Stretch reflex changes in ACL-deficient individuals and healthy controls during normal and surprise landings.
No studies in ACL-D individuals have examined neuromuscular adaptations during landing from a jump where an unexpected mechanical event changes the pre-programmed course of movement. The purpose of this study was to compare pre- and post-landing muscle activation in ACL-D individuals and uninjured controls during normal and surprise landings. Nineteen ACL-D and 17 uninjured volunteered. Participants performed repeated single leg landings from 30 and 15 cm heights. During 15 cm landings, a single surprise landing was performed where participants unexpectedly fell through a false surface at 15 cm to the solid floor a further 15 cm below. Electromyography (EMG) amplitude from vastus lateralis (VL), lateral hamstrings (LH), and soleus (Sol) was recorded. Pre-landing (-60 to 0 ms), post-landing short latency (31-60 ms), and post-landing medium latency (61-90 ms) periods were examined. Comparisons in EMG amplitudes were made across limbs (ACL-D, ACL intact, and control) in 30 cm landings. Additionally, the ratio of EMG amplitude in surprise:30 cm normal landings was analyzed. Post-landing LH EMG was reduced in the ACL-D compared to control limbs at short latencies (P < 0.05). Post-landing VL EMG was reduced in the ACL-D and ACL intact compared to the control limb at both latencies (P < 0.05). Surprise landings notably increased post-landing EMG in all muscles, across all limbs (P < 0.001). However, the gain in VL EMG was significantly greater in ACL-D and ACL intact limbs (P < 0.05). These changes in neuromuscular control of ACL-D individuals during expected and surprise landings may have important implications for rehabilitation, instability, and the risk of secondary injury.


Donepezil in the prevention and treatment of post-surgical delirium.
Delirium is a frequent complication of major surgery in older persons. The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery. A sample of 80 patients participated in this randomized, double-blind, placebo-controlled trial of donepezil. Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward. Postoperative delirium was assessed with the Delirium Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria for delirium. Subsyndromal delirium was also assessed for each participant. Delirium, diagnosed by DSM-IV criteria, was found on at least 1 postoperative day in 18.8% of subjects, but there were no significant differences between the donepezil and placebo groups. When delirium was present, it lasted only 1 day, and there was no difference between the groups. Subsyndromal delirium was found on at least 1 postoperative day for 68.8% of subjects, and, when this occurred, lasted 2 days or less, on average. There was no difference between the groups in the occurrence or duration of subsyndromal delirium. There was no difference between the groups in disposition to home or to another facility. This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery. Furthermore, postoperative delirium was not a major problem in this population.


Time-dependent density functional theory (TD-DFT) coupled with reference interaction site model self-consistent field explicitly including spatial electron density distribution (RISM-SCF-SEDD).
Theoretical approach to design bright bio-imaging molecules is one of the most progressing ones. However, because of the system size and computational accuracy, the number of theoretical studies is limited to our knowledge. To overcome the difficulties, we developed a new method based on reference interaction site model self-consistent field explicitly including spatial electron density distribution and time-dependent density functional theory. We applied it to the calculation of indole and 5-cyanoindole at ground and excited states in gas and solution phases. The changes in the optimized geometries were clearly explained with resonance structures and the Stokes shift was correctly reproduced.


Dual role of acidic diacetate sophorolipid as biostabilizer for ZnO nanoparticle synthesis and biofunctionalizing agent against Salmonella enterica and Candida albicans.
In the present study, a yeast species isolated from CETP, Vellore, Tamilnadu was identified as Cryptococcus sp. VITGBN2 based on molecular techniques and was found to be a potent producer of acidic diacetate sophorolipid in mineral salt media containing vegetable oil as additional carbon source. The chemical structure of the purified biosurfactant was identified as acidic diacetate sophorolipid through GC-MS analysis. This sophorolipid was used as a stabilizer for synthesis of zinc oxide nanoparticles (ZON). The formation of biofunctionalized ZON was characterized using UV-visible spectroscopy, XRD, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy. The antimicrobial activities of naked ZON and sophorolipid functionalized ZON were tested based on the diameter of inhibition zone in agar well diffusion assay, microbial growth rate determination, protein leakage analysis, and lactate dehydrogenase assay. Bacterial pathogen Salmonella enterica and fungal pathogen Candida albicans showed more sensitivity to sophorolipid biofunctionalized ZON compared with naked ZON. Among the two pathogens, S. enterica showed higher sensitivity towards sophorolipid biofunctionalized ZON. SEM analysis showed that cell damage occurred through cell elongation in the case of S. enterica, whereas cell rupture was found to occur predominantly in the case of C. albicans. This is the first report on the dual role of yeastmediated sophorolipid used as a biostabilizer for ZON synthesis as well as a novel functionalizing agent showing antimicrobial property.


Stage-dependent toxicity of 2,4-dichlorophenoxyacetic on the embryonic development of a South American toad, Rhinella arenarum.
The acute and short term chronic toxicity of both the herbicide butyl ester of 2,4-Dichlorophenoxyacetic acid (2,4-D) and a commercial formulation (CF) were evaluated on Rhinella (= Bufo) arenarum embryos at different developmental stages. Adverse effects were analyzed by means of the isotoxicity curves for lethality, malformations, stage-dependent susceptibility, and ultrastructural features. For all experimental conditions, the CF was more toxic, up to 10 times, than the active ingredient, being the open mouth stage (S.21) the most susceptible to the herbicide. For continuous treatment conditions, the early embryonic development was the most susceptible to 2,4-D and the LC50s for 96 and 168 h were 9.06 and 7.76 mg L(-1) respectively. In addition, both the active ingredient and the CF were highly teratogenic, resulting in reduced body size, delayed development, microcephaly, agenesis of gills, and abnormal cellular proliferation processes as the main adverse effects. According to US EPA, 2,4-D in agricultural scenarios may be up to three times higher than the NOEC values for teratogenic effects reported in this study. Therefore, they might represent a risk for amphibians. This study also points out the relevance of reporting the susceptibility of embryos at different developmental stages to both the active ingredient and the CF of agrochemicals in order to protect nontarget organisms.


Effect of application of benzyl benzoate on house dust mite allergen levels.
Several acaricides have become available for reducing house dust mite allergen levels. The purpose of this study was to assess whether the use of benzyl benzoate (Acarosan) provides additional benefit to the usual mite control measures including encasement of mattress and pillows with vinyl covers. A randomized controlled trial was carried out in 26 homes (14 control versus 12 treatment) of asthmatic patients in two cities (Vancouver and Winnipeg). The control group had the usual house dust mite control measures including the use of vinyl covers for mattresses and pillows while the treatment group had application of benzyl benzoate to mattresses and carpets in the bedroom and the most commonly used room, in addition to the above control measures. Mite allergen levels were measured 3 months and immediately before, 1 week, and 1 and 3 months after the application of house dust mite control measures. Patients kept diary cards on asthma symptoms and peak expiratory flow rates morning and evening one month before and three months after the onset of mite allergen control measures. A reduction of mite allergen level was found in mattress samples in both groups, statistically significant at all times in the treatment group and at one and three months in the control group. Mite allergen levels on floor carpets also showed progressive reduction in both groups, but were significantly different in the treatment group (compared with controls) at 1 week, and were lower compared with baseline in the treatment group up to 3 months. No significant changes in asthma symptoms, peak expiratory flow rates, spirometric measurements, or bronchial hyperresponsiveness were observed among treatment or control group subjects. The addition of benzyl benzoate to conventional house dust mite control measures resulted in a significant reduction in floor carpet dust mite levels that persisted for 3 months. The results of this study should be confirmed in a larger and longer study.


The Effects of Storage Time and Repeated Freeze-Thaw Cycles on Intact Fibroblast Growth Factor 23 Levels.
Background: Fibroblast growth factor 23 (FGF23) has become increasingly important in chronic kidney diseases (CKDs), cardiovascular calcification, and metabolic bone diseases. Fresh or stored blood samples are widely used for the FGF23 assay. Clarifying the factors influencing the FGF23 assay can help to quantify FGF23 more accurately. This study explored the effects of low-temperature storage time and repeated freeze-thaw cycles on the measurement of serum intact FGF23 (iFGF23). Materials and Methods: We selected 60 serum samples from patients with CKD stages 3-5 and hemodialysis patients. An enzyme-linked immunosorbent assay was used to measure the changes in serum iFGF23 levels after 6 years of storage at -80°C. In total, 18 fresh serum samples were frozen and thawed for 0, 1, 3, and 5 cycles to explore the effects of repeated freeze-thaw cycles on serum iFGF23 levels. Results: Median serum iFGF23 concentrations were 252.17 (interquartile range [IQR] 113.82-592.38) pg/mL and 203.85 (IQR 64.76-545.39) pg/mL before and after 6 years. There were no significant differences between them. However, we found a downward trend of 48% in the samples close to the normal level of iFGF23 (<150.34 pg/mL) after 6 years of storage (p = 0.160). In addition, the iFGF23 levels of samples frozen and thawed for 0, 1, 3, and 5 cycles were 278.41 ± 39.51 (mean ± standard deviation) pg/mL, 262.84 ± 38.42 pg/mL, 252.97 ± 34.65 pg/mL and 250.49 ± 37.12 pg/mL, respectively. A slight downward trend in iFGF23 levels was observed with increasing freeze-thaw times; however, no significant differences were found among different freeze-thaw cycles. Conclusion: Serum iFGF23 levels remained stable after storage at -80°C for 6 years. In addition, five freeze-thaw cycles had no significant effects on serum iFGF23 levels.


First Detection of a Splice Acceptor Site β-Thalassemia Mutation: IVS-I-130 (HBB: c.93-1G > C) in a Chinese Patient.
We present the first description of a Chinese patient with a rare β-thalassemia (β-thal) mutation IVS-I-130 (HBB: c.93-1G > C). This mutation is a splice donor site mutation, and is associated with a β(0)-thal phenotype.


