Therapeutic potential of neurotrophic factors in neurodegenerative diseases.
There is a vast amount of evidence indicating that neurotrophic factors play a major role in the development, maintenance, and survival of neurons and neuron-supporting cells such as glia and oligodendrocytes. In addition, it is well known that alterations in levels of neurotrophic factors or their receptors can lead to neuronal death and contribute to the pathogenesis of neurodegenerative diseases such as Parkinson disease, Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, and also aging. Although various treatments alleviate the symptoms of neurodegenerative diseases, none of them prevent or halt the neurodegenerative process. The high potency of neurotrophic factors, as shown by many experimental studies, makes them a rational candidate co-therapeutic agent in neurodegenerative disease. However, in practice, their clinical use is limited because of difficulties in protein delivery and pharmacokinetics in the central nervous system. To overcome these disadvantages and to facilitate the development of drugs with improved pharmacotherapeutic profiles, research is underway on neurotrophic factors and their receptors, and the molecular mechanisms by which they work, together with the development of new technologies for their delivery into the brain.


Mouse models of graft-versus-host disease.
Transplantation of allogeneic hematopoietic stem and progenitor cells (allo-HCT) allows for cure of life-limiting malignant and non-malignant hematologic diseases. Crossing the human leukocyte antigen (HLA) barrier, however, comes at the cost of graft-versus-host disease (GVHD), a life-threatening syndrome mediated in part by the same donor T-lymphocytes that eliminate malignant cells. Acute GVHD occurs in the skin, gut, and/or liver in 25-55% of patients with a mortality rate of 15-40%, while chronic GVHD develops in 30-65% of patients who survive at least 3 months following allo-HCT and is highly debilitating in its extensive form, with a 30-50% 5year mortality rate stemming in part from immune dysregulation and opportunistic infections. Knowledge gaps remain in understanding the pathogenesis and in developing novel and effective treatments for the acute and chronic GVHD, which have distinct biology and yet are both treated with front line systemic corticosteroids. Novel and informative mouse models remain the primary means by which these diseases are studied and drugs initially developed prior to testing in humans. In this chapter, we describe allo-HCT mouse models and protocols using these mouse models by which to study acute and chronic GVHD with the goal of improving prevention and therapy.


Differences in total medical costs across the SSRIs for the treatment of depression and anxiety.
There is growing evidence that adherence to the recommended duration of antidepressant therapy results in reduced medical costs compared with nonadherence, and that the likelihood of adhering to therapy is not equivalent across the selective serotonin reuptake inhibitors (SSRIs). As such, the purpose of this study was to assess differences in 6-month medical costs between paroxetine controlled-release (CR) and immediate-release (IR) SSRI agents in a retrospective analysis of patients initiating SSRI therapy identified from the Integrated Healthcare Information Services National Managed Care Benchmark Database during a 2.5-year time frame. Inferential analyses were performed to evaluate differences in 6-month medical costs, controlling for differences in age, sex, utilization of psychiatric specialty care services, titration, pre-period costs, and comorbidity measures. Of the 146 075 patients included in this study, approximately 7% received paroxetine CR. Approximately 29.5% of patients had an anxiety disorder diagnosis; 26.0% had a depression-only diagnosis; and 13.2% had comorbid anxiety and depression. The 6-month medical costs were 244 US dollars lower for patients initiating with paroxetine CR compared with the average medical costs for patients receiving IR SSRIs. Paroxetine CR also had the lowest medical costs compared with each individual SSRI evaluated. After log transformation of costs and adjustment for baseline covariates, the aggregated IR SSRIs were associated with 8.7% higher 6-month medical costs than paroxetine CR (P <.001) and even greater costs after stratifying by diagnosis: 12.5% higher costs in patients with anxiety, 14.3% higher costs in patients with depression, and 15.9% higher costs in patients with comorbid anxiety and depression (P <.001 for all). Each individual IR SSRI was also associated with significantly higher medical costs than paroxetine CR, irrespective of diagnosis. As demonstrated, medical costs over a 6-month time frame were significantly greater for IR SSRIs versus paroxetine CR, even after adjusting for background characteristics and stratifying by diagnosis. Future studies should measure rates of adherence in relation to medical outcomes over an expanded time frame.


Reaction norms of life history traits in response to zinc in Thlaspi caerulescens from metalliferous and nonmetalliferous sites.
* We examined phenotypic plasticity of fitness components in response to zinc (Zn) in the Zn hyperaccumulator, Thlaspi caerulescens. * Two populations from Zn-enriched soils (M) and two populations from normal soils (NM) were grown in pots at three Zn concentrations (0, 1000 and 8000 mg kg(-1) Zn), for an entire life cycle. Growth, Zn accumulation and fitness components were assessed. * Based on vegetative growth, M and NM populations had similar Zn tolerance at 1000 mg kg(-1) Zn. However, reproductive output was markedly decreased in NM at 1000 and 8000 mg kg(-1) Zn. In M populations, Zn did not affect fitness. However, low Zn status enhanced reproductive output in year 1 compared with year 2 and decreased survival after the first flowering season. * M populations are able to achieve equal fitness across a broad range of Zn concentrations in soil by different combinations of fecundity and longevity. No cost of higher tolerance was demonstrated in M populations. Reproductive traits appeared to be a more sensitive indicator of tolerance than vegetative growth.


Suicide deaths following police contact: A review of coronial inquest findings.
We analyzed 10 years of Australian coronial inquest documents on people who died by suicide or suspected suicide following recent contact with the police. We identified 149 cases of suicide or suspected suicides via coronial websites, 34 of which contained recommendations. We developed four themes from these recommendations, the most common of which was for police to change current practices or policies and modify police officer training. Coroners considered effective working relationships with external stakeholders able to assist police an important means of reducing risk of suicide.


Integral localized approximation description of ordinary Bessel beams and application to optical trapping forces.
Ordinary Bessel beams are described in terms of the generalized Lorenz-Mie theory (GLMT) by adopting, for what is to our knowledge the first time in the literature, the integral localized approximation for computing their beam shape coefficients (BSCs) in the expansion of the electromagnetic fields. Numerical results reveal that the beam shape coefficients calculated in this way can adequately describe a zero-order Bessel beam with insignificant difference when compared to other relative time-consuming methods involving numerical integration over the spherical coordinates of the GLMT coordinate system, or quadratures. We show that this fast and efficient new numerical description of zero-order Bessel beams can be used with advantage, for example, in the analysis of optical forces in optical trapping systems for arbitrary optical regimes.


Post-transcriptional regulation of urokinase-type plasminogen activator receptor expression in lipopolysaccharide-induced acute lung injury.
Urokinase-type plasminogen activator (uPA) receptor (uPAR) is required for the recruitment of neutrophils in response to infection. uPA induces its own expression in lung epithelial cells, which involves its interaction with cell surface uPAR. Regulation of uPAR expression is therefore crucial for uPA-mediated signaling in infectious acute lung injury (ALI). To determine the role of uPA in uPAR expression during ALI caused by sepsis. We used Western blot, Northern blot, Northwestern assay, and immunohistochemistry. Phosphate-buffered saline- and lipopolysaccharide (LPS)-treated wild-type and uPA(-/-) mice were used. Biological activities of uPA, including proteolysis, cell adhesion, migration, proliferation, and differentiation, are dependent on its association with uPAR. Bacterial endotoxin (LPS) is a major cause of pulmonary dysfunction and infection-associated mortality. The present study shows that LPS induces uPAR expression both in vitro and in vivo, and that the mechanism involves post-transcriptional stabilization of uPAR mRNA by reciprocal interaction of phosphoglycerate kinase (PGK) and heterogeneous nuclear ribonucleoprotein C (hnRNPC) with uPAR mRNA coding region and 3' untranslated region determinants, respectively. The process involves tyrosine phosphorylation of PGK and hnRNPC. uPA(-/-) mice failed to induce uPAR expression after LPS treatment. In these mice, LPS treatment failed to alter the binding of PGK and hnRNPC protein with uPAR mRNA due to lack of tyrosine phosphorylation. Our study shows that induction of LPS-mediated uPAR expression is mediated through tyrosine phosphorylation of PGK and hnRNPC. This involves expression of uPA as an obligate intermediary.


Parallel analysis of mRNA and microRNA microarray profiles to explore functional regulatory patterns in polycystic kidney disease: using PKD/Mhm rat model.
Autosomal polycystic kidney disease (ADPKD) is a frequent monogenic renal disease, characterised by fluid-filled cysts that are thought to result from multiple deregulated pathways such as cell proliferation and apoptosis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of many genes associated with such biological processes and human pathologies. To explore the possible regulatory role of miRNAs in PKD, the PKD/Mhm (cy/+) rat, served as a model to study human ADPKD. A parallel microarray-based approach was conducted to profile the expression changes of mRNAs and miRNAs in PKD/Mhm rats. 1,573 up- and 1,760 down-regulated genes were differentially expressed in PKD/Mhm. These genes are associated with 17 pathways (such as focal adhesion, cell cycle, ECM-receptor interaction, DNA replication and metabolic pathways) and 47 (e.g., cell proliferation, Wnt and Tgfβ signaling) Gene Ontologies. Furthermore, we found the similar expression patterns of deregulated genes between PKD/Mhm (cy/+) rat and human ADPKD, PKD1(L3/L3), PKD1(-/-), Hnf1α-deficient, and Glis2(lacZ/lacZ) models. Additionally, several differentially regulated genes were noted to be target hubs for miRNAs. We also obtained 8 significantly up-regulated miRNAs (rno-miR-199a-5p, -214, -146b, -21, -34a, -132, -31 and -503) in diseased kidneys of PKD/Mhm rats. Additionally, the binding site overrepresentation and pathway enrichment analyses were accomplished on the putative targets of these 8 miRNAs. 7 out of these 8 miRNAs and their possible interactions have not been previously described in ADPKD. We have shown a strong overlap of functional patterns (pathways) between deregulated miRNAs and mRNAs in the PKD/Mhm (cy/+) rat model. Our findings suggest that several miRNAs may be associated in regulating pathways in ADPKD. We further describe novel miRNAs and their possible targets in ADPKD, which will open new avenues to understand the pathogenesis of human ADPKD. Furthermore they could serve as a useful resource for anti-fibrotic therapeutics.


