Traumatic brain injury increases TGF beta RII expression on endothelial cells.
Transforming growth factor beta (TGFbeta) modulates a variety of growth related functions following traumatic injury. The cellular response to TGFbeta is predominantly mediated through TGFbeta receptor I (TGFbetaRI) and receptor II (TGFbetaRII) on the cell surface and SMAD proteins intracellularly. We investigated the expression of TGFbeta receptors in the acute and chronic phases of a traumatic cerebral injury (TCI) by immunohistochemistry and in cultures of murine brain microvascular endothelial (EN) cells using cytofluorimetry. Here, we report that TGFbetaRII expression significantly increases on brain endothelial cells in the chronic phase of TCI. SMAD3 and SMAD4 protein expression were also upregulated suggesting the activation of TGFbeta receptor intracellular signaling. When TGFbetaRI and TGFbetaRII expression was studied in in vitro cultures of murine brain microvessel EN cells, TGFbetaRII showed increased expression on proliferating cells that are incorporating BrdU. These data show a differential expression of TGFbetaRI and TGFbetaRII on brain microvessel EN cells in the acute and chronic phases of TCI that might be associated with EN proliferation following injury.


Role of aquaporin water channels in pleural fluid dynamics.
Continuous movement of fluid into and out of the pleural compartment occurs in normal chest physiology and in pathophysiological conditions associated with pleural effusions. RT-PCR screening and immunostaining revealed expression of water channel aquaporin-1 (AQP1) in microvascular endothelia near the visceral and parietal pleura and in mesothelial cells in visceral pleura. Comparative physiological measurements were done on wild-type vs. AQP1 null mice. Osmotically driven water transport was measured in anesthetized, mechanically ventilated mice from the kinetics of pleural fluid osmolality after instillation of 0.25 ml of hypertonic or hypotonic fluid into the pleural space. Osmotic equilibration of pleural fluid was rapid in wild-type mice (50% equilibration in <2 min) and remarkably slowed by greater than fourfold in AQP1 null mice. Small amounts of AQP3 transcript were also detected in pleura by RT-PCR, but osmotic water transport was not decreased in AQP3 null mice. In spontaneously breathing mice, the clearance of isosmolar saline instilled in the pleural space ( approximately 4 ml. kg(-1). h(-1)) was not affected by AQP1 deletion. In a fluid overload model produced by intraperitoneal saline administration and renal artery ligation, the accumulation of pleural fluid (approximately 0.035 ml/h) and was not affected by AQP1 deletion. Finally, in a thiourea toxicity model of acute endothelial injury causing pleural effusions and lung interstitial edema, pleural fluid accumulation in the first 3 h ( approximately 4 ml. kg(-1). h(-1)) was not affected by AQP1 deletion. These results indicate rapid osmotic equilibration across the pleural surface that is facilitated by AQP1 water channels. However, AQP1 does not appear to play a role in clinically relevant mechanisms of pleural fluid accumulation or clearance.


Matrine inhibits PMA-induced MMP-1 expression in human dermal fibroblasts.
Matrix metalloproteinase-1 (MMP-1) plays an important role in the maintenance and turnover of extracellular matrix (ECM) macromolecules. Remodelling of extracellular matrix by MMPs is a hallmark feature of physiological and pathological processes. In this study, in order to establish the therapeutic potential of matrine, we investigated its effect on MMP-1 expression in human dermal fibroblast cells. We found that matrine inhibited both MMP-1 mRNA and protein expression induced by PMA (phorbol myristate acetate). Therefore, we characterized the inhibitory mechanism of matrine on PMA-induced MMP-1 expression. Matrine inhibited PMA-induced activation of the AP-1 promoter, an important nuclear transcription factor in MMP-1 expression. Additionally, we detected that matrine suppressed the PMA-induced phosphorylation of two mitogen-activated protein kinases, extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but did not suppress the PMA-induced phosphorylation of p38 kinase. These results suggest that matrine suppresses PMA-induced MMP-1 expression through inhibition of the AP-1 signaling pathway and also may be beneficial for treatment of some inflammatory skin disorders.


Human corneal aldehyde dehydrogenase: purification, kinetic characterisation and phenotypic variation.
Human corneal aldehyde dehydrogenase (designated ALDH3) was purified to homogeneity and characterised with respect to substrate specificity and inhibition by thiol reagents. The enzyme was present as a major soluble protein (5% of the total soluble protein) and was found to efficiently catalyse the oxidation of medium chain peroxidic aldehydes which may be found in the cornea. These findings are consistent with the proposal that ALDH3 plays a dual role in the absorption of UVR and in the oxidation of peroxidic aldehydes in the mammalian cornea. Disulfiram did not inhibit this enzyme under the conditions used in this study, however p-hydroxymercuribenzoate rapidly inactivated the enzyme. Analysis of the proteins of the cornea and surrounding tissue indicated that in both the cow and the human, changes in the nature and quantity of soluble proteins occurred. Phenotype variants of the ALDH3 were apparent in a small Australian population.


Measles virus V protein blocks Jak1-mediated phosphorylation of STAT1 to escape IFN-alpha/beta signaling.
Viruses have evolved various strategies to escape the antiviral activity of type I interferons (IFN-alpha/beta). For measles virus, this function is carried by the polycistronic gene P that encodes, by an unusual editing strategy, for the phosphoprotein P and the virulence factor V (MV-V). MV-V prevents STAT1 nuclear translocation by either sequestration or phosphorylation inhibition, thereby blocking IFN-alpha/beta pathway. We show that both the N- and C-terminal domains of MV-V (PNT and VCT) contribute to the inhibition of IFN-alpha/beta signaling. Using the two-hybrid system and co-affinity purification experiments, we identified STAT1 and Jak1 as interactors of MV-V and demonstrate that MV-V can block the direct phosphorylation of STAT1 by Jak1. A deleterious mutation within the PNT domain of MV-V (Y110H) impaired its ability to interact and block STAT1 phosphorylation. Thus, MV-V interacts with at least two components of IFN-alpha/beta receptor complex to block downstream signaling.


Crystal structure of the RNA-binding domain from transcription termination factor rho.
Transcription termination factor rho is an ATP-dependent hexameric helicase found in most eubacterial species. The Escherichia coli rho monomer consists of two domains, an RNA-binding domain (residues 1-130) and an ATPase domain (residues 131-419). The ATPase domain is homologous to the beta subunit of F1-ATPase. Here, we report that the crystal structure of the RNA-binding domain of rho (rho130) at 1.55 A confirms that rho130 contains the oligosaccharide/oligonucleotide-binding (OB) fold, a five stranded beta-barrel. The beta-barrel of rho130 is also surprisingly similar to the N-terminal beta-barrel of F1 ATPase, extending the applicability of F1 ATPase as a structural model for hexameric rho.


