High-grade Gliomas Exhibit Higher Peritumoral Fractional Anisotropy and Lower Mean Diffusivity than Intracranial Metastases.
Differentiating high-grade gliomas and intracranial metastases through non-invasive imaging has been challenging. Here, we retrospectively compared both intratumoral and peritumoral fractional anisotropy (FA), mean diffusivity (MD), and fluid-attenuated inversion recovery (FLAIR) measurements between high-grade gliomas and metastases. Two methods were utilized to select peritumoral region of interest (ROI). The first method utilized the manual placement of four ROIs adjacent to the lesion. The second method utilized a semiautomated and proprietary MATLAB script to generate an ROI encompassing the entire tumor. The average peritumoral FA, MD, and FLAIR values were determined within the ROIs for both methods. Forty patients with high-grade gliomas and 44 with metastases were enrolled in this study. Thirty-five patients with high-grade glioma and 30 patients with metastases had FLAIR images. There was no significant difference in age, gender, or race between the two patient groups. The high-grade gliomas had a significantly higher tumor-to-brain area ratio compared to the metastases. There were no differences in average intratumoral FA, MD, and FLAIR values between the two groups. Both the manual sample method and the semiautomated peritumoral ring method resulted in significantly higher peritumoral FA and significantly lower peritumoral MD in high-grade gliomas compared to metastases (p < 0.05). No significant difference was found in FLAIR values between the two groups peritumorally. Receiver operating curve analysis revealed FA to be a more sensitive and specific metric to differentiate high-grade gliomas and metastases than MD. The differences in the peritumoral FA and MD values between high-grade gliomas and metastases seemed due to the infiltration of glioma to the surrounding brain parenchyma.


Relationship between serum Th1/Th2 imbalance and depression in elderly patients with COPD and its clinical implications.
Chronic obstructive pulmonary disease (COPD) causes organic damage as well as anxiety, depression, fear, and other psychological disorders, which seriously affect the quality of life and prognosis of patients and cause a huge economic burden to the family and society. The aim of this study was to investigate the correlation between an imbalance of serum Th1/Th2 indicators and psychiatric depression in elderly patients with COPD and analyze its implications for clinical management. From January 2018 to May 2022, 120 elderly patients with COPD treated at our hospital were categorized into two groups based on the self-rating depression scale (SDS): COPD with depression (SDS score ⩾ 50) and COPD alone (SDS score < 50). Blood gas analysis, pulmonary function, and serum Th1/Th2 index were determined. Receiver operating characteristic (ROC) curves were analyzed to explore the diagnostic value of serum Th1/Th2 ratios for COPD complicated by depression. Compared with the group without depression, the partial pressure of carbon dioxide and COPD assessment test scores were significantly higher, and the oxygenation index, forced expiratory volume in one second (FEV1), and percent predicted FEV1 were significantly lower in the COPD with depression group (P< 0.05). Interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were significantly higher in the COPD with depression group than in the group without depression (P< 0.05). Logistic regression analysis indicated that the imbalance of serum IL-1β, IL-2, IL-6, IL-8, IL-10, and TNF-α was a risk factor for mental depression in elderly patients with COPD. When comparing prognostic indices, the interval before the first onset of clinically noticeable deterioration (CID-C) in the COPD with depression group was noticeably shorter than that in the COPD without depression group; the incidence of CID-C within 6 months was noticeably higher in the COPD with depression group than in the group without depression. Elderly patients with COPD and depression had reduced pulmonary function and higher serum Th1/Th2 levels, and an imbalance in serum Th1/Th2 indicators was a potential risk factor for depression. Moreover, elderly patients with COPD and depression were at a higher risk of disease progression and had a worse prognosis. Thus, an imbalance in serum Th1/Th2 indicators is a potential prognostic factor for evaluating depression in patients with COPD.


Genetic relationship between anxiety-related and fear-related behaviors in BXD recombinant inbred mice.
Mood and anxiety disorders, and rodent phenotypic measures modeling these disorders, have a strong genetic component. Various assays are used to study the neurobiological basis of fear-related and anxiety-related behaviors, phenotype genetically modified mice, and elucidate pharmacological modulation of these behaviors for medication development. Earlier work, however, suggests that different trait measures are mediated by partly overlapping but ultimately distinct genetic factors. In this study, we assessed a novel panel of 23 C57BL/6JxDBA/2J (BXD) recombinant inbred strains on various trait measures of Pavlovian fear conditioning and anxiety-like behavior (novel open field, elevated plus-maze), as well as sensory (acoustic startle, prepulse inhibition of startle) and motor (baseline coordination and learning on accelerating rotarod) function. Results showed that traits were continuously distributed across strains and had modest to strong R values. Principal components analysis resolved the data into five factors: factor 1 loaded fear-related traits, factor 2 loaded elevated plus-maze measures as well as context fear, factor 3 loaded novel open field measures and plus-maze closed arm entries, factor 4 loaded rotarod motor function, and factor 5 loaded acoustic startle and prepulse inhibition. These data add to evidence that murine measures of fear-like and anxiety-like traits reflect distinct constructs mediated by dissociable gene variants.


Fertility Preservation for Transgender Adolescents.
To describe fertility preservation (FP) utilization by transgender adolescents within a pediatric gender clinic between July 2013 and July 2016. A retrospective chart review was conducted to abstract demographic and clinical information among adolescents initiating gender-affirming hormones, including patient age at initial FP consultation, birth-assigned sex, race/ethnicity, and outcome of FP consultation. In our sample of 105 transgender adolescents, a total of 13 (seven transgender men and six transgender women) between the age of 14.2 and 20.6 years were seen in formal consultation for FP before initiating hormones. Of these adolescents, four completed sperm cryopreservation and one completed oocyte cryopreservation. Rates of FP utilization among transgender youth were low, which is consistent with a recently published report of FP utilization among transgender youth at another pediatric institution. Identified barriers to FP in our sample included cost, invasiveness of procedures, and desire not to delay medical transition.


Evaluating the performance of quantum point contacts as nanoscale terahertz sensors.
Quantum point contacts (QPCs) are nanoscale constrictions that are realized in a high-mobility two-dimensional electron gas by applying negative bias to split Schottky gates on top of a semiconductor. Here, we explore the suitability of these nanodevices to THz detection, by making use of their ability to rectify THz signals via the strong nonlinearities that exist in their conductance. In addition to demonstrating the configuration of these devices that provides optimal THz sensitivity, we also determine their noise equivalent power and responsivity. Our studies suggest that, with further optimization, QPCs can provide a viable approach to broadband THz sensing in the range above 1 THz.


Characterization of intrahepatic space-occupying lesions by magnetic resonance imaging.
Hepatic neoplasia can be accurately characterized with magnetic resonance imaging of architectural, signal and dynamic gradient-echo contrast-enhancing features. Architectural characteristics valuable in determining the nature of hepatic neoplasia include the outer and inner contours of the lesion; the presence of fibrous encapsulation; the presence, signal and enhancing characteristics of a central scar; the presence and distribution of hemorrhage or necrosis; the relation of the lesion to regional vasculature and bile ducts; and lesion multiplicity. The signal characteristics in spin-echo and gradient-echo pulse sequences of the adjacent hepatic parenchyma and the lesion itself provide further information. In certain instances hepatic neoplasia can be definitively characterized on dynamic gradient-echo pulse sequences obtained after administration of the contrast agent gadolinium.


One Year of Newborn Screening for SMA - Results of a German Pilot Project.
Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. The study was conducted to assess the impact of early detection of SMA by newborn screening (NBS) on the clinical course of the disease. Screening was performed in two federal states of Germany, Bavaria and North Rhine Westphalia, between January 2018 and February 2019. The incidence in the screening population was calculated as number of detected patients with a homozygous deletion in the SMN1-gene per number of screened patients. To get an idea about the incidence of newly diagnosed SMA in the year prior to screening a survey covering all neuropediatric centers in the state of Bavaria was conducted, identifying all SMA-cases in 2017 and 2018. Following positive NBS and confirmatory diagnostic test, treatment was advised according to the recommendations of the "American SMA NBS Multidisciplinary Working Group". Immediate treatment with Nusinersen was recommended in children with 2 and 3 SMN2 copies and a conservative strict follow-up strategy in children with ≥4 copies. All children underwent regular standardized neuropediatric examination, CHOP INTEND and HINE-2 testing as well as electrophysiological exams every 2-3 months. 165,525 children were screened. 22 cases of SMA were identified, meaning an incidence rate of 1:7524. SMN2 copy number analysis showed 2 SMN2 copies in 45% of patients, 3 SMN2 copies in 19 % and 4 SMN2 copies in 36%. These findings are confirmed in the most recent statistical data-cut from 31st August 2019 (incidence 1:7089, 2 SMN2 copies in 44%, 3 in 15% and 4 in 38%). Comparison with up-to-date German data on SMA incidence and the Bavarian survey give evidence that NBS did not lead to a relevant increase in incidence. 10 patients with 2 or 3 SMN2 copies were treated with Nusinersen, starting between 15- 39 days after birth, in 7/10 patients before onset of symptoms. Presymptomatically treated patients (age at last examination: 1- 12 months, median 8 months) showed no muscle weakness by the age of one month to one year. One child with 4 SMN2 copies became symptomatic at the age of 8 months. Newborn screening, resulting in presymptomatic treatment, improves outcome in children with genetically proven SMA. Newborn screening for SMA should be introduced in all countries where therapy is available. An immediate therapy in cases with 4 SMN2 copies should be considered.


Road sign recognition with fuzzy adaptive pre-processing models.
A road sign recognition system based on adaptive image pre-processing models using two fuzzy inference schemes has been proposed. The first fuzzy inference scheme is to check the changes of the light illumination and rich red color of a frame image by the checking areas. The other is to check the variance of vehicle's speed and angle of steering wheel to select an adaptive size and position of the detection area. The Adaboost classifier was employed to detect the road sign candidates from an image and the support vector machine technique was employed to recognize the content of the road sign candidates. The prohibitory and warning road traffic signs are the processing targets in this research. The detection rate in the detection phase is 97.42%. In the recognition phase, the recognition rate is 93.04%. The total accuracy rate of the system is 92.47%. For video sequences, the best accuracy rate is 90.54%, and the average accuracy rate is 80.17%. The average computing time is 51.86 milliseconds per frame. The proposed system can not only overcome low illumination and rich red color around the road sign problems but also offer high detection rates and high computing performance.


