Appraisal of the sensitising potential of orally and dermally administered mercaptobenzothiazole by a biphasic protocol of the local lymph node assay.
Mercaptobenzothiazole (MBT) is used while manufacturing natural rubber products. Our study deals with assessing its allergenic potential following dermal and oral routes of exposure, using a biphasic local lymph node assay (LLNA). Female Balb/c mice were treated with MBT (dermally 3, 10, 30% concentrations in DMSO; orally 1, 10, 100 mg/kg doses in corn oil) on the back (dermal study) or through oral administration (oral study) on days 1-3 followed by auricular application of 3, 10 and 30% concentrations, respectively, on days 15-17. End points determined on day 19 included ear thickness, ear punch weight, lymph node weight, lymph node cell count, and lymphocyte subpopulations (CD4+, CD8+, CD45+). After dermal application of 3% or 10% solution, a significant increase in cell count and lymph node weight along with significant decrease in CD8+ cells was observed. After initial oral administration of 1 mg/kg, we noticed a significant amplification in cell count. Following oral administration of 10 mg/kg, we observed a similar increase in cell count and lymph node weight. The results of our study show that the modified biphasic LLNA protocol can be used to study the sensitising potential of a compound also following the oral route of exposure.


Subtype identification in acutely dissociated rat nodose ganglion neurons based on morphologic parameters.
Nodose ganglia are composed of A-, Ah- and C-type neurons. Despite their important roles in regulating visceral afferent function, including cardiovascular, pulmonary, and gastrointestinal homeostasis, information about subtype-specific expression, molecular identity, and function of individual ion transporting proteins is scarce. Although experiments utilizing the sliced ganglion preparation have provided valuable insights into the electrophysiological properties of nodose ganglion neuron subtypes, detailed characterization of their electrical phenotypes will require measurements in isolated cells. One major unresolved problem, however, is the difficulty to unambiguously identify the subtype of isolated nodose ganglion neurons without current-clamp recording, because the magnitude of conduction velocity in the corresponding afferent fiber, a reliable marker to discriminate subtypes in situ, can no longer be determined. Here, we present data supporting the notion that application of an algorithm regarding to microscopic structural characteristics, such as neuron shape evaluated by the ratio between shortest and longest axis, neuron surface characteristics, like membrane roughness, and axon attachment, enables specific and sensitive subtype identification of acutely dissociated rat nodose ganglion neurons, by which the accuracy of identification is further validated by electrophysiological markers and overall positive predictive rates is 89.26% (90.04%, 76.47%, and 98.21% for A-, Ah, and C-type, respectively). This approach should aid in gaining insight into the molecular correlates underlying phenotypic heterogeneity of nodose ganglia. Additionally, several critical points that help for neuron identification and afferent conduction calibration are also discussed.


Microstructures, mechanical behavior, cellular response, and hemocompatibility of bulk ultrafine-grained pure tantalum.
Bulk ultrafine-grained (UFG) pure Ta had been successfully prepared by equal channel angular pressing (ECAP) technique till eight passes. The 1st, 2nd, 4th, and 8th ECAPed Ta samples were investigated in the current study, with the 0th ECAPed Ta sample as the microcrystalline counterpart control. The microstructure and grain size distribution were characterized by X-ray diffractometer patterns, scanning electron microscopy, and transmission electron microscopy analysis by means of histogram. Although the mechanical behavior of all the experimental samples were analyzed through uniaxial tensile measurement and microhardness test, in vitro biological interactions onto the substrates such as protein adsorption, cellular responses derived from different types of cell lines, and the activity of erythrocyte and platelets were further evaluated and specifically assessed by bicinchoninic acid assay, enzyme-linked immunosorbent assay, and the method of colorimetric reading. A superior percentage of protein adsorption can be observed on the substrate of the UFG 8th ECAPed Ta (around 90%), even above those on the tissue culture plate (control) and the other ECAPed Ta samples. Furthermore, the UFG 8th ECAPed Ta shows no cytotoxic within 4 days culture when incubated with the murine fibroblast cell lines (L929). In addition, a priority order in the growth of endothelial cells (ECV304) other than vascular smooth muscle cells was observed in the case of the UFG 8th ECAPed Ta. In terms of hemolysis rate and adhered platelets (both the amount and the individual morphology), an evolutionary outcome of preferentially enhanced hemocompatibility can be concluded for the case of the UFG 8th ECAPed Ta.


Clinical features and outcomes of Sweet's syndrome associated with non-tuberculous mycobacterial infection and other associated diseases.
Sweet's syndrome (SS) is associated with various diseases including non-tuberculous mycobacterial infection (NTM). Recent reports have shown that SS associated with NTM is increasing. Clinical features of SS associated with NTM may be different from SS associated with other associated diseases. The aim of the present study was to compare clinical parameters and treatment outcomes of SS associated with NTM and other associated diseases. Patients from January 2004 to April 2014 diagnosed with SS were retrospectively enrolled. Clinical variables were compared between SS patients with and without NTM infection. There were 51 SS patients during the study period; 36 patients (70.59%) had NTM. Clinical variables between the NTM and other associated diseases were comparable: age, sex, and pattern and locations of skin lesions. Five laboratory factors were significantly different between the groups including white blood cell counts (NTM 25 800 vs 12 850 cells/mm(3) ), lymphocyte percentages (13.0% vs 18.7%), monocytes (3.0% vs 7.2%), blood urea nitrogen (BUN) (11.7 vs 8.1 mg/dL) and serum creatinine (Cr) (1.0 vs 0.7 mg/dL). The presence of markedly high white blood cell counts, a low percentage of mononuclear cells and high BUN/Cr levels in SS may be a clinical clue to recognize the association with NTM infections; particularly in dissemination.


Weight loss in patients with advanced cancer: effects, causes, and potential management.
The past 2 years have yielded interesting observations that have challenged our understanding of and approach to treating cancer-associated weight loss in patients with advanced, incurable malignancies. This review provides an update of such observations and places them within the context of previous work. The mechanisms that underlie cancer-associated weight loss remain elusive, but recent studies suggest that this weight loss might be mediated by downregulation of insulin-like growth factor-1; macrophage inhibitory cytokine-1 has also been implicated. Although recent clinical trials have not provided major additions to the armamentarium of palliative approaches, such laboratory-based findings provide targets for future palliative trials. The limited palliative options available to patients with cancer-associated weight loss underscore the need for continued laboratory and clinical investigation.


Assessment of the role of Leydig cell products other than testosterone in spermatogenesis and fertility in adult rats.
Adult male rats were treated with ethane dimethanesulphonate (EDS) to destroy the Leydig cells and were then supplemented for 3-10 weeks with testosterone esters (TE) by injection every 3 days. The latter treatment prevented Leydig cell regeneration but maintained quantitatively the androgen-dependent aspects of spermatogenesis, as judged by germ cell counts at stage VII of the spermatogenic cycle. Other than the absence of Leydig cells, the testes of EDS-treated, TE-supplemented rats showed only two morphological changes, (1) the appearance of mast cells throughout the interstitium, and (2) a 3- to 4-fold increase in the number of degenerating germ cells (secondary spermatocytes) at stages XIV-I; this was reflected in a significant decrease in the ratio of spermatids to pachytene spermatocytes at stage VII. These changes were not observed in either oil-treated or TE-treated control rats although similar, but less marked, changes in cell degeneration at stages XIV-I were observed in rats actively immunized against oxytocin. Epididymal sperm number was reduced marginally (approximately 15%) in EDS-treated, TE-supplemented rats while sperm motility was affected even less. In a serial mating trial, some of these treated rats showed evidence of subfertility/infertility, but this was mostly transient and may have been the result of epididymal effects of EDS. These results suggest that Leydig cell products other than testosterone are not essential for maintenance of spermatogenesis and fertility in rats, although because of increased germ cell degeneration during the final stages of meiosis (perhaps as the result of oxytocin withdrawal), a small reduction in sperm count may occur.


[The effect of glycine with timoptol on the rabbit IOP physiological values].
the mixture of 10% L-glycine.HCl in 0.5% Timoptol, intensity and duration of effect on the physiological IOP is evaluated in this work. Experiments were performed on 5 rabbits of the New Zealand White species. The mixture and its components were individually instilled into the left conjunctival sac. The right eye was used as control. after instillation of the 10% L-glycine.HCl and 0.5% Timoptol mixture the IOP showed significant decrease compared with the control eye during 24 hour evaluation. Maximal decrease for 33% (8.5 torr) was measured in 60th min., compared with the decrease for 30.5% (7.6 torr) in 120th and for 28% in 30th min. On the contrary, both substances alone--the 10% L-glycine.HC1 and 0.5% Timoptol decrease the physiological IOP values only no significantly compared with their mixture and the control eyes. The mean value of the pupilar diameter was 7.8 mm on both eyes. We assume that the decrease of the physiological IOP value is caused by a new metabolite--the "bioantiglaucomatic" created by interaction of glycine and Timoptol in vitro. The effect of this mixture on the decrease of the physiological IOP values is 8-times stronger compared with Timoptol and 4.3-times stronger compared with glycine. Application of such already prepared bioantiglaucomatic in the clinical practice can contribute to the more effective, safe and reliable therapeutic effect on the IOP in glaucomatic disease.


Norvaline Restores the BBB Integrity in a Mouse Model of Alzheimer's Disease.
Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia. The disease progression is associated with the build-up of amyloid plaques and neurofibrillary tangles in the brain. However, besides the well-defined lesions, the AD-related pathology includes neuroinflammation, compromised energy metabolism, and chronic oxidative stress. Likewise, the blood-brain barrier (BBB) dysfunction is suggested to be a cause and AD consequence. Accordingly, therapeutic targeting of the compromised BBB is a promising disease-modifying approach. We utilized a homozygous triple-transgenic mouse model of AD (3×Tg-AD) to assess the effects of L-norvaline on BBB integrity. We scrutinized the perivascular astrocytes and macrophages by measuring the immunopositive profiles in relation to the presence of β-amyloid and compare the results with those found in wild-type animals. Typically, 3×Tg-AD mice display astroglia cytoskeletal atrophy, associated with the deposition of β-amyloid in the endothelia, and declining nitric oxide synthase (NOS) levels. L-norvaline escalated NOS levels, then reduced rates of BBB permeability, amyloid angiopathy, microgliosis, and astrodegeneration, which suggests AD treatment agent efficacy. Moreover, results undergird the roles of astrodegeneration and microgliosis in AD-associated BBB dysfunction and progressive cognitive impairment. L-norvaline self-evidently interferes with AD pathogenesis and presents a potent remedy for angiopathies and neurodegenerative disorders intervention.