Deprivation, occupational hazards and perinatal outcomes in pregnant workers.
Recent global economic difficulties have widened social inequalities, but their impact on pregnant workers is not known. To investigate the association between deprivation, exposure to occupational hazards and adverse perinatal outcomes in pregnant workers. A cross-sectional study performed in 2014 in French occupational health services. Eligible workers were women who had worked during their pregnancy and had a medical visit by occupational health physicians (OHPs) after delivery and at the time of returning to work. Deprivation was measured using the EPICES scale (Evaluation of Precariousness and Inequalities in Health Examination Centres). Information on birth outcomes was self-reported. Occupational risks for pregnancy were assessed by OHPs. Jobs were coded by the occupational health team using standardized French nomenclature. The groups (deprivation/no deprivation) were compared using univariate (chi-squared test) and multivariate Poisson regression analyses. Of 1402 pregnant workers, 293 (21%) were classed as deprived. This group more frequently encountered occupational hazards, particularly for physical exposures (P < 0.001), and had a higher risk of cumulated occupational hazards of three or more for pregnancy [adjusted relative risk (RRa) = 4.2; 95% confidence interval (CI) 2.2-7.9]. Our findings suggest that deprivation and exposure to three or more occupational hazards during pregnancy cumulatively increased the risk of pre-term birth (RRa = 3.9; 95% CI 1.2-12.4). Our data suggest that deprived pregnant workers are an occupationally vulnerable group.


Mechanisms of Liver Injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions.
Polymorphonuclear leukocytes (neutrophils) are a vital part of the innate immune response to microbial infections and tissue trauma, e.g., ischemia-reperfusion injury, in many organs including the liver. However, an excessive inflammatory response can lead to a dramatic aggravation of the existing injury. To design interventions, which selectively target the detrimental effects of neutrophils, a detailed understanding of the pathophysiology is critical. Systemic or local exposure to proinflammatory mediators causes activation and priming of neutrophils for reactive oxygen formation and recruits them into the vascular beds of the liver without causing tissue injury. However, generation of a chemotactic signal from the parenchyma will trigger extravasation and an attack on target cells (e.g., hepatocytes). Adhesion to the target induces degranulation with release of proteases and formation of reactive oxygen species including hydrogen peroxide and hypochlorous acid, which can diffuse into hepatocytes and induce an intracellular oxidant stress and mitochondrial dysfunction. Various neutrophil-derived proteases are involved in transmigration and cell toxicity but can also promote the inflammatory response by processing of proinflammatory mediators. In addition, necrotic cells release mediators, e.g., high-mobility group box-1, which further promotes neutrophilic hepatitis and tissue damage. On the basis of these evolving insights into the mechanisms of neutrophil-mediated liver damage, the most selective strategies appear not to interfere with the cytotoxic potential of neutrophils, but rather strengthen the target cells' defense mechanisms including enhancement of the intracellular antioxidant defense systems, activation of cell survival pathways, or initiation of cell cycle activation and regeneration.


Bupropion: overview and prescribing guidelines in depression.
Bupropion is a new antidepressant medicine that is chemically distinct from previous agents. Clinical studies have shown it to be as effective as the standard antidepressant drugs currently used in the treatment of major depression. It is useful in patients resistant to other agents as well as in patients with atypical depression. Bupropion is 10 to 100 times less likely to induce cardiac conduction problems than the tricyclic drugs, and orthostatic hypotension is rare. Minimal anticholinergic effects account for its being generally well tolerated. The most common side effect is dry mouth. An epileptogenic potential is prominently reported. Because it may lower the convulsive threshold, bupropion is not recommended for individuals who may be predisposed to seizures. In people without an increased ictal risk factor, and when dosage is maintained at 450 mg/day or less in a divided schedule, the seizure rate is comparable to that of other antidepressant drugs.


Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms.
The purpose of the present study was to investigate whether former childhood cancer patients who developed a subsequent secondary primary neoplasm (SPN) are characterized by elevated spontaneous chromosomal instability or cellular and chromosomal radiation sensitivity as surrogate markers of compromised DNA repair compared to childhood cancer patients with a first primary neoplasm (FPN) only or tumor-free controls. Primary skin fibroblasts were obtained in a nested case-control study including 23 patients with a pediatric FPN, 22 matched patients with a pediatric FPN and an SPN, and 22 matched tumor-free donors. Clonogenic cell survival and cytogenetic aberrations in Giemsa-stained first metaphases were assessed after X-irradiation in G1 or on prematurely condensed chromosomes of cells irradiated and analyzed in G2. Fluorescence in situ hybridization was applied to investigate spontaneous transmissible aberrations in selected donors. No significant difference in clonogenic survival or the average yield of spontaneous or radiation-induced aberrations was found between the study populations. However, two donors with an SPN showed striking spontaneous chromosomal instability occurring as high rates of numerical and structural aberrations or non-clonal and clonal translocations. No correlation was found between radiation sensitivity and a susceptibility to a pediatric FPN or a treatment-associated SPN. Together, the results of this unique case-control study show genomic stability and normal radiation sensitivity in normal somatic cells of donors with an early and high intrinsic or therapy-associated tumor risk. These findings provide valuable information for future studies on the etiology of sporadic childhood cancer and therapy-related SPN as well as for the establishment of predictive biomarkers based on altered DNA repair processes.


A Whole Germline BRCA2 Gene Deletion: How to Learn from CNV In Silico Analysis.
BRCA1/2 screening in Hereditary Breast and Ovarian Syndrome (HBOC) is an essential step for effective patients' management. Next-Generation Sequencing (NGS) can rapidly provide high throughput and reliable information about the qualitative and quantitative status of tumor-associated genes. Straightforwardly, bioinformatics methods play a key role in molecular diagnostics pipelines. BRCA1/2 genes were evaluated with our NGS workflow, coupled with Multiplex Amplicon Quantification (MAQ) and Multiplex Ligation-dependent Probe Amplification (MLPA) assays. Variant calling was performed on Amplicon Suite, while Copy Number Variant (CNV) prediction by in house and commercial CNV tools, before confirmatory MAQ/MLPA testing. The germline profile of BRCA genes revealed a unique HBOC pattern. Although variant calling analysis pinpointed heterozygote and homozygote polymorphisms on BRCA1 and BRCA2, respectively, the CNV predicted by our script suggested two conflicting interpretations: BRCA1 duplication and/or BRCA2 deletion. Our commercial software reported a BRCA1 duplication, in contrast with variant calling results. Finally, the MAQ/MLPA assays assessed a whole BRCA2 copy loss. In silico CNV analysis is a time and cost-saving procedure to powerfully identify possible Large Rearrangements using robust and efficient NGS pipelines. Our layout shows as bioinformatics algorithms alone cannot completely and correctly identify whole BRCA1/2 deletions/duplications. In particular, the complete deletion of an entire gene, like in our case, cannot be solved without alternative strategies as MLPA/MAQ. These findings support the crucial role of bioinformatics in deciphering pitfalls within NGS data analysis.


Dietary calcium content, calcium balance and mode of uptake in a subterranean mammal, the Damara mole-rat.
Calcium flux and mode of uptake were investigated in an underground dwelling mole-rat, Cryptomys damarensis, fed diets of varying Ca content. The amount of dietary Ca positively influenced the amounts ingested, absorbed and retained. The linear relationship between ingested and absorbed Ca was significantly (P less than 0.001) correlated, implying that this process is nonsaturable. When mole-rats were fed a diet low in Ca, apparent fractional absorption of Ca was high (85.88%). This increased still further when the diet was changed to a food of greater Ca content (96.13%, carrots; 96.97%, gemsbok cucumber). Mineral homeostasis is regulated at the intestinal level in most mammals. Regardless of dietary Ca content, uptake of 45Ca (examined via the everted gut sac technique) was passive, confirming that absorption is via a nonsaturable process. Plasma Ca concentrations were not tightly regulated, yet when fed the diet with the highest Ca content, mole-rats were not hypercalcemic. Regardless of diets, Ca apparent fractional retention was positive, and approached physiological maxima (greater than 97%). Cryptomys damarensis, in using highly efficient modes of mineral uptake and retention, is therefore capable of fully exploiting the limited food resources of their arid ecotope.


Expression cloning and molecular characterization of HAS protein, a eukaryotic hyaluronan synthase.
We developed a mammalian transient expression system to isolate cDNA clones that determine hyaluronan expression. HAS-, a mouse mammary carcinoma mutant cell line, which is defective in hyaluronan synthase activity, was first established and used as a recipient for the expression cloning. One cloned cDNA that overcame the deficiency was isolated. The cDNA termed HAS contains an open reading frame of 1749 base pairs encoding a new protein of 583 amino acids. Homology analysis of the amino acid sequence suggests that HAS protein is related to streptococcal hyaluronan synthase and also to Xenopus laevis DG42 protein that was found to be homologous to bacterial hyaluronan synthase. Expression of HAS cDNA in HAS- cells complemented not only their mutant phenotypes such as deficient hyaluronan-matrix deposition but also hyaluronan synthase activity itself. Therefore, HAS cDNA is responsible for the activity of the hyaluronan synthase, a key enzyme of hyaluronan synthesis in eukaryotic cells.


Flexible Photodiodes Based on Nitride Core/Shell p-n Junction Nanowires.
A flexible nitride p-n photodiode is demonstrated. The device consists of a composite nanowire/polymer membrane transferred onto a flexible substrate. The active element for light sensing is a vertical array of core/shell p-n junction nanowires containing InGaN/GaN quantum wells grown by MOVPE. Electron/hole generation and transport in core/shell nanowires are modeled within nonequilibrium Green function formalism showing a good agreement with experimental results. Fully flexible transparent contacts based on a silver nanowire network are used for device fabrication, which allows bending the detector to a few millimeter curvature radius without damage. The detector shows a photoresponse at wavelengths shorter than 430 nm with a peak responsivity of 0.096 A/W at 370 nm under zero bias. The operation speed for a 0.3 × 0.3 cm2 detector patch was tested between 4 Hz and 2 kHz. The -3 dB cutoff was found to be ∼35 Hz, which is faster than the operation speed for typical photoconductive detectors and which is compatible with UV monitoring applications.


