventions. A novel system for continuously monitoring heart motion signals from within the heart was presented. Heart motion signals in response to physiologic manipulations were characterized.


Increased secretion of salivary glands produced by facial vibrotactile stimulation.
Patients with low-back pain can be evaluated immediately by means of an electrical tool that produces bony vibration to the lumbar spinal processes (Yrjama M, Vanharanta H. Bony vibrotactile stimulation: A new, non-invasive method for examining intradiscal pain. European Spine Journal 1994;3:233-235). In the rehabilitation of masticatory disturbance and dysphagia, an electric toothbrush is commonly used as an oral motor exercise tool for the facilitation of blood flow and metabolism in the orofacial region in Japanese hospitals. However, subjects receiving vibration in the facial regions reported increased salivary secretion. We attempted to develop an oral motor exercise apparatus modified by a headphone headset that was fixed and could be used for extended periods. The vibration apparatus of the heating conductor is protected by the polyethyle methacrylate (dental mucosa protective material), and electric motors for vibration control of the PWM circuit. We examined the amount of salivation during vibration stimuli on the bilateral masseter muscle belly, using a cotton roll positioned at the opening of the secretory duct for 3 min. Although the quantity of salivation in each subject showed various and large fluctuations in the right and left sides of the parotid and submandibular and sublingual glands, one or more of the salivary glands were effectively stimulated by 89 Hz vibration. The reported apparatus will be useful as an additional method in orofacial rehabilitation.


Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling.
4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes - higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article.


Tuning multiple motor travel via single motor velocity.
Microtubule-based molecular motors often work in small groups to transport cargos in cells. A key question in understanding transport (and its regulation in vivo) is to identify the sensitivity of multiple-motor-based motion to various single molecule properties. Whereas both single-motor travel distance and microtubule binding rate have been demonstrated to contribute to cargo travel, the role of single-motor velocity is yet to be explored. Here, we recast a previous theoretical study, and make explicit a potential contribution of velocity to cargo travel. We test this possibility experimentally, and demonstrate a strong negative correlation between single-motor velocity and cargo travel for transport driven by two motors. Our study thus discovers a previously unappreciated role of single-motor velocity in regulating multiple-motor transport.


New drug therapies for advanced renal cell carcinoma.
The incidence of renal cell cancer is increasing and surgery is the only curative treatment for patients presenting with localized disease at diagnosis. The treatment of metastatic renal cell cancer is palliative and, until recently, immunotherapy has been the standard treatment approach with response rates between 10 and 20%. An increase in the appreciation of the biology of this disease has resulted in a number of new 'targeted' therapies being developed. Most notable is the introduction of tyrosine kinase inhibitors with significant activity in both treatment-naive and cytokine-refractory renal cell cancer. Drugs targeting angiogenic pathways also appear promising. These agents are being rapidly introduced into clinical practice, but further studies are needed to establish their optimal place in the management of renal cell cancer and, in particular, the role of combination and/or sequential therapy.


T-cell vaccination in multiple sclerosis: immunoregulatory mechanism and prospects for therapy.
Vaccination with inactivated autoreactive T cells (T-cell vaccination) was originally developed to study immune regulation in experimental autoimmune conditions. During the last two decades, research in this area has led to the new understanding of cellular and molecular mechanisms whereby autoreactive T cells are regulated in vivo and the development of new therapeutic strategies using synthetic peptides and plasmid or viral DNA vectors. Recently T-cell vaccination has been advanced to human trials in patients with multiple sclerosis. These early clinical studies were designed to test the potential treatment efficacy of T-cell vaccination and have shown some promising results. In this article, new insights in the understanding of the regulatory mechanism induced by T-cell vaccination and the results of the clinical trials are reviewed. In particular, issues related to the improvement of the current T-cell vaccination protocol are discussed in relationship to the concept of immune regulation and clinical considerations.


A Review of the Existing and Emerging Topics in the Supply Chain Risk Management Literature.
This review examines supply chain risk publications across nine prestigious management, operations, and supply chain journals with respect to exploring trends and emerging topics. Using a refined set of keywords, we extract and filter the most relevant supply chain risk management (SCRM) articles from Scopus between 2001 and 2019. Unlike previous reviews of the SCRM literature, our methodology utilizes both bibliometric and cocitation analyses of publications in selective management and operations and supply chain management journals. In addition to analyzing the current state of the SCRM literature via bibliometric analysis, we delve deeply into the clusters of literature informing SCRM studies through a cocitation analysis. By conducting a text analysis on these clusters, we identify the main themes and provide insights regarding article relevance, theoretical frameworks, and methodologies for each cluster. In addition, we categorize the themes within each cluster into three main groups of matured, developing, and emerging. Based on the identified categories, we provide detailed discussions on the promising avenues for research and practice in three main areas of sustainable SCRM, behavioral SCRM, and nascent methodologies and theories in SCRM studies. Finally, we dedicate a section in our review to discussing the direction of SCRM research during and after the coronavirus disease 2019 era.


Predicting Psychosocial Maladjustment in Emerging Adulthood From High School Experiences of Peer Victimization.
The aim of the present study was to compare recollections of sexual, physical, verbal, social, and cyber peer victimization experienced in high school in terms of depressed affect, self-esteem, and loneliness experienced in university. In all, 247 university students (70 males and 177 females; M = 20.62, SD = 2.54) completed online measures assessing retrospective accounts of their experiences of different forms of peer victimization during high school (i.e., sexual, physical, verbal, social, and cyber) and their current psychosocial adjustment (i.e., self-esteem, depressed affect, and loneliness). Three separate hierarchical multiple regressions were conducted to determine whether different indices of negative psychosocial adjustment are more strongly predicted by experiencing sexual or nonsexual forms of peer victimization. Although many university students recalled experiencing sexual peer victimization in high school at least once at an even higher percentage than verbal and social forms of peer victimization, the results of the present study suggest that social peer victimization in high school predicts higher levels of depressed affect and loneliness in university students than sexual peer victimization experienced in high school. Surprisingly, the young adults reporting higher levels of cyber peer victimization in high school were less lonely in university. Although the hypothesized relationships between each form of peer victimization and specific indices of psychosocial functioning were not consistently supported, these findings suggest that the form of peer victimization matters and may be differentially associated with well-being in emerging adulthood. It is important that future research explores how individual characteristics may further predict varied experiences of peer victimization and the long-term impact of those experiences.


Two families with autosomal dominant progressive external ophthalmoplegia.
We report here the clinical and genetic features of two new families with autosomal dominant progressive external ophthalmoplegia (adPEO). The examination of index patients included a detailed clinical characterisation, histological analysis of muscle biopsy specimens, and genetic testing of mitochondrial and nuclear DNA extracted from muscle and leucocytes. Index patients in both families presented with PEO and developed other clinical disease manifestations, such as myopathy and cardiomyopathy (patient 1) and axonal neuropathy, diabetes mellitus, hearing loss, and myopathy (patient 2), later in the course of illness. Both patients had ragged red fibres on muscle histology. Southern blot of mtDNA from muscle of patient 2 showed multiple deletions. In this case, a novel heterozygous missense mutation F485L was identified in the nuclear encoded putative mitochondrial helicase Twinkle. The mutation co-segregated with the clinical phenotype in the family and was not detected in 150 control chromosomes. In the other index patient, sequencing of ANT1, C10orf2 (encoding for Twinkle), and POLG1 did not reveal pathogenic mutations. Our cases illustrate the clinical variability of adPEO, add a novel pathogenic mutation in Twinkle (F485L) to the growing list of genetic abnormalities in adPEO, and reinforce the relevance of other yet unidentified genes in mtDNA maintenance and pathogenesis of adPEO.


Cancer of unknown primary sites: what radiologists need to know and what oncologists want to know.
In this article, we review the role of imaging in cancer of unknown primary site (CUP) diagnosis and management and the utility of immunohistochemistry, serum tumor markers, and molecular profiling in the optimized care of CUP patients. With advances in imaging, pathology, and molecular medicine, the diagnosis and management of CUP have evolved into more personalized and site-specific therapies. A multidisciplinary integrated approach among oncologists, pathologists, and radiologists is extremely important.


Glutathione Transferases Superfamily: Cold-Inducible Expression of Distinct GST Genes in Brassica oleracea.
Plants, as sessile organisms, can suffer serious growth and developmental consequences under cold stress conditions. Glutathione transferases (GSTs, EC 188.8.131.52) are ubiquitous and multifunctional conjugating proteins, which play a major role in stress responses by preventing oxidative damage by reactive oxygen species (ROS). Currently, understanding of their function(s) during different biochemical and signaling pathways under cold stress condition remain unclear. In this study, using combined computational strategy, we identified 65 Brassica oleracea glutathione transferases (BoGST) and characterized them based on evolutionary analysis into 11 classes. Inter-species and intra-species duplication was evident between BoGSTs and Arabidopsis GSTs. Based on localization analyses, we propose possible pathways in which GST genes are involved during cold stress. Further, expression analysis of the predicted putative functions for GST genes were investigated in two cold contrasting genotypes (cold tolerance and susceptible) under cold condition, most of these genes were highly expressed at 6 h and 1 h in the cold tolerant (CT) and cold susceptible (CS) lines, respectively. Overall, BoGSTU19, BoGSTU24, BoGSTF10 are candidate genes highly expressed in B. oleracea. Further investigation of GST superfamily in B. oleracea will aid in understanding complex mechanism underlying cold tolerance in plants.


Draft Genome Sequence of Enterobacter cloacae Strain S611.
We report draft genomes of Enterobacter cloacae strain S611, an endophytic bacterium isolated from surface-sterilized germinating wheat seeds. We present the assembly and annotation of its genome, which may provide insights into the metabolic pathways involved in adaptation.


