The pontomesencephalotegmental cholinergic system does not degenerate in Alzheimer's disease.
The pedunculopontine and laterodorsal tegmental nuclei comprising the pontomesencephalotegmental (PMT) cholinergic system were examined for the presence of neuropathology and loss of presumed cholinergic cells in patients diagnosed with Alzheimer's disease-senile dementia of the Alzheimer type (AD-SDAT), Parkinsonian dementia, and multi-infarct dementia. Although neurofibrillary changes and plaque-like entities were observed in both nuclei in AD-SDAT and Parkinson's disease dementia, these pathologic indices were not seen consistently in control individuals or in those with multi-infarct dementia, and in none of the diagnostic categories was loss of neuronal somata found in the PMT cholinergic complex. Because appreciable degeneration of cholinergic neurons does occur in the basal forebrain in AD-SDAT, it is concluded that cholinergic phenotype alone is not a sufficient condition indicating predilection for neuronal loss in that dementing illness.


In search of genome annotation consistency: solid gene clusters and how to use them.
Maintaining consistency in genome annotations is important for supporting many computational tasks, particularly metabolic modeling. The SEED project has implemented a process that improves annotation consistencies across microbial genomes for proteins with conserved sequences and genomic context. In this research report, we describe this process and show how this effort has resulted in improvements to microbial genome annotations in the SEED. We also compare SEED annotation consistencies with other commonly used resources such as IMG (the Joint Genome Institute's Integrated Microbial Genomes system), RefSeq (the National Center for Biotechnology Information's Reference Sequence Database), Swiss-Prot (the annotated protein sequence database of the Swiss Institute of Bioinformatics, European Molecular Biology Laboratory and the European Bioinformatics Institute) and TrEMBL (Translated European Molecular Biology Laboratory nucleotide sequence data Library). Our analysis indicates that manual and computational efforts are paying off for the databases where consistency is a major goal.


Involvement of central H1 and H2 receptors in water intake induced by hyperosmolarity, hypovolemia and central cholinergic stimulation.
In the present study we investigated the participation of central H1 and H2 histaminergic receptors in water intake induced by hyperosmolarity (evoked by intragastric salt load), by hypovolemia (promoted by the subcutaneous administration of polyethyleneglycol) and by the pharmacological stimulation of central cholinergic pathways by the muscarinic agonist carbachol in male Wistar rats. The data presented here show that the pharmacological blockade of central H1 histaminergic receptors by third ventricle injections of mepyramine significantly decreased water intake induced by hyperosmolarity, hypovolemia and by the intracerebroventricular injections of carbachol. On the other hand, the pharmacological blockade of central H2 histaminergic receptors by third ventricle injections of cimetidine significantly reduced water intake in hypovolemic and hyperosmotic animals, but failed to alter water intake induced by central cholinergic stimulation by carbachol. We conclude that H1 and H2 brain histaminergic receptors are involved in inducing thirst during hyperosmolarity and hypovolemia and that H1 histaminergic receptors located post-synaptically in relation to cholinergic pathways seem to be important in triggering drinking following central pharmacological cholinergic stimulation.


Debating war-trauma and post-traumatic stress disorder (PTSD) in an interdisciplinary arena.
Researchers have tried to determine and verify the effects of violent conflicts on the mental health of those affected by focusing on war trauma, posttraumatic stress disorder (PTSD), and other trauma-related disorders. This, in turn, led to the development of different kinds of theories and aid programs that aim at preventing and treating the consequences of violence and mental health. Until now, there is no agreement on the public health value of the concept of PTSD and no agreement on the appropriate type of mental-health care. Instead, psychiatrists have engaged in sometimes fierce discussions over the universality of war trauma, PTSD, and other trauma-related disorders. The two most polar positions are those who try to validate PTSD as a universal and cross-culturally valid psychopathological response to traumatic distress which may be cured or ameliorated with (Western) clinical and psychosocial therapeutic measures, and those who argue that the Western discourse on trauma only makes sense in the context of a particular cultural and moral framework and, therefore, becomes problematic in the context of other cultural and social settings. Although these positions seem mutually exclusive, their debates have led to the development of less radical approaches toward war-trauma and PTSD. The purpose of this literature review is to analyse the discourses on and debates over war-trauma and PTSD in the psychiatric literature in order to establish a better understanding for the diverse conceptualizations, interpretations and proposed healing strategies. Moreover, I discuss the cultural construction and conceptualization of war-trauma and PTSD from an anthropological perspective and show how anthropologists contribute to psychiatric debates so as to ensure more sophisticated diagnoses and healing strategies in culturally diverse contexts.


Characterization of the Arabidopsis heterotrimeric G protein.
We have used fluorescence resonance energy transfer and co-immunoprecipitation to analyze the interactions among the alpha, beta, and gamma1 subunits of the Arabidopsis heterotrimeric G protein. Using cyan and yellow fluorescent protein fusion constructs, we show that overexpressed Ggamma1 localizes to protoplast membranes, but Gbeta exhibits membrane localization only when the Ggamma1 protein is co-overexpressed. Overexpressed Galpha shows membrane localization unaccompanied by overexpression of either Gbeta or Ggamma1. We detect fluorescence resonance energy transfer between Gbeta and Ggamma1 in the absence of Galpha overexpression and between Galpha and Ggamma1 but only when all three subunits are co-overexpressed. Both Galpha and Gbeta are associated with large macromolecular complexes of approximately 700 kDa in the plasma membrane. Galpha is present in both large complexes and as free Galpha in plasma membranes from wild type plants. In plants homozygous for a null allele of the Gbeta gene, Galpha is associated with smaller complexes in the 200-400-kDa range, indicating that its presence in the large complex depends on association with Gbetagamma. Activation of the Galpha subunit with guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) results in partial dissociation of Galpha from the complex. Hydrogen peroxide (H2O2) promotes extensive dissociation of the Galpha complex but does not interfere with binding of GTPgammaS to purified recombinant Galpha, suggesting that reactive oxygen species affect the stability of the large complex but not the activity of Galpha itself.


Distinguishing multiple rice body formation in chronic subacromial-subdeltoid bursitis from synovial chondromatosis.
Multiple rice body formation is a complication of chronic bursitis. Although it resembles synovial chondromatosis clinically and on imaging, the literature suggests that analysis of radiographic and MR appearances should allow discrimination. We report the imaging findings in a 41-year-old man presenting with rice body formation in chronic subacromial-subdeltoid bursitis. We found that the signal intensity of the rice bodies is helpful in making the diagnosis.


Problems of test choice and data analysis in behavioral teratology: the case of prenatal benzodiazepines.
Higher-tier tests for the assessment of early treatment effects should be aimed at providing specific information on the behavior processes affected, rather than simply at extending the descriptive data base. The contrast between positive and negative results can be useful to point out possible mechanisms of action. For example, late prenatal oxazepam exposure of mice produced a reduction of the amphetamine hyperactivity at the end of the second postnatal week, but did not significantly affect the response to scopolamine at the end of the third week. An impairment of active locomotor avoidance was observed at the young adult stage, which contrasted with the absence or scarcity of changes in passive avoidance and extinction responding in the same go-no go tests. These changes in response-activating mechanisms appear to be in agreement with the medium- and long-term effects on CNS monoamine metabolism described in the literature. As concerns statistical analysis, dichotomous or polytomous data obtained, e.g., by the Fox battery are not yet amenable to an adequate processing, due to the shortcomings of the available nonparametric tests. By contrast, mixed-model ANOVAs can cope with complex data obtained, e.g., in activity and learning tests. However, the available checks on various assumptions (normality, homogeneity of variance, sphericity) are not valid when nested factors, block factors and repeated measures coexist. Finally, the more usual cross-fostering procedures provide adequate information on some aspects (e.g., separation of main effects of prenatal treatments from postnatal maternal effects) but not on others.(ABSTRACT TRUNCATED AT 250 WORDS)


Collagen-rich deposit formation in the sciatic nerve after injury and surgical repair: A study of collagen-producing cells in a rabbit model.
Posttraumatic scarring of peripheral nerves produces unwanted adhesions that block axonal growth. In the context of surgical nerve repair, the organization of the scar tissue adjacent to conduits used to span the gap between the stumps of transected nerves is poorly understood. The goal of this study was to elucidate the patterns of distribution of collagen-rich scar tissue and analyze the spatial organization of cells that produce fibrotic deposits around and within the conduit's lumen. Employing a rabbit model of sciatic nerve transection injury, we studied the formation of collagen-rich scar tissue both inside and outside conduits used to bridge the injury sites. Utilizing quantitative immunohistology and Fourier-transform infrared spectroscopy methods, we measured cellular and structural elements present in the extraneural and the intraneural scar of the proximal and distal nerve fragments. Analysis of cells producing collagen-rich deposits revealed that alpha-smooth muscle actin-positive myofibroblasts were only present in the margins of the stumps. In contrast, heat shock protein 47-positive fibroblasts actively producing collagenous proteins were abundant within the entire scar tissue. The most prominent site of transected sciatic nerves with the highest number of cells actively producing collagen-rich scar was the proximal stump. Our findings suggest the proximal region of the injury site plays a prominent role in pro-fibrotic processes associated with the formation of collagen-rich deposits. Moreover, they show that the role of canonical myofibroblasts in peripheral nerve regeneration is limited to wound contracture and that a distinct population of fibroblastic cells produce the collagenous proteins that form scar tissue. As scarring after nerve injury remains a clinical problem with poor outcomes due to incomplete nerve recovery, further elucidation of the cellular and spatial aspects of neural fibrosis will lead to more targeted treatments in the clinical setting.


