Comparison of animal studies between interstitial magnetic resonance lymphography and radiocolloid SPECT/CT lymphoscintigraphy in the head and neck region.
To comparatively assess two techniques, radiocolloid SPECT/CT lymphoscintigraphy and interstitial MR lymphography using SPIO and gadoxetate disodium, in animal models. We used twenty one 8-week-old male nude mice of strain BALB/c Slc-nu/nu, weighing 23-27 g. The 4.7-T MRI equipment was used to detect the SNs. T2*WI of gradient-echo sequences was acquired sequentially up to 24 h after administering SPIO, ferucarbotran. T1WI was acquired sequentially up to 80 min after administering gadoxetate disodium. (99m)Tc-phytate SPECT/CT lymphoscintigraphy was taken at 30 min after the injection to detect the SNs using animal-dedicated whole-body SPECT/CT hybrid scanner. The injection was submucosally performed in the right tongue margin of each mouse. Reading performances concerning SN visualization and its quality on interstitial MR lymphogram and SPECT/CT lymphoscintigram were performed by 3 radiologists. The SN intensities were 0.43 for the right, 0.61 for the left at 30 min after ferucarbotran injection, with gradual decrease in intensity, and 1.43 for the right, 1.33 for the left at 10 min after gadoxetate disodium injection with a fast decrease in intensity. The base value of 1.0 was at pre-examination. The mean numbers of lymph nodes visualized were 4.00 nodes for on SPECT/CT lymphoscintigram and 2.0 for interstitial MR lymphogram. There was a statistically significant difference in the mean scores between SPECT/CT lymphoscintigraphy and interstitial MR lymphography (two factor mixed design with repeated measures on one factor: p < 0.0002). In our comparative study using mice, the results of radiocolloid SPECT/CT lymphoscintigraphy were superior to those of interstitial MR lymphography, while both SPIO and gadoxetate disodium have a potential of being employed for sentinel node navigation surgery by interstitial MR lymphography in the head and neck region.


Ruxolitinib ameliorated coxsackievirus B3-induced acute viral myocarditis by suppressing the JAK-STAT pathway.
Accumulating evidences have demonstrated that overwhelming inflammation occurs in the process of Coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVM). No specific therapy is available. More than an effective Janus-associated kinase (JAK) inhibiter, ruxolitinib exerts a critical role in the inflammatory diseases. In this study, we investigated the potential effect of ruxolitinib on CVB3-induced acute viral myocarditis. In vivo, BALB/c mice were intraperitoneally injected of CVB3, treated of a successive gavage of ruxolitinib for seven days, and subjected to a series of analysis. In vitro, primary bone marrow-derived macrophages (BMDMs) and cardiac fibroblasts were isolated, cultured, treated, harvested and finally detected. In vivo, acute viral myocarditis was successfully induced by the injection of CVB3 characterized by impaired cardiac function, predominant infiltration of inflammatory cells, necroptosis of myocardium, great increase of cardiac troponin I (cTnI) and cytokine levels, replication of CVB3, and excessive activation of JAK-STAT pathways. Oral administration of ruxolitinib suppressed the activation of JAK-STAT pathway in a dosage-dependent way, lessened the infiltration of inflammatory cells and necroptosis of myocardium, reduced the levels of cTnI and cytokines, and finally alleviated CVB3-induced cardiac dysfunction, with the reduced production of type I interferon and no promising effect on the replication of CVB3. In vitro, the treatment of ruxolitinib inhibited the activation of JAK-STAT pathway and increase of multiple cytokines mRNA levels in BMDMs and had no protective effect against CVB3 replication in cardiac fibroblasts. Our study suggested that ruxolitinib ameliorated CVB3-induced AVM by inhibiting the activation of JAK-STAT pathway, infiltration of inflammatory cells and necroptosis of myocardium, which may provide a novel strategy for AVM therapy.


Eotaxin expression by epithelial cells and plasma cells in chronic asthma.
Chemoattractants such as eotaxin are believed to play an important role in the recruitment of eosinophils into the airways in asthma. We investigated expression of eotaxin in the airway wall in a model of chronic human asthma, in which systemically sensitized mice were exposed to low mass concentrations of aerosolized antigen for 6 weeks. In these animals, the number of intraepithelial eosinophils in the airways was significantly increased 3 hours after exposure and declined by 24 hours. In parallel, immunoreactivity for eotaxin was strikingly up-regulated in airway epithelial cells and in inflammatory cells in the lamina propria. The latter were identified as plasma cells by double immunofluorescent labeling. Increased expression of eotaxin by epithelial cells and plasma cells was also demonstrated in a case of fatal human asthma. In contrast, sensitized mice that received a single exposure to a high mass concentration of aerosolized antigen exhibited delayed eosinophil recruitment, which did not correlate with eotaxin expression. Furthermore, in sensitized chronically exposed interleukin-13-deficient mice there was virtually no recruitment of eosinophils into the airways, although eotaxin expression was greater than or equal to that in wild-type mice. These results indicate that there are striking differences between acute and chronic exposure models in the time course of eotaxin expression and eosinophil recruitment. Although high eotaxin levels alone are not sufficient to cause recruitment of eosinophils into the airways, recurrent exposure may generate or up-regulate additional signals required for eosinophil chemotaxis.


Superior temporal gyrus volumes in pediatric generalized anxiety disorder.
The essential symptoms of generalized anxiety disorder (GAD) are intrusive worry about everyday life circumstances and social competence, and associated autonomic hyperarousal. The amygdala, a brain region involved in fear and fear-related behaviors in animals, and its projections to the superior temporal gyrus (STG), thalamus, and to the prefrontal cortex are thought to comprise the neural basis of our abilities to interpret social behaviors. Larger amygdala volumes were previously reported in pediatric GAD; however, the brain regions involved in social intelligence were not examined in this pilot study. Magnetic resonance imaging (MRI) was used to measure the STG, thalamus, and prefrontal volumes in 13 medically healthy child and adolescent subjects with generalized anxiety disorder (GAD) and 98 comparison subjects, who were at low familial risk for mood and psychotic disorders. Groups were similar in age, gender, height, weight, handedness, socioeconomic status, and full-scale IQ. The total, white matter, and gray matter STG volumes were significantly larger in GAD subjects compared with control subjects. Thalamus and prefrontal lobe volumes did not differ between groups. Findings of significant side-by-diagnosis interactions for STG and STG white matter volumes suggest that there is a more pronounced right > left asymmetry in total and STG white matter volumes in pediatric GAD subjects compared with control subjects. A significant correlation between the STG white matter percent asymmetry index with the child report of the Screen for Child Anxiety Related Emotional Disorders Scale was seen. These data agree with previous work implicating posterior right-hemispheric regions in anxiety disorders and may suggest developmental alterations in pediatric GAD.


Mechanisms of lysis by activated cytotoxic cells expressing perforin and granzyme-B genes and the protein TIA-1 in muscle biopsies of myositis.
Polymyositis (PM) and cermatomyositis (DM) are inflammatory muscle diseases of autoimmune origin. A chronic mononuclear cell infiltrate is always present around PM and DM muscle damage. In PM, the predominant cells are activated cytotoxic cells, natural killer, and CD8+ T lymphocytes. Cytotoxic cells can kill the target cells via 2 mechanisms. Both pathways induce target cell death by releasing the molecules (granule exocytosis) perforin (PF), which attacks the target cell membrane and causes cell death by necrosis, and TIA-1 protein and granzyme-B (GZB), possibly responsible for apoptosis. We studied the mechanisms of lysis in muscle biopsies of myositis. We used a panel of monoclonal antibodies to determine the phenotypes of reactive lymphocyte subsets, in situ hybridization to study the expression of PF and GZB genes, and immunohistochemistry to evaluate TIA-1 protein production in muscle biopsies from 14 patients with myositis (11 PM/3 DM). Results were compared to those obtained from muscle biopsies of 12 control patients with muscle weakness, including patients with muscle dystrophy and vasculitis, but without myositis. Abundant CD8+ cells, especially in endomysial sites in PM, formed the predominant phenotype. The predominant mononuclear cells observed in DM were CD4+ T cells and CD22+ B lymphocytes, in perivascular sites. The GZB and PF genes and the TIA-1 protein were expressed simultaneously in muscle samples from patients with myositis. GZB, PF, and TIA-1 positive cells were predominantly located in endomysial sites of PM, in the nonnecrotic muscle fibers. In DM, these positive cells were rare. In myositis, especially PM, cytotoxic cells may cause muscle damage and muscle cell necrosis and/or apoptosis by releasing several proteins (PF, GZB, and TIA-1 proteins) responsible for the lysis of these stimulating target cells. Some drugs (prednisone and cyclosporine) inhibit the release of GZB and PF. Their efficacy may be due in part to this inhibitory effect.


Isolation, physical, structural characterization and in vitro prebiotic activity of a galactomannan extracted from endosperm splits of Chinese Sesbania cannabina seeds.
The purpose of this study was to identify and determine the physical and structural characterization of the water-soluble galactomannan extracted from endosperm splits of Chinese S. cannabina seeds. The Sesbania galactomannan (SP) was extracted and purified using a novel method with a high yield (40.3 ± 7.2%). The molecular structure of SP was determined by monosaccharide composition, FTIR and NMR spectroscopy. The structural data showed that SP was galactomannan which composed by a β-(1/4)-linked mannose backbone with galactopyranosyl residues attached through α-(1/6) linkages. The constant mannose/galactose (M/G) ratio and average molecular weight (Mw) of SP was 1.6:1 and 2.16 × 105 g/mol, respectively. The physical results revealed that SP had many branches on the backbone and existed as a random coil state in aqueous solution. SP was a good biopolymer which had smooth and clearer surface with homogeneous composition, and had some degree of crystallinity and prebiotic activity. As a consequence, SP could be a potential prebiotic and was expected to be suitable for applications in food, pharmaceutical, biomedical or cosmetic industries as a promising new biomaterial.


Current trends in treatment of thoracic outlet syndrome.
Even though the response from this survey was decent, it is not large enough to draw statistical conclusions. The data therefore are being presented from an interest standpoint and do reflect the current trends of treatment for TOS. Physicians who do not treat TOS do not have an accurate view of this disorder, its treatment, or the success rate of treatment. Surgeons who deal with this problem have encouraging results. Conservative treatment seems effective in approximately half of the patients afflicted with this condition. Surgery carries what seems to be a long-term cure rate of 65% and partial relief in 20% of patients. Significant complications are rare.


