Benzalkonium Chloride Demonstrates Concentration-Dependent Antiviral Activity Against Adenovirus In Vitro.
Purpose: Adenoviral conjunctivitis is the most common cause of conjunctivitis worldwide with no approved antiviral treatment. Benzalkonium chloride (BAK) is a common preservative in ophthalmic medications and is the active ingredient in some skin disinfectants and hand sanitizers. BAK is known to be effective in killing bacteria and enveloped viruses; however, its activity against ocular types of nonenveloped adenoviruses (Ads) is unknown. The goal was to determine whether BAK is an effective antiviral agent against common human ocular types of adenovirus in vitro. Methods: The direct inactivating activity of BAK was determined by incubating several human adenovirus types with BAK concentrations of 0.001%, 0.003%, 0.005%, 0.01%, 0.1%, and 0% for 1 h at 33°C. Resulting adenovirus titers were determined after treatment. Decreases in titers of ≥3 Log10 were considered virucidal, while decreases in titers of <1 Log10 were considered ineffective. Results: BAK 0.1% was virucidal for Ad3, Ad5, Ad7a, Ad19/64, and Ad37, while it reduced titers >1 Log10, but <3 Log10 for Ad4 and Ad8. Decreases in titers >1 Log10 were demonstrated for BAK 0.003%, 0.005%, and 0.01% for Ad5 only. Decreases in titers for the other adenovirus types for those concentrations were ≤0.53 Log10. 0.001% BAK produced minimal decreases in titers for all types. Conclusions: BAK, at 0.01% or less was not consistently effective as an antiviral against adenovirus, but higher concentrations, such as 0.1%, should be further investigated as a possible topical treatment for adenoviral ocular infections, providing ocular toxicity is not an issue.


Flexible Use of Spatial Frames of Reference for Object-Location Memory in Older Adults.
In memory, representations of spatial features are stored in different reference frames; features relative to our position are stored egocentrically and features relative to each other are stored allocentrically. Accessing these representations engages many cognitive and neural resources, and so is susceptible to age-related breakdown. Yet, recent findings on the heterogeneity of cognitive function and spatial ability in healthy older adults suggest that aging may not uniformly impact the flexible use of spatial representations. These factors have yet to be explored in a precisely controlled task that explicitly manipulates spatial frames of reference across learning and retrieval. We used a lab-based virtual reality task to investigate the relationship between object-location memory across frames of reference, cognitive status, and self-reported spatial ability. Memory error was measured using Euclidean distance from studied object locations to participants' responses at testing. Older adults recalled object locations less accurately when they switched between frames of reference from learning to testing, compared with when they remained in the same frame of reference. They also showed an allocentric learning advantage, producing less error when switching from an allocentric to an egocentric frame of reference, compared with the reverse direction of switching. Higher MoCA scores and better self-assessed spatial ability predicted less memory error, especially when learning occurred egocentrically. We suggest that egocentric learning deficits are driven by difficulty in binding multiple viewpoints into a coherent representation. Finally, we highlight the heterogeneity of spatial memory performance in healthy older adults as a potential cognitive marker for neurodegeneration, beyond normal aging.


Intestinal in vitro and ex vivo Models to Study Host-Microbiome Interactions and Acute Stressors.
The gut microbiome is extremely important for maintaining homeostasis with host intestinal epithelial, neuronal, and immune cells and this host-microbe interaction is critical during times of stress or disease. Environmental, nutritional, and cognitive stress are just a few factors known to influence the gut microbiota and are thought to induce microbial dysbiosis. Research on this bidirectional relationship as it pertains to health and disease is extensive and rapidly expanding in both in vivo and in vitro/ex vivo models. However, far less work has been devoted to studying effects of host-microbe interactions on acute stressors and performance, the underlying mechanisms, and the modulatory effects of different stressors on both the host and the microbiome. Additionally, the use of in vitro/ex vivo models to study the gut microbiome and human performance has not been researched extensively nor reviewed. Therefore, this review aims to examine current evidence concerning the current status of in vitro and ex vivo host models, the impact of acute stressors on gut physiology/microbiota as well as potential impacts on human performance and how we can parlay this information for DoD relevance as well as the broader scientific community. Models reviewed include widely utilized intestinal cell models from human and animal models that have been applied in the past for stress or microbiology research as well as ex vivo organ/tissue culture models and new innovative models including organ-on-a-chip and co-culture models.


Control of thermal runaway and uniformity of heating in the electromagnetic rewarming of a cryopreserved kidney phantom.
Successful cryopreservation of whole organs may require electromagnetic (EM) heating at much faster warming rates than those at which thermal relaxation can smooth out nonuniform power distribution or suppress hot spots which become unstable due to an increase of power absorbtion with temperature in the material being heated. Calculations of the heating distribution for a uniform spherical workpiece in a resonant EM applicator show that the size of a workpiece for which there will be good uniformity of heating has a sharp upper limit given D < or = 0.3 lambda m, where D is the workpiece diameter and lambda m is the EM wavelength in the material. We also introduce three stability factors which indicate whether thermal runaway can occur; they are dependent solely on the material's dielectric properties and the geometry and orientation of any irregularities. These factors provide clear guidelines to the choice of source frequency and applicator geometry that are favorable for intrinsic control of thermal runaway. Experimental results are presented for spherical phantom workpieces of 36- and 45-mm diameter, rewarmed from -90 to above 0 degrees C in 30 to 150 s, in a 434-MHz resonant cavity applicator. The observed spatial temperature distributions for different E-field configurations clearly indicate the effectiveness of the stability factors in predicting uniformity of temperature, and the significance of the workpiece size limit, in practical EM heating situations.


α7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex.
Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the α7 nicotinic acetylcholine receptor (nAChR) agonist SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be normalized once they have already occurred. Here we use semi-quantitative in situ hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d. for 5 days) subsequent to repeated PCP administration (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP-induced increase in Arc mRNA expression in the same regions. In contrast, subsequent administration of SSR180711 does not affect PCP-induced decreases in parvalbumin mRNA in the mPFC, and glutamate decarboxylase 67 mRNA in the mPFC or VLO. These data demonstrate that it is possible to restore some, but not all, of the molecular dysregulations induced by repeated PCP administration with an α7 nAChR agonist. They also suggest that the previously demonstrated cognitive improvement with SSR180711 subsequent to PCP treatment does not require normalization of parvalbumin expression, but may instead be related to a restoration of synaptophysin and/or Arc levels in the frontal cortex. These data lend support to the potential for development of α7 nAChR agonists for the treatment of cognitive deficits in schizophrenia.


High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions.
Somatic mutations activating telomerase reverse-trancriptase promoter were recently identified in several tumour types. Here we identify frequent similar mutations in human hepatocellular carcinomas (59%), cirrhotic preneoplastic macronodules (25%) and hepatocellular adenomas with malignant transformation in hepatocellular carcinomas (44%). In hepatocellular tumours, telomerase reverse-transcripase- and CTNNB1-activating mutations are significantly associated. Moreover, preliminary data suggest that telomerase reverse-trancriptase promoter mutations can increase the expression of telomerase transcript. In conclusion, telomerase reverse-trancriptase promoter mutation is the earliest recurrent genetic event identified in cirrhotic preneoplastic lesions so far and is also the most frequent genetic alteration in hepatocellular carcinomas, arising from both the cirrhotic or non-cirrhotic liver.


[Randomized phase II trial to compare S-1 and S-1/PSK for advanced or recurrent gastric cancer-lessons from the results].
This is a randomized phase II trial to evaluate non-inferiority of progression-free surviva(l PFS) by comparing S-1 and S-1/PSK for advanced or recurrent gastric cancer. Sample size was calculated to be 120. However, the trial was terminated because of slow accrual. This exploratory analysis was done by collecting the minimum data. Only 8 patients were enrolled. Four patients were randomly assigned to S-1 and the others to S-1/PSK. Performance status was 0 in all 8 patients. Median age was 64. Median overall survival was 13.7 months in all 8 patients, 8 . 9 months in S-1 group, and 13 . 7 months in S-1/PSK group. When considering PS 0 in 8 patients enrolled, an overall survival was comparable to that observed in S-1 group of other phase III trials. Standard chemotherapy for advanced gastric cancer was changed to S-1/CDDP by SPIRITS phase III trial which was presented just after this trial was initiated, which would be a major cause of slow accrual. When conducting phase III trial, we should carefully determine design and standard arm by considering on-going phase III trial.


Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5.
Neutral lipid storage disease (NLSD) is a group of autosomal recessive disorders characterized by the excessive accumulation of neutral lipids in multiple tissues. Recently, two genes, adipose triglyceride lipase (ATGL/PNPLA2) and comparative gene identification-58 (CGI-58/ABHD5), have been shown to cause NLSD. ATGL specifically hydrolyzes the first fatty acid from triacylglycerols (TG) and CGI-58/ABHD5 stimulates ATGL activity by a currently unknown mechanism. Mutations in both the ATGL and the CGI-58 genes are associated with systemic TG accumulation, yet the resulting clinical manifestations are not identical. Patients with defective ATGL function suffer from more severe myopathy (NLSDM) than patients with defective CGI-58 function. On the other hand, CGI-58 mutations are always associated with ichthyosis (NLSDI), which was not observed in patients with defective ATGL function. These observations indicate an ATGL-independent function of CGI-58. This review summarizes recent findings with the goal of relating structural variants of ATGL and CGI-58 to functional consequences in lipid metabolism.


Molecular architecture via coordination: self-assembly of nanoscale hexagonal metallodendrimers with designed building blocks.
The first self-assembly of nanoscale metallodendrimers that have a hexagonal cavity as a core via the directional-bonding approach is reported. All metallodendrimers were characterized by multinuclear NMR (1H and 31P), mass spectrometry (ESI-MS and ESI-FT-ICR), and elemental analysis.