Hydrophobicity at low temperatures and cold denaturation of a protein.
We elucidate the microscopic mechanism of the weakening of the hydrophobicity at low temperatures by investigating cold denaturation of a protein. We employ an elaborate statistical-mechanical theory combined with a realistic water model. At low temperatures, the ordered structure with enhanced hydrogen bonds of water molecules is formed near nonpolar groups, leading to entropic loss and energy gain which are both quite large. However, they are canceled out and make no contribution to the free-energy change. We argue that a different factor, which is responsible for the weakening of the hydrophobicity at low temperatures, induces cold denaturation.


Important considerations when providing mental health first aid to Iraqi refugees in Australia: a Delphi study.
Refugees are one of the most vulnerable groups in Australian society, presenting high levels of exposure to traumatic events and consequently high levels of severe psychological distress. While there is a need for professional help, only a small percentage will receive appropriate care for their mental health concerns. This study aimed to determine cultural considerations required when providing mental health first aid to Iraqi refugees experiencing mental health problems or crises. Using a Delphi method, 16 experts were presented with statements about possible culturally-appropriate first aid actions via questionnaires and were encouraged to suggest additional actions not covered by the questionnaire content. Statements were accepted for inclusion in a guideline if they were endorsed by ≥90 % of panellists as 'Essential' or 'Important'. From a total of 65 statements, 38 were endorsed (17 for cultural awareness, 12 for cross-cultural communication, 7 for stigma associated with mental health problems, and 2 for barriers to seeking professional help). Experts were able to reach consensus about how to provide culturally-appropriate first aid for mental health problems to Iraqi refugees, demonstrating the suitability of this methodology in developing cultural considerations guidelines. This specific refugee study provided potentially valuable cultural knowledge required to better equip members of the Australian public on how to respond to and assist Iraqi refugees experiencing mental health problems or crises.


Antihypertensive and cardiovascular effects of combined blockade of renin-angiotensin system with ACE inhibitor and angiotensin II type 1 receptor blocker in hypertensive patients: A 24-week randomized controlled double-dummy trial.
BACKGROUND.: In this study the effects of 24 weeks losartan and ramipril treatment, both alone and in combination, on blood pressure and left ventricular mass (LVM) and function, have been evaluated in hypertensives. METHODS.: 57 hypertensives with stage 1 and 2 essential hypertension were included. After 4 weeks run in, a randomized double-blind, 3 arm, double dummy, independent trial was used. All patients were randomly allocated to 3 treatment arms consisting of losartan (50 mg/daily), ramipril (5 mg/daily), and combined (losartan 50 mg/ramipril 5 mg/daily) for 24 weeks. LVM, LVM/h(2.7) and other echocardiographic measurements, BUN, creatinine and clearance and potassium were determined after run in and 24 weeks. RESULTS.: All groups were comparable for gender, age, BMI, BP and LVM. The prevalence of baseline left ventricular hypertrophy (LVH) was not significantly different among 3 groups. At the end of treatment, a significant (p<0.05) reduction in SBP, DBP, MBP, LVM and LVM/h(2.7) were observed in all groups. The absolute and percent reduction in LVM/h(2.7) were significantly higher in combined than losartan or ramipril groups and also in hypertensives with LVH. No significant change in absolute and percent reduction of SBP, DBP and MBP were found. CONCLUSIONS.: These data indicate an additional cardioprotective effect of dual blockade of RAS in hypertensive patients with and without left ventricular hypertrophy.


Consumption of fermented dairy products is associated with lower anxiety levels in Azorean university students.
A growing number of studies have found that the gut microbiota is involved in a variety of psychological processes and neuropsychiatric disorders, which include mood and anxiety disorders. Consumption of dairy products may contain bioactive compounds and probiotic bacteria with various therapeutic benefits. The aim of the study was to investigate possible associations between the frequency of consumption of different types of dairy products and the state of anxiety in university students. The subjects were 311 Azorean university students, 231 women and 80 men, with an average age of 20.5 years. Subjects completed a quantitative questionnaire on the frequency of dairy product consumption and a short version of the Spielberger State-Trait Anxiety Inventory (STAI) test. Among dairy products, semi-skimmed milk was the most commonly consumed, followed by cheese (ripened), drinking yogurt, skim milk, and set yogurt, while fresh cheese, whole milk, and dairy ice cream were the least common. Discriminant analysis showed that consumption of fermented products (yogurt and cheese) was significantly higher (P < 0.05) in the group with low anxiety level (score <40 in STAI test) than in the group with higher anxiety level (score ≥ 40). In this analysis, 62.4% of the initially grouped cases were correctly classified according to the frequency of fermented products consumption. No correlations were found between anxiety and unfermented dairy products. The results indicate that the consumption of fermented dairy products has a positive effect on reducing anxiety in young Azorean university students.


Shared computational principles for language processing in humans and deep language models.
Departing from traditional linguistic models, advances in deep learning have resulted in a new type of predictive (autoregressive) deep language models (DLMs). Using a self-supervised next-word prediction task, these models generate appropriate linguistic responses in a given context. In the current study, nine participants listened to a 30-min podcast while their brain responses were recorded using electrocorticography (ECoG). We provide empirical evidence that the human brain and autoregressive DLMs share three fundamental computational principles as they process the same natural narrative: (1) both are engaged in continuous next-word prediction before word onset; (2) both match their pre-onset predictions to the incoming word to calculate post-onset surprise; (3) both rely on contextual embeddings to represent words in natural contexts. Together, our findings suggest that autoregressive DLMs provide a new and biologically feasible computational framework for studying the neural basis of language.


[Effect of boayuan qiangshen II tablet on plasma and urine superoxide dismutase and malondialdehyde in patients with chronic renal failure].
To observe the effect of Chinese herbs of replenishing Kidney in treating chronic renal failure (CRF). Forty patients with CRF wrer randomly divided into two groups, Baoyuan Qiangshen (BQ) II tablet group and essential amino acid added capoten group. The changes of plasma and urine superoxide dismutase (SOD) and malondialdehyde (MDA) and the kidney function indices were investigated before and after treatment. Before treatment, SOD reduced and MDA of both groups increased (P < 0.01), while urine SOD and MDA increased (P < 0.01). After treatment, plasma SOD increased but MDA was reduced and urine SOD, MDA were also reduced (P < 0.01). Although the BUN and serum creatinine reduced significantly, creatinine clearance rate elevated significantly (P < 0.01). The BQ II tablet could strengthen antioxidation and inhibit lipid peroxidation, so it was effective to improve kidney function.


Carotenoid coloration is related to fat digestion efficiency in a wild bird.
Some of the most spectacular visual signals found in the animal kingdom are based on dietarily derived carotenoid pigments (which cannot be produced de novo), with a general assumption that carotenoids are limited resources for wild organisms, causing trade-offs in allocation of carotenoids to different physiological functions and ornamentation. This resource trade-off view has been recently questioned, since the efficiency of carotenoid processing may relax the trade-off between allocation toward condition or ornamentation. This hypothesis has so far received little exploratory support, since studies of digestive efficiency of wild animals are limited due to methodological difficulties. Recently, a method for quantifying the percentage of fat in fecal samples to measure digestive efficiency has been developed in birds. Here, we use this method to test if the intensity of the carotenoid-based coloration predicts digestive efficiency in a wild bird, the house finch (Haemorhous mexicanus). The redness of carotenoid feather coloration (hue) positively predicted digestion efficiency, with redder birds being more efficient at absorbing fats from seeds. We show for the first time in a wild species that digestive efficiency predicts ornamental coloration. Though not conclusive due to the correlative nature of our study, these results strongly suggest that fat extraction might be a crucial but overlooked process behind many ornamental traits.


Patient with dissociation of corneal topography and epithelial mapping.
A 21-year-old man was referred for refractive surgery evaluation. Spectacle dependence and poor visual quality in his left eye is his chief complaint. He cannot tolerate contact lenses (CLs). The corrected distance visual acuity (CDVA) was 20/20 in the right eye (-1.50 -2.00 × 180) and 20/30 in the left eye (-1.25 -1.50 × 170). The patient denied any history of ocular trauma, systemic disease, or medications. Corneal topography with different technologies revealed an inferior steepening in the left eye (Figure 1), whereas keratoconus indices from different strategies are within normal limits in both eyes (Supplemental Figures 1-4, http://links.lww.com/JRS/A496). Pachymetry maps from different devices present absolute values of thinnest point within normal ranges. Epithelial mapping revealed a localized thickening in the left eye (Supplemental Figures 5 and 6, http://links.lww.com/JRS/A496). Slitlamp showed a total clear cornea with no signs of abnormality. The patient presents no signs of blepharitis or dry-eye syndrome either. Intraocular pressure is 14 mm Hg in both eyes. The retina was normal, bilaterally. Considering the findings, what would be your main diagnostic hypothesis and, if any, which refractive surgery option would you consider for this patient?


Value of radiomics model based on multi-parametric magnetic resonance imaging in predicting epidermal growth factor receptor mutation status in patients with lung adenocarcinoma.
The epidermal growth factor receptor (EGFR) is an important therapeutic target for patients with non-small-cell lung cancer (NSCLC). Radiomics and radiogenomics have emerged as attractive research topics aiming to extract mineable high-dimensional features from medical images and show potential to correlate with the gene mutation. Herein, we aim to develop a magnetic resonance imaging (MRI)-based radiomics model for pretreatment prediction of the EGFR status in patients with lung adenocarcinoma. A total of 92 patients with pathologically confirmed lung adenocarcinoma were retrospectively enrolled in this study. EGFR genotype was analyzed by sequence testing. All patients were randomized into training and test group in a 7:3 ratio using the R software. Radiomics features were extracted from T2 weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC); radiomics signatures were built using the least absolute shrinkage and selection operator (LASSO) and logistic regression. Preoperative clinical factors and image features associated with EGFR were also evaluated. A nomogram including sex, smoking status, and radiomics signatures was constructed. A total of five radiomics models were built, and the area under the curve (AUC) was used to evaluate their performance of EGFR mutation prediction. Among the three single-sequence models, the ADC model showed the best prediction performance. The AUCs of the ADC, DWI, T2WI prediction model in the test cohort were 0.805 (95% CI: 0.610 to 1.000), 0.722 (95% CI: 0.519 to 0.924), and 0.655 (95% CI: 0.438 to 0.872), respectively. Compared with the single-sequence model, the multi-sequence prediction model showed better performed [AUCtest =0.838 (95% CI: 0.685 to 0.992)]. The AUC of the nomogram in the training group was 0.925 (95% CI: 0.855 to 0.994) and 0.727 (95% CI: 0.531 to 0.924) in the test group, respectively. The radiomics model based on MRI might have the potential to predict EGFR mutation in patients with lung adenocarcinoma. The multi-sequence model had better performance than other models.