FURTHER PHARMACOLOGY AND CHEMOTHERAPY OF CLOXACILLIN.
In concentrations greatly in excess of therapeutic blood levels cloxacillin has a slight hypotensive action. As with other antibiotics, it sometimes causes diarrhoea in rabbits but, in doses up to 200 mg/kg, it does not have a teratogenic effect on the rabbit foetus. Cloxacillin is distributed throughout the body. High concentrations are found only in the liver and kidney, these reflecting the high concentrations in the bile and urine respectively. It differs from other penicillins investigated in that there appears to be little or no renal tubular secretion as demonstrated in experiments on the hen. Cloxacillin is excreted as the unchanged drug and as an active metabolite in the urine and bile. After oral administration it is metabolized in the caecum giving a penicillin which differs from the urinary metabolite and which has a greater antibiotic action against Sarcina lutea than the parent penicillin. The activity of the caecal metabolite against resistant and sensitive strains of Staphylococcus, however, remains similar to that of cloxacillin. Against infections due to resistant and sensitive Staphylococcus in animals cloxacillin is active by both the oral and subcutaneous routes and it is more effective orally than an equal subcutaneous dose of methicillin.


Neurulation in the rabbit embryo.
Among a broad range of factors and mechanisms involved in the complex process of neurulation a relationship between the curvature of the craniocaudal body axis and rate of neural tube closure has been proposed, but more examples and models are needed to further substantiate the existence of this relationship. This is particularly true for mammals, where marked differences in embryonic body curvature between species exist. The rabbit embryo has virtually no curvature during the main phase of neurulation and is therefore a suitable model, but neurulation is hardly documented in this species. In the present study, therefore, neural tube closure in the rabbit embryo is presented in detail by morphological and morphometrical parameters, as well as from scanning electron microscopic investigations. At the stages of 6-8 somites, the flat neural plate transforms into a V-shaped neural groove, beginning at the rhombo-cervical level. Between the stages of 8 and 9 somites, multiple closure sites occur simultaneously at three levels: at the incipient pros-mesencephalic transition, at the incipient mes-rhombencephalic transition, and at the level of the first pairs of somites. This results in four transient neuropores. The anterior and rhombencephalic neuropores close between the stages of 9-11 somites. The mesencephalic neuropore is very briefly present. The posterior neuropore is the largest and remains longest. Its tapered (cranial) portion closes fast within somite stages 9-10. Subsequently its wide (caudal) portion closes up to a narrow slit, but further closure slows down till full closure is achieved at the 22-somite stage. In comparing rabbit neurulation with that of chick and mouse, the sequence of multiple site closure resembles that of the mouse embryo, but other important aspects of neurulation resemble those of the chick embryo. In contrast to mouse and chick, no time lag between closure at the three closure sites in the rabbit was seen.


Audiovestibular function in patients with juvenile idiopathic arthritis (JIA).
It was found that JIR children had potential sensory neural hearing loss and vestibular affection. Therefore, this study recommends: early complete audiologic evaluation of JIA child followed by regular follow-up, including TOAEs, extended high-frequency audiometry, and VNG. This follow-up is important for preliminary diagnosis and management in order to prevent the negative impact of hearing loss on a child's life. The aim of this study was to assess hearing in children with Juvenile idiopathic arthritis (JIA) and compare them with a healthy control group. In addition to conventional audiometry, extended high-frequency audiometry and Transient otoacoustic emission (TOAEs) were used. This study also tried to investigate the vestibular function in JIR children by videonystagmography (VNG). The study group comprised of 28 children with JIR and 28 healthy children. All subjects were examined audiologically using basic audiological evaluation, high-frequency audiometry, TOAEs, and VNG. Children with JIR had apparent normal peripheral hearing in conventional audiometry; sub-clinical sensory neural hearing loss was detected. This sub-clinical hearing loss appeared in statistically significant difference between them and normal in high-frequency audiometry and TOAEs. VNG test results showed affected tracking and second tests.


Simultaneous detection of multiple mycotoxins in broiler feeds using a liquid chromatography tandem-mass spectrometry.
Mycotoxins are secondary fungal metabolites that are typically present in grain and feed ingredients used for animal feeds. An analytical method using LC-ESI-MS/MS was developed to quantify nine mycotoxins, consisting of aflatoxin B1 (AFB1), AFB2, AFG1, AFG2, T-2 toxin, deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEA) and ochratoxin A (OTA) in broiler feeds. In total, 100 samples of broiler feeds were collected from poultry farms in Central Thailand. The survey found that AFB1 and ZEA were the most prevalent mycotoxins in the feed samples at percentages of 93% and 63%, respectively. The limit of detections (LODs) of investigated mycotoxins was 0.20-0.78 ng/g. AFB2, DON, AFG1, NIV and T-2 toxin were also detectable at low contamination levels with percentages of 20%, 9%, 7%, 5% and 1%, respectively, whereas OTA and AFG2 were not detected in any of the feed samples. These results suggest that there is a very low level of risk of the exposure to mycotoxins in feeds obtained from broiler farms in Central Thailand.


[Complex-formation between myeloperoxidase and fibronectin and its modulation by fibronectin ligands].
Human blood plasma fibronectin immobilised on agarose in physiological interacts with soluble myeloperoxidase (Kd = 2.43 mM). Interaction of myeloperoxidase with fibronectin adsorbed on immobilised gelatin a, natural fibronectin ligand, resulted in formation more stable complex (Kd = 0.94 mM). The presence of thermoaggregated (but not native) IgG in the liquid phase increased a stability of the complex (0.06 mM). It is suggested that myeloperoxidase could represent a component of complex super molecular structure, real immune complex.


[Dexmedetomidine combined with ropivacaine for continuous femoral nerve block improved postoperative sleep quality in elderly patients after total knee arthroplasty].
Objective: To investigate the effect of dexmedetomidine adding to ropivacaine for continuous femoral nerve block on the improvement of postoperative sleep quality in elderly patients after total knee arthroplasty. Methods: One hundred and sixty patients aged 60 years or older in Jishuitan Hospital scheduled for single total knee arthroplasty between Nov. 2016 and Jun. 2017 were recruited. All patients received spinal anesthesia and were randomized to receive either combined ropivacaine and dexmedetomidine (0.2% ropivacaine 250 ml and 5 μg/kg dexmedetomidine, at a rate of 5 ml/h or 0.1 μg·kg-1·h-1 dexmedetomidine, dexmedetomidine group) or only ropivacaine (0.2% ropivacaine, at a rate of 5 ml/h, controlled group) for continuous femoral nerve block as postoperative analgesia after surgery. The severity of postoperative pain was assessed with numeric rating scale at 4, 24, and 48 hours after surgery both at rest and with movement. Subjective sleep quality and delirium were evaluated daily during the first 3 days postoperatively. Results: The subjective sleep quality scores were 2(1-4), 2(1-4) and 4(2-8), 4(2-7) in dexmedetomidine group and controlled group respectively on the 1st and 2nd days after surgery. The scores of dexmedetomidine group were much better than those of controlled group (Z=-4.597, -4.183, both P<0.05). The difference was statistically significant. The NRS pain scores at rest were 2(1-2), 2(1-4), and 3(2-5), 3(2-6) in dexmedetomidine group and controlled group respectively at 24 and 48 hours after surgery. The scores of dexmedetomidine group were lower than those of controlled group (Z=-6.671, -4.010, both P<0.05). The difference was statistically significant. The NRS pain scores with movement were 1(1-2), 3(2-4), 3(2-3) and 3(2-4), 5(3-6), 5(4-7)in dexmedetomidine group and controlled group respectively at 4, 24 and 48 hours after surgery. The scores of dexmedetomidine group were lower than those of controlled group (Z=-7.167, -6.824, -7.473, all P<0.05). The difference was statistically significant. The incidence of 3-day delirium was lower in dexmedetomidine group (5%) than that in controlled group (15%) (χ2=4.444, P<0.05). The difference was statistically significant. There were no significant differences between groups regarding the incidences of adverse events. Conclusion: Dexmedetomidine combined with ropivacaine for continuous femoral nerve block may improve subjective sleep quality, postoperative analgesia, and reduce delirium in the elderly after total knee arthroplasty.


[PET and PET/CT in relapsing prostate carcinoma].
Of patients with carcinoma of the prostate undergoing therapeutic regimes with curative intent, 15-23% will ultimately relapse and 16-35% will need some sort of salvage therapy within 5 years. Of relapsing patients, 50% will have local recurrence and 50% systemic disease with or without local recurrence. Therefore, localization of recurrent prostate cancer is critical for selecting a local or systemic therapeutic strategy. Modern fusion imaging with PET/CT and 11C/18F-choline or 11C-acetate has augmented the diagnostic imaging spectrum for assessment of relapsing prostate cancer. In 60-70% of patients with biochemical relapse, recurrent tumor can be detected and anatomically precisely localized. Detection sensitivity is probably negatively correlated with serum PSA concentration. Below a PSA level of 1 ng/ml, mean detection sensitivity is probably 50-66%. Fusion imaging with 11C-choline PET/CT and MRI possesses a high potential for early localization of recurrent prostate carcinoma.


Low-Temperature Process for Atomic Layer Chemical Vapor Deposition of an Al2O3 Passivation Layer for Organic Photovoltaic Cells.
Flexible organic photovoltaic (OPV) cells have drawn extensive attention due to their light weight, cost efficiency, portability, and so on. However, OPV cells degrade quickly due to organic damage by water vapor or oxygen penetration when the devices are driven in the atmosphere without a passivation layer. In order to prevent damage due to water vapor or oxygen permeation into the devices, passivation layers have been introduced through methods such as sputtering, plasma enhanced chemical vapor deposition, and atomic layer chemical vapor deposition (ALCVD). In this work, the structural and chemical properties of Al2O3 films, deposited via ALCVD at relatively low temperatures of 109 degrees C, 200 degrees C, and 300 degrees C, are analyzed. In our experiment, trimethylaluminum (TMA) and H2O were used as precursors for Al2O3 film deposition via ALCVD. All of the Al2O3 films showed very smooth, featureless surfaces without notable defects. However, we found that the plastic flexible substrate of an OPV device passivated with 300 degrees C deposition temperature was partially bended and melted, indicating that passivation layers for OPV cells on plastic flexible substrates need to be formed at temperatures lower than 300 degrees C. The OPV cells on plastic flexible substrates were passivated by the Al2O3 film deposited at the temperature of 109 degrees C. Thereafter, the photovoltaic properties of passivated OPV cells were investigated as a function of exposure time under the atmosphere.