The intravenous urogram in acute epididymo-orchitis.
In a series of patients presenting with acute epididymo-orchitis, the abnormalities detected on intravenous urography were analysed. Urography is recommended in patients aged over 50 and in pre-pubertal boys, but it did not prove useful in adult patients under 50 years of age without other symptoms.


Hereditary progressive mucinous histiocytosis: first report in a male patient.
Progressive mucinous histiocytosis is a very rare, benign, non-Langerhans' cell histiocytosis limited to the skin. In total ten patients (all women) in four families and three sporadic cases have been reported. We report here the first published case of a male patient with progressive mucinous histiocytosis. The multiple red papules on the scalp and forearms were asymptomatic and had slowly increased over approximately the past 20 years. The patient's mother had similar lesions. Histological examination revealed nodules in the dermis with histiocytes and mucin deposition. The histiocytes stained positively with CD31 and negative with CD34, CAM 5.2, PGM-1 and factor XIIIa. Ultrastructurally, the histiocytes showed numerous circular myelin bodies and zebra bodies reminiscent of those seen in lysosomal storage diseases. The genetic transmission of hereditary progressive mucinous histiocytosis remains unclear; we assume an autosomal dominant transmission with some hormonal factor that makes hereditary progressive mucinous histiocytosis more likely in women.


Combustion Synthesis of High Density ZrN/ZrSi2 Composite: Influence of ZrO2 Addition on the Microstructure and Mechanical Properties.
In this study, a high-density ZrN/ZrSi2 composite reinforced with ZrO2 as an inert phase was synthesized under vacuum starting with a Zr-Si4N3-ZrO2 blend using combustion-synthesis methodology accompanied by compaction. The effects of ZrO2 additions (10-30 wt%) and compression loads (117-327 MPa) on the microstructure, porosity and hardness of the samples were studied. The process was monitored using XRD, SEM, EDS, porosity, density and hardness measurements. Thermodynamic calculations of the effect of ZrO2 addition on the combustion reaction were performed including the calculation of the adiabatic temperatures and the estimation of the fractions of the liquid phase. The addition of up to 20 wt% ZrO2 improved the hardness and reduced the porosity of the samples. Using 20 wt% ZrO2, the sample porosity was reduced to 1.66 vol%, and the sample hardness was improved to 1165 ± 40.5 HV at 234 MPa.


Advancing neuroscience through epigenetics: molecular mechanisms of learning and memory.
Humans share 96% of our 30,000 genes with Chimpanzees. The 1,200 genes that differ appear at first glance insufficient to describe what makes us human and them apes. However, we are now discovering that the mechanisms that regulate how genes are expressed tell a much richer story than our DNA alone. Sections of our DNA are constantly being turned on or off, marked for easy access, or secluded and hidden away, all in response to ongoing cellular activity. In the brain, neurons encode information-in effect memories-at the cellular level. Yet while memories may last a lifetime, neurons are dynamic structures. Every protein in the synapse undergoes some form of turnover, some with half-lives of only hours. How can a memory persist beyond the lifetimes of its constitutive molecular building blocks? Epigenetics-changes in gene expression that do not alter the underlying DNA sequence-may be the answer. In this article, epigenetic mechanisms including DNA methylation and acetylation or methylation of the histone proteins that package DNA are described in the context of animal learning. Through the interaction of these modifications a "histone code" is emerging wherein individual memories leave unique memory traces at the molecular level with distinct time courses. A better understanding of these mechanisms has implications for treatment of memory disorders caused by normal aging or diseases including schizophrenia, Alzheimer's, depression, and drug addiction.


Field-dependence/independence: considerations in staff development.
Clinical nurse preceptors, staff development specialists, and staff nurses are becoming more involved with the clinical learning experiences of new graduates, nursing school students, and the highly mobile, experienced nurse. Assessment of learning styles and the cognitive process is necessary for the implementation of successful orientation programs. Consideration of the bipolar learning style of field-dependence/independence can be useful for preceptors involved with teaching in the clinical setting. This article reviews the development of the concept of field-dependence/independence, identifies associated characteristics, and discusses assessment of learning style. Specific teaching strategies for both field-dependent and field-independent learners are discussed.


Mobilization of endothelial progenitor cells in patients with acute myocardial infarction.
Endothelial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNC(CD34+)), are mobilized into PB in acute ischemic events in humans. Flow cytometry revealed that circulating MNC(CD34+) counts significantly increased in patients with acute myocardial infarction (n=16), peaking on day 7 after onset, whereas they were unchanged in control subjects (n=8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively correlated with circulating MNC(CD34+) counts (r=0.35, P=0.01). This is the first clinical demonstration showing that lineage-committed EPCs and MNC(CD34+), their putative precursors, are mobilized during an acute ischemic event in humans.


The hybrid perventricular closure of apical muscular ventricular septal defect with Amplatzer duct occluder.
Apical muscular ventricular septal defects (MVSDs), especially in small infants, can be difficult to manage using surgical and percutaneous closure. An intraoperative perventricular procedure is a good option for closing apical MVSDs in small children with or without associated cardiac anomalies. We evaluated the results of hybrid perventricular closure of apical MVSDs performed using an Amplatzer duct occluder (ADO). We retrospectively reviewed the medical records of 5 patients who underwent hybrid perventricular closure of MVSDs with ADOs, from March 2006 to May 2011. The median patient age at the time of the procedure was 12 months (range, 25 days to 25 months), and the median body weight was 9.1 kg (range, 4.3 to 15 kg). Two patients had multiple ventricular septal defects (VSDs; additional perimembranous VSD in 1 patient and multiple MVSDs in the other) and 3 patients had associated cardiac anomalies; complete transposition of the great arteries in 1 patient and an atrial septal defect in 2 patients. All the procedures were performed on beating hearts, exception in 1 case. The ADO selected for the aortic side was at least 1 to 2 mm larger than the largest VSD in the left ventricle side. The procedure was successful in all patients and each device was well positioned. During the median follow-up of 2.4 years, a small residual VSD was noted in 2 patients who had multiple VSDs and no leakage was seen in the other 3 patients. Perventricular closure of MVSD with an ADO is a good option for patients with apical MVSD. However, careful manipulation is important, especially in the case of small infants.


Magnetic resonance imaging of perfusion in the isolated rat heart using spin inversion of arterial water.
Measurement of regional myocardial perfusion is important for the diagnosis and treatment of coronary artery disease. Currently used methods for the measurement of myocardial tissue perfusion are either invasive or not quantitative. Here, we demonstrate a technique for the measurement of myocardial perfusion using magnetic resonance imaging (MRI) with spin tagging of arterial water. In addition, it is shown that changes in perfusion can be quantitated by measuring changes in tissue T1. Perfusion images are obtained in Langendorff-perfused, isolated rat hearts for perfusion rates ranging from 5 to 22 ml/g/min. The MRI-determined perfusion rates are in excellent agreement with perfusion rates determined from measurement of bulk perfusate flow (r = 0.98). The predicted linear dependence of the measured T1 (T1app) on perfusion is also demonstrated. The ability of perfusion imaging to measure regional variations in flow is demonstrated with hearts in which perfusion defects were created by ligation of a coronary artery. These results indicate that MRI of perfusion using spin inversion of arterial water gives quantitative maps of cardiac perfusion.


Quorum Sensing System in Bacteroides thetaiotaomicron Strain Identified by Genome Sequence Analysis.
This study is a bioinformatics assay on the microbial genome of Bacteroides thetaiotaomicron. The study focuses on the problem of quorum sensing as a result of adverse factors such as chemotherapy and antibiotic therapy. In patients with severe intestinal diseases, two strains of microorganisms were identified that were distinguished as new. Strains were investigated by conducting genome sequencing. The current concepts concerned with the quorum sensing system regulation by stationary-phase sigma factor and their coregulation of target genes in B. thetaiotaomicron were considered. The study suggested using bioinformatics data for the diagnosis of gastrointestinal disorders. In the course of the study, 402 genes having a greater than twofold change were identified with the 95% confidence level. The shortest and longest coding genes were predicted; the noncoding genes were detected. Biological pathways (KEGG pathways) were classified into the following categories: cellular processes, environmental information processing, genetic information processing, human disease, metabolism, and organismic systems. Among notable changes in the biofilm population observed in parallel to the planktonic B. thetaiotaomicron was the expression of genes in the polysaccharide utilization loci that were involved in the synthesis of O-glycans.


The Vital Role of 131 I-MIBG in Localization of Paraganglioma at Unusual Sites.
Paragangliomas (PGLs) are extra-adrenal neuroendocrine tumors. PGL of the urinary bladder are very rare and commonly present with features of hypertensive crisis, headache, syncope, and other symptoms of sympathetic excess. A few of these tumors are silent at the presentation. Here, we report a case of a urinary bladder PGL, presenting with lower abdominal pain.