[Spiral computed tomographic analysis of frontal recess regions].
The purpose of the study was to determine the prevalence of frontal recess cells in Chinese patients who did not have frontal sinus disease related symptoms. Forty-nine Chinese patients without frontal sinus disease symptoms were undergone spiral computed tomography (CT). Then multiplanar reconstruction images were evaluated using a standard triplanar reconstruction protocol on a computer workstation. The prevalence of agge rnasi cell was 94% (92/98). Sixty-four uncinate processes (65%, 64/98) had one superior attachment for each uncinate process, the other thirty-four uncinate processes (35%, 34/98) had two superior attachments for each uncinate process. The uncinate process' single superior attachment into the surrounding structures was identified to have the following distribution: 53% (52/98) to the lamina papyracea, 9% (9/98) to the middle turbinate, 3% (3/98) to the skull base. Most of the uncinate process' two superior attachments were either into the lamina papyracea and the skull base (24%, 23/98) or into the lamina papyracea and the middle turbinate (10%, 10/98). Only one uncinate process (1%) superiorly attached to the skull base and the middle turbinate. The prevalence of recessus terminalis was 87% (85/98). Of all the frontal cells identified in 32 sides (33%) of frontal recesses, the prevalence of type I, type II, type II and type IV cells were 23% (23 sides), 2% (2 sides), 7% (7 sides) and 0% (0 side) respectively. Supra bullar cell, frontal bullar cell and interfrontal septal cell were identified in 30 sides (31%), 7 sides (7%) and 7 patients (14%) respectively. The result characterized normal frontal recess pneumatization in Chinese. That, together with the variations of the uncinate process' superior attachment emphasized the roles of agger nasi cell and the uncinate process in endoscopic frontal sinus surgery.


Maillard glycation of beta-lactoglobulin induces conformation changes.
Glycation by the Maillard reaction is an ubiquitous reaction of condensation of a reducing sugar with amino groups of proteins, which products could improve the functional and/or biological properties for food and non-food uses. It can induce structural modifications in proteins, modifying their properties. The aim of this work was to investigate the association behavior and the conformational changes of beta-lactoglobulin (BLG) after its glycation by the Maillard reaction with several alimentary sugars (arabinose, galactose, glucose, lactose, rhamnose and ribose). Protein samples were heated in the presence or in the absence (heated control) of different sugars during 3 days at 60 degrees C. Glycation induced oligomerization of BLG monomers. Depending on the reactivity of the sugar, the population of produced oligomers showed smaller or greater heterogeneity in molecular masses. Analysis of modified BLG by circular dichroism and by its susceptibility to pepsinolysis showed that the conditions of heating used did not significantly alter the conformation of BLG. Heating of BLG in presence of sugars induced only minor structural modification, when using the less reactive sugars such as lactose and rhamnose. It was, however, at the origin of major three-dimensional destructuring in the case of the more reactive sugars such as arabinose and ribose. Pepsinolysis of glycated BLG did not affect about 62 and 35% of the protein molecules modified with lactose or rhamnose, and arabinose or ribose, respectively. The increase of susceptibility of glycated BLG to pepsinolysis could be related to the alteration of the conformation of the protein when glycation was performed with highly reactive sugars, as observed by circular dichroism and calorimetry analysis.


Diagnostic Value of Cytomegalovirus IgM Antibodies at Birth in PCR-Confirmed Congenital Cytomegalovirus Infection.
Although cytomegalovirus (CMV) DNA detection in urine is the standard method for diagnosing congenital cytomegalovirus infection (CCMVI), polymerase chain reaction (PCR) is not comprehensively available. Currently, the efficacy of CMV-specific IgM (CMV-IgM) and CMV-specific IgG (CMV-IgG) detection remains unclear. To determine the sensitivity and specificity of CMV-specific antibodies at birth, we investigated CMV-IgM and CMV-IgG titers in CCMVI cases and non-CCMVI controls, with confirmed diagnoses by urine quantitative real-time PCR within 3 weeks after birth. We included 174 infants with suspected CCMVI in whom serological testing was performed within the first 2 weeks after birth during 2012-2018. We classified the participants into a CCMVI group (n = 32) and non-CCMVI group (n = 142) based on their urine PCR results. The CMV-IgM-positive rate was 27/32 (84.4%) in the CCMVI group, compared with 1/142 (0.7%) in the non-CCMVI group (p < 0.0001). The positive CMV-IgG rates were 32/32 (100%) in the CCMVI group and 141/142 (99.3%) in the non-CCMVI group. The positive predictive value for CMV-IgM was high at 96.4% (27/28). This value may be sufficient for clinical use, especially in settings with limited resources where PCR is unavailable. However, CCMVI screening by CMV-IgM alone appears insufficient because of the considerable number of false-negative cases.


Effects of nicorandil on QT prolongation and myocardial damage caused by citalopram in rats.
Citalopram is a selective serotonin re-uptake inhibitor (SSRI) antidepressant; it exhibits the greatest cardiotoxic effect among SSRIs. Citalopram can cause drug-induced long QT syndrome (LQTS) and ventricular arrhythmias. We investigated the protective effect of nicorandil, a selective mitochondrial KATP (mito-KATP) channel opener, on LQTS and myocardial damage caused by citalopram in male rats. In a preliminary study, we determined that the minimum citalopram dose that prolonged the QT interval was 102 mg/kg injected intraperitoneally. For the main study, rats were divided randomly into five experimental groups: untreated control, normal saline + citalopram, nicorandil + citalopram, 5-hydroxydecanoate (5-HD) + citalopram, 5-HD + nicorandil + citalopram. Biochemical and histologic data from blood and heart tissue samples from six untreated control rats were evaluated. Electrocardiographic parameters including QRS duration, QT interval, corrected QT interval (QTc) and heart rate (HR) were assessed, and biochemical parameters including malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase were measured. We also performed histomorphologic and immunohistochemical examination of heart tissue. Citalopram prolonged QT-QTc intervals significantly and increased significantly the histomorphologic score and proportion of apoptotic cells, but produced no differences in the oxidant and antioxidant parameters. Nicorandil did not prevent citalopram induced QT-QTc interval prolongation and produced no significant changes in oxidant and antioxidant parameters; however, it did reduce histologic damage and apoptosis caused by citalopram.


Frequency of thrombosis and post-thrombotic conditions of the foot at phlebography.
In 350 consecutive ascending phlebographies thrombosis was demonstrated in 60, 6 of which were limited to the foot. The veins of the foot is an overlooked place for the origin of thrombosis and emboli.


Nested case-control study of tumors of the hemopoietic and lymphatic systems among workers in the meat industry.
Workers in the meat industry are exposed to viruses that cause leukemia and lymphoma in cattle and chickens, and also to carcinogenic chemical agents. This case-control study, nested in a cohort of members of a meatcutters' union in Baltimore, Maryland, investigated whether occupational exposures are associated with death from tumors of the hemopoietic and lymphatic systems. Cases of these tumors represent all deaths which occurred in the cohort between 1949 and 1980. Excess risks of tumors of the hemopoietic and lymphatic systems were observed throughout the meat industry, except in meatpacking plants. Slaughtering activities involving heavy exposure to oncogenic viruses were strongly associated with these tumors, especially with lymphomas. Thus, elevated risks were observed for butchers who killed animals (odds ratio (OR) = 5.3, 95% confidence interval (CI) 1.0-27.0); workers in chicken-slaughtering plants (OR = 3.3, 95% CI 0.8-13.1); and workers in cattle/sheep/pig abattoirs (OR = 2.8, 95% CI 0.8-9.5). Among supermarket workers, wrapping meat (mainly a female activity) was associated with increased risk of tumors of the hemopoietic and lymphatic systems (OR = 3.8, 95% CI 1.0-14.3), with the odds of both lymphomas and tumors of the myeloid stem cell being elevated. On the other hand, meatcutting in supermarkets (almost exclusively a male activity) was associated with multiple myeloma; the odds ratio for men was 18.0 (95% CI 1.6-207.5), with no myeloma cases being recorded in women. These associations persisted after limited control for exposures outside the industry that have also been observed to be associated with excess risk, such as exposure to pesticides, working/living on pig farms, and exposure to X-rays. The findings provide evidence that workers in the meat industry may be at elevated risk of tumors of the hemopoietic and lymphatic systems. Further studies with larger sample sizes are needed to identify more conclusively which exposures play an etiologic role in the occurrence of the different histologic types of these tumors.


Intestinal microbiota modulation at the strain level by the olive oil polyphenols in the diet.
Previously we have reported a r16S gene next generation sequencing study on the effect of high fat diets in the intestinal microbiota using a murine model. However, many important microbial traits occur at strain level and, in order to detect these population changes, culture-dependent approaches need to be applied. With this goal, we decided to study a very well-known commensal genus, Enterococcus, and therefore, intestinal enterococci methodically isolated during the above-mentioned experiment were analyzed. A collection of 75 distinct enterococcal strains isolated from feces of mice fed a standard diet or high-fat diets enriched with butter, refined olive oil, or extra virgin olive oil and after 0, 6 or 12 weeks of diet, were genetically and phenotypically characterized in search of virulence factors, biogenic amine production and antibiotic resistance. All strains were tested for the susceptibility in vitro to two virgin olive oil polyphenols, oleuropein (the bitter principle of olives) and hydroxytyrosol (derived from oleuropein by enzymatic hydrolysis and responsible for the high stability of olive oil). No drastic polyphenol effect was found except at high concentrations. However, when carrying out a comparative statistical study in the 75 strains of the collection according to the different diets, we have detected significant differences between the strains isolated from mice fed with a diet enriched with virgin olive oil and the rest of the diets. EVOO strains also presented less resistance to antibiotics and a more beneficial profile overall. These results support the prebiotic role of polyphenols, showing how they are able to modulate the set of strains that comprises a genus in the gut, allowing them to adapt to a changing environment in the host's intestine and possibly exerting effects on its physiology.