Bactericidal Efficacy of a Two-Dimensional Array of Integrated, Coaxial, Microhollow, Dielectric Barrier Discharge Plasma Against Salmonella enterica Serovar Heidelberg.
We studied the efficacy of cold atmospheric-pressure plasma (CAP), generated by a two-dimensional array of integrated, coaxial, microhollow, dielectric barrier discharge plasma, against Salmonella enterica serovar Heidelberg (SH) on stainless steel, romaine lettuce, and chicken breast. Exposure of SH to CAP on a dry stainless steel surface had low bactericidal efficacy; only 2.5 log10 colony-forming units (CFUs) were inactivated after 10 min of exposure. On the other hand, the presence of moisture led to decontamination of ∼6.5 log10 CFUs after only 3 min. Although complete decontamination was not achieved on lettuce and chicken breast samples after 10 min of exposure, SH counts were reduced by ∼4.5 and 3.7 log10 CFUs, respectively. A partial suppression of bactericidal effects was observed on steel surfaces when it was coated with bovine serum albumin before spiking with bacteria and exposure to plasma, indicating that the proteinaceous nature of chicken meat may be partially responsible for lower efficacy of CAP on chicken muscles. The initial bacterial load was also found to affect the anti-SH efficacy; at high (∼6.5 log CFUs) and low (∼3.5 CFUs) initial counts, the time required for complete decontamination on stainless steel and lettuce decreased from 3 to 0.5 min and >10 to 1 min, respectively. However, the analysis of inactivation kinetics showed that effects of initial loads of contamination on the rate of bacterial inactivation were not statistically significant. This is consistent with other findings for conditions where both bacterial loads were under the multilayering threshold that might have affected the rate of killing.


Effects of hyperbaric oxygenation on vascular reactivity to angiotensin II and angiotensin-(1-7) in rats.
To assess and elucidate the mechanisms of hyperbaric oxygenation (HBO2) effects on vascular reactivity to angiotensin-(1-7) [ANG-(1-7)] and angiotensin II (ANG II). Rat aortic rings (HBO2 vs. control group) were used to test responses to ANG II, ANG II+ ANG-(1-7) or ANG-(1-7) after noradrenaline precontraction in the presence/absence of MS-PPOH, a specific CYP 450-epoxygenase inhibitor, and glibenclamide, a KATP channels inhibitor. mRNA expression studies of specific CYP isozymes have been conducted as well. The mean contraction (expressed as percent of maximal contraction) for ANG II was similar between groups. Contraction for ANG II + ANG-(1-7) was 15% +/- 10 (HBO2) and 20% +/- 9 (control). There was a significant decrease between the contraction response to ANG II (HBO2) and the response to ANG II + ANG-(1-7) in the HBO2 group, without such a difference within the control group. Mean percentage of noradrenaline precontraction decrease after ANG-(1-7) addition was significantly different [10% +/- 9 (control) and 19% +/- 11 (HBO2)]. The epoxygenase inhibitor MS-PPOH in HBO2 animals reversed these changes. Glibenclamide had no effect on relaxation in response to ANG-(1-7). Expression of CYP4A2, CYP4A3 and CYP2J3 mRNA was not significantly altered with HBO, whereas CYP4A1 was significantly upregulated. Our results suggest a role for epoxyeicosatrienoic acids in modulating relaxation response to ANG-(1-7) with HBO2 that is conducted via potassium channels other than KATP channels. HBO2 increased the responses to ANG-(1-7) after precontraction with noradrenaline. The difference between the response to ANG II in the HBO2 group and ANG II + ANG-(1-7) in the HBO2 group (the contraction force of the peptide combination being lower), without such difference in the control group, suggests an influence ofHBO2 on vascular reactivity.


[ATPase and 5-nucleotidase in human breast and stomach tumors].
It has been concluded from the studies on the activity and location of ATPase and 5-nucleotidase in mammary and gastric tumours that some neoplasms of the mammary gland and stomach showing a high ATPase activity are histochemically related, in the former case, to the lobular myoepithelium and in the latter case, to non-differentiated cells of gastric glands which acquired a capacity for intestinal metaplasia and preserved it in the course of malignant transformation. No essential changes have been recorded in the activity of 5-nucleotidase, depending on the tumour histologic structure and degree of its maturity.


Immunophenotypic Characterization of Germ Cell Tumor-Derived Primitive Neuroectodermal Tumors: Evidence for Frequent Neuronal and/or Glial Differentiation.
Primitive neuroectodermal tumors (PNETs) may arise as a somatic-type malignancy in germ cell tumors. In this setting, most PNETs resemble those of the central nervous system and lack chromosome 22 translocations. However, description of the morphologic and differentiation spectrum of PNETs arising from germ cell tumors is lacking. To investigate the morphologic and immunohistochemical features of these tumors, concentrating on neuronal and glial features. We selected cases based on a morphologically identifiable glial and/or differentiated neuronal component in association with the undifferentiated PNET. Immunohistochemistry for glial fibrillary acidic protein, S100 protein, synaptophysin, chromogranin A, and SOX11 was performed on tumors with available material, with the scoring of both staining intensity (0-3) and extent (0-3). Thirteen qualifying PNETs of testicular origin with available immunohistochemical stains or stainable material were identified. The complete stain panel was performed in 10 tumors. SOX11 demonstrated positive staining in the undifferentiated PNET component of all tumors (10 of 10) and was rarely positive in the differentiated (ie, neuronal/glial) component (1 of 10; focal and weak); synaptophysin was slightly less sensitive in the undifferentiated component (12 of 13; often focal and weak) and also showed positivity in the neuronal/glial component (5 of 13). Glial fibrillary acidic protein and S100 were more frequently positive in the differentiated areas (83% and 77%, respectively) compared with undifferentiated areas (25% and 17%, respectively). SOX11 is a sensitive immunohistochemical marker for testicular PNET, particularly those lacking differentiation. Testicular PNETs often demonstrate glial and/or neuronal differentiation. Differentiation is marked by the acquisition of S100 and glial fibrillary acidic protein expression and SOX11 loss.


Air-Quality Impacts and Intake Fraction of PM2.5 during the 2013 Rim Megafire.
The 2013 Rim Fire was the third largest wildfire in California history and burned 257 314 acres in the Sierra Nevada Mountains. We evaluated air-quality impacts of PM2.5 from smoke from the Rim Fire on receptor areas in California and Nevada. We employed two approaches to examine the air-quality impacts: (1) an evaluation of PM2.5 concentration data collected by temporary and permanent air-monitoring sites and (2) an estimation of intake fraction (iF) of PM2.5 from smoke. The Rim Fire impacted locations in the central Sierra nearest to the fire and extended to the northern Sierra Nevada Mountains of California and Nevada monitoring sites. Daily 24-h average PM2.5 concentrations measured at 22 air monitors had an average concentration of 20 μg/m3 and ranged from 0 to 450 μg/m3. The iF for PM2.5 from smoke during the active fire period was 7.4 per million, which is slightly higher than representative iF values for PM2.5 in rural areas and much lower than for urban areas. This study is a unique application of intake fraction to examine emissions-to-exposure for wildfires and emphasizes that air-quality impacts are not only localized to communities near large fires but can extend long distances and affect larger urban areas.


The possible use of amniotic membrane in chronic leg ulcers.
A trial of living amniotic membrane is suggested as a suitable dressing for certain indolent ulcers. The type of ulcer which is large and chronic both in rate of healing as well as time since onset is well known to everyone. After eliminating any venous defect, oedema, cellulitis, correction of stiff joints, anaemia, we are left with a local indolent problem. What is the ideal dressing? Comfortable or relieves pain; harmless to the tissues and encourages removal of slough; encourages vascularity of the granulation tissue. Method of application: Amnion is applied for five days prior to skin grafting. Better results in those ulcers which have a venous origin rather than arterial. In most cases a clean delicate layer of granulation tissue forms. Histopathology: biopsy of the ulcer base: before application of amnion - dense fibrous tissue, few thick-walled vessels; after application of amnion - more delicate connective tissue, numerous vessels, with thinner walls. The formation of an amnion bank: To facilitate the availability of living amnion. To investigate the possibility of an extract of amnion which would produce the same results as the membrane itself.


Cross-Sectional Relationships Between Household Food Insecurity and Child BMI, Feeding Behaviors, and Public Assistance Utilization Among Head Start Children From Predominantly Hispanic and American Indian Communities in the CHILE Study.
Associations between food insecurity and overweight/obesity, feeding behaviors, and public food assistance utilization have been explored to a greater extent among adults and adolescents than among young children. This cross-sectional study examines a subset of pre-intervention implementation data (n = 347) among families participating in the Child Health Initiative for Lifelong Eating and Exercise (CHILE) study conducted in rural New Mexico among predominantly Hispanic and American Indian Head Start centers. No significant relationships emerged between food insecurity and child overweight/obesity, certain feeding behaviors, or public food assistance utilization. Additional research is necessary to understand relationships between food insecurity and child overweight/obesity status, use of public assistance benefits, and certain feeding behaviors among rural preschool-aged children in predominantly Hispanic and American Indian communities.