Cortical atrophy distinguishes idiopathic normal-pressure hydrocephalus from progressive supranuclear palsy: A machine learning approach.
Progressive supranuclear palsy (PSP) and idiopathic normal pressure hydrocephalus (iNPH) share several clinical and radiological features, making the differential diagnosis challenging. In this study, we aimed to differentiate between these two diseases using a machine learning approach based on cortical thickness and volumetric data. Twenty-three iNPH patients, 50 PSP patients and 55 control subjects were enrolled. All participants underwent a brain 3T-MRI, and cortical thickness and volumes were extracted using Freesurfer 6 on T1-weighted images and compared among groups. Finally, the performance of a machine learning approach with random forest using the extracted cortical features was investigated to differentiate between iNPH and PSP patients. iNPH patients showed cortical thinning and volume loss in the frontal lobe, temporal lobe and cingulate cortex, and thickening in the superior parietal gyrus in comparison with controls and PSP patients. PSP patients only showed mild thickness and volume reduction in the frontal lobe, compared to control subjects. Random Forest algorithm distinguished iNPH patients from controls with AUC of 0.96 and from PSP patients with AUC of 0.95, while a lower performance (AUC 0.76) was reached in distinguishing PSP from controls. This study demonstrated a more severe and widespread cortical involvement in iNPH than in PSP, possibly due to the marked lateral ventricular enlargement which characterizes iNPH. A machine learning model using thickness and volumetric data led to accurate differentiation between iNPH and PSP patients, which may help clinicians in the differential diagnosis and in the selection of patients for shunt procedures.


Current concepts and techniques in percutaneous vertebroplasty.
Percutaneous vertebroplasty is a safe and effective alternative for the treatment of many different types of painful vertebral lesions, including osteoporotic compression fractures,hemangiomas, or malignancy-induced pathologic vertebral fractures. Medical therapy often is limited to pain control and immobilization. Because surgery is contraindicated frequently in patients who have osteoporotic compression fractures, and because patients who have widespread metastatic disease often are not surgical candidates, vertebroplasty may be the only practical option. In experienced hands and with appropriately selected patients, percutaneous vertebroplasty is a safe, inexpensive, and highly efficacious procedure; however, because of the potential for devastating complications, all efforts must be made to optimize patient safety.


Do smoke-free policies in work and public places increase smoking in private venues?
To evaluate the correlation between the implementation of tobacco control policies, particularly smoke-free bans at work and in public places, and smoking prevalence in private venues in the 27 countries of the European Union. Ecological study with the country as the unit of analysis. Data analysis of tobacco control activities in European countries in 2007 as compiled in the Tobacco Control Scale (TCS) and information on the level of smoking permissiveness in houses and cars from the Special Eurobarometer on Tobacco conducted in 2009. Spearman rank-correlation coefficients (rsp) and their 95% confidence intervals (CIs) were calculated. The correlation between the TCS score and the prevalence of smoking in private venues (houses and cars) where smoking inside was always allowed was close to zero. A similar lack of association was observed between the TCS score of specific bans at work and in public places and smoking rules inside houses and cars. There was a non-significant direct correlation between the TCS score and the prevalence of smoke-free houses (rsp=0.21, 95% CI -0.19 to 0.55) and a non-significant inverse correlation with smoking allowed in certain rooms inside the house (rsp=-0.34; 95% CI -0.64 to 0.05). Smoke-free legislation in workplaces and public places is not correlated with increased smoking prevalence in private venues (houses and cars) at an ecological level.


HIV-Related Stigma, Shame, and Avoidant Coping: Risk Factors for Internalizing Symptoms Among Youth Living with HIV?
Youth living with HIV (YLH) are at elevated risk of internalizing symptoms, although there is substantial individual variability in adjustment. We examined perceived HIV-related stigma, shame-proneness, and avoidant coping as risk factors of internalizing symptoms among YLH. Participants (N = 88; ages 12-24) completed self-report measures of these potential risk factors and three domains of internalizing symptoms (depressive, anxiety, and PTSD) during a regularly scheduled HIV clinic visit. Hierarchical regressions were conducted for each internalizing symptoms domain, examining the effects of age, gender, and maternal education (step 1), HIV-related stigma (step 2), shame- and guilt-proneness (step 3), and avoidant coping (step 4). HIV-related stigma, shame-proneness, and avoidant coping were each correlated with greater depressive, anxiety, and PTSD symptoms. Specificity was observed in that shame-proneness, but not guilt-proneness, was associated with greater internalizing symptoms. In multivariable analyses, HIV-related stigma and shame-proneness were each related to greater depressive and PTSD symptoms. Controlling for the effects of HIV-related stigma and shame-proneness, avoidant coping was associated with PTSD symptoms. The current findings highlight the potential importance of HIV-related stigma, shame, and avoidant coping on the adjustment of YLH, as interventions addressing these risk factors could lead to decreased internalizing symptoms among YLH.


Automated 2-Dimensional Measurement of Vestibular Schwannoma: Validity and Accuracy of an Artificial Intelligence Algorithm.
Validation of automated 2-dimensional (2D) diameter measurements of vestibular schwannomas on magnetic resonance imaging (MRI). Retrospective validation study using 2 data sets containing MRIs of vestibular schwannoma patients. University Hospital in The Netherlands. Two data sets were used, 1 containing 1 scan per patient (n = 134) and the other containing at least 3 consecutive MRIs of 51 patients, all with contrast-enhanced T1 or high-resolution T2 sequences. 2D measurements of the maximal extrameatal diameters in the axial plane were automatically derived from a 3D-convolutional neural network compared to manual measurements by 2 human observers. Intra- and interobserver variabilities were calculated using the intraclass correlation coefficient (ICC), agreement on tumor progression using Cohen's kappa. The human intra- and interobserver variability showed a high correlation (ICC: 0.98-0.99) and limits of agreement of 1.7 to 2.1 mm. Comparing the automated to human measurements resulted in ICC of 0.98 (95% confidence interval [CI]: 0.974; 0.987) and 0.97 (95% CI: 0.968; 0.984), with limits of agreement of 2.2 and 2.1 mm for diameters parallel and perpendicular to the posterior side of the temporal bone, respectively. There was satisfactory agreement on tumor progression between automated measurements and human observers (Cohen's κ = 0.77), better than the agreement between the human observers (Cohen's κ = 0.74). Automated 2D diameter measurements and growth detection of vestibular schwannomas are at least as accurate as human 2D measurements. In clinical practice, measurements of the maximal extrameatal tumor (2D) diameters of vestibular schwannomas provide important complementary information to total tumor volume (3D) measurements. Combining both in an automated measurement algorithm facilitates clinical adoption.


Human-induced arsenic pollution modeling in surface waters - An integrated approach using machine learning algorithms and environmental factors.
In recent years, assessment of sediment contamination by heavy metals, i.e., arsenic, has attracted the interest of scientists worldwide. The present study provides a new methodology to better understand the factors influencing surface water vulnerability to arsenic pollution by two advanced machine learning algorithms including boosted regression trees (BRT) and random forest (RF). Based on the sediment quality guidelines (Effects range low) polluted and non-polluted arsenic sediment samples were defined with concentrations >8 ppm and <8 ppm, respectively. Different conditioning factors such as topographical, lithology, erosion, hydrological, and anthropogenic factors were acquired to model surface waters' vulnerability to arsenic. We trained and validated the models using 70 and 30% of both polluted and non-polluted samples, respectively, and generated surface vulnerability maps. To verify the maps to arsenic pollution, the receiver operating characteristics (ROC) curve was implemented. The results approved the acceptable performance of the RF and BRT algorithms with an area under ROC values of 85% and 75.6%, respectively. Further, the findings showed higher importance of precipitation, slope aspect, distance from residential areas, and slope length in arsenic pollution in the modeling process. Erosion, lithology, and land use maps were introduced as the least important factors. The introduced methodology can be used to define the most vulnerable areas to arsenic pollution in advance and implement proper remediation actions to reduce the damages.


Nanoparticle transport and deposition in a heterogeneous human lung airway tree: An efficient one path model for CFD simulations.
Understanding nano-particle inhalation in human lung airways helps targeted drug delivery for treating lung diseases. A wide range of numerical models have been developed to analyse nano-particle transport and deposition (TD) in different parts of airways. However, a precise understanding of nano-particle TD in large-scale airways is still unavailable in the literature. This study developed an efficient one-path numerical model for simulating nano-particle TD in large-scale lung airway models. This first-ever one-path numerical approach simulates airflow and nano-particle TD in generations 0-11 of the human lung, accounting for 93% of the whole airway length. The one-path model enables the simulation of particle TD in many generations of airways with an affordable time. The particle TD of 5 nm, 10 nm and 20 nm particles is simulated at inhalation flow rates for two different physical activities: resting and moderate activity. It is found that particle deposition efficiency of 5 nm particles is 28.94% higher than 20 nm particles because of the higher dispersion capacity. It is further proved that the diffusion mechanism dominates the particle TD in generations 0-11. The deposition efficiency decreases with the increase of generation number irrespective of the flow rate and particle size. The effects of the particle size and flow rate on the escaping rate of each generation are opposite to the corresponding effects on the deposition rate. The quantified deposition and escaping rates at generations 0-11 provide valuable guidelines for drug delivery in human lungs.


Biomedical applications of selective metal complexes of indole, benzimidazole, benzothiazole and benzoxazole: A review (From 2015 to 2022).
Indole, benzoxazole benzothiazole and benzimidazole are excellent classes of organic heterocyclic compounds. These compounds show significant application in pharmacy, industries, dyes, medicine, polymers and food packages. These compounds also form metal complexes with copper, zinc, cadmium, nickel, cobalt, platinum, gold, palladium chromium, silver, iron, and other metals that have shown to be significant applications. Recently, researchers have attracted enormous attention toward heterocyclic compounds such as indole, benzimidazole, benzothiazole, benzoxazole, and their complexes due to their excellent medicinal applications such as anti-ulcerogenic, anti-cancer, antihypertensive, antifungal, anti-inflammatory, antitubercular, antiparasitic, anti-obesity, antimalarial, antiglycation, antiviral potency, antineuropathic, analgesic antioxidant, antihistaminic, and antibacterial potentials. In this article, we summarize the medicinal applications of these compounds as well as their metal complexes. We hope this article will help researchers in designing and synthesizing novel and potent compounds with significant applications in various fields.