Treatment of domestic wastewater in an up-flow anaerobic sludge blanket reactor followed by moving bed biofilm reactor.
The performance of a laboratory-scale sewage treatment system composed of an up-flow anaerobic sludge blanket (UASB) reactor and a moving bed biofilm reactor (MBBR) at a temperature of (22-35 degrees C) was evaluated. The entire treatment system was operated at different hydraulic retention times (HRT's) of 13.3, 10 and 5.0 h. An overall reduction of 80-86% for COD(total); 51-73% for COD(colloidal) and 20-55% for COD(soluble) was found at a total HRT of 5-10 h, respectively. By prolonging the HRT to 13.3 h, the removal efficiencies of COD(total), COD(colloidal) and COD(soluble) increased up to 92, 89 and 80%, respectively. However, the removal efficiency of COD(suspended) in the combined system remained unaffected when increasing the total HRT from 5 to 10 h and from 10 to 13.3 h. This indicates that, the removal of COD(suspended) was independent on the imposed HRT. Ammonia-nitrogen removal in MBBR treating UASB reactor effluent was significantly influenced by organic loading rate (OLR). 62% of ammonia was eliminated at OLR of 4.6 g COD m(-2) day(-1). The removal efficiency was decreased by a value of 34 and 43% at a higher OLR's of 7.4 and 17.8 g COD m(-2) day(-1), respectively. The mean overall residual counts of faecal coliform in the final effluent were 8.9 x 10(4) MPN per 100 ml at a HRT of 13.3 h, 4.9 x 10(5) MPN per 100 ml at a HRT of 10 h and 9.4 x 10(5) MPN per 100 ml at a HRT of 5.0 h, corresponding to overall log(10) reduction of 2.3, 1.4 and 0.7, respectively. The discharged sludge from UASB-MBBR exerts an excellent settling property. Moreover, the mean value of the net sludge yield was only 6% in UASB reactor and 7% in the MBBR of the total influent COD at a total HRT of 13.3 h. Accordingly, the use of the combined UASB-MBBR system for sewage treatment is recommended at a total HRT of 13.3 h.


Hormone levels in methadone-treated drug addicts.
To test the effect of methadone on hormone release in man, plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17-beta-estradiol (E2), estrone (E1), progesterone (P), testosterone (T), dehydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone sulphate (DS), and prolactin (PRL) have been evaluated in 25 male subjects in treatment wit 30 mg/day methadone per os for at least two months after a minimum of one year of heroin addiction. All subjects had a history of sexual difficulties. The levels of E1, E2, P and LH were always within normal values whereas FSH showed lower values than normal and A, DS and PRL noticeably increased in many subjects. Modest variations were noted for T and DHT. These data seem to indicate that methadone abuse affects the hypophysis, the testiculum and the adrenal cortex. More details will probably be obtained when the variations in hormone rates and opiate serum concentrations are checked at a later date.


Localization of plasma membrane CD38 is domain specific in rat hepatocyte.
CD38 is a 42- to 45-kDa type II transmembrane glycoprotein with the ability to synthesize cADPR, a metabolite with potent calcium mobilizing properties independent of IP(3). We report here the primary characterization and localization of CD38 in the plasma membrane fraction of rat hepatocyte. Western blot analysis of a partially purified plasma membrane fraction with a panel of polyclonal antibodies against CD38 detected a 42- to 45-kDa protein band which is characteristic of CD38. ADP-ribosyl cyclase activity was found to be present in the plasma membrane fraction, indicating the presence of functionally active CD38. Subfractionation of the plasma membrane to the sinusoidal and bile canalicular membrane fractions showed the presence of ADP-ribosyl cyclase activity in both fractions with the sinusoidal membrane fraction having a 10-fold higher specific activity than the bile canalicular membrane fraction. Immunohistochemical staining with the same panel of polyclonal antibodies showed exclusive differential spatial localization to both the nuclei and sinusoidal domain of the plasma membrane. It is possible that the different spatial distribution of CD38 in the rat hepatocyte might be responsible for its myriad of previously known functional roles.


How are family caregivers of people with a serious illness supported by healthcare professionals in their caregiving tasks? A cross-sectional survey of bereaved family caregivers.
Due to medical advances and an increasingly ageing population, the number of people living with a serious illness is rising. This has major implications for the burden on family members of assisting with care. Support of family caregivers by healthcare professionals is needed to ensure they can provide quality care for people with serious illness. To investigate how family caregivers of people with serious illness are supported by healthcare professionals in their caregiving tasks. Population-based cross-sectional survey of bereaved family caregivers of people with serious illness (N = 3000) who cared for a person who had died 2-6 months before the sample was drawn (November 2019), as identified through three sickness funds in Flanders, Belgium. The survey explored support from healthcare professionals for family caregivers 3 months prior to bereavement. Response rate was 55.0%. Most family caregivers received support from one or more healthcare professionals for family caregiving tasks, ranging from 71% for promoting social interaction to 95% for managing symptoms. The type of support mostly involved providing information. Use of palliative care services was the strongest predictor of such support across physical, psychosocial and practical tasks. Most family caregivers of those with serious illness get some form of support from healthcare professionals for their tasks. However, an empowering support strategy for example one aimed at increasing self-efficacy of the family caregiver is rare and end-of-life communication between healthcare professionals and family caregivers needs improvement.


Acquisition and extinction of human avoidance behavior: attenuating effect of safety signals and associations with anxiety vulnerabilities.
While avoidance behavior is often an adaptive strategy, exaggerated avoidance can be detrimental and result in the development of psychopathologies, such as anxiety disorders. A large animal literature shows that the acquisition and extinction of avoidance behavior in rodents depends on individual differences (e.g., sex, strain) and might be modulated by the presence of environmental cues. However, there is a dearth of such reports in human literature, mainly due to the lack of adequate experimental paradigms. In the current study, we employed a computer-based task, where participants control a spaceship and attempt to gain points by shooting an enemy spaceship that appears on the screen. Warning signals predict on-screen aversive events; the participants can learn a protective response to escape or avoid these events. This task has been recently used to reveal facilitated acquisition of avoidance behavior in individuals with anxiety vulnerability due to female sex or inhibited personality. Here, we extended the task to include an extinction phase, and tested the effect of signals that appeared during "safe" periods. Healthy young adults (n = 122) were randomly assigned to a testing condition with or without such signals. Results showed that the addition of safety signals during the acquisition phase impaired acquisition (in females) and facilitated extinction of the avoidance behavior. We also replicated our recent finding of an association between female sex and longer avoidance duration and further showed that females continued to demonstrate more avoidance behavior even on extinction trials when the aversive events no longer occurred. This study is the first to show sex differences on the acquisition and extinction of human avoidance behavior and to demonstrate the role of safety signals in such behavior, highlighting the potential relevance of safety signals for cognitive therapies that focus on extinction learning to treat anxiety symptoms.


The phenolic fraction of extra virgin olive oil modulates the activation and the inflammatory response of T cells from patients with systemic lupus erythematosus and healthy donors.
Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease characterized by immune deregulation, which involves altered T-cell response and imbalance of cytokine production. The phenolic fraction (PE) of extra virgin olive oil (EVOO) possesses anti-inflammatory and immunomodulatory properties and exerts preventive effects in murine models of immune-inflammatory diseases, such as SLE. The present study was designed to determine the in vitro effects of the PE from EVOO on peripheral blood mononuclear cells (PBMC) from inactive patients with SLE and healthy donors. T-cell phenotype was investigated by flow cytometry, cytokine levels were determined by ELISA, and protein expression was detected by Western blot. The PE of EVOO decreased the frequency of CD69+ cells and the secretion of IFN-γ, TNF-α, IL-6, IL-1β, and IL-10. Moreover, PE increased the expression of I-kappa-B-α and decreased extracellular signal regulated kinase phosphorylation on PBMC from patients with SLE and healthy donors. PE modulates cytokine production and attenuates induced T-cell activation, probably through NF-κB signaling pathway, providing the first evidence that PE from EVOO has an anti-inflammatory and immunomodulatory role in SLE patients and it might therefore be considered as a dietary complement in SLE management.


Induction of Biofilm Formation in Klebsiella pneumoniae ATCC 13884 by Several Drugs: The Possible Role of Quorum Sensing Modulation.
Bacterial resistance is caused by several biochemical factors, the formation of biofilm being one of the main causes. This process is triggered by Quorum Sensing (QS), through the production of endogenous molecules, although other substances such as natural products can also do this. In this work, we aimed to determine whether some drugs are involved in the induction of biofilm formation in Klebsiella pneumoniae ATCC 13884, and thus, increase bacterial resistance. For this, the effect of 22 drugs on K. pneumoniae ATCC 13884 growth was determined at sub-plasmatic concentrations; the production of autoinducer lactones was established by HPLC and with a biosensor. The induction of biofilm formation was determined through crystal violet assay at 585 nm in a microplate reader and using urethral catheters. According to the in vitro assays, some drugs were found to induce biofilm formation in K. pneumoniae ATCC 13884. The effect of acetaminophen, hydrochlorothiazide, and progesterone stood out. The first drug caused several changes in the biochemistry of K. pneumoniae ATCC 13884 related to QS: high synthesis of N-hexanoyl-homoserine lactone, increasing bacterial populations by 27% and biofilm formation by 49%, and a more gentamicin resistant biofilm. Furthermore, it increased the colonization area of urethral catheters. Hydrochlorothiazide showed the biggest increase in the induction of biofilm formation of 51%, and progesterone displayed the greatest ability to provoke bacterial mass adherence but had no effects on K. pneumoniae ATCC 13884 bacterial population growth.