[Clinical features and prognosis of pulmonary sarcomatoid carcinoma].
Objective: To investigate the clinical features and prognosis of patients with pulmonary sarcomatoid carcinoma (PSC). Methods: The study retrospectively reviewed the clinical, radiological, pathological characteristics and prognosis of 76 patients with PSC who were treated in the First Affiliated Hospital of Medical School of Zhejiang University from January 2011 to December 2016. Gender, age, smoking history, tumor location, tumor size, lymph node metastasis, distant metastasis, TNM staging and treatment methods were analyzed to determine the factors affecting the prognosis of PSC patients. Results: The 76 patients with PSC consisted of 61 men and 15 women, the average age was (62.9±9.8) years old. Cough (31 cases, 40.8%), hemoptysis (29 cases, 38.2%) and chest pain (15 cases, 19.7%) were the main clinical manifestations; the average diameter of tumor was (4.7±2.3) cm; the peripheral type (48 cases, 63.2%), right lung (51 cases, 67.1%) and upper lobe of the lung (46 cases, 60.5%) were the common locations. The tumors usually were with a smooth margin, showing an irregular annular enhancement around the area, but the central part of the tumors were not enhanced obviously. The main pathologic type was pleomorphic carcinoma, and immunohistochemistry showed that vimentin and cytokeratin were usually expressed.Tumor size, lymph node metastasis, distant metastasis, TNM staging and early surgical treatment (P<0.05) were prognostic factors for survival, and distant metastasis and TNM staging (P<0.001) were independent prognostic factors affecting the prognosis of patients. Conclusions: There are no specificity in the clinical and radiological features of PSC patients in our study, and the diagnosis of PSC depends mainly on pathological analysis. Distant metastasis and TNM staging are independent prognostic factors.


Sonodynamic therapy combined with novel anti-cancer agents, sanguinarine and ginger root extract: Synergistic increase in toxicity in the presence of PANC-1 cells in vitro.
The presence of ultrasound-induced cavitation in sonodynamic therapy (SDT) treatments has previously enhanced the activity and delivery of certain sonosensitisers in biological systems. The purpose of this work was to investigate the potential for two novel anti-cancer agents from natural derivatives, sanguinarine and ginger root extract (GRE), as sonosensitisers in an SDT treatment with in vitro PANC-1 cells. Both anti-cancer compounds had a dose-dependent cytotoxicity in the presence of PANC-1 cells. A range of six discreet ultrasound power-frequency configurations were tested and it was found that the cell death caused directly by ultrasound was likely due to the sonomechanical effects of cavitation. Combined treatment used dosages of 100μM sanguinarine or 1mM of GRE with 15s sonication at 500kHz and 10W. The sanguinarine-SDT and GRE-SDT treatments showed a 6% and 17% synergistic increase in observed cell death, respectively. Therefore both sanguinarine and GRE were found to be effective sonosensitisers and warrant further development for SDT, with a view to maximising the magnitude of synergistic increase in toxicity.


Dynamics in the quantum/classical limit based on selective use of the quantum potential.
A classical limit of quantum dynamics can be defined by compensation of the quantum potential in the time-dependent Schrödinger equation. The quantum potential is a non-local quantity, defined in the trajectory-based form of the Schrödinger equation, due to Madelung, de Broglie, and Bohm, which formally generates the quantum-mechanical features in dynamics. Selective inclusion of the quantum potential for the degrees of freedom deemed "quantum," defines a hybrid quantum/classical dynamics, appropriate for molecular systems comprised of light and heavy nuclei. The wavefunction is associated with all of the nuclei, and the Ehrenfest, or mean-field, averaging of the force acting on the classical degrees of freedom, typical of the mixed quantum/classical methods, is avoided. The hybrid approach is used to examine evolution of light/heavy systems in the harmonic and double-well potentials, using conventional grid-based and approximate quantum-trajectory time propagation. The approximate quantum force is defined on spatial domains, which removes unphysical coupling of the wavefunction fragments corresponding to distinct classical channels or configurations. The quantum potential, associated with the quantum particle, generates forces acting on both quantum and classical particles to describe the backreaction.


Clinical Evaluation of Perspiration Reducing Effects of a Kampo Formula, Shigyaku-san, on Palmoplantar Hidrosis.
Palmoplantar hidrosis is common in patients who are susceptible to strains on the autonomic nervous system, and stress and mental strain have been proven to produce sweating in this population. Shigyaku-san (Sini san, TJ-35: Tsumura & Co.) is effective for relieving stagnation of 'liver Qi and vital energy' in traditional Chinese medicine theory; this brings about improvement of palmoplantar hidrosis. The effect of Shigyaku-san on 40 patients was evaluated based on changes in palmoplantar sweat volume and skin temperature before and after stress loading. We also measured changes in the palmoplantar sweat volume and skin temperature due to stress load in 35 healthy controls who did not receive Shigyaku-san. Before treatment, the pre-stress sweat volume in patients was larger than that in healthy controls, however, after Shigyaku-san treatment, their pre-stress sweat volume decreased. With stress, the sweat volume increased in both patients and controls, but the net increase in the patients was larger than that in healthy controls. After Shigyaku-san treatment, the net increase of sweat volume due to stress was smaller than that of pretreatment, however, it did not show a significant difference with that of healthy controls. The palmoplantar skin temperature of the patients before treatment was lower than that of healthy controls. Palmoplantar skin temperature rose with stress loading in healthy controls, but decreased in pretreatment patients. Shigyaku-san treatment reduced the palmoplantar perspiration in palmoplantar hidrosis patients at rest and under stress. Furthermore, it also improved other serious complications, especially coldness of the extremities.


[Walking in Crustacea: motor program and peripheral regulation (author's transl)].
1. Rock lobsters can walk in all directions. In the present study, we report the organization of the motor output of the three muscles which control the mero-carpopodite joint (M-C): the extensor E, the flexor F and the accuracy flexor FA, during unrestrained locomotion (fig. 1). 2. During lateral walking, movements of the M-C joint provide most of the propulsive force, whereas during forward and backward walking this joint function more as a strut (fig. 2). Corresponding differences are observed in the motor discharge in the different walking modes. During lateral walking, discharge in the M-C extensor and M-C flexor alternates, whereas during forward and backward walking these antagonists are coactivated (fig. 3 and 4). 3. We have also examined the effects of alterations of proprioceptive feedback: the FA tendon has been cut to eliminate MCO afferents during walking. This ablation does not modify the burst period and the temporal structure of the output pattern is largely unaffected (fig. 5, 6 and 7). MCO may influence the motor output of a given muscle depending upon whether it participates in the return stroke or the power stroke.


[Primary headache - risk factor or comorbid pathology in cognitive impairment].
Currently, the relationship between headache and dementia is considered more widely than just a comorbidity. The severity of migraine and tension-type headache and the severity of cognitive impairment are strongly correlated. Common pathophysiological mechanisms underlie the relationship between primary headache and cognitive impairment. Antinociceptive changes in primary headaches and in glutamate excitotoxicity in dementia developed due to hyper excitability of NMDA receptors are strongly interdependent. It is important in the aspect of possible correction of this pathology by NMDA-antagonists. Memantine not only slows the progression of cognitive symptoms in dementia, but also significantly influences the frequency and severity of primary headache.


Core stabilization exercise with real-time feedback for chronic hemiparetic stroke: a pilot randomized controlled trials.
The purpose of this study was to examine the feasibility of core stabilization exercise with real-time feedback on balance and gait function in patients with chronic hemiparetic stroke. Nineteen stroke subjects were enrolled in this study. The patients were randomly divided into the experimental (n = 10) and control groups (n = 9). Subjects in the experimental group performed core stabilization exercise with real-time feedback training for 30 minutes per day during a period of six weeks. Subjects in the control group performed core stabilization exercise during the same period. This study assessed the kinematic parameters using a portable walkway system, and timed up-and-go test. Gait velocity showed significantly greater improvement in the experimental group (7.3 ± 5.0 sec) than in the control group (-0.7 ± 10.6). Stride length showed significantly greater increase in the experimental group (13.2 ± 7.9 on the affected side and 12.6 ± 8.0 on the less affected side) than the control group (3.5 ± 8.7 on the affected side and 3.4 ± 8.5 on the less affected side). After training, change in results on the timed up and go test was significantly greater in the experimental group than in the control group. Core stabilization exercise using real-time feedback produces greater improvement in gait performance in chronic hemiparetic stroke patients than core stabilization exercise only.


Warming accelerates decomposition of decades-old carbon in forest soils.
Global climate carbon-cycle models predict acceleration of soil organic carbon losses to the atmosphere with warming, but the size of this feedback is poorly known. The temperature sensitivity of soil carbon decomposition is commonly determined by measuring changes in the rate of carbon dioxide (CO(2)) production under controlled laboratory conditions. We added measurements of carbon isotopes in respired CO(2) to constrain the age of carbon substrates contributing to the temperature response of decomposition for surface soils from two temperate forest sites with very different overall rates of carbon cycling. Roughly one-third of the carbon respired at any temperature was fixed from the atmosphere more than 10 y ago, and the mean age of respired carbon reflected a mixture of substrates of varying ages. Consistent with global ecosystem model predictions, the temperature sensitivity of the carbon fixed more than a decade ago was the same as the temperature sensitivity for carbon fixed less than 10 y ago. However, we also observed an overall increase in the mean age of carbon respired at higher temperatures, even correcting for potential substrate limitation effects. The combination of several age constraints from carbon isotopes showed that warming had a similar effect on respiration of decades-old and younger (<10 y) carbon but a greater effect on decomposition of substrates of intermediate (between 7 and 13 y) age. Our results highlight the vulnerability of soil carbon to warming that is years-to-decades old, which makes up a large fraction of total soil carbon in forest soils globally.


The soil microbiome increases plant survival and modifies interactions with root endosymbionts in the field.
Evidence is accumulating that the soil microbiome-the community of microorganisms living in soils-has a major effect on plant traits and fitness. However, most work to date has taken place under controlled laboratory conditions and has not experimentally disentangled the effect of the soil microbiome on plant performance from the effects of key endosymbiotic constituents. As a result, it is difficult to extrapolate from existing data to understand the role of the soil microbiome in natural plant populations. To address this gap, we performed a field experiment using the black medick Medicago lupulina to test how the soil microbiome influences plant performance and colonization by two root endosymbionts (the mutualistic nitrogen-fixing bacteria Ensifer spp. and the parasitic root-knot nematode Meloidogyne hapla) under natural conditions. We inoculated all plants with nitrogen-fixing bacteria and factorially manipulated the soil microbiome and nematode infection. We found that plants grown in microbe-depleted soil exhibit greater mortality, but that among the survivors, there was no effect of the soil microbiome on plant performance (shoot biomass, root biomass, or shoot-to-root ratio). The soil microbiome also impacted parasitic nematode infection and affected colonization by mutualistic nitrogen-fixing bacteria in a plant genotype-dependent manner, increasing colonization in some plant genotypes and decreasing it in others. Our results demonstrate the soil microbiome has complex effects on plant-endosymbiont interactions and may be critical for survival under natural conditions.