Knowledge-based approaches to drug discovery for rare diseases.
The conventional drug discovery pipeline has proven to be unsustainable for rare diseases. Herein, we discuss recent advances in biomedical knowledge mining applied to discovering therapeutics for rare diseases. We summarize current chemogenomics data of relevance to rare diseases and provide a perspective on the effectiveness of machine learning (ML) and biomedical knowledge graph mining in rare disease drug discovery. We illustrate the power of these methodologies using a chordoma case study. We expect that a broader application of knowledge graph mining and artificial intelligence (AI) approaches will expedite the discovery of viable drug candidates against both rare and common diseases.


Pseudoperipheral palsy: a case of subcortical infarction imitating peripheral neuropathy.
Vascular damage in the central hand knob area can mimic peripheral motor nerve deficits. We describe the case of a woman presenting with apparent peripheral neuropathy. Brain magnetic resonance imaging and computed tomography angiography revealed an infarct in the precentral hand knob area, with significant stenosis in the right proximal middle cerebral artery trunk. Subsequent 3-Tesla magnetic resonance imaging of the brain suggested cerebral angiitis. The patient experienced improved hand function following combined glucocorticoid and cyclophosphamide treatment. Vascular damage in the hand knob area should be considered when evaluating peripheral motor nerve deficits in the presence of normal nerve conduction velocities. The diagnosis of cerebral angiitis remains a major challenge for clinicians.


PCDD and PCDF depletion in milk from dairy cows according to the herd metabolic scenario.
High level of PCDD+PCDF contamination in bulk milk (9.7 pg WHO-TE g(-1) fat) from 1604 Holstein Fresian lactacting cows was observed just four weeks after the beginning of their exposure to a feed supplement contaminated at 10.4 ng WHO-TE kg(-1) dry matter. In-farm produced hay and silage showed levels not exceeding 0.2 ng WHO-TE kg(-1) dry matter. After the supplement withdrawal, it was possible to monitor the depletion phase for a following 75-day period in milk, until the levels dropped well below 3.0 pg WHO-TE g(-1) fat, the EU regulatory Maximum Residue Level for PCDD+PCDF. During this phase, the half-life was calculated as 17+/-3 days, on WHO-TEQ basis. The full availability of farm data on both cow nutrition and milk production allowed the calculation of the carry-over rate (COR) (PCDD+PCDF milk excretion vs. feed), which was 46% at the end of the exposure. This COR value is justified from the main TE contribution of Penta-CDD and -CDF congeners (63%), and the half-life is among the shortest of all those described in the literature both for experimental and naturally-exposed dairy cows. A fugacity-based model predicts a bulk milk contamination of 5 pg WHO-TE g(-1) fat, compared to the 10 pg WHO-TE g(-1) fat level observed. Such findings are discussed in light of the lactation and metabolic status of the herd for which the transition period, characterised by a negative metabolic energy balance and a consequent adipose tissue mobilization, could play a relevant role.


Opposite physiological and pathological mTORC1-mediated roles of the CB1 receptor in regulating renal tubular function.
Activation of the cannabinoid-1 receptor (CB1R) and the mammalian target of rapamycin complex 1 (mTORC1) in the renal proximal tubular cells (RPTCs) contributes to the development of diabetic kidney disease (DKD). However, the CB1R/mTORC1 signaling axis in the kidney has not been described yet. We show here that hyperglycemia-induced endocannabinoid/CB1R stimulation increased mTORC1 activity, enhancing the transcription of the facilitative glucose transporter 2 (GLUT2) and leading to the development of DKD in mice; this effect was ameliorated by specific RPTCs ablation of GLUT2. Conversely, CB1R maintained the normal activity of mTORC1 by preventing the cellular excess of amino acids during normoglycemia. Our findings highlight a novel molecular mechanism by which the activation of mTORC1 in RPTCs is tightly controlled by CB1R, either by enhancing the reabsorption of glucose and inducing kidney dysfunction in diabetes or by preventing amino acid uptake and maintaining normal kidney function in healthy conditions.


On the discriminability of hROIs, human visually selected regions-of-interest.
Many studies have tried to answer an important question: is it possible to predict human visually selected regions-of-interest (hROIs)? hROIs are defined as the loci of eye fixations and they can be analyzed by their spatial distribution over the visual stimulus and their temporal ordering. We used a simplified set of geometrical spatial kernels and linear filter models as bottom-up conspicuity operators that produce algorithmically selected regions-of-interest, aROIs. As a direct approach we measured the ability of these aROIs to predict human scanpaths. The level of prediction is measured by two similarity indices: Sp for spatial similarity and Ss for temporal ordering similarity. At the same time we assessed the discriminability of the hROI loci, in terms of conspicuity, with respect to non-selected (not of interest) regions of an image. We prove that this discrimination is possible and further correlates with the positional similarity index Sp. Other human scanpath experimental conditions are presented in parsing diagrams and discussed. A general top-down/bottom-up scanpath model is finally formulated.


Phosphorylation of nuclear receptors: Novelty and therapeutic implications.
Nuclear receptors (NR) collectively regulate several biological functions in various organs. While NRs can be characterized by activation of the transcription of their signature genes, they also have other diverse roles. Although most NRs are directly activated by ligand binding, which induces cascades of events leading to gene transcription, some NRs are also phosphorylated. Despite extensive investigations, primarily focusing on unique phosphorylation of amino acid residues in different NRs, the role of phosphorylation in the biological activity of NRs in vivo has not been firmly established. Recent studies on the phosphorylation of conserved phosphorylation motifs within the DNA- and ligand-binding domains confirmed has indicated the physiologically relevance of NR phosphorylation. This review focuses on estrogen and androgen receptors, and highlights the concept of phosphorylation as a drug target.


Photoelastic stress analysis of external versus internal implant-abutment connections.
Common complications of implant restorations are abutment screw loosening and screw fracture. The geometry of the implant-abutment connection may affect stresses generated from loading, and these stresses may have a role in screw loosening or fracture. This study compared the load transfer characteristics of a complete-arch restoration supported by 4 implants with external and internal implant-abutment connections. Loads were applied to the prostheses in 3 positions. Two-dimensional photoelastic models were used to simulate bone. Two types of implants (ReplaceSelect Internal-Interface Tapered Implants and ReplaceSelect External-Interface Tapered Implants) were placed in the photoelastic models. Complete-arch metal frameworks were fabricated on the abutments. Artificial teeth were arranged on the framework, and the prosthesis was screwed onto the abutments. The specimens were analyzed at 2 levels (implant-abutment level and apical to the implant level) with 3 loading conditions (4-point load; 2-point anterior load; and 2-point lateral load). The numbers of fringe orders were recorded and compared. With the 4-point load, no stress differences occurred between the external-implant abutment connection and internal-implant abutment connection at the connection level and at the apical level. With the 2-point anterior load, the internal-implant abutment connection resulted in lower stresses at the connection level both in the loaded and non-loaded areas. With the 2-point lateral load, the internal-implant abutment connection resulted in lower stresses at the connection level at the non-loaded area. When loaded off-center, the internal-implant abutment connection produced less stress when compared with the external-implant abutment connection.


H3K27M-mutant diffuse midline glioma presenting as synchronous lesions involving pineal and suprasellar region: A case report and literature review.
The differential diagnoses for multifocal lesions with pineal and suprasellar involvement in a young adult include germ cell tumour and intracranial metastasis. Other differentials include atypical teratoid/rhabdoid tumour and pineoblastoma. We present the first known case of multicentric H3K27M mutant diffuse midline glioma, which is typically defined by its diffuse nature, midline location, and H3K27M mutation. A young Chinese female presented subacutely with giddiness, right abducens nerve palsy and unsteady gait. Magnetic resonance imaging (MRI) of the brain with contrast revealed a moderately sized pineal region tumour, extending into the third ventricle, associated with hydrocephalus. There were two other synchronous lesions noted in the suprasellar and left occipital region. Serum and cerebrospinal fluid tumour markers, along with a computed tomography scan of her thorax and abdomen and were unremarkable. She underwent an endoscopic third ventriculostomy and biopsy of pineal and suprasellar lesions. Histology demonstrated a poor prognosis variant multifocal glioblastoma multiforme that was IDH wildtype, H3K27M positive, and MGMT unmethylated. MRI of the whole spine did not reveal any drop metastasis. The patient subsequently underwent adjuvant chemotherapy and radiotherapy after she was deemed to be unsuitable for surgical resection. Although rare, multicentric H3K27M mutant diffuse midline glioma should be included in the list of differential diagnoses for multifocal enhancing lesions with involvement of the pineal and suprasellar regions, especially if the lesions demonstrate imaging features atypical for more common diagnosis such as germ cell tumours.


Preparation of a silicon-iron amendment from acid-extracted copper tailings for remediating multi-metal-contaminated soils.
Industrial by-products provide materials for remediation measures. In this study, a silicon-iron amendment was prepared from residue originating from acid-extracted copper (Cu) tailings based on thermal activation at temperatures ranging from 550 °C to 1150 °C for 30 min with the use of additives (CaO, Na2CO3, NaOH). The remediation performance of the amendment was evaluated through soil incubation and greenhouse pot experiments with vetiver (Vetiveria zizanioides). The results showed that the highest levels of soluble Si (6.11% of the total Si) and Fe (2.3% of the total Fe) in the amendment were achieved with thermal activation at 1150 °C for 30 min using an optimal ratio between residue and additives (residue: CaO: Na2CO3: NaOH = 1: 0.4: 0.4: 0.2). Heavy metal release indicated that the amendment could be safely used for soil remediation. The incubation experiments showed that the DTPA-extractable Cd, Cr and Pb in contaminated soils decreased with increasing amendment rate, which was not observed for As. The amendment-induced decrease in the Cd, Cr and Pb availability in contaminated soils could be explained by pH-change induced immobilization, Fe-induced chemisorption, Si-induced co-precipitation, and Ca-induced ion exchange. Correlation analysis suggested that there were significant negative correlations between DTPA-extractable Cd, Cr and Pb and the pH, Fe, Si, and Ca in soil pore water and soil. The most suitable amendment rate was determined to be 1% by balancing the efficacy and wise utilization of the amendment. The pot experiment demonstrated that the amendment promoted the vetiver growth and stimulated the accumulation of Cd and Cr in the roots. The amendment was proved to be promising for the phytostabilization of Cd, Cr and Pb in contaminated soils. Further investigations are required to determine whether the amendment is a tool for the long-term remediation of multi-metal-contaminated soils at the field scale.