To culture or not to culture: careful assessment of metabarcoding data is necessary when evaluating the microbiota of a modified-atmosphere-packaged vegetarian meat alternative throughout its shelf-life period.
As the increased consumption of ready-to-eat meat alternatives is a fairly recent trend, little is known about the composition and dynamics of the microbiota present on such products. Such information is nonetheless valuable in view of spoilage and food safety prevention. Even though refrigeration and modified-atmosphere-packaging (MAP) can extend the shelf-life period, microbial spoilage can still occur in these products. In the present study, the microbiota of a vegetarian alternative to poultry-based charcuterie was investigated during storage, contrasting the use of a culture-dependent method to a culture-independent metagenetic method. The former revealed that lactic acid bacteria (LAB) were the most abundant microbial group, specifically at the end of the shelf-life period, whereby Latilactobacillus sakei was the most abundant species. Metabarcoding analysis, in contrast, revealed that DNA of Xanthomonas was most prominently present, which likely was an artifact due to the presence of xanthan gum as an ingredient, followed by Streptococcus and Weissella. Taken together, these results indicated that Lb. sakei was likely the most prominent specific spoilage organisms (SSO) and, additionally, that the use of metagenetic analysis needs to be interpreted with care in this specific type of product. In order to improve the performance of metagenetics in food samples with a high DNA matrix but a low bacterial DNA load, selective depletion techniques for matrix DNA could be explored.


Antitumor activity of ribonuclease multimers created by site-specific covalent tethering.
Site-specific cross-linking can generate homogeneous multimeric proteins of defined valency. Pancreatic-type ribonucleases are an especially attractive target, as their natural dimers can enter mammalian cells, evade the cytosolic ribonuclease inhibitor (RI), and exert their toxic ribonucleolytic activity. Here, we report on the use of eight distinct thiol-reactive cross-linking reagents to produce dimeric and trimeric conjugates of four pancreatic-type ribonucleases. Both the site of conjugation and, to a lesser extent, the propinquity of the monomers within the conjugate modulate affinity for RI, and hence cytotoxicity. Still, the cytotoxicity of the multimers is confounded in vitro by their increased hydrodynamic radius, which attenuates cytosolic entry. A monomeric RI-evasive variant of bovine pancreatic ribonuclease (RNase A) inhibits the growth of human prostate and lung tumors in mice. An RI-evasive trimeric conjugate inhibits tumor growth at a lower dose and with less frequent administration than does the monomer. This effect is attributable to an enhanced persistence of the trimers in circulation. On a molecular basis, the trimer is ∼300-fold more efficacious and as well tolerated as erlotinib, which is in clinical use for the treatment of lung cancer. These data encourage the development of mammalian ribonucleases for the treatment of human cancers.


Adrenaline (via alpha(1B)-adrenoceptors) and ethanol stimulate OH* radical production in isolated rat hepatocytes.
Adrenaline is able to increase the oxidative damage caused by some xenobiotic agents in the liver. Ethanol produces oxidative changes in hepatic tissue, while an acute intoxication with alcohol increases adrenaline blood levels. The aim of this study was to determine whether adrenaline increases ethanol-induced hydroxyl free radical production in isolated hepatocytes. Adrenaline augmented hydroxyl radicals in a concentration-dependent manner and was blocked by chloroethylclonidine, an alpha(1B)-adrenoceptor antagonist, while adrenaline plus ethanol added their individual effects. It is suggested that adrenaline increases hydroxyl radicals by an alpha(1B)-adrenoceptor-mediated mechanism, while ethanol does so by a receptor-independent mechanism.


Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab.
Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out. This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls. In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1 year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p = 0.05); study B, 0 of 49 versus 3 of 24 (p = 0.06); and study C, 0 of 34 versus 3 of 22 (p = 0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p = 0.02); study B, 1 of 49 versus 7 of 24 (p = 0.005); and study C, 2 of 34 versus 5 of 22 (p = 0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival. The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR.


[Effect of polypeptide from Chlamys farreri on ultraviolet A-induced Fas and c-fos expression in HaCaT cells].
To observe the effect of Polypeptide from Chlamys farreri (PCF) on expression levels of Fas and c-fos in HaCaT cells after ultraviolet A (UVA) radiation, and investigate the molecular mechanism of PCF protecting against UVA-induced damage in HaCaT cells. HaCaT cells were divided into five groups: control group, UVA model group, 5.69 mmol/L PCF group, 2.84 mmol/L PCF group, and 1.42 mmol/L PCF group. Expression levels of Fas and c-fos mRNA was assayed by PCR. Western blot analysis was used to determine the protein levels of Fas and c-fos. After UVA exposure, Fas and c-fos expression increased significantly (P < 0.01). 1.42 - 5.69 mmol/L PCF inhibited UVA-induced mRNA and protein expressions of Fas and c-fos in HaCaT cells in dose-dependent manner (P < 0.05). PCF could attenuate UVA-induced Fas and c-fos expression, which may attribute to its protective effect against UVA-induced damage in HaCaT cells.


Some Characteristics of the System Converting 1-Aminocyclopropane-1-carboxylic Acid to Ethylene.
The rate of C(2)H(4) production in plant tissue appears to be limited by the level of endogenous 1-aminocyclopropane-1-carboxylic acid (ACC). Exogenous ACC stimulated C(2)H(4) production considerably in plant tissues, but this required 10 to 100 times the endogenous concentrations of ACC before significant increases in C(2)H(4) production were observed. This was partially due to poor penetration of ACC into the tissues. Conversion of ACC to C(2)H(4) was inhibited by free radical scavengers, reducing agents, and copper chelators, but not by inhibitors of pyridoxal phosphate-mediated reactions. The system for converting ACC to C(2)H(4) may be membrane-associated, for it did not survive treatment with surface-active agents and cold or osmotic shock reduced the capacity of the system to convert ACC to C(2)H(4). The reaction rate was sensitive to temperatures above 29 and below 12 C, which suggests that the system may be associated with membrane-bound lipoproteins. The data presented support the possibility that the conversion of exogenous ACC to C(2)H(4) proceeds via the natural physiological pathway.


[Soil microflora characteristics under different vegetation patches in a desert steppe of Ning-xia, Northwest China.]
Vegetation patch is one of the most basic characteristics of natural grazing grassland. To explore the effects of vegetation patch on soil microbial community, the changes of soil microbial biomass and community structure under four different vegetation patches in Ningxia desert steppe were quantified using phospholipid fatty acid (PLFA) analysis. The results showed that: 1) Soil microbial groups were abundant in vegetation patches, with the highest bacterial content, low fungal and actinomycete content, and the Gram-positive bacteria content being higher than that of Gram-negative bacteria in the patches of the four plant communities; 2) The total soil microbial biomass of Glycyrrhiza uralensis patch was significantly higher than that of Artemisia scoparia, Sophora alopecuroides, and Astragalus melilotoides patches; 3) Total PLFAs, Gram-positive bacteria, Gram-negative bacteria, fungi, anaerobic bacteria and fungi/bacteria were significantly positively correlated with soil organic C, and significantly negatively correlated with soil pH, indicating that soil organic C and pH were important factors affecting the growth and development of soil microorganisms in desert steppe.


Consistency of pupillary abnormality in children and adolescents with diabetes.
Repeat measurements on pupillary adaptation to darkness were performed in a cohort of 66 children and adolescents with insulin-dependent diabetes mellitus (IDDM) (initial age 6.9-17.0 years) after a mean interval of 3.5 years, using a portable pupillometer. While there was a close correlation between the results of the two studies (r = 0.94, p < 0.001), the pupillary dilatation, the ratio of the pupil diameter to the iris diameter % (PD%), had decreased significantly (61.5% vs 62.9%, p < 0.001) over these 3.5 years in children with diabetes. The same measurements were performed on 89 healthy control children in the first study and 66 in the reassessment period and PD% was not significantly different in the two control groups. Five children with diabetes identified as having abnormal pupillary dilatation in the first study were outside the normal range 3.5 years later. In addition 4 children in whom initial testing had been normal, showed abnormality at the time of the second study. None of these children had symptoms of autonomic neuropathy. These findings suggest that abnormality in pupillary adaptation in diabetic children is consistent and increases with time and may serve as an early marker of tissue damage associated with diabetes.


Acute ventilatory response to green coffee dust extract.
The lung function response to inhalation of an extract of green coffee was studied in ten healthy subjects who were prescreened for airway hyperresponsiveness to an aerosol of green coffee extract. The effects of this provocation were evaluated at rest and following moderate exercise as well as with and without pretreatment with 80 mg of disodium cromoglycate (DSCG). There was a statistically significant decrement in lung function over time (P less than .001) following coffee provocation both at rest and following exercise. No significant protection against this response was observed with DSCG pretreatment. While the majority of these "healthy" coffee reactors exhibited baseline nonspecific airway hyperresponsiveness to methacholine (PC20 FEV1 less than 25 mg/mL in 7/10), there was no correlation in these ten subjects between baseline responsiveness to methacholine and the degree of lung function decrement following coffee (P greater than .05). Also, no correlation was observed between skin prick and lung function response to coffee extract. We conclude that inhalation of green coffee extract causes significant bronchoconstriction in selected healthy volunteers and that this response is not prevented by pretreatment with DSCG.


Nematic cells with quasicrystalline-patterned alignment layers.
Nematic cells with surface anchoring fields exhibiting quasicrystalline symmetry can be fabricated using linear photopolymerizable polymers and suitable optics. Using the Lebwohl-Lasher model we carry out Monte Carlo simulations of a nematic cell where the top and bottom surfaces have an anchoring field with the symmetry of a periodic approximant to a Penrose lattice. We show that the anchoring field has point topological defects, nearly all with topological charge +/-1 . Our simulations, which assume infinitely strong anchoring of the nematic to the anchoring field, show that half-integer disclination lines emerge from the point defects and either traverse the thickness of the cell for small cell thicknesses, hug the patterned surfaces for large thicknesses, or combine these behaviors for intermediate thicknesses. We show that estimates of the values of the thicknesses separating these three behaviors can be obtained using the properties of Penrose tilings.