Aqua-{N,N-dimethyl-N'-[1-(2-pyrid-yl)ethyl-idene]ethane-1,2-diamine-κN,N',N''}bis-(thio-cyanato-κN)nickel(II).
In the title compound, [Ni(NCS)(2)(C(11)H(17)N(3))(H(2)O)], the Ni(II) ion is six-coordinated by the N,N',N"-tridentate Schiff base N atoms, two cis-positioned N-bound isothio-cyanate groups and one water mol-ecule. In the crystal, O-H⋯S hydrogen bonds link adjacent mol-ecules into infinite layers parallel to the ac plane. The layers are further connected into a three-dimensional network via C-H⋯π inter-actions. The -CH(2)-N(CH(3))(2) fragment is disordered over two sets of sites in a 0.556 (5):0.444 (5) ratio.


Spontaneous development of hepatocellular carcinoma with cancer stem cell properties in PR-SET7-deficient livers.
PR-SET7-mediated histone 4 lysine 20 methylation has been implicated in mitotic condensation, DNA damage response and replication licensing. Here, we show that PR-SET7 function in the liver is pivotal for maintaining genome integrity. Hepatocyte-specific deletion of PR-SET7 in mouse embryos resulted in G2 phase arrest followed by massive cell death and defect in liver organogenesis. Inactivation at postnatal stages caused cell duplication-dependent hepatocyte necrosis, accompanied by inflammation, fibrosis and compensatory growth induction of neighboring hepatocytes and resident ductal progenitor cells. Prolonged necrotic regenerative cycles coupled with oncogenic STAT3 activation led to the spontaneous development of hepatic tumors composed of cells with cancer stem cell characteristics. These include a capacity to self-renew in culture or in xenografts and the ability to differentiate to phenotypically distinct hepatic cells. Hepatocellular carcinoma in PR-SET7-deficient mice displays a cancer stem cell gene signature specified by the co-expression of ductal progenitor markers and oncofetal genes.


Status of drug-eluting coronary stents.
Significant advances in interventional cardiology have occurred over the past 30 years, leading to substantial increases in the number and anatomic complexity of treated patients, the long-term success of these procedures, and a reduction in the need for coronary bypass surgery. While the risk ofrestenosis has been dramatically reduced by drug-eluting stents, delayed neo-intimal healing has led to a small, but significant occurrence of "late" stent thrombosis. This thrombotic risk is substantially reduced by continuation of dual-anti-platelet therapy for one or more years following DES placement. Current guidelines for patient selection for DES, for duration of DAT following DES, and for facing surgical and invasive procedures after DES were discussed, and the avoidance of early discontinuation of anti-platelet therapy following DES was emphasized.


Computed tomography of the abdomen.
In a few short years, computed tomography has become an important diagnostic procedure in the examination of the abdomen and pelvis. Its forte lies in its ability to provide cross-sectional views of excellent anatomical detail. Imaging of deep-seated structures such as the pancreas, adrenal glands, and enlarged retroperitoneal lymph nodes is now possible. The ability to distinguish small variations in tissue density enables the radiologist to evaluate the texture of solid structures, and to differentiate them from cysts or abscesses. The addition of contrast enhancement makes it possible to determine the vascularity of a lesson. The major limitation of CT is poorer delineation of structures in thin patients, and in patients in whom voluntary and involuntary motion cannot be interrupted. Computed tomography is compared with other complementary imaging procedures to include sonography, radionuclide imaging, and conventional radiograph procedures. It has replaced invasive diagnostic procedures in many instances. In a given situation, one or more imaging modalities may be appropriate.


CD4+ T Cell Immune Specificity Changes After Vaccination in Healthy And COVID-19 Convalescent Subjects.
The immune response promoted by SARS-CoV-2 vaccination is relevant to develop novel vaccines and optimized prevention strategies. We analyzed the adaptive immunity in healthy donors (HD) and convalescent individuals (CD), before and after administering BNT162b2 vaccine. Our results revealed specific changes in CD4+ T cell reactivity profile in vaccinated HD and CD, with an increase in S1 and S2 positive individuals, proportionally higher for S2. On the contrary, NCAP reactivity observed in HD and CD patients was no longer detectable after vaccination. Despite the substantial antibody response in CD, MPro-derived peptides did not elicit CD4+ lymphocyte activation in our assay in either condition. HD presented an increment in anti-S and anti-RBD IgG after first dose vaccination, which increased after the second vaccination. Conversely, anti-S and anti-RBD IgG and IgA titers increased in already positive CD after first dose administration, remaining stable after second dose inoculation. Interestingly, we found a strong significant correlation between S1-induced CD4+ response and anti-S IgA pre-vaccination, which was lost after vaccine administration.


Purification and characterization of pepsinogens and pepsins from the stomach of rice field eel (Monopterus albus Zuiew).
Three pepsinogens (PG1, PG2, and PG3) were highly purified from the stomach of freshwater fish rice field eel (Monopterus albus Zuiew) by ammonium sulfate fractionation and chromatographies on DEAE-Sephacel, Sephacryl S-200 HR. The molecular masses of the three purified PGs were all estimated as 36 kDa using SDS-PAGE. Two-dimensional gel electrophoresis (2D-PAGE) showed that pI values of the three PGs were 5.1, 4.8, and 4.6, respectively. All the PGs converted into corresponding pepsins quickly at pH 2.0, and their activities could be specifically inhibited by aspartic proteinase inhibitor pepstatin A. Optimum pH and temperature of the enzymes for hydrolyzing hemoglobin were 3.0-3.5 and 40-45 °C. The K (m) values of them were 1.2 × 10⁻⁴ M, 8.7 × 10⁻⁵ M, and 6.9 × 10⁻⁵ M, respectively. The turnover numbers (k(cat)) of them were 23.2, 24.0, and 42.6 s⁻¹. Purified pepsins were effective in the degradation of fish muscular proteins, suggesting their digestive functions physiologically.


Highly efficient and selective photocatalytic oxidation of sulfide by a chromophore-catalyst dyad of ruthenium-based complexes.
Electronic coupling across a bridging ligand between a chromophore and a catalyst center has an important influence on biological and synthetic photocatalytic processes. Structural and associated electronic modifications of ligands may improve the efficiency of photocatalytic transformations of organic substrates. Two ruthenium-based supramolecular assemblies based on a chromophore-catalyst dyad containing a Ru-aqua complex and its chloro form as the catalytic components were synthesized and structurally characterized, and their spectroscopic and electrochemical properties were investigated. Under visible light irradiation and in the presence of [Co(NH3)5Cl]Cl2 as a sacrificial electron acceptor, both complexes exhibited good photocatalytic activity toward oxidation of sulfide into the corresponding sulfoxide with high efficiency and >99% product selectivity in neutral aqueous solution. The Ru-aqua complex assembly was more efficient than the chloro complex. Isotopic labeling experiments using (18)O-labeled water demonstrated the oxygen atom transfer from the water to the organic substrate, likely through the formation of an active intermediate, Ru(IV)═O.


The Effect of Process Conditions on Sulfuric Acid Leaching of Manganese Sludge.
Manganese sludge, an industrial waste product in the ferroalloy industry, contains various components and holds significant importance for sustainable development through its valorization. This study focuses on characterizing a manganese sludge and investigating its behavior during sulfuric acid leaching. The influence of process conditions, including temperature, acid concentration, liquid to solid ratio, and leaching duration, was examined. The results revealed that Mn, Zn, and K are the main leachable components, and their overall leaching rates increase with increasing temperature, liquid to solid ratio, and time. However, the acid concentration requires optimization. High leaching rates of 90% for Mn, 90% for Zn, and 100% for K were achieved. Moreover, it was found that Pb in the sludge is converted to sulfate during the leaching, which yields a sulfate concentrate rich in PbSO4. The leaching process for Mn and Zn species appears to follow a second or third order reaction, and the calculation of rate constants indicated that Mn leaching kinetics are two to five times higher than those for Zn. Thermodynamic calculations were employed to evaluate the main chemical reactions occurring during leaching.


Dengue in a changing climate.
Dengue is the world's most important arboviral disease in terms of number of people affected. Over the past 50 years, incidence increased 30-fold: there were approximately 390 million infections in 2010. Globalization, trade, travel, demographic trends, and warming temperatures are associated with the recent spread of the primary vectors Aedes aegypti and Aedes albopictus and of dengue. Overall, models project that new geographic areas along the fringe of current geographic ranges for Aedes will become environmentally suitable for the mosquito's lifecycle, and for dengue transmission. Many endemic countries where dengue is likely to spread further have underdeveloped health systems, increasing the substantial challenges of disease prevention and control. Control focuses on management of Aedes, although these efforts have typically had limited effectiveness in preventing outbreaks. New prevention and control efforts are needed to counter the potential consequences of climate change on the geographic range and incidence of dengue, including novel methods of vector control and dengue vaccines.


The occurrence of ochratoxin A in rice in six provinces of Iran.
Three hundred and eight samples of rice purchased from retail markets in six different provinces in Iran from March 2012 to January 2013 were surveyed for the presence of ochratoxin A (OTA) using enzyme-linked immunosorbent assay. The recovery percentages of OTA from spiked rice samples at concentrations of 5 and 10 ng/g were found to be 85.3% and 86.7%, respectively. Analytical results showed a 9.4% frequency of contamination from total analyzed rice samples with a mean OTA level of 3.60 ± 2.66 ng/g. Concentrations of OTA in positive samples ranged from 0.84 ng/g to 11.37 ng/g, and in 17.3% of contaminated rice samples the concentrations exceeded the maximum tolerance limit set by European regulations for OTA in cereals (5 ng/g). Based on the results of this study, the estimated daily intake of OTA in rice was 0.62 ng/kg body weight/day for Iranian consumers.