[Culicidae insect fauna from rural zone in Amazonas State with incidence of sylvatic yellow fever].
After the occurrence of 14 sylvatic yellow fever cases in 10 cities in the State of Amazonas during 1996, an investigation into the presence of sylvatic yellow fever vectors was carried out. The material of larvae and adult insects was collected around residences and canopy trees within forests, using a light trap (CDC) and human bait. A total of 424 insects was collected. Thirty seven species were identified, some of which were sylvatic yellow fever vectors: Haemagogus janthinomys, Ha. leucocelaenus, Aedes fulvus.


Laparoscopic local resection based on sentinel node evaluation for early gastric cancer: a preliminary report.
We previously reported that lymphatic mapping using isosulfan blue can be used to identify sentinel nodes (SNs). This study was undertaken to evaluate the feasibility of using the SN technique in treating early gastric cancer and to explore its usefulness for minimal invasive surgery. Twenty-three patients with early gastric cancer who underwent SN biopsy were retrospectively evaluated. Based on SN evaluation, individualized surgery was performed in five patients with T1N0M0 gastric cancer. When pathological examination of frozen sections revealed metastasis in SNs, we performed a standard D2 gastrectomy. Laparoscopic local resection was applied when the SN biopsy was negative. Our results showed that the success rate with SN biopsy in early gastric cancer was 100%, as were the accuracy, sensitivity, and specificity. All five patients with early gastric cancer had SNs negative for metastases both by frozen section and by postoperative pathology. Thus, all these patients underwent laparoscopic local resection without extended lymphadenectomy. We conclude that SN biopsy is a useful tool to individualize the operative procedure, and laparoscopic local resection can be safely performed using SN guidance in selected patients with early gastric cancer.


Decoys 'R' Us: a database of incorrect conformations to improve protein structure prediction.
The development of an energy or scoring function for protein structure prediction is greatly enhanced by testing the function on a set of computer-generated conformations (decoys) to determine whether it can readily distinguish native-like conformations from nonnative ones. We have created "Decoys 'R' Us," a database containing many such sets of conformations, to provide a resource that allows scoring functions to be improved.


Relationship between gallbladder contraction and progesterone receptors in patients with gallstones.
Stasis of bile within the gallbladder has long been suspected of having an important role in the pathogenesis of gallstone disease. We postulated that the female preponderance of gallstone disease might partly be related to the effects of progesterone, a known smooth muscle relaxant, on specific receptors in the gallbladder wall, leading to stasis of bile. A total of 42 patients with gallstone disease and 28 control subjects underwent radionuclide scan imaging and their gallbladder ejection fractions were calculated in response to intravenous infusion of cholecystokinin octapeptide. Patients then underwent cholecystectomy and a piece of gallbladder fundus was assayed for the presence of progesterone receptors. Receptors were present in 60 percent of patients. As a group, gallstone patients had a decreased ejection fraction compared with control subjects. The presence of progesterone receptors in the gallbladder wall was associated with a decreased percentage of ejection compared with both healthy control subjects and patients whose gallbladders were receptor-negative. We conclude that progesterone receptors are present in the gallbladder wall of gallstone patients and that their presence correlates with impaired gallbladder emptying.


Generation of a host cell line containing a MAR-rich landing pad for site-specific integration and expression of transgenes.
In recent years, targeted gene integration (TI) has been introduced as a strategy for the generation of recombinant mammalian cell lines for the production of biotherapeutics. Besides reducing the immense heterogeneity within a pool of recombinant transfectants, TI also aims at shortening the duration of the current cell line development process. Here we describe the generation of a host cell line carrying Matrix-Attachment Region (MAR)-rich landing pads (LPs), which allow for the simultaneous and site-specific integration of multiple genes of interest (GOIs). We show that several copies of each chicken lysozyme 5'MAR-based LP containing either BxB1 wild type or mutated recombination sites, integrated at one random chromosomal locus of the host cell genome. We further demonstrate that these LP-containing host cell lines can be used for the site-specific integration of several GOIs and thus, generation of transgene-expressing stable recombinant clones. Transgene expression was shown by site-specific integration of heavy and light chain genes coding for a monospecific antibody (msAb) as well as for a bi-specific antibody (bsAb). The genetic stability of the herein described LP-based recombinant clones expressing msAb or bsAb was demonstrated by cultivating the recombinant clones and measuring antibody titers over 85 generations. We conclude that the host cell containing multiple copies of MAR-rich landing pads can be successfully used for stable expression of one or several GOIs.


Awareness about and willingness to use long-acting injectable pre-exposure prophylaxis (LAI-PrEP) among people who use drugs.
In the Bangkok Tenofovir Study of oral pre-exposure prophylaxis (PrEP; TDF/FTC), adherence was poor. Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) for HIV prevention may help overcome adherence challenges and is currently being tested in clinical trials, but not in people who use drugs (PWUD), an important key population that remains highly vulnerable to HIV. Since PWUD are not currently included in trials of LAI-PrEP, we sought to examine awareness about LAI-PrEP and factors associated with willingness to use LAI-PrEP in this understudied population. Participants included 234 HIV-negative people with opioid use disorder and self-reported HIV-risk behaviors recruited from Connecticut's largest addiction treatment program. We analyzed data from a standardized assessment using audio computer-assisted self-interview (ACASI) to assess the independent factors associated with willingness to use LAI-PrEP. While only 25.6% of participants were aware of LAI-PrEP (67.1% had heard of oral PrEP), after being given a description of it, 73.5% were willing to use it, if it were available. Participants were most commonly concerned about long-term side effects (76.9%) of LAI-PrEP. Independent correlates of willingness to use LAI-PrEP were female sex (aOR = 2.181, p = 0.018), recent visit to healthcare provider (aOR = 2.9, p = 0.023), high perceived risk of acquiring HIV (aOR = 3.3, p = 0.007), and having previously taken oral PrEP (aOR = 3.284, p = 0.017). Findings suggest that PWUD are highly interested in PrEP, especially in LAI-PrEP formulations. Our results indicate the potential for LAI-PrEP, as an alternative to oral daily PrEP, to be implemented into existing evidence-based HIV-based HIV prevention efforts that target high-risk PWUD.


Physical properties and Tris inhibition of an insect trehalase and a thermodynamic approach to the nature of its active site.
The midgut from Rhynchosciara americana larvae display a trehalase (alpha,alpha'-trehalose glucohydrolase, EC 126.96.36.199) which is soluble with a molecular weight of 122 000 and pI 4.6. The optimum pH of the enzyme is 6.0, its apparent Km for trehalose is 0.67 mM and its energy of activation is 16.7 kcal/mol. Sulfhydryl reagents do not inhibit the trehalase. The results suggest the existence of two carboxyl groups in the active site, one of which has a very high (8.3) pK. The increase of the pK values of the essential groups of the free enzyme in the presence of increasing concentrations of dioxane supports the hypothesis that these groups are carboxyls. The purified enzyme hydrolyzes only alpha,alpha'-trehalose and it is competitively inhibited by several compounds.


Standalone effects of focus mode and social comparison functions on problematic smartphone use among adolescents.
Problematic smartphone use (PSU) has been reported, particularly among adolescents. Digital interventions may be offered for preventing and reducing PSU. This study evaluated the effects of two smartphone-based interventions among adolescents. Grounded in nudge theory, the focus function allowed users to hide smartphone applications (apps) for a selected length of time, while the feedback function provided a social comparison of the smartphone use of the user and other users. In total, 305 adolescents with Android smartphones were randomly allocated to the focus-function group, feedback-function group or control group. Participants used their smartphones as usual during the two-week baseline period, followed by the one-week period of intervention app instillation and four-week period of intervention use. The primary outcome was self-reported PSU after the intervention period. The secondary outcomes were self-reported smartphone use time during weekdays and app-recorded smartphone use time and frequency. The Group × Time interaction effects showed reduced self-reported PSU in the focus-function and feedback-function groups, Cohen's d = -0.32, 95% CI [-0.63, -0.008], Cohen's d = -0.36, 95% CI [-0.66, -0.06], respectively. The app-recorded smartphone use frequency was also reduced in the focus-function and feedback-function groups, Cohen's d = -0.16, 95% CI [-0.07, -0.25], Cohen's d = -0.32, 95% CI [-0.23, -0.41], respectively. The findings suggest that both utilizing time-outs from nonessential apps and engaging in social comparison lower PSU and smartphone use frequency with small effect sizes. These functions may be noncoercive interventions for preventing and reducing PSU.


Brain abscess due to Candida glabrata in an immunocompetent patient. A case report with update and literature review.
Candida spp. brain abscess is scare. Clinical presentation is unspecific. Diagnosis requires mycological culture of a puncture or biopsy specimen. Therapeutic management is based on prolonged course of azole or liposomal amphotericin B. We reported the case of Candida glabrata brain abscess in a 27 year-old female patient, with no past history and not secondary to candidemia. The fungus was isolated from a puncture of abscess with complete resection. The outcome was favorable under antifungal treatment by voriconazole.


Postoperative pneumonia causes the loss of skeletal muscle volume and poor prognosis in patients undergoing esophagectomy for esophageal cancer.
This retrospective study investigated the effect of postoperative pneumonia on the loss of skeletal muscle volume after esophagectomy for esophageal cancer. A total of 123 patients who had undergone esophagectomy for esophageal cancer and had (30 patients) or did not have (93 patients) postoperative pneumonia were included in the analysis. The association of clinicopathological characteristics with loss of skeletal muscle volume and long-term survival were evaluated in patients with or without postoperative pneumonia. There were no differences in the psoas muscle volume index (PI), lymphocyte count, serum albumin level, or prognostic nutritional index between the two groups both preoperatively and at 6 months after surgery. The decrease in PI at 6 months after surgery was significant in patients with postoperative pneumonia (- 9.9 ± 2.5%) but not in those without pneumonia (- 2.6 ± 1.6%). Patients with postoperative pneumonia had a significantly increased frequency of asymptomatic pneumonia at 6 months after surgery compared with those who did not have postoperative pneumonia (36.7% vs. 19.4%). Overall survival was significantly poorer in patients with postoperative pneumonia than in those without pneumonia (p < 0.05). Postoperative pneumonia was associated with the loss of skeletal muscle volume and asymptomatic pneumonia within 6 months of surgery as well as poorer overall survival.