A person-centred approach to modelling population experiences of trauma and mental illness.
Exposure to traumatic events has been implicated in the onset and development of a range of psychiatric disorders. People can be exposed to multiple traumatic events and previous research suggests that traumatic experiences may cluster at the individual level. This study aimed to examine the distribution of traumatic experiences in a large nationally representative sample using latent class analysis, and estimate the relationship between these classes and a number of demographic and clinical variables. Data from the National Comorbidity Survey was used. Four latent classes, each representative of a range of traumatic experiences were identified. The classes were labelled 'high risk' (class 1), 'exposure to non-sexual adult interpersonal/non-interpersonal trauma' (class 2), 'intermediate risk/sexual abuse' (class 3), and 'low risk' (class 4). Each of the latent classes was predicted by several of the demographic variables. In addition, membership of classes 1, 2, and 3 increased the risk of each of the clinical variables. The findings have clinical implications for the assessment of trauma histories across a range of psychiatric diagnoses.


Prevention and management of complications arising from external fixation pin sites.
The use of external fixation devices to assist in the management of lower extremity trauma and reconstruction continues to rise. Despite the distinct advantages of external fixation, complications from external fixators continue to exist. The complicated external fixator-associated pin site may be a potential source of significant morbidity, especially in the at-risk patient, which may lead to soft tissue healing problems and infections, as well as osteomyelitis. This article describes both simple as well as more complex techniques that the authors use in the prevention and management of complications arising from external fixator pin sites, and solutions to the difficult task of incorporating external fixator wires into negative-pressure dressings.


Assessment of cerebrovascular reserve impairment using the breath-holding index in patients with leukoaraiosis.
Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many controversies. This study aimed to investigate hemodynamic changes in symptomatic leukoaraiosis using transcranial Doppler ultrasonography and the breath-holding test in a Chinese Han population, from northern China. A total of 203 patients who were diagnosed with ischemic stroke or clinical chronic progressive ischemic symptoms were enrolled in this study, including 97 males and 106 females, with an age range of 43-93 years. The severity of leukoaraiosis was evaluated according to the Fazekas grading scale, and patients were divided into four groups accordingly. Grade 0 was no leukoaraiosis, and grades I, II, and III were mild, moderate, and severe leukoaraiosis, respectively, with 44, 79, 44, and 36 cases in each group. Transcranial Doppler ultrasonography and the breath-holding test were performed. The mean blood flow velocity of the bilateral middle cerebral artery was measured and the breath-holding index was calculated. The breath holding index was correlated with leukoaraiosis severity and cognitive impairment. Patients with a low breath holding index presented poor performance in the Montreal Cognitive Assessment (MoCA) and executive function tests. That is, the lower the breath holding index, the lower the scores for the MoCA and the higher for the trail-making test Parts A and B. These results indicate that the breath-holding index is a useful parameter for the evaluation of cerebrovascular reserve impairment in patients with leukoaraiosis. In addition, the breath-holding index can reflect cognitive dysfunction, providing a new insight into the pathophysiology of leukoaraiosis. This study was approved by the Ethics Committee of the Fifth People's Hospital of Shenyang, China (approval No. 20160301) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800014421).


Selective Production of Phenol-Rich Bio-Oil From Corn Straw Waste by Direct Microwave Pyrolysis Without Extra Catalyst.
We report a sustainable strategy to cleanly address biomass waste with high-value utilization. Phenol-rich bio-oil is selectively produced by direct pyrolysis of biomass waste corn straw (CS) without use of any catalyst in a microwave device. The effects of temperature and power on the yield and composition of pyrolysis products are investigated in detail. Under microwave irradiation, a very fast pyrolysis rate and bio-oil yield as high as 46.7 wt.% were obtained, which were competitive with most of the previous results. GC-MS analysis showed that temperature and power (heating rate) had great influences on the yield of bio-oil and the selectivity of phenolic compounds. The optimal selectivity of phenols in bio-oil was 49.4 area% by adjusting the operating parameters. Besides, we have made detailed statistics on the change trend of some components and different phenols in bio-oil and given the law and reason of their change with temperature and power. The in situ formed highly active biochar from CS with high content of potassium (1.34 wt.%) is responsible for the improvement of phenol-rich oils. This study offers a sustainable way to fully utilize biomass waste and promote the achievement of carbon neutrality.


Measuring clinical performance using routinely collected clinical data.
Following the well-publicized problems with paediatric cardiac surgery at the Bristol Royal Infirmary, there is wide public interest in measures of hospital performance. The Kennedy report on the BRI events suggested that such measures should be meaningful to the public, case-mix-adjusted, and based on data collected as part of routine clinical care. We have found that it is possible to predict in-hospital mortality (a measure readily understood by the public) using simple routine data-age, mode of admission, sex, and routine blood test results. The clinical data items can be obtained at a single venesection, are commonly collected in the routine care of patients, are already stored on hospital core IT systems, and so place no extra burden on the clinical staff providing care. Such risk models could provide a metric for use in evidence-based clinical performance management. National application is logistically feasible.


Comparison of the Efficacy of Dexamethasone and Methylprednisolone in Infiltration Injection for Postendodontic Pain in Patients with Necrotic Pulp: A Randomized Controlled Clinical Trial.
Postendodontic pain is one of the problems of root canal therapy. This clinical study aimed to evaluate the effect of infiltration injection of dexamethasone and methylprednisolone on postendodontic pain in patients with necrotic pulp. A total of 80 volunteers with necrotic pulp teeth were included and assigned to two groups (n = 40). After the administration of local anesthesia and before root canal therapy, in group 1, an infiltration injection of 1 ml of dexamethasone was done and in group 2, an infiltration injection of 1 ml of methylprednisolone was done in the buccal vestibule of each tooth. Patients' pain was reported using a visual analogue scale at pretreatment and 6, 12, 24, and 48 hours after treatment. There was no significant difference between the two groups receiving dexamethasone and methylprednisolone at pretreatment and 6, 12, 24, and 48 hours after endodontic treatment. Infiltration injection of dexamethasone and methylprednisolone had a significant effect in reducing pain after the endodontic treatment in necrotic pulp teeth, but between 6 and 12 hours, methylprednisolone had significantly more effect on pain relief than dexamethasone. Overall, the use of any of these drugs to reduce postendodontic pain is recommended.


Benign peritoneal mesothelioma. Histopathology in a case.
A case of peritoneal mesothelioma was histopathologically diagnosed in a 40-year-old woman. Localized solitary firm nodules found in omentum appeared microscopically as trabecular proliferations with a plexiform pattern in a myxoid stroma. The tumors were penetrated by clefts and cystic cavities lined by a cuboidal or endotheliform epithelium. Rare psammoma bodies were present. The stroma was rich in hyaluronic acid and slightly positive for neutral mucopolysaccharides.


Primary vascular tumours of the kidney.
Primary vascular tumours of the kidney are rare and may pose diagnostic difficulties because of their similar clinical, morphological, and immunohistochemical features. This article summarizes the clinical and pathological features of primary renal angiosarcoma and anastomosing haemangioma of the kidney including epidemiology, genetics, and prognosis. Renal anastomosing haemangiomas are benign neoplasms characterized by anastomosing capillary-sized vascular channels. These tumours are rare, with about 75 cases reported in the literature. Most anastomosing haemangiomas are found incidentally on ultrasound, computed tomography, or magnetic resonance imaging. Common symptoms include abdominal pain, haematuria, and abdominal mass. Renal anastomosing haemangiomas are characterized by recurrent mutations in GNAQ and GNA14 genes. The prognosis of anastomosing haemangioma is excellent. Primary renal angiosarcomas are malignant tumours showing endothelial differentiation. To date, 76 cases have been described in the literature. Primary renal angiosarcomas are frequently symptomatic. The clinical features of renal angiosarcomas are similar to those of renal anastomosing haemangiomas, including abdominal pain, haematuria, and abdominal mass. Angiogenesis-related genes and vascular-specific receptor tyrosine kinases such as KDR, TIE1, SNRK, TEK, and FLT1 are upregulated in angiosarcomas. Primary renal angiosarcomas are highly aggressive neoplasms with a poor prognosis despite surgical treatment, chemotherapy, radiotherapy, or targeted therapy.


How the NHMRC got its fingers burnt.
On 20 December 1996, Justice J Finn of the Federal Court of Australia handed down his judgment in the case of the Tobacco Institute of Australia (TIA) Ltd and others v the National Health and Medical Research Council (NHMRC) and others. Justice Finn concluded that, in developing its recommendations for control of environmental tobacco smoke, the NHMRC's Working Party on Passive Smoking erred significantly in regard to the consultative procedures that it employed. As the following discussion shows, the legal decision has profound implications for the NHMRC and the provision of expert advice to Australian governments on matters of health and health policy. The discussion has been prepared by three members of the NHMRC Working Party, but reflects their personal views and not necessarily those of the Working Party as a whole or those of the NHMRC.


Clostridium difficile infection in the "oldest" old: clinical outcomes in patients aged 80 and older.
Clostridium difficile infection (CDI) represents a cause of substantial morbidity, particularly for older adults. Although older age is a risk factor for CDI, few studies have specifically focused on clinical outcomes in older adults, particularly the "oldest" old. Retrospective review. University of Michigan Health System. All patients aged 80 and older with a positive cytotoxin assay for C. difficile and a clinical course consistent with CDI during 2006. Clinical data were recorded, including comorbid conditions and treatment regimens, as well as outcomes, including treatment failure, infection relapse, and 90-day mortality. Seventy patients aged 80 and older (mean 84.0+/-4.1) with CDI were identified. Metronidazole was given as initial therapy in 65 (92.8%); 18 of these 65 (27.7%) experienced treatment failure, requiring subsequent use of oral vancomycin. Serious adverse events included three episodes of toxic megacolon, two requiring colectomy. One death was directly attributable to CDI. All-cause mortality was 8.6% at 30 days and 17.1% at 90 days. Higher white blood cell (WBC) counts were independently associated with treatment failure (P=.02) and coronary artery disease with 90-day mortality (P=.02). In older adults with CDI, treatment failure on metronidazole occurred frequently and was associated with higher WBC count. Larger prospective studies are needed to determine risk factors for treatment failure and relapse in order to develop better paradigms for CDI treatment in older adults. Initial therapy with vancomycin may be appropriate for elderly patients, especially those with elevated WBC counts.