Discrimination between the lens fiber cell 115 kd cytoskeletal protein and alpha-actinin.
The lens fiber cell cytoskeleton includes a protein with a relative molecular weight, by SDS PAGE, of 115 kD. This protein has been purported to be, or be related to alpha-actinin, a highly-conserved family of actin-binding cytoskeletal proteins common to many tissues across a wide phylogenetic range. In this report we assess the relationship between the 115 kd lens fiber cell protein and alpha-actinin. Assessment of relative molecular weight, immunologic cross-reactivity, and partial sequence analysis suggest that the 115 kD lens fiber cell cytoskeletal protein and alpha-actinin are either unrelated, or, at best, that the lens protein represents an unusually divergent isoform of the alpha-actin family of proteins. Immunochemical analysis of homogenates of bovine heart and red blood cells indicate that these tissues express a protein which is weakly cross-reactive with the lens 115 kD protein, but that this cross-reactive protein is not alpha-actinin.


Calculation of the specific rate of catabolic activity (Ac) from the heat flow rate of soil microbial reactions measured by calorimetry: significance and applications.
The calculation of parameters involved in the kinetics of the microbial soil reactions linked to the carbon cycle is strongly limited by the methodologies employed. Hence, a mathematical model is proposed to quantify easily the specific rate of catabolic activity A(c) by microcalorimetry based on Belaich's model. It permits to quantify A(c) from the plots of the heat flow rate vs. time recorded from soil samples amended with glucose. It was applied for several soil samples collected in the Amazon. The results obtained were compared, and statistical and graphical analyses were used to provide the biophysical significance of A(c) in soils. Results suggest that A(c) could be used as an empirical measure of stress. It correlates positively with the heat yield, Y(Q/X), of the soil microbial growth reactions, indicating that higher specific rates of catabolic activity cause higher dissipation of energy per unit of cell, yielding less-efficient metabolic reactions, which could affect negatively the soil quality. It is strongly affected by the initial microbial population and by the percentage of nitrogen in the samples. The statistical analysis also demonstrated that A(c) is more sensitive to changing environmental conditions than Y(Q/X), yielding more-accurate information about the soil metabolic processes.


Hierarchical phylogenetic models for analyzing multipartite sequence data.
Debate exists over how to incorporate information from multipartite sequence data in phylogenetic analyses. Strict combined-data approaches argue for concatenation of all partitions and estimation of one evolutionary history, maximizing the explanatory power of the data. Consensus/independence approaches endorse a two-step procedure where partitions are analyzed independently and then a consensus is determined from the multiple results. Mixtures across the model space of a strict combined-data approach and a priori independent parameters are popular methods to integrate these methods. We propose an alternative middle ground by constructing a Bayesian hierarchical phylogenetic model. Our hierarchical framework enables researchers to pool information across data partitions to improve estimate precision in individual partitions while permitting estimation and testing of tendencies in across-partition quantities. Such across-partition quantities include the distribution from which individual topologies relating the sequences within a partition are drawn. We propose standard hierarchical priors on continuous evolutionary parameters across partitions, while the structure on topologies varies depending on the research problem. We illustrate our model with three examples. We first explore the evolutionary history of the guinea pig (Cavia porcellus) using alignments of 13 mitochondrial genes. The hierarchical model returns substantially more precise continuous parameter estimates than an independent parameter approach without losing the salient features of the data. Second, we analyze the frequency of horizontal gene transfer using 50 prokaryotic genes. We assume an unknown species-level topology and allow individual gene topologies to differ from this with a small estimable probability. Simultaneously inferring the species and individual gene topologies returns a transfer frequency of 17%. We also examine HIV sequences longitudinally sampled from HIV+ patients. We ask whether posttreatment development of CCR5 coreceptor virus represents concerted evolution from middisease CXCR4 virus or reemergence of initial infecting CCR5 virus. The hierarchical model pools partitions from multiple unrelated patients by assuming that the topology for each patient is drawn from a multinomial distribution with unknown probabilities. Preliminary results suggest evolution and not reemergence.


Genetic control of immune responses in vitro. II. Cellular requirements for the development of primary plaque-forming cell responses to the random terpolymer 1-glutamic acid 60-1-alanine30-1-tyrosine10 (GAT) by mouse spleen cells in vitro.
The cellular requirements for the development of primary IgG GAT-specific PFC responses in cultures of spleen cells from responder, C57Bl/6, mice stimulated with GAT and GAT-MBSA and in cultures of spleen cells from nonresponder, SJL and B10.S, mice stimulated with GAT-MBSA were investigated. Macrophages were required for development of responses to GAT and GAT-MBSA in cultures of spleen cells from responder mice and for responses to GAT-MBSA in cultures of spleen cells from nonresponder mice. Macrophages from nonresponder mice supported the development of responses to GAT by nonadherent responder spleen cells, indicating that the failure of nonresponder mice to respond to GAT is not due to a macrophage defect. Furthermore, responder macrophages supported the responses of nonadherent, nonresponder spleen cells to SRBC and GAT-MBSA, but not to GAT. This indicates that the capacity to respond to GAT is a function of the nonadherent population which is composed of thymus-derived (T) helper cells and precursors of antibody-producing cells. Treatment of spleen cells with anti-theta serum and complement before culture initiation abolished PFC responses to GAT and GAT-MBSA thus establishing the requirement for T cells in the development of PFC responses to these antigens. Since precursors of antibody-producing cells in nonresponder mice are capable of synthesizing antibody specific for GAT after stimulation with GAT-MBSA and since the response to GAT is thymus-dependent, it appears that nonresponder mice lack GAT-specific helper T cell function.


Safety and efficacy of the structured onboarding steps and initiation protocol for MiniMed™ 780G system among an Egyptian cohort of young people living with type 1 diabetes.
The aim of the current study was to evaluate the safety and efficacy of initiation protocol for MiniMed ™ 780G system among an Egyptian cohort of young people living with type 1 diabetes (T1D). A prospective single-arm study including 72 participants with T1D. Five days of structured education and training were provided to all users and continuous glucose monitoring (CGM) was initiated on the first day of the training. Users initiated the pump initially in manual mode, with suspend before low feature, for 3 days before shifting to Auto Mode. The mean HbA1c decreased from 8.72 ± 2.01 % to 6.7 ± 0.4 % (p<0.01). Time in range (70-180 mg/dL) substantially improved from 55.24 % ± 10.35 to 81.7 % ± 5.12 % after spending 84 days in auto mode (p<0.001) with 2.03 % of the time spent below 70 mg/dL. Regarding AHCL compatibility, users spent at least 90 % of time in auto mode. Young people with T1D successfully initiated the AHCL system, using a tailored structured on-boarding protocol. Structured stepwise initiation protocol and onboarding steps are important prerequisite for participants' adherence and engagement with the system. Patient education together with optimized pump settings are important predictors of glycemic outcomes.


Predictors of long-term decannulation in patients with disorders of consciousness.
The predictors of tracheostomy decannulation in patients with disorders of consciousness (DOC) are not comprehensively understood, making prognosis difficult. The primary objective of this study was to identify predictors of tracheostomy decannulation in patients with disorders of consciousness (DOC). The secondary aim was to evaluate the feasibility and safety of the modified Evans blue dye test (MEBDT) in tracheostomized DOC patients. This retrospective study included all patients with disorders of consciousness (DOC) who underwent tracheostomy and were admitted between January 2016 and September 2022. Age, sex, etiology, initial Glasgow coma scale (GCS), initial Coma Recovery Scale-Revised (CRS-R), diagnosis of unresponsive wakefulness syndrome (UWS) or minimal consciousness state (MCS), MEBDT, initial modified Rankin scale (mRS), and initial Functional Oral Intake Scale (FOIS) were collected upon study enrollment. The relationship between clinical characteristics and cannulation status was investigated through a Cox regression model. A total of 141 patients were included in the study. The average age of these patients was 52.5 ± 16.7 years, with 42 (29.8%) being women. During the study period, 86 subjects (61%) underwent successful decannulation. Univariate analysis revealed that decannulated patients exhibited a significantly better conscious state compared to those without decannulation (CRS-R: p < 0.001; GCS: p = 0.023; MCS vs. UWS: p < 0.001). Additionally, a negative modified Evans blue dye test (MEBDT) result was significantly associated with tracheostomy decannulation (p < 0.001). In the multivariate analysis, successful decannulation was associated with a higher level of consciousness (MCS vs. UWS, p < 0.001, HR = 6.694) and a negative MEBDT result (negative vs. positive, p = 0.006, HR = 1.873). The Kaplan-Meier analysis further demonstrated that MEBDT-negative patients and those in the MCS category had a higher probability of decannulation at 12 months (p < 0.001). The findings of this study indicate that a negative MEBDT result and a higher level of consciousness can serve as predictive factors for successful tracheostomy decannulation in DOC patients.


Mixed-Pattern Ameloblastoma of the Anterior Mandible: A Rare Histopathological Presentation at an Infrequent Location.
Ameloblastoma is a benign odontogenic tumor of epithelial origin that exhibits a locally aggressive behavior with a high level of recurrence and multiple factors involved in its molecular pathogenesis. This article is a case report of a 46-year-old male patient suffering from a progressively enlarging tumor of the anterior mandible that caused gradual expansion of the lingual cortical plate and root displacement without resorption of the involved teeth. Incisional biopsy was consistent with "conventional" ameloblastoma, showing a mixed pattern of both the follicular and acanthomatous subtypes. This diagnosis was corroborated through a histopathological examination of the resected specimen. The patient was submitted to en bloc resection (marginal mandibulectomy) with preservation of the lower mandibular border; dental rehabilitation was achieved through a removable prosthesis. He remains disease-free for 5.5 years postoperatively and is highly satisfied with mastication and speech. The objective of this report is to highlight a relatively rare histopathological presentation of the "conventional" ameloblastoma, involving a site not commonly affected by ameloblastomas, the anterior mandible and crossing the midline, in a relatively young male patient.