Psychosocial factors associated with broadly defined bulimia nervosa during early pregnancy: findings from the Norwegian Mother and Child Cohort Study.
The purpose of the present study was to investigate the relationship between psychosocial characteristics and broadly defined bulimia nervosa during early pregnancy, including factors associated with continuation, incidence and remission. A total of 41 157 women completed questionnaires at approximately gestation week 18, including items on eating disorders and psychosocial characteristics as a part of Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Incident bulimia nervosa during the first trimester was significantly associated with symptoms of anxiety and depression and low self-esteem and life satisfaction, whereas remission was significantly associated with higher self-esteem and life satisfaction. Continuation was not significantly related to any of the psychosocial variables tested. Onset of bulimia nervosa during pregnancy is associated with mood and anxiety symptoms. Remission of bulimic symptoms and new onset of bulimia nervosa are associated with opposite profiles of self-esteem, and life satisfaction measures.


[Asthma classification].
Asthma, as chronic inflammatory disease, shows variations in clinical manifestations and the degree of airflow obstruction, so its severity may change over time in the same patient. The Global Initiative for Asthma (GINA) established a practical system of classification, considering clinical and functional aspects as frequency of diurnal and nocturnal respiratory symptoms and lung function, their combination allows for classifying asthma severity as intermittent and persistent ( mild, moderate and severe). Recently, it has been proposed to classify the asthma according to degree of control: controlled, partly controlled and uncontrolled. The parameters used in this system are: frequency of diurnal and nocturnal respiratory symptoms, activity limitation, use of rescue therapy, determining the forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) and the exacerbations. The patient's participation on the asthma classification has also been considered through the self application of asthma control questionnaire (ACT). Patients with high risk of death are classified in the group of difficult asthma control (ADC), requiring major and minor criteria to define it; the common denominator is the decontrol of the disease, high dose steroids and appropriate treatment previously established. Sort asthma with any of these systems, information about its impact on the patient's life and thus establish the recommended treatment schedule for each patient group.


Studies of cloned simian immunodeficiency virus-specific T lymphocytes. gag-specific cytotoxic T lymphocytes exhibit a restricted epitope specificity.
CD8+ CTL inhibit the replication of HIV and simian immunodeficiency virus of macaques (SIVmac) in PBL and, therefore, are likely to play an important role in containing the spread of the AIDS virus in infected individuals. We have generated a series of gag-specific lytic T lymphocyte clones from PBL: of an SIVmac-infected rhesus monkey. These T cell clones are CD3+CD8+ and are MHC class I-restricted in their target specificity. They are, therefore, CTL. Interestingly, all gag-specific CTL clones, as well as the gag-specific lytic activity of PBL of this monkey, demonstrated specificity for a single 25 amino acid fragment of the SIVmac gag protein. Moreover, they were restricted in their lytic function by a single MHC class I allele. These findings illustrate a powerful method for cloning AIDS virus-specific T lymphocytes and demonstrate a remarkably restricted epitope specificity of this AIDS virus-specific CTL response.


Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer.
A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17,20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of 1a in the homology model of 17,20-lyase, the 6,7-dihydro-5H-pyrrolo[1,2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17,20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.


Detection of intraoperative myocardial ischaemia--a comparison among electrocardiographic, myocardial metabolic, and haemodynamic measurements in patients with reduced ventricular function.
This study determined the sensitivity and specificity of haemodynamic and ECG monitors to detect the development of intraoperative myocardial ischaemia utilizing myocardial lactate production as the standard. In 29 patients with reduced ejection fraction (0.27-0.50) undergoing coronary artery revascularization, measurements were made at the awake, post-induction, post-intubation, first skin incision, post-sternotomy, pre-protamine, immediately post-cardiopulmonary bypass, and skin suture intervals. At each interval, measurement of a haemodynamic profile (including pulmonary artery occlusion (PAOP) and central venous (CVP) pressures, heart rate, and pressure rate quotient); myocardial lactate extraction and flux; changes in ST segments in ECG leads, V5 and II utilizing a Siemens 1280 intraoperative monitor, and a Marquette 8500 Holter monitor utilizing leads V5, V2, and AVF were made. "Ischaemia" was considered to be present when myocardial lactate production (MLP) occurred, PAOP or CVP increased by 5 mmHg above the baseline value, the pressure rate quotient was < 1, or ST segment deviation (> 1 mm) occurred in any lead for > 1 min. Variables positive when MLP was positive were the pressure rate quotient (sensitivity 32.8%, specificity 71.9%), CVP (sensitivity 10.9%, specificity 92.6%), and PAOP (sensitivity 1.6%, specificity 99.2%). Holter monitoring had a 100% positive predictive value but poor sensitivity (1.6%). The ECG (Lead V5 + II) measures of ischaemia were insensitive (17.5%) and relatively non-specific (87.7%). We conclude that, in this patient group and using myocardial lactate production as the standard, the pressure rate quotient, elevations in CVP or PAOP, or ST segment changes are insensitive measures of intraoperative myocardial ischaemia.


Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients.
Postmortem analyses from clinical neural transplantation trials of several subjects with Parkinson's disease revealed surviving grafted dopaminergic neurons after more than a decade. A subset of these subjects displayed isolated dopaminergic neurons within the grafts that contained Lewy body-like structures. In this review, we discuss why this isolated cell damage is unlikely to affect the overall graft function and how we can use these observations to help us to understand age-related neurodegeneration and refine our future cell replacement therapies.


Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).
In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.


Classification of essential tremor.
Classification of essential tremor was attempted using tremor frequency; tremor duration; family history of tremor; responsiveness to alcohol, propranolol, and primidone; muscle contraction pattern; and long-latency reflexes. Sixty-one patients were evaluated. The majority of patients had a tremor frequency less than 7.0 Hz, a positive family history, and a positive response to alcohol. Approximately 46% of patients had a beneficial response with propranolol and 71% with primidone. Tremor frequency was inversely correlated with age and directly correlated with an antagonist pattern of muscle contraction. Enhanced long-latency reflexes were not found. Other characteristics of essential tremor were not significantly correlated. It is concluded that essential tremor can not be classified into subtypes.


Direct regulation of beta3-integrin subunit gene expression by HOXA10 in endometrial cells.
Estrogen and progesterone regulate HOXA10 expression in the endometrium, where HOXA10 is necessary for implantation. The integrins are also involved in early embryo-endometrial interactions. Here we show that HOXA10 directly regulates beta3-integrin subunit expression in the endometrium, likely mediating the effect of sex steroids on beta3-integrin expression. beta3-Integrin expression was decreased in endometrium shown to have low HOXA10 expression. beta3-Integrin mRNA levels were increased in endometrial adenocarcinoma cells (Ishikawa) transfected with pcDNA3.1/HOXA10, and decreased in cells treated with HOXA10 antisense. Seven consensus HOXA10 binding sites were identified 5' of the beta3-integrin gene. Direct binding of HOXA10 protein to four sites was demonstrated by EMSA. Reporter gene expression increased in BT-20 cells cotransfected with pcDNA3.1/ HOXA10 and pGL3-promoter vector containing region F (encompassing all seven HOXA10 consensus sites). A 41-bp segment (Region A) showed highest affinity binding to HOXA10 protein. Increased reporter expression, equal in magnitude to that obtained with Region F, was obtained with Region A. HOXA10 protein binding within Region A was localized by deoxyribonuclease I footprinting. beta3-Integrin expression was directly up-regulated by HOXA10 through a 41-bp 5'-regulatory element. Sex steroids regulate the expression of endometrial beta3-integrin through a pathway involving HOXA10.