Association of Sociodemographic and Psychosocial Factors With COVID-19-Related Post-Traumatic Stress Disorder Risk Group Among Medical Students.
Several previous studies have reported the negative psychological impact of the coronavirus disease (COVID-19) pandemic on medical students worldwide. This study investigated the sociodemographic and psychosocial factors associated with COVID-19-related post-traumatic stress disorder (PTSD) risk among medical students in Daegu, a region that experienced a high concentration of infections. A total of 270 students completed the self-reported questionnaires including COVID-19 exposure, psychological measurement, and sociodemographic factors. We evaluated the COVID-19-related PTSD risk group using the Korean version of the Impact of Event Scale-Revised. Logistic regression analysis was performed to evaluate the odds ratio for the COVID-19-related PTSD risk group in sociodemographic and psychosocial factors. The prevalence of the COVID-19-related PTSD risk group was 10.4% in medical students. Among sociodemographic factors, lower grades (specially, first-year medical students) and current smokers were associated with the COVID-19-related PTSD risk. Indirect exposure to COVID-19 was also associated with this risk. Meanwhile, having higher resilience, self-esteem, and social support were less likely to be associated with COVID-19-related PTSD risk. This study suggested that it is necessary to develop a system for the screening and managing of COVID-19-related PTSD risk group among medical students, especially high-risk groups during the COVID-19 pandemic.


Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer's disease patients from non-demented subjects.
Alzheimer's disease (AD) is the most common age-related dementia. Among its major challenges is identifying molecular signatures characteristic for the early AD stage in patients with Mild Cognitive Impairment (MCI-AD), which could serve for deciphering the AD pathomechanism and also as non-invasive, easy-to-access biomarkers. Using qRT-PCR we compared the microRNA (miRNA) profiles in blood plasma of 15 MCI-AD patients, whose diagnoses were confirmed by cerebrospinal fluid (CSF) biomarkers, with 20 AD patients and 15 non-demented, age-matched individuals (CTR).To minimize methodological variability, we adhered to standardization of blood and CSF assays recommended by the international Joint Programming for Neurodegenerative Diseases (JPND) BIOMARKAPD consortium, and we employed commercially available Exiqon qRT-PCR-assays. In the first screening, we assessed 179 miRNAs of plasma. We confirmed 23 miRNAs reported earlier as AD biomarker candidates in blood and found 26 novel differential miRNAs between AD and control subjects. For representative 15 differential miRNAs, the TargetScan, MirTarBase and KEGG database analysis indicated putative protein targets among such AD hallmarks as MAPT (Tau), proteins involved in amyloidogenic proteolysis, and in apoptosis. These 15 miRNAs were verified in separate, subsequent subject groups. Finally, 6 miRNAs (3 not yet reported in AD context and 3 reported in AD blood) were selected as the most promising biomarker candidates differentiating early AD from controls with the highest fold changes (from 1.32 to 14.72), consistent significance, specificities from 0.78 to 1 and sensitivities from 0.75 to 1. (patent pending, PCT/IB2016/052440).


Concise synthesis of multisubstituted isoquinolines from pyridines by regioselective Diels-Alder reactions of 2-silyl-3,4-pyridynes.
A four-step regioselective synthesis of multisubstituted isoquinoline derivatives from 3-bromopyridines was developed by the Diels-Alder (DA) reactions of 2-silyl-3,4-pyridynes with furans, followed by functional-group transformations. In particular, the silyl group at the C2-position of the 3,4-pyridynes played two important roles: firstly, it functioned as the directing group for the DA reaction, and secondly, it served to introduce diverse substituents at the C1-position of the isoquinolines by electrophilic ipso-substitution.


Smoking behavior and hypertension among health workers during the COVID-19 pandemic: a case study in Java and Bali-Indonesia.
Health workers who should be role models for the community not to smoke and live a healthy life are still consuming cigarettes. Java and Bali (especially Java) are the biggest contributors to health worker deaths due to COVID-19 in Indonesia. This study aims to determine the association of smoking behavior and hypertension among health workers in Java and Bali. The researchers conducted this study in 2021 and designed it with a cross-sectional design. Data was collected online using the Lime Survey as a data collection tool. The data analysis used was logistic regression to determine the association of smoking and hypertension. A number of 7.6% of health workers were still smoking and 10.4% were suffering from hypertension during the COVID-19 pandemic. This study shows that the proportion of health workers with hypertension is two times that of smokers (18.0%) compared to non-smokers (9.8%). Logistic regression showed that smoking has a 20% higher risk of developing hypertension (OR = 1.97; 95%CI = 1.01-1.41; p = 0.034). Among health workers on the islands of Java and Bali, there are still many who smoke, and this puts them at a higher risk of experiencing hypertension.


Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis.
The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival.


Human papillomavirus type 31 life cycle: methods for study using tissue culture models.
The life cycle of human papillomaviruses (HPVs) has been difficult to study in tissue culture owing to its dependence on epithelial differentiation. In this chapter several methods are described to imitate the important steps in the HPV life cycle. Normal human keratinocytes (NHKs) harvested from neonatal foreskins were transfected with HPV type 31 genomes in order to generate stable cell lines containing episomal copies of HPV genomes. HPV-positive keratinocyte cultures were maintained in E medium in the presence of mitomycin C-treated J2 3T3 fibroblast feeders. Finally, the keratinocytes were induced to undergo epithelial differentiation in semisolid medium to provoke viral late functions like genomic amplification and late transcription.


Combined effect of acute denervation and ischemia on the microcirculation of skeletal muscle.
Using direct in vivo videomicroscopy and a fluorescein dye technique, reperfusion injury after 3 h of ischemia was studied in the acutely denervated cremaster muscle of the rat. Compared with normally innervated controls, ischemia-induced reperfusion injury was more severe in the denervated group and included a delay of blood flow recovery, vortex formation, edema, hemorrhage, and vessel spasm. Vessel size was reduced at the arteriole and small artery level, and there was a decrease of reactive hyperemia. The injury mechanism may be related to a loss of active vasomotion and vascular response to vasoactive substances after denervation. The results suggest that shortening the ischemia time of denervated tissues may reduce ischemia-induced reperfusion injury. Similarly, given the same ischemia time, improved tissue reperfusion may be expected if the nerve supply is maintained.


Design of textured multi-layered structures via magnetically assisted slip casting.
Multi-layered composites in nature often show functional properties that are determined by the specific orientation of inorganic building blocks within each layer. The shell of bivalve molluscs and the exoskeleton of crustaceans constitute prominent examples. An effective approach to artificially produce textured microstructures inspired by such complex composites is magnetically assisted slip casting (MASC). MASC is a colloidal process in which anisotropic particles are magnetically oriented at arbitrarily defined angles and collected at the surface of a porous mould to grow the material in an additive manner. Whereas a number of proof-of-concept studies have established the potential of the technique, the full design space available for MASC-fabricated structures, and the limits of the approach, have so far not been explored systematically. To fill this gap, we have studied both theoretically and experimentally the various torques that act on the particles at the different stages of the assembly process. We define the boundary conditions of the MASC process for magnetically responsive alumina platelets suspended in a low-viscosity aqueous suspension, considering the composition of the colloidal suspension and the dynamics of the particle alignment process under a rotating magnetic field. These findings lead to design guidelines for the fabrication of bio-inspired composites with customized multi-scale structures for a broad range of applications.


Integrating Human Barriers in Human Reliability Analysis: A New Model for the Energy Sector.
Human reliability analysis (HRA) is a major concern for organizations. While various tools, methods, and instruments have been developed by the scientific community to assess human error probability, few of them actually consider human factors impact in their analysis. The active role that workers have in shaping their own performance should be taken into account in order to understand the causal factors that may lead to errors while performing a task and identifying which human factors may prevent errors from occurring. In line with this purpose, the aim of this study is to present a new methodology for the assessment of human reliability. The proposed model relies on well-known HRA methodologies (such as SPAR-H and HEART) and integrates them in a unified framework in which human factors assume the role of safety barriers against human error. A test case of the new method was carried out in a logistics hub of an energy company. Our results indicate that human factors play a significant role in preventing workers from making errors while performing tasks by reducing human error probability. The limits and implications of the study are discussed.


Plasma membrane proteome analyses of Arabidopsis thaliana suspension-cultured cells during cold or ABA treatment: Relationship with freezing tolerance and growth phase.
Cold acclimation (CA) and abscisic acid (ABA) treatments affected freezing tolerance of Arabidopsis thaliana suspension-cultured cells: cells at the lag and log phases increased their freezing tolerance but cells at the stationery phase rather decreased after the treatments. To further characterize the differential responses of the cells to these treatments depending on growth phase, plasma membrane (PM) proteome were analyzed using label-free protein quantification technology. Abundance of 841 proteins changed during the progression of growth phase, CA and/or ABA treatment. Among them, 392 proteins changed in their abundance in cells during growth phase progression and were categorized into various functional groups, suggesting changes in physiological characteristics of the PM depending on the growth phase. Comparison of CA- and ABA-responsive proteins indicated that ABA is one of the important signals for PM proteome changes in response to CA, but multiple signals are required for the response of PM proteins to CA. Involvement of ABA in the CA process diminished with the progression of growth phase. Taken together, the results suggest that dynamic alterations of the PM proteome with the progression of growth phase influence the PM proteome responses to CA and ABA, which may effect the difference in freezing tolerance capability. SIGNIFICANCE: After cold acclimation (CA) or abscisic acid treatment (ABA), Arabidopsis thaliana suspension-cultured cells (T87 line) exhibited freezing tolerance capability dependent on the cell growth phase. However, whether the plasma membrane (PM) proteome profile differs among growth phases and the differences are associated with growth-phase-dependent freezing tolerance have not been elucidated. In the present study, PM proteomics was conducted in association with CA and ABA treatment of Arabidopsis suspension-cultured cells at three growth phases. Characteristics of the PM proteome changed considerably with progression of the growth phase and ABA was indicated to be an important signal for PM protein changes during CA. The results also revealed that multiple signals are required to complete the response of PM proteins to CA. Therefore, dynamic alterations of the PM proteome with the advance of the growth phase influence the responses of PM proteome to CA and ABA, which may result in the differences in freezing tolerance of the cultured cells.