Translation, Adaptation and Psychometric Properties of SATAQ-4R for Brazilian Children.
The Sociocultural Attitudes Towards Appearance Questionnaire (SATAQ) is one of the most investigated instruments for the evaluation of sociocultural pressure and internalization of the beauty standard, and it is considered to be one of the most robust instruments for this purpose. The most recent version of this questionnaire is the SATAQ-4R, originally designed for adults and teenagers, which has been used in different countries, contexts, and populations. The cross-cultural adaptation and validation of the SATAQ-4R for Brazilian children are appropriate and necessary. The general objective of this study was to translate, adapt, and verify the psychometric qualities of the SATAQ-4R for Brazilian girls and boys aged between 7 and 11 years old. Study 1 describes the cross-cultural adaptation, from the translation stage to the pretest in children of both sexes (n = 36, M = 8.76, SD = 1.59 years). SATAQ-4R has been demonstrated to be easily understood by Brazilian children. Studies 2 and 3 analyze the psychometric qualities of such an instrument in 566 girls (M = 9.18, SD = 1.23 years) and in 592 boys (M = 9.18, SD = 1.23), respectively. Exploratory and confirmatory factor analyses have been performed with independent samples. Both instruments presented factor structures composed of five factors, good reliability, and convergent validity. We concluded that SATAQ-4R-Female and SATAQ-4R-Male are useful tools for evaluating the internalization of beauty standards and of sociocultural pressure on Brazilian children.


Is relative mortality of type 2 diabetes mellitus decreasing?
There is concern that the increasing prevalence of type 2 diabetes may diminish improving trends in life expectancy. This study aimed to determine whether the mortality of type 2 diabetes, relative to mortality in the general population, is remaining constant. The study included a cohort of 48,556 subjects with type 2 diabetes first diagnosed between 1996 and 2006, drawn from 197 family practices in the United Kingdom General Practice Research Database. There were 6,630 deaths observed. Expected mortality was estimated from United Kingdom life tables. Relative mortality was modeled using Poisson regression. In men with diabetes, from 1996 to 2006, the age-standardized all-cause mortality rate decreased by 0.82/1,000 per year (95% confidence interval (CI): 0.36, 1.27) and by 0.49 (95% CI: 0.29, 0.68) in women with diabetes. After adjustment for age, sex, and diabetes duration, there was a consistent decrease in relative mortality during the period of study. Relative mortality for subjects diagnosed in 1996 was 13% (95% CI: 2, 25) higher than that in 2001; for subjects diagnosed in 2006, relative mortality was 26% (95% CI: 8, 40) lower than that in 2001. Relative mortality of type 2 diabetes appears to be decreasing in men and women in the United Kingdom.


Calcium-mediated activation of c-Jun NH2-terminal kinase (JNK) and apoptosis in response to cadmium in murine macrophages.
Cadmium is a well-known carcinogenic and immunotoxic metal commonly found in cigarette smoke and industrial effluent. An altered intracellular calcium ([Ca(2+)](i)) level has been implicated in the pathophysiology of immune dysfunction. The present study was designed to determine the possible involvement of calcium (Ca(2+)) and mitogen-activated protein kinases (MAPKs) signaling pathways on cadmium-induced cell death in J774A.1 murine macrophage cells. Cadmium caused a low-amplitude [Ca(2+)](i) elevation at 20 microM and rapid and high-amplitude [Ca(2+)](i) elevation at 500 microM. Exposure to cadmium dose-dependently induced phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and deactivated p38 MAPK. Use of the selective JNK inhibitor SP600125 suggested that activation of JNK is pro-apoptotic and pro-necrotic. Buffering of the calcium response with 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxy-methyl) ester (BAPTA-AM) and ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) completely blocked cadmium-induced apoptotic response. The pretreatment of cells with BAPTA-AM and EGTA suppressed the cadmium-induced cell injury, including growth arrest, mitochondrial activity impairment, and necrosis, and it also recovered the cadmium-altered JNK and p38 MAPK activity. Chelating [Ca(2+)](i) also reversed cadmium-induced hydrogen peroxide generation, suggesting that production of reactive oxygen species (ROS) is related to [Ca(2+)](i). The present study showed that cadmium induces a [Ca(2+)](i)-ROS-JNK-caspase-3 signaling pathway leading to apoptosis. Furthermore, cadmium-induced [Ca(2+)](i) regulates phosphorylation/dephosphorylation of JNK and p38, and it modulates signal transduction pathways to proliferation, mitochondrial activity, and necrosis.


Sestrin2 as a Novel Biomarker and Therapeutic Target for Various Diseases.
Sestrin2 (SESN2), a highly conserved stress-inducible metabolic protein, is known to repress reactive oxygen species (ROS) and provide cytoprotection against various noxious stimuli including genotoxic and oxidative stress, endoplasmic reticulum (ER) stress, and hypoxia. Studies demonstrate that the upregulation of Sestrin2 under conditions of oxidative stress augments autophagy-directed degradation of Kelch-like ECH-associated protein 1 (Keap1), which targets and breaks down nuclear erythroid-related factor 2 (Nrf2), a key regulator of various antioxidant genes. Moreover, ER stress and hypoxia are shown to induce Sestrins, which ultimately reduce cellular ROS levels. Sestrin2 also plays a pivotal role in metabolic regulation through activation of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibition of mammalian target of rapamycin complex 1 (mTORC1). Other downstream effects of Sestrins include autophagy activation, antiapoptotic effects in normal cells, and proapoptotic effects in cancer cells. As perturbations in the aforementioned pathways are well documented in multiple diseases, Sestrin2 might serve as a potential therapeutic target for various diseases. Thus, the aim of this review is to discuss the upstream regulators and the downstream effectors of Sestrins and to highlight the significance of Sestrin2 as a biomarker and a therapeutic target in diseases such as metabolic disorders, cardiovascular and neurodegenerative diseases, and cancer.


Biomimetic Organocatalytic Approach to 4-Arylquinolizidine Alkaloids and Application in the Synthesis of (-)-Lasubine II and (+)-Subcosine II.
An enantioselective, biomimetic organocatalytic synthesis of 4-arylquinolizidin-2-ones, key intermediates in the synthesis of several Lythraceae alkaloids, was developed. The methodology features S-proline-mediated Mannich/aza-Michael reactions of readily available arylideneacetones and Δ1-piperideine. The total syntheses of (-)-lasubine II and (+)-subcosine II as well as the formal syntheses of structurally related Lythraceae alkaloids were achieved. The use of Δ1-pyrroline in the Mannich/aza-Michael reaction provides enantiomerically enriched 5-arylindolizidin-7-ones, which are precursors to nonopiate antinociceptive agents.


[The role of asbestos fibre dimensions in the pathogenesis and prevention of mesothelioma].
The particular point of view, recently published by Gerolamo Chiappino, on the pathogenetic role of asbestos fibres size in the origin of mesothelioma and on the possibility of mesothelioma prevention until the middle of the '80s needs to be critically clarified. The suggestion of an exclusive role of ultrashort and ultrathin fibres in the origin of mesothelioma is based on a biased interpretation of the literature. A review of the epidemiological, experimental, and molecular literature suggests that Chiappino's statements on the role of dose, dose-response effect, and genetic susceptibility are scientifically unsound Chiappino states that, in the past, in the workplaces where use and exposure to asbestos were not stopped, any reduction in the intensity of exposure by means of dust control measures or personal protective equipment would not have contributed to reduce the frequency of mesothelioma. In the authors' opinion the underlying assumptions are invalid.


Fixation of patella fractures with a minimally invasive tensioned wire method: compressive external fixation.
Current fixation methods of patella fractures are associated with hardware prominence, infection, and failure of fixation. These complications necessitate repeat surgical treatment, increase costs, and limit function. We investigated whether a novel device can effectively treat patella fractures with few complications. A consecutive series of patients with displaced patella fractures with transverse and select other patterns were treated with the technique of compressive external fixation (CEF), a device based on an external tensioned wire construct. Patients were allowed unrestricted motion and weight bearing postoperatively. Patient outcomes were evaluated retrospectively. Eighty-four fractures (26 open) were treated with CEF with 23 performed percutaneously. All of the fractures attained union. The device was removed in the office at 6 weeks. Sixty-one patients regained excellent motion with a mean Insall knee score of 97 points, at an average follow-up of 4 years. Minor complications presented in 11% of patients but did not affect the overall outcome. Complications included minor wire irritation in 14 patients and one case of poor knee motion in a patient presenting with fibroankylosis of the joint. Treatment using the CEF technique is a safe and effective method of treatment of patella fractures with advantages over traditional forms of fixation particularly in cases with a poor soft tissue envelope, salvage situations, and in locations with limited resources. It allows for rapid recovery with minimal complications and no secondary surgery. Its use should be considered in the treatment of these injuries. V, therapeutic study.


Two case reports of vertical and horizontal augmentation with autogenous bone blocks; seven years follow-up.
The current very high success rate of dental implants osseointegration has led to patients having increasingly high expectations in regards to aesthetic outcomes; therefore, effective management of soft tissues and healing of attached gingiva and papillae are essential in the effort to obtain satisfying aesthetic results for the patient. Obtaining papillae to address aesthetic requirements cannot be accomplished without bone reconstruction; an adequate volume of bone is essential in providing necessary long-term dimensional stability. The aim of this work was to highlight the advantages of autogenous bone grafting combined with plasma rich in growth factors (PRGF) in order to improve healing and reduce dehiscence risks. Two clinical cases were presented, both with important (horizontal and vertical) bone loss: in the first case, bone augmentation was performed at the same time as tooth extraction with no surgery needed for reconstruction of dental papillae, keratinized and attached mucosa; in the second case, vertical augmentation was performed by placing the bone graft in contact with an uninfected tooth. In both cases, aesthetic outcomes were as desired at the completion of treatment and also satisfactory at seven years follow-up.


Hepatic involvement in congenital cytomegalovirus infection - infrequent yet significant.
Congenital cytomegalovirus (cCMV) infection can reside in many organ systems; however, the virus has a particular predilection towards inhabiting the reticuloendothelial system, especially the liver. Specific studies focusing only on hepatic involvement in infants with cCMV are lacking. We report our experience with a large cohort of infants treated in our hospital clinic due to cCMV and hepatic involvement. Hepatic involvement was defined either as hepatitis (elevated alanine transaminases (ALT) >80 units/L without cholestatic disease) or cholestatic disease (elevated ALT >80 units/L combined with direct bilirubin >2 mg/dL). During the study period, 198 infants were diagnosed with symptomatic cCMV in our clinic. Hepatic involvement was observed in 13 infants (6.6%); 7 (3.5%) with hepatitis and 6 (3%) with cholestatic disease. Maternal primary infection with cytomegalovirus during pregnancy was diagnosed in 7 (53.8%) of the 13 infants, nonprimary in 3 (23.1%) and unknown in 3 (23.1%). Among these 13 infants, central nervous system (CNS) involvement was observed in 11 (84.6%) and hearing impairment in 7 (53.8%). Treatment with an antiviral agent was initiated in all cases. Gradual improvement of hepatic enzymes and cholestasis was observed over a prolonged period. We found that the incidence of hepatic involvement in infants with cCMV is much less frequent than previously reported. The hepatic involvement in these infants may manifest in two different ways, and thus, a high index of suspicion and a stepwise approach will help in correctly diagnosing these infants. Antiviral treatment due to CNS involvement is warranted and prognosis is excellent.