Ultrasound-guided Hartmann's solution enema: first-choice procedure for reducing idiopathic intussusception.
This study was undertaken to compare the effectiveness of ultrasound-guided Hartmann's solution enema (US-E) and radiological liquid enema (RX-E) in reducing idiopathic ileocecocolic intussusceptions in relation to patient age and symptom duration. The study group consisted of 42 patients with idiopathic ileocecocolic intussusception treated with US-E (20 patients) or RX-E (23 patients), with one patient undergoing both procedures owing to recurrence. Patients were divided into subgroups according to age (<6 months, 6-12 months, >12 months) and symptom duration (<12 h, 12-24 h, >24 h). Complete reduction was achieved in 15/20 patients treated with US-E (75%) and in 10/23 treated with RX-E (43.5%) (p=ns). Recurrence was observed in 1/20 US-E and 0/23 RX-E (p=ns) patients. No complications were encountered. US-E had a significantly higher success rate than RX-E in patients >12 months (p=0.0063) and with symptom duration >24 h (p=0.0361). No differences were found in the other subgroups (p=ns). US-E and RX-E are procedures of comparable value and safety in reducing idiopathic intussusception. US-E seems to be more effective in patients >12 months or with symptom duration >24 h. As US-E avoids radiation exposure, it should be considered the first-choice procedure for reducing idiopathic ileocecocolic intussusception, particularly in these two subgroups of patients.


Association of APOA5 -1131T>C and S19W gene polymorphisms with both mild hypertriglyceridemia and hyperchylomicronemia in type 2 diabetic patients.
Two minor apolipoprotein A5 (APOA5) gene haplotypes, represented by -1131T>C and S19W polymorphisms, are strong determinants of plasma triglyceride (TG) concentration variability across human populations. Hypertriglyceridemia is frequent in type 2 diabetes (T2D) and hyperchylomicronemia is not uncommon. We investigated the association of -1131T>C and S19W polymorphisms with diabetic dyslipidemia in 400 Caucasian T2D patients divided in 2 groups: group N with 130 normotriglyceridemics (TG<90th percentile) and group M with 270 moderately hypertriglyceridemics. A third group of 51 diabetic patients (group H) with history of hyperchylomicronemia (TG>15 mM) was also studied. The -1131C allele was more frequent in both mild and severe hypertriglyceridemia (20.6% vs 9.8% vs 5.0%, group H vs M vs N, p<0.001). The 19W allele was more frequent only in patients with hyperchylomicronemia (14.0% vs 6.5% vs 6.1%, group H vs M vs N, p=0.001). In group N+M, the -1131C allele was associated with higher TG (+13%, p=0.034) and lower HDLc (-10%, p=0.004). The 19W allele was only associated with lower HDLc (-9%, p=0.022). These results suggest that in T2D APOA5 polymorphisms contribute to modulate dyslipidemia. Both -1131T>C and S19W polymorphisms are associated with hyperchylomicronemia and only -1131T>C polymorphism with mild hypertriglyceridemia.


Structure and metal-binding properties of PA4063, a novel player in periplasmic zinc trafficking by Pseudomonas aeruginosa.
The capability to obtain essential nutrients in hostile environments is a critical skill for pathogens. Under zinc-deficient conditions, Pseudomonas aeruginosa expresses a pool of metal homeostasis control systems that is complex compared with other Gram-negative bacteria and has only been partially characterized. Here, the structure and zinc-binding properties of the protein PA4063, the first component of the PA4063-PA4066 operon, are described. PA4063 has no homologs in other organisms and is characterized by the presence of two histidine-rich sequences. ITC titration detected two zinc-binding sites with micromolar affinity. Crystallographic characterization, performed both with and without zinc, revealed an α/β-sandwich structure that can be classified as a noncanonical ferredoxin-like fold since it differs in size and topology. The histidine-rich stretches located at the N-terminus and between β3 and β4 are disordered in the apo structure, but a few residues become structured in the presence of zinc, contributing to coordination in one of the two sites. The ability to bind two zinc ions at relatively low affinity, the absence of catalytic cavities and the presence of two histidine-rich loops are properties and structural features which suggest that PA4063 might play a role as a periplasmic zinc chaperone or as a concentration sensor useful for optimizing the response of the pathogen to zinc deficiency.


Naturally occurring combinations of receptors from single cell transcriptomics in endothelial cells.
VEGF inhibitor drugs are part of standard care in oncology and ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for more effective therapies of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to understand how cells communicate and to identify targets for drug combinations. We also develop and share a new software tool called DECNEO to identify them. Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and humans) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. Multiple statistical tests from large datasets, including an independent validation set, support the reproducibility, evolutionary conservation and role in angiogenesis of these naturally occurring combinations of receptors. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate paper. The results and methods presented here advance the understanding of signaling to endothelial cells. The methods are generally applicable to the decoding of intercellular combinations of signals.


A pre-visit tailored website enhances counselees' realistic expectations and knowledge and fulfils information needs for breast cancer genetic counselling.
Counselees who are the first in their family to request breast cancer genetic counselling often don't know what to expect or have unrealistic expectations of genetic counselling. Receiving tailored information might help them to prepare for their first visit. We conducted a study of the effects of a pre-visit website providing computer-tailored information (E-info gene(ca)), on counselees' expectations, knowledge about breast cancer and heredity and information needs. Counselees were randomized to receive usual care (UC) or UC plus website. All counselees completed a baseline questionnaire and those randomized to the intervention group also completed a questionnaire after having viewed the website. After having accessed E-info gene(ca) counselees (n = 101) better knew what to expect of their first visit (χ(2) = 4.43; P = .04) and less often showed unrealistic expectations about possibilities for DNA-testing (χ(2) = 4.84; P = .03) than counselees in the UC group (n = 89). In addition, the website increased counselees' knowledge of breast cancer and heredity (B = .23; P = .003) and lowered their information needs (B = -.16; P = .000) compared to the UC group. Especially, information concerning procedural aspects and emotional consequences of genetic counselling was considered less important. This study showed that counselees know more and need less when they are provided with extended pre-visit information through a tailored website and counselees enter the visit with more realistic expectations of genetic counselling. This might facilitate and focus communication within the subsequent consultation.


Appraisal of marketing approaches for consultation-liaison psychiatry.
The high prevalence of undetected and undertreated mental disorders in the general health care sector suggests that the active "marketing" strategies proposed in these articles are overdue. However, a more extensive data base that documents the need for psychiatric involvement in the medical setting and assesses the capacities of other mental health professionals to substitute for consultation-liaison (C-L) psychiatrists in clinical care, teaching, and research is urgently needed and will prove to be the most potent marketing tool available to the specialty.


Ameliorative effect of Fennel (Foeniculum vulgare) essential oil on chlorpyrifos toxicity in Cyprinus carpio.
Chlorpyrifos (CPF) is an organophosphate pesticide that is frequently and widely used to control both agricultural and domestic pests worldwide. In this study, the protective effect of Fennel (Foeniculum vulgare) essential oil (FEO) was investigated in carp (Cyprinus carpio) exposed to CPF. The fish were divided into six groups that one control group (no treatment) and five experimental groups (FEO (3ml/100g diet) group, CPF1 (0.023 mg/l) group CPF2 (0.046 mg/l) group, CPF1 (0.023 mg/l) plus FEO (3ml/100g diet) group, CPF2 (0.046 mg/l) plus FEO (3ml/100g diet) group). Blood and tissue (liver, kidney, gill, and brain) samples were taken from the fish at the end of 14 days of application. Hemoglobin (Hb) level, nitoblue tetrazolium (NBT) activity, and total immunoglobulin (TI) level were measured in blood samples of fish. Acetylcholinesterase (AChE) activity was determined in brain tissue while malondialdehyde (MDA) level, reduced glutathione (GSH) level, catalase (CAT), and glutathione peroxidase (GPx) activity were determined in liver, kidney, and gill tissues. The results showed that there was a significant decrease in Hb level, NBT activity, and TI levels in CPF-treated fish compared to the control group. In addition, increased in MDA levels and significant decreases in GSH level, AChE, CAT, and GPx activities were observed in CPF-treated groups. However, FEO-treated was showed a significant improvement in all parameters except AChE activity compared to CPF groups. These study findings showed that FEO could improve CPF-induced toxicity in C. carpio, except inhibition of AChE activity.


New trends in telescopic remote Raman spectroscopic instrumentation.
Raman spectroscopy is a powerful analytical technique in many areas of research for several reasons. These include the sensitivity to small structural changes, non-invasive sampling capability, minimal sample preparation, narrow line widths of Raman lines, and high spatial resolution in the case of micro-Raman spectroscopy. Advancements in lasers, spectrographs and holographic optical components have made Raman spectroscopy an effective tool for analyzing natural and synthetic materials. These advances have led to the development of both in situ Raman spectroscopy and telescopic remote Raman spectroscopy for a lander or rover for planetary exploration. A telescopic Raman spectroscopic system capable of measuring Raman spectra of minerals, inorganic and organic chemicals, and biogenic materials to radial distances in the range 10-100 m has been developed. In this work, the author reviews the current status of telescopic remote Raman spectroscopic instrumentation and examines new trends in the field of remote Raman spectroscopy and its combination with time-resolved remote laser-induced native fluorescence (LINF) and laser-induced breakdown spectroscopy (LIBS), and their applications in earth and planetary science.


Neurodynamics of Awareness Detection in Tibetan Immigrants: Evidence from Electroencephalography Analysis.
The psychological effects of long-term exposure to high-altitude environments have attracted great attention. These effects are usually attributed to the diminished cognitive resources due to high-altitude exposure. This study employed electroencephalography (EEG) to investigate the effects of exposure duration on awareness detection tasks. Neither reaction time nor accuracy showed the direct effects of the exposure duration, so did the model indexes obtained from drift diffusion model analysis. However, event-related potentials (ERP) analysis revealed that exposure duration was associated with changes in the visual awareness negativity (VAN) and the late positivity (LP) components, which in turn affected reaction time. Specifically, longer exposure durations were associated with lower VAN and higher LP, resulting in shorter reaction times and greater drift rate. In contrast to previous studies, the reverse relationship between VAN and LP may reflect a compensatory response to the reduced cognitive resources caused by high-altitude exposure. Additionally, increased LP and shorter reaction times with exposure duration may reflect a resistance to the high-altitude environment. We also conducted time-frequency analysis and found that theta power did not vary with exposure duration, suggesting that the reduction in cognitive resources remains stable in these individuals over time. Overall, our study provides new insights into the dynamic effects of high-altitude environments on awareness detection in the presence of reduced cognitive resources.