Genetic Markers Analyses and Bioinformatic Approaches to Distinguish Between Olive Tree (Olea europaea L.) Cultivars.
The genetic diversity of 22 olive tree cultivars (Olea europaea L.) sampled from different Mediterranean countries was assessed using 5 SNP markers (FAD2.1; FAD2.3; CALC; SOD and ANTHO3) located in four different genes. The genotyping analysis of the 22 cultivars with 5 SNP loci revealed 11 alleles (average 2.2 per allele). The dendrogram based on cultivar genotypes revealed three clusters consistent with the cultivars classification. Besides, the results obtained with the five SNPs were compared to those obtained with the SSR markers using bioinformatic analyses and by computing a cophenetic correlation coefficient, indicating the usefulness of the UPGMA method for clustering plant genotypes. Based on principal coordinate analysis using a similarity matrix, the first two coordinates, revealed 54.94 % of the total variance. This work provides a more comprehensive explanation of the diversity available in Tunisia olive cultivars, and an important contribution for olive breeding and olive oil authenticity.


Dde chlorinated insecticide 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDD) increases intracellular calcium in rat myometrial smooth muscle cells.
A previous report from this laboratory showed that two DDT isomers, o,p'-DDT and p,p'-DDD, increased the frequency of spontaneous oscillatory contractions to a similar extent in isolated rat uterine segments. Because regulation of intracellular calcium is fundamental for the development of oscillatory contractions, the present study examined the effects of p,p'-DDD on intracellular free calcium concentration ([Ca2+]i) in individual rat myometrial smooth muscle cells loaded with the fluorescent Ca2+ indicator fura 2. In the presence of extracellular calcium, 50 and 100 microM p,p'-DDD significantly increased peak [Ca2+]i 586 and 921%, respectively, over basal [Ca2+]i. No significant effect was observed with 10 microM p,p'-DDD. In the absence of extracellular calcium, the response to 100 microM p,p'-DDD was significantly attenuated, with cells averaging a 108% increase in peak [Ca2+]i over basal levels, presumably through Ca2+ release from intracellular stores. Nifedipine and cadmium chloride, blockers of voltage-dependent calcium channels, inhibited 100 microM p,p'-DDD-stimulated increases in [Ca2+]i such that peak [Ca2+]i was increased 250% and 259%, respectively. Because of the prominent inhibition observed with the voltage-dependent calcium channel blockers, the effect of p,p'-DDD on membrane depolarization was examined using a cationic fluorescent indicator of membrane potential, [diS-C2(5)]. A concentration of 50 microM p,p'-DDD depolarized the cells by 35% of maximum during treatment with p,p'-DDD. The data demonstrate that p,p'-DDD increased [Ca2+]i in rat myometrial smooth muscle cells in a concentration-related manner, and that this increase was largely dependent on influx of extracellular calcium through dihydropyridine-sensitive, voltage-dependent calcium channels. The data further show that p,p'-DDD depolarized the plasma membrane, providing a possible mechanism for activation of voltage-dependent calcium channels. Additionally, another calcium source, perhaps an intracellular pool, contributes significantly less to the rise of [Ca2+]i. Whether p,p'-DDD initiates the calcium response by direct actions on the plasma membrane or by other means remains to be determined.


Advanced molecular and cytogenetic technologies in birth defect diagnosis and prevention.
Fluorescence in situ hybridization (FISH) has become an important diagnostic tool as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of specific nucleic acid sequences tagged with fluorescent molecules to identify the number and location of specific DNA sequences in human cells. These probes can be used to determine various numerical and structural chromosomal aberrations, in many cases, gene dosage and/or structure alterations. Chromosomal abnormalities are responsible for a considerable number of birth defects, and more than 50% of spontaneous abortions. These numbers have been significantly higher since the advent of FISH technology that allows the detection of submicroscopic chromosome alterations. The clinic application of FISH technology in postnatal, prenatal, and preimplantation diagnoses has been playing an important role in the diagnosis and prevention of birth defects. As new technologies evolve, more and more new FISH techniques-such as subtelomeric FISH, multicolor FISH (M-FISH), comparative genomic hybridization (CGH), and microarray-are used in clinical diagnoses, the role of FISH technology in both research and clinical aspects of birth defects will surely continue to expand.


A randomised double-blind placebo-controlled trial of prednisolone therapy in HBeAg and HBV DNA positive Chinese patients with chronic active hepatitis B.
Forty-one hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA positive Chinese patients with chronic active hepatitis B were randomized to receive either prednisolone or placebo oral for 8 weeks. The prednisolone group received 60 mg daily for 2 weeks, 40 mg for 2 weeks, 20 mg for 2 weeks, 10 mg for 1 week and 5 mg for 1 week. In 18 patients receiving prednisolone, serum HBV DNA levels rose during the course of therapy, but dropped abruptly within 1 month of cessation of treatment. Conversely, their serum alanine aminotransferase (ALT) levels decreased during high doses of prednisolone therapy, and then became transiently elevated during the period of withdrawal of prednisolone. At 1 year from initial treatment, the serum HBV DNA and ALT levels were similar between the groups of patients treated with prednisolone or placebo. In the prednisolone treated group, 66.7% of patients became HBV DNA negative, 50% became HBeAg negative, and 33.3% seroconverted to antibody to HBeAg (anti-HBe). In the placebo treated group, 60.9% of patients became HBV DNA negative, 60.9% became HBeAg negative, and 56.5% seroconverted to anti-HBe. Hepatic decompensation was not noted in any of the prednisolone-treated patients. Thus, the effects of the withdrawal prednisolone therapy on serum ALT and HBV DNA levels was temporary, and no differences in serum viral markers or biochemical parameters of liver inflammation between these two groups were noted at the 1 year follow-up period.


Annual ovarian cycles in an aseasonal breeder, the springbok (Antidorcas marsupialis).
The springbok is an arid-adapted antelope inhabiting the desert and semidesert regions of southern Africa. Because it thrives in these sparsely vegetated areas, the springbok is of potential agricultural importance and the prospect of domestication has been speculated for many years. However, apart from observational studies on its breeding in the wild, suggesting it is an aseasonal breeder, little is known about the underlying reproductive endocrinology of this species. In this study, biweekly peripheral blood samples were collected from eight captive springbok ewes from October 1995 until September 1998 and analyzed for progesterone. At the start of the study, six ewes were prepubertal and cycling commenced spontaneously between November 1995 and June 1996. Cycling had already commenced in two ewes. At the end of November 1996, estrous cycles ceased abruptly in all ewes and restarted in April 1997. Cycling ceased again between December 1997 and February 1998 and restarted in June 1998 in six ewes; there was no cessation of estrous cycles in two ewes. Thus, although some individuals cycle continuously, there is a clear endocrine anestrus of between 4 and 5 mo in springbok, the timing and duration of which is synchronized between some individuals but the time of onset and cessation is variable from year to year. To ensure that the fluctuations we observed in progesterone levels were reliable indicators of changes in the estrous cycle, blood samples were collected every 6 h for 16 days in August 1998. A surge in LH secretion was observed in all ewes 55 +/- 5 h after the fall in progesterone. Progesterone levels increased again 45 +/- 8 h after the surge. A final study showed that the pattern of melatonin release in springbok exhibits a normal day/night profile, and thus photoperiodic information is transformed into an endocrine code to springbok but does not appear to affect reproduction. Rather, our data raise the possibility that the prevailing ambient temperature may influence the onset of ovarian activity in this species.