Severity factors in Algerian patients hospitalized for COVID-19.
Determining the profile of COVID-19 patients with low pulsed hemoglobin saturation in oxygen (SpO2) could help clinicians identify those with a poor prognosis. To identify and to compare the clinical, biological and radiological data of Algerian patients hospitalized for COVID-19 and divided according to the SpO2 measured at admission, at rest, and in ambient air. A prospective study was carried out on Algerian patients hospitalized for COVID-19 during the period from March 9 to April 30, 2020. The general characteristics of the patients and the clinical, biological and radiological data were determined. 86 patients were included in the study [G1: SpO2 >95% (n=51) and G2: SpO2 ≤95% (n=35)]. Compared to G1, G2 was older (48±14 vs. 61±12 years, p=0.0001), included more patients aged ≥ 50 years (37.2 vs. 80.0%, p=0.0001), having an arterial-hypertension (21.6 vs. 45.7%, p=0.0180), a cancer (0.0 vs. 14.3%, p=0.0054), an anemia (25.6 vs. 56.3%, p=0.0069), a leukocytosis (4.7 vs. 21.9%, p=0.0236), a biological inflammatory syndrome (82.5 vs. 100%, p=0.0142), a hyper-uremia (7.0 vs. 37.5%, p=0.0185), a hyper-creatininaemia (4.7 vs. 18.8%, p=0.0356), a tissue damage (41.0 vs. 66.7%, p=0.0341), a diffuse ground-glass opacity (52.0 vs. 71.4%, p=0.0397), band condensations (30.0 vs. 54.3%, p=0.0244), a severe extension (2.0 vs. 25.7%, p=0.0008), and included fewer patients who complained from diarrhea (49.0 vs. 22.9%, p=0.0145), having a nodular ground-glass (66.0 vs. 40.0%, p=0.0177) and a slight extension (78.0 vs. 40.0%, p=0.0004). Criteria associated with low SpO2 in hospitalized COVID-19 patients were advanced age, a history of arterial-hypertension and cancer, high frequencies of certain biological abnormalities or radiological signs. The diarrhea symptom, the radiological appearance of nodular ground glass, and a slight extension of the radiological lesions appear as protective elements.


HPV infections and oesophageal cancer.
The first reports suggesting an involvement of human papillomavirus (HPV) in the development of both benign and malignant squamous cell tumours of the oesophagus date back to 1982. Since then, a substantial amount of literature has accumulated on this subject, summarised in this review. To date, 239 oesophageal squamous cell papillomas have been analysed in 29 separate studies using different HPV detection methods, with HPV being detected in 51 (21.3%) cases. Many more squamous cell carcinomas have been analysed: of the 1485 squamous cell carcinomas analysed by in situ hybridisation, 22.9% were positive for HPV DNA, as were 15.2% of the 2020 cases tested by the polymerase chain reaction. In addition, evidence derived from large scale serological studies, animal experiments, and in vitro studies is discussed in the light of the highly variable geographical incidence rates of oesophageal carcinoma worldwide. It may be that the (multifactorial) aetiology of oesophageal cancer differs greatly between those geographical areas with a low risk and those with a high risk for this disease. Oncogenic HPV types seem to play an important causal role, particularly in high risk areas.


Linear stochastic system with delay: energy balance and entropy production.
We study the energy balance in a linear stochastic dynamics with delay under the impact of an external periodic force. The linearity of the model, in combination with a response function method, enables us to perform detailed analytic calculations of each term in the energy balance equation. From this, we discuss thermodynamics and entropy production rate sigma . With use of the delay time tau and strength of the external force A0 , sigma is simply expressed as sigma=sigma_{D,1}(tau)+A_{0};{2}eta(tau) , with both sigma_{D,1}(tau) and eta(tau) positive definite. We thus conclude that even when there is no external force (A_{0}=0) , the entropy production rate sigma=sigma_{D,1}(tau) is positive, meaning that the delay force produces work, which is dissipated into a reservoir. Numerical experiments are performed to confirm theoretical results.


[Selection of low instrumentation vertebrae with CD hybrid technique in king-types III and IV scoliosis].
To review the King-types III and IV patients treated by the CD hybrid technique and evaluate clinical results on the shorter fusion levels. Fifty-eight patients with idiopathic scoliosis were treated by the CD hybrid method from March 2000 to January 2003, among whom 40 were grouped as King-type I and 18 as King-type N; 41 were female and 17 were male. The Cobb angle of the thoracic curve was averaged 64 degrees (range 50-83 degrees), and the curve flexibility was 62%. The compensative lumbar curve was averaged 37 degrees (range 16-48 degrees), and the curve flexibility was 105%. With the neutral rotational vertebrae as a basis to select the low instrumentation vertebrae, the neutral rotational vertebrae or the vertebrae at 1 or 2 levels proximal to the neutral rotational vertebrae were selected as the low instrumentation vertebrae in all the patients. Standing AP and lateral radiographs were taken respectively at the discharge, during the follow-up after discharge, and at the final follow-up. The patients were followed up for an average of 2. 4 years (range 1.8-3.2). The corrected curves lost an average of 3.1 degrees (range--1-5 degrees)and the correction rate of the thoracic curve was 68% at the final follow-up. The plumb line from C7 was parallel to the sacral midline in 56 patients. The lumbar curves were corrected to an average of 8 degrees (2-13 degrees) automatically. The lumbosacral angle was corrected automatically by 53% and the low instrumentation vertebrae in 48 patients turned into stable vertebrae. The low instrumentation vertebrae lost 1.4 segments on average compared with the Harrington principle. No spinal imbalance was clinically observed in all the patients. The choice of the low instrumentation vertebrae as the neutral rotational vertebrae can have a good result in the clinical practice. It can be applied in the CD hybrid technique in treatment of idiopathic thoracic curves.


Primary pulmonary nodular amyloidosis.
Primary nodular amyloidosis of the lung is an uncommon manifestation. The disease runs a benign course, but offers diagnostic problems due to non-specific radiological features entering the big field of the solitary nodule. We describe the case of a 60 year old man with multiple nodules on the left lung operated on diagnostic and therapeutic video-assisted thoracoscopy and discuss the possibilities, if any, of suspecting such a disease through radiologic characteristics along with findings from the patient's history, physical examination and laboratory tests.


Mechanisms of T-cell inhibition: implications for cancer immunotherapy.
Cancer vaccines designed to augment effector T-cell responses have been disappointing with respect to clinical efficacy. This lack of effectiveness may be due to the fact that regulatory mechanisms, both intrinsic and extrinsic to activated T cells, play important roles in inhibiting vaccine-induced effector T-cell responses. This concept raises the possibility that blockade of these regulatory checkpoints might enhance anti-tumor immune responses. In this review, we discuss several regulatory mechanisms that act to control effector T-cell responses and identify strategies to circumvent these mechanisms in order to improve clinical responses.


Metacognitive Precursors: An Analysis in Children with Different Disabilities.
The analysis of Metacognitive skills is a key element to guide the learning process. Current research has shown the initiation of these skills from an early age. The present study had two aims: (1) to validate a Scale Measuring Precursor Metacognitive Skills (SMPMS) in children with diverse disabilities, and (2) to study possible significant different between different disabilities in precursor metacognitive skill use. We worked with 87 children with different disabilities, with an average age range of 24-37 months. The results have shown high indicators of reliability and validity of the SMPMS. We isolated two factors related to cognitive and metacognitive and self-regulation skills response to an adult. We also found significant differences in the acquisition of metacognitive and self-regulation skills among children with global developmental retardation as compared to children with expressive language and comprehension disability.


Comparative effects of traditional Chinese and Western migraine medicines in an animal model of nociceptive trigeminovascular activation.
Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.


Reducing statistical dependencies in natural signals using radial Gaussianization.
We consider the problem of transforming a signal to a representation in which the components are statistically independent. When the signal is generated as a linear transformation of independent Gaussian or non-Gaussian sources, the solution may be computed using a linear transformation (PCA or ICA, respectively). Here, we consider a complementary case, in which the source is non-Gaussian but elliptically symmetric. Such a source cannot be decomposed into independent components using a linear transform, but we show that a simple nonlinear transformation, which we call radial Gaussianization (RG), is able to remove all dependencies. We apply this methodology to natural signals, demonstrating that the joint distributions of nearby bandpass filter responses, for both sounds and images, are closer to being elliptically symmetric than linearly transformed factorial sources. Consistent with this, we demonstrate that the reduction in dependency achieved by applying RG to either pairs or blocks of bandpass filter responses is significantly greater than that achieved by PCA or ICA.


[Long-term cultivation of human bone marrow and its importance for clinical practice].
In vitro analysis of early steps in hemopoiesis has become feasible by culture systems allowing long-term maintenance and proliferation of self-renewing pluripotent stem cells. In this long-term bone marrow culture system, hemopoietic stem cells can be maintained for weeks due to the inductive capacity of a marrow-derived stromal microenvironment. In order to be able to analyze multiple samples, we have miniaturized the culture system. Studies were performed on the proliferative potential of pluripotent hemopoietic stem cells after intensive polychemotherapy of patients with either lymphoma or leukemia. Moreover, in long-term bone marrow cultures, the effects of cytokines on the pluripotent stem cell compartment were studied.


Dysmenorrhea in adolescents and young adults: from pathophysiology to pharmacological treatments and management strategies.
Dysmenorrhea is the most common gynecologic complaint among adolescent and young adult females. Dysmenorrhea is usually primary and is associated with normal ovulatory cycles and with no pelvic pathology. In approximately 10% of females with severe dysmenorrhea symptoms, pelvic abnormalities such as endometriosis or uterine anomalies may be found. To review the current knowledge regarding the pathophysiology of dysmenorrhea, as well as review pharmacological treatments and strategies for management of dysmenorrhea in adolescent and young adult females. Review of original articles on dysmenorrhea that have been published in the medical literature. Potent prostaglandins and potent leukotrienes play an important role in generating primary dysmenorrhea symptoms. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common pharmacologic treatment for dysmenorrhea. A loading dose of NSAIDs (typically twice the regular dose) should be used as initial treatment for dysmenorrhea, followed by a regular dose until symptoms abate. Adolescents and young adults with symptoms that do not respond to treatment with NSAIDs for three menstrual periods should be offered hormonal treatment such as combined estrogen/progestin oral contraceptive pills (OCPs) for three menstrual cycles. If dysmenorrhea does not improve within 6 months of treatment with NSAID and OCPs, a laparoscopy is indicated to look for endometriosis. The goal of pharmacological treatment for endometriosis is to block its abnormal positive feedback loop. The abnormal loop consists of high local levels of estrogen in the lesions, which induce transcription of COX-2 and synthesis of prostaglandin E(2.) This results in further expression and activity of aromatase and a further increase in estrogen.


