Model suggests potential for Porites coral population recovery after removal of anthropogenic disturbance (Luhuitou, Hainan, South China Sea).
Population models are important for resource management and can inform about potential trajectories useful for planning purposes, even with incomplete monitoring data. From size frequency data on Luhuitou fringing reef, Hainan, South China Sea, a matrix population model of massive corals (Porites lutea) was developed and trajectories over 100 years under no disturbance and random disturbances were projected. The model reflects a largely open population of Porites lutea, with low local recruitment and preponderance of imported recruitment. Under no further disturbance, the population of Porites lutea will grow and its size structure will change from predominance of small size classes to large size classes. Therewith, total Porites cover will increase. Even under random disturbances every 10 to 20 years, the Porites population could remain viable, albeit at lower space cover. The models suggest recovery at Luhuitou following the removal of chronic anthropogenic disturbance. Extending the area of coral reef reserves to protect the open coral community and the path of connectivity is advisable and imperative for the conservation of Hainan's coral reefs.


Contrast enhanced phototrichogram pinpoints scalp hair changes in androgen sensitive areas of male androgenetic alopecia.
In male androgenetic alopecia (AGA), global changes of scalp hair observed on many years are the cumulative result of discrete changes. Such changes reflect structural and/or functional modifications occurring at the level of individual hair follicles. The patterning of scalp hair loss is the phenotypic expression of clusters of hormone sensitive follicles located in specific scalp areas. The aim of this study was to evaluate, in 21 untreated male subjects with AGA, the relation between various hair measurements using a new validated photographic method with clinical staging (modified Norwood-Hamilton scale) as compared with five controls. As recently demonstrated by comparison with transverse sectioning of scalp biopsies, dynamic changes occurring at the level of individual hair follicles can be accurately explored with the contrast enhanced phototrichogram technique (CE-PTG). This is a further improvement of the PTG (combined analysis of two photographs taken at 48 h interval) using contrast enhancement together with the scalp immersion proxigraphy method. Visible hair counts per unit area were first evaluated on photographs without and with CE. Then other scalp hair variables (anagen hair counts and proportion of thin hair (<or= 40 microm thickness)) were established on CE-PTGs. Thickness of scalp hair sampled during the preparation of these sites was also calibrated against an objective ruler with a light microscope. We confirm that the CE improves hair detection. Controls showed higher densities in the top of the head sites as compared with the occipital ones. In the presumably less hormone responsive scalp occipital sites, AGA subjects did not differ from controls. The top of the head sites, i.e. highly androgen sensitive areas of AGA subjects showed a reduction of total and anagen hair counts as compared to controls. These changes were observed even in mildly affected subjects. The clinical severity of AGA seems to be related to the reduction of anagen counts and the associated relative increase of thin hair. Because the thinnest hair usually lacks pigmentation, they escape detection by PTG in the absence of contrast enhancement. The CE-PTG also detects higher proportions of thin hair at early stages of AGA as compared with light microscopy. This probably reflects lack of control during the sampling process, i.e. the clipping- collection-display sequence required for light microscopy observations. These results indicate that CE-PTG is a powerful tool for analysis of hair growth and loss and may cast some doubt on results obtained with other methods. The potential use of the CE-PTG method for calibration of innovative tools is also alluded to. Indeed encouraging results have been obtained with the scalp coverage scoring (SCS) method. These SCS scores were correlated with shortening of anagen phase and hair miniaturization, the two processes apparently involved in the clinical development of male AGA.


[Bronchogenic cysts of the mediastinum in childhood].
Bronchogenic cysts are rare congenital anomalies result of abnormal development of the tracheobronchial tree. They develop in the lung parenchyma or in the mediastinum. For a period of 17 years (1975-1991) a total of 46 children with bronchogenic cysts have been treated; in 6 the cysts were localized in the mediastinum. Two patients were one-year-old, 3 were in the age group 1 to 3 years and 1 was older than 3 years. Four patients were boys and 2 girls. Two children had hacking cough and attacks of dyspnea; one had swallowing difficulties. In 3 children the disease produced no symptoms and was detected on examination for pneumonia (1 child) and acute upper respiratory tract infection (2 children). All children had conventional X-ray; 5 had esophagography as well, 4--computer axial tomography, 3--echography. All children were operated (total extirpation of the cyst) and left the hospital cured.


Physical Activity Device Reliability and Validity during Pregnancy and Postpartum.
Current physical activity (PA) recommendations for women experiencing a normal pregnancy reflect recent research showing numerous health benefits for mother and offspring. However, few studies have evaluated PA devices' reliability and validity during pregnancy, because anatomical and physiological changes throughout gestation could affect an instrument's accuracy. This study aimed to determine the reliability and validity of PA devices worn on the hip, ankle, and triceps during pregnancy and postpartum. Thirty-three women performed six activities of daily living and one treadmill walk at approximately 21 and 32 wk of pregnancy, and 12 wk postpartum. There were two visits at each time period, 1 wk apart. Energy expenditure (oxygen consumption) was measured by using indirect calorimetry (IC; criterion measure), whereas PA was quantified by using accelerometers and pedometers placed at the right hip and ankle and left triceps. Interclass reliability and monitor validity compared with IC in relative (mL·kg·min) terms were calculated using Pearson correlation. Both multitrial and single-trial intraclass reliabilities (ICC) were estimated using ANOVA to assess monitor reliability at each time period. SEM values were calculated in relative terms for each time period. The reliability of the devices was moderate/strong because 66% of the Pearson correlations were between 0.6 and 1.0. Multitrial ICC values were largely in the moderate/strong range because 38% of the ICC values were between 0.6 and 0.79 and 50% were between 0.8 and 1.0. The SEM values for each device between visits ranged from 7% to 23% of the mean values. Comparison between IC and devices showed that 40% and 46% of the validity coefficients were between 0.4 and 0.59 and between 0.6 and 0.79, respectively. PA devices show moderate/strong reliability and moderate validity for measuring PA during pregnancy and postpartum.


Hydrogen atom reactivity toward aqueous tert-butyl alcohol.
Through a combination of pulse radiolysis, purification, and analysis techniques, the rate constant for the H + (CH(3))(3)COH → H(2) + (•)CH(2)C(CH(3))(2)OH reaction in aqueous solution is definitively determined to be (1.0 ± 0.15) × 10(5) M(-1) s(-1), which is about half of the tabulated number and 10 times lower than the more recently suggested revision. Our value fits on the Polanyi-type, rate-enthalpy linear correlation ln(k/n) = (0.80 ± 0.05)ΔH + (3.2 ± 0.8) that is found for the analogous reactions of other aqueous aliphatic alcohols with n equivalent abstractable H atoms. The existence of such a correlation and its large slope are interpreted as an indication of the mechanistic similarity of the H atom abstraction from α- and β-carbon atoms in alcohols occurring through the late, product-like transition state. tert-Butyl alcohol is commonly contaminated by much more reactive secondary and primary alcohols (2-propanol, 2-butanol, ethanol, and methanol), whose content can be sufficient for nearly quantitative scavenging of the H atoms, skewing the H atom reactivity pattern, and explaining the disparity of the literature data on the H + (CH(3))(3)COH rate constant. The ubiquitous use of tert-butyl alcohol in pulse radiolysis for investigating H atom reactivity and the results of this work suggest that many other previously reported rate constants for the H atom, particularly the smaller ones, may be in jeopardy.


R174 of Escherichia coli FtsZ is involved in membrane interaction and protofilament bundling, and is essential for cell division.
We investigated the interaction between FtsZ and the cytoplasmic membrane using inside-out vesicles. Comparison of the trypsin accessibility of purified FtsZ and cytoplasmic membrane-bound FtsZ revealed that the protruding loop between helix 6 and helix 7 is protected from trypsin digestion in the latter. This hydrophobic loop contains an arginine residue at position 174. To investigate the role of R174, this residue was replaced by an aspartic acid, and FtsZ-R174D was fused to green fluorescent protein (GFP). FtsZ-R174D-GFP could localize in an FtsZ and in an FtsZ84(Ts) background at both the permissive and the non-permissive temperature, and it had a reduced affinity for the cytoplasmic membrane compared with wild-type FtsZ. FtsZ-R174D could also localize in an FtsZ depletion strain. However, in contrast to wild-type FtsZ, FtsZ-R174D was not able to complement the ftsZ84 mutation or the depletion strain and induced filamentation. In vitro polymerization experiments showed that FtsZ-R174D is able to polymerize, but that these polymers cannot form bundles in the presence of 10 mM CaCl2. This is the first description of an FtsZ mutant that has reduced affinity for the cytoplasmic membrane and does not support cell division, but is still able to localize. The mutant is able to form protofilaments in vitro but fails to bundle. It suggests that neither membrane interaction nor bundling is a requirement for initiation of cell division.


Depletion of hnRNP A2/B1 overrides the nuclear retention of the HIV-1 genomic RNA.
hnRNP A2 is a cellular protein that is important for nucleocytoplasmic and cytosolic trafficking of the HIV-1 genomic RNA. Both hnRNP A2's interaction with HIV-1 RNA and its expression levels influence the activities of Rev in mediating nucleocytoplasmic export of the HIV-1 genomic RNA. While the lack of Rev expression during HIV-1 gene expression results in nuclear retention of HIV-1 genomic RNA, we show here by fluorescence in situ hybridization and fractionation studies that the genomic RNA translocates to the cytoplasm when hnRNP A2/B1 are depleted from cells. Polyribosome analyses revealed that the genomic RNA was shunted into a cytoplasmic, dense polyribosomal fraction. This fraction contained several RNA-binding proteins involved in viral gene expression and RNA trafficking but did not contain the translation initiation factor, eIF4G1. Amino acid incorporation into nascent polypeptides in this fraction was also greatly reduced, demonstrating that this fraction contains mRNAs that are poorly translated. These results demonstrate that hnRNP A2/B1 expression plays roles in the nuclear retention of the HIV-1 genomic RNA in the absence of Rev and in the release of the genomic RNA from translationally inactive, cytoplasmic RNP complexes.