Effect of arsenite on induction of CYP1A, CYP2B, and CYP3A in primary cultures of rat hepatocytes.
In earlier studies, sodium arsenite treatment was shown to decrease induction of enzymatic activities associated with hepatic CYPs in rats. Here we investigated the effect of sodium arsenite on induction of CYP2B, CYP1A, and CYP3A in primary cultures of rat hepatocytes. Arsenite decreased the induction of all three families of CYP, as measured enzymatically and immunochemically. These decreases in CYPs occurred at concentrations of arsenite (2.5-10 microM) at which no toxicity was observed; however, toxicity was observed at 25 microM arsenite. With 3-methylcholanthrene as inducer, 5 microM arsenite caused a 55% decrease in CYP1A1 immunoreactive protein and enzyme activity, but only a 25% decrease in CYP1A1 mRNA. With phenobarbital (PB) as the inducer, 2.5 microM arsenite decreased CYP2B enzyme activity and immunoreactive protein 50%, with only a 25% decrease in CYP2B1 mRNA. 5 microM Arsenite decreased CYP2B enzyme activity and immunoreactive protein 80%, but decreased CYP2B1 mRNA only 50%, while CYP3A protein was decreased greater than 75% with no decrease in CYP3A23 mRNA. With dexamethasone (DEX) as inducer, 5 microM sodium arsenite caused a 50% decrease in immunoreactive CYP3A and a 30% decrease in CYP3A23 mRNA. Although arsenite-mediated increases in heme oxygenase (HO) inversely correlated with decreases in CYP2B or CYP1A activity, inclusion of heme in cultures treated with inducers of CYP1A or CYP2B did not prevent the arsenite-mediated decreases in these CYPs. Even though added heme induced HO to similar levels with and without arsenite, decreases in CYPs were only observed in the presence of arsenite. These results suggest that, in rat hepatocytes, elevated levels of HO alone are not responsible for arsenite-mediated decreases in CYP.


In vitro developmental potential of macaque oocytes, derived from unstimulated ovaries, following maturation in the presence of glutathione ethyl ester.
The inadequacies of oocyte in vitro maturation (IVM) systems for both non-human primates and humans are evidenced by reduced fertilization and poor embryonic development, and may be partly explained by significantly lower glutathione (GSH) contents compared with in vivo matured (IVO) oocytes. As this influence has not been fully explored, this study investigated the effect of the GSH donor, glutathione ethyl ester (GSH-OEt), on the IVM and development of macaque oocytes as a model of human oocyte IVM. Macaque oocytes derived from unstimulated ovaries were cultured in mCMRL-1066 alone or supplemented with 3 or 5 mM GSH-OEt. In vitro matured oocytes were subjected to the GSH assay, fixed for the assessment of spindle morphology or prepared ICSI. Embryo development of zygotes cultured in mHECM-9 was assessed up to Day 9 post-ICSI. RESULTS Supplementation of the maturation medium with GSH-OEt significantly increased oocyte maturation and normal fertilization rates compared with control oocytes, but only 5 mM GSH-OEt significantly increased the oocyte and cumulus cell GSH content. Confocal microscopy revealed significant differences in the spindle morphology between IVO and control in vitro matured metaphase II oocytes. Oocytes matured with 5 mM GSH-OEt exhibited spindle area and spindle pole width similar to that seen in the IVO oocyte. While no significant differences were observed in blastocyst rates, addition of 3 mM GSH-OEt during IVM significantly increased the proportion of embryos developing to the 5-8 cell stage while 5 mM GSH-OEt significantly increased the proportion of morula-stage embryos compared with controls. Supplementation of the IVM medium with GSH-OEt promotes better maturation and normal fertilization of macaque oocytes compared with non-supplemented medium. However, further improvement of the primate oocyte IVM culture system is required to support better blastocyst development of oocytes derived from unstimulated ovaries.


[Perceptions of adolescents Jalisco campaign on breast cancer].
Breast cancer campaigns and awareness strategies with limited evidence of their effectiveness in youth. Behavioral model of perception that shows how individuals choose, organize and interpret information. This study shows the perceptions of youth from Jalisco regarding breast cancer campaigns. Cross-sectional qualitative exploratory study based on constructionist and associationist theories of perception. Informed consent interviews with 13 focus groups, 129 men and women between 12 and 19 years old, enrolled students, residents of 6 regions of Jalisco. The sampling consisted in snowball technique. Interviews transcribed and processed with Atlas Ti version 4.1, open coding analysis. 10 campaigns were identified and the perceptions about them showed 3 processes: 1) SELECTION: permeated by the campaign design elements; 2) ORGANIZATION: influenced by pre-structured meanings of the color pink, scope and limitations of the campaigns; and 3) INTERPRETATION: showed judgments about the visibility of breast cancer, accessibility of knowledge and resources, permeability of positive ads and cultural codes and the lack of coverage meeting expectations. A high awareness of breast cancer among teenagers was evident as well as the extensive need of information and services. We recommend creating strategies for formal education about breast cancer during adolescence.


Effects of Taichi exercise on knee and ankle proprioception among individuals with knee osteoarthritis.
The study aimed to investigate the effects of 24 weeks Taichi intervention on knee and ankle proprioception amongst individuals with knee osteoarthritis (KOA). Ninety-two patients with KOA were included in the current study, involving 52 participants in the intervention group and 40 participants in the control group. The intervention group performed Taichi exercise for 24 weeks, the control group accepted the health education lectures. The main outcome of this study was the proprioception of the knee and ankle which was measured by an electric-driven movable frame. Between- and within-group differences were evaluated through the repeated-measurement ANOVA. For the Taichi group, the differences in the changes in ankle proprioception were significant on ankle plantarflexion (p = 0.03), ankle dorsiflexion (p = 0.043), ankle varus (p = 0.019) and knee flexion (p = 0.01) between the baseline and post-test measures. Twenty-four weeks Taichi exercise may improve the ankle and knee proprioception of patients with KOA.


VKORC1 gene variations are the major contributors of variation in warfarin dose in Japanese patients.
To compare the genetic and clinical factors that cause large interpatient variability and ethnic differences in warfarin efficacy, we investigated variations of the VKORC1, CYP2C9, and CYP2C19 genes in Japanese subjects. Furthermore, we evaluated the genetic variations and clinical data as contributors of variation in warfarin maintenance dose. Gene variations of VKORC1, CYP2C9, and CYP2C19 in 125 patients treated with warfarin and 114 healthy subjects were analyzed. The daily dose of warfarin, concentrations of S- and R-warfarin in plasma, and prothrombin time expressed as the international normalized ratio were used as the pharmacokinetic and pharmacodynamic indices. Data were evaluated by a multivariate analysis method. Three missense mutations (47 G>C, 113 A>C, and 1338 A>G) in VKORC1 were newly identified in the Japanese population. The 113 A>C (Asp38Ser) variant decreased the warfarin dose requirement from 3.33 +/- 1.54 mg/d (n = 122) to 1.5 mg/d (n = 1). The variants -1639 G>A in the 5'-upstream region, 1173 C>T in intron 1, and 1542 G>C in intron 2 were in complete linkage disequilibrium, and the frequency of the -1639 G>A variation was only 0.8%, which contrasts with the frequency (39.8%-45.8%) reported previously for white persons. The dose of warfarin was larger in the VKORC1 -1639 GA genotype group (4.55 +/- 1.75 mg/d, P < .001) than in the -1639 AA group (2.94 +/- 1.15 mg/d). The mean daily dose of warfarin was lower in subjects with CYP2C9*1/*3 (1.86 +/- 0.80 mg/d, P = .007) than in subjects with CYP2C9*1/*1 (3.36 +/- 1.43 mg/d). When the relative contributions of the VKORC1 variants, CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3, as well as the clinical characteristics of the patients, diagnoses, and concurrent medications, were compared, the VKORC1 -1639 GA genotype group accounted for 16.5% and CYP2C9 variants accounted for 13.4% of variation in warfarin dose. The ethnic difference in warfarin maintenance dose was mainly dependent on the linked VKORC1 variants. Genotyping of -1639 G>A of the VKORC1 gene could be clinically important for predicting individual variability in anticoagulant responses to warfarin.


Phylogeny, biogeography, and molecular dating of cornelian cherries (Cornus, Cornaceae): tracking Tertiary plant migration.
Data from four DNA regions (rbcL, matK, 26S rDNA, and ITS) as well as extant and fossil morphology were used to reconstruct the phylogeny and biogeographic history of an intercontinentally disjunct plant group, the cornelian cherries of Cornus (dogwoods). The study tests previous hypotheses on the relative roles of two Tertiary land bridges, the North Atlantic land bridge (NALB) and the Bering land bridge (BLB), in plant migration across continents. Three approaches, the Bayesian, nonparametric rate smoothing (NPRS), and penalized likelihood (PL) methods, were employed to estimate the times of geographic isolations of species. Dispersal and vicariance analysis (DIVA) was performed to infer the sequence and directionality of biogeographic pathways. Results of phylogenetic analyses suggest that among the six living species, C. sessilis from western North America represents the oldest lineage, followed by C. volkensii from Africa. The four Eurasian species form a clade consisting of two sister pairs, C. mas-C. officinalis and C. chinensis-C. eydeana. Results of DIVA and data from fossils and molecular dating indicate that the cornelian cherry subgroup arose in Europe as early as the Paleocene. Fossils confirm that the group was present in North America by the late Paleocene, consistent with the DIVA predictions that, by the end of the Eocene, it had diversified into several species and expanded its distribution to North America via the NALB and to Africa via the last direct connection between Eurasia and Africa prior to the Miocene, or via long-distance dispersal. The cornelian cherries in eastern Asia appear to be derived from two independent dispersal events from Europe. These events are inferred to have occurred during the Oligocene and Miocene. This study supports the hypothesis that the NALB served as an important land bridge connecting the North American and European floras, as well as connecting American and African floras via Europe during the early Tertiary.