Cost analysis of sialendoscopy for the treatment of salivary gland disorders in children.
Recent advances in Otolaryngology have changed the diagnosis and therapy for salivary gland disorders. Sialendoscopy-assisted surgery is a minimally invasive, conservative procedure for functional preservation of the affected gland. The goals of this study are to assess the indications, use, and outcomes of pediatric sialendoscopy at a tertiary pediatric institution as well as to analyze the direct cost related to the diagnosis and treatment of patients with sialolithiasis and Juvenile Recurrent Parotitis managed with sialendoscopy. Retrospective cohort study of pediatric patients undergoing diagnostic and/or therapeutic sialendoscopy at a tertiary level children's hospital between 2012 and 2020. Demographic, clinical, surgical variables and direct hospital costs 1 year before and after the sialendoscopy procedure were collected and analyzed. Twenty-two pediatric patients were included. There was male predominance (59.3%). The most common indication for sialendoscopy was Juvenile Recurrent Parotitis. Average age of onset was 6.5 years for patients with JPR and 14.2 years for patients with sialolithiasis. All patients had an average of 4.5 episodes before the first procedure. 8 patients required repeat sialendoscopy for recurrent symptoms. Mean total hospital costs were significantly higher in patients with JRP 1 year before and after the sialendoscopy ($4308.8 vs. $3330) compared to patients with sialolithiasis. Costs of the sialendoscopy and related expenses including anesthesia and PACU cost were similar in both studied groups ($13,506 vs. $13,022.9). Complete resolution of symptoms was achieved in 14 patients with JRP and all patients with sialolithiasis. Sialendoscopy is a low-risk procedure that aids in the treatment for pediatric salivary gland disorders. The costs related to sialendoscopy are substantial and patients with JRP incur higher hospital preoperative and postoperative costs compared to patients with sialolithiasis.


Minimally invasive poly-axial screw plating for three-part fractures of the proximal humerus.
The purpose of this study was to evaluate the poly-axial locked plating system inserted through a minimally invasive approach for the treatment of three-part fractures of the proximal humerus. Twenty-three patients with a three-part fracture of the proximal humerus treated with a poly-axial locking plate through a percutaneous approach were available for clinical and radiological analysis at a minimum of 2 years follow up (average 36 months; range, 24-54 months). To assess objective and subjective outcomes the Constant Score (CS) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were obtained. All complications were recorded. There were 17 women and 6 men, with a mean age of 62 years (range, 18-86). All fractures healed. At final follow up, the mean forward flexion, external rotation and internal rotation were 126°, 44° and L1, respectively; the mean CS was 64 and the mean DASH score was 23. Twelve patients (52%) had a postoperative complication, which included screw cut-out, stiffness and infection. The poly-axial locked plating system through a minimally-invasive approach may be an appropriate treatment for three-part fractures of the proximal humerus and may reduce the biological aggression of conventional plate fixation.


The evolution of stability in cervical spinal constructs using either autogenous bone graft or methylmethacrylate cement. A follow-up report on a canine in vivo model.
Thirty-six adult mongrel dogs underwent either a posterior C4-C5 bone graft or methylmethacrylate-cerclage wire construction procedure to simulate the analogous human stabilization procedures. The dogs were divided into groups of six and allowed to live 1, 2, or 3 months after surgery. At the appropriate time they were killed and their C4-C5 spinal segments excised and studied radiologically, mechanically, and histologically. In addition, the C4-C5 spinal segments from 15 other mongrel dogs were excised and either left intact as normal (five) or prepared as one of the two constructs (five each) described above. They were also tested mechanically to provide immediate postoperative stability data. At some time during the first postoperative month the methylmethacrylate constructs lost mechanical stability. In addition, fibrous tissue was noted to have grown between the posterior laminal surface and the cement mass during this same time. Radiologically, loosening was obvious by the second postoperative month. The bone graft constructs were mechanically equivalent to or superior to the normal dogs by the second postoperative month. Likewise, they were well on their way to solid fusion radiologically and histologically by the same time. Impressed by the rapidity of deterioration in mechanical stability for the methylmethacrylate constructs, the authors further questioned their usefulness in cases of traumatic cervical spinal instability. The bone graft constructs continued to appear to be a reliable way to achieve ultimate spinal stability.


Ultrastructural aspects of cytoplasmic ribosomes from Histoplasma capsulatum and Blastomyces dermatitidis as revealed by heavy metal staining.
Cytoplasmic ribosomes were isolated and purified from sonicates of the mycelial and yeastlike growth forms of the pathogenic dimorphic fungi, Histoplasma capsulatum and Blastomyces dermatitidis. Similar ribosomal fractions were prepared from Neurospora crassa and Saccharomyces cerevisiae. These latter organisms were selected as typical filamentous and yeastlike monophasic fungi, and their ribosomes were used as reference standards. High resolution electron microscopy permitted a comparison of both positively and negatively-stained ribosomes to those dehydrated without heavy metal salt. Such studies revealed statistically significant differences in physical dimensions. Cautious interpretations of substructural detail of the various ribosomal preparations suggested both interphasic and interspecies differences.


Temporal integration of acoustic and cutaneous stimuli shown in the blink reflex.
Temporal integration of pairs of brief blink-eliciting acoustic and cutaneous stimuli was investigated to determine if there was integration of stimuli from different modalities. Reflexes elicited by a tone burst or by a brief electrical shock to the supraorbital nerve followed by a second tone burst or shock at short stimulus onset asynchronies (SOAs) were larger and faster than control reflexes elicited by a single stimulus identical to the lead stimulus of the stimulus pairs. Reflex amplitude was augmented at longer SOAs where there was no effect on latency. Temporal integration was evident for all stimulus pairs, showing that it is due, at least in part, to processes that occur outside specific sensory pathways. Heterogeneous stimulus pairs produced greater reflex enhancement than did homogeneous stimulus pairs. This finding was examined further in Experiment 2, which showed that reflex enhancement with pairs of acoustic pulses was unaffected by the frequency of the second stimulus, suggesting that sensory masking was not acting to suppress reflex expression with acoustic pulse pairs. Integration of reflexogenic acoustic stimuli shown in the blink reflex is restricted to shorter intervals than is integration of acoustic stimuli shown by psychophysical procedures, suggesting that the two methods reflect different aspects of stimulus processing. Integration of reflexogenic stimuli may result from summation of activity associated more directly with reflex expression than with perceptual awareness.


Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip.
Our intention was to examine if subnormal testosterone levels in older men were associated with a reduction in quality of life and physical and mental health, and secondly to examine if testosterone treatment could improve these conditions. We performed a nested case-control study and a 1-year testosterone intervention study. Men with subnormal testosterone had significantly higher weight, fat mass and abdominal adipose tissue. They also had significantly higher glucose and insulin levels, and they had higher triglyceride levels. Testosterone treatment had a large impact on body composition with reduced fat mass and abdominal adipose tissue and increased fat-free mass, but it did not affect weight and glucose and lipid metabolism. Bone mineral density in the hip was significantly higher after the testosterone treatment. Older men with subnormal testosterone levels had an unfavorable metabolic profile. Testosterone treatment improved body composition, but it did not reverse the unfavorable metabolic profile.


The accuracy of a novel self-tapping bone fiducial marker for frameless robot-assisted stereo-electro-encephalography implantation and registration techniques.
We aimed to evaluate the accuracy and safety of a novel self-tapping bone fiducial as a registration technique for stereoelectroencephalography (SEEG) implantation. Each patient was installed with five bone fiducial markers. All procedures were performed using the same Sinovation robot system. The accuracy was determined by calculating the target point error (TPE) and the entry point error (EPE) of electrodes. Fourteen patients underwent SEEG implantation surgery; and the average installation time of the markers per patient was 86.1 s. In the operating theatre, the average registration time was 206.6 s, and the average registration error was 0.18 mm. The average TPE of 174 electrodes was 1.98 mm and the average EPE was 0.88 mm. Our study provided a bone fiducial marker installation and registration technique that was convenient and fast, highly accurate in registration, and highly tolerated by patients.


Suppression effect of plant-derived berberine on cyprinid herpesvirus 2 proliferation and its pharmacokinetics in Crucian carp (Carassius auratus gibelio).
Cyprinid herpesvirus 2 (CyHV-2), which infects silver crucian carp including goldfish (Carassius auratus auratus) and Crucian carp (Carassius auratus gibelio) with high mortality, is an emerging viral pathogen worldwide. Previous studies showed that berberine (BBR), a bioactive plant-derived alkaloid, demonstrated potential antiviral actions against many different viruses. Here, we assessed the effect of berberine hydrochloride (BBH) on the replication of CyHV-2 in vitro and in vivo. Cytotoxicity assay indicated that 5-25 μg/mL BBH was non-toxic to the RyuF-2 cells. In viral inhibition assays, real time PCR was employed to titrate the genomic copy number of progeny virus, real time RT-PCR was applied to monitor the transcriptional levels of viral genes, and Western blot analysis was performed to detect the synthetic levels of viral proteins. The results demonstrated that BBH systematically impedes the viral gene transcription and suppressed the replication of CyHV-2 in RyuF-2 cells. In animal challenge test, BBH was confirmed to protect Crucian carps from CyHV-2 infection in a dose-dependent manner, which was supported by suppressed viral replication levels, reduced viral pathogenesis and higher survival rates. Furthermore, pharmacokinetics data of BBH in Crucian carp revealed its rapid absorption (Tmax of 1.5 h), suitable plasma half-life (t1/2z/h of 7-12 h depending on oral dosage), and dose-dependent drug exposure properties following oral administration (revealed by AUC0-t values). These findings shed light on repurposing BBH to treat CyHV-2 infections in silver crucian carp.


CHRNB2 represses pancreatic cancer migration and invasion via inhibiting β-catenin pathway.
Pancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear. Gene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and β-catenin pathway via Western Blot. High LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated β-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2. CHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit β-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.