Topical interferon - A novel treatment for pseudophakic macular edema.
The aim of this study was to evaluate the efficacy of topical interferon (IFN) therapy in pseudophakic cystoid macular edema (P-CME). This is a prospective, interventional case series of patients with P-CME. Patients presenting with P-CME were given the option of topical IFN therapy against conventional treatment with oral, topical, intravitreal, and periocular steroid therapy and antivascular growth factors. Patients who consented for the same were advised to use the IFN drops four times/day. Commercially available injection IFN alfa-2b was reconstituted to prepare the eye drops (1 MIU/ml). Optical coherence tomography (OCT) was done at the baseline and on each review visit until complete resolution of P-CME. Eight eyes of eight patients diagnosed with P-CME were studied. Mean central macular thickness (CMT) on OCT at the presentation (n = 8) and at 4 weeks post topical IFN therapy (n = 6) was 560.1 μm (range: 349-702 μm) and 344.33 μm (range: 250-390 μm), respectively. All eyes except one had posterior capsular rent (PCR). Five patients had regular follow-up until resolution. The mean duration of complete first resolution of P-CME was 5 weeks (range: 4-7.1 weeks) in those patients. Relapse was seen in three patients who responded after resuming or continuing the therapy. Case 1 had 9 months follow-up after completion of IFN therapy, and no recurrence was noted. No ocular or systemic side effects related to the topical IFN therapy were noted clinically, except papillary conjunctivitis in one patient. Topical IFN therapy can be a noninvasive, economical, and effective choice of treatment for P-CME, especially in the case of PCR, and where steroids are contraindicated.


Evaluation of serum cytokines and acute phase proteins as possible pharmacodynamic biomarkers to monitor endoscopic remission during ustekinumab therapy in patients with Crohn's disease.
Since not all Crohn's disease (CD) patients respond adequately to ustekinumab therapy, biomarkers could aid to monitor treatment response and optimize therapeutic outcomes. To explore the dynamics of serum biomarker concentrations to monitor the response to ustekinumab treatment in CD patients. Retrospective, exploratory study to evaluate concentrations of serum cytokines and acute phase proteins and their relation to endoscopic remission in CD patients during ustekinumab treatment. Serum concentrations of 16 proteins including cytokines and acute phase proteins were measured using the Mesoscale Discovery Platform in serum of healthy controls (n = 13), and CD patients (n = 61) at baseline (week 0), week 8 and week 24 during ustekinumab treatment. Endoscopic remission was defined as simple endoscopic score for CD (SES-CD) <3 after 6 months of therapy. Absolute concentrations of serum amyloid A protein (SAA; week 8), IL-6 (week 24), AGP (weeks 8 and 24), interferon (IFN)-γ (weeks 8 and 24), lipopolysaccharide binding protein (LBP; weeks 8 and 24) and IL-22 (weeks 8 and 24) were significantly lower in endoscopic remitters compared to non-responders (p-values ranging between <0.001 and <0.05). SAA (week 8) and AGP (week 24) were the biomarkers with the highest area under the ROC curve (AUROC; 0.761 and 0.760, respectively) for identifying patients in endoscopic remission, though their performance was not superior to C-reactive protein (CRP) or faecal calprotectin. AUROCs of the predictive probability of biomarker combinations showed superiority in discriminating endoscopic remitters from non-responders in comparison to single biomarker measurements, but not as compared to faecal calprotectin. Although not superior to faecal calprotectin, measurement of AGP, SAA, LBF, IFN-γ, IL-6 and IL-22 concentrations, and combinations thereof with or without CRP and faecal calprotectin, during ustekinumab therapy might contribute to adequate monitoring of treatment response in CD patients.


Effect of apraclonidine hydrochloride on acute introacular pressure rise after argon laser iridotomy.
To determine the effect of apraclonidine hydrochloride on the acute intraocular pressure (IOP) rise after argon laser iridotomy (ALI), a double-masked comparative study was carried out. Twenty-nine eyes (20 patients) with angle-closure glaucoma underwent ALI. Eighteen eyes were treated with apraclonidine, and the remainder received a placebo 1 hour before and immediately after ALI. The mean IOP increase in the apraclonidine group was lower than that in the placebo group at each postlaser interval (p less than 0.01). Although the average value of the maximal increases of IOP after ALI in the apraclonidine group was 4 mmHg, that in the placebo group was 16 mmHg. In the placebo group, 27.3% (3 out of 11 eyes) experienced an IOP rise greater than or equal to 10 mmHg. However, that kind of IOP rise was not found in the apraclonidine group (0 out of 18 eyes) (p less than 0.01). Ocular or systemic side effects were not found in a series of examinations in both groups. Therefore, apraclonidine proved to be effective in lowering the IOP rise after ALI.


Association of human leukocyte antigen DQ1 and dengue fever in a white Southern Brazilian population.
Dengue is an infectious disease of viral etiology transmitted by the mosquitoes Aedes aegypti, A. albopictus, and A. scutellaris. It can develop either as a benign form or as a severe hemorrhagic form. Previous work showed an association of the hemorrhagic form with human leukocyte antigens (HLA), suggesting a role of genetic factors in disease susceptibility. Nevertheless, data on HLA association with the classical form of the disease is scarce in literature. Sixty-four patients and 667 normal individuals, living in the state of Parana, Southern Brazil, were used as test and control group, respectively. The patients developed the disease during a virus 1 dengue outbreak either in Maringa city in 1995 (47) or in Paranavai city in 1999 (17). The diagnostic was confirmed through serology and/or viral culture. HLA class I and II typing was performed by the classical microlynfocitotoxicity test using monoclonal antisera and fluorobeads. Qui-square statistical analysis confirmed a positive association with HLA-DQ1 (76.6% vs 57.7%; p = 0.005243; pc = 0.026215). HLA-DR1 also presented an increased frequency in the test group, not statistically significant after p correction though (32.8% vs 15.9%; p = 0.005729; pc = 0.080206). In conclusion, genetic factors may play a role on the susceptibility to the classical dengue, virus 1, in the Brazilian population. Further independent studies should be performed in the Brazilian population to confirm these preliminary data.


[Postimplantation development of rat embryos following application of injurious agents to male gametes].
It was shown that in the embryos whose fathers had been subjected to x-ray irradiation, there appeared pathological alterations involving all parts of the embryo, resulting in high postimplantation mortality. In contrast to x-ray irradiation, chloridine affecting male gametes did not result in the increased embryonic death rate and disorders in embryogenesis as compared with controls. It permitted a conclusion of the process of rat spermatogenesis being resistant to this preparation.


Therapeutic advances in second-line treatment of advanced non-small-cell lung cancer.
A majority of patients with lung cancer present with advanced disease: approximately 30% with locally advanced disease and 45% with metastatic disease. The prognosis for these patients is poor, with 5-year survival rates ranging from 5% to 15% for stage IIIB disease and < 5% for stage IV disease. For patients confronting advanced disease, chemotherapy is an essential option for disease control and palliation. Although a number of effective first-line regimens exist, virtually all patients with advanced non-small-cell lung cancer (NSCLC) will have disease relapse. For these patients, identifying the optimal treatment course remains a challenge. This article reviews approved and investigational second-line therapeutic options in patients with relapsed advanced NSCLC. Recently, docetaxel has been shown to improve survival in patients with advanced NSCLC who had progressive disease following treatment with platinum-containing chemotherapy. Subsequently, permetrexed was compared with docetaxel in a second-line treatment study that showed survival for both patient groups was virtually identical. Recently, erlotinib was associated with significantly longer survival compared with best supportive care in the second- or third-line treatment settings. Salvage treatment for NSCLC is reviewed, and the relative merits of the currently available treatments as well as agents that are pending Food and Drug Administration approval as second-line treatments are discussed.


Aspergillus volatiles regulate aflatoxin synthesis and asexual sporulation in Aspergillus parasiticus.
Aspergillus parasiticus is one primary source of aflatoxin contamination in economically important crops. To prevent the potential health and economic impacts of aflatoxin contamination, our goal is to develop practical strategies to reduce aflatoxin synthesis on susceptible crops. One focus is to identify biological and environmental factors that regulate aflatoxin synthesis and to manipulate these factors to control aflatoxin biosynthesis in the field or during crop storage. In the current study, we analyzed the effects of aspergillus volatiles on growth, development, aflatoxin biosynthesis, and promoter activity in the filamentous fungus A. parasiticus. When colonies of Aspergillus nidulans and A. parasiticus were incubated in the same growth chamber, we observed a significant reduction in aflatoxin synthesis and asexual sporulation by A. parasiticus. Analysis of the headspace gases demonstrated that A. nidulans produced much larger quantities of 2-buten-1-ol (CA) and 2-ethyl-1-hexanol (EH) than A. parasiticus. In its pure form, EH inhibited growth and increased aflatoxin accumulation in A. parasiticus at all doses tested; EH also stimulated aflatoxin transcript accumulation. In contrast, CA exerted dose-dependent up-regulatory or down-regulatory effects on aflatoxin accumulation, conidiation, and aflatoxin transcript accumulation. Experiments with reporter strains carrying nor-1 promoter deletions and mutations suggested that the differential effects of CA were mediated through separate regulatory regions in the nor-1 promoter. The potential efficacy of CA as a tool for analysis of transcriptional regulation of aflatoxin biosynthesis is discussed. We also identify a novel, rapid, and reliable method to assess norsolorinic acid accumulation in solid culture using a Chroma Meter CR-300 apparatus.


Comparison of Endoscopic Discectomy Versus Non-Endoscopic Discectomy for Symptomatic Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.
Systematic review. The authors aimed to systematically compare the effectiveness and safety of endoscopic discectomy (ED) with non-endoscopic discectomy (NED) for treatment of symptomatic lumbar disc herniation (LDH). A systematic search was performed on PubMed, EMBASE, the Cochrane Library and China National Knowledge Infrastructure for randomized controlled trial from inception until August 13, 2020. Trials which investigated multiple operative approaches on lumbar disc herniation were identified without language restrictions. In total, 25 trials involving 2258 patients with symptomatic LDH were included. Twenty trials performed the comparison between ED and NED. Five trials performed the comparison between percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). The operative time of micro-endoscopic discectomy (MED) was longer than open discectomy (OD). The length of hospital stay of percutaneous endoscopic lumbar discectomy (PELD) was shorter than fenestration discectomy (FD). Significant differences in intraoperative blood loss volumes were found between PELD with FD and MED with OD. The complication rate of PELD was lower than FD (PELD: 4.3%; FD: 14.6%) and the complication rate of full-endoscopic discectomy (FE) was lower than microscopic discectomy (MD) (FE: 13.4%; MD: 32.1%). PELD and FE have the advantage of limiting intraoperative damages. ED and NED can be both considered sufficient to achieve good clinical outcomes. PETD and PEID are able to achieve similar results but the learning curve of PETD was steeper. More independent high-quality RCTs with sufficiently large sample sizes performing cost-effectiveness analyzes are needed.