Regional brain atrophy and functional connectivity changes related to fatigue in multiple sclerosis.
Fatigue is one of the most frequent symptoms in multiple sclerosis (MS), and recent studies have described a relationship between the sensorimotor cortex and its afferent and efferent pathways as a substrate of fatigue. The objectives of this study were to assess the neural correlates of fatigue in MS through gray matter (GM) and white matter (WM) atrophy, and resting state functional connectivity (rs-FC) of the sensorimotor network (SMN). Eighteen healthy controls (HCs) and 60 relapsing-remitting patients were assessed with the Fatigue Severity Scale (FSS). Patients were classified as fatigued (F) or nonfatigued (NF). We investigated GM and WM atrophy using voxel-based morphometry, and rs-FC changes with a seed-based method and independent component analysis (ICA). F patients showed extended GM and WM atrophy focused on areas related to the SMN. High FSS scores were associated with reductions of WM in the supplementary motor area. Seed analysis of GM atrophy in the SMN showed that HCs presented increased rs-FC between the primary motor and somatosensory cortices while patients with high FSS scores were associated with decreased rs-FC between the supplementary motor area and associative somatosensory cortex. ICA results showed that NF patients presented higher rs-FC in the primary motor cortex compared to HCs and in the premotor cortex compared to F patients. Atrophy reduced functional connectivity in SMN pathways and MS patients consequently experienced high levels of fatigue. On the contrary, NF patients experienced high synchronization in this network that could be interpreted as a compensatory mechanism to reduce fatigue sensation.


The influence of different dressings on the pH of the wound environment.
This study examines the effect of various wound dressings on the pH levels of a wound, using a simulated wound environment. The pH levels of a 4 different wound dressings (manuka honey dressing, sodium carboxymethylcellulose hydrofiber dressing, polyhydrated ionogen-coated polymer mesh dressing, and a protease modulating collagen cellulose dressing) were tested in a simulated horse serum wound environment. The effect of local buffering was observed and pH changes in real time were measured. All dressings were found to have low pH (below pH 4), with the lowest being the protease modulating collage cellulose dressing, with a pH of 2.3. The dressing with the strongest acid concentration was the polyhydrated, ionogen-coated, polymer mesh dressing. The low pH and strong acidic nature of the dressing investigated indicate that they may play a role in influencing the healing process in a wound. The authors have no conflicts of interest to declare. This study was funded by the EPSRC.


HPV communication: review of existing research and recommendations for patient education.
The potential for human papillomavirus (HPV) DNA testing in cervical cancer prevention programs has been a topic at the forefront of cervical cancer policy discussions in recent years. To prevent some of the anxiety and psychological distress often experienced on HPV diagnosis and during the period of management, mass patient education must accompany the incorporation of HPV DNA testing into screening protocols. To contribute to a growing body of work that provides an empiric basis for development of effective counseling messages about HPV and HPV testing, this paper highlights women's most common information gaps and psychosocial concerns and describes the different perspectives offered by women's usual sources of information about HPV, including the crucial role of the clinical community in creating a shared decision making environment in which screening decisions and results can be discussed.


Pitfalls in avoiding operation for autoimmune pancreatitis.
Despite improved clinical characterization, autoimmune pancreatitis is often still diagnosed only after a major operative procedure. This study seeks to elucidate the circumstances that contribute to an inaccurate preoperative diagnosis. Two independent reviewers identified retrospectively an institutional cohort of 68 patients with adequate clinical data to support the diagnosis of autoimmune pancreatitis. Further data regarding presentation, diagnostic studies, and clinical course was abstracted from medical records. Comparative analyses were performed between those patients who underwent major operative procedures and those who did not. Fifty-three patients underwent operative intervention as their initial treatment. Compared to the 15 patients avoiding operation, these patients were less likely to have diffuse pancreatic enlargement identified on pretreatment imaging (8% vs 80%) or to have pretreatment serum IgG4 level evaluations (11% vs 100%). Among the 21 patients in whom IgG4 levels were first checked postoperatively, only 12 had increases of at least twice the upper limit of normal. Pretreatment fine needle aspirates were interpreted incorrectly as definite or suspicious for adenocarcinoma in 12 patients, of whom 10 underwent operation. Clinically important postoperative disease recurrence was suspected or proven in 13 patients. Pitfalls leading to major pancreatic resections in autoimmune pancreatitis include unnecessarily high thresholds for initiating serum IgG4 evaluation, false positive cytologic evaluations for malignancy, and failure to recognize non-classic initial presentations, or recurrence of disease. Better diagnostic strategies are needed, but awareness of these specific findings should help to decrease the number of patients undergoing operation for unrecognized autoimmune pancreatitis.


Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue.
Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale. Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1-2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse. Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.


MCycDB: A curated database for comprehensively profiling methane cycling processes of environmental microbiomes.
Methane is a critical greenhouse gas with significant impacts on environmental and global change. However, CH4 cycling processes and coupling mechanisms with the biogeochemical cycling of carbon, nitrogen, sulfur and metals in the environment remain elusive. To fill such knowledge gaps, we constructed a manually curated methane cycling database (MCycDB) for comprehensive and accurate analysis of methane cycling microbial communities. MCycDB contains 298 methane cycling gene families covering 10 methane metabolism pathways with 610,208 representative sequences, and associated reference sequences from the NCBI RefSeq database with 48 phyla and 2,197 genera, and five phyla and 100 genera for bacteria and archaea, respectively. Also, homologous groups from public orthology databases were identified and included in MCycDB to reduce false positive assignments. We applied MCycDB to profile methane cycling gene families and associated taxonomic groups from various environments. Gene families involved in methanogenesis were abundant in hot spring sediment and less abundant in freshwater, whereas the ones involved in aerobic oxidation of methane were abundant in permafrost and peatland. This study demonstrates that MCycDB is a useful tool for studying microbially-driven methane cycling processes with high specificity, coverage and accuracy.


Inflammation in neurological disorders: a help or a hindrance?
Inflammation of the central nervous system (CNS) (neuroinflammation) is now recognized to be a feature of all neurological disorders. In multiple sclerosis, there is prominent infiltration of various leukocyte subsets into the CNS. Even when there is no significant inflammatory infiltrates, such as in Parkinson or Alzheimer disease, there is intense activation of microglia with resultant elevation of many inflammatory mediators within the CNS. An extensive dataset describes neuroinflammation to have detrimental consequences, but results emerging largely over the past decade have indicated that aspects of the inflammatory response are beneficial for CNS outcomes. Benefits of neuroinflammation now include neuroprotection, the mobilization of neural precursors for repair, remyelination, and even axonal regeneration. The findings that neuroinflammation can be beneficial should not be surprising as a properly directed inflammatory response in other tissues is a natural healing process after an insult. In this article, we review the data that highlight the dual aspects of neuroinflammation in being a hindrance on the one hand but also a significant help for recovery of the CNS on the other. We consider how the inflammatory response may be beneficial or injurious, and we describe strategies to harness the beneficial aspects of neuroinflammation.


Isolation of equine multipotent mesenchymal stromal cells by enzymatic tissue digestion or explant technique: comparison of cellular properties.
The treatment of tendon lesions with multipotent mesenchymal stromal cells (MSCs) is widely used in equine medicine. Cell sources of MSCs include bone marrow, as well as solid tissues such as adipose tissue. MSCs can be isolated from these solid tissues either by enzymatic digestion or by explant technique. However, the different preparation techniques may potentially influence the properties of the isolated MSCs. Therefore, the aim of this study was to investigate and compare the effects of these two different methods used to isolate MSCs from solid tissues.Equine adipose tissue, tendon and umbilical cord matrix served as solid tissue sources of MSCs with different stiffness and density. Subsequent to tissue harvest, MSCs were isolated either by enzymatic digestion with collagenase or by explant technique. Cell yield, growth, differentiation potential and tendon marker expression were analysed. At first passage, the MSC yield was significantly higher in enzymatically digested tissue samples than in explanted tissue samples, despite a shorter period of time in primary culture. Further analysis of cell proliferation, migration and differentiation revealed no significant differences between MSCs isolated by enzymatic digestion and MSCs isolated by explant technique. Interestingly, analysis of gene expression of tendon markers revealed a significantly higher expression level of scleraxis in MSCs isolated by enzymatic digestion. Both isolation techniques are feasible methods for successful isolation of MSCs from solid tissues, with no major effects on cellular proliferation, migration or differentiation characteristics. However, higher MSC yields were achieved in a shorter period of time by collagenase digestion, which is advantageous for the therapeutic use of MSCs. Moreover, based on the higher level of expression of scleraxis in MSCs isolated by enzymatic digestion, these cells might be a better choice when attempting tendon regeneration.


MicroRNA-302 switch to identify and eliminate undifferentiated human pluripotent stem cells.
The efficiency of pluripotent stem cell differentiation is highly variable, often resulting in heterogeneous populations that contain undifferentiated cells. Here we developed a sensitive, target-specific, and general method for removing undesired cells before transplantation. MicroRNA-302a-5p (miR-302a) is highly and specifically expressed in human pluripotent stem cells and gradually decreases to basal levels during differentiation. We synthesized a new RNA tool, miR-switch, as a live-cell reporter mRNA for miR-302a activity that can specifically detect human induced pluripotent stem cells (hiPSCs) down to a spiked level of 0.05% of hiPSCs in a heterogeneous population and can prevent teratoma formation in an in vivo tumorigenicity assay. Automated and selective hiPSC-elimination was achieved by controlling puromycin resistance using the miR-302a switch. Our system uniquely provides sensitive detection of pluripotent stem cells and partially differentiated cells. In addition to its ability to eliminate undifferentiated cells, miR-302a switch also holds great potential in investigating the dynamics of differentiation and/or reprograming of live-cells based on intracellular information.