Vulnerable populations in research.
Clinical research studies, both nursing and medical, occur in many critical care units. As with any clinical study, it is necessary to obtain informed consent from any person participating in the study. Although many patients are able to agree or refuse to participate in the study, many are unable to do so for a variety of reasons. These patients make up vulnerable populations or people with questionable capacity. This brief article will review patients who may be vulnerable and define the role of the critical-care nurse when caring for these patients.


Peripheral axon caliber and conduction velocity are decreased after burn injury in mice.
Peripheral neuropathies are reported to arise as a result of the systemic inflammatory response produced by a full-thickness cutaneous burn injury. This study was designed to characterize the magnitude and time course of functional and morphological changes in peripheral axons that arise after a full-thickness dermal burn injury in an animal model. A 20% body surface area (20% BSA) full-thickness dermal burn was applied to the back of C57BL6 female mice. Longitudinal H- and M-wave recordings were used to determine the conduction velocities (CV) of large myelinated motor and sensory axons in the tibial nerve of sham control and burn-injured mice. Motor CVs were significantly reduced from 6 h to 28 days after the burn, and sensory CVs were significantly reduced from 7 to 14 days after the burn. Morphological evaluation also showed that the mean caliber of large axons in tibial nerves and L5 ventral and dorsal roots in burned mice was significantly decreased. The results demonstrate that both functional and morphological deficits may be produced in peripheral nerve axons at sites well removed from a full-thickness dermal burn injury. The neural deficits may contribute to changes in neuromuscular transmission and the development of limb and respiratory muscle weakness that also accompany burn injury.


Down's syndrome in Wallonia (South Belgium), 1971-1978: cytogenetics and incidence.
During the 8 year-period 1971-1978 inclusive, 268 newborn with Down's syndrome (DS) were ascertained in Wallonia (South Belgium). The chromosomes of all patients were analyzed. A standard trisomy 21 was observed in 259 cases (96.6%) and translocations in seven (2.6%). One mosaic (0.4%) and one case with a 47,XX,+21,5 p-karyotype (0.4%) were also found. The overall incidence at birth for the 8 year-period was of 0.123%. However, the comparison of the 2 four-year periods 1971-1974 and 1975-1978 showed an increased incidence in mothers below 35 during the second period, reaching a statistical significant level in Charleroi, and industrial and densely populated area of the region (Fisher's exact test: P = 0.016 less than 0.025). Young women have now become the principal source of DS patients in Wallonia. This change from the previous pattern happened abruptly in 1975, and strongly suggests that one or more persisting factors relating to meiotic non-disjunction of chromosome 21 are operating in this region since 1974, and affecting DS births from 1975 onwards.


Safety and Feasibility of the Transcatheter Approach to Create a Reverse Potts Shunt in Children With Idiopathic Pulmonary Arterial Hypertension.
The reversed Potts shunt improves right ventricular (RV) function in patients with suprasystemic pulmonary arterial hypertension (PAH). The proximity of the left pulmonary artery (LPA) to the descending aorta (DAo) permits the creation of a transcatheter connection. We sought to assess the safety, feasibility, and hemodynamic efficacy of the transcatheter Potts shunt (TPS) in children. The TPS procedure was performed using radiofrequency energy for vessel perforation and deployment of a covered stent to connect the DAo and LPA. Procedural details and clinical follow-up data were collected prospectively. A TPS was successfully created in 6 children (mean age, 11.0 ± 4.2 years) with drug-refractory suprasystemic PAH and deteriorating RV function. All patients exhibited nearly complete equalization of aortic and pulmonary pressures and improvement in RV contractility within days after TPS placement. Two patients with pre-existing severe biventricular dysfunction and pericardial effusion experienced acute low-output states immediately after shunt creation because of sudden reductions in left ventricular (LV) preload, resulting in cardiac arrest, irreversible brain damage, and death. Stent dislodgement and embolization into the iliac artery occurred in 1 patient. The stent was successfully secured and followed by placement of a second stent at the target location. The procedure was uncomplicated in 4 patients, who remain alive after a mean follow-up of 10 ± 2.6 months. Intravenous vasodilator therapy was weaned uneventfully after TPS in 3 patients. TPS creation in children is feasible and results in hemodynamic improvement. Further insights into high-risk markers, such as reduced preprocedural LV function and preload reserves, are important for guiding patient selection.


[National quality indicators in Swiss nursing homes : Questionnaire survey on data reliability and users' view on the usefulness].
The publication of quality indicators is used internationally to compare the quality of nursing homes and initiate quality improvement processes. From 2019 onwards, Switzerland will nationally measure and subsequently publish the results of six quality indicators on four measurement topics (use of physical restraint measures, malnutrition, polypharmacy, self-assessed and observed pain). To assess the reliability of data collection as well as the understandability and usability of the newly developed quality indicators from the perspective of healthcare providers. An online survey in a convenience sample from 155 Swiss nursing homes was conducted. The participants answered the items used to measure the quality indicators based on five case study examples. They assessed the understandability of the items and the usability of the indicators for internal quality improvement as well as benchmarking with other nursing homes with a 4-point agreement Likert scale. A total of 303 persons from 127 nursing homes completed the survey. In 4 out of the 5 case studies the rating of more than 90% of the respondents led to a correct classification of the quality indicator. The counting of active ingredients for polypharmacy and the assessment of observed pain proved to be difficult. More than 80% of the respondents found the items understandable. The respondents agreed more with the usability of the quality indicators for internal quality improvement (78-91%) than for external benchmarking (63-79%). The majority of the quality indicators were correctly classified and rated as useful. For polypharmacy, an electronic support for counting the active ingredients is recommended and for the external assessment of pain the use of a validated pain intensity scale.


Negative affective consequences of thinking about disease detection behaviors.
It was proposed that thinking about disease-detection behavior would lead to more negative moods than thinking about health-promotion behavior. Detection behaviors produce more negative moods because they can threaten perceptions of good health. In a laboratory study, the initial mood states of 121 participants recruited from undergraduates and the general community were measured using a neutral-words rating procedure. Then participants were randomly assigned to think about performing a disease-detection behavior or a health-promotion behavior. Subsequently, they wrote down their responses to the behavior and evaluated these as either positive, negative, or neutral. Finally, the participant's mood was remeasured using both a neutral words-rating procedure and a more traditional bipolar rating measure. Results indicated that thought about disease-detection behavior produced more negative affective responses and more negative mood change than did thought about health-promotion behavior.