Effects of mutations in the WD40 domain of α-COP on its interaction with the COPI coatomer in Saccharomyces cerevisiae.
Replacement of glycine 227 in the fifth WD40 motif of α-COP/Ret1p/Soo1p by charged or aromatic amino acids is responsible for the temperature-dependent osmo-sensitivity of Saccharomyces cerevisiae, while truncations of WD40 motifs exerted a reduction in cell growth rate and impairment in assembly of cell-wall associated proteins such as enolase and Gas1p. Yeast two-hybrid analysis revealed that the ret1-1/soo1-1 mutation of α-COP abolished the interaction with β- and ɛ-COP, respectively, and that the interaction between α-COP and β-COP relied on the WD40 domain of α-COP. Furthermore, although the WD40 domain is dispensable for interaction of α-COP with ɛ-COP, structural alterations in the WD40 domain could impair the interaction.


Structural characterization of a dimerization interface in the CD28 transmembrane domain.
CD28 has a crucial role in regulating immune responses by enhancing T cell activation and differentiation. Recent studies have shown that the transmembrane helix (TMH) of CD28 mediates receptor assembly and activity, but a structural characterization of TMH is still lacking. Here, we determined the dimeric helix-helix packing of CD28-TMH using nuclear magnetic resonance (NMR) technology. Unexpectedly, wild-type CD28-TMH alone forms stable tetramers in lipid bicelles instead of dimers. The NMR structure of the CD28-TMH C165F mutant reveals that a GxxxA motif, which is highly conserved in many dimeric assemblies, is located at the dimerization interface. Mutating G160 and A164 can disrupt the transmembrane helix assembly and reduces CD28 enhancement in cells. In contrast, a previously proposed YxxxxT motif does not affect the dimerization of full-length CD28, but it does affect CD28 activity. These results imply that the transmembrane domain of CD28 regulates the signaling transduction in a complicated manner.


Prevalence, types and treatment of bradycardia in obstructive sleep apnea - A systematic review and meta-analysis.
The association of obstructive sleep apnea (OSA) with bradycardia is not well-characterized, which may confer significant morbidity and mortality if left untreated. We sought to clarify the prevalence of comorbid OSA and bradycardia, and the effect of continuous positive airway pressure (CPAP) therapy on bradycardia outcomes. We systematically searched four electronic databases (PubMed, Embase, Cochrane Library, Scopus) for randomized or observational studies reporting the co-prevalence of sleep apnea and bradycardia or evaluated the use of CPAP on the incidence of bradycardias. We used random-effects models in all meta-analyses and evaluated heterogeneity using I2. We included 34 articles from 7204 records, comprising 4852 patients. Among patients with OSA, the pooled prevalence of daytime and nocturnal bradycardia were 25% (95% CI: 18.6 to 32.7) and 69.8% (95% CI: 41.7 to 88.2) respectively. Among patients with bradycardia, the pooled prevalence of OSA was 56.8% (95% CI: 21.5 to 86.3). CPAP treatment, compared to those without, did not significantly reduce the risk of daytime (two randomized trials; RR: 0.50; 95% CI: 0.11 to 2.21) or nocturnal bradycardia (one randomized-controlled trial and one cohort study; RR: 0.76; 95% CI: 0.48 to 1.20). This meta-analysis demonstrates a high comorbid disease burden between OSA and bradycardia. Future research should explore the treatment effect of CPAP on bradycardia incidence, as compared to placebo.


Regional differences of standardised mortality rates for ischemic heart diseases in the Slovak Republic for the period 1996-2013 in the context of income inequality.
The aim of paper is to analyse the development of standardised mortality rates for ischemic heart diseases in relation to the income inequality in the regions of Slovakia. This paper assesses different types of income indicators, such as mean equivalised net income per household, Gini coefficient, unemployment rate, at risk of poverty threshold (60 % of national median), S80/S20 and their effect on mortality. Using data from the Slovak mortality database 1996-2013, the method of direct standardisation was applied to eliminate variances resulted from differences in age structures of the population across regions and over time. To examine the relationships between income indicators and standardised mortality rates, we used the tools of descriptive statistics and methods of correlation and regression analysis. At first, we show that Slovakia has the worst values of standardised mortality rates for ischemic heart diseases in EU countries. Secondly, mortality rates are significantly higher for males compared with females. Thirdly, mortality rates are improving from Eastern Slovakia to Western Slovakia; additionally, high differences in the results of variability are seen among Slovak regions. Finally, the unemployment rate, the poverty rate and equivalent disposable income were statistically significant income indicators. Main contribution of paper is to demonstrate regional differences between mortality and income inequality, and to point out the long-term unsatisfactory health outcomes.


Acute renal failure caused by renal infiltration by hematolymphoid malignancy.
Renal involvement by a malignant infiltrative process is often suspected in patients with bilaterally enlarged kidneys and concurrent malignancies. Acute renal failure (ARF) can rarely occur secondary to such an infiltrative process. We present 2 cases in which ARF is attributable to malignant hematolymphoid infiltration. The first case involves diffuse, bilateral involvement of the kidneys by non-Hodgkin's lymphoma. The patient's renal function improved dramatically after the initiation of chemotherapy, clearly linking the development of ARF to the malignant process. In the second case, infiltration of the kidneys by plasma cell leukemia resulted in dialysis dependence. To our knowledge, this represents the first reported case of ARF attributable to documented renal infiltration by plasma cell leukemia. A review of the potential causes of renal failure in hematolymphoid malignancy, focusing on the direct impact of the infiltrative process and on the spectrum of renal disease in plasma cell dyscrasia, is presented.


[Diagnosis of malignant non-Hodgkin lymphoma on the basis of the Kiel-classification].
In short form a survey is given concerning the division of the malignant non-Hodgkin-lymphoma according to the classification of Kiel. The subdivision in stages and a proposal for a comprehensive clinical and laboratory investigation programme complete the compilation concerning the diagnostics of the malignant non-Hodgkin-lymphomas.


EPA Consensus Project Paper: The Influence of Prosthetic Factors on the Incidence of Peri-implantitis Around Single Implants: A Systematic Review.
The purpose of this systematic review was to evaluate how prosthetic factors affect the incidence of peri-implantitis in patients treated with single implant restorations. Electronic and manual search of two indexed databases up to April 2023 were conducted, to identify clinical studies reporting on the effect of different prosthetic factors on the incidence of peri-implantitis around single implants and with at least 1 year follow-up. The risk of bias was assessed with the Joanna Briggs Institute critical appraisal checklist, the ROB2 and the ROBINS-I tools. From the 521 screened articles, 11 studies (1 randomized controlled trial, 7 cross-sectional, 3 retrospective) met the inclusion criteria. Based on three studies, emergence angle⟩30°, convex emergence profile and external connection are associated with a higher incidence of peri-implantitis. Nine studies pertaining to the effect of retention type on the prevalence of peri-implantitis reported conflicting results. Six out of eleven included studies presented some risk of bias. There is insufficient evidence regarding the influence of prosthetic factors on the incidence of peri-implantitis around single implants. Further studies are needed to draw definitive conclusions on this issue.


Sepsis in Immunocompromised Host and a Hematologic Complication.
A 43-year-old Puerto Rican man with a kidney transplant presented to the ED with 2 weeks of flu-like symptoms, nausea, and vomiting. He had plasma exchange therapy 2 months before for acute transplant rejection and has been tolerating a heightened immunosuppressive regimen. CT scans characterized opacities as possibly early tree-in-bud opacities (Fig 1A). Patient remained stable throughout hospital stay with an unremarkable workup and was discharged with doxycycline for nonspecific pneumonia.


The forensic deaths caused by pesticide poisoning between the years 2006 and 2009 in Izmir, Turkey.
Pesticide poisoning is still a significant health problem in Turkey. We conducted a retrospective study of autopsy cases at Izmir Branch of the Council of Forensic Medicine to describe the characteristics of deaths caused by pesticide poisoning between 2006 and 2009. The distributions of the cases according to gender and age were as follows: men 74.1% (n = 40, mean [±SD] age, 44.7 ± 14.1), women 25.9% (n = 14, mean [±SD] age, 39.2 ± 18.9). The majority of pesticide-poisoning deaths were suicides (n = 43, 80%) followed by accidents (n = 4, 8%) and homicide (n = 1, 2%). The manner of death could not be determined in six cases (11%). Suicides mostly occurred at home (n = 26, 63%) (p < 0.05). Methomyl was the most frequent pesticide (n = 9, 17%) among the all cases. This study reported that most of the pesticides found in poisoning cases were highly hazardous types. Combined efforts of medical professionals and law makers are needed for enacting strict laws against highly hazardous pesticides.


4-Amino-5-(4-bromo-benzo-yl)-3-(benzo[d]thia-zol-2-yl)-2-[(2',3',4',6'-tetra-O-acetyl-β-d-galacto-pyran-osyl-)sulfanyl]-thio-phene.
In the title compound, C32H29BrN2O10S3, the benzo-thia-zole and thio-phene ring systems subtend an inter-planar angle of 7.43 (12)°. The NH2 group forms intra-molecular hydrogen bonds to Nthia-zole and Ocarbon-yl. The Sgalactose-Cthio-phene bond is short [1.759 (2) Å]. The mol-ecules are connected to form ribbons parallel to the b axis by two 'weak' hydrogen bonds and a short Namino⋯Sgalactose contact.


New multiresidue analytical method dedicated to trace level measurement of brominated flame retardants in human biological matrices.
A new method has been developed for the multi-residue measurement of the main brominated flame retardants (alpha- and gamma-hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBP-A) and polybrominated diphenyl ethers including decabromodiphenyl ether) in human biological matrices (serum, adipose tissue and breast milk). The proposed sample preparation procedure focused on reduced solvent and consumable consumption and associated procedural contamination, as well as reduced sample size. This protocol was fully validated and was proved to be suitable for identification of brominated flame retardant residues at ultra-trace level, as attested by preliminary results on real samples.