Changes in Chloroplast DNA Levels during Development of Pea (Pisum sativum).
Determinations were made of the percentage of chloroplast DNA (ct DNA) in total cell DNA isolated from shoots of pea at different stages of development. Labeled pea ct DNA was reassociated with a high concentration of total DNA; the percentage of ct DNA was estimated by comparing the rate of reassociation of this reaction with that of a model reaction containing a known concentration of unlabeled ct DNA. The maximum change in ct DNA content was from 1.3% of total DNA in young shoots to 7.3% in fully greened shoots. Analyses were also performed on DNA from embryos, etiolated tissue, roots, and leaves. The first leaf set to develop in pea was excised over a growth period of 8 days during which leaf length increased from 4 to 12 millimeters. Young leaves contained about 8% ct DNA; in fully greened leaves the level of ct DNA approached 12%, equivalent to as many as 9,575 copies of ct DNA per cell. Root tissue contained only 0.4% ct DNA.


Optoelectronic array that computes error and weight modification for a bipolar optical neural network.
The design, fabrication, and results of an optoelectronic device that computes the weight changes required by the delta-rule learning algorithm and encodes the result on a pair of optical beams are presented. This very-large-scale-integrated ferroelectric liquid-crystal array was designed specifically to permit bipolar optoelectronic neural networks to learn without the limitations of an external controlling computer. The device contains 64 smart pixels, which represent the processing elements in an artificial neural network. Each processing element consists of two photodetectors, a current-to-voltage converter, two comparators, two switches, and two output liquid-crystal modulating pads. The device has a measured contrast ratio of 10:1, a 10%-to-90% rise time of 350 micros, and a 90%-to-10% fall time of 150 micros.


Whole Genomic Copy Number Alterations in Circulating Tumor Cells from Men with Abiraterone or Enzalutamide-Resistant Metastatic Castration-Resistant Prostate Cancer.
Purpose: Beyond enumeration, circulating tumor cells (CTCs) can provide genetic information from metastatic cancer that may facilitate a greater understanding of tumor biology and enable a precision medicine approach.Experimental Design: CTCs and paired leukocytes from men with metastatic castration-resistant prostate cancer (mCRPC) were isolated from blood through red cell lysis, CD45 depletion, and flow sorting based on EpCAM/CD45 expression. We next performed whole genomic copy number analysis of CTCs and matched patient leukocytes (germline) using array-based comparative genomic hybridization (aCGH) from 16 men with mCRPC, including longitudinal and sequential aCGH analyses of CTCs in the context of enzalutamide therapy.Results: All patients had mCRPC and primary or acquired resistance to abiraterone acetate or enzalutamide. We compiled copy gains and losses, with a particular focus on those genes highly implicated in mCRPC progression and previously validated as being aberrant in metastatic tissue samples and genomic studies of reference mCRPC datasets. Genomic gains in >25% of CTCs were observed in AR, FOXA1, ABL1, MET, ERG, CDK12, BRD4, and ZFHX3, while common genomic losses involved PTEN, ZFHX3, PDE4DIP, RAF1, and GATA2 Analysis of aCGH in a sample with sequential enzalutamide-resistant visceral progression showed acquired loss of AR amplification concurrent with gain of MYCN, consistent with evolution toward a neuroendocrine-like, AR-independent clone.Conclusions: Genomic analysis of pooled CTCs in men with mCRPC suggests a reproducible, but highly complex molecular profile that includes common aberrations in AR, ERG, c-MET, and PI3K signaling during mCRPC progression, which may be useful for predictive biomarker development. Clin Cancer Res; 23(5); 1346-57. ©2016 AACR.


Inhibiting Heat Shock Protein 90 Protects Nucleus Pulposus-Derived Stem/Progenitor Cells From Compression-Induced Necroptosis and Apoptosis.
Nucleus pulposus-derived stem/progenitor cells (NPSCs) provide novel prospects for the regeneration of degenerated intervertebral disc (IVD). Nevertheless, with aging and degeneration of IVD, the frequency of NPSCs markedly decreases. Excessive cell death could be the main reason for declined frequency of NPSCs, however, the exact mechanisms remain elusive. Thus, the present study was undertaken to explore the mechanisms of compression-induced NPSCs death, and the effects of heat shock protein 90 (HSP90) on NPSCs survival. Here, we found that compression could trigger receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis of NPSCs. Furthermore, we found that elevated expression of HSP90 was involved in compression-induced NPSCs death, and inhibiting HSP90 could dramatically attenuate compression-induced necroptosis of NPSCs via regulating the expression and activity of RIPK1/RIPK3/MLKL, and alleviating the mitochondrial dysfunction (mitochondrial membrane potential loss and ATP depletion) and oxidative stress [production of mitochondrial reactive oxygen species (ROS), cellular total ROS and malondialdehyde, and downregulation of superoxide dismutase 2]. Besides necroptosis, compression-induced apoptosis of NPSCs was also attenuated by HSP90 inhibition. In addition, we found that enhanced expression of HSP70 contributed to the cytoprotective effects of inhibiting HSP90. More encouragingly, our results demonstrated that inhibiting HSP90 could also mitigate the exhaustion of NPSCs in vivo. In conclusion, RIPK1/RIPK3/MLKL-mediated necroptosis participates in compression-induced NPSCs death. Furthermore, targeting HSP90 to simultaneously inhibit necroptosis and apoptosis of NPSCs might be an efficient strategy for preventing the death of NPSCs, thus rescuing the endogenous repair capacity of NP tissue.


Happenings in histopathology - a post-World War II perspective.
There have been several important developments in the practice of histopathology since World War II; those reviewed in this lecture are grouped under 4 headings: new techniques (cytopathology, electron microscopy, immunohistochemistry and molecular pathology), organisational issues (recruitment, training and certification, subspecialties, quality control and consultations), ethical and legal issues (service costs, and the ownership and uses of biopsy tissues) and globalisation (international associations, standardised classification and nomenclature, and telepathology). Advances in the fields of molecular pathology and telepathology are expected to have the greatest impact on the practice of pathology in the next decade.


Spontaneous priapism after radical retropubic prostatectomy.
We present the first case of priapism following radical prostatectomy. A 66-year-old man with normal erections underwent radical retropubic prostatectomy with unilateral nerve sparing. Pathology showed a pT2c pN0 Gleason score 3 + 3 = 6 prostate cancer and the postoperative course was uneventful. Ten days after surgery he recognized a spontaneous painful penile erection without sexual stimulation which occurred in a standing position and disappeared in a supine position. These episodes recurred several times during the next 3 weeks and then completely vanished. Pathophysiologically, we postulate intermittent position-depending venous obstruction due to local hematoma or thrombosis.


Variation of psychological and anthropometrics measures before and after dieting and factors associated with body dissatisfaction and quality of life in a Lebanese clinical sample.
The primary objective of this study was to assess a change in the psychological states (stress, self-esteem, anxiety and depression), anthropometric measurements and physical/mental quality of life before and after diet in a sample of Lebanese subjects visiting a diet clinic. The secondary objectives included the evaluation of factors associated with body dissatisfaction, mental and physical quality of life (QOL) before the intervention of the diet program and the change in quality of life after this intervention among those participants. This cross-sectional study, conducted between May and August 2018, enrolled 62 participants recruited from three diet clinics. The QOL was measured using the 12-item Short Form Health Survey (SF-12) and the psychological states was measured using the following scales: The Rosenberg Self-esteem Scale, Perceived Stress Scale, Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. A significant reduction in body dissatisfaction, anxiety, waist, weight and body fat and a significant increase in the physical and mental quality of life was seen after diet compared to before it (p < 0.001 for all). No significant variation in perceived stress (p = 0.072), self-esteem (p = 0.885), and depression (p = 0.353) after diet were found. Higher BMI (β = 0.440) and higher anxiety (β = 0.132) were associated with higher body dissatisfaction scores, whereas higher self-esteem (β = - 0.818) was significantly associated with lower body dissatisfaction. Higher perceived stress (β = - 0.711), higher body dissatisfaction (β = - 0.480) and being a female (β = - 4.094) were associated with lower mental QOL. Higher Physical Activity Index was significantly associated with higher mental and physical QOL (β = 0.086 and β = 0.123 respectively). The results indicate the effectiveness of diet programs in enhancing the quality of life, psychological and anthropometric measures.


Targetless T cells in cancer immunotherapy.
Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell transfer (ACT) using expanded tumor infiltrating lymphocytes (TIL) or genetically modified cytotoxic T cells. However, despite clear clinical responses, only a fraction of patients respond to treatment and there is an urgent call for characterization of predictive biomarkers. CD8 positive T cells can infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However, it is also well established that cancer cells are often characterized by loss or down regulation of HLA class I molecules, documented in a variety of human tumors. Consequently, immune therapy building on CD8 T cells will be futile in patients harboring HLA class-I negative or deficient cancer cells. It is therefore mandatory to explore if these important molecules for T cell cytotoxicity are expressed by cancer target cells. We have indications that different types of immunotherapy can modify the tumor microenvironment and up-regulate reduced HLA class I expression in cancer cells but only if the associated molecular mechanisms is reversible (soft). However, in case of structural (hard) aberrations causing HLA class I loss, tumor cells will not be able to recover HLA class I expression and as a consequence will escape T-cell lysis and continue to growth. Characterization of the molecular mechanism underlying the lack or downregulation of HLA class I expression, seems to be a crucial step predicting clinical responses to T cell mediated immunotherapy, and possibly aid the selection of strategies that could condition patients for response. Thus, characterization of HLA expression by cancer cells could therefore represent an important predictive marker for immunotherapy of cancer.