Sample preparation methods for determination of drugs of abuse in hair samples: A review.
Hair analysis has assumed increasing importance in the determination of substances of abuse, both in clinical and forensic toxicology investigations. Hair analysis offers particular advantages over other biological matrices (blood and urine), including a larger window of detection, ease of collection and sample stability. In the present work, an overview of sample preparation techniques for the determination of substances of abuse in hair is provided, specifically regarding the principal steps in hair sample treatment-decontamination, extraction and purification. For this purpose, a survey of publications found in the MEDLINE database from 2000 to date was conducted. The most widely consumed substances of abuse and psychotropic drugs were considered. Trends in simplification of hair sample preparation, washing procedures and cleanup methods are discussed. Alternative sample extraction techniques, such as head-space solid phase microextraction (HS-SPDE), supercritical fluid extraction (SFE) and molecularly imprinted polymers (MIP) are also reported.


Efficient Photocatalytic Hydrogen Evolution via Band Alignment Tailoring: Controllable Transition from Type-I to Type-II.
Considering the sizable band gap and wide spectrum response of tin disulfide (SnS2 ), ultrathin SnS2 nanosheets are utilized as solar-driven photocatalyst for water splitting. Designing a heterostructure based on SnS2 is believed to boost their catalytic performance. Unfortunately, it has been quite challenging to explore a material with suitable band alignment using SnS2 nanomaterials for photocatalytic hydrogen generation. Herein, a new strategy is used to systematically tailor the band alignment in SnS2 based heterostructure to realize efficient H2 production under sunlight. A Type-I to Type-II band alignment transition is demonstrated via introducing an interlayer of Ce2 S3 , a potential photocatalyst for H2 evolution, between SnS2 and CeO2 . Subsequently, this heterostructure demonstrates tunability in light absorption, charge transfer kinetics, and material stability. The optimized heterostructure (SnS2 -Ce2 S3 -CeO2 ) exhibits an incredibly strong light absorption ranging from deep UV to infrared light. Significantly, it also shows superior hydrogen generation with the rate of 240 µmol g-1 h-1 under the illumination of simulated sunlight with a very good stability.


Surgery of proximal anterior cerebral artery aneurysms.
Aneurysms of the proximal segment of anterior cerebral artery (A1) are uncommon, but present a unique challenge to surgeons because of the risk of injury to the nearby perforating arteries. Surgical issues and treatment options, however, have not been detailed in the previous literature. We report a consecutive series of 11 patients with A1 aneurysms focusing on the surgical considerations. The A1 aneurysms represented 3.4% of the 322 cerebral aneurysms treated in our hospital in the last 6 years. All patients presented with subarachnoid hemorrhage, and 8 patients (73%) had multiple aneurysms. All aneurysms were secured by neck clipping via pterional craniotomy without any surgery-related morbidity. All of the aneurysms projected superiorly or posteriorly from the origin of the perforating artery of the A1 segment. The aneurysm dome was tightly adherent to the perforating arteries in 7 cases (64%) and the base extended broadly along the axis of the parent artery in 4 cases (36%). Separating the perforating arteries from the neck or dome of the A1 aneurysm and preserving the vessel presents a substantial challenge to the surgeon, because the aneurysm is almost always behind the parent artery in the surgical field, making it difficult to achieve good access for this particular type of dissection. Consideration should be given to additional orbitotomy, wide opening of the Sylvian fissure, mobilization of the MCA and ICA, selection of aperture clip and intra-operative shortening of the clip blades.


Endobronchial tuberculosis complicated with Staphylococcus aureus pneumonia and empyema in a child.
Childhood tuberculosis might have unusual clinical presentation. A seven-year-old female patient was admitted with fever and pleural effusion. Her pneumonia resolved following 21-day treatment period. An atelectatic appearance remained on the right middle zone in her chest X-ray. Tuberculin skin test showed 13 mm induration. Triple drug antituberculosis treatment was started. Since atelectasis persisted on her follow-up radiograph one month later, bronchoscopy was performed which revealed a hemorrhagic polypoid mass occluding the right upper lobe anterior segment orifice. Surgical removal was performed by right upper lobectomy. The pathological diagnosis was necrotizing granulomatous infection suggesting tuberculosis. The patient has been well on follow-up after completing a nine-month course of antituberculous treatment.


Evaluation of natriuretic peptide recommendations in heart failure clinical practice guidelines.
The B-type naturietic peptides (NPs) are associated with heart failure (HF). This investigation was designed to evaluate heart failure clinical practice guideline (CPG) recommendations for the use of NPs. A search for English language CPGs for HF published since 2011 was conducted. A search for systematic reviews (SR) and meta-analysis for NPs in HF was conducted for the years 2004-2012. Each HF CPG was evaluated by two independent reviewers. Key recommendations for NPs and the supporting references were abstracted. The key findings from each SR were abstracted. Seven English language HF CPGs were found, all of which made recommendations for the use of NPs in diagnosis. Four made recommendations for prognosis and three for management. The European CPG scored highly for rigor of development with the Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II) while the others did not. North American CPGs made stronger recommendations citing higher grades of evidence for the use of NPs in HF than the European or Australian CPGs. The CPGs mostly cited primary studies 47/66 to support the recommendations. From twelve available SRs, five were cited by CPGs. One CPG conducted a SR. The SR evidence to support NP use in CPGs has not been well cited in the CPGs and the recommendations are only partially supported by the SR evidence. Future CPGs should consider improving the methodology used to evaluate laboratory tests.


Multipurpose effectiveness of Couroupita guianensis-synthesized gold nanoparticles: high antiplasmodial potential, field efficacy against malaria vectors and synergy with Aplocheilus lineatus predators.
Mosquito-borne diseases represent a deadly threat for millions of people worldwide. According to recent estimates, about 3.2 billion people, almost half of the world's population, are at risk of malaria. Malaria control is particularly challenging due to a growing number of chloroquine-resistant Plasmodium and pesticide-resistant Anopheles vectors. Newer and safer control tools are required. In this research, gold nanoparticles (AuNPs) were biosynthesized using a cheap flower extract of Couroupita guianensis as reducing and stabilizing agent. The biofabrication of AuNP was confirmed by UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD), zeta potential, and particle size analysis. AuNP showed different shapes including spheres, ovals, and triangles. AuNPs were crystalline in nature with face-centered cubic geometry; mean size was 29.2-43.8 nm. In laboratory conditions, AuNPs were toxic against Anopheles stephensi larvae, pupae, and adults. LC50 was 17.36 ppm (larva I), 19.79 ppm (larva II), 21.69 ppm (larva III), 24.57 ppm (larva IV), 28.78 ppm (pupa), and 11.23 ppm (adult). In the field, a single treatment with C. guianensis flower extract and AuNP (10 × LC50) led to complete larval mortality after 72 h. In standard laboratory conditions, the predation efficiency of golden wonder killifish, Aplocheilus lineatus, against A. stephensi IV instar larvae was 56.38 %, while in an aquatic environment treated with sub-lethal doses of the flower extract or AuNP, predation efficiency was boosted to 83.98 and 98.04 %, respectively. Lastly, the antiplasmodial activity of C. guianensis flower extract and AuNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. IC50 of C. guianensis flower extract was 43.21 μg/ml (CQ-s) and 51.16 μg/ml (CQ-r). AuNP IC50 was 69.47 μg/ml (CQ-s) and 76.33 μg/ml (CQ-r). Overall, our results showed the multipurpose effectiveness of C. guianensis-synthesized AuNPs, since they may be proposed as newer and safer tools in the fight against CQ-r strains of P. falciparum and for field control of malaria vectors, in synergy with wonder killifish predators.