INNER MACULAR CHANGES AFTER VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING FOR RHEGMATOGENOUS RETINAL DETACHMENT: Similarity With Alport Syndrome.
The internal limiting membrane (ILM), the innermost basement membrane of the retina, is peeled occasionally during vitreous surgery. This study aimed to investigate the effect of ILM loss on the retina. We used optical coherence tomography to retrospectively evaluate retinal changes in 26 eyes (11 ILM-peeled and 15 ILM-unpeeled eyes) of 26 patients after vitrectomy for retinal detachment. In addition, we studied six eyes of three patients with Alport syndrome, in which ILM is genetically impaired. We observed significant inner retinal displacement of the foveal pit toward the optic disk with inner retinal thickening in the nasal area (fellow, 191.9 ± 24.3 μm vs. affected, 210.3 ± 31.4 μm; P = 0.048), inner retinal thinning in the temporal area (fellow, 174.3 ± 18.3 μm vs. affected, 142.2 ± 23.6 μm; P < 0.001), foveal thickening (ILM-unpeeled, 217.0 ± 39.4 μm vs. ILM-peeled, 302.0 ± 86.2 μm; P = 0.006), inner retinal dimples predominantly in the temporal area, and deviation between the foveal pit and foveal bulge. Eyes with Alport syndrome exhibited similar findings. Internal limiting membrane loss seems to cause characteristic inner retinal changes of the macula in both congenital and acquired conditions.


Concentrations and determinants of lead, mercury, cadmium, and arsenic in pooled donor breast milk in Spain.
To measure concentrations of lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) in longitudinally collected donor breast milk samples and to determine associated factors. Pb, Hg, Cd, and As concentrations were measured in 242 pooled breast milk samples from 83 donors to a Human Milk Bank in Spain, in 2015-2018, determining their association with the donors' sociodemographic profile, dietary and lifestyle habits, and post-partum time, among other factors, and with the nutritional characteristics of samples. Mixed-effect linear regression was used to identify predictors of Hg and As concentrations in breast milk and mixed-effect logistic regression to identify predictors of the presence of Pb and Cd. As was the element most frequently detected in milk samples (97.1%), followed by Hg (81.2%), Pb (50.6%), and Cd (38.0%). Their median breast milk concentrations were 1.49 μg/L, 0.26 μg/L, 0.14 μg/L, and <0.04 μg/L, respectively. Concentrations of As were higher in breast milk from primiparous donors, while Hg was higher in donors with a greater intake of fatty fish and meat and lower in samples collected after a longer post-partum time and with higher lactose content. Detection of Pb was higher among multiparous donors, those gaining weight since before pregnancy, and ex-smokers and was lower in samples collected more recently and from donors with greater intake of red meat and eggs. Cd detection was higher for donors with university education and those with greater intake of fried and canned food and more frequent use of hand cream and was lower for donors with greater bread intake. These findings reveal relatively high As concentrations, moderate Hg concentrations, and low Pb and Cd concentrations in pooled donor breast milk. Several factors including post-partum time, parity, smoking habit, and the intake of certain food items were associated with the metal content of milk samples.


The PAX5-JAK2 translocation acts as dual-hit mutation that promotes aggressive B-cell leukemia via nuclear STAT5 activation.
While PAX5 is an important tumor suppressor gene in B-cell acute lymphoblastic leukemia (B-ALL), it is also involved in oncogenic translocations coding for diverse PAX5 fusion proteins. PAX5-JAK2 encodes a protein consisting of the PAX5 DNA-binding region fused to the constitutively active JAK2 kinase domain. Here, we studied the oncogenic function of the PAX5-JAK2 fusion protein in a mouse model expressing it from the endogenous Pax5 locus, resulting in inactivation of one of the two Pax5 alleles. Pax5Jak2/+ mice rapidly developed an aggressive B-ALL in the absence of another cooperating exogenous gene mutation. The DNA-binding function and kinase activity of Pax5-Jak2 as well as IL-7 signaling contributed to leukemia development. Interestingly, all Pax5Jak2/+ tumors lost the remaining wild-type Pax5 allele, allowing efficient DNA-binding of Pax5-Jak2. While we could not find evidence for a nuclear role of Pax5-Jak2 as an epigenetic regulator, high levels of active phosphorylated STAT5 and increased expression of STAT5 target genes were seen in Pax5Jak2/+ B-ALL tumors, implying that nuclear Pax5-Jak2 phosphorylates STAT5. Together, these data reveal Pax5-Jak2 as an important nuclear driver of leukemogenesis by maintaining phosphorylated STAT5 levels in the nucleus.


Mucosal delivery of allergen peptides expressed by Lactococcus lactis inhibit allergic responses in a BALB/c mouse model.
Allergen-specific immunotherapy (SIT) is considered to be the only curative treatment of allergy, but its safety is always affected by immunologic properties and quality of allergen. Recombinant allergen derivative could be a potential therapeutic strategy, but clinical studies showed that macromolecular derivatives could not avoid T cell-mediated side effects. In this study, five Der p2-derived peptides (DPs) containing major T cell epitopes of Der p2 were first artificially synthesized. Compared with Der p2 macromolecular derivative DM, these DPs not only fully eliminated IgE-binding capacity but also reduced T cells reactivity, suggesting these DPs could be better therapeutic molecules. For their application in vivo, Lactococcus lactis was engineered to express these DPs, and their protective effects were evaluated in BALB/c mice models. Western blot showed that all DPs could be produced in the recombinant strains. Mucosal delivery of these strains could inhibit Der p2-induced allergic responses in Der p2-sensitized mice, characterized by a reduction in specific IgE antibody and lung inflammatory responses. These protective effects were associated with an increase of specific IgG2a in serum and regulatory T cells in the mesenteric lymph nodes. On the whole, the suppressive effect induced by the DP mixture could be better than single DP, but a bit weaker than DM. These DPs could be promising candidate molecules for active vaccination and induction of tolerance, and thus promote the development of non-allergenic peptide in the treatment and prevention of allergy.


Bilateral single ectopic ureter.
A case of single bilateral ureteral ectopia is presented. Patient underwent bilateral ureteral reimplantation with right ureteral tailoring, with a satisfactory result.


Systematic review of laparoscopic versus open surgery for colorectal cancer.
This study compares the efficacy and safety of laparoscopic surgery (LS) and open surgery (OS) for colorectal cancer. An electronic search of the literature was undertaken to identify primary studies and systematic reviews. Information on the efficacy and safety of LS versus OS was analysed. A meta-analysis was conducted to examine long-term outcomes. A systematic review published in 2000 and 12 more recent randomized clinical trials were identified. Compared with OS, LS reduced blood loss and pain, and resulted in a faster return of bowel function and earlier resumption of normal diet. Hospital stay was up to 2 days shorter after LS. No significant differences between the techniques were noted in the incidence of complications or postoperative mortality. The time required to complete LS was significantly longer (0.5-1.0 h more). No significant differences were found between the two procedures in terms of overall mortality, cancer-related mortality or disease recurrence. LS takes longer than OS but offers several short-term benefits. However, complication rates are similar for both procedures and no differences were found in long-term outcomes.


Structural changes and molecular interactions of hydrophobin SC3 in solution and on a hydrophobic surface.
The hydrophobin SC3 belongs to a class of small proteins functioning in the growth and development of fungi. Its unique amphipathic property and remarkable surface activity make it interesting not only for biological studies but also for medical and industrial applications. Biophysical studies have revealed that SC3 possesses at least three distinct conformations, named "soluble-state SC3" for the protein in solution, and "alpha-helical-state SC3" and "beta-sheet-state SC3" for the different states of the protein associated at a hydrophobic-water interface. The present fluorescence study shows that the microenvironment of the dansyl-labeled N terminus of soluble-state SC3 is relatively hydrophobic, whereas it is hydrophilic for alpha-helical-state and beta-sheet-state SC3. Fluorescence collisional quenching indicates that the N terminus of soluble-state SC3 is more solvent-accessible than those of alpha-helical-state and beta-sheet-state SC3, with Stern-Volmer constants for acrylamide of 4.63, 0.02, and 0.2 M(-1) for the different states, respectively. Fluorescence resonance energy transfer measurements show that soluble-state SC3 tends to associate in solution but dissociates in TFA. Fluorescence energy transfer was eliminated by conversion of soluble-state SC3 to alpha-helical-state SC3 on a hydrophobic surface, indicating a spatial separation of the molecules in this state. By inducing the beta-sheet state, structural changes were observed, both by CD and by fluorescence, that could be fit to two exponentials with lifetimes of about 10 min and 4 h. Molecules in the beta-sheet state also underwent a slow change in spatial proximity on the hydrophobic surface, as revealed by the reappearance of fluorescence resonance energy transfer in time.


Differential profiles of binding of a radiolabeled agonist and antagonist at a glycine recognition domain on the N-methyl-D-aspartate receptor ionophore complex in rat brain.
Addition of several polyamines, including spermidine and spermine, was effective in inhibiting binding of the antagonist ligand [3H]5,7-dichlorokynurenic acid ([3H]-DCKA) a Gly recognition domain on the N-methyl-D-aspartic acid (NMDA) receptor ionophore complex in rat brain synaptic membranes. In contrast, [3H]DCKA binding was significantly potentiated by addition of proposed polyamine antagonists, such as ifenprodil and (+/-)-alpha-(4-chlorophenyl)-4-[(4-fluorophenyl) methyl]-1-piperidine ethanol, with [3H]Gly binding being unchanged. The inhibition by spermidine was significantly prevented by inclusion of ifenprodil. In addition, spermidine significantly attenuated the abilities of four different antagonists at the Gly domain to displace [3H]DCKA binding virtually without affecting those of four different agonists. Phospholipases A2 and C and p-chloromercuribenzosulfonic acid were invariably effective in significantly inhibiting [3H]DCKA binding with [3H]Gly binding being unaltered. Moreover, the densities of [3H]DCKA binding were not significantly different from those of [3H]-Gly binding in the hippocampus and cerebral cortex, whereas the cerebellum had more than a fourfold higher density of [3H]Gly binding than of [3H]DCKA binding. These results suggest that the Gly domain may have at least two different forms based on the preference to agonists and antagonists in the rodent brain.


Retracted: Comparison of DNA Damage and Apoptosis Induced By Silver Nanoparticle-containing Dressing Materials During Wound Healing.
The Editor and Publisher regretfully have to retract the following two publications due to faulty study design.