Outcomes following Notched Ruthenium-106 Plaque Brachytherapy for Juxtapapillary Choroidal Melanomas.
This study aimed to evaluate the outcomes of juxtapapillary choroidal melanomas treated with notched ruthenium-106 plaques. Juxtapapillary choroidal melanomas (tumours within 2 disc diameters from the optic disc) treated with notched ruthenium-106 plaques (Eckert & Ziegler, BEBIG, Berlin, Germany) at the Scottish Ocular Oncology Service between 2009 and 2015 were retrospectively reviewed. The data were analysed with respect to various outcome measures including recurrence, complications, vision, and eye preservation. We reviewed 40 patients with a median tumour diameter of 8.4 mm (range 5-17 mm) and a median thickness of 2.5 mm (range 1.1-6 mm). AJCC tumour category distribution was 62.5% T1, 32.5% T2, and 5% T3 tumours. The mean presenting vision was 0.3 logMAR, and the mean final vision was 0.7 logMAR, with 62.5% retaining >1.0 logMAR and 50% retaining >0.3 logMAR at the final follow-up. The median follow-up was 51 months (14-100 months). Over the maximum follow-up time, 13 tumours (32.5%) recurred. Six of these were treated with salvage proton beam therapy (PBT), 2 with transpupillary thermotherapy followed by PBT, and 5 with enucleation. The final eye retention rate was 87.5%. Complications included maculopathy (10%), retinal detachment (5%), neovascular glaucoma (2.5%), and diplopia (2.5%). The observed risk of recurrence over 5 years was 31% (95% CI: 14.1%, 47.8%), and the risk of enucleation over 5 years was 11.5% (95% CI: 0.9%, 21.8%). Juxtapapillary choroidal melanomas treated with notched ruthenium plaques have a high recurrence rate and frequently need salvage treatment with PBT for tumour control. This has led to a change in our practice toward offering PBT as the first-line treatment for these patients.


Relationship between nomophobia of nursing students and their obesity and self-esteem.
The aim of this study is to examine the relationship between student nurses' nomophobia levels and obesity and self-esteem. This study is a descriptive-correlational type study. This study conducted 607 nursing students. Data were collected with "Personal Information Form," "Nomophobia Questionnaire (NMP-Q)," and "The Self Esteem Rating Scale-Short Form." As a result of the research, it was determined that the students had moderate nomophobia. There was no significant relationship between nomophobia and obesity and self-esteem. It was determined that especially when they are bored, the rate of using smartphones is high, and the use of smartphones harms their lives. More studies are needed to examine the relationship of nomophobia with students' body mass index and self-esteem.


Asymmetric γ-Allylation of α,β-Unsaturated Aldehydes by Combined Organocatalysis and Transition-Metal Catalysis.
The first asymmetric regio- and diastereodivergent γ-allylation of cyclic α,β-unsaturated aldehydes based on combined organocatalysis and transition-metal catalysis is disclosed. By combining an aminocatalyst with an iridium catalyst, both diastereomers of branched allylated products can be achieved in moderate to good yields and excellent regio- and stereoselectivities. Furthermore, by replacing the iridium catalyst with a palladium catalyst, the linear allylated products are formed in good yields and excellent regio- and enantioselectivities. The developed method thus provides selective access to all six isomers of the γ-allylated product in a divergent fashion by choosing the appropriate combination of organocatalyst, transition-metal catalyst, and ligand.


Esophageal endoprosthesis therapy.
Currently various methods for the treatment of obstructing esophageal lesions are used in the endoscopy setting. The placement of an endoscopic esophageal endoprosthesis (stent) offers a palliative form of therapy for esophageal cancer designed to enhance the patient's quality of life. The gastroenterology nurse or associate must be familiar with the various types of prostheses available, methods of insertion and patient care needs related to esophageal stent placement in order to provide optimal patient care. This article offers a review of esophageal endoprosthesis therapy. The various types of endoprostheses utilized in the United States, insertion techniques, advantages and disadvantages of stent placement and implications for patient care will be discussed.


Revolutionary change in rheumatoid arthritis management with biological therapy.
Biological agents targeting a specific molecule have extraordinarily fine specificity and powerful functional capabilities. By the introduction of biological therapy, management of rheumatoid arthritis has undergone a revolution and a paradigm shift. In this review, I will summarize the role in the pathogenesis of rheumatoid arthritis of the molecules targeted by biological agents. Providing evidence obtained in clinical trials and investigator-initiated clinical studies in Japan, the effectiveness and safety of biological therapy in rheumatoid arthritis are discussed. Finally, studies aiming at a personalized strategy with biological agents are listed and the future perspectives toward tailor-made medicine in the field of rheumatology are discussed.


[Molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus during 2017-2018 at a hospital in Shanghai].
Objective: To identify the epidemic clones of MRSA isolates at a hospital in shanghai. Methods: A total of 72 MRSA isolates have been isolated from a second grade hospital between 2017 and 2018, including 32 CA-MRSA isolates, 13 HA-MRSA isolates and 26 MRSA isolates from environment. In this study, MLST and PFGE typing methods were used to analyze the molecular epidemiology of the MRSA isolates. Results: A total of 72 MRSA isolates have been obtained including 46 isolates from clinical specimens, 26 isolates from environments. The 46 MRSA isolates from clinical specimens consisted of 33 CA-MRSA (community-acquired MRSA) and 13 HA-MRSA (hospital-acquired MRSA). Furthermore, these patients infected with MRSA isolates were mostly distributed in the department of geriatrics (34.8%, 16/46), internal medicine (26.1%, 12/46) and surgery (26.1%, 12/46). MLST typing results showed that ST764 was predominant in isolates from both clinical specimens and hospital environments. Furthermore, PFGE typing results showed that most ST764 MRSA had high homolog (>90%). Conclusion: ST764 MRSA isolates might spread in community, hospital and environments. Therefore, continuous monitoring of MRSA and its variation may be useful in understanding the involvement of epidemic clone, and in searching new strategies to control MRSA infection.


Excellent Humidity Sensor Based on LiCl Loaded Hierarchically Porous Polymeric Microspheres.
A catalyst-free Friedel-Crafts alkylation reaction has been developed to synthesize hierarchically porous polymeric microspheres (HPPMs) with phloroglucin and dimethoxymethane. HPPMs with uniform size were obtained and the size can be tuned by the concentration of raw materials. The chemical structure and hierarchical porous characteristic of HPPMs were characterized in detail. HPPMs were then loaded with humidity sensitive material LiCl to construct composites for humidity sensor. The optimum sensor based on 3 wt % LiCl-loaded HPPMs shows high sensitivity at the relative humidity (RH) atmosphere of 11-95%, small hysteresis, enhanced durability and rapid response. The sensitive mechanism was discussed through the investigation of complex impedance plots.


Transient Downregulation of Melanopsin Expression After Retrograde Tracing or Optic Nerve Injury in Adult Rats.
To investigate the effect of retrograde tracing or axotomy on melanopsin mRNA expression and immunodetection in albino and pigmented rat retinas. Groups were (1) intact-naïve retinas; (2) optic nerve crush (ONC) analyzed at 7 days (7d) or 2 months (2m); (3) Fluorogold (FG) tracing from the superior colliculi (SCi) analyzed at 7d or 2m; (4) tracing from the intact optic nerve (ON) with FG or hydroxystilbamidine methanesulfonate (OHSt), analyzed 3d later; and (5) sham tracing from the ON or sham surgery. Brn3a and melanopsin were double stained in whole mounts to quantify and assess the distribution of orthotopic and displaced Brn3a(+) retinal ganglion cells (Brn3a(+)RGCs) and melanopsin(+)RGCs (m(+)RGCs). Freshly dissected retinas were used for melanopsin mRNA quantitative PCR. Tracing from the SCi did not affect the number of Brn3a(+)RGCs or m(+)RGCs counted in pigmented rats. However, only 55% of m(+)RGCs were immunodetected in albinos at 7d, although by 2m the m(+)RGCs counts returned to normal. Optic nerve tracing had a more dramatic effect (38% or 77% of m(+)RGCs were immunodetected in albino or pigmented rats) that occurred irrespectively of the tracer (OHSt or FG). This effect was not observed in the sham groups. After ONC, Brn3a(+)RGCs decreased to 37% and 8% by 7d and 2m, respectively. Melanopsin (+)RGC counts diminished to 30% at 7d, but recovered to 49% of controls by 2m. Melanopsin mRNA was downregulated after ON tracing or 7d after ONC, but did not differ from intact values 2m after ONC. Following ON injury or retrograde tracing there is a transient melanopsin downregulation that should be taken into account when assessing m(+)RGC survival.


Primary thrombosis of the anterior descending in a patient with antiphospholipid antibody syndrome
Antiphospholipid antibody syndrome is a heterogeneous clinical and biochemical entity. We present the case of a young male with history of venous thromboembolism. This time he presents because of chest ischemic pain associated with ST segment elevation. He was taken to the cath lab to perform a primary percutaneous coronary intervention and a total occlusion of the left anterior descending artery was noted. Successful thrombus aspiration was performed. No stent was deployed. He was taken to the cath lab for a second look angiography and no atherosclerotic lesions were observed, which was confirmed by intravascular ultrasound.


Relationship between bacterial community composition and bottom-up versus top-down variables in four eutrophic shallow lakes.
Bacterial community composition was monitored in four shallow eutrophic lakes during one year using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified prokaryotic rDNA genes. Of the four lakes investigated, two were of the clearwater type and had dense stands of submerged macrophytes while two others were of the turbid type characterized by the occurrence of phytoplankton blooms. One turbid and one clearwater lake had high nutrient levels (total phosphorus, >100 micro g liter(-1)) while the other lakes had relatively low nutrient levels (total phosphorus, <100 micro g liter(-1)). For each lake, seasonal changes in the bacterial community were related to bottom-up (resources) and top-down (grazers) variables by using canonical correspondence analysis (CCA). Using an artificial model dataset to which potential sources of error associated with the use of relative band intensities in DGGE analysis were added, we found that preferential amplification of certain rDNA genes over others does not obscure the relationship between bacterial community composition and explanatory variables. Besides, using this artificial dataset as well as our own data, we found a better correlation between bacterial community composition and explanatory variables by using relative band intensities compared to using presence/absence data. While bacterial community composition was related to phytoplankton biomass in the high-nutrient lakes no such relation was found in the low-nutrient lakes, where the bacterial community is probably dependent on other organic matter sources. We used variation partitioning to evaluate top-down regulation of bacterial community composition after bottom-up regulation has been accounted for. Using this approach, we found no evidence for top-down regulation of bacterial community composition in the turbid lakes, while grazing by ciliates and daphnids (Daphnia and Ceriodaphnia) was significantly related to changes in the bacterial community in the clearwater lakes. Our results suggest that in eutrophic shallow lakes, seasonality of bacterial community structure is dependent on the dominant substrate source as well as on the food web structure.