The role of methyl-CpG binding protein 2 in liver fibrosis.
Liver injury is induced by various insults such as alcohol abuse, if insults persist, may result in the formation of liver fibrosis. Hepatic stellate cell (HSC) activation and transdifferentiation into hepatic myofibroblast, accompanied with potent pro-inflammatory and pro-fibrogenic activities and the down-regulation of anti-inflammatory anti-fibrogenic in gene expression in coordination with epigenetic modifications at the level of the chromatin structure, are pivotal events in liver fibrogenesis. In this review we focus on the role of the methyl-CpG binding protein 2 (MeCP2) transcriptional regulation of different target genes and the interaction MeCP2 with microRNAs (miRNAs) during liver fibrosis. In addition, we address different signaling pathways interacted with MeCP2 regulated HSC activation. Such approaches provide valuable insights into the potential targets of liver fibrosis, and are useful pointers for the development of future therapeutic strategies.


Thanatophoric dwarfism. Two case reports and survey of the literature.
Thanatophoric dwarfism is a severe form of short-limbed dwarfism in which cardiorespiratory failure uniformly results in death in the neonatal period. Its radiographic features include markedly flattened vertebral bodies with a typical U-shaped deformity, a flat squat pelvis, and short, bowed extremities with flaring and irregularity of the metaphyses. These characteristic features distinguish this entity from the two other most commonly confused congenital short-limbed forms of dwarism--achondroplasia and achondrogenesis. The distinctions are discussed in the text.


Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets.
Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2, BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.


Highly Efficient Electrochemical Nitrate Reduction to Ammonia in Strong Acid Conditions with Fe2 M-Trinuclear-Cluster Metal-Organic Frameworks.
Nitrate-containing industrial wastewater poses a serious threat to the global food security and public health safety. As compared to the traditional microbial denitrification, electrocatalytic nitrate reduction shows better sustainability with ultrahigh energy efficiency and the production of high-value ammonia (NH3 ). However, nitrate-containing wastewater from most industrial processes, such as mining, metallurgy, and petrochemical engineering, is generally acidic, which contradicts the typical neutral/alkaline working conditions for both denitrifying bacteria and the state-of-the-art inorganic electrocatalysts, leading to the demand for pre-neutralization and the problematic hydrogen evaluation reaction (HER) competition and catalyst dissolution. Here, we report a series of Fe2 M (M=Fe, Co, Ni, Zn) trinuclear cluster metal-organic frameworks (MOFs) that enable the highly efficient electrocatalytic nitrate reduction to ammonium under strong acidic conditions with excellent stability. In pH=1 electrolyte, the Fe2 Co-MOF demonstrates the NH3 yield rate of 20653.5 μg h-1 mg-1 site with 90.55 % NH3 -Faradaic efficiency (FE), 98.5 % NH3 -selectivity and up to 75 hr of electrocatalytic stability. Additionally, successful nitrate reduction in high-acidic conditions directly produce the ammonium sulfate as nitrogen fertilizer, avoiding the subsequent aqueous ammonia extraction and preventing the ammonia spillage loss. This series of cluster-based MOF structures provide new insights into the design principles of high-performance nitrate reduction catalysts under environmentally-relevant wastewater conditions.


Soy-derived phytoalexins: mechanism of in vivo biological effectiveness in spite of their low bioavailability.
The well-demonstrated bioefficacy of phytochemicals in spite of their paradoxically low bioavailability has long puzzled scientists. Glyceollins, a family of soy-derived phytoalexins, have been reported to exert a variety of biological effects in vitro and in vivo systems in spite of poor systemic bioavailability after oral administration, suggesting that secondary messengers generated in gastrointestinal tract would transfer signals to target organs and tissues to manifest any effect. This review focuses on the potential mechanisms of how the poorly bioavailable glyceollins could still exert in vivo biological effects.


A new perspective towards in-situ cold plasma remediation of polluted sites: Direct generation of micro-discharges within contaminated medium.
The in-situ treatment of solid wastes might be regarded as cost-effective and minimum environmental fingerprint solution, particularly with reference to contaminated soils, offering several benefits compared to ex-situ methods. In this short communication it is described the study of a lab-scale coaxial dielectric barrier discharge (DBD) plasma reactor simulating the in-situ soil remediation conditions for the first time. In this conceptual design, the contaminated medium is handled as a part of the electrical discharge, while the plasma discharges are produced directly within the contaminated porous medium under treatment, thus scattering reactive species directly in the air contained inside its interconnected pores. The in-situ cold plasma setup was used to remediate bauxite samples highly contaminated by oil sludge contaminants. A very high TOC removal (∼70%) was achieved after 30 min of plasma treatment time with the corresponding energy consumption being 0.53 kWh kg-1. Carbon balance analysis of the exhaust gases revealed that 61% of the removed pollutant was converted to CO2, 19% was decomposed to CO, and 20% was emitted as VOCs. The scale-up of the presented in-situ cold plasma approach could lead to a promising alternative for the fast, cost-effective, and green in-situ remediation of granular porous, heavily contaminated with hydrocarbons contaminated sites.


[Evaluation of the analytical performance characteristics of NT-proBNP immunoassay on dimension RxL-HM (Dade Behring)].
Plasma B-type natriuretic peptide (BNP) and N terminal prohormone (NT-proBNP) are promising markers for the diagnosis, prognosis and follow up of heart failure. Elevated levels have been associated with adverse long-term outcome in patients with acute coronary syndromes. The analytical performance of a new automated NT-proBNP assay on Dimension-HM system (Dade Behring) and comparison with the results obtained with the Roche Diagnostics NT-proBNP assays using the Elecsys instrument have been evaluated according to the Valtec protocol. Total imprecision (CV) was below 9% for NT-proBNP concentrations between 100 and 10,000 pg/mL using quality control samples and pooled patients' plasma. Analytical sensitivity was found 9.8 pg/mL the day of calibration and 10.1 pg/mL ten days later. Dilution linearity showed overall recovery between 98.4 and 104.7%. No hook effect was observed for NT-proBNP concentration up to 96,000 pg/mL. The interference of turbidity was below 4%. Hemoglobin interfered negatively with assay upper 240 micromol/L but less than 10%. A precision profile demonstrated a total imprecision of 10% CV at a NT-proBNP concentration of 70 pg/mL and 20% at 30 pg/mL. Dimension results highly correlated (r = 0.99) with Roche Elecsys NT-proBNP.


Association among type D personality, non-motor symptoms, and quality of life in Parkinson's disease: A cross-sectional study.
Patients with type D personality are vulnerable to stress, show poor prognosis in disease, and experience low quality of life. The aims of this study were to identify the associations among type D personality, non-motor symptoms, and quality of life in patients with Parkinson's disease (PD). Data were collected between May 28 and August 6, 2015 from a convenience sample of 196 PD patients. About 20% of participants were classified into the type D personality group. This group experienced statistically significantly higher non-motor symptoms and lower quality of life compared to the non-type D personality group. Based on stepwise multiple regression analysis, the most significant factor affecting quality of life was non-motor symptoms, followed by type D personality, disease severity, and duration of disease. Understanding the clinical implications of type D personality might be beneficial in the management of non-motor symptoms and quality of life in PD patients.


Anterior Cruciate Ligament Patellar Tendon Autograft Fixation at 0° Versus 30° Results in Improved Activity Scores and a Greater Proportion of Patients Achieving the Minimal Clinical Important Difference For Knee Injury and Osteoarthritis Outcome Score Pain: A Randomized Controlled Trial.
The aim of the current study was to determine the effect of the knee flexion angle (KFA) during tibial anterior cruciate ligament (ACL) graft fixation on patient-reported outcomes, graft stability, extension loss, and reoperation after anatomic single-bundle ACL reconstruction. All 169 included patients (mean age 28.5 years, 65% male) were treated with anatomic single-bundle ACL reconstruction using patellar tendon autograft and were randomized to tibial fixation of the ACL graft at either 0° (n = 85) or 30° (n = 84). The primary outcome was the Knee Injury and Osteoarthritis Outcome Score (KOOS) 2 years after surgery. Secondary outcomes were the Marx Activity Scale (MAS), the rate of reoperation, and physical examination findings at 1 year, including KT-1000 and side-to-side differences in knee extension. The follow-up rate was 82% (n = 139) for the primary outcome. Graft failure rate at 2 years was 1% (n = 2, 1 per group). ACL tibial graft fixation at 0° or 30° did not have a significant effect on KOOS scores at 2 years after ACLR. Patients whose graft was fixed at a knee flexion angle of 0° had greater scores on the MAS (mean 9.6 95% confidence interval [CI] 8.5 to 10.6, versus 8.0, 95% CI 6.9 to 9.1; P = .04), and a greater proportion achieved the minimal clinical important difference (MCID) for the KOOS pain subdomain (94% versus 81%; P = .04). There was no significant difference in knee extension loss, KT-1000 measurements, or reoperation between the 2 groups. In the setting of anatomic single-bundle ACLR using patellar tendon autograft and anteromedial portal femoral drilling, there was no difference in KOOS scores between patients fixed at 0° and 30°. Patient fixed in full extension did demonstrate higher activity scores at 2 years after surgery and a greater likelihood of achieving the MCID for KOOS pain. II, prospective randomized trial.


Inhibitory effect of infliximab on orthodontic tooth movement in male rats.
This study aimed to investigate the effect of infliximab on orthodontic tooth movement in rats. Sixty male Sprague-Dawley rats were randomly divided into two groups: saline group and infliximab group. The two groups of rats received weekly intraperitoneally injection of saline or infliximab (5 mg/kg), respectively. After four weeks of injection, five rats in each group were euthanized and orthodontic appliances were placed in the other twenty-five rats each. On days 1, 3, 7, 14 and 21, five rats from each group were euthanised. Maxillae of all the rats were collected and examined by micro-computed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, and immunohistochemical staining of tumour necrosis factor (TNF)-α, receptor activator of nuclear factor κB ligand (RANKL), receptor activator of nuclear factor κB (RANK), and osteoprotegerin (OPG). All data were analysed with Mann-Whitney test. Infliximab inhibited orthodontic tooth movement and decreased osteoclastogenesis on the compression side during orthodontic tooth movement. The elevated TNF-α level, induced by orthodontic force, was decreased by infliximab. Furthermore, infliximab reduced the expression of RANKL and RANK, while increased the expression of OPG on the compression side. Infliximab inhibits orthodontic tooth movement by reducing levels of TNF-α, RANKL, and RANK, while increasing level of OPG, and decreasing osteoclastogenesis on the compression side of periodontium.