Prevalence and population analysis of Vibrio parahaemolyticus in aquatic products from South China markets.
Vibrio parahaemolyticus is a common foodborne pathogen in aquatic products. To investigate the prevalence of Vibrio parahaemolyticus in aquatic products in South China, 224 samples were collected from markets in four provinces (11 cities) from May 2013 to January 2014. One hundred and fifty isolates were isolated from 98 samples. All isolates were analyzed for the presence of thermostable direct haemolysin (TDH) and TDH-related haemolysin (TRH) by PCR, antibiotic susceptibility analysis by disk diffusion method, serotyping by multiplex PCR and molecular typing by enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) typing. Although all 150 isolates were negative for tdh, 61 strains were trh positive (40.67%). Antimicrobial susceptibility results indicated that most strains were resistant to streptomycin (88.67%), cefazolin (66.00%) and ampicillin (62.67%). All strains were susceptible to chloramphenicol. Forty percent of all isolates were O2 type. The 150 isolates were grouped into three clusters by ERIC-PCR typing. The results demonstrated the presence of V. parahaemolyticus in aquatic products from the retail market and this methodology can be used for microbiological risk assessment in China.


BOLA-DRB3 gene polymorphisms influence bovine leukaemia virus infection levels in Holstein and Holstein × Jersey crossbreed dairy cattle.
Bovine leukemia virus (BLV) infections, causing persistent lymphocytosis and lethal lymphosarcoma in cattle, have reached high endemicity on dairy farms. We observed extensive inter-individual variation in the level of infection (LI) by assessing differences in proviral load in peripheral blood. This phenotypic variation appears to be determined by host genetics variants, especially those located in the BoLA-DRB3 MHCII molecule. We performed an association study using sequencing-based typed BOLA-DRB3 alleles from over 800 Holstein and Holstein × Jersey cows considering LI in vivo and accounting for filial relationships. The DBR3*0902 allele was associated with a low level of infection (LLI) (<1% of circulating infected B-cells), whereas the DRB3*1001 and DRB3*1201 alleles were related to a high level of infection (HLI). We found evidence that 13 polymorphic positions located in the pockets of the peptide-binding cleft of the BOLA-DRB3 alleles were associated with LI. DRB3*0902 had unique haplotypes for each of the pockets: Ser13 -Glu70 -Arg71 -Glu74 (pocket 4), Ser11 -Ser30 (pocket 6), Glu28 -Trp61 -Arg71 (pocket 7) and Asn37 -Asp57 (pocket 9), and all of them were significantly associated with LLI. Conversely, Lys13 -Arg70 -Ala71 -Ala74 and Ser13 -Arg70 -Ala71 -Ala74 , corresponding to the DRB3*1001 and *1201 alleles respectively, were associated with HLI. We showed that the specific amino acid pattern in the DRB3*0902 peptide-binding cleft may be related to the set point of a very low proviral load level in adult cows. Moreover, we identified two BOLA-DRB3 alleles associated with a HLI, which is compatible with a highly contagious profile.


Hadamard-transform spectral acquisition with an acousto-optic tunable filter in a broadband stimulated Raman scattering microscope.
We present a novel configuration for high spectral resolution multiplexing acquisition based on the Hadamard transform in stimulated Raman scattering (SRS) microscopy. The broadband tunable output of a dual-beam femtosecond laser is filtered by a fast, narrowband, and multi-channel acousto-optic tunable filter (AOTF). By turning on and off different subsets of its 8 independent channels, the AOTF generates the spectral masks given by the Hadamard matrix. We demonstrate a seamless and automated operation in the Raman fingerprint and CH-stretch regions. In the presence of additive noise, the spectral measurements using the multiplexed method show the same signal-to-noise ratio of conventional single-wavenumber acquisitions performed with 4 times longer integration time.


[The effect of the degree of deacetylation of chitosan on the biocompatibility of chitosan membrane with corneal stromal cells].
Some different membranes were prepared by Chitosan with the degree of deacetylation (DD) of 63.7%, 73.7%, 83% and 97% respectively. To study the biocompatibility of Chitosan membrane toward corneal stromal cells, the rabbit cells were cultured on the surface of different DD chitosan membranes. The morphological characteristics, the cell-adhesion, the cell proliferation and the activity of LDH in the medium were investigated. The results of experiment shows that the DD of Chitosan has very significant effect on the biocompatibility of Chitosan membrane toward corneal stromal cells. The more DD of Chitosan, the less injury was made to corneal stromal cells by the chitosan membrane, which is favor of the growing and adhesion of corneal stromal cells. The biocompatibility of the membrane made with low DD Chitosan with corneal stromal cells became worse.


Substrates and products of purified rat liver bilirubin UDP-glucuronosyltransferase.
To determine whether the isoform of UDP-glucuronosyltransferase which catalyzes the formation of bilirubin monoglucuronide also mediates the formation of bilirubin diglucuronide and other specific sugar conjugates of bilirubin, Wistar rats were treated with clofibrate (300 mg per kg i.p. X 7 days); this resulted in a 200% increase in hepatic transferase specific activity for bilirubin. Proteins from hepatic microsomal fractions were solubilized, and the transferase isoform with activity toward bilirubin was purified by a combination of chromatofocusing, affinity chromatography and hydrophobic chromatography, to apparent homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified isoform catalyzed the formation of monoglucuronide and diglucuronide (with UDP-glucuronic acid as a cosubstrate), and glucoside and xyloside (with UDP-glucose and UDP-xylose as respective cosubstrates) of bilirubin and glucuronidation of the carcinogen metabolite 4'-hydroxydimethylaminoazobenzene. It also catalyzed the conversion of bilirubin monoglucuronide to diglucuronide (with UDP-glucuronic acid as cosubstrate, pH optimum 7.8), to mixed glucuronide-glucoside conjugate (with UDP-glucose as a cosubstrate) and to unconjugated bilirubin (with UDP as a cosubstrate, pH optimum 5.5). Each transferase activity was copurified at each purification step. Results of enzyme kinetic studies suggest that UDP-glucuronic acid, UDP-glucose and UDP-xylose recognize a common site. Transferase activities toward bilirubin were not detectable in homozygous Gunn rats liver microsomal fractions; in heterozygous Gunn rats, these activities were reduced by 40 to 60%. The results suggest that conjugation of bilirubin with glucuronic acid, glucose or xylose is catalyzed by a single transferase isoform.


[Tracheobronchial injuries and fistulas].
This paper reviews the pathophysiological processes occurring after contact of blood with artificial surfaces during continuous haemofiltration and the predominant role of platelets in the genesis of extracorporeal thrombosis. A basic prerequisite for effective renal replacement therapy is adequate anticoagulation in order to inhibit activation of coagulation and to avoid haemofilter clotting. Antithrombotic regimens controlling plasma coagulation activation and platelet-surface interactions, as well as methods of coagulation monitoring are reviewed. In patients at risk for bleeding, combined antithrombotic regimens with short-acting antiaggregatory prostaglandins and unfractionated or fractionated heparin were more effective in reducing bleeding complications and morbidity during and after haemofiltration then heparinisation alone. Heparinoids and hirudine are indicated in patients with heparin-induced thrombocytopenia II. In patients at risk for thromboembolism, regional citrate anticoagulation may be beneficial. Performing continuous haemofiltration without antithrombotic therapy is not recommended.


Ultrastructural pathology of neuronal membranes in the oedematous human cerebral cortex.
Surgical biopsies of frontal, parietal and temporal regions of thirty two patients with clinical diagnosis of congenital hydrocephalus, brain trauma, tumours, and vascular anomalies were examined with the transmission electron microscope. The main goal was to study the submicroscopic alterations of somatodendritic, axonal, and synaptic plasma membranes, cytomembranes, and the cytoskeleton. In both, moderate and severe oedema, fragmentation of plasma membrane, enlargement and focal necrosis of rough endoplasmic cisterns and nuclear envelope, detachment of membrane-bound ribosomes and reduction of polysome were observed. The degenerated myelinated axons exhibited discontinuities of the axolemma, disorganisation of multiple myelin lamellae, myelin sheath vacuolization, and formation of myelin ovoids. In severe oedema, synaptic disassembly was frequently found characterized by separate pre- and postsynaptic endings and loss of perisynaptic glial ensheathment. Fragmented and intact microtubules and actin-like filaments also were distinguished. The alterations of plasma membranes and cytomembranes are related with the anoxic-ischaemic conditions of brain parenchyma. The role of free radical and lipid peroxidation, disturbed energy metabolism, altered metabolic cascades, excitotoxicity, protein aggregation, and presence of extracellular oedema fluid is discussed in relation with the derangement of neuronal membranes.


Involuntary hospitalization, stigma stress and suicidality: a longitudinal study.
People with severe mental illness and a history of involuntary hospitalization may experience stigma-related stress and suffer negative consequences as a result. However, the long-term impact of stigma stress on suicidality in this population remains unknown. This longitudinal study therefore examined stigma stress, self-stigma, self-esteem and suicidal ideation among 186 individuals with mental illness and recent involuntary hospitalization. After adjusting for age, gender, diagnoses and symptoms, more stigma stress at baseline predicted suicidal ideation after 2 years, mediated by increased self-stigma and decreased self-esteem after 1 year. Anti-stigma interventions that reduce stigma stress and self-stigma could therefore support suicide prevention.


Endometrial adenocarcinoma presenting in a voided urine cytology specimen: Case report.
Though the primary diagnostic utility of urine cytology is in the detection of high grade urothelial carcinoma, malignancies other than those of urinary tract origin may also be present. Direct invasion of the bladder by an adjacent neoplasm, metastasis from a distant primary, or inadvertent contamination during specimen collection may all result in nonurothelial tumor cells being present in a urine cytology specimen. Here, we report a case of endometrial adenocarcinoma that was first identified in a voided urine specimen collected for the routine evaluation of hematuria. The presence of cohesive clusters with apparent glandular differentiation raised the possibility of a nonurothelial neoplasm and prompted an additional workup. Immunohistochemical stains performed on cell block material demonstrated that the glandular cells were positive for PAX8 and negative for GATA3, suggestive of gynecologic origin. A subsequent endometrial curettage and hysterectomy revealed endometrial adenocarcinoma. When faced with papillary groups in a voided urine specimen, the cytopathologist must remember to consider a broad differential diagnosis to include malignancies outside of the urinary tract. It was our awareness of valuable clinical information and keen cytologic assessment which allowed for an accurate diagnosis in the setting of this unexpected finding.