Early treatment with isoflurane attenuates left ventricular dysfunction and improves survival in experimental Takotsubo.
Takotsubo syndrome (TS) is an acute cardiac condition, often triggered by critical illness, for which no specific treatment exists. Previously, we showed that isoflurane can prevent experimental TS. The aim of this study was to evaluate the potential treatment effects of isoflurane. Our primary hypothesis was that early treatment with isoflurane attenuates left ventricular akinesia in experimental TS. In propofol-sedated animals, TS was induced by an intraperitoneal bolus of isoprenaline (50 mg/kg). Animals were randomized to one of six groups (n = 15 in each group), and 1% isoflurane was administered for 90 min in all groups. Isoflurane treatment was started at 0, 10, 30 (early treatment) or 120 (late treatment) minutes after isoprenaline injection. One additional late treatment group received isoflurane 0.5% for 180 min. A control group did not receive isoflurane. Left ventricular (LV) echocardiographic examination was performed at 90 min and 48 h after isoprenaline. Mortality was assessed at 48 h. Median degree of LV akinesia at 90 min was 24% in the control group and 0% in the early treatment groups (P < 0.001). Stroke volume, cardiac output and LV ejection fraction were higher in the early treatment groups vs. controls (P < 0.01). Mortality was lower in the early treatment groups (24%) vs. controls (86%) (P < 0.001). Mortality did not differ between the late treatment groups and controls. Early treatment with isoflurane attenuates the LV akinesia and improves survival in experimental TS. Isoflurane sedation in patients at risk of developing Takotsubo syndrome could be a subject for future studies.


The influence of respiratory motion on the cumulative SUV-volume histogram and fractal analyses of intratumoral heterogeneity in PET/CT imaging.
The purpose of this study was to investigate the influence of respiratory motion on the evaluation of the intratumoral heterogeneity of FDG uptake using cumulative SUV-volume histogram (CSH) and fractal analyses. We used an NEMA IEC body phantom with a homogeneous hot sphere phantom (HO) and two heterogeneous hot sphere phantoms (HE1 and HE2). The background radioactivity of (18)F in the NEMA phantom was 5.3 kBq/mL. The ratio of radioactivity was 4:2:1 for the HO and the outer rims of the HE1 and HE2 phantoms, the inner cores of the HE1 and HE2 phantoms, and background, respectively. Respiratory motion was simulated using a motion table with an amplitude of 2 cm. PET/CT data were acquired using Biograph mCT in motionless and moving conditions. The PET images were analyzed by both CSH and fractal analyses. The area under the CSH (AUC-CSH) and the fractal dimension (FD) was used as quantitative metrics. In motionless conditions, the AUC-CSHs of the HO (0.80), HE1 (0.75) and HE2 (0.65) phantoms were different. They did not differ in moving conditions (HO, 0.63; HE1, 0.65; HE2, 0.60). The FD of the HO phantom (0.77) was smaller than the FDs of the HE1 (1.71) and HE2 (1.98) phantoms in motionless conditions; however, the FDs of the HO (1.99) and HE1 (2.19) phantoms were not different from each other and were smaller than that of the HE2 (3.73) phantom in moving conditions. Respiratory motion affected the results of the CSH and fractal analyses for the evaluation of the heterogeneity of the PET/CT images. The influence of respiratory motion was considered to vary depending on the object size.


Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats.
A replication-defective variant of feline leukemia virus was molecularly cloned directly from infected tissue and found to induce a rapid and fatal immunodeficiency syndrome in cats. Studies with cloned viruses also showed that subtle mutational changes would convert a minimally pathogenic virus into one that would induce an acute form of immunodeficiency. The data suggest that acutely pathogenic viruses may be selected against by current methods for isolation of the human and simian immunodeficiency viruses.


Development of t(8;21) and RUNX1-RUNX1T1 in the Philadelphia-positive clone of a patient with chronic myelogenous leukemia: additional evidence for multiple steps involved in disease progression.
A 65-year-old patient with a high hemoglobin and hematocrit was treated for 14 months with therapeutic phlebotomy when cytogenetics of bone marrow revealed 100% cells with the Ph chromosome and 45% of the Ph+ cells contained trisomy 8. Treatment with tyrosine kinase inhibitors did not reduce the BCR-ABL1 fusion positive clone. Instead, the Ph positive cells acquired further the t(8;21)/RUNX1-RUNX1T1, del(4q) and trisomy 15 chromosomal abnormalities which were resistant to further treatment. Literature review revealed eight other patients who either had t(9;22) and t(8;21) simultaneously or developed t(8;21) in the Ph positive clone. We conclude that there are rare patients with CML who either present in blast crisis with coexistence of t(9;22) and t(8;21) with or without +8, or progress to blast crisis with acquiring RUNX1-RUNX1T1 in the BCR-ABL1 clone which may or may not be therapy related and represent a later event in a multistep pathogenesis.


Depression in Older Adults: A Palliative Medicine Perspective.
This article aims to discuss the rapidly growing field of palliative medicine and its unique approach to treating depression in older adults.


Angiogenesis and p53 expression in the colorectal adenoma-carcinoma sequence.
Angiogenesis, the formation of new vessels, is essential for tumor growth and metastasis. Mutations of p53 tumor suppressor gene are frequent and play an important role in colorectal oncogenesis. A role of p53 as an angiogenesis inhibitor has also been proposed. We evaluated angiogenesis and p53 expression in 16 hyperplastic polyps, 35 solitary tubular and tubulovillous adenomas, and 47 cases of sporadic colorectal carcinomas arising on the basis of preexisting adenomas, with standard immunohistochemical techniques. The mean microvessel density (MVD) in carcinomas was significantly higher compared with the respective adenomatous part of the same tumor (27.9 vs. 7; P=0.0001). Linear regression analysis of MVD between cancerous and adenomatous areas showed a significant correlation (P = 0.0001, r = 0.56), raising the possibility that carcinomas arising from better vascularized adenomas might show increased vascularity. The MVD was significantly higher in stage C compared with stage A cases (P=0.04). p53 positivity was detected in 26 of 47 cancerous (55%) and in 14 of 47 adenomatous areas (30%; P = 0.0002). All carcinomas arising from p53-positive adenomas were also p53 positive. p53 positivity associated with a higher MVD in adenomas (P = 0.02), but not in carcinomas (P = 0.78). We conclude that angiogenesis and p53 play a critical role in colorectal neoplasia, and the process of malignant transformation in tumors arising from highly angiogenic adenomas, particularly those carrying p53 mutations, is accelerated with rapid tumor progression from stage to stage, indicating a more aggressive tumor phenotype.