Characterization of a rare clinical isolate of A. spinulosporus following a central nervous system infection.
A rarely reported clinical specimen of Aspergillus spinulosporus was isolated from an immunocompetent 22-month-old boy who was suffering from central nervous system aspergillosis and meningitis. The patient had no comorbidity, organ transplantation, or other surgical operations that lead to invasive aspergillosis. A. spinulosporus is mostly a soil borne strain, and only three invasive aspergillosis cases involving this strain have been reported. We isolated this strain from cerebrospinal fluid, cultured it successfully on PDA medium, and named it BJCH M5. We performed a complete genomic and phenotypic analysis, evolutionary relationship, secondary metabolites analysis, identification of virulence factor, and pairwise synteny analysis. We sequenced the complete 31.6 MB genome of A. spinulosporus, including the eight chromosomes and mitochondria. 11,356 protein-coding genes were predicted. BJCHM 5 has a high sequence identity with ten virulent factors of Aspergillus fumigatus. It also encodes two unique BGCs (Biosynthetic gene clusters) which are involved in human infection. Pairwise synteny analysis demonstrated that this strain has chromosome arrangement differences from A. nidulans. In conclusion, we isolated a specimen of the rarely reported pathogen A. spinulosporus and performed a complete genome assembly and functional characteristic analysis.


Occurrence of extensive spherical amyloid deposits in a prolactin-secreting pituitary macroadenoma: a radiologic-pathologic correlation.
Pituitary adenomas are the most common tumors of the sellar region, but the occurrence of spherical amyloid deposits in a pituitary adenoma is rare. We describe the clinical features, radiologic characteristics, and pathologic findings of 45-year-old man who presented with galactorrhea, hypogonadism, and hyperprolactinemia who had a pituitary adenoma with extensive spherical amyloid deposits. Approximately 30 cases have been reported, almost exclusively in patients with prolactinomas. Treatment with dopaminergic agonists will result in the expected reduction in prolactin levels; however, in most cases, macroadenomas with spherical amyloid deposits fail to decrease in size. The source of the amyloid deposits in prolactinomas is not clearly defined but may be due to abnormal processing of prolactin or its prohormone. These adenomas with spherical amyloid have a characteristic appearance on magnetic resonance imaging with low or heterogeneous intensity on T1 and low intensity on T2-weighted images. Following infusion of gadolinium, there is enhancement of the periphery but not most of the tumor mass. These magnetic resonance imaging characteristics are different than those of typical pituitary adenomas. These differences should alert clinicians to the possibility of extensive spherical amyloid deposits in a prolactin-secreting pituitary adenoma, which may have important clinical implications. In this report, we correlate the radiologic finds with the pathology and compared them with other sellar and parasellar lesions.


Clinical Effectiveness of Endovascular Therapy for Total Occlusion of the Subclavian Arteries: A Study of 67 Patients.
Endovascular therapy is a feasible option for total occlusion of the subclavian artery. The purpose of this study was to evaluate the effectiveness of stenting therapy by comparing it with that of surgical treatment in patients with total subclavian artery occlusion. Between May 2007 and October 2013, 52 stents were placed in 67 patients who underwent endovascular therapy for the treatment of total atherosclerosis subclavian artery occlusion. During the same period, 21 patients underwent bypass surgery. All patients were followed at 3, 6, and 12 months after treatment and annually thereafter. Technical success was achieved in 77.6% patients in the endovascular group, while clinical success was achieved in 74.6%. Technical failure was noted in 15 patients, while the symptoms failed to resolve in 2. The rate of primary patency was 98.2% at 12 months, 94.3% at 24 months, and 92.1% at 3 years. Significant recurrent obstruction developed in 5 patients. No complications were observed in 5 patients with right side occlusion in whom embolic protection filters were used. Meanwhile, the technical success rate was 100% in the surgery group. One patient developed a major ischemic stroke during surgery (4.8%). The rate of primary patency was 100% at 12 months, 96.3% at 24 months, and 93.1% at 3 years. When performed by skilled surgeons, percutaneous revascularization with primary stenting is a safe and effective therapy for symptomatic total occlusion of the proximal subclavian artery. However, we recommend the use of embolic protection devices during the treatment of right side occlusions. Otherwise, surgery may be the best choice.


Genotoxicity studies with an ethanolic extract of Kalanchoe pinnata leaves.
Kalanchoe pinnata is a medicinal plant, used mainly in African, Brazilian, and Indian traditional medicine for the treatment of several human disorders. Whole leaf extracts, crude juice of the leaves, and aqueous and organic extracts of the leaves are used. Over the last decade, ethanolic extracts have become the most popular form of Kalanchoe medicinal preparation. In this study, an ethanolic extract of this plant leaf was tested in a battery of standard regulatory genetic toxicology tests. This extract did not induce reverse mutations in the Salmonella/microsome assay but induces a weak genotoxic response in the mouse lymphoma assay and the in vivo micronucleus assay in mice. Our results indicate that this material may cause DNA damage, and its use should be restricted.


Surgical therapy for biliary dyskinesia: a meta-analysis and review of the literature.
Although biliary dyskinesia is treated commonly with cholecystectomy, the supporting literature is limited. A review and meta-analysis of the literature were performed to assess the efficacy of surgical therapy for biliary dyskinesia. A MEDLINE search for the period 1965 to 2003, using the search strings "biliary," "acalculous," "dyskinesia," "cholecystitis," "cholecystectomy," and "therapy" returned 187 articles. Inclusion criteria required a study design that placed patients with biliary dyskinesia into one of two treatment groups, cholecystectomy or nonoperative therapy, and a follow-up assessment of symptomatic improvement. Five studies met the inclusion criteria, representing a total of 274 patients. Surgical therapy resulted in 98% symptomatic relief compared to 32% with nonoperative management (P<0.0001). Patients undergoing surgical therapy for biliary dyskinesia were 2.79 times more likely to have symptomatic relief versus nonoperative therapy (95% confidence interval, 2.05-3.79). Based on this meta-analysis, cholecystectomy for biliary dyskinesia is an effective therapy and offers significant symptomatic relief over nonoperative therapy.


Can schizophrenia be related to prenatal exposure to alcohol? Some speculations.
There is a growing body of evidence implicating prenatal insults in the etiology of schizophrenia, although the etiological process is unclear. In this article we propose that prenatal exposure to alcohol may relate to a small fraction of patients who later develop schizophrenia.


Specialist management of routine dental procedures in adults with refractory epilepsy.
Little published information exists about the management of dental treatment procedures for people with epilepsy who, despite their medication, continue to have seizures. This paper draws on relevant literature in neurology and anaesthetics to provide a multi-speciality consensus on methods of assessment and adjunctive treatment options in order to manage the risk of a clinically significant seizure occurring during a procedure. It aims to enhance current guidelines and practice in the provision of specialist care for this diverse group.


How a soluble enzyme can be forced to work as a transport system: description of an experimental design.
The cellular transport systems which have been studied up to now have been found to be based on the functioning of specialized proteins anchored asymmetrically in cell membranes. In the present paper we show that a single soluble enzyme inserted at random in a gel slab can drive an uphill transport, provided that asymmetrical boundary conditions force the reversible reaction catalyzed by this enzyme to work forward on one face of the gel slab and backward on the other face. Experimentally, we have used a yeast alcohol dehydrogenase to induce an uphill transport of NADH. It cannot be excluded that comparable structurally symmetrical transport systems also exist in living cells. Such systems would be particularly well suited to preserving cell homeostasis with regard to small solutes.


T-lymphocyte subpopulations in the peripheral blood and bone marrow of patients with aplastic anemia.
A decrease in the absolute number of total lymphocytes, OKT3+ and OKT4+ lymphocytes, and a normal number of OKT8+ lymphocytes were found in the peripheral blood of patients with aplastic anemia. The OKT4:OKT8 ratio was decreased in patients due to a reduction in the percentage of OKT4+ cells and 3 out of 18 patients had a ratio less than 1. The values of the OKT4:OKT8 ratio were not associated either with the severity of the disease or with treatment with androgens. There was no correlation between the OKT4:OKT8 ratio and the number of transfusions received by patients. On the other hand, studies performed with bone marrow lymphocytes showed that the OKT4:OKT8 ratio for both patients and controls was lower than that of the peripheral blood. Since the ratio of OKT4:OKT8 cells in aplastic and control bone marrow was similar no direct pathogenic role can be assigned to the marrow for the imbalance detected in the peripheral blood.


Treatment adherence in the Estonian postmenopausal hormone therapy (EPHT) trial [ISRCTN35338757].
To investigate treatment adherence and factors related to non-adherence in the Estonian postmenopausal hormone therapy (EPHT) trial. A total of 1823 postmenopausal women aged 50-64 years were recruited into the EPHT trial from 1999 to 2001. They were randomised into the blind group receiving continuous orally administered postmenopausal hormone therapy (PHT) or a placebo and to a non-blind group receiving open-label PHT or no drugs. A woman was classified as non-adherent, if she had stopped treatment for at least 6-month period in treatment arms or used PHT for at least 6-month period in the control group. Adherence was calculated by the Kaplan-Meier method, and factors affecting adherence were studied with Cox proportional hazard modelling. The rate of adherent women declined approximately 50% during the first year in all treatment arms. Less than 10% of the control group women started taking prescribed PHT. Older women, with lower education, with only one birth, never used oral contraceptives (OC), with lower physical activity or who were dissatisfied with the information received from the trial staff, were more likely to discontinue. In treatment arms, the two most often cited reasons for non-adherence were side-effects and woman's loss of interest in participation. Control group women started PHT due to the menopausal symptoms or on doctor's recommendation. The adherence was similar to that found for PHT use in everyday life. Higher adherence was related to younger age, higher education, previous OC use, physical activity and satisfaction with received information.


Plant-soil interactions in primary succession at Hawaii Volcanoes National Park.
Plant nutrient status and physiological processes were examined in relation to soil nutrient characteristics under individuals of five species colonizing a young cinder deposit in Hawaii Volcanoes National Park. Two exotic species, Buddeleja asiatica and Myrica faya, had high photosynthetic rates and high nitrogen concentrations and relatively easily decomposed leaves; soils under them had high concentrations of nitrogen, cations, and organic matter and high rates of net nitrogen mineralization. At the other extreme, the natives Metrosideros polymorpha and Vaccinium reticulatum had low plant concentrations and photosynthetic rates, and low concentrations and turnover rates of N in the soil. Thus, a strong correlation exists between soil processes and plant processes, suggesting a positive feedback cycle.