Functional analysis of the ver gene using antisense transgenic wheat.
The function of ver203, a gene related to vernalization in winter wheat, was investigated by expression of a complementary DNA as an antisense RNA in transgenic plants. A verc203:gus fusion-expression plasmid was constructed in pBI221, which contains a CaMV (cauliflower mosaic virus) 35S-promoter, a gus gene and a nos terminator. The construct was then introduced into the plant by the pollen-tube pathway. The results showed that heading was strongly inhibited in 6 of 326 vernalized antisense transgenic winter wheat plants, until both the vernalized control winter wheat and sense transgenic plants ripened. The hybridization analysis of DNA, amplification of the insert DNA sequences with PCR, northern blot analysis with double- and single-stranded probes, and detection of GUS activity by X-gluc assay gave strong positive results. This suggests that the VER203 protein plays an important role in controlling heading and flower development in winter wheat.


Fitness Intention and Its Relationship With Eating Attitudes: A Cross-Sectional Study of Iranian Female Medical College Students.
Fitness is a very important goal among young adults that may lead to eating disorders. The aim of this study was to identify the factors influencing fitness intention based on the theory of planned behavior (TPB) and its relationship to eating attitudes. A cross-sectional study was conducted among 231 female college students during the winter of 2012. Participants were randomly selected in proportion to their distribution among the different faculties at Hamadan University of Medical Sciences. A structured questionnaire was applied for collecting data and data was analyzed by SPSS version 21 using a T-test, ANOVA, bivariate correlations, and linear regression at a 95% significant level. Nearly 21.6% of the participants had abnormal eating attitudes. The TPB variables accounted for 40% of the variation in fitness intention. Bivariate correlations indicated a positive correlation between fitness intention and eating attitude (r = 0.417, P < 0.05). Based on our results, it seems that designing and implementing educational programs to reduce positive attitudes and encourage subjective norms toward fitness may be useful for preventing abnormal eating attitudes.


An integrated hospital-district performance evaluation for communicable diseases in low-and middle-income countries: Evidence from a pilot in three sub-Saharan countries.
The last two decades saw an extensive effort to design, develop and implement integrated and multidimensional healthcare evaluation systems in high-income countries. However, in low- and middle-income countries, few experiences of such systems implementation have been reported in the scientific literature. We developed and piloted an innovative evaluation tool to assess the performance of health services provision for communicable diseases in three sub-Saharan African countries. A total of 42 indicators, 14 per each communicable disease care pathway, were developed. A sub-set of 23 indicators was included in the evaluation process. The communicable diseases care pathways were developed for Tuberculosis, Gastroenteritis, and HIV/AIDS, including indicators grouped in four care phases: prevention (or screening), diagnosis, treatment, and outcome. All indicators were calculated for the period 2017-2019, while performance evaluation was performed for the year 2019. The analysis involved four health districts and their relative hospitals in Ethiopia, Tanzania, and Uganda. Substantial variability was observed over time and across the four different districts. In the Tuberculosis pathway, the majority of indicators scored below the standards and below-average performance was mainly reported for prevention and diagnosis phases. Along the Gastroenteritis pathway, excellent performance was instead evaluated for most indicators and the highest scores were reported in prevention and treatment phases. The HIV/AIDS pathway indicators related to screening and outcome phases were below the average score, while good or excellent performance was registered within the treatment phase. The bottom-up approach and stakeholders' engagement increased local ownership of the process and the likelihood that findings will inform health services performance and quality of care. Despite the intrinsic limitations of data sources, this framework may contribute to promoting good governance, performance evaluation, outcomes measurement and accountability in settings characterised by multiple healthcare service providers.


Antitumor activity of paclitaxel is significantly enhanced by a novel proapoptotic agent in non-small cell lung cancer.
Newer targeted agents are increasingly used in combination chemotherapy regimens with enhanced survival and improved toxicity profile. Taxols, such as paclitaxel, independently potentiate tumor destruction via apoptosis and are used as first line therapy in patients with advanced non-small cell lung cancer (NSCLC). Procaspase-3-activating compound-1 (PAC-1) is a novel proapoptotic agent that directly activates procaspase-3 (PC-3) to caspase-3, leading to apoptosis in human lung adenocarcinoma cells. Hence, we sought to evaluate the antitumor effects of paclitaxel in combination with PAC-1. Human NSCLC cell lines (A-549 and H-322m) were incubated in the presence of PAC-1 and paclitaxel. Tumor cell viability was determined by a tetrazolium-based colorimetric assay (MTT assay). Western blot and flow cytometric analysis were performed to evaluate expression of PC-3 and the proportion of apoptotic cells, respectively. A xenograft murine model of NSCLC was used to study the in vivo antitumor effects of PAC-1. PAC-1 significantly reduced the inhibitory concentration 50% of paclitaxel from 35.3 to 0.33 nM in A-549 and 8.2 to 1.16 nM in H-322m cell lines. Similarly, the apoptotic activity significantly increased to 85.38% and 70.36% in A-549 and H322m, respectively. Significantly enhanced conversion of PC-3 to caspase-3 was observed with PAC-1 paclitaxel combination (P < 0.05). Mice treated with a drug combination demonstrated 60% reduced tumor growth rate compared with those of controls (P < 0.05). PAC-1 significantly enhances the antitumor activity of paclitaxel against NSCLC. The activation of PC-3 and thus the apoptotic pathway is a potential strategy in the treatment of human lung cancer.


Expression of morphogenic genes in mature ovarian and testicular tissues: potential stem-cell niche markers and patterning factors.
Morphogens are developmental regulators that modulate different tissue patterning, proliferation, differentiation, or remodeling processes in embryonic and adult tissues. Morphogens may also evoke specific regulatory programs in stem cells. Some of the morphogens involved in these processes have been characterized, while others remain unidentified. A microarray containing 3,557 salmonid cDNAs was used to compare the transcriptomes of rainbow trout precocious ovary at three different stages during second year (June, August, and October) with a reference (June normal ovary) transcriptome. During this study, we detected morphogen transcript hybridizations to salmonid elements and the study was enlarged to investigate these activities in various developmental stages of both ovary and testis. Genes from diverse development regulator families such as Anterior gradient-2, BMP, Epimorphin, Flightless, Frizzled, Notch, Tiarin, Twisted gastrulation, and Wnt were demonstrated to be expressed in the adult trout gonads. In mice or rats, expression of mammalian bmp-4, epimorphin, flightless, twisted gastrulation, and GW112 transcripts were localized to cell types isolated from the developed ovary and testis. Comparisons of salmonid and mammalian morphogens at the amino acid residue level show high similarities, suggesting functional conservation. This report provides evidence for local regulation by various morphogens and their potential to control distinct programs of gene expression in the gametes and their accessory cells during gametogenesis.


Translational predictive biomarker analysis of the phase 1b sorafenib and bevacizumab study expansion cohort.
Predictive biomarkers are needed to triage patients to the best therapy. We prospectively planned examination of sequential blood, biopsy, and functional imaging with which to confirm the mechanism and to identify potential predictive biomarkers in a phase Ib clinical trial expansion of patients with solid tumors receiving sorafenib/bevacizumab. The maximally tolerated doses of sorafenib at 200 mg twice daily with bevacizumab at 5 mg/kg every other week were given to biopsiable patients. Patients were randomized to receive either sorafenib or bevacizumab monotherapy for the first 28-day cycle with the second drug added with cycle 2. Biopsies, dynamic contrast-enhanced MRI, and fluorodeoxyglucose-proton emission tomography were done pre-therapy and at 2 and 6 weeks (2 weeks into combination therapy). Tumor and serum proteomics, Ras/Raf mutational analysis, and functional imaging results were examined individually and across the dataset to identify potential changes predictive of response to therapy and those that confirm the biochemical drug mechanism(s). Therapy with sorafenib/bevacizumab resulted in clinical benefit in 45% of this mixed solid tumor group. ERK activation and microvessel density were decreased with monotherapy treatment with sorafenib or bevacizumab, respectively; whereas a decreased signal over the group of total AKT, phospho(p)-VEGF receptor2, p-endothelial nitric-oxide synthase, b-RAF, and cleaved poly(ADP-ribose) polymerase was associated with earlier progression of disease. Tumor metabolic activity decreased in those patients with clinical benefits lasting longer than 4 months, and activity increased with progression of disease. Cleavage of caspase 3 and poly(ADP-ribose) polymerase was increased, and Ki67 expression decreased in patients with prolonged clinical benefits, consistent with decreased proliferation and increased apoptosis. The conglomerate analysis, incorporating pharmacodynamic and tumor biochemistry, demonstrated sorafenib/bevacizumab-targeted vascular activity in the tumor. Results suggest potential biomarkers for which changes, as a group, during early therapeutic exposure may predict clinical benefit.


Connections between poultry biting lice and microflora.
Microorganisms were found in about 300 Mallophaga ( Menopon gallinae, Eomenacanthus stramineus , Goniocotes gallinae) and 11 host hens. The majority of isolated bacteria was determined as grampositive cocci. The microflora found on the surface of and inside the Mallophaga as well as in the samples of hen's skin did not exhibit significant qualitative differences. The internal microflora in Mallophaga appeared qualitatively a little poorer than the external. Breeding of bacteria from interior tissues of nymphs of G. gallinae seldom succeeded, although bacteria were found in all microscopical preparations. The results indicate the bacteriostatical effect of an unknown agent in the digestive system of Mallophaga, as well as the presence of microorganisms (probably specific to the insects investigated) which, however, cannot be distinguished by the usual methods.


Letter to the Editor: "Detection of Ribosomal DNA Sequence Polymorphisms in the Protist Plasmodiophora brassicae for the Identification of Geographical Isolates".
In the publication "Detection of Ribosomal DNA Sequence Polymorphisms in the Protist Plasmodiophora brassicae for the Identification of Geographical Isolates", Laila et al.[...].


Dengue vaccine: a valuable asset for the future.
Dengue has emerged as one of the major global public health problems. The disease has broken out of its shell and has spread due to increased international travel and climatic changes. Globally, over 2.5 billion people accounting for >40% of the world's population are at risk from dengue. Since the 1940s, dengue vaccines have been under investigation. A live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue virus (CYD-TDV) has progressed to phase III efficacy studies. Dengue vaccine has been found to be a cost-effective intervention to reduce morbidity and mortality. Current dengue vaccine candidates aim to protect against the 4 dengue serotypes, but the recent discovery of a fifth serotype could complicate vaccine development. In recent years, an urgent need has been felt for a vaccine to prevent the morbidity and mortality from this disease in a cost-effective way.