Therapeutic effects of imidapril on cerebral lesions observed by magnetic resonance imaging in malignant stroke-prone spontaneously hypertensive rats.
Magnetic resonance imaging (MRI) was used to investigate the therapeutic effects of imidapril, a newly synthesized angiotensin converting enzyme (ACE) inhibitor, on cerebral stroke lesions. Pretreatment with ACE inhibitors is known to prevent stroke in stroke-prone spontaneously hypertensive rats, prolonging their lifespan. Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) were treated with imidapril after the onset of stroke. M-SHRSP with proved stroke were divided into two groups. One group received 40 mg/kg per day imidapril and the other group was used as a control. For 4 weeks, neurological symptoms were scored daily, and MRI images were taken and scored once a week. In the control group the MRI score for cerebral lesions increased during the experiment, and seven out of eight control rats died within 17 days. In rats treated with imidapril the major finding was that imidapril rapidly ameliorated the damage to the blood-brain barrier and resolved brain oedema within 1 week. At the same time the neurological symptoms observed after stroke disappeared. Furthermore, none of the rats treated with imidapril showed recurrence of stroke, and their survival rate was improved. These results suggest that imidapril has therapeutic effects on stroke lesions, as well as prophylactic effects on the recurrence of stroke.


Adjunctive uses of the radial artery for emergency infrapopliteal bypass in patients presenting with acute limb-threatening ischemia.
Although the radial artery has proven to be a reliable conduit for arterial bypass procedures in cardiac surgery, its use in lower extremity revascularization has been limited due to its length. In patients who have undergone multiple cardiovascular procedures, venous conduit options can be limited, and infrapopliteal bypass with prosthesis has been shown to yield poor patency rates. In this report, the authors describe 3 different uses of the radial artery in patients with acute limb-threatening ischemia in the redo setting, which resulted in limb salvage.


[Use of isotonic NaCl solution in patients with acute rhinosinusitis].
The mucous membrane of the nose and paranasal sinuses has several important physiological functions. Inflammation of the nose and paranasal sinuses impairs filtration, humidification and warming of the inhaled air. It also affects the beating of cilia and the mucociliary clearance within the nose and lumen of the sinuses. The result is impairment of the mechanism by which the removal of the stagnant pathological discharge from the paranasal sinuses and of foreign matter (environmental pollutants) from the nasal mucosa would be otherwise effected. The use of special products to cleanse the nasal mucosa may considerably improve its function. Day-to-day ENT practice offers evidence of beneficial effects of nasal douching with isotonic sea water solutions. Products which cleanse nasal mucosa are now used as an adjunct to treatment of rhinosinusitis and rhinitis co-existing with nasal polyps. was a retrospective assessment of symptoms in patients with acute rhinosinusitis depending on the therapeutic modality used, especially in a group of patients using an isotonic solution (0.9% NaCl) in addition to standard treatment. Medical records of 80 patients, males and females with symptoms of acute rhinosinusitis were included in the final evaluation. The following medical records including fully documented medical history and physical findings in compliance with the EP3OS were randomly selected from the medical records at the ENT Outpatient Clinic: 40 patients with acute rhinosinusitis treated symptom-relieving medication (Group A) and symptom-relieving medication with topical nasal corticosteroids (Group C); 40 patients with acute rhinosinusitis treated symptom-relieving medication plus isotonic NaCl solution twice a day (Group B) and symptom-relieving medication with topical nasal corticosteroids plus isotonic NaCl solution twice a day (Group D). Seven-days-treatment resulted in the decreasing of severity of the disease by 39.59% in control group and by 73.62% in patients using isotonic solution NaCl. The use of isotonic NaCl solutions as an adjunct to the treatment of acute rhinosinusitis results in highly statistically significant improvement of nasal patency (by 45.1% in control group and by 72.0% in patients using isotonic solutions) due to decreased swelling of the mucosa of the nasal turbinate. The use of isotonic NaCl solutions as an adjunct to the treatment of acute rhinosinusitis results in a highly statistically significant improvement in function of smell. Treatment with local nasal corticosteroids in combination with isotonic NaCl solutions produces a significant reduction in the severity of symptoms in patients with rhinosinusitis. The therapeutic effect in these patients is statistically significantly better than in patients treated with local nasal corticosteroids alone. The findings of the present study support the investigators' opinion that the isotonic solution (0.9% NaCl) should be recommended for nasal douching may be a valuable adjunct to the standard medical treatment of acute rhinosinusitis.


Oxidative removal of arsenite by Fe(II)- and polyoxometalate (POM)-amended zero-valent aluminum (ZVAl) under oxic conditions.
Abiotic transformation of As(III) to As(V) is possible which would decrease As toxicity. This study investigated the potential applications of zero-valent Al (ZVAl) or Al wastes, such as Al beverage cans, for converting As(III) to As(V) in an acidic solution under aerobic conditions. Results showed that As(III) could not be oxidized by ZVAl within 150 min reaction at pH 1 because of the presence of an oxide layer on ZVAl. However, 85 μM As(III) could be completely oxidized with the addition of Fe(II) or POM due to the generation of a Fenton reaction or the enhancement of H2O2 production, respectively, on the ZVAl surfaces. Because Fe(II) or polyoxometalate (POM) exhibited more stable at low pH and scavenged rapidly the H2O2 produced on the aerated ZVAl surfaces, OH radical productions were more efficient and As(III) was rapidly oxidized in the ZVAl/O2 system with theses two catalysts. The catalytic oxidation kinetics of As(III) in the presence of Fe(II) or POM were best described by zero-order reaction, and the rate constants increased with a decrease of pH from 2 to 1. Following the oxidative conversion of As(III) to As(V) in the ZVAl/Fe/O2 system, As(V) was removed by the newly formed hydrous Al/Fe precipitates by increasing the solution pH to 6. Nonetheless, the As(V) removal was incomplete in the ZVAl/POM/O2 system because the hydrolyzed products of POM, e.g., PO4(3-), inhibited As(V) removal due to the competitive adsorption of the oxyanion on Al precipitates. Discarded Al-based beverage cans exhibit a higher efficiency for As(III) oxidation and final As removal compared with that of ZVAl, and thus, the potential application of Al beverage cans to scavenge As in solutions is feasible.