Sex-Related Differences in Sleep-Related PSG Parameters and Daytime Complaints in a Clinical Population.
Recent research suggested that perception of sleep impairments might present sex-related effects (ie, women appear to be more prone to report fatigue rather than sleepiness). The latter has been evidenced in sleep-related breathing disorders (SRBD). Differently, it has been suggested that sleep-related movement disorders may also be associated to fatigue rather than to sleepiness. Whether sex-related differences would be similar irrespective of diagnosis remains unclear. During a one-year period, systematic clinical evaluation, by means of structured symptom scales, was performed for a cohort of 921 consecutive patients attending an academic sleep center for polysomnography. The Brugmann Fatigue Scale (BFS), an instrument designed for the assessment of rest propensity was used among other scales (ie, Epworth Sleepiness Scale, ESS). According to inclusion and exclusion criteria, 420 men and 376 women were finally included in the study and retained for data analysis. While men and women presented with similar age, BMI, total sleep time and sleep efficiency, men presented with higher levels of respiratory events and more periodic limb movements. Irrespective of diagnosis, women presented with significantly higher levels of sleep-associated complaints on all scales. Comparative stratifications of daytime symptoms, per diagnostic groups (SRBD, Movement Disorders (SRMD) and Insomnia), revealed significant main effects for diagnosis alongside with main effects of biological sex. Associations between common markers of disease severity for SRBD or SRMD and sleep or rest propensity, respectively, only showed significant correlation between periodic limb movements and rest propensity. The strength of association was similarly significant for both sexes. While men displayed more objective impairment on polysomnography (PSG) and lower symptom levels, the opposite was true in women. However, both men and women present with statistically significant associations between SRMD severity (PLMS index) and physical fatigue.


Aloe-Emodin Isolated from Rheum Undulatum L. Regulates Cell Cycle Distribution and Cellular Senescence in Human Prostate Cancer LNCaP Cellsfv.
Senescence can promote hyperplastic pathologies, such as cancer. Prostate cancer is the second most common type of cancer in men. The p21-mediate cellular senescence, facilitated through the tumor suppressor p53-dependent pathway, is considered the primary mechanism for cancer treatment. Aloe-emodin, has been reported to exert anticancer effects in various types of cancers. This study aimed to investigate the bioactivity of aloe-emodin in LNCaP cells via the activation of p21-mediated cellular senescence. Aloe-emodin treatment increased the percentage of cells in the G1 phase while decreasing the percentage in the S phase. This effect was reflected in the expression levels of proteins associated with cell cycle progression, such as p21CIP, retinoblastoma protein, and cyclin-dependent kinase2/4 in LNCaP cells. However, aloe-emodin-treated LNCaP cells did not induce cell cycle arrest at G2/M checkpoint. Moreover, increased senescence-associated-galactosidase activity was observed in a dose-dependent manner following treatment with aloe-emodin. Aloe-emodin also induced DNA damage by modulating the expression of histone H2AX and lamin B1. Furthermore, aloe-emodin inhibited the proliferation of LNCaP cells, contrasting with the exponential growth observed in the nontreated cells. Importantly, this inhibition did not impact the immune system, as evidenced by the increased proliferation of splenocytes isolated from mice. These findings provide preliminary evidence of the anticancer effect of aloe-emodin in LNCaP cells, necessitating further investigations into the underlying mechanisms in vivo and human subjects.


Intramyocellular lipids: maker vs. marker of insulin resistance.
Intramyocellular triglyceride (imcTG) content in skeletal muscle is abnormally high in lipid oversupply models in obesity, type 2 diabetes (T2D) and other metabolically diseased conditions. The imcTG abnormality was also found to be significantly correlated with muscle insulin resistance (MIR). As skeletal muscle is the main site for insulin-mediated glucose utilization, the research on this topic has been active since. However, to date the pathways responsible for the imcTG excess and the mechanisms underlying the imcTG-MIR correlation have not been identified. A current view is focused on a backward mechanism that fatty acid oxidation by muscle is impaired causing imcTG to accumulate and, therefore, an enlarged imcTG pool is merely a marker of MIR. However, based on kinetic studies, it is more likely that imcTG is a source of MIR. On one hand, an enlarged and fast turning over imcTG pool interferes with insulin signaling by producing excess amounts of signaling molecules that activate PKC pathways. On the other hand, it may promote mitochondrial beta-oxidation that suppresses glucose metabolism via substrate competition. Therefore, it is hypothesized that imcTG is a source of MIR.


Bioactive and biocontrol potential of endophytic fungi associated with Brugmansia aurea Lagerh.
This study describes 32 fungal endophytes isolated from different tissues of Brugmansia aurea Lagerh. Each fungal strain was authenticated based on internal transcribed spacer rDNA sequence. Phylogenetic analysis showed that these fungi are distributed in three classes, seven orders and 12 genera. The dichloromethane extracts of endophytic strains were screened for anticancer and antimicrobial activity. Anticancer activity of extracts against human cancer cell lines revealed that 50% strains are active with IC 50 < 10 μg/mL. While analysing antimicrobial potential against both Gram-positive and Gram-negative bacteria, 56.25% endophytic strains displayed activity at least against one of the tested human pathogenic bacteria with minimum inhibitory concentration of 12.5-100 μg/mL. In vitro antagonistic activity of endophytes was analysed against Sclerotinia sp ., Aspergillus fumigatus, Fusarium solani, A. flavus and F. oxysporum pathogen . The broad-spectrum anti-phytopathogenic activity was shown by R2BA. The presence of ketoacyl synthase domain of polyketide synthase gene and high degree of bioactivity shown by endophytic fungi suggested that they have potential to produce therapeutic compounds and to serve as biocontrol agent.


Effects of dietary fatty acids on insulin sensitivity and secretion.
Globalization and global market have contributed to increased consumption of high-fat, energy-dense diets, particularly rich in saturated fatty acids( SFAs). Polyunsaturated fatty acids (PUFAs) regulate fuel partitioning within the cells by inducing their own oxidation through the reduction of lipogenic gene expression and the enhancement of the expression of those genes controlling lipid oxidation and thermogenesis. Moreover, PUFAs prevent insulin resistance by increasing membrane fluidity and GLUT4 transport. In contrast, SFAs are stored in non-adipocyte cells as triglycerides (TG) leading to cellular damage as a sequence of their lipotoxicity. Triglyceride accumulation in skeletal muscle cells (IMTG) derives from increased FA uptake coupled with deficient FA oxidation. High levels of circulating FAs enhance the expression of FA translocase the FA transport proteins within the myocites. The biochemical mechanisms responsible for lower fatty acid oxidation involve reduced carnitine palmitoyl transferase (CPT) activity, as a likely consequence of increased intracellular concentrations of malonyl-CoA; reduced glycogen synthase activity; and impairment of insulin signalling and glucose transport. The depletion of IMTG depots is strictly associated with an improvement of insulin sensitivity, via a reduced acetyl-CoA carboxylase (ACC) mRNA expression and an increased GLUT4 expression and pyruvate dehydrogenase (PDH) activity. In pancreatic islets, TG accumulation causes impairment of insulin secretion. In rat models, beta-cell dysfunction is related to increased triacylglycerol content in islets, increased production of nitric oxide, ceramide synthesis and beta-cell apoptosis. The decreased insulin gene promoter activity and binding of the pancreas-duodenum homeobox-1 (PDX-1) transcription factor to the insulin gene seem to mediate TG effect in islets. In humans, acute and prolonged effects of FAs on glucose-stimulated insulin secretion have been widely investigated as well as the effect of high-fat diets on insulin sensitivity and secretion and on the development of type 2 diabetes.


Depression as a potential explanation for gender differences in health-related quality of life among patients on maintenance hemodialysis.
The reasons for lower health-related quality of life (HRQOL) scores in women compared to men on maintenance hemodialysis (MHD) are unknown. We investigated whether depression accounts for gender differences in HRQOL. Cross-sectional study of 868 (40.9% women) Brazilian MHD patients (PROHEMO Study). We used the Kidney Disease Quality of Life Short Form to assess HRQOL and the Center for Epidemiological Studies Depression (CES-D) scale (scores from 0-60) to assess depression with scores >or=18 indicating high depression probability. Higher depression scores were associated with lower HRQOL in both sexes. Women had higher depression scores; 51.8% of women versus 38.2% of men (p < 0.001) had CES-D scores >or=18. Women scored lower on all 9 assessed HRQOL scales. The female-to-male differences in HRQOL were slightly reduced with inclusion of Kt/V and comorbidities in regression models. Substantial additional reductions in female-to-male differences in all HRQOL scales were observed after including depression scores in the models, by 50.9% for symptoms/problems related to renal failure, by 71.6% for mental health and by 87.1% for energy/vitality. Lower HRQOL among women was largely explained by depression symptoms. Results support greater emphasis on treating depression to improve HRQOL in MHD patients, particularly women.


Admission time and mortality rates.
The objective of this study was to determine whether there there are any associations between time of admission and mortality rates in the pediatric intensive care unit. We analyzed retrospectively 210 consecutive admissions to the PICU from November 2005 to April 2006 for patients aged 1 mth to 18 yr. There was no significant difference for overall mortality rates between weekend and weekday admissions (12.2% vs 17.4%, p=0.245), and daytime and evening admissions (11.3 % vs 15.4%, p=0.254). There was also no significant difference between different admission times for within 24 hours, 48 hours and 72 hours mortality rates. In respect of the overall mortality rates, it can be said that in a closed system PICU management under the control of a pediatric intensivist there is no association between time of admission and mortality rates.


Levels of C-reactive protein and protein C in periodontitis patients with and without cardiovascular disease.
Since periodontitis is a chronic and inflammatory disease, a number of hypotheses have proposed that it has an etiological or modulating role in cardiovascular disease (CVD). This study aimed to ascertain the changes in the plasma levels of C-reactive protein (CRP) and protein C (PC), a natural anticoagulant also having an anti-inflammatory effect, in patients who have mild-to-severe periodontitis with or without CVD. The test group consisted of 26 patients with CVD and chronic periodontitis and the control group consisted of 26 patients with chronic periodontitis and no systemic disease. In both groups Community Periodontal Index of Treatment Needs scores were recorded and blood samples were collected. CRP levels were significantly high and PC activity was significantly low in the test group compared to the control group (p < 0.001). There was a negative correlation between tooth loss and PC and between CRP and PC. How PC is affected by the inflammatory events and its association with CRP is an active area of investigation.