Ischemic injury to the spinal cord as a cause of transient paraplegia.
Spinal cord ischemia presenting as acute paraplegia is an uncommon occurrence not previously reported in the emergency medicine literature. Paraplegia due to spinal ischemia is seen most commonly after intraoperative aortic manipulation; however, acute hypotension and prolonged cardiopulmonary resuscitation are also reported settings. The differential diagnosis of acute, non-traumatic paraplegia includes mechanical spinal cord compression, acute transverse myelitis, and polyneuritis.


Normal and pathological aging--findings of positron-emission-tomography.
Normal aging of the brain is predominantly characterized by metabolic changes in the prefrontal cortex. While in middle age there is a trend to hyperfrontality, PET demonstrates in old age a decline of regional cerebral glucose metabolism in frontal areas. In progeric diseases, clinically apparent as premature aging, the metabolic pattern is similar like in normal aging but qualitatively more severe. In patients with the diagnosis of probable Alzheimer's disease (AD) hypometabolism in early dementia is typically present in heteromodal association areas. Hypometabolism then spreads to other cortical and subcortical regions suggesting a characteristic pattern of degeneration that reflects selective vulnerability within limbic-cortical networks. Synaptic plasticity, clinically apparent as cognitive reserve capacity, can be assessed by PET under specific cognitive activation. In AD it is reduced in comparison to age-matched normals and may be influenced by drugs giving trophic support to neurochemical systems.


Frictional melting mechanisms of rocks during earthquake fault slip.
Rapid slip, at rates in the order of 1 m/s or more, may induce frictional melting in rocks during earthquakes. The short-lived melting has been thought to be a disequilibrium process, for decades. We conducted frictional melting experiments on acidic, basic, and ultrabasic silicate rocks at a slip rate of 1.3 m/s. The experiments and microstructural observations reveal that all minerals in the rocks are melted at temperatures below their known melting temperatures (Tm); e.g., quartz is melted at ~ 1000-1200 °C, not ~ 1720 °C, while olivine at ~ 1300 °C, rather than ~ 1700 °C. The low-temperature melting is incompatible with the conventional disequilibrium melting, and may be caused predominantly by grain size reduction and phase boundary reactions during the early and later stages of slip, respectively. The newly estimated Tm and the melting mechanisms should be considered for understanding the mechanics of earthquakes, landslides, and caldera collapses.


Diuretics. Clinical pharmacology and therapeutic use (Part I).
25 years have elapsed since the introduction of the first effective oral diuretic, chlorothiazide. Diuretics are now amongst the most widely prescribed drugs in clinical practice worldwide. Availability of these drugs has not only brought therapeutic benefit to countless numbers of patients but it has at the same time provided valuable research tools with which to investigate the functional behaviour of the kidney and other electrolyte-transporting tissues. Despite many remaining gaps in our knowledge of the biochemical processes involved in diuretic drug action, available compounds can be divided into 5 groups on the basis of their preferential effects on different segments of the nephron involved in tubular reabsorption of sodium chloride and water. Firstly, there is heterogeneous group of chemicals that share the common property of powerful, short-lived diuretic effects that are complete within 4 to 6 hours. These agents act on the thick ascending limb of Henle's loop and are known as 'high ceiling' or 'loop' diuretics. The second group are the benzothiadiazines and their many related heterocyclic variants, all of which localise their effects to the early portion of the distal tubule. The third group comprises the potassium-sparing diuretics which act exclusively on the Na+-K+/H+ exchange mechanisms in the late distal tubule and cortical collecting duct. The action of drugs in groups 2 and 3 is prolonged to between 12 and 24 hours. The fourth group consists of diuretics that are chemically related to ethacrynic acid but have the unusual property of combining within the same molecule the property of saluresis and uricosuria. These compounds have actions, to different individual extents, in the proximal tubule, thick ascending limb, and early distal tubule and are known as 'polyvalent' diuretics. Finally, there is a mixed group of weak or adjunctive diuretics which includes the vasodilator xanthines such as aminophylline, and the osmotically active compounds such as mannitol. Available evidence on the molecular mechanisms of action of diuretics in each group is reviewed. The haemodynamic, humoral and physical factors involved in control of electrolyte and fluid handling by the kidney in normal conditions and pathological states are discussed in relation to rational choices of different diuretics in the treatment of various oedematous and non-oedematous conditions.


Effect of water mobility on drug hydrolysis rates in gelatin gels.
The stability of drugs incorporated in gelatin gels was studied, with a focus on the water mobility in the gels. Trichlormethiazide hydrolysis and kanamycin-catalyzed flomoxef hydrolysis in gelatin gels were chosen as models for apparent first-order and second-order hydrolysis, respectively. The mobility of water in gelatin gels was determined by NMR, ESR, and dielectric relaxation spectroscopies. The amount of bound water in the gels was determined from dielectric relaxation spectra. Spin-lattice relaxation time of water determined by 17O NMR and rotational correlation time of an ESR probe determined by an ESR probing method were useful in determining the microviscosity of the gels. The hydrolysis rate of trichlormethiazide in the gels was found to depend on the amount of free water available for the reaction, while that of flomoxef depended on the microviscosity of the gels, which reflected the mobility of water molecules. Thus the dependence of hydrolysis rates on the water mobility was influenced by the hydrolysis mechanism.


Biocompatibility and colorectal anti-cancer activity study of nanosized BaTiO3 coated spinel ferrites.
In the present work, different nanoparticles spinel ferrite series (MFe2O4, Co0.5M0.5Fe2O4; M = Co, Mn, Ni, Mg, Cu, or Zn) have been obtained via sonochemical approach. Then, sol-gel method was employed to design core-shell magnetoelectric nanocomposites by coating these nanoparticles with BaTiO3 (BTO). The structure and morphology of the prepared samples were examined by X-ray powder diffraction (XRD), scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscope (HR-TEM), and zeta potential. XRD analysis showed the presence of spinel ferrite and BTO phases without any trace of a secondary phase. Both phases crystallized in the cubic structure. SEM micrographs illustrated an agglomeration of spherical grains with nonuniformly diphase orientation and different degrees of agglomeration. Moreover, HR-TEM revealed interplanar d-spacing planes that are in good agreement with those of the spinel ferrite phase and BTO phase. These techniques along with EDX analyses confirmed the successful formation of the desired nanocomposites. Zeta potential was also investigated. The biological influence of (MFe2O4, CoMFe) MNPs and core-shell (MFe2O4@BTO, CoMFe@BTO) magnetoelectric nanocomposites were examined by MTT and DAPI assays. Post 48 h of treatments, the anticancer activity of MNPs and MENCs was investigated on human colorectal carcinoma cells (HCT-116) against the cytocompatibility of normal non-cancerous cells (HEK-293). It was established that MNPs possess anti-colon cancer capability while MENCs exhibited a recovery effect due to the presence of a protective biocompatible BTO layer. RBCs hemolytic effect of NPs has ranged from non- to low-hemolytic effect. This effect that could be attributed to the surface charge from zeta potential, also the CoMnFe possesses the stable and lowest zeta potential in comparison with CoFe2O4 and MnFe2O4 also to the protective effect of shell. These findings open up wide prospects for biomedical applications of MNPs as anticancer and MENCs as promising drug nanocarriers.


Quantification of Resident Work in Colorectal Surgery.
To examine resident intraoperative participation, perceived autonomy, and communication patterns between residents and attending surgeons using a novel survey tool. This was a prospective multi-institutional study. Operative residents completed the survey tool immediately after each colorectal resection performed during the study period. Resident intraoperative participation was quantified including degree of involvement in the technical aspects of the case, self-perception of autonomy, and communication strategies between the resident and attending. This study was conducted at 7 general surgery residency programs: 5 academic medical centers, and 2 independent training programs. Residents and fellows rotating on a colorectal surgery service or general surgery service. Sixty-three residents participated in this study with 417 surveys completed (range 19-79 per institution) representing a 95.4% response rate across all sites. Respondents ranged from clinical year 1 (CY1) to fellows. CY3s (35.7%) and CY5s (34.7%) were most heavily represented. Residents completed ≥50% of the skin closure in 88.7% of cases, ≥50% of the fascial closure in 87.1%, and t ≥ 50% of the anastomosis in 78.4% of the cases. Increasing resident participation was associated with advancing resident CY across all technical aspects of the case. This trend remained significant when controlling for site (p < 0.001). Resident self-perception of autonomy revealed learners of all stages: Observer (11.5%, n = 48), Assistant (53.7%, n = 224), Surgeon (33.8%, n = 141), and Teacher (0.96%, n = 4). Level of perceived autonomy increased with resident CY when controlling for site (p < 0.001). Residents who discussed the case before the day of surgery were twice as likely to rate themselves as Surgeon or Teacher (OR = 2.01) when controlling for CY (p = 0.011). Brief surveys can easily capture resident work in the operating room. Resident intraoperative involvement and perceived autonomy are associated with CY. Early communication with the attending is significantly associated with increased perception of autonomy regardless of CY.


Effects of bovine growth hormone (GH) expression in transgenic mice on serum and pituitary immunoreactive mouse GH levels and pituitary GH-releasing factor binding sites.
Pituitary and serum levels of homologous growth hormone (GH) and characteristics of specific GH-releasing factor (GHRF) binding to pituitary homogenates were examined in transgenic mice expressing bovine GH (bGH) gene regulated by different promoters [mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase (PEPCK)] and in their normal littermates. Pituitary GH concentration and GHRF binding were reduced by approximately 50% in transgenic MT-bGH mice in which serum bGH levels were about 20 micrograms/l and by approximately 95% in transgenic PEPCK-bGH mice in which serum bGH levels were tenfold higher. Suppression of plasma immunoreactive mouse GH (mGH) levels was detected in MT-bGH but not in PEPCK-bGH animals, presumably due to cross-reaction of the antiserum employed with bGH. Scatchard plots of GHRF binding to washed homogenates of pituitary glands from normal and young adult MT-bGH transgenic mice were curvilinear, indicating the presence of two types of binding sites, with low and high affinities. Both types of binding sites were reduced in number in MT-bGH transgenic mice without changes in their affinity. In 5-7-month-old MT-bGH transgenic mice there were changes in pituitary GH levels, in GHRF binding levels and in characteristics of GHRF binding that closely resembled the alterations described previously in aging rats. We conclude that over-expression of heterologous GH genes in transgenic mice can lead to partial or virtually complete suppression of somatotroph function, depending on the levels of heterologous GH in the circulation, and that transgenic MT-bGH mice exhibit symptoms of remarkably early onset of neuroendocrine aging.