Acidic fibroblast growth factor promotes vascular repair.
Intravascular injury to arteries can result in thickening of the intimal smooth muscle layer adjacent to the lumen by migration and proliferation of cells from the underlying medial smooth muscle layer accompanied by deposition of extracellular matrix. This pathological response, which decreases lumen diameter, might, in part, be the result of the access of smooth muscle cells to plasma and platelet-derived growth factors as a consequence of denudation of the overlying confluent monolayer of vascular endothelial cells. Injured rat carotid arteries were treated by i.v. administration of acidic fibroblast growth factor, a heparin-binding protein that is chemotactic and mitogenic for vascular endothelial cells. The growth factor treatment resulted in dose-dependent inhibition of intimal thickening with parallel promotion of endothelial regeneration over the injured area. Therefore, acidic fibroblast growth factor might be efficacious in the prevention of restenosis caused by intimal thickening following angioplasty in humans.


Taxonomy of Neotyphodium endophytes of Chinese native Roegneria plants.
In this study we describe a new Neotyphodium species, Neotyphodium sinicum, found in natural symbiosis with asymptomatic Roegneria spp. (Elymus spp.) native to China. We investigated the host specificity, morphology, mating compatibility and molecular phylogenetic evidence for recognition of this new species. N. sinicum is host specific and seedborne and widely distributed in China. Most morphological characteristics of this new species are typical of other Neotyphodium species, but the growth on PDA plates tends to be more rapid. Three of five N. sinicum strains examined had double alleles of tefA and two of the five strains had double alleles of both tubB and tefA. Phylogenetic relationships based on sequences of tubB introns and tefA introns revealed that the allele-1 of tefA and tubB clustered together in a distinct subclade in the Epichloe bromicola/E. yangzii clade. The allele-2 grouped in the Epichlok" typhina clade (ETC). N. sinicum therefore appears to be an interspecific hybrid related to both E. yangzii and members of ETC. In mating tests N. sinicum failed to hybridize with E. yangzii.


Early-phase adaptations to a split-body, linear periodization resistance training program in college-aged and middle-aged men.
An 8-week, split-body, linear periodized resistance training program was completed by college-aged (CA: 18-22 years; n = 24) and middle-aged (MA: 35-50 years; n = 25) men to determine early-phase adaptations in body composition and upper- and lower-body strength. Participants completed 2 upper-body and 2 lower-body resistance training workouts each week. During weeks 1-4, subjects completed 3-6 sets at a 10-repetition maximum (RM) intensity and increased to 8RM for weeks 5-8. The 1RM strength levels were determined on the bench press and leg press, and 30-second Wingate tests were assessed at baseline and after 8 weeks of resistance training. Body composition was assessed using dual-energy X-ray absorptiometry (DXA). For selected data, delta values (post - pre values) were calculated and reported as mean +/- SEM. No changes (p > 0.05) were reported for peak and average Wingate power. Bench press (CA, 3.2 +/- 1.9 kg; MA, 6.2 +/- 3.3 kg; p < 0.001) and leg press (CA, 25.0 +/- 4.4 kg; MA, 18.2 +/- 13.3 kg; p < 0.001) 1RM significantly increased in both groups over time. Lean mass significantly increased over time in both groups (CA, 0.9 +/- 2.4 kg; MA, 1.1 +/- 1.9 kg; p < 0.001). Significant group x time effects were seen for fat mass changes (CA, 0.5 +/- 1.3 kg; MA, -0.5 +/- 1.1 kg; p = 0.01) and % body fat changes (CA, 0.4 +/- 1.4%; MA, -0.7 +/- 1.1%; p = 0.01). These results indicate that performing a split-body, linearly periodized resistance training program for 8 weeks significantly increases bench press 1RM, leg press 1RM, and DXA lean mass in CA and MA men. Furthermore, MA men lost significantly more fat mass and significantly decreased % body fat compared with CA men. A split-body, linearly periodized resistance training program may be used as an effective program to increase strength and lean mass in both young and MA populations.


Surface adsorption in strontium chloride ammines.
An adsorbed state and its implications on the ab- and desorption kinetics of ammonia in strontium chloride ammine is identified using a combination of ammonia absorption measurements, thermogravimetric analysis, and density functional theory calculations. During thermogravimetric analysis, ammonia desorption originating from the adsorbed state is directly observed below the bulk desorption temperature, as confirmed by density functional theory calculations. The desorption enthalpy of the adsorbed state of strontium chloride octa-ammine is determined with both techniques to be around 37-39 kJ∕mol. A simple kinetic model is proposed that accounts for the absorption of ammonia through the adsorbed state.


On the nature of real and perceived bias in the mainstream media.
News consumers expect news outlets to be objective and balanced in their reports of events and opinions. However, there is a growing body of evidence of bias in the media caused by underlying political and socio-economic viewpoints. Previous studies have tried to classify the partiality of the media, but there is little work on quantifying it, and less still on the nature of this partiality. The vast amount of content published in social media enables us to quantify the inclination of the press to pre-defined sides of the socio-political spectrum. To describe such tendencies, we use tweets to automatically compute a news outlet's political and socio-economic orientation. Results show that the media have a measurable bias, and illustrate this by showing the favoritism of Chilean media for the ruling political parties in the country. This favoritism becomes clearer as we empirically observe a shift in the position of the mass media when there is a change in government. Even though relative differences in bias between news outlets can be observed, public awareness of the bias of the media landscape as a whole appears to be limited by the political space defined by the news that we receive as a population. We found that the nature of the bias is reflected in the vocabulary used and the entities mentioned by different news outlets. A survey conducted among news consumers confirms that media bias has an impact on the coverage of controversial topics and that this is perceivable by the general audience. Having a more accurate method to measure and characterize media bias will help readers position outlets in the socio-economic landscape, even when a (sometimes opposite) self-declared position is stated. This will empower readers to better reflect on the content provided by their news outlets of choice.


Neuroticism and conscientiousness respectively constrain and facilitate short-term plasticity within the working memory neural network.
Individual differences in cognitive efficiency, particularly in relation to working memory (WM), have been associated both with personality dimensions that reflect enduring regularities in brain configuration, and with short-term neural plasticity, that reflects task-related changes in brain connectivity. To elucidate the relationship of these two divergent mechanisms, we tested the hypothesis that personality dimensions, which reflect enduring aspects of brain configuration, inform about the neurobiological framework within which short-term, task-related plasticity, as measured by effective connectivity, can be facilitated or constrained. As WM consistently engages the dorsolateral prefrontal (DLPFC), parietal (PAR), and anterior cingulate cortex (ACC), we specified a WM network model with bidirectional, ipsilateral, and contralateral connections between these regions from a functional magnetic resonance imaging dataset obtained from 40 healthy adults while performing the 3-back WM task. Task-related effective connectivity changes within this network were estimated using Dynamic Causal Modelling. Personality was evaluated along the major dimensions of Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Only two dimensions were relevant to task-dependent effective connectivity. Neuroticism and Conscientiousness respectively constrained and facilitated neuroplastic responses within the WM network. These results suggest individual differences in cognitive efficiency arise from the interplay between enduring and short-term plasticity in brain configuration.


Everyday Memory in Patients with Alzheimer's Disease: Fragmentary and Distorted.
Errors of omission are an established hallmark of memory impairment in Alzheimer's disease (AD). Much less is known about other memory errors in AD such as false memories. We investigated false memories in healthy elderly controls (HC; n = 23) and patients with AD (n = 20) using real-life tasks of watching news and commercials. Participants received a comprehensive neuropsychological assessment and were shown original news and commercials with a subsequent recognition task to assess veridical and false memories. Subjective estimate of the number of errors were alike in HC and patients with AD. However, memory performance in both the news and the commercials task was significantly worse in patients with AD. Trail-Making Test and Symbol-Span Test were significant predictors of false memories on viewing news and commercials. In patients with AD, levels of Aβ1 - 42, but not levels of tau-protein were correlated with false memories in both tasks. Everyday life in patients with AD is impeded not due to the incompleteness of memory but also due to its distortions. Furthermore, it is hindered by the lack of awareness towards these deficits. False memory content in patients with AD is associated with Aβ42 levels in the CSF as a surrogate of the overall extent to which the brain has been affected by AD pathology. Future studies will need to address the impact of this duality of memory failure on everyday life of patients with AD and their proxies in greater detail.


The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis.
Ventricular myocardium in larger mammals is composed of three distinct cell types: epicardial, M, and endocardial cells. Epicardial and M cell, but not endocardial cell, action potentials have a prominent I(to)-mediated notch. M cells are distinguished from the other cell types in that they display a smaller I(Ks), but a larger late I(Na) and I(Na-Ca). These ionic differences may account for the longer action potential duration (APD) and steeper APD-rate relationship of the M cell. The difference in the time course of repolarization of phase 1 and phase 3 contributes to the inscription of the electrocardiographic J wave and T wave, respectively. These repolarization gradients are modulated by electrotonic interactions, [K(+)](o), and agents or mutations that alter net repolarizing current. An increase in late I(Na), as occurring under a variety of pathophysiological states or in response to certain toxins, leads to a preferential prolongation of the M cell action potential, thus prolonging the QT interval and increasing transmural dispersion of repolarization (TDR), which underlies the development of torsade de pointes (TdP) arrhythmias. Agents that reduce late I(Na) are effective in reducing TDR and suppressing TdP. A reduction in peak I(Na) or an increase in net repolarizing current in the early phases of the action potential can lead to a preferential abbreviation of the action potential of epicardium in the right ventricle, and thus the development of a large TDR, phase 2 reentry, and polymorphic ventricular tachycardia associated with the Brugada syndrome.


Heteromultimetallic catalysis for sustainable organic syntheses.
Fully complementary bimetallic catalysis has been identified as an increasingly powerful tool for molecular transformations, which was largely inspired by early examples of sequential catalytic transformations. Thus, energy-efficient one-pot reactions involving different metal catalysts orchestrated in concert constitute an attractive alternative to multi-step protocols, with major recent progress through the elegant ligand design in heterobimetallic catalysis as well as sustainable photo-induced C-H transformations, among others. This review provides a critical assessment of the state of the art in heterobimetallic catalysis for sustainable organic syntheses (SOS), highlighting key advances and representative examples until summer 2017.