Suppression of retinal spike discharge by dipropylacetate (Depakene): a possible involvement of GABA.
Effects of dipropylacetate (DPA) were studied on spike discharges in the isolated carp retina. (1) DPA, applied electrophoretically or by pressure-microinjection in the vicinity of the recording electrode at the inner plexiform layer, consistently activated spike discharges. (2) DPA introduced into the perfusate produced complex actions; some units responded to DPA with an initial activation followed by suppression of spike discharges. (3) When gamma-aminobutyric acid (GABA) was applied electrophoretically together with perfusion of DPA, the depressing effect was greater than that obtained with each of these compounds alone. Bicuculline in the perfusate markedly attenuated the depressing actions of GABA or DPA singly, or in combination. (4) It is concluded that the delayed suppression of spike discharges by perfused DPA appears to be mediated by GABA-receptors on ganglion cells in the carp retina.


Effects and mechanisms of extremely cold environment on body response after trauma.
With the outbreak of the Ukrainian crisis, extremely cold environment warfare has once again become the focus of international attention. People exposed to extremely cold environments may suffer from cold damage, further aggravate trauma, trigger high disability and mortality rates, and even cause serious sequelae. To declare the effects and mechanisms of the extremely cold environment on the body after trauma, this paper reviews, firstly, physiological reaction of human body in an extremely cold environment. Then, the post-traumatic body response in an extremely cold environment was introduced, and finally, the sequelae of trauma in extremely cold environment was further summarized in the paper. The results indicated that extremely cold environment can cause a series of damage to the body, especially the body after trauma. The extremely cold factor is a double-edged sword, showing a favorable and unfavorable side in different aspects. Moreover, in addition to the trauma suffered by the body, the subsequent sequelae such as cognitive dysfunction, anxiety, depression and even post-traumatic stress disorder may also be induced. The paper summarizes the human body's physiological response in an extremely cold environment, and declares the effects and mechanisms of the extremely cold environment on the body after trauma, which may provide a theoretical basis for effectively improving the level of combat trauma treatment in extremely cold regions.


Purification of membranes and identification of phase-specific proteins of the dimorphic pathogenic fungus Histoplasma capsulatum.
Plasma membrane vesicles from the yeast and mycelial phases of Histoplasma capsulatum have been purified and characterized. The method of purification involved differential centrifugation of ballistically fractured cells followed by sedimentation through discontinuous sucrose density gradient and equilibrium centrifugation. Purity of the preparation was assessed by electron microscopy. The protein composition of the membrane preparations from the yeast and mycelial phases of the fungus was analyzed by polyacrylamide gels. A comparison of the two morphologic phases revealed quantitative and qualitative differences in the expressions of several membrane-specific proteins. Physical differences in the appearance of the membranes were also observed by electron micrography of membrane preparations. Alteration in membrane fluidity may be one of the many causes for differences in the appearance of membrane vesicles in the two phases.


A versatile qPCR assay to quantify trypanosomatidic infections of host cells and tissues.
The majority of PCR-based detection systems for Leishmania spp. and Trypanosoma cruzi aim at high sensitivity and specificity, rather than an accurate parasite load quantification required for experimental infections in basic research and drug development. Here, we describe the use of a dual-labelled probe qPCR to detect and quantify intracellular Old World Leishmania spp. and T. cruzi amastigotes after in vitro and in vivo infection experiments. We show that quantification of parasite actin gene DNA relative to the host cell actin gene DNA accurately reflects the parasite load relative to the host cells and that qPCR quantification is highly sensible to drug-induced cell death. Furthermore, qPCR allows to determine parasite loads even after host cell detachment and/or rupture, important when comparing untreated versus drug-treated samples. The method is also suitable for the quantification of parasites from infected mouse tissue, making it suitable for drug testing and mutant phenotype analysis.


Comparison of air-Q(®) and Soft Seal(®) laryngeal mask for airway management by novice doctors during infant chest compression: a manikin study.
Recent resuscitation guidelines for infant cardiopulmonary resuscitation (CPR) emphasise that rescuers should minimise the interruption of chest compressions. To that end, supraglottic devices such as laryngeal mask airways (LMAs) are suggested as a backup for airway management during infant CPR. We therefore compared the utility of the air-Q(®) LMA (air-Q) with that of the Soft Seal(®) LMA (Soft Seal) for infant CPR in an infant manikin. Twenty-four novice doctors in the anaesthesia department performed insertion and ventilation with air-Q and Soft Seal on an infant manikin with or without chest compression. Two doctors failed to insert the Soft Seal without chest compression, while nine failed during chest compression (P<0.05). However, only one doctor failed to insert the air-Q without chest compression, and two doctors failed during chest compression. Insertion time was not significantly increased with chest compression using either device. Insertion time during chest compression was significantly shorter for the air-Q than for the Soft Seal (P<0.05). The visual analogue scale (VAS) was used to evaluate difficulty of use (0mm (extremely easy) to 100mm (extremely difficult)). VAS scores did not change significantly by the addition of chest compression with either device; however, VAS scores during chest compression were significantly higher with Soft Seal than with the air-Q device. We conclude that novice doctors find the air-Q easier to use than Soft Seal for emergency airway management during chest compression in infants, in an infant manikin.


Effects of low frequency magnetic field on myoglobin oxidation stability.
The effects of low frequency magnetic field on myoglobin (Mb) oxidation stability were evaluated by treatments at 0, 3, 6, 9, 12 mT and storage for 10 h. The results showed that Mb oxidation was inhibited under all magnetic field treatments, due to the increase of total sulfhydryl and free amino groups (9 or 12 mT) from unfolding of Mb clusters (3, 9, 12 mT) as well as β-turn and β-sheet structures (9 or 12 mT). The unfolding also induced (i) the destruction or burial of iron porphyrin and tyrosine residues; (ii) the exposure of tryptophan; (iii) more uniform Mb particle size distribution (3, 9, 12 mT) and increased zeta potential (3, 6, 12 mT). Overall, magnetic field promoted exposed active groups as the preferred oxidation target, thus decreasing the oxidation rate of central iron atoms. It also promoted Mb stability by redistributing particle size and increasing zeta potential.


Value of postoperative heparin therapy in peripheral arterial thromboembolism.
The experience with 359 patients with arterial thromboembolism from 1963 to 1982 has been reported. Combined operative and anticoagulant therapy appears the most beneficial form of treatment. Treatment with heparin after catheter embolectomy was associated with a decrease in mortality (7.6 percent), number of amputations (5 percent), and recurrent emboli (6 percent). Serious wound complications occurred less frequently than anticipated (8 percent). We advocate prompt arteriography and revascularization procedures to ensure long-term limb function after initial embolectomy for salvage, if the result is less than optimal or expected. Postoperative heparin seems to buy time in marginal cases, enabling secondary operations to ensure a satisfactory outcome in most patients.


Green synthesis of silver nanoparticles from Mahonia fortunei extracts and characterization of its inhibitory effect on Chinese cabbage soft rot pathogen.
The pathogenic bacterium Pectobacterium carotovorum causes soft rot in cabbage and significantly reduces plant yield. In this study, we employed Mhonia fortunei extracts to synthesis silver nanoparticles (Mf-AgNPs) and investigated their functions against P. carotovorum. The results showed that the surface plasmon resonance (SPR) peak of AgNP was 412 nm under optimal synthesis conditions. Furthermore, the results of Scanning electron microscope-Energy dispersive spectrometer (SEM-EDS) and High-resolution transmission electron microscopy (HR-TEM) revealed that the Mf-AgNPs had a spherical structure with an average diameter of 13.19 nm and the content of Ag0 ions accounted for 82.68% of the total elemental content. The X-Ray diffraction (XRD) results confirmed that AgNPs had a face-centered cubic (FCC) crystal structure, while Fourier transform infrared spectroscopy (FTIR) results indicated the presence of various biomolecules as reducing and stabilizing agents on the AgNP surface. Antibacterial activity was first evaluated by an inhibitory zone test, which revealed that 500 μg ml-1 of AgNPs had antibacterial activity against P. carotovorum and four model bacteria including Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa, respectively with an antibacterial function comparable to 1 mM AgNO3 solution. The Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for P. carotovorum were 8 μg ml-1, respectively. Furthermore, AgNPs at 8 μg ml-1 completely inhibited the growth of P. carotovorum, decreased their tolerance to 0.25 mM H2O2 as well as considerably reduced colony formation after 1 h of treatment and thereafter. Treatment with Mf-AgNPs resulted in bacterial cell membrane destruction and biofilm formation inhibition, respectively. With an FIC (fractional inhibitory concentration) index of 0.174, AgNP and zhongshengmycin showed a significant synergistic effect. The infection of P. carotovorum to cabbage explants was significantly inhibited in vitro by a combination of 2 μg ml-1 Mf-AgNP and 5 μg ml-1 zhongshengmycin. In conclusion, the synthesized Mf-AgNP exhibited significant antibacterial activity against P. carotovorum.


Functional significance of interrenal cell zonation in the adrenal gland of the duck (Anas platyrhynchos).
Slices of whole adrenal gland tissue, incubated in vitro in the presence of ACTH for 1 h and 2 h produced corticosterone and aldosterone in constant ratio (16:1). Tangential slices taken from the region immediately below the connective tissue capsule and slices taken from deeper regions of the gland consisted primarily of cells conforming to the distinct structural characteristics of the subcapsular zone (SCZ) and inner zone (IZ) tissues respectively. When samples were incubated in the presence of ACTH for 1 h and 2 h, the interrenal cells of the SCZ produced relatively more aldosterone than cells taken from the IZ of the gland. The corticosterone: aldosterone ratio for the IZ after 1 h (68:1) and after 2 h (102:1) were ten times greater than the ratios for the SCZ after 1 h (7:1) and after 2 h (10:1). The SCZ slices were not more than 60 cells thick and consisted of cells arranged in cords. These cells contained irregular nuclei, mitochondria with shelf-like cristae and a moderate abundance of smooth endoplasmic reticulum. In contrast, the production of large amounts of corticosterone by the cells of the IZ was associated with tissue containing more vascular space than the SCZ and the cells contained large round nuclei surrounded by an abundance of smooth endoplasmic reticulum and the mitochondria had tubular rather than shelf-like cristae.