Cardiac calmodulin-stimulated protein phosphatase: purification and identification of specific sarcolemmal substrates.
A calmodulin-stimulated protein phosphatase has been purified from bovine myocardium. The purification procedure involves sequential DEAE-Sephacel ion exchange chromatography, calmodulin-Sepharose affinity chromatography, and high performance liquid chromatography using a Spherogel TSK DEAE 5PW column. By SDS polyacrylamide gel electrophoresis, the purified cardiac phosphatase consists of two subunits of Mr 61,000 and 19,000, similar to the brain enzyme, calcineurin. Protein phosphatase activity of the cardiac enzyme is stimulated by Ca2+-calmodulin and inhibited by the calmodulin antagonist drug, calmidazolium. Effects of a series of divalent cations on catalytic activity of the cardiac calmodulin-stimulated protein phosphatase are similar to those observed with calcineurin, when the two enzymes are assayed under identical conditions. Highly enriched preparations of bovine cardiac sarcolemma contain substrates of cAMP-dependent protein kinase of Mr 166 K, 133 K, 108 K, 79 K, 39 K, and 14 K, which are specifically dephosphorylated by the calmodulin-stimulated phosphatase with pseudofirst-order rate constants of 0.23, 0.46, 0.69, 0.35, 0.69, and 0.115 min-1, respectively. These substrates are not present in purified preparations of cardiac sarcoplasmic reticulum. These results support a role of the calmodulin-stimulated phosphatase in the Ca2+-regulation of specific sarcolemmal processes by protein dephosphorylation.


Growth kinetics of colloidal chains and labyrinths.
Particles interacting by a combination of isotropic short-range attraction and long-range repulsion have been shown to form complex phases despite the apparent simplicity of the interparticle potential. Using computer simulations we study the behavior of two-dimensional systems of colloids with such an interaction, focusing on how area fraction and repulsion range at fixed repulsion gradient may be used to tune the resulting kinetics and nonequilibrium structure. While the short-range attraction leads to aggregation, the long-range repulsion encourages growth of chains of particles due to repulsive intercluster interactions. Depending on area fraction/repulsion range we observe chain labyrinths, chain-compact aggregate coexistence, and connected networks of chains. The kinetics of cluster growth displays a sequence of connected networks and disconnected cluster or chain systems with increasing repulsion range, indicating the competing roles of connectivity of growing chains and repulsion-driven breakup of chains into compact aggregates. Chain-dominated systems show approximately logarithmic coarsening at late time that we interpret as the result of chains performing random walks in the randomly fluctuating potential landscape created by their neighbors, a situation reminiscent of glassy systems.


The impact of mycotoxicoses on human history.
Mycotoxicoses are acute or chronic diseases of humans and animals caused by mycotoxins, toxic compounds produced by moulds. Of about 400 known mycotoxins only a small number are known to cause mycotoxicoses in humans. Organs that are most targeted are those in which mycotoxins are metabolised, that is, the liver and kidneys, but the lesions may affect the neurological, respiratory, digestive, haematological, endocrine, and immune systems as well. The epidemics of mycotoxicoses are often connected with times of famine, when population consumes food that would not be consumed in normal circumstances. Mycotoxicoses have influenced human history, causing demographic changes, migrations, or even influencing the outcomes of wars. Fortunately, epidemics affecting so many persons and with so many fatalities belong to the past. Today they only appear in small communities such as schools and factory canteens. This paper presents epidemics and pandemics of mycotoxicoses that influenced human history.


In situ carcinomas of the breast. Types, growth pattern, diagnosis, and treatment.
The paper presents a prospective study comprising 40 consecutive patients with in situ carcinomas of the breast and two with atypical ductal hyperplasia (ADH) who underwent operation during a 2-year period at a single hospital. Out of the 40 in situ carcinomas 13 were of the lobular type (LCIS) and 27 of the ductal type (DCIS). They made up about 9% of all newly diagnosed breast cancers. Histologically a distinction could be made between three different growth patterns: microfocal, tumour-forming, and a diffuse form. With the exception of one case, the 26 microfocal growths (2 ADH, 13 LCIS, 11 DCIS) were accidental findings in otherwise benign breast biopsies, whereas the tumour-forming and diffuse forms (16 DCIS) were diagnosed in the great majority clinically and/or by mammography. Of the tumour-forming and diffuse DCIS 25% were demonstrated solely by mammography. The surgical treatment in the 26 patients showing microfocal changes was exclusively biopsy in 23, while three had mastectomy, because of a papillary focus in two and patient preference in one. Of six patients with tumour-forming DCIS three had segmental resection and three mastectomy, the latter because of papillary foci, while all 10 with diffuse growth had mastectomy. On the basis of their experience of types and growth patterns, the authors set up a surgical strategy which might add new aspects to our knowledge about the biological nature of in situ lesions.


Immunothrombosis and the molecular control of tissue factor by pyroptosis: prospects for new anticoagulants.
The interplay between innate immunity and coagulation after infection or injury, termed immunothrombosis, is the primary cause of disseminated intravascular coagulation (DIC), a condition that occurs in sepsis. Thrombosis associated with DIC is the leading cause of death worldwide. Interest in immunothrombosis has grown because of COVID-19, the respiratory disease caused by SARS-CoV-2, which has been termed a syndrome of dysregulated immunothrombosis. As the relatively new field of immunothrombosis expands at a rapid pace, the focus of academic and pharmacological research has shifted from generating treatments targeted at the traditional 'waterfall' model of coagulation to therapies better directed towards immune components that drive coagulopathies. Immunothrombosis can be initiated in macrophages by cleavage of the non-canonical inflammasome which contains caspase-11. This leads to release of tissue factor (TF), a membrane glycoprotein receptor that forms a high-affinity complex with coagulation factor VII/VIIa to proteolytically activate factors IX to IXa and X to Xa, generating thrombin and leading to fibrin formation and platelet activation. The mechanism involves the post-translational activation of TF, termed decryption, and release of decrypted TF via caspase-11-mediated pyroptosis. During aberrant immunothrombosis, decryption of TF leads to thromboinflammation, sepsis, and DIC. Therefore, developing therapies to target pyroptosis have emerged as an attractive concept to counteract dysregulated immunothrombosis. In this review, we detail the three mechanisms of TF control: concurrent induction of TF, caspase-11, and NLRP3 (signal 1); TF decryption, which increases its procoagulant activity (signal 2); and accelerated release of TF into the intravascular space via pyroptosis (signal 3). In this way, decryption of TF is analogous to the two signals of NLRP3 inflammasome activation, whereby induction of pro-IL-1β and NLRP3 (signal 1) is followed by activation of NLRP3 (signal 2). We describe in detail TF decryption, which involves pathogen-induced alterations in the composition of the plasma membrane and modification of key cysteines on TF, particularly at the location of the critical, allosterically regulated disulfide bond of TF in its 219-residue extracellular domain. In addition, we speculate towards the importance of identifying new therapeutics to block immunothrombotic triggering of TF, which can involve inhibition of pyroptosis to limit TF release, or the direct targeting of TF decryption using cysteine-modifying therapeutics.


Amelioration of metabolic acidosis by dietary potassium restriction in hyperkalemic patients with chronic renal insufficiency.
Hyperkalemia has been implicated in the pathogenesis of metabolic acidosis in chronic renal insufficiency because acidosis is ameliorated after administration of medications that correct hyperkalemia: mineralocorticoids, diuretics, intestinal K+-binding agents. However, the acidosis-ameliorating effect of these medications may be a consequence not of their ability to correct hyperkalemia, but of their ability to directly stimulate renal or intestinal excretion of acid. To investigate the specific effect of correcting hyperkalemia, balance studies were performed wherein hyperkalemia was corrected solely by restriction of dietary K+ in three patients with moderate chronic renal insufficiency (Ccreat 36, 44, and 58 ml/min/1.73 m2, respectively). Reduction of K+ intake was effected by substitution of Na+ for K+ in the electrolyte supplement to a whole-food diet of low K+ content. This maneuver resulted in correction of hyperkalemia and sustained amelioration of metabolic acidosis in each patient. Net acid excretion increased only transiently, and not enough to fully account for the magnitude of the increment in plasma [HCO3-], suggesting that an extrarenal mechanism of HCO3- input to the systemic circulation was the major factor that ameliorated the systemic acidosis. Evidence of an extrarenal mechanism was obtained only during the phase of decreasing plasma [K+]. Subsequently, during sustained normokalemia, the increased plasma [HCO3-] was maintained as a consequence of a sustained increase in total renal H+ secretion, evidenced by complete reabsorption of the increased filtered load of HCO3- and no reduction in net acid excretion from control values. These results indicate that in some patients with moderate chronic renal insufficiency, metabolic acidosis is ameliorated when hyperkalemia is corrected by restriction of dietary K+ (Na+ substitution) without otherwise changing diet composition and without administration of medication. Amelioration of the acidosis is predominantly effected by extrarenal mechanisms, and is sustained by an increase in the set point at which plasma [HCO3-] is regulated by the kidney.


A study evaluating noise levels at selected schools in the Czech Republic.
Worldwide, primary schools are the most important segment of childhood education. The main disturbing source of noise in schools is human speech, the primary component of the learning process. School noise has a negative impact on information processing, teachers and pupils, and communication in the classroom. The study aimed at assessing A-weighted sound pressure levels in primary school classrooms. It was concerned with A-weighted sound pressure levels and their fluctuation during various classes. The noise was measured with the static calibrated Brüel and Kjær 2260 Investigator sound level meter. The sound pressure levels were measured twice in 12 classes as 11 different subjects were taught to reduce the uncertainty of results due to their potential variability in time. From the instantaneous values, LA (t), equivalent continuous A-weighted sound pressure levels (LAeq,T) and LAmax were calculated. The mean equivalent A-weighted sound pressure level during lessons irrespective of age and subjects taught was 68.0 ± 3.4 dB (uncertainty of measurement). The highest levels of noise were in physical education and arts; the lowest levels were found for English taught as a foreign language. There were no statistically significant differences in LAeq,T depending on the numbers of children in the classes. The main source of noise is pupils. Attention should be paid to negative feelings of noise to reduce LAeq,T in schools. Continuous noise pollution, in combination with stress and the mentally demanding nature of the teaching profession, may lead to numerous negative effects on human personality.