Microarray Analysis Reveals Potential Biological Functions of Histone H2B Monoubiquitination.
Histone H2B monoubiquitination is a key histone modification that has significant effects on chromatin higher-order structure and gene transcription. Multiple biological processes have been suggested to be tightly related to the dynamics of H2B monoubiquitination. However, a comprehensive understanding of biological roles of H2B monoubiquitination is still poorly understood. In the present study, we developed an efficient tool to disrupt endogenous H2B monoubiquitination levels by using an H2BK120R mutant construct expressed in human cells. Genome-wide microarray analysis of these cells revealed a potential global view of biological functions of H2B monoubiquitination. Bioinformatics analysis of our data demonstrated that while H2B monoubiquitination expectedly affected a number of previously reported biological pathways, we also uncovered the influence of this histone modification on many novel biological processes. Therefore, our work provided valuable information for understanding the role of H2B monoubiquitination and indicated potential directions for its further studies.


Cerebral Microdialysate Metabolite Monitoring using Mid-infrared Spectroscopy.
The brains of patients suffering from traumatic brain-injury (TBI) undergo dynamic chemical changes in the days following the initial trauma. Accurate and timely monitoring of these changes is of paramount importance for improved patient outcome. Conventional brain-chemistry monitoring is performed off-line by collecting and manually transferring microdialysis samples to an enzymatic colorimetric bedside analyzer every hour, which detects and quantifies the molecules of interest. However, off-line, hourly monitoring means that any subhourly neurochemical changes, which may be detrimental to patients, go unseen and thus untreated. Mid-infrared (mid-IR) spectroscopy allows rapid, reagent-free, molecular fingerprinting of liquid samples, and can be easily integrated with microfluidics. We used mid-IR transmission spectroscopy to analyze glucose, lactate, and pyruvate, three relevant brain metabolites, in the extracellular brain fluid of two TBI patients, sampled via microdialysis. Detection limits of 0.5, 0.2, and 0.1 mM were achieved for pure glucose, lactate, and pyruvate, respectively, in perfusion fluid using an external cavity-quantum cascade laser (EC-QCL) system with an integrated transmission flow-cell. Microdialysates were collected hourly, then pooled (3-4 h), and measured consecutively using the standard ISCUSflex analyzer and the EC-QCL system. There was a strong correlation between the compound concentrations obtained using the conventional bedside analyzer and the acquired mid-IR absorbance spectra, where a partial-least-squares regression model was implemented to compute concentrations. This study demonstrates the potential utility of mid-IR spectroscopy for continuous, automated, reagent-free, and online monitoring of the dynamic chemical changes in TBI patients, allowing a more timely response to adverse brain metabolism and consequently improving patient outcomes.


In Silico Studies of Active Probe Dynamics in Crowded Media.
Active systems are made of agents, each of which takes energy from the environment and converts it to directed motion. Therefore, by construction, these systems function out of equilibrium and cannot be described using equilibrium statistical mechanics. Though the most studied aspect has been the collective motion of active particles, the motion at the individual particle level in crowded media is also of prime importance. Examples include the motion of bacteria in hydrogels, single cell migration as a way to search for food or escape from toxic agents, and synthetic active agents transporting through soft crowded media. This review presents an overview of our understanding of single active probe dynamics in crowded media from computer simulations. The active probe is a Janus or a dumbbell-shaped particle, and the medium is made of crowders that are either sticky or repulsive to the probe and could be frozen or mobile. The density and the topology of the crowders also play an important role. We hope our in silico studies will help to elucidate the mechanism of activity-driven transport in crowded media in general and design nanomachines for targeted delivery.


Metformin: effects on micro and macrovascular complications in type 2 diabetes.
The antihyperglycaemic agent metformin is widely used in the treatment of type 2 diabetes. Data from the UK Prospective Diabetes Study and retrospective analyses of large healthcare databases concur that metformin reduces the incidence of myocardial infarction and increases survival in these patients. This apparently vasoprotective effect appears to be independent of the blood glucose-lowering efficacy. Metformin has long been known to reduce the development of atherosclerotic lesions in animal models, and clinical studies have shown the drug to reduce surrogate measures such as carotid intima-media thickness. The anti-atherogenic effects of metformin include reductions in insulin resistance, hyperinsulinaemia and obesity. There may be modest favourable effects against dyslipidaemia, reductions in pro-inflammatory cytokines and monocyte adhesion molecules, and improved glycation status, benefiting endothelial function in the macro- and micro-vasculature. Additionally metformin exerts anti-thrombotic effects, contributing to overall reductions in athero-thrombotic risk in type 2 diabetic patients.


Swing, release, and escape mechanisms contribute to the generation of phase-locked cluster patterns in a globally coupled FitzHugh-Nagumo model.
We investigate the mechanism of generation of phase-locked cluster patterns in a globally coupled FitzhHugh-Nagumo model where the fast variable (activator) receives global feedback from the slow variable (inhibitor). We identify three qualitatively different mechanisms (swing-and-release, hold-and-release, and escape-and-release) that contribute to the generation of these patterns. We describe these mechanisms and use this framework to explain under what circumstances two initially out-of-phase oscillatory clusters reach steady phase-locked and in-phase synchronized solutions, and how the phase difference between these steady state cluster patterns depends on the clusters relative size, the global coupling intensity, and other model parameters.


Levels and disappearance of prostaglandin F2alpha in cerebral spinal fluid: a clinical and experimental study.
The concentration of prostaglandin F2alpha (PGF2alpha) was measured in cerebrospinal fluid (CSF) obtained by lumbar puncture in patients with subarachnoid hemorrhage and compared to control values. The level of this prostaglandin was elevated at some time in most patients during the course of their illness. However, this could not be correlated with the severity of neurological deficits observed. The possibility that the concentration of PGF2alpha in lumbar fluid may not reflect that present intracranially was tested experimentally in anesthetized dogs. In these experiments only a small fraction of the radioactive PGF2alpha injected into the cisterna magna appeared in lumbar CSF. Prostaglandin F2alpha rapidly disappeared from the cisterna magna, half time 8 minutes, and radioactivity was present in blood from the jugular vein indicating that normally this prostaglandin rapidly egresses from the CSF into blood. These findings suggest that PGF2alpha can be rapidly transported away from the brain. This could explain the low concentrations of PGF2alpha in CSF of normal individuals and in some patients who have severe cerebral vasospasm. Conversely, the elevation of PGF2alpha in lumbar CSF noted in some patients might be due, in part, to an impairment of transport caused by the size and location of the hemorrhage.


A real-time PCR for specific detection of the Legionella pneumophila serogroup 1 ST1 complex.
Legionella pneumophila serogroup 1 (Lp1) sequence type (ST) 1 is globally widespread in the environment and accounts for a significant proportion of Legionella infections, including nosocomial Legionnaires' disease (LD). This study aimed to design a sensitive and specific detection method for Lp ST1 that will underpin epidemiological investigations and risk assessment. A total of 628 Lp genomes (126 ST1s) were analyzed by comparative genomics. Interrogation of more than 900 accessory genes revealed seven candidate targets for specific ST1 detection and specific primers and hydrolysis probes were designed and evaluated. The analytical sensitivity and specificity of the seven primer and probe sets were evaluated on serially diluted DNA extracted from the reference strain CIP107629 and via qPCR applied on 200 characterized isolates. The diagnostic performance of the assay was evaluated on 142 culture-proven clinical samples from LD cases and a real-life investigation of a case cluster. Of seven qPCR assays that underwent analytical validation, one PCR target (lpp1868) showed higher sensitivity and specificity for ST1 and ST1-like strains. The diagnostic performance of the assay using respiratory samples corresponded to a sensitivity of 95% (19/20) (95% CI (75.1-99.9)) and specificity of 100% (122/122) (95% CI (97-100)). The ST1 PCR assay could link two out of three culture-negative hospitalized LD cases to ST1 during a real-time investigation. Using whole genome sequencing (WGS) data, we developed and validated a sensitive and specific qPCR assay for the detection of Lp1 belonging to the ST1 clonal complex by amplification of the lpp1868 gene. The ST1 qPCR is expected to deliver an added value for Lp control and prevention, in conjunction with other recently developed molecular assays.


A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-β and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis.
The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-β and IL-1. Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-β significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.


Molecular crowding enhanced ATPase activity of the RNA helicase eIF4A correlates with compaction of its quaternary structure and association with eIF4G.
Enzymatic reactions occur in a crowded and confined environment in vivo, containing proteins, RNA and DNA. Previous reports have shown that interactions between macromolecules, and reactions rates differ significantly between crowded environments and dilute buffers. However, the direct effect of crowding on the level of high-resolution structures of macromolecules has not been extensively analyzed and is not well understood. Here we analyze the effect of macromolecular crowding on structure and function of the human translation initiation factors eIF4A, a two-domain DEAD-Box helicase, the HEAT-1 domain of eIF4G, and their complex. We find that crowding enhances the ATPase activity of eIF4A, which correlates with a shift to a more compact structure as revealed with small-angle X-ray scattering. However, the individual domains of eIF4A, or the eIF4G-HEAT-1 domain alone show little structural changes due to crowding except for flexible regions. Thus, the effect of macromolecular crowding on activity and structure need to be taken into account when evaluating enzyme activities and structures of multidomain proteins, proteins with flexible regions, or protein complexes obtained by X-ray crystallography, NMR, or other structural methods.


Mechanisms underpinning longitudinal increases in the knee adduction moment following arthroscopic partial meniscectomy.
Knee osteoarthritis is common following arthroscopic partial meniscectomy and a higher external peak knee adduction moment is believed to be a contributor. The peak knee adduction moment has been shown to increase over 2 years (from 3-months post-arthroscopic partial meniscectomy). The aim of this study was to evaluate mechanisms underpinning the increase in peak knee adduction moment over 2 years observed in people 3-months following arthroscopic partial meniscectomy. Sixty-six participants with medial arthroscopic partial meniscectomy were assessed at baseline and again 2 years later. Parameters were evaluated at time of peak knee adduction moment as participants walked barefoot at their self-selected normal and fast pace for both time points. For normal pace walking, an increase in frontal plane ground reaction force-to-knee lever arm accounted for 30% of the increase in peak knee adduction moment (B=0.806 [95% CI 0.501-1.110], P<0.001). For fast pace walking, an increase in the frontal plane ground reaction force magnitude accounted for 21% of the increase in peak knee adduction moment (B=2.343 [95% CI 1.219-3.468], P<0.001); with an increase in tibia varus angle accounting for a further 15% (B=0.310 [95% CI 0.145-0.474], P<0.001). Our data suggest that an increase in lever arm and increase in frontal plane ground reaction force magnitude are contributors to the increased knee adduction moment observed over time in people following arthroscopic partial meniscectomy.