The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway.
Purpose: The purpose of the present study was to estimate the effect of shionone (SHI) on sepsis-induced acute lung injury (ALI). Methods: The cecal ligation and puncture (CLP) surgery was performed to induce sepsis in mice. Pulmonary hematoxylin and eosin staining, the wet/dry ratio, myeloperoxidase (MPO) activity, and the survival rate were detected. The RAW264.7 cells were treated with SHI and stimulated with lipopolysaccharide (LPS). The cells were also overexpressed by extracellular mechanism protein 1 (ECM1) adenovirus. The relative levels of granulocyte-macrophage colony-stimulating factor, IL-6, IL-1β, TNF-α, IL-10, and TGF-β in the serum and supernatant were measured by ELISA. The protein expressions of ECM1, p-STAT5, signal transducer and activator of transcription 5 (STAT5), p-NF-κB, nuclear factor kappa-B (NF-κB), Arg1, CD206, CD16/32, and iNOS in the CLP-induced lung tissues and LPS-induced cells were detected by western blot. The cell counts of Ly6G, F4/80, CD16/32, and CD206 were evaluated by flow cytometry. The ECM1 expression was also observed by immunohistochemistry and immunofluorescence staining. Results: As a result, the histopathological change, pulmonary edema, and the MPO activity were relieved by SHI. SHI treatment increased the percentage of neutrophil and macrophage in the bronchoalveolar lavage fluid. Besides, SHI administration inhibited pro-inflammatory cytokines and M1 phenotype indices, as well as augmented the anti-inflammatory cytokines and M2 phenotype indices. SHI also attenuated the ECM1/STAT5/NF-κB pathway both in vivo and in vitro. The overexpression of ECM1 confirmed that the regulated effect of SHI was due to ECM1 signaling. Conclusion: In conclusion, the present study suggests that SHI ameliorated sepsis-induced ALI by screwing M1 phenotype to M2 phenotype macrophage via the ECM1/STAT5/NF-κB pathway.


PaO2/FiO2 Deterioration During Stable Extracorporeal Membrane Oxygenation Associates With Protracted Recovery and Increased Mortality in Severe Acute Respiratory Distress Syndrome.
During extracorporeal membrane oxygenation (ECMO), arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2; PF ratio reflects native and artificial lung blood oxygenation). In this study we analyzed PF ratio during ECMO support and its association with clinical outcome. This was a single-center observational study of adult patients (n = 81) undergoing veno-venous ECMO support for severe acute respiratory distress syndrome. In 37 patients (46%) PF ratio decreased from ECMO-day 1 to ECMO-day 7 (PF ratio deterioration [PF-d]; -37 ± 6.1 mm Hg), whereas in 44 patients PF ratio improved (PF-i; 65 ± 10.8 mm Hg). PF-d group required prolonged ECMO (median 21 days [interquartile range (IQR)]:14-35 days] versus 13 days [IQR: 10-20 days]) and invasive mechanical ventilation (median 33 days [IQR: 24-52 days] versus 26 days [IQR: 22-34 days]), longer intensive care unit (median 44 days [IQR: 32-74 days] versus 30 days [IQR: 25-47 days]), and hospital (median 66 days [IQR: 39-95 days] versus 36 days [IQR: 28-54 days]) lengths of stay, with higher hospital mortality rates (48.7% versus 22.7%). ECMO oxygenation did not explain PF ratio variation that remained stable in PF-d and decreased in PF-i (198 ± 12.7 mL/min versus 171 ± 8.8 mL/min). Pre-ECMO PF ratio, neuromuscular blockade, and prone position, as well as ventilatory variables did not differ between groups. The PF-d group was older (49 ± 2.1 years versus 41 ± 1.8 years) and presented lower Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) scores (0.57 ± 0.63 versus 2.2 ± 0.52). With the use of logistic regression, PF ratio variation remained an independent predictor of hospital mortality after adjusting for age or RESP score. In severe acute respiratory distress syndrome, PF ratio deterioration during stable ECMO associates with protracted recovery and increased mortality, not accounted for by patient baseline characteristics, acute respiratory distress syndrome severity, or pre-ECMO management.


Battery-Operated Atomic Emission Analyzer for Waterborne Arsenic Based on Atmospheric Pressure Glow Discharge Excitation Source.
In this paper, a sensitive atomic emission spectrometer (AES) based on a new low power and low argon consumption (<8 W, 100 mL min-1) miniature direct current (dc) atmospheric pressure glow discharge (APGD) plasma (3 mm × 5 mm) excitation source was developed for the determination of arsenic in water samples. In this method, arsenic in water was reduced to AsH3 by hydride generation (HG), which was then transported to the APGD source for excitation and detected by a compact CCD (charge-coupled device) microspectrometer. Different parameters affecting the APGD and the hydride generation reactions were investigated. The detection limit for arsenic with the proposed APGD-AES was 0.25 μg L-1, and the calibration curves were found to be linear up to 3 orders of magnitude. The proposed method was successfully applied to the determination of certified reference material (GBW08605), tap water, pond water, groundwater, and hot spring samples. Measurements from the APGD analyzer showed good agreement with the certified value/values obtained with well-established hydride generation atomic fluorescence spectrometry (HG-AFS). These results suggest that the developed robust, cost-effective, and fast analyzer can be used for field based arsenic determination and may provide an important tool for arsenic contamination and remediation programs.


Synthesis and characterization of novel antimicrobial emulsifiers from epsilon-polylysine.
epsilon-Polylysine (EPL) has been used in the food industry as an antimicrobial additive and also a dietary agent. To generate amphiphilic molecules from EPL, hydrophobically modified epsilon-polylysine graft copolymers, which were denoted as OSA-g-EPLs, were synthesized by reacting EPL with octenyl succinic anhydride (OSA). The success of synthesis was confirmed by (1)H NMR and FT-IR spectroscopy. It was found that OSA-g-EPLs had glass transition temperatures lower than EPL. Furthermore, they were able to form polymer micelles in water and to lower the surface tension of water, confirming their amphiphilic properties. The antimicrobial activities of OSA-g-EPLs were also examined, and the minimum inhibitory concentrations of OSA-g-EPLs against Escherichia coli O157:H7 remained the same as that of EPL. Therefore, OSA-g-EPLs have the potential of becoming bifunctional molecules, which can be used either as surfactants or emulsifiers in the encapsulation of nutraceuticals or drugs or as antimicrobial agents.


Freezing injury in potato leaves.
Time-temperature profiles of freezing leaves from frost-resistant (Solanum acaule Bitt.) and frost-susceptible (Solanum tuberosum L. subsp. tuberosum Hawkes) types of potatoes did not reveal any major differences. The pattern of change in resistance of leaves to low voltage, low frequency current during freezing was different in the frost-resistant and susceptible leaves. In tissue sections from both types of leaves, cells freeze extracellularly at cooling velocities lower than 5 C per minute. Cells from leaves of resistant plants showed a higher osmotic pressure but not a higher water permeability than those from susceptible plants. The extent of injury caused by even very slow freezing was greater than that caused by equivalent isopiestic desiccation, particularly in susceptible leaves. The higher osmotic pressure in cells of leaves from resistant plants can account for the greater desiccation resistance but not for the frost resistance observed.


Dual-zone material assignment method for correcting partial volume effects in image-based bone models.
In image-based finite element analysis of bone, partial volume effects (PVEs) arise from image blur at tissue boundaries and as a byproduct of geometric reconstruction and meshing during model creation. In this study, we developed and validated a material assignment approach to mitigate partial volume effects. Our validation data consisted of physical torsion testing of intact tibiae from N = 20 Swiss alpine sheep. We created finite element models from micro-CT scans of these tibiae using three popular element types (10-node tetrahedral, 8-node hexahedral, and 20-node hexahedral). Without partial volume management, the models over-predicted the torsional rigidity compared to physical biomechanical tests. To address this problem, we implemented a dual-zone material model to treat elements that overlap low-density surface voxels as soft tissue rather than bone. After in situ inverse optimization, the dual-zone material model produced strong correlations and high absolute agreement between the virtual and physical tests. This suggests that with appropriate partial volume management, virtual mechanical testing can be a reliable surrogate for physical biomechanical testing. For maximum flexibility in partial volume management regardless of element type, we recommend the use of the following dual-zone material model for ovine tibiae: soft-tissue cutoff density of 665 mgHA/cm3 with a soft tissue modulus of 50 MPa (below cutoff) and a density-modulus conversion slope of 10,225 MPa-cm3/mgHA for bone (above cutoff).


Assessing the Elevation of Cardiac Biomarkers and the Severity of COVID-19 Infection: A Meta-analysis.
- Purpose: Since December 2019, coronavirus disease 2019 infection has become a global pandemic. The cases of Coronavirus Disease 2019 (COVID-19)-related acute cardiac injury with unknown pathophysiologic mechanism has become increasingly prevalent. However, it is not yet understood how the extent of cardiac injury differs with the intensity of viral infection. In the current study, we aimed to assess the association between elevated cardiac biomarkers and the severity of COVID-19 infection. A systematic literature search was performed across PubMed and Embase databases from December 1, 2019 to July 10, 2020, to identify studies that reported cardiac biomarkers of troponin (TnI) and creatine kinase-myocardial band (CK-MB) in patients with COVID-19. These studies compared non-severe patients with severe patients, or survivors with non-survivors or medical patients with critically ill patients. The data were extracted for TnI, CK-MB, N-terminal-brain natriuretic peptide (NT-BNP), D-dimer, and lactate dehydrogenase (LDH), C-reactive protein (CRP), and interleukin 6 (IL-6). Wherever possible, the data were pooled for meta-analysis (Review Manager, RevMan. version 5.3) with standard or weighted mean or median difference and corresponding 95% confidence intervals (95% CI). A total of 25 studies involving 5,626 patients were included in the present analysis. More severe COVID-19 infection was found to be associated with higher mean values of TnI (-0.54 [-0.72, -0.36]) (ng/mL), CK-MB (-1.55 [-2.23, -0.88]) (ng/mL) and (-4.75 [-13.31, 3.82]) (units/L), NT-BNP (-815.7 [-1073.97, -557.42]) (pg/mL), D-dimer (-1.4 [-2.04, -0.77]) (mcg/mL), and LDH (-176.59 [-224.11, -129.06]) (units/L), as well as CRP (-64.03 [-68.88, -59.19]) (mg/L) and IL-6 (-22.59 [-29.39, -15.79]) (pg/mL). There is significant association between elevated cardiac biomarkers and the severity of COVID-19, which underlines the increased risk of acute cardiac injury with more severe viral infection. This highlights the need to understand the cardiac history among the COVID-19 patients during initial assessment and for monitoring.