[The dynamics of hemispheric restructuring during human short-term adaptation].
In work studied intimate (hidden) mechanism conversion information in the making new adaptive program and evidence role different stage of sleep in this process, which conclude in reorganization information on degree its value for organism. Discovered, that evaluation received information on criterion novelty occur in 2 day, but its selection on criterion emotional (biological) value for organism--in 3 day adaptation. Evaluation novelty realize left hemisphere, but its emotional (biological) value--right hemisphere brain. Reveal functional inequivalence of cerebral hemisphere under adaptation in process emergence creation new program reaction in change condition existence. Herewith left-hemisphere mechanism direct on reproduction already have available program reaction (how genetic bolt, so and newly obtained), but right-hemisphere--on production new adaptive program (perception and conversion enter information).


Polycation-Based Ternary Gene Delivery System.
Recent progress in gene therapy has opened the door for various human diseases. The greatest challenge that gene vectors still face is the ability to sufficiently deliver nucleic acid into target cells. To overcome various barriers, plenty of researches have been undertaken utilizing diverse strategies, among which a wide variety of polycation/pDNA vectors have been developed and explored frequently. For enhanced transfection efficiency, polycations are constantly utilized with covalent modifications, which however lead to reduced positive charge density and changed properties of polycation/pDNA complexes. Accordingly, non-covalent or ternary strategy is proposed. The cationic properties of polycations can be retained and the transfection efficiency can be enhanced by introducing additional polymers with functional groups via non-covalent assembly. This review will discuss the construction and advantages of ternary complexes gene delivery system, including low toxicity and enhanced gene expression both in vitro and in vivo. Recent progress and expectations with promising results that may have some reference for clinical application are also discussed.


Senile (type II) osteoporosis: pathogenesis and prevention of estrogen deficiency-related bone loss at the proximal femur.
Fractures of the proximal femur are associated with considerable morbidity and mortality. The residual effects of estrogen deficiency-related bone loss (partially) account for the higher incidence of hip fracture in elderly women compared to elderly men. This accelerated phase of postmenopausal bone loss can be prevented by estrogen substitution therapy. However, when estrogen substitution is discontinued, bone density declines at a rate similar to the perimenopausal one. In line with these densitometric data, several studies have provided evidence that the protective effect of estrogen therapy on hip fracture incidence does not persist after discontinuation of substitution. To prevent hip fractures in old age, estrogen treatment may have to be initiated perimenopausally and never discontinued. At present, however, such a strategy cannot be recommended as it has not been settled yet whether the benefits of estrogen substitution outweigh the risks.


Will Americans support the individual mandate?
An individual mandate is an important feature of many recent plans to achieve universal health insurance coverage in the United States, without radically changing the way most Americans get health care and coverage. Using national public opinion data, we find that on its own, an individual mandate does not have broad support across partisan and sociodemographic groups. Policymakers who choose to pursue an individual mandate for policy reasons may expand the base of supporters by incorporating it into a "shared-responsibility" plan that includes requirements for employers, government, and insurers.


A Scalable Synthesis of the Blue Fluorescent Amino Acid 4-Cyanotryptophan and the Fmoc Derivative: Utility Demonstrated with the Influenza M2 Peptide Tetramer.
A scalable synthesis of the Fmoc-protected blue fluorescent amino acid, l-4-cyanotryptophan (W4CN), that exploits an enantioselective phase transfer-catalyzed alkylation is reported. The red-shifted emission of water-exposed W4CN residues was leveraged to investigate the solvation state of tryptophan (Trp) residues within the influenza M2 proton channel. The correlation of the channel's conformation (i.e., open or closed) with the fluorescence spectrum of a mutated W4CN residue suggests that the channel's conformational state does not impact the hydration status of the Trp residues.


Violence risk instruments may be culturally unsafe for use with Indigenous patients.
Violence risk assessment assumes a critical medico-legal role addressing offender/patient needs and informing forensic mental health decision making. Yet questions remain over the cross-cultural applicability of such measures. In their current form, violence risk instruments may not reflect the unique life and cultural experiences of Indigenous Australians rendering them culturally unsafe. To realize equitable forensic assessment, it is necessary to ascertain whether there are cultural differences across risk factors for violence and that risk instruments are validated as culturally appropriate. Greater cross-cultural rigour in forensic mental health risk assessment, research and practice is proposed.


Clozapine N-Oxide Administration Produces Behavioral Effects in Long-Evans Rats: Implications for Designing DREADD Experiments.
Clozapine N-oxide (CNO) is a ligand for a powerful chemogenetic system that can selectively inhibit or activate neurons; the so-called Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system. This system consists of synthetic G-protein-coupled receptors, which are not believed to be activated by any endogenous ligand, but are activated by the otherwise inert CNO. However, it has previously been shown that the administration of CNO in humans and rats leads to detectable levels of the bioactive compounds clozapine and N-desmethylclozapine (N-Des). As a follow-up, experiments were conducted to investigate the effects of CNO in male Long-Evans rats. It was found that 1 mg/kg CNO reduced the acoustic startle reflex but had no effect on prepulse inhibition (PPI; a measure of sensorimotor gating). CNO (2 and 5 mg/kg) had no effect on the disruption to PPI induced by the NMDA antagonist phencyclidine or the muscarinic antagonist scopolamine. In locomotor studies, CNO alone (at 1, 2, and 5 mg/kg) had no effect on spontaneous locomotion, but 5 mg/kg CNO pretreatment significantly attenuated d-amphetamine-induced hyperlocomotion. In line with the behavioral results, fast-scan cyclic voltammetry found that 5 mg/kg CNO significantly attenuated the d-amphetamine-induced increase in evoked dopamine. However, the effects seen after CNO administration cannot be definitively ascribed to CNO because biologically relevant levels of clozapine and N-Des were found in plasma after CNO injection. Our results show that CNO has multiple dose-dependent effects in vivo and is converted to clozapine and N-Des emphasizing the need for a CNO-only DREADD-free control group when designing DREADD-based experiments.


Granulomatous angiopanniculitis of the breast. A case report.
Granulomatous angiopanniculitis (GAP) is a rare benign condition of the breast of unknown etiology. Clinically and by fine needle examination, GAP may simulate breast carcinoma. The cytologic characteristics have not been described before. A 63-year-old female exhibited a palpable mass in her left breast. The fine needle aspirate contained both epithelioid and stromal elements. The epithelioid component consisted of dissociated individual cells and small groups and clusters of atypical cells. The stromal component showed a uniform, not-atypical pattern. The lumpectomy specimen showed nonnecrotizing granulomatous panniculitis and lymphoid angiitis without involvement of ducts or lobules. Granulomatous lesions should be borne in mind in the differential diagnosis of breast cancer in fine needle aspiration cytology. GAP must be histopathologically distinguished from granulomatous inflammation in the breast of autoimmune or infectious origin as specific medical therapy may be available for these latter diseases.


Multicolour immuno-staining of fibrinogen polypeptide chains for identification of their derivatives in electrophoregrams.
A novel electrophoretic procedure enabling multiple, direct immunoprobing of electrophoregrams without depending on Western blotting is described, and applied to the identification of the derivatives formed in the early stages of clot stabilization. Multicolour immunostainings for positive identification of cross-linked chains in partially stabilized fibrin clots indicated that the early products of alpha-chain cross-linking by factor XIII are largely hybrids of co-cross-linking of alpha- and gamma-chains rather than alpha-chain polymers suggested from previous studies employing non-specific staining of electrophoregrams. Furthermore, plasma-fibrinogen dimers were found to contain cross-linked alpha-chains with an electrophoretic mobility very near that of gamma-gamma-dyads. A similar product is produced by tissue-transglutaminase, but not by factor XIII.


EFFECTIVE DOSE COEFFICIENTS FOR RADON AND PROGENY: A REVIEW OF ICRP AND UNSCEAR VALUES.
The International Commission on Radiological Protection (ICRP) publishes guidance on protection against radon exposure in homes and workplaces. ICRP Publication 137 recommends a dose coefficient of 3 mSv per mJ h m-3 (~10 mSv WLM-1) to be used in most circumstances of radon exposure, for workers in buildings and in underground mines. Recently, United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) reviewed radon epidemiology and dosimetry and concluded that its established dose coefficient of 1.6 mSv per mJ h m-3 (5.7 mSv WLM-1) should be retained for use in its comparisons of radiation exposures from different sources in a population. This paper explains and compares the reviews of the scientific evidence from UNSCEAR and ICRP. It is shown that the UNSCEAR and ICRP reviews are consistent and support the use of the ICRP reference dose coefficients for radiation protection purposes. It is concluded that the ICRP dose coefficient should be used to calculate doses to workers.


Internal motions of transfer RNA: a study of exchanging protons by magnetic resonance.
Proton exchange is a probe of macromolecular structure and kinetics. Its value is enhanced when the exchanging protons can be identified by nmr. After dilution of tRNA-H2O samples in D2O, slowly exchanging imino protons are observed, with exchange times ranging from minutes to days. In many cases they originate from the dihydro-uracil region. Most slow exchangers are sensitive to buffer catalysis. Extrapolation to infinite buffer concentration yields the life-time of the closed form, in a two-state model of each base-pair. As predicted by the model, the lifetime obtained by extrapolation is independent of the buffer. Typical lifetimes are 14 minutes for CG11 of yeast tRNAPhe at 17 degrees C, or 5 minutes for U8-A14 of yeast tRNA(Asp) at 20 degrees C, without magnesium. For most slow exchangers, magnesium increases the lifetime of the closed form, but moderately, by factors never more than five. The exchange rates of other, fast-exchanging, imino protons, as determined by line-broadening, are found to depend on buffer concentration. Base-pair lifetimes are determined as above. For instance UA6 of yeast tRNA(Phe) has a lifetime of 14 ms at 17 degrees C. Base-pairs 4 and 6 have shorter lifetimes than the rest of the acceptor stem. Imidazole is a good catalyst for proton exchange of both the long-and the short-lived base-pairs, whereas phosphate is not. Tris is efficient except for cases where, possibly, access is impeded by its size; magnesium reduces the efficiency of catalysis by tris buffer. From the variation of exchange time vs buffer concentration, one determines the buffer concentration for which the exchange rate from the open state is equal to the closing rate. Remarquably, this concentration takes comparable values for most base-pairs, whether short-lived or long-lived. Buffer effects have also been observed in poly(rA).poly(rU), for which we derive a lifetime of 2.5 ms at 27 degrees C, and in other polynucleotides. Some of the exchange times identified in the literature as base-pair lifetimes may instead reflect incomplete catalysis.