Distinct roles for LFA-1 affinity regulation during T-cell adhesion, diapedesis, and interstitial migration in lymph nodes.
During the course of homing to lymph nodes (LNs), T cells undergo a multistep adhesion cascade that culminates in a lymphocyte function-associated antigen 1 (LFA-1)-dependent firm adhesion to the luminal surface of high endothelial venules (HEVs). The importance of LFA-1 affinity regulation in supporting T-cell arrest on HEVs has been well established, however, its importance in the postadhesion phase, which involves intraluminal crawling and diapedesis to the extravascular space, remains elusive. Here we have shown that LFA-1 affinity needs to be appropriately regulated to support these essential steps in the homing cascade. Genetically engineered T cells that were unable to properly down-regulate LFA-1 affinity underwent enhanced, chemokine-independent arrest in HEVs but showed perturbed intravascular crawling to transmigration sites and compromised diapedesis across HEVs. By contrast, the extravascular migration of T cells was insensitive to the affinity-enhancing LFA-1 mutation. These results highlight the requirement for balanced LFA-1 affinity regulation in intravascular and transvascular, but not extravascular, T-cell migration in LNs.


Development of vessels in the foetal cortical transplant depending on the place of grafting in the rat brain.
Formation of new blood vessels within the graft is crucial for the survival of brain grafts. Moreover, it must occur rapidly to prevent ischaemic changes in the grafted neurons. A study was made of the development of the vascular system in the foetal cortical grafts depending on the place of grafting in the rat brain. Pieces of neocortical tissue from an 18-day old rat foetus were transplanted into the lateral ventricle, the striatum or the corpus callosum of 2 months old Wistar rats. The vascular system of the graft was visualized from coronal sections of the brain by means of Pickworth's technique 3, 7, 14 and 28 days after transplantation. After 3 days the vessels in the graft were absent. After 7 days the vessel pattern was poor and very simple and after 14 days the vessels formed large number of branches in the graft. After 28 days the pattern of the vascular network in the graft was similar to that of the vessels of the host brain. The size and branching of the vessels showed considerable variations depending on the localization of the graft.


Antibacterial epipolythiodioxopiperazine and unprecedented sesquiterpene from Pseudallescheria boydii, a beetle (coleoptera)-associated fungus.
Pseudallescheria boydii residing in the gut of coleopteran (Holotrichia parallela) larva produces four new epipolythiodioxopiperazine (ETP) boydines A-D (3-6) and two novel sesquiterpene boydenes A (7) and B (10), in addition to bisdethiobis(methylthio)-deacetylaranotin (1), bisdethiodi(methylthio)-deacetylapoaranotin (2), AM6898 A (8) and ovalicin (9). The structure elucidation was accomplished by a combination of spectral methods with quantum chemical calculations of optical rotations and electronic circular dichroism (ECD) spectra. Boydine B (4) was shown to be active against the clinical strains Bifidobacterium sp., Veillonella parvula, Anaerostreptococcus sp., Bacteroides vulgatus and Peptostreptococcus sp. with an MIC range of 0.2-0.8 μM, and the pharmacophore 3-hydroxy-2,4,6-trimethyl-5-oxooct-6-enoyl chain of 4 was shown to have (2R,3S,4S)-configurations. Boydene A (7) possessed an unprecedented carbon skeleton, suggesting an unusual biochemistry that allows an intramolecular Aldol addition in the fungus. Collectively, the finding may inspire the discovery of new antibacterial agents and the understanding on biosyntheses of polythiodioxopiperazine and sesquiterpene metabolites.


Cardiac index vs oxygen-derived parameters for rational use of dobutamine in patients with congestive heart failure.
In patients with congestive heart failure (CHF), catecholaminergic agents may exert thermogenic effects that limit their beneficial effects in terms of global tissue oxygenation. Oxygen extraction ratio (O2ER) or mixed venous blood saturation (SvO2) might take into account better than cardiac index (CI) the resultant effect of such agents on peripheral oxygenation. We tested this hypothesis in a series of 20 patients with severe CHF and normal blood lactate levels undergoing pulmonary artery catheterization and receiving incremental doses of dobutamine: 0 (Do), 5 (D5), 10 (D10), and 15 micrograms/kg/min (D15). A significant dose-effect relationship (p < 0.01) was found between dose of dobutamine and CI (CI = 0.06 dose + 1.82). By contrast, no dose-effect relationship was observed between dobutamine dose and either O2ER or SvO2. Indeed, a biphasic profile was observed for O2ER and SvO2. From D0 to D10, O2ER decreased (from 45 +/- 6 to 35 +/- 7 percent) and SvO2 increased (from 52 +/- 7 to 62 +/- 7 percent). From D10 to D15, no further change was observed for both parameters. This latter finding was related to a significant increase in VO2 at D15 (p < 0.01). In these normolactatemic patients with unchanged VO2 from D0 to D10 while DO2 linearly increased (from D0 to D15), the increase in VO2 at D15 was probably due to an increase in oxygen demand induced by the drug. Our results suggest that dobutamine at a dose of 15 micrograms/kg/min can induce an increase in O2 demand that might offset the improvement in CI. Thus, in patients with CHF, oxygen-derived parameters such as O2ER and SvO2 should be more appropriate than CI to assess the efficacy of dobutamine.


Morbidity of severely obese subjects.
The prevalences of several risk factors and diseases are dramatically increased in obesity. In contrast, considerable inconsistencies have been reported for the relationship of obesity to the incidence of cardiovascular disease and total mortality. Suggested reasons for these inconsistencies have been confounders and surrogate risk factors, but the single most important cause is that far-reaching conclusions have been drawn from small short-term studies. Several large studies have recently proven that the incidence of cardiovascular disease is increased in obesity. Correct classification of obesity and its subgroups is also of great importance. Visceral obesity constitutes one subgroup at high risk. It seems possible to link diabetes, hypertriglyceridemia, reduced fibrinolysis, and hypertension to elevated portal free fatty acid concentrations because of an increased visceral adipose tissue depot. The quantitation of visceral adipose tissue has been improved by techniques based on computed tomography (CT) and by CT-calibrated anthropometric methods. Results from controlled intervention studies of obesity are entirely lacking but one such study has been started.


Solubilization of microsomal-associated phosphatidylinositol synthase from germinating soybeans.
CDP-1,2-diacyl-sn-glycerol (CDP-diacylglycerol):myo-inositol phosphatidyltransferase (EC 220.127.116.11, phosphatidylinositol synthase) catalyzes the final step in the de novo synthesis of phosphatidylinositol in the endoplasmic reticulum fraction of germinating soybeans (Glycine max L. var Cutler 71). A variety of solubilization agents were examined for their ability to release phosphatidylinositol synthase activity from the microsome fraction. The most effective agent to solubilize the enzyme was the nonionic detergent Brij W-1. A 2.1-fold increase in specific activity was achieved using 1% Brij W-1 with 69% activity solubilized.Maximal solubilization of phosphatidylinositol synthase was completely dependent on Brij W-1 (1%), potassium ions (0.3 m), and manganese ions (0.5 mm). Solubilization of the enzyme was not affected by the protein concentration of microsomes between 3 to 20 milligrams per milliliter. Solubilization was not affected by the pH of solubilization buffer between 6.5 to 8.5. To our knowledge, this is the first phospholipid biosynthetic enzyme solubilized from plant membranes. The Brij W-1-solubilized phosphatidylinositol synthase remained at the top of a glycerol gradient, whereas the membrane-associated enzyme sedimented to the bottom of the gradient. Maximal activity of the Brij W-1-solubilized phosphatidylinositol synthase was dependent on manganese (5 mm) or magnesium (30 mm) ions, and Triton X-100 (3.6 mm) at pH 8.0 with Tris-HCl buffer. The apparent K(m) values for CDP-diacylglycerol and myo-inositol for the solubilized enzyme was 0.1 mm and 46 mum, respectively. Solubilized phosphatidylinositol synthase activity was thermally inactivated at temperatures above 30 degrees C.


First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq.
Obesity is associated with an increased risk of psoriasis. In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis. In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival. A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36-56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10-4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23-2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04-2.19). This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.


Diverse Physiological Functions of FAB1 and Phosphatidylinositol 3,5-Bisphosphate in Plants.
Biological membranes are predominantly composed of structural glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Of the membrane glycerophospholipids, phosphatidylinositol (PtdIns) and its phosphorylated derivatives (phosphoinositides) constitute a minor fraction yet exert a wide variety of regulatory functions in eukaryotic cells. Phosphoinositides include PtdIns, three PtdIns monophosphates, three PtdIns bisphosphates, and one PtdIns triphosphate, in which the hydroxy groups of the inositol head group of PtdIns are phosphorylated by specific lipid kinases. Of all the phosphoinositides in eukaryotic cells, phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] constitutes the smallest fraction, yet it is a crucial lipid in animal and yeast membrane trafficking systems. Here, we review the recent findings on the physiological functions of PtdIns(3,5)P2 and its enzyme-formation of aploid and binucleate cells (FAB1)-along with the regulatory proteins of FAB1 and the downstream effector proteins of PtdIns(3,5)P2 in Arabidopsis.


[Palliative radiotherapy of bone metastases. Comparison between 2 fractionations].
One hundred and twenty two symptomatic osseous metastases in 74 patients were treated with palliative irradiation, using two dose/time treatment plans. Pain relief was obtained in 92% of valuable cases (complete response in 68% and improvement in 24%). The complete responses were obtained in 4 weeks in 64% of responsive patients. The median duration of response was 166 days. In advanced cancer patients the short course radiotherapy achieved the same quality and duration of pain relief as conventional treatment.