Transitory development of rough endoplasmic reticulum aggregates during embryo maturation in seeds of mustard (Sinapis alba L.).
During the final period of maturation of mustard (Sinapis alba L.) seeds conspicuous aggregates of rough endoplasmic reticulum are found specifically in some tissues of the differentiation zone of the radicle. The appearance of these structures is temporally correlated with the disappearance of single-stranded reticulum and the onset of seed dehydration. These aggregates can be demonstrated also in the dry, mature seed and during the first few hours after imbibition with water; they disappear however during germination. In germinated root tips reformation of the aggregates can be induced by severe water stress. It is concluded that the observed membrane aggregates represent a storage form of rough endoplasmic reticulum during periods of low protoplasmic hydration.


Interparticle interactions and direct imaging of colloidal phases assembled from microsphere-nanoparticle mixtures.
We investigate the interparticle interactions, phase behavior, and structure of microsphere-nanoparticle mixtures that possess high size and charge asymmetry. We employ a novel Monte Carlo simulation scheme to calculate the effective microsphere interactions in suspension, yielding new insight into the origin of the experimentally observed behavior. The initial settling velocity, final sediment density, and three-dimensional structure of colloidal phases assembled from these binary mixtures via gravitational settling of silica microspheres in water and index-matched solutions exhibit a strong compositional dependence. Confocal laser scanning microscopy is used to directly image and quantify their structural evolution during assembly. Below a lower critical nanoparticle volume fraction (phi(nano) < phi(L,C)), the intrinsic van der Waals attraction between microspheres leads to the formation of colloidal gels. These gels exhibit enhanced consolidation as phi(nano) approaches phi(L,C). When phi(nano) exceeds phi(L,C), an effective repulsion arises between microspheres due to the formation of a dynamic nanoparticle halo around the colloids. From this stable fluid phase, the microspheres settle into a crystalline array. Finally, above an upper critical nanoparticle volume fraction (phi(nano) > phi(U,C)), colloidal gels form whose structure becomes more open with increasing nanoparticle concentration due to the emergence of an effective microsphere attraction, whose magnitude exhibits a superlinear dependence on phi(nano).


Virtual reality applications for motor rehabilitation after stroke.
Hemiparesis is the primary physical impairment underlying functional disability after stroke. A goal of rehabilitation is to enhance motor skill acquisition, which is a direct result of practice. However, frequency and duration of practice are limited in rehabilitation. Virtual reality (VR) is a computer technology that simulates real-life learning while providing augmented feedback and increased frequency, duration, and intensity of practiced tasks. The rate and extent of relearning of motor tasks could affect the duration, effectiveness, and cost of patient care. The purpose of this article is to review the use of VR training for motor rehabilitation after stroke.


Receptivity to e-cigarette marketing, harm perceptions, and e-cigarette use.
To test whether exposure and receptivity to e-cigarette marketing are associated with recent e-cigarette use among young adults through increased beliefs that e-cigarettes are less harmful than cigarettes. Data were collected from 307 multiethnic 4- and 2-year college students; approximately equal proportions of current, never, and former cigarette smokers [mean age = 23.5 (SD = 5.5); 65% female]. Higher receptivity to e-cigarette marketing was associated with perceptions that e-cigarettes are less harmful than cigarettes, which in turn, were associated with higher recent e-cigarette use. The findings provide preliminary support to the proposition that marketing of e-cigarettes as safer alternatives to cigarettes or cessation aids is associated with increased e-cigarette use among young adults. The findings have implications for development of e-cigarette regulations.


Deficit irrigation improves phenolic content and antioxidant activity in leafy lettuce varieties.
This study investigated the effect of deficit irrigation at three management allowable depletion levels (MAD) 25%, 50%, and 75% on phytochemicals, ascorbic acid, antioxidant activity, glucose, fructose, and fresh and dry mass in two green leafy lettuce cultivars (Lollo Bionda and Vera) at harvest. Genotype response was observed during deficit irrigation on fresh and dry mass at harvest. Vera revealed similar fresh mass at MAD levels 25% and 50%. Chicoric acid, caftaric acid, and chlorogenic and caffeic acid tended to increase at 50% MAD, while kaempferol, quercetin, and myricetin increased at 75% MAD in both cultivars indicating increasing antioxidant properties. Ascorbic acid content declined with increasing MAD levels and no definite trend on β-carotene content was noted in these cultivars with respect to MAD irrigation. Deficit irrigation at 50% and 70% increased glucose concentration in cv. Lollo Bionda. Deficit irrigation influences the abiotic stress condition that stimulates the biosynthesis of phytochemicals in plants and improves crop quality. However, deficit irrigation can affect marketable crop yield. Based on findings of this study, the lettuce cv. Vera can be recommended as a suitable cultivar for deficit irrigation (at MAD 50% levels) for improving dietary phytochemicals and crop quality without compromising fresh mass for marketing.


Post cardiac arrest therapeutic hypothermia in adult patients, state of art and practical considerations.
The importance of therapeutic hypothermia in selected categories of patients has been widely demonstrated. Laboratory, animal, and human studies permitted to understand the molecular mechanisms underlying cooling and its importance in preventing the ischemia/reperfusion injury of the brain. The development of new technologies offered the possibility to reach the desired temperature effectively and rapidly, reducing related side effects. Nevertheless, the application of systematic protocols of cooling has not been adequately reached in many hospitals. In this paper the most recent findings regarding hypothermia, its physiological bases and ways of application are reviewed.


Triplet chemotherapy in patients with metastatic colorectal cancer: toward the best way to safely administer a highly active regimen in clinical practice.
A major problem concerning the addition of more drugs in a chemotherapy combination is designing a proper schedule assuring the balance between dose intensity of each drug, efficacy of the combination, and tolerability lessening the burden of drug toxicity. We evaluated triplet chemotherapy-based intensive regimens proposed as first-line treatment in patients with metastatic colorectal cancer. Using a FOLFOXIRI (5-fluorouracil [5-FU], irinotecan, and oxaliplatin) combination regimen, patients with metastatic colorectal cancer now have the possibility of longer survival, but disappointingly, with increased toxicities. Triplet chemotherapy regimen according to 5-fluorouracil, irinotecan /5-fluorouracil, oxaliplatin, characterized by timed flat-infusion 5-FU administration, without leucovorin, obtained efficacy equivalent to other reported similar combination regimens (5-FU, irinotecan, and oxaliplatin), with increased received 5-FU dose intensity and lower grade 3 to 4 neutropenia. To guarantee the proper balance between dose intensities, efficacy, and toxicity, triplet chemotherapy schedules could be further improved by abrogation of folinic acid and bolus 5-FU, a new and easy modality of 5-FU administration, such as timed flat-infusion 5-FU, associated with alternating irinotecan and oxaliplatin; this could favor diffusion of this intensive treatment in clinical practice.


Effect of Virgin Coconut Oil Application on the Skin of Preterm Newborns: A Randomized Controlled Trial.
Preterm constitutes a major part of neonatal mortality, particularly in India. Due to dermal immaturity, preterm neonates are susceptible to various complications like infection, hypothermia, etc. Emollient application is a traditional practice in our subcontinent. To find out the efficacy of coconut oil application for skin maturity, prevention of sepsis, hypothermia and apnea, its effect on long-term neurodevelopment and adverse effect of it, if any. A randomized controlled trial was conducted in the rural field practice area of Department of Community Medicine, Burdwan Medical College from March 2014 to August 2018. Preterm born in the study period was divided into Group A (received virgin coconut oil application) and Group B (received body massage without any application). Neonatal skin condition was assessed on 7th, 14th, 21st and 28th day of life. Neurodevelopmental status was assessed on 3rd, 6th and 12th months. A total of 2294 preterm were included in the study. Groups A and B consisted of 1146 and 1148 preterm infants, consecutively. Mean gestational age of the study population was 31.9 ± 3.4 weeks and 50.4% were male. Mean weight loss in first few days was less in group A but mean weight gain per day was higher in group B. Lesser incidences of hypothermia and apnea, and better skin maturity and neurodevelopmental outcome were noted in group A. No significant adverse effect was noted with coconut oil application. Use of coconut oil helps in dermal maturity and better neurodevelopmental outcome. Further studies are warranted for universal recommendation.


Biomarkers of reproductive toxicity.
A biomarker can be broadly defined as any biological index capable of being measured, which is associated with or indicative of a defined biological endpoint such as a developmental or disease stage. Identification and verification of anatomical, endocrine, cellular and molecular biomarkers is crucial for successful clinical diagnosis and treatment of toxicity and disease, as well as basic toxicological, epidemiological and other research. Various biomarkers of reproductive development and health have been identified, including those associated with pubertal development, adult reproductive health and pregnancy outcome. Herein we discuss those in situ biomarkers which have been more closely associated with toxicant action on the reproductive system. Biomarkers of toxicant exposure and susceptibility are addressed, but the majority of the review focuses on those biomarkers which may prove useful for determining current pathophysiological status or predicting future adverse outcomes. In males these are primarily associated with altered spermatogenesis and sperm parameters, and in females with altered endocrine function. We conclude that although few robust in situ biomarkers are currently available which are specific for toxicant exposure, susceptibility or effect in reproductive systems, there is expectation that post-genomic technologies offer a new paradigm for identifying and verifying such biomarkers as may exist.


Proliferation, phenotype, and cytotoxicity of human lymphocytes isolated from lymph nodes invaded by melanoma cells.
The effects of human recombinant interleukin-4 (rIL-4) on metastatic melanoma (lymph node)-derived T lymphocytes cultured with human recombinant interleukin-2 (rIL-2) were studied. Lymphocytes isolated from melanoma-invaded lymph nodes were cultured in media with rIL-2 in the presence (MB-2,4) or absence (MB-2) or rIL-4 for up to 48 days. A majority of lymphocytes grown in both cultures were CD3+ T lymphocytes. Addition of rIL-4 to the rIL-2 culture abrogated the growth of the CD3-, CD56+ cell population [natural killer (NK) cell], which were present in culture with rIL-2 alone. Lymph-node-derived T lymphocytes that had expanded under MB-2,4 conditions lysed only autologous melanoma cells and they maintained the autologous-specific cytolytic activity during the entire culture period. They did not lyse K562, Daudi, or allogeneic target cells. Monoclonal antibodies (MAbs) against CD3 molecules and MHC class I molecules but not MHC class II molecules inhibited the specific lytic functions of T lymphocytes under MB-2,4 culture conditions. Collectively, these data indicate that in lymphocyte culture derived from melanoma-invaded lymph nodes, rIL-4 inhibits the rIL-2-dependent proliferation of NK cells and antigen nonspecific killer T lymphocytes and also effectively abrogates the rIL-2-induced NK and lymphokine-activated killer (LAK) activities.