Cardiovascular Changes in Patients With COVID-19 From Wuhan, China.
Background: Coronavirus disease 2019 (COVID-19) is rapidly spreading and resulting in a significant loss of life around the world. However, specific information characterizing cardiovascular changes in COVID-19 is limited. Methods: In this single-centered, observational study, we enrolled 38 adult patients with COVID-19 from February 10 to March 13, 2020. Clinical records, laboratory findings, echocardiography, and electrocardiogram reports were collected and analyzed. Results: Of the 38 patients enrolled, the median age was 68 years [interquartile range (IQR), 55-74] with a slight female majority (21, 55.3%). Nineteen (50.0%) patients had hypertension. Seven (33.3%) had ST-T segment and T wave changes, and four (19%) had sinus tachycardia. Twenty (52.6%) had an increase in ascending aorta (AAO) diameter, 22 (57.9%) had an increase in left atrium (LA) size, and 28 (73.7%) presented with ventricular diastolic dysfunction. Correlation analysis showed that the AAO diameter was significantly associated with C-reactive protein (r = 0.4313) and creatine kinase-MB (r = 0.0414). LA enlargement was significantly associated with C-reactive protein (r = 0.4377), brain natriuretic peptide (r = 0.7612), creatine kinase-MB (r = 0.4940), and aspartate aminotransferase (r = 0.2947). Lymphocyte count was negatively associated with the AAO diameter (r = -0.5329) and LA enlargement (r = -0.3894). Conclusions: Hypertension was a common comorbidity among hospitalized patients with COVID-19, and cardiac injury was the most common complication. Changes in cardiac structure and function manifested mainly in the left heart and AAO in these patients. Abnormal AAO and LA size were found to be associated with severe inflammation and cardiac injury. Alternatively, ascending aortic dilation and LA enlargement might be present before infection but characterized the patient at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.


Impaired follicle development and infertility in female mice lacking steroidogenic factor 1 in ovarian granulosa cells.
The nuclear receptor steroidogenic factor 1 (SF-1 [officially designated NR5A1]) is essential for fetal gonadal development, but its roles in postnatal ovarian function are less well defined. Herein, we have extended our analyses of knockout (KO) mice with markedly decreased SF-1 expression in granulosa cells. As described, these SF-1 KO mice had hypoplastic ovaries that contained a decreased number of follicles and lacked corpora lutea. In the present study, we showed that SF-1 KO mice exhibited abnormal estrous cycles, were infertile, and released significantly fewer oocytes in response to a standard superovulation regimen. Moreover, they had blunted induction of plasma estradiol in response to gonadotropins. The granulosa cell-specific SF-1 KO also significantly affected ovarian expression of putative SF-1 target genes. Consistent with their decreased follicle number, these mice had reduced ovarian expression of anti-müllerian hormone (Amh), which correlates with the reserve pool of ovarian follicles, as well as decreased gonadotropin-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2). In contrast, perhaps because of their abnormal cyclicity, SF-1 KO ovaries had higher basal expression of inhibin-alpha. They also had decreased immunoreactivity for genes related to proliferation (Ccnd2 and Mki67 [also known as Ki67]) and increased expression of Cdkn1b, also known as p27, which inhibits cyclin-dependent kinases, arguing for a role of SF-1 in granulosa cell proliferation. These findings demonstrate that SF-1 has a key role in female reproduction via essential actions in granulosa cells.


[Current Status of Researches on Brain-imaging Responses of Acupuncture Stimulation Based on Functional Magnetic Resonance Imaging].
Using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanisms of acupuncture therapy attracts an increasing attention nowadays. In the present article, the authors make a brief analysis on the progresses of researches about the intra-brain responses of acupuncture stimulation following collecting original research papers with key words of "acupuncture","fMRI" and "magnetic resonance imaging" in PubMed and CNKI databases from January 2003 to December 2014. As a result, a total of 253 original research articles were collected. We found that:1) in the past 10 years, the amount of fMRI studies on acupuncture is growing; 2) most of these studies (183) are conducted in healthy subjects, and fewer studies (44) conducted in patients with problems of neurology, psychonosology, gastroenterology, circulation system, pediatrics, myopia and dermatology, or with pain; 3)a larger population of studies are designed to reveal the specificity of responses of acupuncture point stimulation, and fewer focus on analyzing the regularities of acupuncture points combination. The authors suggest that the coming acupuncture-neuroimaging studies need to expand the research ranges or contents, and improve experimental designs, data analysis and quality control (for example, reducing differences of baseline data, age span, psychological state, etc., and increasing sample size, etc).


Influence of MHCIITA rs3087456 and rs4774 polymorphisms in the susceptibility to cardiovascular disease of patients with rheumatoid arthritis.
MHCIITA is a major regulator of MHC expression that has been reported to be involved in the susceptibility to rheumatoid arthritis (RA) and myocardial infarction. In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA. 1302 patients fulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analysed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively. No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events, or not, were found. This was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination (p=0.08; odds ratio: 0.63 [95% confidence interval: 0.37-1.05]). Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of patients with RA.


Immuno-reactive human epidermal growth factor (h-EGF) in rheumatoid synovial fluids.
The immuno-reactive human epidermal growth factor (h-EGF) level, measured by a sensitive enzyme immunoassay, was significantly higher in synovial fluids or synovial tissue extracts from 89 patients with rheumatoid arthritis (RA) than in those from 53 patients with osteoarthritis. RA synovial immuno-reactive h-EGF was predominantly of a low molecular weight form (LMW h-EGF) on gel filtration chromatography. Furthermore, in the RA group, the synovial immuno-reactive h-EGF correlated positively with C-reactive protein, an acute-phase reactant, in the blood examination and with synovial immunoglobulin M. These results suggest that synovial h-EGF is specifically produced by RA synovium from the initial stage of arthritis, and that the measurement of synovial h-EGF serves as an early indicator to appraise the RA activity. A pathogenesis of RA including growth factors and growth inhibitory factors are discussed.


Transit of receptors for epidermal growth factor and transferrin through clathrin-coated pits. Analysis of the kinetics of receptor entry.
Selective enrichment of clathrin-coated membranes by anticlathrin immunoadsorption was used to examine the internalization of receptor-ligand complexes through coated pits. Using Staphylococcus aureus-anticlathrin antibody and [35S]methionine-labeled KB cells, the kinetics of association of the epidermal growth factor (EGF-R) and transferrin receptors (TF-R) with coated membranes were directly examined. The accumulation of EGF-R in coated pits at the cell surface was dependent upon EGF binding. EGF-R then passed sequentially through a compartment which did not react with anticlathrin antibody and a second clathrin-coated compartment. The EGF-R was degraded in lysosomes with a half-life of approximately 41-55 min. The tumor promoter, 4 beta-phorbol 12-myristate 13-acetate, appears to mimic the action of EGF in inducing EGF-R accumulation in coated pits at the cell surface and receptor internalization. In contrast to the results with EGF-R, the TF-R was found in clathrin-coated membranes in the presence or absence of TF, and the concentration of TF-R in clathrin-coated membranes did not significantly change with time. The method presented should be of great utility for examining the biochemical changes that occur during the receptor-mediated endocytosis and sorting of ligands and receptors.


Accuracy of Flash Glucose Monitoring in a Patient with Dravet Syndrome on a Ketogenic Diet.
We herein report the case of a 3-year-old girl with severe myoclonic epilepsy of infancy known as Dravet syndrome (DS) on a ketogenic diet (KD) whose glucose concentrations were controlled by using a flash glucose monitoring system. Two-hundred ninety-three events of moderate hypoglycemia with a minimum of 45 mg/dL, not related to day or night, were recorded during the observational period. Hypoglycemia rate declined from 24.5% of all measurements to 11.8% over time; one hypoglycemia-associated seizure and one seizure due to ketone concentrations below the therapeutic range were observed. In summary, this case report broadens our understanding of hypoglycemia risk in patients with DS on a KD. Especially in childhood, the painless and easy detection of low glucose concentrations might lead to improved cognitive performance, and the reduction of hypoglycemia-induced seizures.


The effect of changes in the financing and organization of health services on health promotion and disease prevention.
In sum, we are in the midst of a revolution in health care delivery. We have opportunities now to promote health and prevent disease that may disappear very quickly if action is not taken to encourage the participation in HP/DP of all health care professionals and health care delivery organizations. Some have argued that since these professionals have not been trained in health promotion and disease prevention, and have not shown sufficient commitment to its values, they should be passed over, written off. Given the huge resource base the health care delivery system represents, this may be a shortsighted approach. It could be argued equally that, like all major institutions in our society, the health care delivery system has a responsibility to participate in health promotion and disease prevention. More, given their fundamental concern with health, the health care delivery system should be taking the lead.