Clinical implications of visceral hyperalgesia.
Based on clinical experience and our understanding of chronic pain, both affective and sensory pathways may be involved in the visceral hyperalgesia seen in most patients with functional bowel disorders. This new awareness has changed the focus of treatment.


Food Volume Estimation Based on Deep Learning View Synthesis from a Single Depth Map.
An objective dietary assessment system can help users to understand their dietary behavior and enable targeted interventions to address underlying health problems. To accurately quantify dietary intake, measurement of the portion size or food volume is required. For volume estimation, previous research studies mostly focused on using model-based or stereo-based approaches which rely on manual intervention or require users to capture multiple frames from different viewing angles which can be tedious. In this paper, a view synthesis approach based on deep learning is proposed to reconstruct 3D point clouds of food items and estimate the volume from a single depth image. A distinct neural network is designed to use a depth image from one viewing angle to predict another depth image captured from the corresponding opposite viewing angle. The whole 3D point cloud map is then reconstructed by fusing the initial data points with the synthesized points of the object items through the proposed point cloud completion and Iterative Closest Point (ICP) algorithms. Furthermore, a database with depth images of food object items captured from different viewing angles is constructed with image rendering and used to validate the proposed neural network. The methodology is then evaluated by comparing the volume estimated by the synthesized 3D point cloud with the ground truth volume of the object items.


Gastric bronchogenic cyst presenting as a gastrointestinal stromal tumor.
Bronchogenic cyst (BC) is congenital abnormality of the tracheobronchial bud derived from the primitive foregut which is predominantly found in the mediastinum. Surgery remains the most common treatment when malignancy is suspected, or when there are presenting. Only infrequently, is BC located at an extrathoracic site. Although rarely located in the stomach, BC should be considered as a differential diagnosis of gastric neoplasm. For these cases, surgery remains a common choice. Minimally invasive procedures such as endoscopic ultrasonography-guided fine needle biopsy aspiration (EUS-FNA) and endoscopic submucosal dissection (ESD) should also be considered when the diagnosis of BC is suspected. They are valuable diagnostic methods that can assess and identify the location of the lesion, and facilitate histological examination of the cyst. In some cases of more superficial lesions ESD can take the place of surgery as it avoids unnecessary complications of a more invasive procedure. Here we present a case of gastric BC located in the fundus of the stomach that resembled a gastrointestinal stromal tumor (GIST). We discuss its embryology, pathogenesis, radiological, clinical and treatment modalities. We also provide a thorough review of 14 cases (including our own case), which completely meet pathological criteria has been undertaken focusing on symptom, location, treatment, and histological features.


The final straw: a qualitative study to explore patient decisions to undergo total hip arthroplasty.
Research focusing on the complex factors leading to patients decisions to replace their arthritic hip has been limited in favor of quantitative studies focusing on surgery outcomes. The purpose of this study was twofold: (1) to further explore patients experiences and their decision-making processes to undergo total hip arthroplasty and (2) to examine the factors that influenced patients decisions about the type of surgical procedure (approach, implants). In 2005, 18 patients who were either scheduled for an upcoming total hip arthroplasty or had completed total hip arthroplasty participated in semi-structured interviews (N = 9) or a focus group (N = 9) regarding their decision to undergo hip arthroplasty. The canons and procedures of the grounded theory approach to qualitative research guided the coding and content analysis of the data derived from the focus group and semi-structured interviews. Three main categories or core concepts that emerged from the interviews and focus group were labeled (1) limitations, (2) psychological distress, and (3) perceptions about hip arthroplasty. These three categories yielded a total of ten subcategories. The participants in our study had lived with a hip arthritis to a point beyond which all decided to have hip replacement surgery ("the final straw"). Decisions to undergo surgery were based upon an increasing severity of limitations affecting their basic quality of daily living, relationships and psychological well-being. Participants acknowledged that their choice of surgeon, type of procedure and implants were largely based on their desire to choose a technique that minimized disruption to their muscles and led to a quick recovery. Having decided on the type of surgery, participants used colleagues, family, and the internet to identify the most qualified surgeons in their area. Our study sheds further light on the complex process of patients "final straw" towards a total hip arthroplasty. Surgeons should be aware of patients personal processes in order to optimize their surgical experiences and outcomes. Future research should aim to resolve optimal approaches to arthroplasty in light of patients preferences for muscle-sparing and "minimally invasive" approaches.


Optically Controlled Dissolution Kinetics of Vaterite Microcapsules: Toward Novel Crystal Growth Strategies.
Controllable continuous release of functional materials from capsules is one of the unmet functions of theragnosis particles; on this way, understanding cargo-fluid interactions in vitro is an essential milestone. We develop a flexible platform to investigate single particle-fluid interactions utilizing a glass micropipette as a highly localized flow source around an optically trapped particle. In proof-of-concept experiments, this microparticle is sensitive to local microflow distribution, thus serving as a probe. The very same flows are capable of the particle rotating (i.e., vaterite drug cargo) at frequencies dependent on the mutual particle-pipette position. Platform flexibility comes from different interactions of a tweezer (optical forces) and a pipette (mechanical/hydrodynamical) with a microparticle, which makes this arrangement an ideal microtool. We studied the vaterite dissolution kinetics and demonstrated that it can be controlled on demand, providing a wide cargo release dynamic rate. Our results promote the use of inorganic mesoporous nanoparticles as a nanomedicine platform.


Volume-controlled cavity expansion for probing of local elastic properties in soft materials.
Cavity expansion can be used to measure the local nonlinear elastic properties in soft materials, regardless of the specific damage or instability mechanism that it may ultimately induce. To that end, we introduce a volume-controlled cavity expansion procedure and an accompanying method that builds on the Cavitation Rheology technique [J. A. Zimberlin et al., Soft Matter, 2007, 3, 763-767], but without relying on the maximum recorded pressure. This is achieved by determining an effective radius of the cavity that is based on the volume measurements, and is further supported by numerical simulations. Applying this method to PDMS samples, we show that it consistently collapses the experimental curves to the theoretical prediction of cavity expansion prior to the occurrence of fracture or cavitation, thus resulting in high precision measurement with less than 5% of scatter and good agreement with results obtained via conventional techniques. Moreover, since it does not require visual tracking of the cavity, this technique can be applied to measure the nonlinear elastic response in opaque samples.


Calcium/calmodulin-activated phosphodiesterase expressed in olfactory receptor neurons.
We show that calmodulin-dependent phosphodiesterase (CAM-PDE) is selectively expressed in mature olfactory receptor neurons within the olfactory mucosa. Immunocytochemical staining reveals neuronal immunoreactivity that is most pronounced within cilia, dendritic knobs, and axon bundles. Neither sustentacular cells nor basal cells display immunoreactivity. The extent of loss of neuronal immunoreactivity following bulbectomy resembles loss of the neuronal population. High-affinity CAM-PDE activity in olfactory cilia is fivefold greater than in brain, when assayed at low micromolar cAMP. This activity is depleted in turbinates following bulbectomy. Olfactory mucosal PDE activity is composed of a minimum of two major forms. In the absence of Ca(2+), rolipram-sensitive PDE comprises 65% of total activity. Following stimulation by Ca2+, CAM-PDE activity is elevated sixfold to become the predominant form, thereby increasing total activity 300%, with half-maximal effect at 1 microM Ca2+. We propose that Ca2+ stimulation of CAM-PDE may be necessary for termination of olfactory signals.


Ceratocystis pirilliformis, a new species from Eucalyptus nitens in Australia.
Several species of Ceratocystis have been recorded on Eucalyptus. These include C. fimbriata, C. eucalypti, C. moniliformis and C. moniliformopsis. Of these, only C. fimbriata is known as a pathogen; it recently has been found causing serious wilt diseases in Uganda, Congo and Brazil. This study was undertaken to collect Ceratocystis species, including C. eucalypti, from artificially induced wounds on Eucalyptus nitens near Canberra in southeastern Australia. Trees were wounded in October 2000, and wounds were examined approximately one month later. Ascomata characteristic of a Ceratocystis species were found covering the wounds, and this fungus also was isolated from the wood using carrot baiting. This species of Ceratocystis has hat-shaped ascospores similar to those of C. fimbriata, but it differs from C. fimbriata and all other species of Ceratocystis in that it possesses ascomata with a pyriform base. Comparison of DNA sequences from the ITS and 5.8S rRNA operon confirmed that the fungus from E. nitens in Australia is unique, and we describe it here as a new species, C. pirilliformis.


Low physical activity and risk of cardiovascular and all-cause mortality in renal transplant recipients.
Low physical activity (PA) is a risk factor for mortality in the general population. This is largely unexplored in renal transplant recipients (RTRs). We studied whether PA is associated with cardiovascular and all-cause mortality in a prospective cohort of RTR. Between 2001 and 2003, 540 RTRs were studied (age, 51 ± 12 years; 54% male). PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire). Cardiovascular and all-cause mortality were recorded until August 2007. Independent of age, PA was inversely associated with metabolic syndrome, history of cardiovascular disease, fasting insulin, and triglyceride concentration, and positively associated with kidney function and 24-hour urinary creatinine excretion (i.e., muscle mass). During follow-up for 5.3 years (range, 4.7 to 5.7 years), 81 RTRs died, with 37 cardiovascular deaths. Cardiovascular mortality was 11.7, 7.2, and 1.7%, respectively, according to gender-stratified tertiles of PA (P=0.001). All-cause mortality was 24.4, 15.0, and 5.6% according to these tertiles (P<0.001). In Cox regression analyses, adjustment for potential confounders including history of cardiovascular disease, muscle mass, and traditional risk factors for cardiovascular disease did not materially change these associations. Low PA is strongly associated with increased risk for cardiovascular and all-cause mortality in RTRs. Intervention studies are necessary to investigate whether PA improves long-term survival after renal transplantation.