A Stability Indicating HPLC Method for the Determination of Nitisinone in Capsules.
In this study a simple and efficient stability-indicating HPLC method with short run time was developed for the determination of nitisinone. The stress degradation of nitisinone was studied in different acidic, basic, oxidative, thermal and photolytic conditions. The chromatographic separation was achieved on a Nova-Pak C18 column using a mixture of 50 mM NaH2PO4 (pH 2.5) and acetonitrile (45:55, v/v) as mobile phase. UV detection was performed at 280 nm. Good linearity was observed over the concentration range of 0.5-50 μg/ml with r(2)>0.999. The within-day and between-day precision values were less than 2%. The proposed method could be used for the determination of nitisinone in the presence of its degradation products and also dosage form excipients for the quality control purposes.


Effects of theophylline withdrawal in severe chronic obstructive pulmonary disease.
To determine the value of theophylline in the maintenance therapy of patients with severe chronic obstructive pulmonary disease (COPD), we conducted a trial of theophylline therapy withdrawal in 38 clinically stable patients with severe COPD (FEV1 < 60 percent) predicted. Symptoms, lung function, blood gases, and 6-min walking distance were assessed on days 1 and 2. Quality of life and overall dyspnea were scored using four different clinical rating scales. Theophylline therapy was continued in 20 patients and replaced by placebo from day 3 on in the remainder; measurements were repeated on days 5 and 6. Withdrawal of theophylline therapy resulted in significant (p < 0.05) deterioration in lung function, exercise performance, and two indices of overall dyspnea, and a significant increase in scoring of symptoms and auscultation findings. Individual analysis revealed a clinically relevant deterioration in 72 percent of patients from whom theophylline therapy was withdrawn, while only 15 percent of patients receiving theophylline exhibited deterioration. No major side effects were observed. Our data show that about half of the patients with severe COPD can be considered as theophylline responders. The response of these patients to withdrawal of theophylline therapy suggests that the clinical effectiveness of this drug cannot be explained exclusively by bronchodilation. Due to the inherent difficulties in predicting response to theophylline, its effectiveness in patients with severe COPD should be determined individually, including assessment of exercise performance and ratings of dyspnea.


Musculoskeletal Pain in Melancholic and Atypical Depression.
Pain and depressive disorders often present together, but little is known about the prevalence of pain in depression subgroups. The objective of this study was to examine the possible differences in the prevalence of musculoskeletal pain between participants in melancholic and atypical depression subgroups. Cross-sectional study. Depression nurse case managers where depression patients receive treatment in primary health care. Participants included 413 depression patients and 401 controls. Depressive symptoms were determined with the Beck Depression Inventory (BDI-21), and diagnosis of depression was confirmed with the Mini-International Neuropsychiatric Interview (MINI). The participants were dichotomized into subgroups with melancholic depression (n = 269), atypical depression (n = 144), and controls (n = 401). Musculoskeletal pain was identified during last four weeks. Participants were enrolled in the study between 2008 and 2009. The prevalence of pain was 37% in controls, 57% in atypical depression, and 71% in melancholic depression (P < 0.001, after adjusting for sex and age). A logistic regression model showed that the odds ratio of pain after adjusting for confounding factors was 2.35 (1.56 to 3.56) with atypical depression compared with controls (P < 0.001) and 4.38 (3.03 to 6.33) with melancholic depression compared with atypical depression (P = 0.006). BDI scores were higher for those with melancholic depression than for those with atypical depression (P < 0.001). Melancholic depression showed to be associated with a higher prevalence of musculoskeletal pain in comparison with atypical depression. This finding highlights the need for further studies about the mechanisms behind the association, particularly in melancholic depression.


HIF-1α Silencing Inhibits the Growth of Osteosarcoma Cells by Inducing Apoptosis.
Osteosarcoma (OS) is a malignant tumor of mesenchymal origin, which is generally locally aggressive and tends to produce early systemic metastases. Therefore, an identification of a novel therapeutic target is required. We investigated the effect of small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) on the growth of Osteosarcoma MG-63 and U2-OS cells. Two cell-lines were transfected with various concentrations of HIF-1α or control siRNA, and the effect on HIF-1α expression was analyzed by using quantitative polymerase chain reaction and western blot analysis. The effects of HIF-1α siRNA on growth inhibition and apoptosis were then evaluated by standard methods. HIF-1α siRNA treatment reduced HIF-1α mRNA and protein expression in MG-63 and U2-OS cells significantly. The downregulation of HIF-1α expression upregulated caspase-3 expression subsequently inhibited the growth of MG-63 and U2-OS cells and induced apoptosis of the two cells. Our in vitro data indicate that the downregulation of HIF-1α is capable of suppressing OS cells growth, through the induction of apoptosis. HIF-1α inhibition may be a new strategy for the treatment of Osteosarcoma.


Epstein-Barr virus in Hodgkin's disease patients in Japan.
The association of Epstein-Barr virus (EBV) and Hodgkin's disease (HD) has been suggested by serologic, epidemiologic, and molecular biologic studies. The high level of EBV association with HD in the developing countries was discussed in relation to the high HD incidence in these areas. Japanese HD shows a distinct peak incidence in older adults. In contrast, Western HD shows a bimodal pattern, the first peak in young adulthood and a second peak in older patients. In the present study, the EBV association with HD in Japan was investigated, and the results were compared with those reported from industrialized and developing countries. Fifty-seven patients with HD were studied for the presence or absence of the EBV genome by the polymerase chain reaction and in situ hybridization methods. Seven cases were excluded from the analysis for EBV because of poor preservation of nucleotides in the specimens. EBV genomes were detected in the Reed-Sternberg (R-S) cells of 32 of the 50 patients examined (64%). The EBV association was independently affected by histologic subtype (84% in mixed cellularity and 44% in others), sex (76% in males and 31% in females), and age (76% in patients aged 40 years and older and 38% in patients younger than 40 years of age; P < 0.01). High EBV association is found at the peak in older adults predominantly with mixed cellularity type. Previous studies revealed that the high EBV was associated with the older peak of the bimodal peaks in Western HD, and a unimodal peak in childhood in developing countries. The EBV subtype was predominantly type A, which is identical to the immunocompetent type of HD reported previously. The results of the current study, together with those reported previously, showed that the presence of the Epstein-Barr virus correlated with mixed cellularity type, age older than 40 years, and male sex.


Registered Nurses' Experiences Taking Breaks on Night Shift: A Qualitative Analysis.
Fatigue mitigation strategies among night shift workers can include deliberate use of restful work breaks, taking naps, and consuming caffeine. However, nurses have frequently reported missing break opportunities, and the rationale for missed breaks remains unclear. The purpose of this study was to describe and interpret the lived experience of hospital night shift nurses taking breaks and the meaning of this phenomenon as it relates to the workplace. Registered nurses (n = 16) from a U.S. community hospital were interviewed about how they took rest breaks during their shift. Data were analyzed with methods consistent to interpretive phenomenology. Identified themes about the breaks included (a) breaks are a time to eat, (b) breaks are inconsistently supported by unit-level structures and processes, and (c) breaks are a luxury, not a right. Nurses in this study reported an absence of consistent and restorative breaks. Organizations should analyze gaps within systems and processes to optimize a consistent, restorative nature of the break experience among nurses working night shift.


In vitro evidence of the presence of mesenchymal stromal cells in cervical cancer and their role in protecting cancer cells from cytotoxic T cell activity.
Mesenchymal stromal cells (MSCs) have been isolated from different tumors and it has been suggested that they support tumor growth through immunosuppression processes that favor tumor cell evasion from the immune system. To date, however, the presence of MSCs in cervical cancer (CeCa) and their possible role in tumor growth remains unknown. Herein we report on the presence of MSCs in cervical tissue, both in normal conditions (NCx-MSCs) and in CeCa (CeCa-MSCs), and described several biological properties of such cells. Our study showed similar patterns of cell surface antigen expression, but distinct differentiation potentials, when we compared both cervical MSC populations to MSCs from normal bone marrow (BM-MSCs, the gold standard). Interestingly, CeCa-MSCs were negative for the presence of human papilloma virus, indicating that these cells are not infected by such a viral agent. Also, interestingly, and in contrast to NCx-MSCs, CeCa-MSCs induced significant downregulation of surface HLA class I molecules (HLA-A*0201) on CaSki cells and other CeCa cell lines. We further observed that CeCa-MSCs inhibited antigen-specific T cell recognition of CaSki cells by cytotoxic T lymphocytes (CTLs). HLA class I downregulation on CeCa cells correlated with the production of IL-10 in cell cocultures. Importantly, this cytokine strongly suppressed recognition of CeCa cells by CTLs. In summary, this study demonstrates the presence of MSCs in CeCa and suggests that tumor-derived MSCs may provide immune protection to tumor cells by inducing downregulation of HLA class I molecules. This mechanism may have important implications in tumor growth.


Impact of contrast-induced acute kidney injury on long-term major adverse cardiovascular events and kidney function after percutaneous coronary intervention: insights from a territory-wide cohort study in Hong Kong.
The impact of contrast-induced acute kidney injury (CI-AKI) on long-term major adverse cardiovascular events (MACE) remains controversial. This was a retrospective cohort study from 14 hospitals under the Hospital Authority of Hong Kong between 2004 and 2017. Severe CI-AKI was defined as an increase in serum creatinine of >50% from the baseline value, an absolute increase of >1 mg/dL (88 μmol/L) or requiring dialysis after percutaneous coronary intervention (PCI). Mild CI-AKI was defined as an increase in serum creatinine of >25% from the baseline value or an absolute increase of >0.5 mg/dL (44 μmol/L) after PCI but not fulfilling the criteria for severe CI-AKI. The primary endpoint was MACE, defined as a composite outcome of all-cause mortality, non-fatal myocardial infarction after hospital discharge, stroke or any unplanned coronary revascularization, in a time-to-first-event analysis up to 5 years after PCI. The secondary endpoints were individual components of MACE and cardiovascular mortality. A total of 34 576 patients were analysed. After adjustment for cardiovascular risk factors, procedural characteristics and medication use, the risk of MACE at 5 years was significantly higher with mild CI-AKI {hazard ratio [HR], 1.18 [95% confidence interval (CI) 1.12-1.26); P < 0.001} and severe CI-AKI [HR 1.92 (95% CI 1.78-2.07); P < 0.001]. Severe CI-AKI was associated with higher adjusted risks of each secondary end point and the risks monotonically accrued over time. Among patients undergoing a first-ever PCI, CI-AKI of any severity was associated with a higher adjusted risk of MACE at 5 years. Severe CI-AKI has a stronger association with MACE and its individual components, with an excess of early and late events.