Studies of Root Function in Zea mays: III. Xylem Sap Composition at Maximum Root Pressure Provides Evidence of Active Transport into the Xylem and a Measurement of the Reflection Coefficient of the Root.
The cut ends of excised Zea mays roots were sealed to a pressure transducer and their root pressures recorded. These rose approximately hyperbolically to a maximum value of 4.21 +/- 0.34 bar after 30 to 40 minutes. Xylem exudate could not be collected at this pressure since the flow rate was zero. Samples of exudate were collected at lower applied pressures (DeltaP), however, and Deltapi, the osmotic pressure difference between them and the solution bathing the root, was measured by freezing point depression. A plot of DeltaP/Deltapi against J(v)/Deltapi, where J(v) is the volume flux, proved to be a straight line whose intercept, equal to sigma, the reflection coefficient, was 0.853 +/- 0.016. The maximum xylem concentrations of various chemical species were found by a similar extrapolative method and compared with those in the cell sap. This indicated that (a) Ca(2+), Mg(2+), NO(3) (2-), SO(4) (2-), and most amino acids move from the cells to the xylem down an electrochemical potential gradient; (b) relative to these ions H(+), NH(4) (+), glutamine and asparagine are actively transported into the xylem; and (c) H(2)PO(4) (-), and K(+) are actively retained in the symplasm.


Making endoscopy mobile: a novel initiative for public healthcare.
Public healthcare has progressed immensely in the past few decades. However, the rural masses in the developing and underdeveloped countries very often have limited access to the advanced healthcare technology. At the Asian Institute of Gastroenterology, Hyderabad, India, the Rural Health Care Project has been initiated in an attempt to provide cost-effective gastrointestinal care to the rural population. The Project was implemented by traveling to remote rural areas in a bus that had been converted into a mobile hospital and equipped with basic diagnostic facilities including a custom-made endoscopy unit. The mobile hospital and endoscopy unit is accompanied by a telemedicine vehicle that transmits all procedures and data to the main telemedicine center at the parent institute in Hyderabad. Our efforts have resulted in cost-effective management and robust data collection of several common gastrointestinal illnesses in remote rural areas of the Indian state of Andhra Pradesh. To date, 32756 endoscopic procedures have been carried out in a population of over 10 million people spanning 4837 villages. Overall, 72% of the population has had a positive finding on upper gastrointestinal endoscopy (primarily related to acid peptic diseases). Interestingly, <1% of the population have had colonic polyps on screening colonoscopy, whereas the prevalence of infective colitis has been high. This whole exercise has produced a high level of satisfaction among both beneficiaries and care-givers; it has also offered doctors in training the opportunity to encounter and manage common public health-related problems. This program is funded by philanthropic donations.


Role of the Fur regulon in iron transport in Bacillus subtilis.
The Bacillus subtilis ferric uptake regulator (Fur) protein mediates the iron-dependent repression of at least 20 operons encoding approximately 40 genes. We investigated the physiological roles of Fur-regulated genes by the construction of null mutations in 14 transcription units known or predicted to function in siderophore biosynthesis or iron uptake. We demonstrate that ywbLMN, encoding an elemental iron uptake system orthologous to the copper oxidase-dependent Fe(III) uptake system of Saccharomyces cerevisiae, is essential for growth in low iron minimal medium lacking citric acid. 2,3-Dihydroxybenzoyl-glycine (Itoic acid), the siderophore precursor produced by laboratory strains of B. subtilis, is of secondary importance. In the presence of citrate, the YfmCDEF ABC transporter is required for optimal growth. B. subtilis is unable to grow in minimal medium containing the iron chelator EDDHA unless the ability to synthesize the intact bacillibactin siderophore is restored (by the introduction of a functional sfp gene) or exogenous siderophores are provided. Utilization of the catecholate siderophores bacillibactin and enterobactin requires the FeuABC importer and the YusV ATPase. Utilization of hydroxamate siderophores requires the FhuBGC ABC transporter together with the FhuD (ferrichrome) or YxeB (ferrioxamine) substrate-binding proteins. Growth with schizokinen or arthrobactin is at least partially dependent on the YfhA YfiYZ importer and the YusV ATPase. We have also investigated the effects of a fur mutation on the proteome and documented the derepression of 11 Fur-regulated proteins, including a newly identified thioredoxin reductase homolog, YcgT.


Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes.
Acquisition of reliable and robust neural recordings with intracortical neural probes is a persistent challenge in the field of neuroprosthetics. We developed a multielectrode array technology to address chronic intracortical recording reliability and present in vivo recording results. The 2 × 2 Parylene sheath electrode array (PSEA) was microfabricated and constructed from only Parylene C and platinum. The probe includes a novel three-dimensional sheath structure, perforations, and bioactive coatings that improve tissue integration and manage immune response. Coatings were applied using a sequential dip-coating method that provided coverage over the entire probe surface and interior of the sheath structure. A sharp probe tip taper facilitated insertion with minimal trauma. Fabricated probes were subject to examination by optical and electron microscopy and electrochemical testing prior to implantation. 1 × 2 arrays were successfully fabricated on wafer and then packaged together to produce 2 × 2 arrays. Then, probes having electrode sites with adequate electrochemical properties were selected. A subset of arrays was treated with bioactive coatings to encourage neuronal growth and suppress inflammation and another subset of arrays was implanted in conjunction with a virally mediated expression of Caveolin-1. Arrays were attached to a custom-made insertion shuttle to facilitate precise insertion into the rat motor cortex. Stable electrophysiological recordings were obtained during the period of implantation up to 12 months. Immunohistochemical evaluation of cortical tissue around individual probes indicated a strong correlation between the electrophysiological performance of the probes and histologically observable proximity of neurons and dendritic sprouting. The PSEA demonstrates the scalability of sheath electrode technology and provides higher electrode count and density to access a greater volume for recording. This study provided support for the importance of creating a supportive biological environment around the probes to promote the long-term electrophysiological performance of flexible probes in the cerebral cortex. In particular, we demonstrated beneficial effects of the Matrigel coating and the long-term expression of Caveolin-1. Furthermore, we provided support to an idea of using an artificial acellular tissue compartment as a way to counteract the walling-off effect of the astrocytic scar formation around the probes as a means of establishing a more intimate and stable neural interface.


Tissue-reactive drugs enable materials-free local depots.
Local, sustained drug delivery of potent therapeutics holds promise for the treatment of a myriad of localized diseases while eliminating systemic side effects. However, introduction of drug delivery depots such as viscous hydrogels or polymer-based implants is highly limited in stiff tissues such as desmoplastic tumors. Here, we present a method to create materials-free intratumoral drug depots through Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs diffuse into tissue and attach locally for sustained drug release. In TRAPs, potent drugs are modified with ECM-reactive groups and then locally injected to quickly react with accessible amines within the ECM, creating local drug depots. We demonstrate that locally injected TRAPs create dispersed, stable intratumoral depots deep within mouse and human pancreatic tumor tissues. TRAPs depots based on ECM-reactive paclitaxel (TRAP paclitaxel) had better solubility than free paclitaxel and enabled sustained in vitro and in vivo drug release. TRAP paclitaxel induced higher tumoral apoptosis and sustained better antitumor efficacy than the free drug. By providing continuous drug access to tumor cells, this material-free approach to sustained drug delivery of potent therapeutics has the potential in a wide variety of diseases where current injectable depots fall short.


Assessment of the transcriptional activation potential of the HMG chromosomal proteins.
Chromosomal proteins HMG-14, HMG-17, and HMG-1 are among the most abundant, ubiquitous, and evolutionarily conserved nonhistone proteins. Analysis of their structure reveals features which are similar to those of certain transcription factors. The distribution of charged amino acid residues along the polypeptide chains is asymmetric: positive charges are clustered toward the N-terminal region, while negative charges are clustered toward the C-terminal region. The residues in the C-terminal region have the potential to form alpha helices with negatively charged surfaces. The abilities of HMG-14, -17, and -1 to function as transcriptional activators were studied in Saccharomyces cerevisiae cells expressing LexA-HMG fusion proteins (human HMG-14 and -17 and rat HMG-1) which bind to reporter molecules containing the beta-galactosidase gene downstream from a lexA operator. Fusion constructs expressing deletion mutants of HMG-14, -17, and -1 were also tested. Analysis of binding to the lexA operator with in vitro-synthesized fusion proteins shows that there are more sites for HMG-14, -17, and -1 binding than for LexA binding and that only the fusion constructs which contain the C-terminal, acidic domains of HMG-17 bind the lexA operator specifically. None of the LexA-HMG fusion protein constructs elevate the level of beta-galactosidase activity in transfected yeast cells. Thus, although HMG-14, -17, and -1 are structurally similar to acidic transcriptional activators, these chromosomal proteins do not function as activators in this test system.


Immunogenicity of tissue plasminogen activators in rhesus monkeys: antibody formation and effects on blood level and enzymatic activity.
The immunogenicity of a tissue-type plasminogen activator analog, mt-PA6, consisting of the second kringle and protease domains, was compared to that of the native-sequence protein (nt-PA) in rhesus monkeys. Antibody responses were compared in groups of eight monkeys that were treated by i.v. injection twice, 1 month apart, using doses and regimens chosen to mimic therapy (0.5 mg/kg mt-PA6 bolus, 1.25 mg/kg nt-PA bolus + infusion). An additional group was treated with a 0.5 mg/kg nt-PA bolus. A single positive response was obtained in a monkey treated with 0.5 mg/kg nt-PA after the primary injection. Following the secondary injection, responses were obtained in 1/8, 3/8, and 6/8 monkeys treated with mt-PA6, nt-PA as a bolus, or nt-PA as a bolus + infusion, respectively. Several monkeys were selected to determine whether circulating tPA antibody altered the pharmacokinetics of mt-PA6. Clearance was found to decrease without affecting peak blood levels as antibody concentrations increased from 0.02 to 100 micrograms/ml. In contrast, the peak blood level was reduced by 99% at an antibody concentration of 152 micrograms/ml in a monkey that had been exposed to mt-PA6 in adjuvant 14 months previously. Further, only the serum from this and three other hyperimmunized monkeys inhibited the enzymatic activity of tPA in vitro. It is concluded that mt-PA6 is not more immunogenic than nt-PA in rhesus, and that low levels of antibody are more likely to influence the pharmacokinetic properties of tPA than to inhibit its enzymatic activity. It is unlikely that mt-PA6 would present a serious immunogenic risk in humans.