Cognitive functioning in long-term cancer survivorship: A survey utilizing both standardized neuropsychological and self-report measures.
Since long-term cancer survivorship is a reality for an increasing number of people, understanding their cognitive functioning is useful for both research and clinical purposes. This study described the cognitive functioning of Italian long-term cancer survivors, using both an objective standardized battery and a self-report questionnaire. A total of 136 Italian adults 5+ years free from cancer and its treatments were administered the Esame Neuropsicologico Breve, the Self-Assessment Scale of Cognitive Functioning, and assessments of other psychological dimensions. A total amount of 15% of the sample showed impaired performance on 2+ of the assessed cognitive functions, and 32% had 1+ impaired function. The subjective perception of their cognitive functioning was worse in the present sample, compared to the normative data (p < 0.001). Cognitive functioning, objectively and subjectively measured were significantly correlated (p = 0.006). The number of tests scored outside the normal range correlated positively with depression (p = 0.042) and negatively with both the estimated total IQ (p < 0.001) and with estimated performance IQ (p = 0.001). Self-perceived cognitive functioning correlated positively (p < 0.001) with depression, anxiety, and fatigue. These data document how cognitive difficulties may remain for a long time in cancer patients, who are likely to continue to subjectively perceive themselves as impaired, although sometimes to a greater extent than objective impairment.


Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in children.
Paradoxical tuberculosis (TB)-associated Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of combination antiretroviral treatment (cART) initiation in adults residing in resource-limited regions. Little is known about the burden and presentation of TB-IRIS in children initiating cART while receiving TB treatment. Prospective cohort study of South African children initiating cART while on TB treatment. Children were assessed clinically and by chest x-ray before starting cART and at 2, 4, 6, and 12 weeks post cART initiation. All children who presented with any signs or symptoms suggestive of paradoxical TB-IRIS were classified according to the consensus adult TB-IRIS case definition developed by the International Network for Study of HIV-associated IRIS (INSHI) and reviewed by an independent expert panel. In 7 of the 104 children enrolled in the cohort, symptoms and/or clinical or radiological signs suggestive of paradoxical TB-IRIS developed after a median of 14 days of cART. In two of these cases, there was agreement between the INSHI case definition and the expert panel. In an additional 3 cases, the INSHI criteria were fulfilled but the expert panel made an alternative diagnosis of pneumonia (n = 2) and poor adherence to cART (n = 1). The burden of paradoxical TB-IRIS in children with underlying TB initiating cART is low. Including response to antibiotic treatment for pneumonia as a criterion for an alternative diagnosis may improve the specificity of the INSHI case definition.


[GPs' perceptions of the Institute for Rational Pharmacotherapy].
A questionnaire study was conducted among Danish general practitioners (GPs) as part of an international evaluation of the Institute for Rational Pharmacotherapy (IRF). The aim was to investigate GPs' use and opinion of the IRF's activities. A questionnaire was sent to a random sample of 500 GPs, who were asked about their level of knowledge and frequency of use of IRF's activities, as well as their opinion on the relevance, credibility and independence of the IRF's activities. The response rate was 59%. IRF is generally not the first source of information about new drugs, but is frequently used in the search for information about comparability between drugs and in relation to sudden drug warnings. IRF's Rational Pharmacotherapy bulletin and its GP courses, which nine out of ten GPs knew about, were considered to be highly relevant by 80% and 71%, respectively. All of IRF's activities were considered highly credible. Most GPs felt that the IRF's information increased their confidence in prescribing decisions (84%) and supported them in their role as a GP (88%). IRF's activities support the GP's prescribing role through the production of credible, neutral and evidence-based pharmacotherapeutic information that is not available elsewhere. IRF could further refine its dissemination methods, however, in order to reach more GPs and to increase the use of its information.


The potential of virtual reality and gaming to assist successful aging with disability.
Using the advances in computing power, software and hardware technologies, virtual reality (VR), and gaming applications have the potential to address clinical challenges for a range of disabilities. VR-based games can potentially provide the ability to assess and augment cognitive and motor rehabilitation under a range of stimulus conditions that are not easily controllable and quantifiable in the real world. This article discusses an approach for maximizing function and participation for those aging with and into a disability by combining task-specific training with advances in VR and gaming technologies to enable positive behavioral modifications for independence in the home and community. There is potential for the use of VR and game applications for rehabilitating, maintaining, and enhancing those processes that are affected by aging with and into disability, particularly the need to attain a balance in the interplay between sensorimotor function and cognitive demands and to reap the benefits of task-specific training and regular physical activity and exercise.


Prolonged treatment with the synthetic glucocorticoid methylprednisolone affects adrenal steroidogenic function and response to inflammatory stress in the rat.
Synthetic glucocorticoids are widely prescribed for the treatment of numerous inflammatory and autoimmune diseases and they can also affect the way the adrenal gland produces endogenous glucocorticoids. Indeed, patients undergoing synthetic glucocorticoid treatment can develop adrenal insufficiency, a condition characterised by reduced responsiveness of the adrenal to ACTH stimulation or stressors (e.g. surgical or inflammatory stress). To better elucidate the long-term effect of synthetic glucocorticoids treatment and withdrawal on adrenal function, we have investigated the long-term effects of prolonged treatment with methylprednisolone on HPA axis dynamics and on the adrenal steroidogenic pathway, both in basal conditions and in response to an inflammatory stress (lipopolysaccharide, LPS). We have found that 5-days treatment with methylprednisolone suppresses basal ACTH and corticosterone secretion, as well as corticosterone secretion in response to a high dose of ACTH, and down-regulates key genes in the adrenal steroidogenic pathway, including StAR, MRAP, CYP11a1 and CYP11b1. These effects were paralleled by changes in the adrenal expression of transcription factors regulating steroidogenic gene expression, as well as changes in the expression of adrenal clock genes. Importantly, 5 days after withdrawal of the treatment, ACTH levels are restored, yet basal levels of corticosterone, as well as most of the key steroidogenic genes and their regulators, remain down regulated. We also show that, although 5-days treatment with methylprednisolone reduces the corticosterone response to LPS, an increase in intra-adrenal pro-inflammatory cytokine gene expression was observed. Our data suggests that the steroidogenic pathway is directly affected by synthetic glucocorticoid treatment in the long-term, presumably via a mechanism involving activation of the glucocorticoid receptor. Furthermore, our data suggests a pro-inflammatory effect of synthetic glucocorticoids treatment in the adrenal gland.


Cyclooxygenase-2 is involved in the up-regulation of matrix metalloproteinase-9 in cholangiocarcinoma induced by tumor necrosis factor-alpha.
Matrix metalloproteinase-9 (MMP-9) is an important enzyme in tumor invasion and metastasis in malignant tumors, including cholangiocarcinoma (CC). Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, was recently reported to induce the up-regulation of MMP-9 in cultured CC cells. We examined whether cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2), another endogenous tumor promoter, are involved in the up-regulation of MMP-9 in CC using CC tissue specimens and a CC cell line, HuCCT-1. MMP-9 and COX-2 were immunohistochemically expressed in 58% and 89% of 110 CC cases, respectively; the expression of MMP-9 and COX-2 was correlated (r = 0.32, P = 0.00072). Using zymography, latent MMP-9 was detectable in all cases and active MMP-9 was detected in 24% of cases of the CC specimens. The TNF-alpha/TNF-receptor 1 (TNF-R1) interaction induced MMP-9 production and activation, as well as COX-2 overexpression and PGE2 production, and increased the migration of CC cells. MMP-9 up-regulation was inhibited by COX inhibitors, antagonists of EP2/4 (receptors of PGE2), and COX-1 and COX-2 siRNAs. Inhibitors of both MMP-9 and MMP-9 siRNA treatment abrogated the increase in the migration of CC cells induced by TNF-alpha. In conclusion, we propose a novel signaling pathway of MMP-9 up-regulation in CC cells such that TNF-alpha induces the activation of COX-2 and PGE2 via TNF-R1 followed by the up-regulation of MMP-9 via the PGE2 (EP2/4) receptor.


Qualitative differences in cellular immunogenicity elicited by hepatitis C virus T-Cell vaccines employing prime-boost regimens.
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis. Overall, our data indicate that the memory cells induced by Ad5 were inferior to those induced by VV or MVA. We found that Ad5 boosting resulted in rapid expansion and significantly higher frequencies of NS3-specific T-cells compared to VV and MVA boosting. However, the functional profiles, assessed through analysis of the memory cell marker CD127 and the anti-apoptotic molecule Bcl-2 in the blood, spleen, and liver; and measurements of interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 production indicated significantly lower frequencies of long-lived memory T-cells following Ad5 boosting compared to VV and MVA. This same set of analyses suggested that the memory cells induced following boosting with MVA were superior to those induced by both Ad5 and VV. This superiority of the MVA-induced CD8+ T-cells was confirmed following surrogate challenge of mice with a recombinant mouse herpes virus expressing the HCV NS3 protein. Higher levels of NS3-specific CD8+ T-cells displaying the functional markers CD69, Ki67 and Granzyme B were found in the spleens of mice boosted with MVA compared to VV and Ad5, both alone and in combination. These data suggest that MVA may be a more successful viral vector for induction of effective CD8+ T-cell responses against hepatitis C virus.