Rim-differentiated pillar[5]arene based nonporous adaptive crystals.
The first rim-differentiated pillar[5]arene based nonporous adaptive crystals (NACs) were developed and used to separate dichloromethane from a halomethane mixture with 99.1% purity.


Reviews of chromosome studies in urological tumors. III. Cytogenetics and genes in testicular tumors.
We reviewed available cytogenetic and molecular findings in testicular germ cell tumors, and their possible application to clinical, pathological and basic parameters. Findings in the literature on testicular germ cell tumors as well as those from our laboratory were summarized, including a listing of the cytogenetic findings on testicular germ cell tumors to date with some illustrations. Testicular germ cell tumors are characterized in most cases by the presence of an i(12p) isochromosome. In tumors without such an abnormal chromosome studies using fluorescence in situ hybridization and molecular approaches have demonstrated either masking of the i(12p) or the presence of extra 12p sequences in the karyotype. Although testicular germ cell tumors are often associated with chromosome changes in addition to the i(12p), no other specifically recurrent structural chromosome changes have been found. Based on the cytogenetic and molecular findings in testicular germ cell tumors, a hypothetical scheme for the genetic events leading to these tumors is presented. The genetic events leading to genesis of testicular germ cell tumors in men appear to be related to aneuploidization followed by the formation of an i(12p) isochromosome, the latter characterizing the preponderant number of testicular germ cell tumors. The exact role of the i(12p) isochromosome in testicular germ cell tumor pathogenesis remains to be determined, as is true of the genes involved in or affected by these tumors. Based on presently available information, a hypothetical pathogenetic and oncogenetic model for the development of testicular germ cell tumors is presented.


Thermodynamic Stability, Structure, and Optical Properties of Perovskite-Related CsPb2Br5 Single Crystals under Pressure.
CsPb2Br5 belongs to all inorganic perovskite-related quasi-two-dimensional materials that have attracted considerable attention due to their potential for optoelectronic applications. In this study, we solve numerous controversies on the physical properties of this material. We show that optical absorption in the visible spectrum and green photoluminescence are due to microcrystallites of the three-dimensional CsPbBr3 perovskite settled on the CsPb2Br5 plates and that carefully cleaned crystal plates are devoid of these features. The high-pressure structural and spectroscopic experiments, performed on the single crystals free of CsPbBr3 impurities, evidenced that the layered tetragonal structure of CsPb2Br5 is stable at least up to 6 GPa. The absorption edge is located in the ultraviolet at around 350 nm and continuously red shifts under pressure. Moderate band gap narrowing is well correlated to the pressure-induced changes in the crystal structure. Although the compressibility of CsPb2Br5 is much higher than for CsPbBr3, the response in optical properties is weaker because the Pb-Br layers responsible for the optical absorption are much less affected by hydrostatic pressure than those built of Cs+ cations. Our study clarifies the confusing data in the literature on the optical properties and thermodynamic stability of CsPb2Br5.


[Association of urinary albumin excretion rate and hyperuricemia with macrovascular atherosclerosis in type 2 diabetic patients].
To investigate the association of urinary albumin excretion rate (UAER) and hyperuricemia with macrovascular atherosclerosis in type 2 diabetic patients. Ninety-seven type 2 diabetic patients were divided into two groups according to the UAER, namely group A with UAER between 20 and 200 microg/min (n=63) and group B with UAER > or = 200 microg/min (n=34); the patients were also classified into hyperuricemia group (group C, n=59) and normal blood uric acid (BUA) group (group D, n=38). The disease course, BUA, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL), UAER and arteria carotis intima-media thickness (IMT) were determined in these patients. The relationship of UAER and hyperuricemia with carotid arterial IMT was analyzed statistically. The levels of TG, TC, LDL and HDL showed no significant differences between the 4 groups (P>0.05). The disease course, BUA, UAER, and FBG levels and IMT in groups A and C were significantly higher than those in groups C and D (P<0.05), but no such differences were found between groups A and C or between groups B and D (P>0.05). Arotid arterial IMT was independently correlated to the disease course, BUA and UAER (r=0.201, 0.1999, 0.211, respectively, P<0.05), and a significant positive correlation was noted between BUA and UAER (r=0.221, P<0.05). Macrovascular atherosclerosis in type 2 diabetic patients is significantly correlated to the disease course, BUA and UAER levels, which can be used to evaluate and predict macrovascular atherosclerosis in type 2 diabetic patients.


Evaluation of vertical variations in hydraulic conductivity in unconsolidated sediments.
Detailed information on vertical variations in hydraulic conductivity (K) is essential to describe the dynamics of groundwater movement at contaminated sites or as input data used for modeling. K values in high vertical resolution should be determined because K tends to be more continuous in the horizontal than in the vertical direction. To determine K in shallow unconsolidated sediments and in the vertical direction, the recently developed direct-push injection logger can be used. The information obtained by this method serves as a proxy for K and has to be calibrated to obtain quantitative K values of measured vertical profiles. In this study, we performed direct-push soil sampling, sieve analyses and direct-push slug tests to obtain K values in vertical high resolution. Using the results of direct-push slug tests, quantitative K values obtained by the direct-push injection logger could be determined successfully. The results of sieve analyses provided lower accordance with the logs due to the inherent limitations of the sieving method.


[Association of Morris' syndrome with squamous cell carcinoma of the vulva].
We described a case of squamous cell carcinoma of the vulva in a patient with Morris' syndrome. In these patients, there is an increased risk of gonadal neoplasms. On the contrary, neoplasms originating from the vulvo-vaginal tract are very rare. Neoplasms arising from the neovagina have been reported. Therefore, a continued periodic surveillance of the external genitalia and the vagina is indicated.


Definitive and differential diagnosis of desquamative gingivitis through direct immunofluorescence studies.
Desquamative gingivitis (DG) is a common clinical manifestation of oral autoimmune vesiculobullous diseases (VBDs). Their polymorphous clinical presentations coupled with similar histologic features make diagnosis indistinguishable among the different VBDs. Direct immunofluorescence (IF) studies are valuable gold-standard diagnostic tests that allow for discrimination among the various VBDs that present with DG. There have been no recent detailed analyses done that have used conventional light microscopy and direct IF in diagnosis to document the clinical associations of DG with various autoimmune oral diseases. The aim of this study is to examine retrospectively a large cohort of patients with DG for associated diseases and to determine the utility of direct IF and conventional light microscopy in establishing a definitive diagnosis. During a 14-month period, our laboratory in Buffalo, New York, received 239 consecutive archival cases of gingival biopsy with a clinical diagnosis of DG. These specimens were submitted to establish or rule out a diagnosis of a direct IF-positive VBD. The demographic, clinical, and microscopic findings were tabulated using established inclusion and diagnostic criteria. Approximately half the number (48.1%) of biopsies received for direct IF studies were submitted by periodontists. Slightly more than half of the patients (53%) previously had biopsies submitted for both hematoxylin and eosin (H & E) and direct IF testing. There was a female predilection for all the diseases studied except for pemphigus and linear immunoglobulin A disease. Oral lichen planus was the most common disease presenting as DG, followed by pemphigoid. The clinical diagnosis of lichen planus correlated with the biopsy findings in 80% of the cases and with pemphigoid in 60%. Definitive diagnosis was rendered to ≈80% of the gingival biopsies submitted. Negative cases of direct IF presenting as DG had significant pathology, such as dysplasia and carcinoma, which would have been otherwise missed if H & E studies had not been performed. This study has the largest cohort of patients with DG suspected of VBD reported in the literature. The patients were predominantly females who had most often been seen by a periodontist. The definitive diagnosis of DG was most accurately achieved when H & E along with two biopsies for direct IF studies were submitted for testing. H & E studies were particularly important for definitive diagnosis of negative cases. Oral lichen planus was the most common disease presenting as DG, which is consistent with recent studies. Systemic connective tissue disorders that present as DG at initial clinical examination require direct IF and serum studies for a conclusive diagnosis. Clinical pathologic correlation, including history, presentation, H & E, and direct IF studies, are essential in establishing a definitive and differential diagnosis for cases presenting with DG.


Radionuclide ventriculography: evaluation of automated and visual methods for regional wall motion analysis.
Regional wall motion (RWM) abnormalities are sensitive indicators of left ventricular (LV) dysfunction, but quantitation of RWM with gated radionuclide ventriculography (RVG) has been limited, particularly in the left anterior oblique (LAO) projection. Regional LV performance was studied in 18 patients undergoing LAO RVG immediately prior to contrast ventriculography (CVG). Wall motion was analyzed by semiautomated and visual methods using several coordinate systems. For semiautomated methods, RVG and CVG wall motion were closely related in the two 90 degrees polar sectors at the apex and posterior wall (r = .85) and in the five 45 degrees polar sectors from midseptum through posterior wall (r = .82). The basal sectors on RVG had weak relationship to CVG, due to adjacent vascular structures. Semiautomated and visual grades for polar sectors on both CVG and RVG were closely related (r = .88- .94). Measured regional wall motion on LAO RVG compared favorably with near-simultaneous CVG in nonoverlapping portions of the LV and allowed objective quantitation of regional LV performance.


Molecular mechanisms of response to low oxygen tension in the vascular wall.
A number of human diseases are linked to local reduced oxygen availability. Hypoxemia, the condition in which oxygen partial pressure in blood falls below 40 mmHg, generates a distress which leads the cells in the vascular wall to activate a genetic program inducing a homeostatic response. The effectiveness of this response is conditioned by the degree and duration of the hypoxic stress and depends on the equilibrium among several factors which are worked out mainly in the vascular endothelial cell layer. Among them are vasoconstrictors such as angiotensin II, endothelins, prostaglandins and thromboxans, and vasodilators such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. A present challenge of the research is understanding the physiological and pathophysiological relevance of the growing body of data collected, disclosing the potential therapeutical application of the basic knowledge in this field.