Comparison of firing patterns in oxytocin- and vasopressin-releasing neurones during progressive dehydration.
The electrical activity of neurosecretory cells in the supraoptic nucleus of the urethane-anaesthetized lactating rat was examined after periods of water deprivation ranging from 0-24 h. Supraoptic units were identified by antidromic activation following stimulation of the neurohypophysis, and classified as oxytocin or vasopressin cells according to their response during reflex milk ejection. In 65 vasopressin cells, dehydration increased the mean firing rate from 2.1 spikes/sec at 0 h to 6.8 spikes/sec at 24 h and caused a change from a slow irregular to a phasic firing pattern. Thus, after 6 h or more of dehydration, 84-100% of the vasopressin cells fired phasically, compared to 12% under normal conditions. In phasic vasopressin cells , the intraburst firing rates were closely related to the stages of dehydration, rising from a mean of 6.3 spikes/sec at 6 h to 12.0 spikes/sec at 24 h. However, no systematic relationship was observed between the stages of dehydration and the mean burst or silence durations. In 77 identified oxytocin units, dehydration increased the firing rate from 0.9 spikes/sec to 2.8 spikes/sec after 24 h, but only 3 (4%) of the cells showed phasic firing. Instead, the oxytocin units changed from a slow irregular to a fast continuous discharge. In conclusion, both vasopressin and oxytocin neurones are activated during chronic dehydration, but there is a marked difference in the pattern of their response. The phasic firing of the vasopressin cells may be important in increasing the occurrence of short interspike intervals and thus facilitating hormone release.


An electrochemiluminescence immunosensor based on signal magnification of luminol using OER-activated NiFe2O4@C@CeO2/Au as effective co-reaction accelerator.
In this work, a novel, label-free electrochemiluminescence (ECL) immunosensor was constructed for the ultrasensitive detection of carbohydrate antigen 15-3 (CA15-3) by the combined use of NiFe2O4@C@CeO2/Au hexahedral microbox and luminol luminophore. The synthesis of the co-reaction accelerator (NiFe2O4@C@CeO2/Au) was related to the calcination of FeNi-based metal-organic framework (MOF), as well as the ingrowth of CeO2 nanoparticles and modification of Au nanoparticles. To be specific, the electrical conductivity will be boosted due to the Au nanoparticles, the synergetic effect generated between CeO2 and calcination FeNi-MOF could offer better activity of oxygen evolution reaction (OER). Herein, the NiFe2O4@C@CeO2/Au hexahedral microbox as a co-reaction accelerator has excellent OER activity and production of reactive oxygen species (ROS), thus increasing the ECL intensity of luminol in a neutral medium without other co-reactants such as H2O2. Because of these benefits, the constructed ECL immunosensor was applied to detect CA15-3 as an example under optimum conditions, the designed ECL immunosensor exhibited high-level selectivity and sensitivity for CA15-3 biomarker within a linear response range of 0.01-100 U mL-1 and an ultralow detection limit of 0.545 mU mL-1 (S/N = 3), demonstrating its potentially valuable application in the area of clinical analysis.


Metabolic syndrome among pre- and post-menopausal rural women in Bangladesh: result from a population-based study.
Prevalence of non-communicable diseases are a challenging problems among menopausal women specially in a least developed country like Bangladesh, where majority of women suffering from at least one chronic diseases after menopausal age. So, the main objective of this study was to determine the prevalence of metabolic syndrome and related risk factors in Bangladeshi pre- and post-menopausal women living in the rural setting. This study is based on a community based cross-sectional survey among 1802 rural women aged ≥15 years. Metabolic syndrome was defined according to the criteria of NCEP-ATP III. Logistic regression was used to estimate the association between menopausal status and metabolic syndrome and its components. Metabolic syndrome was presented in 25.6% respondents and it was more prevalent among post-menopausal (39.3%) as compared to pre-menopausal (16.8%) women. Logistic regression analysis reveals that prevalence of metabolic syndrome was 1.78 times higher in post-menopausal women than pre-menopausal women (P = 0.001). Prevalence of high blood pressure, elevated fasting blood glucose, and high triglyceride were significantly higher in post-menopausal women than pre-menopausal women (P < 0.05). However, prevalence of low high-density lipoprotein cholesterol was significantly lower in post-menopausal women than pre-menopausal women (P < 0.001). Metabolic syndrome seems to be a major health problem among post-menopausal women in many developing countries like Bangladesh and proper policy emphasis should be given on its prevention and control.


Editorial: Prevention's Power: Depression Incidence Halved 15 Years After Participation in the Family Bereavement Program.
Prevention can be powerful. In the current issue of this Journal, Sandler et al. report on the long-term effects of the Family Bereavement Program (FBP), an intervention designed to promote resilience among parentally bereaved youth, as assessed 15 years after receipt of the initial intervention.1 Youth who received the FBP had half the rate of depression compared to those who received the comparison condition (13.46% vs 28.05%). This effect is as large or larger than many of our evidence-based treatments for depression, and considerably more enduring.2 An additional, elegant feature of this paper is that it identifies some mechanisms by which the FBP appears to exert its preventive effects.


Common Variable Immunodeficiency: Diagnosis, Management, and Treatment.
Common variable immunodeficiency (CVID) refers to a grouping of antibody deficiencies that lack a more specific genetic or phenotypic classification. It is the immunodeficiency classification with the greatest number of constituents, likely because of the numerous ways in which antibody production can be impaired and the frequency in which antibody production becomes impaired in human beings. CVID comprises a heterogeneous group of rare diseases. Consequently, CVID presents a significant challenge for researchers and clinicians. Despite these difficulties, both our understanding of and ability to manage this grouping of complex immune diseases has advanced significantly over the past 60 years.


Human placental lactogen, estradiol-17beta, and progesterone levels in the third trimester and their respective values for detecting twin pregnancy.
Plasma levels of HPL, P, and E2 was serially measured between weeks 30 to 36 in simplex and duplex pregnancies. Levels of both HPL and P were significantly higher in duplex than in simplex pregnancies. However, this was not the case for E2. There was a significant correlation between HPL and P levels. It is indicated that measurement of plasma P levels, as those of HPL levels, but not E2 levels is of value for detecting twin pregnancy.


Stenting or not prior to extracorporeal shockwave lithotripsy for ureteral stones? Results of a prospective randomized study.
To determine the need for pre-treatment stenting in patients undergoing extracorporeal shockwave lithotripsy (ESWL) for ureteral stones sized 4-10 mm. A prospective randomized study was conducted between September 2009 and March 2011. Included 156 patients randomized in stented and non-stented groups and underwent a maximum of 3 ESWL sessions. Radiographic follow-up was used to assess the stone fragmentation and clearance. Results were compared in terms of stone-free rates, post-treatment morbidity and complications. Overall efficacy was 76.9%. Stone-free rates were statistically significantly lower (P = 0.026) in the stented group (68.6%) compared to the non-stented ones (83.7%). Furthermore, stenting was significantly correlated with post-treatment lower urinary tract symptoms (P ≤ 0.001), need for more ESWL sessions (P = 0.019) and possibility for operation due to ESWL failure (P = 0.026). A multivariate analysis was conducted to identify the parameters which may predict complete stone removal after ESWL. Stone size (P = 0.026), stone location (P = 0.011) and stenting (P = 0.007) were the most significant factors. ESWL is an efficient and safe treatment for 4- to 10-mm ureteral stones. Pre-treatment stenting is limiting stone-free rates and is significantly influencing post-ESWL morbidity and quality of life in a negative manner, while it contributes minimally to the prophylaxis of complications.


Trends in HIV seroprevalence, AIDS and prevention policy among intravenous drug users and men who have sex with men, before and after 1990 in Austria.
This study reports for the first time on secular trends in human immunodeficiency virus (HIV) infection and AIDS, and possible associations with prevention policy in Austria. We analysed HIV seroprevalence and AIDS cases among intravenous drug users (IDU) and men who have sex with men (MSM). In this study we found a diminished rate of increase in new cases of AIDS and a decline in HIV seroprevalence among IDU but not among MSM. Among clients visiting HIV counselling and testing centres in Austria between 1987 and 1990, seroprevalence among IDU was estimated at 27.9% as compared to 19.6% between 1990 and 1992 (odds ratio (OR): 0.62; 0.45-0.85). Among MSM corresponding prevalence for these two periods was 12.1% and 10.9%, respectively, which was not a significant decline. In the period 1990 to 1994, the increase in AIDS cases per half-year levelled off for IDU (incidence rate ratio (IRR) :1.00; 0.99-1.01) but to a lesser extent among MSM (IRR: 1.01; 1.01-1.02). The most effective prevention policy intervention was considered to be the national Methadone Maintenance Program (MMTP), started in 1987, and the provision of sterile injection equipment. We observed that in the recent period there was a decline in the frequency of attendance among young (less than 28 years of age) MSM at counselling centres (OR: 1.27; 95 % CI: 1.08-1.49), accompanied by the observation that the rate of seroprevalence among this group did not decline. This is in contrast to young IDU where attendance did not decline but seroprevalence did. Although inference is limited from cross sectional studies, we argue for a reoriented and effectively monitored HIV prevention policy focused on young MSM.


Usefulness and problems of Y-Stent and T-Stent assisted coiling for unruptured cerebral aneurysms.
We are going to discuss about usefulness and problems of Y-stent and T-stent assisted coiling for unruptured cerebral aneurysms. A retrospective review was performed to identify patients who were treated using Y-stent or T-stent assisted coiling (Y-SAC, T-SAC) for 25 unruptured cerebral aneurysms from April 2017 to September 2021. Fifteen cases were treated using Y-SAC, 10 were done using T-SAC. Only a case was treated with Low-profile Visualized Intraluminal Support (LVIS; MicroVention TRUMO, Aliso Viejo, California, USA) and Neuroform ATLAS (Striker, Kalamazoo, Michigan, USA), Others were done with two Neuroform ATLAS stents. Y-SAC and T-SAC were succeeded in all cases. In two cases that were treated using Y-SAC, ischemic complications were observed. A patient received additional embolization because subarachnoid hemorrhage (SAH) was appeared after discharge. On follow-up imaging, complete occlusion (CO) was confirmed in all cases. The position of deployment of stents was the most important issue. In particular, the second stent should be deployed as to contact the first stent, as possible. The case that the position of the second stent was shifted, and neck was not covered was observed. In the cases that are treated by using T-SAC, microcatheter must be navigated to distal position as possible. In that point, Y-SAC is more applicable. The familiarization of Y-SAC or T-SAC will expand the indication of endovascular treatment for unruptured cerebral aneurysms.