Fractures of the supraorbital rim: principles and management.
Dentists may be asked to provide consultations for patients who have sustained trauma to their facial structures. Supraorbital rim fractures, although uncommon, must be recognized and promptly referred to an oral and maxillofacial surgeon or other specialist skilled in the management of facial bone fractures. Supraorbital rim fractures commonly coexist with other craniomaxillofacial injuries, especially with fractures of the anterior table of the frontal sinus. In this article, we review the frequency, management and complications associated with the treatment of supraorbital rim fractures in adults. A series of 5 cases was reviewed; 4 of the 5 patients were male, with a mean age of 21.6 years (range 17-28 years). All injuries involved the supraorbital rim and the anterior table of the frontal sinus and occurred concurrently with other facial injuries. Treatment ranged from conservative observation to open reduction and internal fixation of the fractures. No associated perioperative or postoperative complications occurred. The follow-up ranged from 6 months to 26 years, with satisfactory subjective esthetic outcomes in all cases.


Breast Cancer Cells Transition from Mesenchymal to Amoeboid Migration in Tunable Three-Dimensional Silk-Collagen Hydrogels.
Invading cancer cells adapt their migration phenotype in response to mechanical and biochemical cues from the extracellular matrix. For instance, mesenchymal migration is associated with strong cell-matrix adhesions and an elongated morphology, while amoeboid migration is associated with minimal cell-matrix adhesions and a rounded morphology. However, it remains challenging to elucidate the role of matrix mechan-ics and biochemistry, since these are both dependent on ECM protein concentration. Here, we demonstrate a composite silk fibroin and collagen I hydrogel where stiffness and microstructure can be systematically tuned over a wide range. Using an overlay assay geometry, we show that the invasion of metastatic breast cancer cells exhibits a biphasic dependence on silk fibroin concentration at fixed collagen I concentration, first increasing as the hydrogel stiffness increases, then decreasing as the pore size of silk fibroin decreases. Indeed, mesenchymal morphology exhibits a similar biphasic depen-dence on silk fibroin concentration, while amoeboid morphologies were favored when cell-matrix adhesions were less effective. We used exogenous biochemical treatment to perturb cells towards increased contractility and a mesenchymal morphology, as well as to disrupt cytoskeletal function and promote an amoeboid morphology. Overall, we envision that this tunable biomaterial platform in a 96-well plate format will be widely applicable to screen cancer cell migration against combinations of designer biomaterials and targeted inhibitors.


Quality of Life in Pediatric Patients with Allergic Rhinitis treated at the Medical Clinic of Integrated Education - Unisul.
Introduction Allergic rhinitis is a common disease among children and adolescents, reaching up to 40% of the population. During childhood, it is usually underdiagnosed because it has nonspecific symptoms. It has a negative impact on quality of life and may predispose to comorbidities. The diagnosis is clinical and treatment aims prevention. Objective The objective of this study is to evaluate the quality of life in pediatric patients with allergic rhinitis. Methods This is an observational study with cross-sectional design. The population consisted of pediatric patients with allergic rhinitis treated at the Medical Clinic of Integrated Education (MCIE) - Universidade do Sul de Santa Catarina - Unisul, Tubarão, SC, Brazil. We collected data from March to June 2016 through the application of the Sociodemographic and Health Questionnaire, rhinitis module of the International Study of Asthma and Allergies in Childhood Questionnaire and the Rhinoconjunctivitis Quality of Life Questionnaire Modified. Results Out of the 69 respondents, 52.2% were boys with a mean age of 10.13 years old. The predominant education level of parents/guardians was incomplete second grade and average income level was two minimum wages. 81.2% said they had previous treatment for AR, 30.4% had asthma and 7.2% eczema. Incidence of patients smoking was absent and family (parents/guardians) smoking was 17.4%. March to July were the months of highest symptom occurrence, slightly disturbing daily activities. The mean value of severity was 51.9, nasal symptoms were the most uncomfortable, and nasal itchiness was the most cited. Conclusion Our results highlight that allergic symptoms negatively impact the life of people with allergic rhinitis, with a predominance of nasal symptoms, especially nasal itchy, representing a poor quality of life of the interviewed.


The advanced practice nurse-nephrologist care model: effect on patient outcomes and hemodialysis unit team satisfaction.
The tertiary care nurse practitioner/clinical nurse specialist (NP/CNS) is an advanced practice nurse with a relatively new role within the health-care system. It is stated that care provided by the NP/CNS is cost-effective and of high quality but little research exists to document these outcomes in an acute-care setting. The clinical coverage pattern by nephrologists and NP/CNS of a hemodialysis unit in a large academic center allowed such a study. Two NP/CNS plus a nephrologist followed two of three hemodialysis treatment shifts per day; only a nephrologist followed the third shift. The influence of this care pattern of patients was examined using a cross-sectional review of outcomes such as adequacy of delivered dialysis, anemia management, phosphate control, hospitalizations, etc. In addition, the level of satisfaction of the dialysis team and perceptions of care delivered with the care models was assessed. The care model staff-to-patient-number ratio was similar in both groups (1:27 for NP/CNS plus nephrologist; 1:29 for nephrologist alone). Patient demographics were similar in both groups but the NP/CNS-nephrologist group had patients with more comorbidities. No statistically significant (p < 0.05) differences existed between the groups in patient laboratory data, adherence to standards, medications, inter- and intradialytic blood pressure, achievement of target postdialysis weights, and hospitalizations or emergency room visits. Significantly more adjustments were made to target weights and medications and more investigations were ordered by the NP/CNS-nephrologist team. Team satisfaction and perceptions of care delivery were higher with the NP/CNS-nephrologist model. It is concluded that the NP/CNS-nephrologist care model may increase the efficiency of the care provided by nephrologists to chronic hemodialysis patients. The model may also be a solution to the problem of providing nephrologic care to an ever-growing hemodialysis population.


Activation of AMPK by Medicinal Plants and Natural Products: Its Role in Type 2 Diabetes Mellitus.
Type-2 Diabetes (T2D) is a metabolic disease characterized by permanent hyperglycemia, whose development can be prevented or delayed by using therapeutic agents and implementing lifestyle changes. Some therapeutic alternatives include regulation of glycemia through modulation of different mediators and enzymes, such as AMP-activated protein kinase (AMPK), a highly relevant cellular energy sensor for metabolic homeostasis regulation, with particular relevance in the modulation of liver and muscle insulin sensitivity. This makes it a potential therapeutic target for antidiabetic drugs. In fact, some of them are standard drugs used for treatment of T2D, such as biguanides and thiazolidindiones. In this review, we compile the principal natural products that are activators of AMPK and their effect on glucose metabolism, which could make them candidates as future antidiabetic agents. Phenolics such as flavonoids and resveratrol, alkaloids such as berberine, and some saponins are potential natural activators of AMPK with a potential future as antidiabetic drugs.


The prospects for vaginal delivery in gestations beyond 43 weeks.
To reveal factors influencing the prospect for vaginal delivery in very prolonged pregnancy. Thirty-six nulliparae and 14 multiparae delivered beyond 43 weeks followed a routine surveillance protocol. Labor was induced on strict indications (n = 11; oligohydramnios, large fetus, hypertension) and on "soft' indications (n = 24; favorable cervix, emotional stress). Receiver operating characteristic curves were obtained for maternal stature and birthweight with regard to mode of delivery. Student's unpaired t-test, Mann-Whitney U test, and Fisher's exact test were used with a two-tailed p < 0.05 considered statistically significant. Labor started spontaneously within three days in > 50% of cases managed expectantly. All multiparae had nonoperative vaginal deliveries. Of nulliparae, 89% delivered vaginally if spontaneous labor and 56% if induced. Failure to progress was the most common reason for operative delivery. A maternal height of < or = 160 cm, a very unripe cervix, and a birthweight > 4250 g were unfavorable factors in induced nulliparae. No case of perinatal mortality, severe birth asphyxia, meconium aspiration, or shoulder dystocia occurred. Fetal meconium release, fetal distress in labor, and birth asphyxia did not significantly differ with regard to parity or mode of labor. The prospect for vaginal delivery was strongly associated with parity. All multiparae had nonoperative vaginal deliveries, irrespective of spontaneous or induced labor. In nulliparae, a spontaneous onset was favorable but a maternal height of < or = 160 cm, a very unripe cervix, and a birthweight > 4250 g were unfavorable factors. In uncomplicated pregnancy with favorable factors spontaneous labor can be awaited for a few days.


[Rehabilitation of psychiatric patients in the halfway house--a 10-year retrospective study].
In a period of ten years 159 residents were admitted to a transitional home. 90% of them were diagnosed as chronic schizophrenics with a marked psychic and social handicap. With an average age of 28.7 years and a mean duration of illness of 6.8 years most of the patients had been hospitalized several times; 95% had no job, lived on social assistance or were invalidity pensioners. There was poor success in vocational rehabilitation (22%). Better results were seen in solving the housing problems, showing a clear-cut tendency to move from the family of origin into protected group homes or independent living. Positive effects of social training with gains in life-coping abilities and social competence, i.e., in autonomy in everyday life could be observed as well.


The socioeconomic correlates of hysterectomies in the United States.
The purpose of this study was to examine the relationship between incidence of prior hysterectomy and education, income, and race. Data concerning previous hysterectomy and socioeconomic information were collected from 12,465 women 18 years or older as part of the Behavioral Risk Factor Surveillance System conducted in 16 states in 1988. The results indicate that women with less education and lower incomes were more likely to have had a hysterectomy. Race was not related to hysterectomy rate.