Pediatric Bartonella henselae Infection: The Role of Serologic Diagnosis and a Proposed Clinical Approach for Suspected Acute Disease in the Immunocompetent Child.
Bartonella henselae serology is commonly used to diagnose cat-scratch disease (CSD). Titers above a threshold for positivity suggest either a recent or remote infection. Recent infection can be confirmed by a 4-fold rise in the convalescent titer in some cases. Many atypical presentations attributed to CSD utilize a low threshold for positivity without supportive evidence from convalescent sera or supplemental testing, raising a concern for the overdiagnosis of CSD. We conducted a retrospective chart review of immunocompetent pediatric patients at the Hospital for Sick Children, Toronto, spanning an 11-year period. A total of 154 cases were included with serologic titers ≥1:128. These were divided into 3 groups: group 1 = 1:128, group 2 = 1:256, and group 3 ≥ 1:512. Cases within groups were evaluated with respect to cat contact, clinical presentation, further testing, and final diagnosis. One-third of patients with a titer of 1:128 had an alternative diagnosis. Most cases with a titer of 1:128 or 1:256 did not have convalescent serologic testing performed. Within these 2 groups, only 1 case had a 4-fold rise in the convalescent titer. A trend of decreasing number of cases with alternative diagnoses (P = 0.03) and increasing number of cases presenting with regional lymphadenopathy (P = 0.07) was associated with higher titers in group 3 compared with group 1. Concerns about the serologic diagnosis of CSD include the use of low titers for positivity, incomplete diagnostic evaluation, and the lack of convalescent serologic testing. We propose a clinical guide to assist in managing suspected cases of CSD.


Is boiled food spice curcumin still biologically active? An experimental exploration.
As the major active component of turmeric (Curcuma longa), curcumin is widely used as a spice and food coloring agent, and also possesses multiple biological activities and therapeutic potential for neurodegenerative diseases. To answer the paradox between curcumin's biological activities and poor systemic bioavailability, we proposed that degradation products of curcumin may make important contributions to its biological activities, which needs to be verified. In addition, curcumin is usually heated or boiled used as a spice, it is necessary to explore whether boiled curcumin, which degrades readily, is still biologically active. Thus, in the present study we investigated the protective effects of curcumin and boiled curcumin mixture on H2O2-induced oxidative damage in PC12 cells, a widely used model for neurons. Results showed that in spite of high degradation rates, boiled curcumin mixture still possessed similar protective activities like parent curcumin, and could effectively rescue PC12 cells against H2O2-induced damage, via decreasing production of reactive oxygen species and malondialdehyde, reducing caspase-3 and caspase-9 activities. Moreover, curcumin's degradation products including ferulic acid, vanillin and vanillic acid could also improve PC12 cells survival rate. Our findings indicated that boiled curcumin mixtures still possessed protective activity for PC12 cells, and supported the contribution of degradation products to biological activities of curcumin.


Effects of aromatase complex selective inhibition on insulin-like growth factor 1 and insulin-like growth factor binding protein 3 circulating levels in breast cancer.
The aim of our study is to evaluate insulin-like growth factor (IGF) and IGF binding protein (IGFBP)-3 circulating levels in postmenopausal women treated with type I aromatase inhibitor formestane for breast cancer. Sixty-three patients at their first relapse entered the trial and were randomly given formestane at 250 mg or 500 mg i.m. fortnightly. Effects of the endocrine treatment on IGF-1 and IGFBP-3 were measured before and during therapy at scheduled times. IGF-1 and IGFBP-3 seems to slightly increase in both the dose groups, but only IGFBP-3 levels showed statistically significant fluctuation (baseline vs 4 weeks, p=0.01925; baseline vs 10 weeks, p=0.04537). These modifications are unlikely to be related to clinical status because they were observed both in responsive and unresponsive patients. This report demonstrates that hormonal treatments for breast cancer (particularly, aromatase inhibitor administration) can modify growth factor disposition to tumour.


Formation of Neptunium(V) Carbonates: Examining the Forceful Influence of Alkali and Alkaline Earth Cations.
Herein, neptunium(V) carbonates containing sodium or potassium cations were synthesized via chemical precipitation. Various techniques such as scanning electron microscopy, energy-dispersive X-ray spectroscopy, thermogravimetry combined with differential scanning calorimetry, X-ray diffraction, and X-ray absorption spectroscopy were used to analyze the microstructures and elemental compositions of these samples. The crystal structures of hydrated NaNpO2CO3·3H2O (P1, a = 4.3420(2) Å, b = 4.8962(2) Å, c = 10.0933(11) Å, α = 91.014(7)°, β = 77.834(11)°, and γ = 90.004(10)°) and KNpO2CO3 (P63/mmc, a = b = 5.0994(2) Å, c = 10.2210(15) Å) were determined for the first time using the Rietveld method. The synthesized carbonates exhibited distinct structural features and decomposition behaviors, as demonstrated through thermogravimetry analysis, which revealed the presence of crystalline hydrate water in sodium neptunium(V) carbonate. Furthermore, calcium-containing neptunium(V) carbonates were synthesized and characterized. Samples with the general composition Ca0.5NpO2CO3 were obtained using the ion exchange method and chemical precipitation from solutions containing competing cations (Ca2+, Na+, K+, and Mg2+). The synthesis conditions notably affected the diffraction patterns of the obtained calcium neptunium(V) carbonates. This investigation enhances our understanding of the structural properties and thermodynamic stability of neptunium(V) carbonates in the presence of diverse cations commonly found under radioactive waste disposal conditions.


Lymantria dispar nucleopolyhedrovirus hrf-1 expands the larval host range of Autographa californica nucleopolyhedrovirus.
The gypsy moth (Lymantria dispar) is nonpermissive for Autographa californica nucleopolyhedrovirus (AcNPV) infection. We previously isolated a gene, host range factor 1 (hrf-1), from L. dispar nucleopolyhedrovirus that promotes AcNPV replication in Ld652Y cells, a nonpermissive L. dispar cell line (S. M. Thiem, X. Du, M. E. Quentin, and M. M. Berner, J. Virol. 70:2221-2229, 1996). In the present study, we investigated the ability of hrf-1 to alter the larval host range of AcNPV. Bioassays using recombinant AcNPV bearing hrf-1 were conducted with insect larvae by use of oral infection. AcNPV bearing hrf-1 was infectious for neonate L. dispar larvae, with a 50% lethal concentration of 1.2 x 10(5) polyhedral inclusion bodies/ml of diet, which is similar to that of wild-type AcNPV for permissive hosts. AcNPV can kill neonate L. dispar larvae at high doses, but it does not kill third-instar larvae. However, electron microscopy studies of AcNPV-inoculated third-instar larvae revealed virus replication in the midgut cells. PCR analyses indicated that the virus was AcNPV. These results suggest that the block for AcNPV infection of L. dispar larvae is its inability to spread systematically from primary infection sites in the midgut epithelium and that this barrier is leaky in neonates. hrf-1 allows AcNPV to overcome this barrier. AcNPV recombinants bearing hrf-1 were also significantly more infectious for Helicoverpa zea, a resistant species, suggesting that the blocks for AcNPV infection of L. dispar and H. zea larvae may be similar.


Molecular dynamics investigation of the structural properties of phosphatidylethanolamine lipid bilayers.
We report a 14 ns microcanonical (NVE) molecular dynamics simulation of a fully hydrated bilayer of 1-stearoyl-2-oleoyl-phosphatidyethanolamine. This study describes the structure of the bilayer in terms of NMR order parameters and radial distribution functions, and compares them to experimental results and simulations of other lipids. A focus of this work is the characterization of the lipid-water interface, particularly the hydrogen bonding network of the phosphatidylethanolamine (PE) headgroups. We find that hydrogen bonding between the primary amine and phosphate groups has a pronounced effect on the structure of PE relative to phosphatidylcholine, and is evident in, for example, the P-N radial distribution functions.


Oral Care in Critically Ill Infants and the Potential Effect on Infant Health: An Integrative Review.
Critically ill infants admitted to the neonatal intensive care unit are at risk for ventilator-associated pneumonia and abnormal oral colonization. Adherence to evidence-based guidelines for oral care in critically ill adults is associated with improved short- and long-term health outcomes. However, oral care guidelines for critically ill infants admitted to the neonatal intensive care unit have not been established, possibly increasing their risk of ventilator-associated pneumonia and other health complications. To describe and summarize the evidence regarding oral care for critically ill infants admitted to the neonatal intensive care unit and to identify gaps needing further investigation. The MEDLINE (through PubMed) and CINAHL databases were searched for observational studies and randomized controlled trials investigating the effect of oral care on oral colonization, ventilator-associated pneumonia, and health outcomes of infants in the neonatal intensive care unit. This review of 5 studies yielded evidence that oral care may promote a more commensal oral and endotracheal tube aspirate microbiome. It may also reduce the risk of ventilator-associated pneumonia and length of stay in the neonatal intensive care unit. However, the paucity of research regarding oral care in this population and differences in oral care procedures, elements used, and timing greatly limit any possible conclusions. Oral care in critically ill infants may be especially important because of their suppressed immunity and physiological immaturity. Further appropriately powered studies that control for potential covariates, monitor for adverse events, and use recommended definitions of ventilator-associated pneumonia are needed to make clinical recommendations.


AraPathogen2.0: An Improved Prediction of Plant-Pathogen Protein-Protein Interactions Empowered by the Natural Language Processing Technique.
Plant-pathogen protein-protein interactions (PPIs) play crucial roles in the arm race between plants and pathogens. Therefore, the identification of these interspecies PPIs is very important for the mechanistic understanding of pathogen infection and plant immunity. Computational prediction methods can complement experimental efforts, but their predictive performance still needs to be improved. Motivated by the rapid development of natural language processing and its successful applications in the field of protein bioinformatics, here we present an improved XGBoost-based plant-pathogen PPI predictor (i.e., AraPathogen2.0), in which sequence encodings from the pretrained protein language model ESM2 and Arabidopsis PPI network-related node representations from the graph embedding technique struc2vec are used as input. Stringent benchmark experiments showed that AraPathogen2.0 could achieve a better performance than its precedent version, especially for processing the test data set with novel proteins unseen in the training data.