Clonal T-cell proliferations occasionally occur in Kikuchi-Fujimoto disease.
Kikuchi-Fujimoto disease (KFD) is a benign self-limiting disorder that frequently leads to swelling of cervical lymph nodes in young women. It has a characteristic histologic appearance with sharply demarcated foci containing apoptotic debris, histiocytes, and proliferating large T-cells. Since in the past years, core needle biopsies have been increasingly used for diagnostic work-up, a small biopsy of the pathognomonic proliferating T-cell foci may lead to misinterpretation as a large T-cell neoplasia. The aim of the present study therefore was to analyze how frequently clonal T-cell receptor (TCR) amplificates may be obtained in KFD using a commonly used TCR gamma rearrangement clonality assay. In 88 KFD cases, TCR gamma clonality assays could be successfully applied. Clonal peaks of TCR gamma in front of a polyclonal background were observed in 15 cases (18%). The investigated clinical parameters (age, gender, extent of infiltration of the lymph node, percentage of proliferative compartment) did not differ between patients with detectable TCR gamma clones from those patients who had polyclonal TCR gamma results. Our study therefore demonstrates that clonal TCR gamma amplificates may be obtained in any type of KFD and that an over-interpretation of clonal T-cell proliferates in diagnostically equivocal material should be avoided.


The challenge of keeping it off, a descriptive systematic review of high-quality, follow-up studies of obesity treatments.
The aim of this systematic review is to answer the question: Is substantial, stable, and long-term weight loss a viable goal for adults with obesity? To answer this question, we conducted a broad systematic search of non-surgical and non-pharmacological obesity treatment studies with the following strict criteria: (a) minimum 3-year follow-up, (b) 5% body mass lost, (c) no continued interventions in the follow-up-period, (d) prospective design, and (e) less than 30% attrition from the start of the follow-up period. While the search revealed a very large number of published articles, only eight studies met the inclusion criteria. Several of the nonincluded studies report a majority of participants achieving satisfactory weight loss and little regain, especially among studies with continued interventions during the follow-up period. In contrast, the eight high-quality studies included in this study demonstrate a trend of weight regain towards pretreatment baseline. This review concludes that the majority of high-quality follow-up treatment studies of individuals with obesity are not successful in maintaining weight loss over time. The results suggest that excess weight can be lost but is likely regained over time, for the majority of participants.


Feasibility of low-concentration iodinated contrast medium with lower-tube-voltage dual-source CT aortography using iterative reconstruction: comparison with automatic exposure control CT aortography.
To evaluate the feasibility of low-concentration contrast medium (CM) for vascular enhancement, image quality, and radiation dose on computed tomography aortography (CTA) using a combined low-tube-voltage and iterative reconstruction (IR) technique. Ninety subjects underwent dual-source CT (DSCT) operating in dual-source, high-pitch mode. DSCT scans were performed using both high-concentration CM (Group A, n = 50; Iomeprol 400) and low-concentration CM (Group B, n = 40; Iodixanol 270). Group A was scanned using a reference tube potential of 120 kVp and 120 reference mAs under automatic exposure control with IR. Group B was scanned using low-tube-voltage (80 or 100 kVp if body mass index ≥25 kg/m(2)) at a fixed current of 150 mAs, along with IR. Images of the two groups were compared regarding attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), iodine load, and radiation dose in various locations of the CTA. In comparison between Group A and Group B, the average mean attenuation (454.73 ± 86.66 vs. 515.96 ± 101.55 HU), SNR (25.28 ± 4.34 vs. 31.29 ± 4.58), and CNR (21.83 ± 4.20 vs. 27.55 ± 4.81) on CTA in Group B showed significantly greater values and significantly lower image noise values (18.76 ± 2.19 vs. 17.48 ± 3.34) than those in Group A (all Ps < 0.05). Homogeneous contrast enhancement from the ascending thoracic aorta to the infrarenal abdominal aorta was significantly superior in Group B (P < 0.05). Low-concentration CM and a low-tube-voltage combination technique using IR is a feasible method, showing sufficient contrast enhancement and image quality.


Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice.
The causative link between focal cortical malformations (FCMs) and epilepsy is well accepted, especially among patients with focal cortical dysplasia type II (FCDII) and tuberous sclerosis complex (TSC). However, the mechanisms underlying seizures remain unclear. Using a mouse model of TSC- and FCDII-associated FCM, we showed that FCM neurons were responsible for seizure activity via their unexpected abnormal expression of the hyperpolarization-activated cyclic nucleotide-gated potassium channel isoform 4 (HCN4), which is normally not present in cortical pyramidal neurons after birth. Increasing intracellular cAMP concentrations, which preferentially affects HCN4 gating relative to the other isoforms, drove repetitive firing of FCM neurons but not control pyramidal neurons. Ectopic HCN4 expression was dependent on the mechanistic target of rapamycin (mTOR), preceded the onset of seizures, and was also found in diseased neurons in tissue resected from patients with TSC and FCDII. Last, blocking HCN4 channel activity in FCM neurons prevented epilepsy in the mouse model. These findings suggest that HCN4 play a main role in seizure and identify a cAMP-dependent seizure mechanism in TSC and FCDII. Furthermore, the unique expression of HCN4 exclusively in FCM neurons suggests that gene therapy targeting HCN4 might be effective in reducing seizures in FCDII or TSC.


Long-term breast cancer survivors' perceptions of support from female partners: an exploratory study.
To describe the social support experiences of long-term breast cancer survivors who have female partners, from the perspective of survivors. Descriptive study using qualitative methods. United States. A purposive convenience sample of 15 partnered sexual minority women (SMW) (e.g., women with female partners) diagnosed with nonmetastatic breast cancer from 2000-2005. One-on-one interviews were conducted by telephone. Interviews were semistructured through the use of an interview guide. Transcribed data were coded and analyzed to identify emergent themes. Perceptions of support and broad aspects of the intimate partner relationship that may critically impact the psychological well-being of SMW following breast cancer. Six salient themes describe SMW survivors' perceptions of support: (a) female partners are the singular source of survivors' most valuable support; partners support survivors by (b) discussing survivors' health and distress, which survivors associate with (c) perceived partner distress, and (d) managing the home and caretaking, which survivors associate with (e) perceived partner burden; and partners support survivors by (f) sharing in a life beyond cancer. Female partners play a central and comprehensive support role as well as experience ongoing stress and burden related to survivors' cancer. Future research and direct investigation may inform healthcare providers about caring for SMW and their families following breast cancer.


Decreasing Influence of Retinal Inputs on the Developing Visual Cortex.
Before vision matures, spontaneous retinal activity drives downstream visual targets. In this issue of Neuron, Gribizis et al. (2019) image activity simultaneously in connected mouse visual areas and demonstrate distinct developmental patterns of signal transformation in thalamocortical versus retinocollicular pathways.


[Study on the compliance of antihypertensive drugs in patients with hypertension].
To study the compliance of antihypertensive drugs and its related factors in inpatients and outpatients patients with hypertension. Clinical data of 816 inpatients and 497 outpatients were reviewed to study the compliance of antihypertensive drugs and related factors as well as to investigate the utilization of anti-hypertensive medicament, the incidence of the side-effect of the medication and to explore the difference of the blood pressure control between the compliant group and the uncompliant group. The main risk factors of the hypertensive patients were in the order as: disorder of lipometabolism, smoking, left ventricular hypertrophy (LVH) and Diabetes mellitus. Sixty point nine percent of the inpatients were followed up. The incidences of compliance were 63.4% in the inpatients, 77.3% when being discharged, and 43.7% in the outpatients. The cause of uncompliance were as follows: side-effect of the medication, failure to control BP, financial problems, etc. Data gathered during follow up period, it was found the side effect of the calcium antagonist and the diuretics improved palpably. Those compliers controlled their BP well, while little fluctuation of BP was observed. However, the uncompliers showed different pictures, and the range of fluctuation of BP was large. The compliance of the medicament was best among the outpatients to the discharge order, and the compliance of the outpatients was the worst.


Assessment of inhalation exposure to indoor air pollutants: Screening for health risks of multiple pollutants in Japanese dwellings.
Over the past few decades, multiple low level indoor pollutants have been found in domestic dwellings. The types and concentrations of these indoor pollutants have not been consistent over time and have changed with alterations in lifestyle, the development of novel products used in housing, and the development of new measurement technologies. To clarify the highest risk pollutants for which health risks should be reduced, we conducted a health risk assessment of 49 indoor air pollutants measured in 602 houses during winter and summer from 2012 to 2014. Inhalation reference concentrations were determined, and the margins of exposure were estimated for each indoor pollutant from measured indoor air concentrations. Health risks due to ammonia and acidic gases, including formic acid, acetic acid, and hydrogen chloride, were also assessed. Overall, during both winter and summer, the highest risk pollutants were acrolein, nitrogen dioxide, benzene, formic acid, and hydrogen chloride. The health risks of propanal, acetaldehyde, and 1,4-dichlorobenzene were also high. Principal component analysis (PCA) suggested an independent principal component for 1,4-dichlorobenzene. The primary source of exposure to 1,4-dichlorobenzene in Japan is an indoor household insect repellent. The improvement of individual lifestyle and housing may be appropriate targets for reducing the risk associated with this compound. The provision of further information on the risk to consumers and promotion of changes in consumer consciousness are needed. PCA suggested that the health risks of indoor air pollutants are amalgamated into similar chemical families, such as aldehydes, aliphatic hydrocarbons, aromatic hydrocarbons, or acetic esters. Our results suggest that health-based guidelines or source control measures, based on these chemical families and similar health endpoints, are appropriate for reducing total health risk due to multiple low level indoor pollutants.