ABC transporters involved in export of cell surface glycoconjugates.
Complex glycoconjugates play critical roles in the biology of microorganisms. Despite the remarkable diversity in glycan structures and the bacteria that produce them, conserved themes are evident in the biosynthesis-export pathways. One of the primary pathways involves representatives of the ATP-binding cassette (ABC) transporter superfamily. These proteins are responsible for the export of a wide variety of cell surface oligo- and polysaccharides in both Gram-positive and Gram-negative bacteria. Recent investigations of the structure and function of ABC transporters involved in the export of lipopolysaccharide O antigens have revealed two fundamentally different strategies for coupling glycan polymerization to export. These mechanisms are distinguished by the presence (or absence) of characteristic nonreducing terminal modifications on the export substrates, which serve as chain termination and/or export signals, and by the presence (or absence) of a discrete substrate-binding domain in the nucleotide-binding domain polypeptide of the ABC transporter. A bioinformatic survey examining ABC exporters from known oligo- and polysaccharide biosynthesis loci identifies conserved nucleotide-binding domain protein families that correlate well with themes in the structures and assembly of glycans. The familial relationships among the ABC exporters generate hypotheses concerning the biosynthesis of structurally diverse oligo- and polysaccharides, which play important roles in the biology of bacteria with different lifestyles.


Anadenanthera Colubrina vell Brenan: anti-Candida and antibiofilm activities, toxicity and therapeutical action.
We evaluated the antifungal and antibiofilm potential of the hydroalcoholic extract of bark from Anadenanthera colubrina (vell.) Brenan, known as Angico, against Candida spp. Antifungal activity was evaluated using the microdilution technique through the Minimum Inhibitory and Fungicide Concentrations (MIC and MFC). The antibiofilm potential was tested in mature biofilms formed by Candida species and analyzed through the counting of CFU/mL and scanning electron micrograph (SEM). In vivo toxicity and therapeutic action was evaluated in the Galleria mellonella model. The treatment with the extract, in low doses, was able to reduce the growth of planktonic cells of Candida species. MIC values range between 19.5 and 39 µg/mL and MFC values range between 79 and 625 µg/mL. In addition was able to reduce the number of CFU/mL in biofilms and to cause structural alteration and cellular destruction, observed via SEM. A. colubrina showed low toxicity in the in vivo assay, having not affected the viability of the larvae at doses below 100mg/kg and high potential in the treatment of C. albicans infection. Considering its high antifungal potential, its low toxicity and potential to treatment of infections in in vivo model, A. colubrina extract is a strong candidate for development of a new agent for the treatment of oral candidiasis.


Zigzag lipid tubules.
We report a method based on poly(dimethylsiloxane) (PDMS) stamp-assisted moving contact line to bend lipid tubules into zigzags on glass substrates. Atomic force microscopy (AFM) reveals that the zigzag lipid tubules buckle at the bent sites. The measurements of buckling heights as a function of bending angles suggest a gradual buckling mode. By imaging the zigzag tubules with AFM under different loading forces, we study the correlation between the loading force and the tubule compression. The reduced stiffness at the buckling sites of zigzag tubules suggests that lipid molecules are reorganized during the gradual buckling.


5'-Heterogeneity of the mineralocorticoid receptor messenger ribonucleic acid: differential expression and regulation of splice variants within the rat hippocampus.
The mineralocorticoid receptor (MR) cDNA we previously isolated from the rat hippocampus differs from the clone isolated from the kidney at the 5'-untranslated (5'UT) region. The kidney clone (alpha MR mRNA) and the hippocampal clone (beta MR mRNA) possess unique 5'UT sequences of 220 and 300 nucleotides, respectively, but share an invariant peptide-coding domain and appear to encode an identical MR protein. The two mRNA variants may represent tissue-specific forms of the MR or may be coexpressed in the rat hippocampus along with other 5'UT variants. Here, we report that three mRNA subtypes were found in the hippocampus; their relative abundance was as follows: alpha = beta >> gamma. The three mRNA variants were differentially distributed within the hippocampal subfields, with the alpha form being highly enriched in CA2, dentate, the fasciculum cinereum, and the indusium griseum, whereas beta and gamma forms were evenly distributed through CA1-4. Adrenalectomy selectively increased alpha MR mRNA content, but the changes were restricted to CA1, CA2, and CA3 regions. We conclude that multiple MR mRNAs are differentially expressed in the rat hippocampus. The expression of alpha MR mRNA is specifically increased during adrenalectomy, suggesting that the increase in total MR mRNA content documented previously arises from a substantial increase in a single MR variant that elevates the total MR mRNA content, with the apparent elevation reflecting the average of regulated and unregulated transcripts. It is suggested from our data that a complex mechanism involving transcription and translation regulates MR expression in the rat hippocampus.


Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.
Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two previous studies reported contradictory results in patients with dementia of Alzheimer's type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer's type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic implications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies.


Coagulopathy and Extremely Elevated PT/INR after Dabigatran Etexilate Use in a Patient with End-Stage Renal Disease.
Introduction. Dabigatran is an oral direct thrombin inhibitor which has been approved for prophylaxis of stroke in patients with atrial fibrillation. The use of dabigatran etexilate increased rapidly due to many benefits. However, questions have been raised constantly regarding the safety of dabigatran etexilate. Case. A 58-year-old Caucasian male with a history of recurrent paroxysmal atrial fibrillation status after pacemaker and end-stage renal disease on hemodialysis came to the Emergency Department with the complaint of severe epistaxis. He had been started on dabigatran 150 mg twice a day about 4 months ago as an outpatient by his cardiologist. His prothrombin time (PT) was 63 seconds with international normalized ratio (INR) of 8.8 and his activated partial thromboplastin time (aPTT) was 105.7 seconds. Otherwise, all labs were unremarkable including the liver function test. Dabigatran was stopped immediately. His INR and aPTT trended downward, reaching normal levels 5 days after admission. Conclusion. Dabigatran is contraindicated in patients with severe kidney insufficiency as it is predominantly excreted via the kidney (~80%). Elderly patients over 75 and patients with chronic renal impairment should be carefully evaluated before starting dabigatran. Despite studies showing only mild increase in aPTT and PT/INR in patients receiving dabigatran, close monitoring may be reasonable in patients with renal insufficiency.


PYCHEM: a multivariate analysis package for python.
We have implemented a multivariate statistical analysis toolbox, with an optional standalone graphical user interface (GUI), using the Python scripting language. This is a free and open source project that addresses the need for a multivariate analysis toolbox in Python. Although the functionality provided does not cover the full range of multivariate tools that are available, it has a broad complement of methods that are widely used in the biological sciences. In contrast to tools like MATLAB, PyChem 2.0.0 is easily accessible and free, allows for rapid extension using a range of Python modules and is part of the growing amount of complementary and interoperable scientific software in Python based upon SciPy. One of the attractions of PyChem is that it is an open source project and so there is an opportunity, through collaboration, to increase the scope of the software and to continually evolve a user-friendly platform that has applicability across a wide range of analytical and post-genomic disciplines. http://sourceforge.net/projects/pychem


Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus.
A comparison of antibody titers to JC virus (JCV) or BK virus (BKV) was made by hemagglutination inhibition (HI) and enzyme immunoassay (EIA) with 114 human plasma samples. Antibody titers to JCV or BKV determined by HI were lower than those determined by EIA. Nevertheless, as HI titers increased so did EIA titers. When antibody data were compared by the Spearman rank correlation test, highly significant correlations were found between HI and EIA titers. Results obtained by plotting EIA antibody titers for JCV against those for BKV generally showed a reciprocal relationship, i.e., samples with high antibody titers to JCV had lower antibody titers to BKV and vice versa. Some samples, however, had antibody titers to both viruses. Of the samples tested, 25.4% (25 of 114) had HI and EIA antibody titers to JCV and BKV which were identical or closely related. This is not the scenario one would expect for cross-reactive epitopes shared by the two viruses, but one suggesting that these samples were from individuals who had experienced infections by both viruses. Adsorption with concentrated JCV or BKV antigen of sera with high antibody titers to both JCV and BKV and testing by JCV and BKV EIA gave results which support this conclusion. Although 52.6% (51 of 97) of the samples from the Japanese population tested had very high antibody titers (>/=40,960) to either JCV or BKV, none of the samples were found by a dot blot immunoassay to have antibodies which cross-reacted with simian virus 40. The results from this study, in agreement with those of others, suggest that humans infected by JCV or BKV produce antibodies to species-specific epitopes on their VP1 capsid protein, which is associated with hemagglutination and cellular binding.


Magnetic resonance neurography studies of the median nerve before and after carpal tunnel decompression.
Recently developed novel MR protocols called MR neurography, which feature conspicuity for nerve, have been shown to demonstrate signal change and altered median nerve configuration in patients with median nerve compression. The postoperative course following median nerve decompression can be problematic, with persistent symptoms and abnormal results on electrophysiological studies for some months, despite successful surgical decompression. The authors undertook a prospective study in patients with carpal tunnel syndrome, correlating the clinical, electrophysiological, and MR neurography findings before and 3 months after surgery. Thirty patients and eight control volunteers were recruited to the study. The MR neurography consisted of axial and sagittal images (TR = 2000 msec, TE = 60 msec) obtained using a temporomandibular surface coil, fat saturation, and flow suppression. Maximum intensity projection images were used to follow the median nerve through the carpal tunnel in the sagittal plane. Magnetic resonance neurography in patients with carpal tunnel syndrome demonstrated proximal swelling (p < 0.001) and high signal change in the nerve, together with increased flattening ratios (p < 0.001) and loss of nerve signal in the distal carpal tunnel (p < 0.05). Sagittal images were very effective in precisely demonstrating the site and severity of nerve compression. After surgery, division of the flexor retinaculum could be demonstrated in all cases. Changes in nerve configuration, including increased cross-sectional area, and reduced flattening ratios (p < 0.001) were seen in all patients. In many cases restoration of the T. signal intensity toward that of controls was seen in the median nerve in the distal carpal tunnel. Sagittal images were excellent in demonstrating expansion of the nerve at the site of surgical decompression. In this study the authors suggest that MR neurography is an effective means of both confirming compression of the median nerve and its successful surgical decompression in patients with carpal tunnel syndrome. This modality may prove useful in the assessment of unconfirmed or complex cases of carpal tunnel syndrome both before and after surgery.