[Analysis of Subclassification by Size and Survival-associated Factors of Stage I Non-small Cell Lung Cancer.].
The sixth edition of TNM system is hard to illuminate the survival of different tumor load precisely. This retrospective study attempted to evaluate the prognostic clinicopathologic features of non-small cell lung cancer (NSCLC). Especially we subclassified tumor sizes to validate the new T classification of international union against cancer (UICC). We reviewed the clinical data of 327 stage I NSCLC with complete resection. Survival was analysed by Kaplan-Meier method and Log-rank test. The multivariate analysis was performed with Cox's proportion risk model. The 5-year survival rate of poorly differentiated histologic grade and moderate-well differentiated histologic grade were 60.49% and 73.98% respectively (P=0.02574); The 5-year survival rate of preoperative anemia or not were 64.44% and 73.00% (P=0.0182); Tumor size was divided into <=2 cm, 2.1 cm-3 cm, 3.1 cm-5 cm and 5.1 cm-7 cm with 5-year survival rate of 86.30%, 72.73%, 62.50% and 58.33% respectively (P<0.0001). Histologic grade, preoperative anemia and tumor size are the independent prognostic factors in complete resection of stage I NSCLC. The patients with moderate-well differentiated histologic grade, non-preoperative anemia and smaller tumor size have longer survival time. Changes in tumor size classification are to subclassify into<=2 cm, 2.1 cm-3 cm, and 3.1 cm-5 cm, which is consistent with new T-staging system protocol of UICC.


Evaluating investments in typhoid vaccines in two slums in Kolkata, India.
New-generation vaccines against typhoid fever have the potential to reduce the burden of disease in areas where the disease is endemic. The case for public expenditure on typhoid Vi polysaccharide vaccines for two low-income, high-incidence slums (Narkeldanga and Tiljala) in Kolkata, India, was examined. Three measures of the economic benefits of the vaccines were used: private and public cost-of-illness (COI) avoided; avoided COI plus mortality risk-reduction benefits; and willingness-to-pay (WTP) derived from stated preference (contingent valuation) studies conducted in Tiljala in 2004. Benefits and costs were examined from a social perspective. The study represents a unique opportunity to evaluate typhoid-vaccine programmes using a wealth of new site-specific epidemiological and economic data. Three typhoid-vaccination strategies (targeting only enrolled school children, targeting all children, and targeting adults and children) would most likely pass a social cost-benefit test, unless benefits are restricted to include only avoided COI. All three strategies would be considered 'very cost-effective' using the standard comparisons of cost per disability-adjusted life-year avoided with per-capita gross domestic product. However, at an average total cost per immunized person of approximately US$ 1.1, a typhoid-vaccination programme would absorb a sixth of existing public-sector spending on health (on a per-capita basis) in India. Because there appears to be significant private economic demand for typhoid vaccines, the Government could design a financially-sustainable programme with user-fees. The results show that a programme where adults pay a higher fee to subsidize vaccines for children (who have higher incidence) would avoid more cases than a uniform user-fee and still achieve revenue-neutrality.


Classification of somatic syndromes in ICD-11.
As a part of the its current revision of the International Classification of Diseases (ICD), the WHO is proposing major changes to the somatoform section of the chapter on Mental and Behavioral Disorders. This article reviews the basis for these changes and presents the highlights of the new category being proposed. As currently classified in ICD-10, somatoform disorders have major problems that limit their clinical utility. Among these are the negative criterion specifications for the diagnosis of the disorders, the rarity of the prototype categories, and the imprecise boundaries between them. To respond to these problems, a new category of Bodily Distress Disorder (BDD) is proposed to replace the current categories. The proposed category is defined by a simplified set of criterion specifications that are based on the presence of positive psycho-behavioral features. The new category, still in proposal stage, offers the prospect of responding to the need for a reliable diagnosis of clinically significant somatic preoccupations that are common in the community as well as in routine clinical practice. It is expected that improved diagnosis should aid the correct identification of these conditions and enhance the ability of clinicians to provide effective treatment.


Paradoxical Reaction to Alprazolam in an Elderly Woman with a History of Anxiety, Mood Disorders, and Hypothyroidism.
With less than 1% of patients who use benzodiazepines being affected, paradoxical responses to benzodiazepines are rare. In this case report, we outline the course of an 80-year-old female who developed a paradoxical response to benzodiazepines. Significant medical and psychiatric history includes anxiety, mood disorder, hypothyroidism, bilateral mastectomy, goiter removal, and triple bypass. The patient presented with mental status changes, anxiety, motor restlessness, and paranoia. Over time, a temporal relationship between the severity of the patient's motor agitation and intake of alprazolam was observed. As doses of alprazolam were decreased, her motor agitation became less severe. In addition to motor agitation, the patient also demonstrated increased aggressiveness, a subjective feeling of restlessness, and increased talkativeness. As her dose of alprazolam decreased, many of the patient's symptoms were observed to decrease. This case report also discusses theories regarding the pathophysiology of paradoxical reactions to benzodiazepines, known risk factors, and appropriate treatment.


Acute pancreatitis associated with lisinopril and olanzapine.
A case of acute pancreatitis associated with lisinopril and olanzapine is described. A 69-year-old woman came to the emergency department after four days of experiencing epigastric pressurelike pain that radiated to the left lower quadrant and worsened with ingestion of food. She had started lisinopril three months prior for treatment of hypertension and had been taking olanzapine regularly for bipolar disorder. Upon admission, she was afebrile and hemodynamically stable and exhibited tenderness of the epigastric region. Elevated pancreatic enzymes and abdominal computed tomography (CT) imaging findings confirmed the diagnosis of pancreatitis. Common causes of pancreatitis were ruled out, and it was determined that the recent combination of lisinopril and olanzapine was the likely cause. Food and liquids were withheld, and all oral medications were stopped at hospital admission. Her pain resolved completely after two days. She was discharged on hospital day 4, and all of her medications except lisinopril and olanzapine were resumed. During a follow-up visit with her primary care physician, she reported to be doing well and had no systemic complaints. Olanzapine was reinitiated at that time but was discontinued a month later by her psychiatrist, who was concerned about the development of recurrent symptoms of pancreatitis. Valsartan was prescribed to achieve optimal blood pressure control three weeks after discharge. A follow-up CT scan of the abdomen a month later found no residual pancreatic abnormalities. The additive effect of two known pancreatitis-causing medications resulted in increased risk and subsequent acute pancreatitis in this patient.


Cardiovascular risk factors in the Czech population.
In 1985 and 1988 as part of the WHO's MONICA project two surveys of cardiovascular risk factors were conducted in the population aged 25 to 64 years and resident in the six districts of the Czech Republic collaborating in MONICA. Over a period of three years, the prevalence of smoking decreased from 46% to 41.8% (p less than 0.05) in men. Daily cigarette consumption declined from 17.9 to 15.1 (p less than 0.001) in men and from 11.1 to 10.1 (p less than 0.05) in women. Despite the unchanged prevalence of hypertension during the three years' period the proportion of population with elevated BP levels declined from 22.25% to 19.1% in men (p less than 0.05), and from 16.8% to 14.0% (p less than 0.05) in women as a result of better hypertension control. The prevalence of obesity in men rose from 18.5% to 23.9% (p less than 0.001). The proportion of individuals with a total cholesterol level over 5.2 mmol/l rose from 78.0% to 83.1% (p less than 0.001) in men and from 75.9% to 80.6% in women (p less than 0.01). The changes were favourable only in those risk factors that were actively influenced by the preventive programmes "A Chance for Three Million" in smoking habits, and the "National Programme of Hypertension Control". The authors believe that consistent nationwide preventive programmes might exert a beneficial effect on the profile of risk factors of the whole Czech population.


Morphometric Shape Analysis of Corpus Callosum in Children With Down Syndrome.
Down syndrome (DS) is characterized by varying degrees of mental retardation and delay in neurocognitive functions. Herein, we analyzed the morphometric shape of the corpus callosum (CC) in children with DS. Twenty-three DS cases underwent magnetic resonance imaging and have grossly normal CC, and 23 control group cases were included in this retrospective study (2012-2020). The CC was obtained from T2-weighted mid-sagittal images, and certain anatomical points were marked on the CC. Statistical geometric shapes and deformations of CC were evaluated for both groups. The age range of patients with DS and control group was 6 to 42 months. A statistically significant difference was found in the shape of CC between the groups (P < .001). Deformation was most evident in the splenium in the DS group.


A Novel Bacteriocin Against Shigella flexneri From Lactiplantibacillus plantarum Isolated From Tilapia Intestine: Purification, Antibacterial Properties and Antibiofilm Activity.
Few bacteriocins with antibacterial activity against Shigella flexneri have been reported. Here, a novel bacteriocin (LFX01) produced by Lactiplantibacillus plantarum strain LF-8 from the intestine of tilapia was purified and extensively characterized. LFX01 possesses a molecular weight of 1049.56 Da and an amino acid sequence of I-T-G-G-P-A-V-V-H-Q-A. LFX01 significantly inhibited S. flexneri strain 14 (S. flexneri_14) growth. Moreover, it exhibited excellent stability under heat and acid-base stress, and presented sensitivity to a variety of proteases, such as proteinase K, pepsin, and trypsin. The minimum inhibitory concentration (MIC) of LFX01 against S. flexneri_14 was 12.65 μg/mL, which was smaller than that of most of the previously found bacteriocins. Furthermore, LFX01 significantly inhibited (p < 0.05) S. flexneri_14 cells and decreased their cell viability. In addition, LFX01 could significantly (p < 0.05) inhibit biofilm formation of S. flexneri_14. Scanning electron microscopy analysis presented that the cell membrane permeability of S. flexneri_14 was demolished by LFX01, leading to cytoplasmic contents leakage and cell rupture death. In summary, a novel bacteriocin of lactic acid bacteria (LAB) was found, which could effectively control S. flexneri in both planktonic and biofilm states.