A novel TRPM6 variant (c.3179T>A) causing familial hypomagnesemia with secondary hypocalcemia.
Familial hypomagnesemia with secondary hypocalcemia (FHSH) is a rare autosomal recessive disorder (OMIM# 602014) characterized by profound hypomagnesemia associated with hypocalcemia. It is caused by mutations in the gene encoding transient receptor potential cation channel member 6 (TRPM6). It usually presents with neurological symptoms in the first months of life. We report a case of a neonate presenting with recurrent seizures and severe hypomagnesemia. The genetic testing revealed a novel variant in the TRPM6 gene. The patient has been treated with high-dose magnesium supplementation, remaining asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to prevent irreversible neurological damage. Loss-of-function mutations of TRPM6 are associated with FHSH. FHSH should be considered in any child with refractory hypocalcemic seizures, especially in cases with serum magnesium levels as low as 0.2 mM. Normocalcemia and relief of clinical symptoms can be assured by administration of high doses of magnesium. Untreated, the disorder may be fatal or may result in irreversible neurological damage.


[Gamma-glutamyltransferase and alkaline phosphatase in the serum and saliva of patients with hepatic tumors and hepatic cirrhosis].
The authors have previously described the presence of gammaglutamyl transferase and alkaline phosphatase in the saliva of healthy individuals and of patients with hepatobiliary and pancreatic diseases. The authors show in this work the values of said enzymes in the blood serum and saliva of 23 cases of liver cirrhosis and 17 patients with liver tumors. Both enzymes increase significantly in the serum of liver tumor patients with respect to the amounts found in liver cirrhosis patients (p less than 0.005). Alkaline phosphatase increased significantly in the saliva of patients with liver cirrhosis (p less than 0.005), where as no differences were found between the two groups of patients with liver cirrhosis (p less than 0.005), where as no differences were found between the two groups of patients for the salivary gamma-glutamyl transferase. The determination of seric alkaline phosphatase and gamma-glutamyl transferase, and of salivary alkaline phosphatase may be useful for the differential diagnosis between liver cirrhosis and liver tumor.


Effects of anandamide administration on components of reward processing during free choice.
Previous research has implicated the positive modulation of anandamide, an endocannabinoid neurotransmitter, on feeding behavior. Anandamide is particularly noteworthy as it acts as an endogenous ligand of the CB1 receptor, the same receptor that is activated by tetrahydrocannabinol, the primary psychoactive component in Cannabis sativa. Cannabis legalization in North America has presented with a need to study endocannabinoid agonists and their effects on behavior. Much has yet to be determined in terms of the role of the endocannabinoid system in decision-making scenarios. The research presented here tested the hypothesis that anandamide would augment motivation and reward processing via appetitive and consummatory measures during an operant, foraging task. A three-box design was used in order to provide the animals with a free choice, exploratory foraging environment. Discrimination, preference, and incentive contrast were analyzed as discrete measures of decision-making in the three-box paradigm. Anandamide administration (1mg/kg) was found to significantly increase motivation for the optimal foraging outcome and alter basic processing of reward information involved in discrimination and relative valuation. The positive effects of anandamide on eating behavior and motivation have implications toward possible treatment modalities for patient populations presenting with disorders of motivation. These findings suggest the need for continued investigation of the endocannabinoid system as a central component of motivated behavior.


Poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles containing chemically conjugated and physically entrapped docetaxel: synthesis, characterization, and the influence of the drug on micelle morphology.
Docetaxel (DTX), a chemotherapeutic agent, was coupled to the hydrophobic block of poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-b-PCL) copolymers synthesized by metal free ring-opening polymerization. Synthesis of the copolymers and the copolymer-drug conjugate (PEG-b-PCL-DTX) were confirmed by (1)H NMR and GPC analyses. The PEG-b-PCL-DTX conjugates had a approximately 1:3 drug/copolymer ratio (w/w) and a low critical micelle concentration in aqueous solution (14 mg/L). Encapsulation of DTX in PEG-b-PCL-DTX micelles resulted in an 1840-fold increase in the aqueous solubility of the drug. Release of physically encapsulated DTX from PEG-b-PCL-DTX micelles was slower than drug release from PEG-b-PCL micelles due to the improved compatibility between DTX and the micelle core. Core-conjugated DTX was released over the course of one week indicating that PEG-b-PCL-DTX micelles have the capacity for sustained drug release in the absence of physically encapsulated drug. Importantly, conjugation of DTX to the core-forming block had a profound effect on the morphology of the copolymer aggregates.


Fluoride varnish application: a new prophylactic method in Albania. Effect on enamel carious lesions in permanent dentition.
The aim of this study is to assess the effects of fluoride varnishes on enamel caries lesions on permanent dentition. 92 children from primary school (Vasil Shanto, Tirana, Albania) aged 11-12 years were divided into varnish (experimental) and control group. The experiment group received the first fluoride varnish application (Fluoridin, Voco) at baseline, the second application after 3 months and the third application at 6 months from baseline, while the children in the control group received no professional fluoride application. Examinations were performed at baseline and after 7 months. We observed a slight increase in caries prevalence in the control group compared with the varnish group at the 7 month interval (P <0.1 for DMFT and P <0.5 for DMFS and DS). When enamel lesions were included the mean of DeMFT, DeMFS, DeS the caries prevalence was significantly lower in the varnish group after 7 months (P <0.001 for DeMFT, DeMFS). Fluoride varnish is an effective mean for arresting early enamel lesions. It is a safe, convenient and well accepted method by patients.


Can Cryopreservation in Assisted Reproductive Technology (ART) Induce Epigenetic Changes to Gametes and Embryos?
Since the birth of Louise Brown in 1978, more than nine million children have been conceived using assisted reproductive technologies (ARTs). While the great majority of children are healthy, there are concerns about the potential epigenetic consequences of gametes and embryo manipulation. In fact, during the preimplantation period, major waves of epigenetic reprogramming occur. Epigenetic reprogramming is susceptible to environmental changes induced by ovarian stimulation, in-vitro fertilization, and embryo culture, as well as cryopreservation procedures. This review summarizes the evidence relating to oocytes and embryo cryopreservation and potential epigenetic regulation. Overall, it appears that the stress induced by vitrification, including osmotic shock, temperature and pH changes, and toxicity of cryoprotectants, might induce epigenetic and transcriptomic changes in oocytes and embryos. It is currently unclear if these changes will have potential consequences for the health of future offspring.


Castration attenuates proteinuria and glomerular injury in hyperlipidemic male Imai rats.
Hyperlipidemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially in males. We investigated the effect of castration on spontaneous proteinuria and progressive renal injury in male Imai ats. Male Imai rats (n = 16) were castrated at 5 weeks of age. Body weight, blood pressure, urinary protein excretion and serum constituents were checked and compared with sham-operated control rats (n = 16) up to 24 weeks. Sham-operated group 1 (n = 5) and castrated group 2 (n = 6) underwent morphological study after 16 weeks of observation and sham-operated group 3 (n = 11) and castrated group 4 (n = 10) were followed for an additional 8 weeks and used for morphological study. Growth rate was significantly stunted in castrated rats as compared with the controls. Castration significantly reduced proteinuria almost throughout the experiment (167 +/- 84 vs. 46 +/- 24 mg/kg/day, p < 0.001, at 8 weeks and 688 +/- 211 vs. 458 +/- 97, p < 0.01, at 20 weeks). The glomerulosclerosis index was significantly higher in sham-operated control rats than in castrated rats (28.8 +/- 18.0 vs. 7.3 +/- 3.1, p < 0.01, at 16 weeks, and 92.1 +/- 35.5 vs. 39.5 +/- 8.9, p < 0.001, at 24 weeks). There were no significant differences in blood pressure, serum cholesterol, plasma renin activity, plasma somatomedin C levels between the two groups. These results raise the possibility that sex hormones may partly contribute to spontaneous proteinuria and progressive renal injury in male Imai rats.


How to join a wave: decision-making processes in shimmering behavior of Giant honeybees (Apis dorsata).
Shimmering is a collective defence behaviour in Giant honeybees (Apis dorsata) whereby individual bees flip their abdomen upwards, producing Mexican wave-like patterns on the nest surface. Bucket bridging has been used to explain the spread of information in a chain of members including three testable concepts: first, linearity assumes that individual "agent bees" that participate in the wave will be affected preferentially from the side of wave origin. The directed-trigger hypothesis addresses the coincidence of the individual property of trigger direction with the collective property of wave direction. Second, continuity describes the transfer of information without being stopped, delayed or re-routed. The active-neighbours hypothesis assumes coincidence between the direction of the majority of shimmering-active neighbours and the trigger direction of the agents. Third, the graduality hypothesis refers to the interaction between an agent and her active neighbours, assuming a proportional relationship in the strength of abdomen flipping of the agent and her previously active neighbours. Shimmering waves provoked by dummy wasps were recorded with high-resolution video cameras. Individual bees were identified by 3D-image analysis, and their strength of abdominal flipping was assessed by pixel-based luminance changes in sequential frames. For each agent, the directedness of wave propagation was based on wave direction, trigger direction, and the direction of the majority of shimmering-active neighbours. The data supported the bucket bridging hypothesis, but only for a small proportion of agents: linearity was confirmed for 2.5%, continuity for 11.3% and graduality for 0.4% of surface bees (but in 2.6% of those agents with high wave-strength levels). The complimentary part of 90% of surface bees did not conform to bucket bridging. This fuzziness is discussed in terms of self-organisation and evolutionary adaptedness in Giant honeybee colonies to respond to rapidly changing threats such as predatory wasps scanning in front of the nest.