Diagnosis of drug allergy by the lymphocyte stimulation test with the MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay.
The lymphocyte stimulation test (LST) is one of the most useful laboratory tests for the identification of allergy to a specific drug. The present study was conducted to examine utility of the LST using the [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay as a method for diagnosing drug allergy. The basic experimental conditions for the MTT assay were determined by using CTLL cells from human T-lymphoma, dependent on IL-2, and human peripheral blood lymphocytes. The amount of MTT needed was 0.5 mg per well and the peak maximum of MTT formazan was close to 565 nm. The blastogenesis of the lymphocytes was expressed as a Stimulation Index (SI). The value of the SI was almost constant at cell numbers ranging from 5 x 10(5) to 1 x 10(6) cells/ml. The SI of some drugs using normal peripheral blood lymphocytes was less than 1.3. We used the MTT assay in the LST to examine the allergenicity of 83 drugs which were used in 43 cases of suspected drug-induced hepatitis. The range of SI was 0.92-2.02. An SI of 1.2 or more was seen in 62.8% of cases, 1.3 or more in 51.2% of cases, and 1.4 or more in 41.9% of cases. There were 26 drugs with SI greater than 1.3. Seven of these were antibiotics, while the rest included antihypertensives, analgesics, psychotropics, antiallergics and antiepileptics. This method is extremely well suited for the diagnosis of drug allergy in a clinical situation. The greatest benefit of the MTT assay is that the complete test procedures can be carried out in a general laboratory.


Pharmacological intervention of tiferron and propolis to alleviate beryllium-induced hepatorenal toxicity.
Intervention of chelating agent tiferron (sodium-4,5-dihydroxy-1,3-benzene disulfonate; 300 mg/kg, intraperitoneal) with propolis (honey beehive product; 200 mg/kg, p.o.) was evaluated to encounter the characteristic biochemical and ultra-morphological alterations following subchronic exposure to beryllium. Female albino rats were challenged with beryllium nitrate (1 mg/kg, i.p.) daily for 28 days followed by treatment of the above-mentioned therapeutic agents either individually or in combination for five consecutive days. Exposure to beryllium increased its concentration in the serum, liver and kidney, and caused significant alterations in cytochrome P450 activity, microsomal lipid peroxidation and proteins. Activities of alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, creatinine and urea in the serum and activity of acid phosphatase, alkaline phosphatase, adenosine triphosphatase, glucose-6-phophatase and succinic dehydrogenase in the liver and kidney were significantly altered after beryllium administration. Beryllium exposure also induced severe hepatorenal alterations at histopathological and ultra-morphological level. Tiferron along with propolis dramatically reversed the alterations in all the variables more towards control rather than their individual treatment. The study concludes that pharmacological intervention of tiferron and propolis is beneficial in attenuating beryllium-induced systemic toxicity.


Death at the end of the 20th century: individual processes and developmental tasks in old age.
In this article, we address the topic of death from historic and contemporary perspectives. In the first section, we describe the changes in life expectancy, personal experience, and public awareness of death that have occurred over the past century. In the next section, we examine the impact these changes have had on the mastery of the two developmental tasks in adulthood, acceptance of one's own mortality and coping with the death of a spouse. We describe select findings from the literature on attitudes, fear or acceptance of death, and grief processes. Implications for research, practice, and social change are considered.


Millimeter-Wave Beam Scattering by Field-Aligned Blobs in Simple Magnetized Toroidal Plasmas.
The first direct experimental measurements of the scattering of a millimeter-wave beam by plasma blobs in a simple magnetized torus are reported. The wavelength of the beam is comparable to the characteristic size of the blob. In situ Langmuir probe measurements show that fluctuations of the electron density induce correlated fluctuations of the transmitted power. A first-principles full-wave model, using conditionally sampled 2D electron density profiles, predicts fluctuations of the millimeter-wave power that are in agreement with experiments.


Application of semiconductor and metal nanostructures in biology and medicine.
Advances in nanotechnology research have led to the creation of new generation of contrast agents, therapeutics, and delivery systems. These applications are expected to significantly improve the diagnosis and treatment of a variety of diseases. Two nanotechnologies-semiconductor and metallic nanostructures-are the most advanced in this young field and have been extensively investigated for clinical use. These nanostructures are currently the "model" for the developments of many novel nanostructures. This review describes their chemical design, tunable properties, and utility in medicine. Furthermore, we will describe the current understanding of their toxicity, which could be barriers to their use for human.


Comparative Transcriptomic Analysis of Cerebral Organoids and Cortical Neuron Cultures Derived from Human Induced Pluripotent Stem Cells.
Human induced pluripotent stem cells (iPSCs) can be differentiated along various neuronal lineages to generate two-dimensional neuronal cultures as well as three-dimensional brain organoids. Such iPSC-derived cellular models are being utilized to study the basic biology of human neuronal function and to interrogate the molecular underpinnings of disease biology. The different cellular models generated from iPSCs have varying properties in terms of the diversity and organization of the cells as well as the cellular functions that are present. To understand transcriptomic differences in iPSC-derived monolayer neuronal cultures and three-dimensional brain organoids, we differentiated eight human iPSC lines from healthy control subjects to generate cerebral organoids and cortical neuron monolayer cultures from the same set of iPSC lines. We undertook RNA-seq experiments in these model systems and analyzed the gene expression data to identify genes that are differentially expressed in cerebral organoids and two-dimensional cortical neuron cultures. In cerebral organoids, gene ontology analysis showed enrichment of genes involved in tissue development, response to stimuli, and the interferon-γ pathway, while two-dimensional cortical neuron cultures showed enrichment of genes involved in nervous system development and neurogenesis. We also undertook comparative analysis of these gene expression profiles with transcriptomic data from the human fetal prefrontal cortex (PFC). This analysis showed greater overlap of the fetal PFC transcriptome with cerebral organoid gene expression profiles compared to monolayer cortical neuron culture profiles. Our studies delineate the transcriptomic differences between cortical neuron monolayer cultures and three-dimensional cerebral organoids and can help inform the appropriate use of these model systems to address specific scientific questions.


Computed tomography angiography vs 3 T black-blood cardiovascular magnetic resonance for identification of symptomatic carotid plaques.
The purpose of this prospective study was to perform a head-to-head comparison of the two methods most frequently used for evaluation of carotid plaque characteristics: Multi-detector Computed Tomography Angiography (MDCTA) and black-blood 3 T-cardiovascular magnetic resonance (bb-CMR) with respect to their ability to identify symptomatic carotid plaques. 22 stroke unit patients with unilateral symptomatic carotid disease and >50% stenosis by duplex ultrasound underwent MDCTA and bb-CMR (TOF, pre- and post-contrast fsT1w-, and fsT2w- sequences) within 15 days of symptom onset. Both symptomatic and contralateral asymptomatic sides were evaluated. By bb-CMR, plaque morphology, composition and prevalence of complicated AHA type VI lesions (AHA-LT6) were evaluated. By MDCTA, plaque type (non-calcified, mixed, calcified), plaque density in HU and presence of ulceration and/or thrombus were evaluated. Sensitivity (SE), specificity (SP), positive and negative predictive value (PPV, NPV) were calculated using a 2-by-2-table. To distinguish between symptomatic and asymptomatic plaques AHA-LT6 was the best CMR variable and presence / absence of plaque ulceration was the best CT variable, resulting in a SE, SP, PPV and NPV of 80%, 80%, 80% and 80% for AHA-LT6 as assessed by bb-CMR and 40%, 95%, 89% and 61% for plaque ulceration as assessed by MDCTA. The combined SE, SP, PPV and NPV of bb-CMR and MDCTA was 85%, 75%, 77% and 83%, respectively. Bb-CMR is superior to MDCTA at identifying symptomatic carotid plaques, while MDCTA offers high specificity at the cost of low sensitivity. Results were only slightly improved over bb-CMR alone when combining both techniques.


Factors correlated with homosexually acquired human immunodeficiency virus infection in the era of "safer sex". Was the prevention message clear and well understood? Alain Brugeat Physician Group.
A cross-sectional survey was conducted between November 1986 and January 1988 among 246 homosexual/bisexual patients by consulting physicians promoting human immunodeficiency virus (HIV) infection prevention, to determine factors correlated with HIV infection a few years after the launch of safer sex recommendations. After adjustment for numbers of sexual partners and frequency of unprotected receptive anal intercourse, seropositive subjects, compared to seronegative ones, had significantly higher frequencies of: (1) receptive anal intercourse using condoms and extraneous lubricants, (2) anorectal douching before or after intercourse, (3) past history of syphilis, and (4) nitrite inhalations. The first three factors remained significant after multivariate analysis. Eighty-three percent of the subjects practicing receptive anal intercourse with condoms plus lubricants used inappropriate lubricants. Some factors identified in our study are well established risk factors for homosexually acquired HIV infection, suggesting that safer sex recommendations still are not followed by all. Our results also elicit additional factors that independently increase the risk. Two of them, extraneous lubrication of the condom for anal receptive intercourse and anorectal douching, may result from a misunderstood notion of "safer sex," or from practices thought by mistake to protect against HIV.