Cisplatin induces apoptosis in LLC-PK1 cells via activation of mitochondrial pathways.
Cisplatin, a commonly used chemotherapeutic agent, has a major limitation because of its nephrotoxicity. Recent studies have shown that cisplatin causes apoptotic cell death in renal tubule cells, but the underlying molecular mechanisms remain to be elucidated. In this study, cisplatin was found to induce apoptosis in a dose- and duration-dependent manner in cultured proximal tubule (LLC-PK1) cells, as evidenced by DNA laddering and TdT-mediated dUTP nick end-labeling assay. Pretreatment with the specific caspase 9 inhibitor LEHD-CHO completely prevented the apoptosis, whereas the caspase 8 inhibitor IETD-fmk had no effect. Furthermore, the activity of caspase 9 was upregulated about sixfold by cisplatin in a dose-dependent manner. These results implicated the caspase 9-dependent mitochondrial apoptotic pathways. Indeed, cisplatin triggered a duration-dependent translocation of cytochrome c from the mitochondria to the cytosol, by immunofluorescence and Western blots. Cisplatin treatment also resulted in the duration-dependent activation and mitochondrial translocation of the pro-apoptotic molecule Bax, by immunofluorescence. Finally, cisplatin induced a duration-dependent onset of the mitochondrial permeability transition. Our results indicate that cisplatin induces apoptosis in LLC-PK1 cells via activation of mitochondrial signaling pathways. The sequence of events may be summarized as follows: activation of Bax induces mitochondrial permeability transition, leading to release of cytochrome c, activation of caspase 9, and entry into the execution phase of apoptosis. Inhibition of this specific pathway may provide a strategy to minimize cisplatin-induced nephrotoxicity.


Pluse Therapy with Dexamethasone in Reiter's Disease.
A patient having Reiter's dsease manifesting as fever, arthritis and skin lesions failed to respond to adequate treatment with oxyphenbutazone, prednisolone, tetracycline, methotrexate, levamisol and haemodialysis in various combinations. Pulse therapy, however, consisting of intravenous infusions of 140 mg dexamethasone in 500 ml of 5% glucose on 3 consecutive days every month led to a dramatic improvement, The patient who was earlier bed-ridden because of, arthritis, was able to walk back home within'6 months. The side effects of systemic corticosteroids with this mode of treatment were far milder compared to the usual mode of therapy in spite of a much higher dose being used during pluse therapy.


[Demographic measures].
"In this article, several measures of comparing demographic phenomena such as birth, death and migration in different years or in different population categories are discussed. In order to measure these phenomena, the demographic events occurring to persons with the same set of characteristics (i.e. with the same age, sex, marital status, place of residence etc.) are related to the number of persons in the category characterized by these same features." The geographic focus is on the Netherlands. (summary in ENG)


Treatment of Epstein-Barr virus lymphoproliferative disease after hematopoietic stem-cell transplantation with hydroxyurea and cytotoxic T-cell lymphocytes.
Epstein-Barr virus (EBV) lymphoproliferative disease (LPD) is a potentially fatal complication that may follow allogeneic hematopoietic stem-cell transplantation (HSCT). In this article, the authors report a 2-year-old girl with Hurler's syndrome who developed multiple central nervous system (CNS) EBV LPD lesions 1 year after unrelated donor HSCT. Before this CNS occurrence, the patient had a complete response to rituximab treatment for EBV LPD of the spleen and lymph nodes; however, treatment of the CNS disease with rituximab proved ineffective. Because of reported favorable response of primary CNS EBV LPD in two human immunodeficiency virus-positive patients, the authors treated this patient with low-dose oral hydroxyurea. The patient improved clinically, with a decrease in size of multiple EBV LPD brain lesions. Subsequently, the patient received EBV-specific cytotoxic T-cell lymphocytes and remains well. The benefit and limited toxicity of hydroxyurea therapy merit its further consideration as treatment for EBV LPD.


Opioid Use Disorder in Children and Adolescents: Risk Factors, Detection, and Treatment.
Opioid medications are an important tool in the management of pain and have been used in clinical practice for centuries. However, due to the highly addictive nature of this class of medications coupled with the life-threatening side effect of respiratory depression, opioid misuse has become a significant public health crisis worldwide. Children and adolescents are at risk for opioid misuse, and early detection is imperative to facilitate treatment and improve outcomes. This review will address the current state of opioid misuse and treatment in children and adolescents in the United States.


[Concomitant labyrinthitis].
The principal pathogenetic mechanism of labyrinthopaty development after traumas and operations lies in autoimmune inflammation of the contralateral ear similar to sympathetic inflammation of the eye. By analogy with sympathetic ophthalmitis, a term <<concomitant labyrinthitis>> is proposed. Due to selective permeability of selective membranes, immune system has no connection with <<extrabarrier>> organs. These organs and tissues are isolated from the key sourse of immunity -- blood. Autotolerance to them is absent and their proteins are autoantigens. In destruction of hemato-labyrinthine barrier these autoantigens can reach lymphoid organs and provoke immune response inducing a cytotoxic action in relation to both the affected and the contralateral labyrinth. Besides pathology of the affected labyrinth, clinical picture of labyrinthopathy is caused by autoimmune labyrinthitis of the contralateral ear whereas in <<dead>> labyrinthitis of the affected ear - slow-progressive autoimmune concomitant labyrinthitis. Case reports are presented.


Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice.
Two selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, both at a daily dose of 20 mg, were compared in patients with unipolar major depression treated in general practice. This was a multicentre, double-blind, randomized trial carried out in France. The duration of treatment was 8 weeks. Patients were assessed by means of the Montgomery-Asberg Depression Rating Scale (MADRS), the 17 items Hamilton Depression Rating Scale (HAMD) and the investigator's Clinical Global Impressions (CGI), Observed and spontaneously reported adverse events were also recorded. A total of 357 patients of both sexes, aged between 21 and 73 years, entered the double-blind phase of the trial. A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments. Apart from back pain recorded more frequently in the citalopram group, no significant difference was found between the two treatment groups with regard to adverse events, and both citalopram and fluoxetine were considered to be well tolerated. It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression. Citalopram showed an earlier onset of recovery than fluoxetine.


Mutational analysis of the att DNA-binding domain of phage Mu transposase.
The transposase (A protein) of phage Mu encodes binding to two families of DNA sites, att sites located at the Mu ends and enhancer sites located internally. Separate subdomains in the N-terminal domain I of Mu A protein are known to be involved in recognition of the att and enhancer sites. We have delineated an approximately 135 aa region within domain I beta gamma that specifies binding to Mu att sites. This peptide was overexpressed and its properties compared with that of the larger domain I beta gamma as well as the intact Mu A protein. Extensive mutagenesis of residues around a putative helix-turn-helix DNA-binding motif within the I beta domain identified several mutants defective in DNA transposition in vivo. Of these, Mu A(K157Q) was completely defective in att DNA-binding. Mu A(F131S) and Mu A(R146N) had a lower affinity for att DNA and low levels of transposition in vitro. Our results indicate that residues in the gamma region are required for activity and that residues outside the beta gamma region must also influence discrimination between the multiple att sites.


Lipoxygenase and hydroperoxide lyase in germinating watermelon seedlings.
Lipoxygenase (EC 126.96.36.199) was found in seedlings of Citrullus lanatus (Thunb.) Matsum. and Nakai (watermelon). The enzyme has pH optima of 4.4 and 5.5 and is inhibited by 0.2 mM nordihydroguaiaretic acid. It is present in two functional units with estimated molecular weights of 120,000 and 240,000, respectively.A new enzyme, tentatively termed hydroperoxide lyase, has been partially purified from watermelon seedlings. The enzyme, located principally in the region of the hypocotyl-root junction, catalyzes the conversion of 13-l-hydroperoxy-cis-9-trans-11-octadecadienoic acid to 12-oxo-trans-10-dodecenoic acid and hexanal. The hydroperoxide lyase enzyme from watermelon has a molecular weight in excess of 250,000, a pH optimum in the range of 6 to 6.5, and is inhibited by p-chloromercuribenzoic acid. Its presence has also been demonstrated in other cucurbits.The maximum activity of both enzymes occurs on the 6th day of germination. The identification of the products of the hydroperoxide lyase reaction suggests that lipoxygenase and hydroperoxide lyase may be involved in the conversion of certain polyunsaturated fatty acids to traumatic acid (trans-2-dodecenedioic acid).


A homozygous ZMPSTE24 null mutation in combination with a heterozygous mutation in the LMNA gene causes Hutchinson-Gilford progeria syndrome (HGPS): insights into the pathophysiology of HGPS.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder normally caused by a spontaneous heterozygous mutation in the LMNA gene that codes for the nuclear lamina protein lamin A. Several enzymes are involved in the processing of its precursor, prelamin A, to the mature lamin A. A functional knockout of one of the enzymes involved in prelamin A processing, the zinc metalloprotease ZMPSTE24, causes an even more severe disorder with early neonatal death described as restrictive dermatopathy (RD). This work describes a HGPS patient with a combined defect of a homozygous loss-of-function mutation in the ZMPSTE24 gene and a heterozygous mutation in the LMNA gene that results in a C-terminal elongation of the final lamin A. Whereas the loss of function mutation of ZMPSTE24 normally results in lethal RD, the truncation of LMNA seems to be a salvage alteration alleviating the clinical picture to the HGPS phenotype. The mutations of our patient indicate that farnesylated prelamin A is the deleterious agent leading to the HGPS phenotype, which gives further insights into the pathophysiology of the disorder.


Benzodiazepine use in breast cancer survivors: findings from a consecutive series of 1,000 patients.
This study reports the percentage of breast cancer survivors receiving ongoing benzodiazepines and the circumstances surrounding their usage. The medical records of 1,000 consecutive breast cancer survivors who were no longer receiving adjuvant chemotherapy were reviewed. Among those patients, 7.9% (95% confidence interval 6.2-9.6; higher than the 3% rate in the general population) were receiving benzodiazepines. Lorazepam was most commonly prescribed. Sixty-eight patients were cancer free at their last visit, and 51 had not been taking benzodiazepines prior to their cancer diagnosis. Anxiety was the single most frequent reason for initiating and continuing benzodiazepines. Anxiety appears to be a common explanation for relatively high rates of benzodiazepine use in breast cancer survivors. This finding merits further study.


Variations in the quality of care for very-low-birthweight infants: implications for policy.
Much of the decline in childhood mortality over the past two decades is attributable to improvements in neonatal intensive care for very-low-birthweight infants. Yet large and persistent disparities persist in the quality of neonatal intensive care across hospitals. Improving care for infants now served by hospitals with poor outcomes can greatly reduce infant mortality, particularly among minority infants who are more likely to be very low birthweight and cared for by hospitals with poor outcomes. Referral of high-risk births to hospitals with the best outcomes is another promising strategy.