Differential epithelial cell response upon stimulation with the Aggregatibacter actinomycetemcomitans strains VT 1169, VT 1560 DAM⁻ and ATCC 4318.
Aggregatibacter actinomycetemcomitans is known to play a role in human inflammatory oral diseases. The present study aimed to test whether GECs from different individuals show an altered immune response when exposed to wild-type A. actinomycetemcomitans biofilms (VT 1169 and ATCC43718) versus VT 1560 lacking a DNA-adenine-methyltransferase (DAM⁻). GECs were cultured from biopsies derived from three healthy subjects (A, B, and C). To obtain A. actinomycetemcomitans biofilms, each strain (VT 1169, ATCC 43718, and VT 1560 DAM⁻) was separately cultured on polymer disks. The mRNA expression of hBD-2, Rnase7, IL-8, and glycerylaldehyd-3-phosphodehydrogenase was analyzed using semi-quantitative RT-PCR. In GECs, the DAM⁻ strain VT 1560 led to a reduced gene expression of hBD-2 and IL-8 compared to VT 1169, but not ATCC 43718. In GECs from subject C, the mRNA expression of hBD-2 and IL-8 was significantly up regulated in response to A. actinomycetemcomitans VT 1169 compared to VT 1560 DAM⁻ and ATCC 43718 (p≤0,05), whereas GECs from subject A and B did not show significant changes for hBD-2 or IL-8 gene expression upon stimulation with either of the strains tested. The present study indicates strain-dependent and subject-specific immune responses in GECs after exposure to DAM(+) or DAM⁻ A. actinomycetemcomitans.


The antioxidant paradox: what are antioxidants and how should they be used in a therapeutic context for cancer.
So-called antioxidants have yet to make a clinical impact on the treatment of human cancer. The reasons for this failure are several. First, many agents that are called antioxidants are truly antioxidants at a given dose, but this dose may not have been given in clinical trials. Second, many agents are not antioxidants at all. Third, not all tumors use reactive oxygen as a signaling mechanism. Finally, reactive oxygen inhibition is often insufficient to kill or regress a tumor cell by itself, but requires sequential introduction of a therapeutic agent for maximal effect. We hope to provide a framework for the logical use of these agents in cancer.


Tapioca Resistant Maltodextrin as a Carbohydrate Source of Oral Nutrition Supplement (ONS) on Metabolic Indicators: A Clinical Trial.
Tapioca resistant maltodextrin (TRM) is a novel non-viscous soluble resistant starch that can be utilized in oral nutrition supplements (ONS). This study aims to evaluate acute and long-term metabolic responses and the safe use of ONS containing TRM. This study comprised of two phases: In Phase I, a randomized-cross over control study involving 17 healthy adults was conducted to evaluate three ONS formulations: original (tapioca maltodextrin), TRM15 (15% TRM replacement), and TRM30 (30% TRM replacement). Plasma glucose, serum insulin, and subjective appetite were evaluated postprandially over 180 min. In Phase II, 22 participants consumed one serving/day of ONS for 12 weeks. Blood glucose, insulin, lipid profile, and body composition were evaluated. Gastrointestinal tolerability was evaluated in both the acute and long-term period. During phase I, TRM30 decreased in area under the curve of serum insulin by 33.12%, compared to the original formula (2320.71 ± 570.76 uIU × min/mL vs. 3470.12 ± 531.87 uIU × min/mL, p = 0.043). In Phase II, 12-week TRM30 supplementation decreased HbA1C in participants (from 5.5 ± 0.07% to 5.2 ± 0.07%, p < 0.001), without any significant effect on fasting glucose, insulin, lipid profile, and body composition. The ONS was well-tolerated in both studies. TRM is therefore, a beneficial functional fiber for various food industries.


Isolation and characterization of Stemphylium sedicola SBU-16 as a new endophytic taxol-producing fungus from Taxus baccata grown in Iran.
In this study, a total of 25 endophytic fungi were successfully isolated from the inner bark of Taxus baccata grown in Iran by the aseptic technique. Genomic DNA was extracted from isolated endophytic fungi and subjected to polymerase chain reaction (PCR) analysis for the presence of the Taxus taxadiene synthase (ts) gene, which encodes the enzyme catalyzing the first committed step of taxol biosynthesis. Four of 25 isolated endophytic fungi isolates showed PCR positive for the ts gene. Subsequently, taxol and 10-deacetylbaccatin III (10-DAB III) were extracted from culture filtrates and mycelia of the PCR positive isolates and analyzed by high-performance liquid chromatography and mass spectrometry. The analysis showed that one isolate (SBU-16) produced taxol (6.9 ± 0.2 μg L(-1) ) and its intermediate compound, 10-DAB III (2.2 ± 0.1 μg L(-1) ). The isolate SBU-16 was identified as Stemphylium sedicola SBU-16, according to its morphological characteristics as well as the internal transcribed spacer nuclear rDNA gene sequence analysis. Interestingly, this is the first report of the genus Stemphylium as a taxol-producing taxon.


Intra-abdominal pressure and abdominal compartment syndrome in acute general surgery.
Intra-abdominal pressure (IAP) is a harbinger of intra-abdominal mischief, and its measurement is cheap, simple to perform, and reproducible. Intra-abdominal hypertension (IAH), especially grades 3 and 4 (IAP > 18 mmHg), occurs in over a third of patients and is associated with an increase in intra-abdominal sepsis, bleeding, renal failure, and death. Increased IAP reading may provide an objective bedside stimulus for surgeons to expedite diagnostic and therapeutic work-up of critically ill patients. One of the greatest challenges surgeons and intensivists face worldwide is lack of recognition of the known association between IAH, ACS, and intra-abdominal sepsis. This lack of awareness of IAH and its progression to ACS may delay timely intervention and contribute to excessive patient resuscitation. All patients entering the intensive care unit (ICU) after emergency general surgery or massive fluid resuscitation should have an IAP measurement performed every 6 h. Each ICU should have guidelines relating to techniques of IAP measurement and an algorithm for management of IAH.


Induction of E-cadherin in lung cancer and interaction with growth suppression by histone deacetylase inhibition.
Loss of E-cadherin confers a poor prognosis in lung cancer patients and is associated with in vitro resistance to endothelial growth factor receptor inhibitors. Zinc finger E box-binding homeobox (ZEB)-1, the predominant transcriptional suppressor of E-cadherin in lung tumor lines, recruits histone deacetylases (HDACs) as co-repressors. NSCLC cell lines were treated with HDAC inhibitors and analyzed for E-cadherin induction, growth inhibition and apoptosis. National Cancer Institute-H157 cells expressing ectopic E-cadherin were tested for tumorigenicity in murine xenografts. We found that treatment with MS-275, compared to vorinostat (SAHA), valproic acid or trichostatin A, was most effective in E-cadherin up-regulation and persistence in non-small cell lung cancers. As with other tumor types and HDAC inhibitors, MS-275 inhibited growth and induced apoptosis. Importantly, blocking E-cadherin induction by short hairpin RNA resulted in less inhibition by MS-275, implicating the epithelial to mesenchymal phenotype process as a contributing factor. In contrast to H460 and H661, H157 cells were resistant to E-cadherin up-regulation by HDAC inhibitors. However, E-cadherin was restored, in a synergistic manner, by combined knockdown of ZEB-1 and ZEB-2. In addition, H157 cells stably transfected with E-cadherin were markedly attenuated in their tumor forming ability. Lastly, combining MS-275 with the microtubule stabilizing agent, paclitaxel, or 17-(allylamino)-17-demethoxygeldanamycin, a heat shock protein 90 inhibitor, resulted in synergistic growth inhibition. Since MS-275 has no reported activity against HDAC6, which regulates both microtubule and heat shock protein 90 functions, other mechanisms of synergy are anticipated. These results support the role of ZEB proteins and HDAC inhibitors in the pathogenesis and treatment of lung cancer.


The scope of antimicrobial resistance in residential aged care facilities determined through analysis of Escherichia coli and the total wastewater resistome.
Antimicrobial resistance (AMR) is a global threat that imposes a heavy burden on our health and economy. Residential aged care facilities (RACFs), where frequent inappropriate antibiotic use creates a selective environment that promotes the development of bacterial resistance, significantly contribute to this problem. We used wastewater-based epidemiology to provide a holistic whole-facility assessment and comparison of antimicrobial resistance in two RACFs and a retirement village. Resistant Escherichia coli, a common and oftentimes problematic pathogen within RACFs, was isolated from the wastewater, and the phenotypic and genotypic AMR was determined for all isolates. We observed a high prevalence of an international high-risk clone, carrying an extended-spectrum beta-lactamase in one facility. Analysis of the entire resistome also revealed a greater number of mobile resistance genes in this facility. Finally, both facilities displayed high fluoroquinolone resistance rates-a worrying trend seen globally despite measures in place aimed at limiting their use.