ATRP from an amino acid-based initiator: A facile approach for α-functionalized polymers.
A L-valine-derived α-haloamide was synthesized and investigated as an initiator for the atom transfer radical polymerization of tert-butyl acrylate using commercially available CuBr, CuBr(2) and N,N,N',N",N"-pentamethyldiethylenetriamine as the catalyst and ligand system. Kinetic studies and extension to a diblock copolymer with styrene, each indicated that the polymerizations were well controlled. Poly(tert-butyl acrylate) having M(n) (NMR) = 8.6 kDa, M(n) (GPC) = 8.3 kDa, PDI = 1.11 and a diblock of poly(tert-butyl acrylate)-b-polystyrene having M(n) (NMR) = 20.2 kDa, M(n) (GPC) = 22.5 kDa, PDI = 1.22 were prepared by the sequential polymerization of tert-butyl acrylate and styrene at 55 °C and 90 °C, respectively.


Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study.
The renin-angiotensin system is a key regulator of blood pressure (BP), with inhibitors of angiotensin-converting enzyme (ACE) used clinically to treat hypertension and other cardiovascular conditions. ACE2 is a newly identified member of this system, which converts angiotensin II to angiotensin, and of which the occurrence in plasma has not been investigated. The aim of this study was to determine the heritability of circulating ACE, ACE2, and neprilysin (NEP), which may also be a regulator of BP, in a family study, and to determine covariates that contribute to the variation in plasma activity. ACE, ACE2, and NEP activities were measured in plasma from 534 subjects in the Leeds Family Study using selective fluorogenic substrates. Genetic factors accounted for 24.5%, 67%, and 22.7% of the phenotypic variation in circulating ACE, ACE2, and NEP, respectively. ACE insertion/deletion polymorphism and other measured covariates accounted for 23.8% of variance in circulating ACE. High-density lipoprotein cholesterol was a significant determinant of circulating ACE2. Measured covariates accounted for 17.3% of variation in circulating NEP. ACE and NEP were associated with systolic and diastolic BP in univariate analyses; however, only ACE was independently associated with systolic and diastolic BP after accounting for covariates and shared childhood household.


Direct measurements of mass-specific optical cross sections of single-component aerosol mixtures.
The optical properties of atmospheric aerosols vary widely, being dependent upon particle composition, morphology, and mixing state. This diversity and complexity of aerosols motivates measurement techniques that can discriminate and quantify a variety of single- and multicomponent aerosols that are both internally and externally mixed. Here, we present a new combination of techniques to directly measure the mass-specific extinction and absorption cross sections of laboratory-generated aerosols that are relevant to atmospheric studies. Our approach employs a tandem differential mobility analyzer, an aerosol particle mass analyzer, cavity ring-down and photoacoustic spectrometers, and a condensation particle counter. This suite of instruments enables measurement of aerosol particle size, mass, extinction and absorption coefficients, and aerosol number density, respectively. Taken together, these observables yield the mass-specific extinction and absorption cross sections without the need to model particle morphology or account for sample collection artifacts. Here we demonstrate the technique in a set of case studies which involve complete separation of aerosol by charge, separation of an external mixture by mass, and discrimination between particle types by effective density and single-scattering albedo.


Y3+@CdTe quantum dot nanoprobe as a fluorescence signal enhancement sensing platform for the visualization of norfloxacin.
Quinolone antibiotics (norfloxacin) pose a serious threat to animal and human health due to their misuse and difficulty in being broken down in surface water and food. Rapid and effective detection of norfloxacin (NOR) is essential for environmental testing and ecosystems. In this study, yttrium was coordinated with mercaptopropionic acid (MPA)-modified CdTe quantum dots (QDs) to obtain a novel fluorescence sensor Y3+@CdTe QDs for the sensitive detection of NOR. NOR can bind to Y3+ to form a complex (NOR-Y3+). This complex enhances the luminescence of NOR and blue-shifts to 423 nm. The fluorescence intensity of NOR-Y3+ at 423 nm (I423) gradually increased with increasing NOR concentration; meanwhile, the fluorescence intensity of CdTe QDs at 634 nm (I634) gradually decreased due to aggregation induction. The ratio of I423 to I634 was used for the quantitative determination of NOR. The linear range of the constructed fluorescent probes was from 1.0 to 150.0 μM, with a detection limit of 31.8 nM. CdTe QDs act as a red fluorescent background, and with the addition of NOR, the color of the system transitions from red to purple and finally blue. This method was rapid (immediate) and visual, providing a simple analysis of various actual samples (tap water, lake water, honey, milk and human serum) for NOR.


Effect of triptorelin on lower urinary tract symptoms in Australian prostate cancer patients.
Prostate cancer is often comorbidly associated with lower urinary tract symptoms (LUTS), but few studies have assessed the effects of androgen deprivation therapy on LUTS in this patient group. We conducted a prospective, noninterventional, multicenter, observational study to assess the effectiveness of triptorelin (11.25 mg every 12 weeks) over 48 weeks in men presenting with local stage T3/4 prostate cancer and moderate to severe LUTS (International Prostate Symptom Score [IPSS] >7) in a routine practice setting in Australia. Of the 44 men who enrolled, effectiveness data were available for 39 men. By the end of the study, 30% of men no longer met the IPSS criteria for moderate to severe LUTS. The proportion of patients with moderate to severe LUTS was 69.6% (16/23) at week 48 and 76.9% (30/39) at the last available visit (coprimary outcomes). An IPSS reduction of ≥3 from week 0 was observed in 47% of men at week 4, 56% at week 24, 61% (14/23) at week 48, and 61.5% (24/39) at the last available visit. Quality of life was rated as mostly satisfied-to-delighted by 39.5% of patients at week 0, 53.9% at week 24, and 77.3% at week 48. Triptorelin was well tolerated with 8 treatment-related adverse events reported, half of which were hot flushes; 5 patients discontinued due to the reported treatment-related adverse events. This observational study suggests that triptorelin improves moderate to severe LUTS in prostate cancer patients in a routine clinical practice setting.


Mapped clock oscillators as ring devices and their application to neuronal electrical rhythms.
The mapped clock oscillator (MCO) is a second-order, Winfree-type oscillator generating two instantaneous clock variables (amplitude and phase) that are mapped to an observable output variable (voltage) via a static nonlinearity. Two fundamental classes of ring devices are presented. Their respective dynamics give rise to two oscillator forms--the labile clock and the clock--which can be coupled together in various configurations to create higher-order systems with sufficient complexity to capture the dynamics of neuronal assemblies. To demonstrate the applicability of MCOs in modelling neuronal rhythms, a hippocampal network model of four coupled oscillators was constructed and shown to exhibit rhythmic activity of varying complexity, depending on model parameters. The dynamics of the network were quantified through estimation of the maximum lyapunov exponent and the correlation dimension. Synthesis of complex neuronal rhythms may have therapeutic implications. The modular and efficient design of the MCO should facilitate the process of implementing coupled MCO networks in electronic hardware as potential neural prostheses for treating dynamic diseases such as epilepsy.


Spontaneous haemorrhage into a large abducens nerve schwannoma: a case report.
Purpose: Abducens schwannomas are rare tumors that are not known to present with acute haemorrhage. We present a case of a 59 year-old female on warfarin who presented acutely with a sudden onset headache, nausea and photophobia. Neuroimaging revealed an acute haemorrhage into a lesion that entered Dorello's canal and was consistent with an abducens nerve schwannoma.Materials and methods: The patient's case notes, imaging, histology and operative recording were reviewed retrospectively to compile this case report.Results: The tumor was resected via a retro-mastoid approach with sacrifice of the abducens nerve. Removal of the haematoma intra-operatively provided more space in the surgical corridor to facilitate resection. Final histological examination confirmed the diagnosis of schwannoma and the patient made a good post-operative recovery.Conclusion: We conclude that accurate pre-operative radiological diagnosis can facilitate surgical planning and removal of haematoma at an early stage during the operation can create space and facilitate resection. Furthermore, abducens schwannoma should be considered in the differential diagnosis of any heamorrhagic cerebello-pontine angle lesion.


Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes.
Acquired bone marrow failure syndromes encompass a unique set of disorders characterized by a reduction in the effective production of mature cells by the bone marrow (BM). In the majority of cases, these syndromes are the result of the immune-mediated destruction of hematopoietic stem cells or their progenitors at various stages of differentiation. Microbial infection has also been associated with hematopoietic stem cell injury and may lead to associated transient or persistent BM failure, and recent evidence has highlighted the potential impact of commensal microbes and their metabolites on hematopoiesis. We summarize the interactions between microorganisms and the host immune system and emphasize how they may impact the development of acquired BM failure.


Capoeira Angola: An alternative intervention program for traumatized adolescent refugees from war-torn countries.
Following resettlement in Australia, young traumatized refugees often face social challenges, including language and cultural barriers and social adjustment, which can lead to behavioral difficulties. Providing support at this vulnerable stage is therefore vital for reducing future setbacks. The STARTTS Capoeira Angola program was developed to help traumatized adolescents successfully integrate into their school environments. As an Afro-Brazilian martial art that incorporates dance, Capoeira appeared an appropriate intervention for adolescent refugees due to its unique ethos of empowerment and group membership. 32 refugeesfrom Middle Eastern and African countries (aged12-17) from the Intensive English Centre (IEC) department of the participant schools were assessed pre- and post- intervention using the Teacher's Strengths and Difficulties Scale (SDQ). Teachers were also asked to observe the students' functioning in a range of different situations at school. A significant overall decrease in behavioral problems was observed, which was associated with improvements in interpersonal skills, confidence, respect for self and others, self-discipline, and overall sense of responsibility.


Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids, with Cranial and Caudal Extension.
A 23-year-old lady presented with vertigo and imbalance in walking, blurring of vision, diplopia, and headache, in addition to numbness in the lower limbs over a period of six days. On examination patient had nystagmus, ataxia, positive Romberg test, and hyperreflexia. MRI examination of the brain and spinal cord showed evidence of faint bright signal intensity foci in T2/FLAIR involving bilateral cerebral hemispheres, subcortical deep white matter, bilateral thalami, posterior pons and left brachium pontis, and basal ganglia, with small nodular enhancement that aligned along curvilinear structures; those lesions also were apparent along the spinal cord at multiple levels. The clinical and radiological features suggested CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) syndrome. Symptoms improved dramatically with high dose oral corticosteroids. Our report addresses the radiological and clinical pattern of a case of CLIPPERS rhombencephalitis, with added superior and inferior extension to involve the brain and spinal cord, which is to emphasize the importance of raising the awareness of this disease and the combined role of radiologist and physicians for the diagnosis of this potentially treatable entity, responsive to glucocorticosteroid immunosuppression.