Comparison of argon and air as thermal insulating gases in drysuit dives during military Arctic diving equipment development tests.
It is vital to protect divers from the cold, particularly in Arctic conditions. The insulating gas layer within the drysuit is crucial for reducing heat loss. The technical diving community has long claimed the superiority of argon over air as an insulating gas. Although argon is widely used, previous studies have shown no significant differences between the two gases. Owing to its lower heat conductivity, argon should be a better thermal insulating gas than air. The study aimed to determine whether argon is beneficial for reducing heat loss in divers during development of military drysuit diving equipment in Arctic water temperatures. Four divers completed 14 dives, each lasting 45 minutes: seven dives used air insulation and seven used argon insulation. Rectal and eight skin temperatures were measured from which changes in calculated mean body temperature (MBT) were assessed. There was a significant reduction in area weighted skin temperature over time (0-45 minute) on air dives (ΔTskin = -4.16°C, SE = 0.445, P ⟨ 0.001). On argon dives the reduction was significantly smaller compared to air dives (difference between groups = 2.26°C, SE = 0.358, P ⟨ 0.001). There were no significant changes in rectal temperatures, nor was a significant difference seen between groups. Compared to air, argon may be superior as a drysuit insulating gas in Arctic water temperatures for some divers. Argon used as insulating gas can make diving safer and may diminish the risks of fatal diving accidents and occupational hazard risks in professional diving.


Hyper-mobile water is induced around actin filaments.
When introduced into water, some molecules and ions (solutes) enforce the hydrogen-bonded network of neighboring water molecules that are thus restrained from thermal motions and are less mobile than those in the bulk phase (structure-making or positive hydration effect), and other solutes cause the opposite effect (structure-breaking or negative hydration effect). Using a method of microwave dielectric spectroscopy recently developed to measure the rotational mobility (dielectric relaxation frequency) of water hydrating proteins and the volume of hydration shells, the hydration of actin filament (F-actin) has been studied. The results indicate that F-actin exhibits both the structure-making and structure-breaking effects. Thus, apart from the water molecules with lowered rotational mobility that make up a typical hydration shell, there are other water molecules around the F-actin which have a much higher mobility than that of bulk water. No such dual hydration has been observed for myoglobin studied as the representative example of globular proteins which all showed qualitatively similar dielectric spectra. The volume fraction of the mobilized (hyper-mobile) water is roughly equal to that of the restrained water, which is two-thirds of the molecular volume of G-actin in size. The dielectric spectra of aqueous solutions of urea and potassium-halide salts have also been studied. The results suggest that urea and I(-) induce the hyper-mobile states of water, which is consistent with their well-known structure-breaking effect. The molecular surface of actin is rich in negative charges, which along with its filamentous structure provides a structural basis for the induction of a hyper-mobile state of water. A possible implication of the findings of the present study is discussed in relation to the chemomechanical energy transduction through interaction with myosin in the presence of ATP.


Stress echocardiography: methods, indications and results.
Stress echocardiography has become an important clinical tool to detect cardiac ischaemia and viability in addition to single photon emission tomography. Stress echocardiography has a high positive and negative predictive value, is less expensive than the nuclear methods and has no radiation exposure. It can easily be used in an emergency room and coronary care unit. Because of its feasibility, low cost and high diagnostic accuracy, it will become a very important technique in every hospital and will soon be a real alternative to the more time-consuming and expensive nuclear techniques. The current article gives a review of the methods of stress echocardiography.


Ginsenoside Rh2 promotes nonamyloidgenic cleavage of amyloid precursor protein via a cholesterol-dependent pathway.
Ginsenoside Rh2 (Rh2) is a ginseng derivative used in Chinese traditional medicine. We investigated whether Rh2 can help prevent Alzheimer's disease symptoms and examined underlying mechanisms. We injected Rh2 into tg2576 Alzheimer's disease model mice and looked for behavioral improvement and senile plaque reduction in brain slices. We measured amyloid precursor protein (APP) metabolism species changes, amyloid beta40 and 42 levels and β, γ secretase activity in primary hippocampal neurons. By living cell staining, we detected surface and endocytosed APP. We also measured cholesterol and lipid rafts in primary neurons. Rh2 treatment significantly improved learning and memory performance at 14 months of age; it also reduced brain senile plaques at this age. Based on in vitro experiments, we found that Rh2 treatment increased soluble APPα (sAPPα) levels, increased CTFα/β ratios, and reduced amyloid beta 40 and 42 concentrations. Surface APP levels dramatically increased. Based on living cell staining, we found that Rh2 inhibited APP endocytosis. Based on lipid removal and reload experiments, we found that Rh2 can modulate APP by reducing cholesterol and lipid raft levels. We concluded that Rh2 improves learning and memory function in Alzheimer's disease model mice, and that this improvement is accomplished by reducing amyloid beta secretion and APP endocytosis, which in turn is achieved by reducing cholesterol and lipid raft concentrations.


Case report of a traumatic abdominal wall hernia resulting from falling onto a flat surface.
This article reports a case of high-energy type traumatic abdominal wall hernia (TAWH) associated with multiple organ injuries including pelvic fractures, liver laceration and ascending colon perforation. The cause of the trauma was falling to the ground from a height of approximately 8 meters. Since the forces affecting the abdomen are unique when falling on a flat surface, the mechanism of defect may be different between a low-energy type handlebar hernia and high-energy type TAWH. Only a few cases of high-energy type TAWH exist in the literature, all reporting falling on or hitting an angled or curved material. To our knowledge, this is the only report of TAWH resulting from falling onto a flat surface. The diagnosis and management are summarized, the literature data are reviewed, and the mechanism of action is discussed.


[Applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou].
Objective: This article was to evaluate the applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou. Hopefully, the results could be used to improve the existing HIV testing services and to support the implementation and scale-up of HIV self-testing programs. Methods: Data were collected from a survey on HIV testing preferences among the Internet-using MSM in April to June, 2015. Univariate and multivariate logistic regression analysis were applied to identify factors associated with the use of HIV self-testing service provided by Lingnanzhun. Information related to the users of Lingnanzhun during September 2014 and December 2018 was also collected. Results: 769 MSM were recruited as participants. Of them, age distribution was 16-77(28.6±6.8) years old, 88.3%(679/769) were unmarried, 42.2%(325/769) were registered residents of Guangzhou, 82.1%(631/769) had university or college education. Among them, 195 (25.4%) used the HIV self- testing program of Lingnanzhun while 574 (74.6%) using the clinic service. Compared with the clinic service users, the Lingnanzhun users showed the following characteristics: longer experience in the MSM community ≥10 years (32.8% vs. 20.9%, 64/195 vs. 120/574); having male casual sexual partners ≥2 (42.1% vs. 29.6%, 82/195 vs. 170/574); having group sex (6.2% vs. 2.6%, 12/195 vs. 15/574) and having commercial sex with men (13.8% vs. 3.0%, 27/195 vs. 17/574). Data from the Lingnanzhun users showed that a total of 3 000 users had practised 5 038 times of self HIV-testings. 11.4% (343/3 000) of the Lingnanzhun users had never been tested. Conclusions: It was applicable and feasible to provide Internet-based HIV self-testing service to MSM as a significant complement to the traditional facility-based HIV testing services. It was also useful in accessing those who were having higher risk or had never received HIV testing so as to increase the testing uptake and the frequency.


The relationship between gut microbiota and insomnia: a bi-directional two-sample Mendelian randomization research.
Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the central nervous system, which may raise the risk of different systemic disorders. The gut microbiota, referred to as the "second genome," has the ability to control host homeostasis. It has been discovered that disruption of the gut-brain axis is linked to insomnia. In this study, we conducted MR analysis between large-scale GWAS data of GMs and insomnia to uncover potential associations. Ten GM taxa were detected to have causal associations with insomnia. Among them, class Negativicutes, genus Clostridiuminnocuumgroup, genus Dorea, genus Lachnoclostridium, genus Prevotella7, and order Selenomonadalesare were linked to a higher risk of insomnia. In reverse MR analysis, we discovered a causal link between insomnia and six other GM taxa. It suggested that the relationship between insomnia and intestinal flora was convoluted. Our findings may offer beneficial biomarkers for disease development and prospective candidate treatment targets for insomnia.


Urinary stone composition in Israel: current status and variation with age and sex--a bicenter study.
The epidemiologic data regarding stone composition in Israel are based on anachronistic methods of stone analysis. Historically, Israel was noted for an unusually high percentage of uric acid stones. The aim of the study was to describe the current stone composition distribution in Israel, using modern techniques of urinary stone analysis. Age and sex correlations were investigated. In a bicenter study, using infrared spectroscopy and X-ray diffraction, stones from five hundred and thirty eight (538) patients were analyzed and demographic data recorded. The study cohort included 401 men (74.5%) and 137 women (25.5%) with a male to female ratio of 2.9:1 and a median age of 48 years (range 2-85 years). While calcium oxalate monohydrate was the predominant component in both sexes, it was lower in female patients (77.3% vs 65%). The rate of infection stones (struvite+carbonate apatite) was significantly higher in women (35.7% vs 10.2%). Uric acid stones were found in only 14.5% of the patients and increased with age. Conversely, the rate of calcium oxalate dihydrate decreased with age. Modern techniques of urinary stone analysis showed that the most frequent stone component in Israel is calcium oxalate monohydrate. In contrast to earlier reports and in accordance with reports from other countries, the overall frequency of uric acid is 14.5%. With age, the frequency of uric acid increases reaching 21% in persons >60 years old. A significant sex difference was noted in the distribution of calcium oxalate stones and infection stones. The classic 3:1 ratio was maintained, however.


Global risk of big earthquakes has not recently increased.
The recent elevated rate of large earthquakes has fueled concern that the underlying global rate of earthquake activity has increased, which would have important implications for assessments of seismic hazard and our understanding of how faults interact. We examine the timing of large (magnitude M≥7) earthquakes from 1900 to the present, after removing local clustering related to aftershocks. The global rate of M≥8 earthquakes has been at a record high roughly since 2004, but rates have been almost as high before, and the rate of smaller earthquakes is close to its historical average. Some features of the global catalog are improbable in retrospect, but so are some features of most random sequences--if the features are selected after looking at the data. For a variety of magnitude cutoffs and three statistical tests, the global catalog, with local clusters removed, is not distinguishable from a homogeneous Poisson process. Moreover, no plausible physical mechanism predicts real changes in the underlying global rate of large events. Together these facts suggest that the global risk of large earthquakes is no higher today than it has been in the past.