Corn silage management III: effects of hybrid, maturity, and processing on nitrogen metabolism and ruminal fermentation.
Two experiments were conducted to evaluate the effects of maturity and mechanical processing of two hybrids of whole plant corn silage on DM and OM digestibility, nitrogen metabolism, ruminal fermentation, and milk production and composition in lactating Holstein cows. In the first experiment, Pioneer hybrid 3845 whole plant corn was harvested at hard dough, one-third milkline, and two-thirds milkline with a theoretical length-of-cut of 6.4 mm. At each stage of maturity, corn was harvested with (1-mm roll clearance) and without (15.9-mm roll clearance) mechanical processing using a John Deere 5830 harvester with an on-board kernel processor. In the second experiment, Pioneer hybrids 3845 and Quanta were harvested at one-third milkline, two-thirds milkline, and blackline stages of maturity with and without mechanical processing. The theoretical length-of-cut was 12.7 mm. Total tract DM and OM digestibilities were lower for cows fed diets containing processed corn silage in experiment 1, and tended to be lower for cows fed diets containing unprocessed corn silage in experiment 2. Ruminal acetate concentrations were greater and ruminal propionate concentrations were lower 2 and 6 h after feeding for cows fed diets containing corn silage harvested at physiological maturity in experiment 2. This was due to decreased digestion of starch at advanced maturities in experiment 2. Ruminal pH tended to decline rapidly after feeding for cows fed hybrid Quanta (2 h) compared to hybrid 3845 (5 h) corn silage based diets. Ruminal acetate concentrations decreased and ruminal propionate concentrations increased 2 and 6 h after feeding for cows fed diets containing hybrid Quanta corn silage compared to hybrid 3845 corn silage. This was related to a greater starch concentration in the corn silage, greater starch intake, and increased rate of starch digestion for cows fed hybrid Quanta corn silage-based diets. Microbial nitrogen flow was lower and feed nitrogen flow was greater for cows fed diets containing hybrid Quanta corn silage. The lower microbial nitrogen flow was due to lower microbial nitrogen concentration and nonammonia nitrogen flow to the duodenum. Milk fat and protein concentrations had a strong quadratic relationship with forage NDF intake as a percentage of body weight. When forage NDF intake as a percentage of body weight dropped below 0.70%, there was a rapid decline in milk fat and protein concentrations.


Junin virus-induced non-specific suppressor cells interact with unrelated antigen-specific suppressor cells.
Junin virus (JV) infection of adult (resistant) BALB/c mice induces antigen non-specific delayed-type hypersensitivity (DTH) suppressor T cells, termed Tsv, bearing the Thy-1+, Ly-1+2- phenotype. These cells may be related to survival to infection since DTH reaction is associated with lethal meningoencephalitis. Employing several xenogeneic red blood cell (RBC) sensitization schedules to induce different cell subpopulations, we have attempted to establish the target of JV-induced suppressor cells (Tsv). The target of Tsv cells was actually included in the antigen-specific suppressor cell compartment, as demonstrated for the RBC system. Tsv cells were able to trigger suppressor cells to act without loss of their specificity. The presence of two sets of sheep RBC-induced DTH suppressor cells bearing the Ly-1+2- and Ly-1-2+ phenotypes was disclosed in low (10(6))-dose sensitized mice. Both sets were simultaneously required by Tsv to achieve DTH suppression. In contrast, in high (10(8] SRBC-dose sensitized animals treated with cyclophosphamide (doses of 50 mg/kg), a single Ly-1-2+ suppressor cell was required.


Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits.
Famciclovir (FCV) is efficacious in the treatment of acute herpes zoster and recurrent genital infections but has not been used to treat ocular herpes simplex virus (HSV) infections. We evaluated the efficacy of orally administered FCV in treating HSV-1 epithelial keratitis and determined its effects on the establishment of latency and subsequent reactivation. Rabbits were inoculated with HSV-1 strain 17 syn+ and treated twice daily with increasing concentrations of FCV (60 to 500 mg/kg of body weight). This resulted in a significant, dose-dependent improvement in keratitis scores, as well as prolonged survival. Regardless of the dose of drug used, all groups exhibited the high rates of spontaneous and induced reactivation characteristic of 17syn+. The efficacy of 250 mg of FCV per kg was also compared to topical treatment with 1% trifluorothymidine (TFT). Although TFT treatment was more effective at reducing eye disease, FCV-treated rabbits had a better survival rate. Real-time quantitative PCR analysis of rabbit trigeminal ganglia (TG) demonstrated that FCV significantly reduced the HSV-1 copy number compared to that after treatment with TFT or the placebo but not in a dose-dependent manner. In summary, oral FCV treatment significantly reduces the severity of corneal lesions, reduces the number of HSV-1 genomes in the TG, improves survival, and therefore may be beneficial in reducing the morbidity of HSV keratitis in the clinic.


Optic neuritis in an immunocompetent 40-year-old female due to fungal sphenoidal sinusitis.
Fungal shpenoidal sinusitis with osteomyelitis is rare in young immunocompetent patients. We present a case of a presumed fungal sphenoidal sinusitis presenting with second and sixth cranial nerve involvement which resolved well with systemic anti-fungal treatment.


Silver(I)-Catalyzed Oxidative Intramolecular Cyclopropanation: Access to Complex Tricyclo[22.214.171.124]nonanediones via Semipinacol-Type Rearrangement.
An unconventional Ag(I)-catalyzed intramolecular cyclopropanation of prochiral alkyne-tethered cyclohexadienones has been developed using simple perchloric acid as an external oxidant. The transformation involves the formation of a perchloryloxy vinyl-silver species, which then proceeds through either intramolecular conjugate addition or an α-oxo silver carbene pathway to yield cyclopropane fused tricyclic enones with high diastereoselectivity. In the case of C-tethered cyclohexadienones, the reaction proceeds further via acid mediated semipinacol-type rearrangement to give complex and highly strained tricyclo[126.96.36.199]nonanediones. This cascade annulation has wide functional-group tolerance and broad substrate scope. Late-stage functionalization of estrone was also demonstrated with excellent diastereoselectivity.


Esophagectomy in esophageal perforations: an analysis.
This study aimed to study the factors that are associated with urgent esophagectomy for the treatment of esophageal perforations and the impact of this therapy. A retrospective review of all esophageal perforations treated at a tertiary care hospital from January 1984 to January 2012 was performed. Compiling demographics, cause and site of perforations, time to presentation, comorbidities, radiological tests, the length of perforation, the hemodynamic status of the patient, type of treatment required, and outcomes were performed. Univariate, multivariate, and Cox regression analyses were conducted. Of 127 cases of esophageal perforation, it was spontaneous in 44 (35%), iatrogenic in 53 (44%), foreign body ingestion in 22 (17%), and traumatic perforation in 7 (6%) cases. Overall, 85 of the 127 (67%) patients were managed operatively, 35 (27.6%) patients were treated conservatively, and 7 (6.3%) patients were treated by endoscopic stent placement. Of the 85 patients who were managed operatively, 21 (16.5%) required esophagectomies, 13 (15.3%) had esophagectomy with immediate reconstruction, 5 (5.9%) patients had esophagectomy followed by delayed reconstruction, and 3 (3.5%) patients failed primary repair and required an esophagectomy as a secondary definitive procedure. Multivariate analysis revealed that esophagectomy in esophageal perforations was associated with the presence of benign or malignant esophageal stricture (P = 0.001) and a perforation >5 cm (P = 0.001). Mortality was mainly associated with the presence of a benign or malignant esophageal stricture (P = 0.04). The presence of pre-existing benign or malignant stricture or large perforation (>5 cm) is associated with the need for an urgent esophagectomy with or without immediate reconstruction. Performing esophagectomy was not found to be a significant prognosticator for mortality.


Socio-economic correlates of bereavement among women - Examining the differentials on social axes.
Death, disease and disaster can inflict anyone, anywhere and at any time. While occurrence of such an event could be absolved of any selective strike, the outcome reflects otherwise. Historical deprivations experienced by certain populations have caused more bereavement and sorrow to them than those who have experienced lesser or no deprivation. Therefore, the process which shapes the factors to yield such a result is important and needs to be understood for any policy suggestions and programmatic inputs. Loss of pregnancy and newborn inflicts sorrow and bereavement across space, time and social labyrinth. The degree of bereavement is likely to reduce with time, but space and social context govern the response to it. Therefore, factors contributing to the differentials vary in their demographic, social and economic characteristics. The loss of pregnancy and newborn remains inadequately addressed. Family and community play a significant role in coping. While the developed countries have institutional structure to address coping with the loss, the South Asian countries rely heavily on the family and the community for such support. The present review examines these trajectories across social groups.


Use of court-appointed advocates to assist in permanency planning for minority children.
Despite federal law on reuniting children in care with their families, minority children remain in dependency longer and are more likely to be placed in long-term foster care than white children. This article describes a program of volunteer, court-appointed advocates to assist in cases of abuse and neglect involving minority families, and an outcome study. Significantly fewer children were placed in long-term foster care and significantly more children were placed in adoptive families than in a comparison group of families.


Tryptophan pyrrolase induced in human liver by hydrocortisone: effect on excretion of kynurenine.
Administration of hydrocortisone causes two- to fourfold increase in the level of activity of tryptophan pyrrolase in human liver, as measured in needle-biopsy specimens. Correlation of the higher levels of the enzyme with the amounts of urinary kynurenine suggests that the tryptophan pyrrolase level, which is regulated by adrenocortical hormones, may be the important variable in the increased excretion of tryptophan metabolites that accompanies various diseases.


Rise in serum soluble intercellular adhesion molecule-1 levels with vasospasm following aneurysmal subarachnoid hemorrhage.
Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule-1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1-2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm. Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, < 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade-matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade-matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001). These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.


Allergy and Uterine Leiomyomas: Cooperative Interaction with ACP1 Genetic Polymorphism.
The possible association between allergy and neoplastic disorders has been the subject of many investigations but no general relationship has been determined. Little attention, however, has been paid to the possible role of allergy in the clinical manifestations of these diseases. In this study, the role of allergy in the susceptibility to uterine leiomyomas and in their growth was investigated. Interaction with ACP1 , a genetic polymorphism associated with the growth of leiomyomas, has been also considered. Two hundred and three White woman from the population of Rome hospitalized for symptomatic leiomyomas requiring surgical intervention have been studied. One hundred thirty eight healthy women have been considered as controls. Allergy has been evaluated by prick test. T-test for equality of means, analysis of variance and linear correlation analysis has been performed. The level of statistical significance was set at 0.05. The frequency of allergic manifestations in women with leiomyomas does not differ from healthy women. The dimension of leiomyomas is lower in allergic than in non allergic women (p=0.004). The ACP1 *B/*B genotype and allergy cooperate in lowering the dimension of leiomyomas; the proportion of woman with small leiomyomas (<10 percentile) is much higher in allergic women carrying the *B/*B genotype as compared to other women (p<0.001). About 8% of variance of leiomyomas dimension is attributable to the joint effect of ACP1 and allergy. Allergic women with high concentration of ACP1 f isoform (*B/*B genotype) are protected from excessive leyomioma growth. If confirmed in other clinical settings, our observation may have practical importance in identifying women at risk of more severe clinical manifestations.