Cross-arch splinting with resin-bonded retainers.
The procedure described can provide innovative cross-arch splinting for patients. The longevity of resin-bonded restorations has not been determined, but the procedure is promising, economical, and reversible. These facts should be made available to patients during presentation of the treatment plan.


Motion sickness increases the risk of accidental hypothermia.
Motion sickness (MS) has been found to increase body-core cooling during immersion in 28 degrees C water, an effect ascribed to attenuation of the cold-induced peripheral vasoconstriction (Mekjavic et al. in J Physiol 535(2):619-623, 2001). The present study tested the hypothesis that a more profound cold stimulus would override the MS effect on peripheral vasoconstriction and hence on the core cooling rate. Eleven healthy subjects underwent two separate head-out immersions in 15 degrees C water. In the control trial (CN), subjects were immersed after baseline measurements. In the MS-trial, subjects were rendered motion sick prior to immersion, by using a rotating chair in combination with a regimen of standardized head movements. During immersion in the MS-trial, subjects were exposed to an optokinetic stimulus (rotating drum). At 5-min intervals subjects rated their temperature perception, thermal comfort and MS discomfort. During immersion mean skin temperature, rectal temperature, the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (DeltaTff), oxygen uptake and heart rate were recorded. In the MS-trial, rectal temperature decreased substantially faster (33%, P < 0.01). Also, the DeltaTff response, an index of peripheral vasomotor tone, as well as the oxygen uptake, indicative of the shivering response, were significantly attenuated (P < 0.01 and P < 0.001, respectively) by MS. Thus, MS may predispose individuals to hypothermia by enhancing heat loss and attenuating heat production. This might have significant implications for survival in maritime accidents.


Ect2, an ortholog of Drosophila Pebble, regulates formation of growth cones in primary cortical neurons.
In collaboration with Marshall Nirenberg, we performed in vivo RNA interference (RNAi) genome-wide screening in Drosophila embryos. Pebble has been shown to be involved in Drosophila neuronal development. We have also reported that depletion of Ect2, a mammalian ortholog of Pebble, induces differentiation in NG108-15 neuronal cells. However, the precise role of Ect2 in neuronal development has yet to be studied. Here, we confirmed in PC12 pheochromocytoma cells that inhibition of Ect2 expression by RNAi stimulated neurite outgrowth, and in the mouse embryonic cortex that Ect2 was accumulated throughout the ventricular and subventricular zones with neuronal progenitor cells. Next, the effects of Ect2 depletion were studied in primary cultures of mouse embryonic cortical neurons: Loss of Ect2 did not affect the differentiation stages of neuritogenesis, the number of neurites, or axon length, while the numbers of growth cones and growth cone-like structures were increased. Taken together, our results suggest that Ect2 contributes to neuronal morphological differentiation through regulation of growth cone dynamics.


Comparison of left atrial and left atrial appendage mechanics in the recurrence of atrial fibrillation after radiofrequency catheter ablation.
Although radiofrequency catheter ablation (RFCA) has become an important treatment strategy for paroxysmal or persistent atrial fibrillation (AF), AF recurrence after RFCA remains an important issue that plagues clinicians and patients. This study aimed to investigate the association of left atrial (LA) and left atrial appendage (LAA) mechanics with AF recurrence after RFCA and to compare their prognostic values in patients with AF undergoing RFCA. A total of 160 patients with non-valvular AF who underwent RFCA for the first time were included in this study. All patients underwent transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) before the procedure. All patients were followed up for one year after RFCA, and AF recurrence was recorded. Speckle-tracking echocardiography was used to measure LA and LAA global longitudinal strain (GLS). LA and LAA mechanical dispersion (MD) were defined as the standard deviation of time to peak strain at each segment standardized by the R-R interval. Logistic regression analysis was used to analyze independent contributors for AF recurrence after RFCA. The prediction efficiency of factors associated with the presence of AF recurrence was evaluated by the receiver operating characteristic (ROC) curve with area under curve (AUC). During 1-year follow-up, 45 (28%) patients had recurrence, and 115 (72%) patients had no recurrence. The age, CHA2 DS2 -VASc score, NT-proBNP, LA volume index (LAVI), LA MD, and LAA MD of patients in recurrence group were significantly higher than those in no recurrent group (p < .05). The LAA emptying fraction (LAAEF), LA GLS, and LAA GLS in recurrence group were significantly lower than those in no recurrent group (p < .05). Logistic regression analysis showed that LA and LAA GLS were independent contributors for AF recurrence (p < .05), providing incremental values. The AUCs of LA and LAA GLS in predicting AF recurrence were higher than that of other factors, and the LA GLS+LAA GLS joint model had higher prediction efficiency. This study demonstrated the LA and LAA GLS were independent contributors for AF recurrence after RFCA and provided incremental values. LA and LAA GLS can be used as the predictor of AF recurrence after RFCA, and they may be beneficial for the risk stratification of AF recurrence.


Construction and evaluation of the eukaryotic expression plasmid encoding two copies of somatostatin genes fused with hepatitis B surface antigen gene S.
The aim of current study was to evaluate the prospects of somatostatin DNA vaccine. Two copies of somatostatin (SS) genes were fused with the hepatitis B surface antigen (HBsAg) S gene using genetic engineering methods, the identified recombinant plasmid designated as pcS/2SS was transfected into HeLa cells to detect expression and antigenicity of target fusion protein, and its immunoreaction as well as safety was evaluated with animal experiments. The expressed target protein had a specific reaction with somatostatin antibody and showed a single strip result. A single injection of this vector stimulated long-term antigen-specific antibody responses in rats, and peak antibody levels occurred at the 2nd week of the initial injection. Additionally, the 50 microg immunized group resulted in a 13.5% increase in growth rate as compared with control group (111.7 g vs. 98.4 g). The genomic DNA was assayed for integrated plasmid using a sensitive PCR method, and the risk of mutation due to integration of pcS/2SS plasmid following intramuscular injection in mice was negligible. The successful construction of pcS/2SS DNA vaccine with good immunogenicity and safety has prospects to promote growth of animals.


The protective role of vitamin E on gill and liver tissue histopathology and micronucleus frequencies in peripheral erythrocytes of Oreochromis niloticus exposed to deltamethrin.
Deltamethrin, is a commonly used pyrethroid pesticide. Vitamin E is a antioxidant that plays an important role in protecting cells against toxicity by inactivating free radicals generated following pesticides exposure. Therefore, it was evaluated whether deltamethrin induced histopathological changes and nuclear abnormalities using micronucleus test in Oreochromis niloticus, and the possible protective effect of vitamin E against deltamethrin inducing adverse effects in O. niloticus were investigated. Fish was fed with no pesticide+control diet, no pesticide+vitamin E-supplemented diet, 1.45μg/l deltamethrin+control diet, 1.45μg/l deltamethrin+vitamin E-supplemented diet for 30 days. Pesticide and diet quality made an impact on histopathological lesions. In treatments of deltamethrin, group fed with control diet showed much greater damage in comparison with group fed with vitamin E supplemented diet. Vitamin E decreased some histopathological changes induced by deltamethrin, but did not confer complete protection. Deltamethrin treatment has been shown to results in a significant increase in the frequency of micronucleus. However, coadministration of deltamethrin and vitamin E showed decrease in the frequency of micronucleus as compared to deltamethrin treated fish. Our results indicate that, the MN assay and histopathology can be used as bioassays for monitoring pollution in aquatic medium. On the other hand, it was observed that vitamin E decreased the genotoxicity and histopathological changes induced by deltamethrin.


The antiviral drug ganciclovir does not inhibit microglial proliferation and activation.
Ganciclovir is effective in the treatment of human infections with viruses of the Herpesviridae family. Beside antiviral properties, recently ganciclovir was described to inhibit microglial proliferation and disease severity of experimental autoimmune encephalomyelitis, an inflammatory model of multiple sclerosis. Microglial activation and proliferation are main characteristics of neuroinflammatory CNS diseases and inhibition of microglial functions might be beneficial in autoimmune diseases, or detrimental in infectious diseases. The objective of this study was to determine potential inhibitory effects of ganciclovir in three different murine animal models of CNS neuroinflammation in which microglia play an important role: Theiler´s murine encephalomyelitis, the cuprizone model of de- and remyelination, and the vesicular stomatitis virus encephalitis model. In addition, in vitro experiments with microglial cultures were performed to test the hypothesis that ganciclovir inhibits microglial proliferation. In all three animal models, neither microglial proliferation or recruitment nor disease activity was changed by ganciclovir. In vitro experiments confirmed that microglial proliferation was not affected by ganciclovir. In conclusion, our results show that the antiviral drug ganciclovir does not inhibit microglial activation and proliferation in the murine CNS.


Reconstructive kidney surgery for organ-preserving therapy of renal tumors.
The objective of this study was to evaluate differences in various clinical endpoints in patients with reconstructive surgery by renal partial nephrectomy for tumors up to 4 cm compared to tumors larger than 4 cm. A total of 170 partial renal resection patients that presented malignant tumors were included in the retrospective study. Data was analyzed retrospectively based on internal clinic files, as well as a questionnaire to enhance the follow-up clinical outcomes data obtained. The most important outcomes determined included post-operative renal function, intra- and post-operative complications, local recurrence rate and total survival time. The local recurrence rate was 6.1% for tumors up to 4 cm in size, compared to 14.9% for tumors that were larger than 4 cm. Compared to results for partial resection of T1a tumors, results for partial resection of tumors larger than 4 cm are worse in terms of post-operative renal function (p=0.007), as well as in terms of a total complications rate (p=0.048). It is important to note that there was not only a higher risk of post-operative bleeding that required transfusions (p=0.012), but also a higher risk of a hypertensive episode during the post-operative period reviewed (p=0.022). In addition, the total survival time for patients presenting tumors of up to 4 cm in size was significantly better (p=0.003). The results of our retrospective study of 170 patients that underwent partial renal resection after the diagnosis of malignant tumors, is that partial renal resection presents an oncologicaly safe surgical solution with low local recurrence rates. Additionally, partial resection in case of tumors that are larger than 4 cm showed worse post-operative renal function, a higher complications rate and a worse survival rate.