Genetic diversity of Sogatella furcifera (Hemiptera: Delphacidae) in China detected by inter-simple sequence repeats.
The white-backed planthopper (WBPH), Sogatella furcifera (Horváth) is a serious pest causing grievous damage to rice plants. In the present study, inter-simple sequence repeats were employed to investigate the genetic diversity of 108 samples from 27 WBPH geographic populations in China. Ten primers were screened out with 147 amplified bands, average percentage of polymorphic bands, polymorphic information content, and marker index were 78.9, 0.456, and 6.753% respectively. The results indicated that genetic diversity was different among populations, but genetic variation was as low as 0.2% among the populations and as high as 99.8% within the same geographic population. Among the examined WBPH populations, genetic distances were weakly correlated to geographic distance, and there was no correlation between genetic identity and elevation. Cluster analysis showed that the 27 WBPH populations studied could be lumped into four clusters, with which the results of principal coordinate analysis (were almost consistent. In conclusion, the molecular genetic data demonstrated that the region consisting of Yunnan, Guizhou, Guangdong, and Guangxi was the first landing area of WBPH in its migrating process from overwintering sites to China.


Psychosis in patients with systemic lupus erythematosus.
Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) are common; however, psychosis per se is bit uncommon. They may be cognitive deficit, lupus headache, psychoses, seizures, peripheral neuropathy, and cerebrovascular events. Psychiatric symptoms in SLE can be functionally independent psychiatric disorders. It can be due to drugs (steroids) used for SLE or secondary to SLE because of its brain involvement, which is termed as neuropsychiatric systemic lupus erythematosus (NPSLE). No single clinical, laboratory, neuropsychological, and imaging test can be used to differentiate NPSLE from non-NPSLE patients with similar neuropsychiatric manifestations. Presently we are discussing about three cases of SLE with psychosis and which had different clinical presentation. The present reports also depict the approach to case differential diagnosis and management of the same.


New data for vitamin D in Australian foods of animal origin: impact on estimates of national adult vitamin D intakes in 1995 and 2011-13.
To assess the potential dietary supply of vitamin D to Australian adults by application of new data for Australian primary foods of animal origin. New published analytical data on the vitamin D contents of Australian primary foods from animal products were obtained and assessed for reliability. Using food consumption data from Australian population dietary surveys for 1995 and 2011-2013, estimates were made of the likely average daily intakes of vitamin D equivalents from these sources by Australian adults. Meats, chicken, fish, eggs and dairy produce may alone have contributed about 4.2 μg vitamin D equivalents per day to average Australian diets of adults >18 years in 1995 and 4.3 μg in 2011-2013. Dietary vitamin D intake in Australia is likely to be higher than previously estimated because new data from improved analytical methods reveal the contributions to vitamin D supply from foods of animal origin. Absence of reliable vitamin D data for milk and milk products, and the gaps in vitamin D data for many commonly consumed seafood, poultry, eggs and processed animal products greatly limit estimation of dietary vitamin D intakes by Australians.


Protamine--antagonist to heparin.
Protamine is used for titration of heparin in vitro for diagnosis of hemorrhagic states and for neutralization of heparin in vivo to terminate heparinization. The protamine equivalent varies with the heparin preparation, conditions of testing and, in vivo, with the amount of heparin present in the circulation. The latter depends on time after administration and the hemodynamic and metabolic state of the patient. Protamine, when injected rapidly, will release histamine and agglutinate platelets. Bleeding (spontaneous hemorrhage) demonstrates a multiple breakdown of hemostatic mechanisms due to surgical stress, drugs, exposure of the blood to foreign surfaces, etc. Simple rules for the amount of protamine required for an individual patient based on clinical judgement will be satisfactory in most cases. When hemostasis is not achieved, it must be appreciated that heparin and protamine are only part of a complex deteriorating situation.


Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity.
Anorexia nervosa (AN) is associated with very low levels of leptin, a cytokine secreted by adipose tissue and known to suppress appetite. Leptin may play a permissive role in onset of puberty and in resumption of gonadal function in conditions of undernutrition. The soluble leptin receptor (sOB-R) is the main leptin binding protein, and the ratio of serum leptin to sOB-R provides a measure of the free leptin index (FLI), which may be a more accurate determinant of leptin function. Determinants of sOB-R and FLI have not been examined in an adolescent population. We examined levels of sOB-R, leptin, and FLI, and body composition and hormonal determinants of these variables in 23 adolescent girls with AN and 21 healthy adolescent girls of comparable maturity prospectively over 1 yr. Measures of insulin resistance and adiponectin were also examined. We determined changes in levels of sOB-R, leptin, and FLI with weight recovery (defined as an increase in body mass index of >/=10%, n = 11), and with resumption of menstrual cycles (n = 13). Girls with AN had significantly higher levels of sOB-R (P = 0.0008) and significantly lower levels of leptin and FLI (P < 0.0001 for both) than healthy controls, and levels of FLI were reduced more than levels of leptin in girls with AN compared with controls. An inverse correlation was noted between levels of leptin and sOB-R for the group as a whole (r = -0.64, P < 0.0001) but not in girls with AN considered alone. The most important predictor of levels of sOB-R was cortisol in the group as a whole (r = 0.61, P < 0.0001) and in girls with AN considered alone (r = 0.66, P = 0.0008). Other independent predictors of sOB-R levels for the entire group were percent body fat (r = -0.44, P = 0.003) and levels of IGF-I (r = -0.37, P = 0.01). The most important predictors of leptin and FLI were body mass index and percent body fat. An inverse relationship was noted between measures of insulin resistance and sOB-R levels, whereas a positive association was noted between these measures and leptin and FLI. Adiponectin values did not differ in girls with AN compared with healthy controls and did not correlate with sOB-R, leptin, or FLI. Weight recovery resulted in significant decreases in levels of the sOB-R (24.7 +/- 1.7 to 17.6 +/- 1.2 U/ml, P = 0.004), and increases in levels of leptin (4.4 +/- 1.0 to 13.7 +/- 2.9 microg/liter, P = 0.02). Resumption of menstrual function, but not weight recovery alone, was associated with significant increases in FLI (0.19 +/- 0.04 to 0.50 +/- 0.09 microg/U x 10(-3), P = 0.02).We demonstrate an increase in levels of sOB-R and a decrease in the FLI in adolescent girls with AN, and also demonstrate that cortisol is the most important predictor of levels of sOB-R in this condition. Levels of leptin and FLI, conversely, are primarily predicted by body composition. Weight recovery is associated with a decrease in sOB-R and an increase in leptin. Resumption of menses is associated with significant increases in the FLI, suggesting that free leptin may be an important determinant of menstrual recovery.


Bidirectional plasticity of GABAergic tonic inhibition in hippocampal somatostatin- and parvalbumin-containing interneurons.
GABAA receptors present in extrasynaptic areas mediate tonic inhibition in hippocampal neurons regulating the performance of neural networks. In this study, we investigated the effect of NMDA-induced plasticity on tonic inhibition in somatostatin- and parvalbumin-containing interneurons. Using pharmacological methods and transgenic mice (SST-Cre/PV-Cre x Ai14), we induced the plasticity of GABAergic transmission in somatostatin- and parvalbumin-containing interneurons by a brief (3 min) application of NMDA. In the whole-cell patch-clamp configuration, we measured tonic currents enhanced by specific agonists (etomidate or gaboxadol). Furthermore, in both the control and NMDA-treated groups, we examined to what extent these changes depend on the regulation of distinct subtypes of GABAA receptors. Tonic conductance in the somatostatin-containing (SST+) interneurons is enhanced after NMDA application, and the observed effect is associated with an increased content of α5-containing GABAARs. Both fast-spiking and non-fast-spiking parvalbumin-positive (PV+) cells showed a reduction of tonic inhibition after plasticity induction. This effect was accompanied in both PV+ interneuron types by a strongly reduced proportion of δ-subunit-containing GABAARs and a relatively small increase in currents mediated by α5-containing GABAARs. Both somatostatin- and parvalbumin-containing interneurons show cell type-dependent and opposite sign plasticity of tonic inhibition. The underlying mechanisms depend on the cell-specific balance of plastic changes in the contents of α5 and δ subunit-containing GABAARs.


Moringa oleifera and Musa sapientum ameliorated 7,12-Dimethylbenz[a]anthracene-induced upregulations of Ki67 and multidrug resistance 1 genes in rats.
Moringa oleifera (MO) and Musa sapientum (MS) are plants of ethnomedicinal importance. We evaluated the effects of MOF6 (extracted from MO leaves) and MSF1 (extracted from MS suckers) on immunomodulations of Ki67 (proliferation biomarker) and multidrug resistance 1 (MDR1) genes in the liver of rats in 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hepatotoxicity and mutagenesis to determine their antiproliferation, anti-drug resistance, and anticancer potentials. Forty-five adult male rats were randomly divided into nine groups (n = 5). Groups 1 and 2 received physiological saline and 15 mg/kg bodyweight of DMBA, respectively. Groups 3 and 4 received 15 mg/kg bodyweight DMBA and were treated with 15 and 30 mg/kg bodyweight of MOF6, respectively. Group 5 received 15 mg/kg bodyweight DMBA and was treated with 10 mg/kg bodyweight of MSF1. Group 6 received 15 mg/kg bodyweight DMBA and was treated with 3.35 mg/kg bodyweight of doxorubicin and intravenous injection of 0.5 ml/200 g of cisplatin. Groups 7-9 received only 15 and 30 mg/kg bodyweight of MOF6 and 10 mg/kg bodyweight of MSF1, respectively. DMBA, doxorubicin, and extracts doses were administered orally. The duration of our experimental procedure was 8 weeks. Consequently, liver histopathology (hematoxylin and eosin technique) and enzyme-linked immunosorbent assay homogenates' concentrations of Ki67 and MDR1 were evaluated. Computed data were statistically analyzed (P ≤ 0.05). Results showed normal histoarchitectures of the liver in all groups. Statistical analyses showed significant (P ≤ 0.05) and non-significant decreased concentrations (P ≥ 0.05) of Ki67 and MDR1 in Groups 3-9 compared with Group 2. Therefore, MOF6 and MSF1 ameliorated DMBA-induced hepatotoxicity, abnormal proliferation, and drug resistance. MOF6 and MSF1 possess antiproliferation, anti-drug resistance, and anticancer potentials.