Chronic diseases and allergies are risk factors predictive of a history of Medial Tibial Stress Syndrome (MTSS) in distance runners: SAFER study XXIV.
Medial Tibial Stress Syndrome (MTSS) is one of the most common causes of exercise-associated lower leg pain in distance runners. To identify risk factors predictive of a history of MTSS in distance runners entering the Two Oceans Marathon races (21.1 km and 56 km). Cross-sectional study. 2012 to 2015 Two Oceans Marathon races (21.1 km and 56 km). Consenting race entrants. 106,743 race entrants completed an online pre-race medical screening questionnaire. 76,654 consenting runners (71.8%) were studied. 558 verified MTSS injuries were reported in the previous 12 months. Risk factors predictive of a history of MTSS were explored using uni - & multivariate analyses: demographics (race distance, sex, and age groups), training/racing history, history of chronic diseases, allergies, and medication use. Independent risk factors predictive of a history of MTSS (adjusted for sex, age group, and race distance) were a higher chronic disease composite score (PR = 3.1 times increase risk for every two additional chronic diseases; p < 0.0001) and a history of allergies (PR = 1.9; p < 0.0001). Chronic diseases (PR > 2) predictive of a history of MTSS were: symptoms of CVD (PR = 4.2; p < 0.0001); GIT disease (PR = 3.3; p < 0.0001); kidney/bladder disease (PR = 3.3; p < 0.0001); nervous system/psychiatric disease (PR = 3.2; p < 0.0001); respiratory disease (PR = 2.9; p < 0.0001) a history of CVD (PR = 2.9; p < 0.0001); and risk factors of CVD (PR = 2.4; p < 0.0001) (univariate analysis). Average running speed was associated with higher risk of MTSS. Novel independent risk factors predictive of a history of MTSS in distance runners (56 km, 21.1 km) were multiple chronic diseases and a history of allergies. Identifying athletes at higher risk for MTSS can guide healthcare professionals in their prevention and rehabilitation efforts.


Test-Retest Instability of Temporal Summation and Conditioned Pain Modulation Measures in Older Adults.
The temporal stability (test-retest reliability) of temporal summation of pain (TS) and conditioned pain modulation (CPM) has yet to be established in healthy older adults. The purpose of this study was to compare the temporal stability of TS and CPM in healthy older and younger adults and to investigate factors that might influence TS and CPM stability. In a test-retest study, 40 healthy older adults and 30 healthy younger adults completed two sessions of quantitative sensory testing within a two-week period that included TS of heat pain, TS of mechanical pain, and CPM with pressure pain thresholds and suprathreshold heat pain as test stimuli and a cold water immersion as a conditioning stimulus. Participants also completed self-report measures of situational catastrophizing, anxiety, clinical pain, and physical activity. Absolute and relative stability were examined for each variable. Bivariate correlations examined the associations of age, clinical, behavioral, and psychological variables with the intra-individual stability of TS and CPM. The results revealed moderate to excellent stability for the TS measures and poor to moderate stability for CPM. The results also revealed significant age differences for two of the TS measures and CPM, with younger adults having greater stability compared with older adults. Additionally, the magnitude and stability of psychological factors were correlated with stability of TS. These findings suggest that TS and CPM may be more reliable in younger compared with older adults. Furthermore, psychological states may be an important factor influencing the stability of TS in healthy adults.


Nitrogen Turnover and Assimilation during Regrowth in Trifolium subterraneum L. and Bromus mollis L.
Subterranean clover (Trifolium subterraneum L. cv Woogenellup) and soft chess grass (Bromus mollis L. cv Blando) were grown in monocultures with (15)NH(4)Cl added to the soil to study nitrogen movement during regrowth following shoot removal. Four clipping treatments were imposed. Essentially all available (15)N was assimilated from the soil prior to the first shoot harvest. Measurements of total reduced nitrogen and (15)N contained within that nitrogen fraction in roots, crowns, and shoots at each harvest showed large, significant (P </= 0.001) declines in excess (15)N of crowns and roots in both species between the first and fourth harvests. There was no significant decline in total reduced nitrogen in the same organs over that period. Similar responses were evident in plants defoliated three times. The simplest interpretation of these data is that reduced nitrogen compounds turn over in plant roots and crowns during shoot regrowth. Calculations for grass and clover plants clipped four times during the growing season indicated that 100 to 143% of the nitrogen present in crowns and roots turned over between the first and fourth shoot harvest in both species, assuming nitrogen in those organs was replaced with nitrogen containing the lowest available concentration of (15)N. If other potential sources of nitrogen were used for the calculations, it was necessary to postulate that larger amounts of total nitrogen flowed through the crown and root to produce the measured dilution of (15)N compounds. These data provide the first quantitative estimates of the amount of internal nitrogen used by plants, in addition to soil nitrogen or N(2), to regenerate shoots after defoliation.


Fibronectin synthesis by high glucose level mediated proliferation of mouse embryonic stem cells: Involvement of ANG II and TGF-beta1.
The role of individual supplements necessary for the long-term self-renewal of embryonic stem (ES) cells is poorly characterized in feeder/serum-free culture systems. This study sought to characterize the relationship between the effects of glucose on ES cell proliferation and fibronectin (FN) synthesis, and to assess the mechanisms responsible for these cellular effects of glucose. Treatment of the two ES cells (ES-E14TG2a and ES-R1) with 25 mM glucose (high glucose) increased the expression levels of FN mRNA and protein. In addition, high glucose and ANG II synergistically increased FN expression level, which coincident with data showing that high glucose increased the mRNA expression of angiotensin II (ANG II) type 1 receptor (AT(1)R), angiotensinogen, and FN, but not ANG II type 2 receptor. High glucose also increased the intracellular calcium (Ca(2+)) concentration and pan-protein kinase C (PKC) phosphorylation. Inhibition of the Ca(2+)/PKC pathway blocked high glucose-induced FN expression. High glucose or ANG II also synergistically increased transforming growth factor-beta1 (TGF-beta(1)) expression, while pretreatment with losartan abolished the high glucose-induced increase in TGF-beta(1) production. Moreover, TGF-beta(1)-specific small interfering RNA inhibited high glucose-induced FN expression and c-Jun N-terminal kinase (JNK) activation. The JNK inhibitor SP600125 blocked high glucose-induced FN expression and inhibited cell cycle regulatory protein expression induced by high glucose or TGF-beta(1). In this study, inhibition of AT(1)R, Ca(2+)/PKC, TGF-beta(1), JNK, FN receptor blocked the high glucose-induced DNA synthesis, increased the cell population in S phase, and the number of cells. It is concluded that high glucose increases FN synthesis through the ANG II or TGF-beta1 pathways, which in part mediates proliferation of mouse ES cells.


An update on recent advances in bone regeneration.
Bone loss from trauma, neoplasia, reconstructive surgery and congenital defects remains a major health problem, making the development of effective bone regeneration therapies a primary priority. The long-term clinical goal is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. Today, the science of bone regeneration is in its infancy with current and emerging therapies still having significant limitations. In addition to bone grafting, current bone regeneration strategies include the application of different bioactive factors, cell types, biologic or artificial scaffolds, alone or in various combinations. Recently, efforts are focused more on understanding the normal bone regenerative process where multiple factors interact in a defined temporal and spatial cascade of events. Bone biology has benefited over the last decade from an explosion of information regarding the molecular mechanisms underlying bone formation and resorption, as well as the feedback signals controlling these complex homeostatic mechanisms. New insights in the complexity of the homeostatic mechanisms regulating bone remodeling have uncovered potential therapeutic strategies for bone repair.


The bisphosphonates alendronate and zoledronate are inhibitors of canine and human osteosarcoma cell growth in vitro.
Bisphosphonates (BPs) are a class of non-hydrolysable analogues of pyrophosphate that have high affinity for bone mineral and are inhibitors of bone resorption. The in vitro effects of two nitrogen-containing BPs, alendronate (ALE) and zoledronate (ZOL), on growth, induction of apoptosis and effects on cell-cycle distribution in two canine and two human osteosarcoma (OSA) cell lines are investigated here. Both significantly (P < 0.001) reduced cell growth in all cell lines, as assessed by a colorimetric assay with IC(50) values in the range of 7.3-61.4 microM and 7.9-36.3 microM for ALE and ZOL, respectively. Both BPs caused a significant (P < 0.001) dose-dependent increase in the proportion of cells undergoing apoptosis, as assessed both by cell-cycle analysis and by annexin-V binding. Both ALE and ZOL altered the proportion of cells in each phase of the cell cycle, but the extent and proportion was both drug and cell line dependent. These data indicate that the nitrogen-containing BPs have direct anti-tumour activity against canine and human OSA cells.


Spin Crossover of Thiophosgene via Multidimensional Heavy-Atom Quantum Tunneling.
The spin-crossover reaction of thiophosgene has drawn broad attention from both experimenters and theoreticians as a prime example of radiationless intramolecular decay via intersystem crossing. Despite multiple attempts over 20 years, theoretical predictions have typically been orders of magnitude in error relative to the experimentally measured triplet lifetime. We address the T1 → S0 transition by the first application of semiclassical golden-rule instanton theory in conjunction with on-the-fly electronic-structure calculations based on multireference perturbation theory. Our first-principles approach provides excellent agreement with the experimental rates. This was only possible because instanton theory goes beyond previous methods by locating the optimal tunneling pathway in full dimensionality and thus captures "corner cutting" effects. Since the reaction is situated in the Marcus inverted regime, the tunneling mechanism can be interpreted in terms of two classical trajectories, one traveling forward and one backward in imaginary time, which are connected by particle-antiparticle creation and annihilation events. The calculated mechanism indicates that the spin crossover is sped up by many orders of magnitude due to multidimensional quantum tunneling of the carbon atom even at room temperature.