Alcohol consumption and mortality and hospital admissions in men from the Midspan collaborative cohort study.
To investigate the relationships between alcohol consumption and mortality and morbidity risk by specific causes. Prospective cohort study. Twenty-seven work-places in West and Central Scotland. A total of 6000 men aged 21-64 years at screening in 1970-1973, median follow-up 29 years. Relative rates, using Cox's proportional hazard models, by weekly reported units of alcohol consumption for all cause, coronary heart disease (CHD), stroke, respiratory, digestive, liver disease and alcohol-related causes of mortality and for specific causes of acute hospital admissions. Mortality risk was increased for men drinking 15-21 or more units per week for all causes, stroke, liver disease and alcohol-related causes. For respiratory mortality, drinkers of 35 or more units had double the risk compared to non-drinkers. CHD mortality showed increasing trends with consumption when adjusted for age and after full adjustment showed no clear patterns, although the 8-14 units group had a lower risk than non-drinkers [relative rate 0.81 (0.68-0.97)]. Hospital admissions had similar patterns to mortality for stroke and liver disease. Increased risk began at 8-14 units for alcohol-related admissions, and at 15-21 units for respiratory admissions. Non-drinkers had higher risks of having a CHD admission than drinkers and there were decreasing trends with increasing consumption (P = 0.019). Consumption of 15-21 units per week and over was associated with increased mortality from most causes and increased risk of hospital admissions from stroke, liver disease and respiratory diseases. Alcohol-related admissions were raised from 8 to 14 units. Alcohol use may have been under-reported in our study, but it was similar to other studies of the time. The apparent protective effect of alcohol with CHD admissions could be due partly to detrimental effects of heavy drinking causing sudden deaths. The associations, including that with respiratory disease, may arise from inadequate adjustment for confounding by other factors such as smoking.


In vitro testing of chemotherapeutic combinations in a rapid thymidine incorporation assay.
A total of 199 solid human tumors were tested with a rapid thymidine incorporation assay for sensitivity to one of several clinically used multi-drug combinations and to each agent in the combination separately. Melanomas, lung and breast cancers accounted for the majority of specimens. In 120 specimens, at least one single agent exhibited in vitro activity (80% or greater inhibition of thymidine incorporation), and in 116 of these (96.7%) the drug combination was active in vitro. In the 79 specimens where no single agent was active in vitro, the combination was also inactive in 62 (78.5%). Overall, there was concordance of in vitro activity of the most active single agent and the combination of agents in 89.5% of specimens tested. A lack of significant in vitro synergy was noted in all of the drug combinations and tumor types tested. Of note is the fact that in 141 of the 199 tests (70.9%) either no drug (n = 79) or only 1 drug (n = 62) demonstrated in vitro activity. We conclude that the rapid thymidine incorporation assay can be used to test for in vitro sensitivity to drug combinations, and that sensitivity to a drug combination can be inferred if a tumor is sensitive to any component drug of the combination.


Transcriptional activation of the non-muscle, full-length dystrophin isoforms in Duchenne muscular dystrophy skeletal muscle.
Despite promoter tissue specificity, up-regulation of the brain and Purkinje cell type dystrophin isoforms was described in skeletal muscle of X-linked dilated cardiomyopathy (XLDCM) and BMD affected individuals. An extended population of 11 Duchenne muscular dystrophy (DMD) and 11 Becker muscular dystrophy (BMD) patients was investigated to determine whether ectopic muscle expression of the two full-length non-muscular isoforms is a common event in dystrophinopathies and if it has functional significance. Up-regulation of the two non-muscle-specific isoforms was detected in four DMD patients but in none of the BMD affected individuals or non-dystrophic controls. This is the first report of an expression of these two isoforms in DMD skeletal muscle. Ectopic expression is not confined to regenerating or revertant fibers and does not correlate with age at biopsy, clinical phenotype, cardiac involvement, deletion size or location. We consider that muscle ectopic expression of the brain and Purkinje cell-type isoforms has no favorable prognostic significance in DMD and BMD patients.


Applying the self-determination theory to develop a school-to-work peer mentoring programme to promote social inclusion.
Social inclusion of individuals with intellectual and developmental disabilities (IDD) is related to positive mental health and social outcomes; yet, individuals with IDD experience societal barriers that limit opportunities for community participation. Providing opportunities for interactions between individuals with and without IDD through peer mentoring may diminish barriers and improve community inclusion. Guided by the self-determination theory, the current report describes the development of a peer mentoring programme to promote the natural process of building intrinsic motivation and personal growth through opportunities for individuals without disabilities to socialize with individuals with IDD on a large university campus and throughout the surrounding community. The theoretical framework that informed the development of the peer mentoring programme is described, as well as the participants, the setting in which the programme is situated, the structure of the programme, the initial impacts and improvement of the programme over time, including approaches to sustainability, and implications for future research and practice.


Patchwise joint sparse tracking with occlusion detection.
This paper presents a robust tracking approach to handle challenges such as occlusion and appearance change. Here, the target is partitioned into a number of patches. Then, the appearance of each patch is modeled using a dictionary composed of corresponding target patches in previous frames. In each frame, the target is found among a set of candidates generated by a particle filter, via a likelihood measure that is shown to be proportional to the sum of patch-reconstruction errors of each candidate. Since the target's appearance often changes slowly in a video sequence, it is assumed that the target in the current frame and the best candidates of a small number of previous frames, belong to a common subspace. This is imposed using joint sparse representation to enforce the target and previous best candidates to have a common sparsity pattern. Moreover, an occlusion detection scheme is proposed that uses patch-reconstruction errors and a prior probability of occlusion, extracted from an adaptive Markov chain, to calculate the probability of occlusion per patch. In each frame, occluded patches are excluded when updating the dictionary. Extensive experimental results on several challenging sequences shows that the proposed method outperforms state-of-the-art trackers.


Olanzapine for nausea and vomiting.
Nausea and vomiting are often encountered in palliative care patients. Multiple medications are available to provide relief. However, several drug combinations are usually used to treat emesis. Current research has identified several receptors that trigger nausea and vomiting, hence the difficulty of using only 1 medication to provide relief. Olanzapine is a drug approved for treatment of schizophrenia and mania. It blocks multiple neurotransmitters dopaminergic, serotonergic, adrenergic (alpha(1)), histaminergic, and muscarinic receptors. Most of these receptors are also involved in causing emesis. Studies have shown that olanzapine could be used to treat nausea and vomiting with promising results.


The women's liberation movement: its impact on marriage.
The author discusses marriages in which a basically insecure husband plays a god-like role and his wife, who initially worshipped him, matures and finds her situation depressing and degrading. With support from the women's liberation movement, many women have found the courage and conviction to challenge such situations. The challenges often bring the husbands' repressed feelings of inadequacy to the surface, which leads to increased turmoil and finally to requests for professional help, first by the wife and later by her husband. During counseling both become more open and develop as individuals. As a result their marriage improves.


Development of pH indicator from PLA/PEO ultrafine fibers containing pigment of microalgae origin.
Phycocyanin is a pigment of intense blue color, constituting the biomass of microalga such as Spirulina. This pigment is sensitive to pH and this instability results in color change. Thus, phycocyanin fading may become interesting for application in intelligent packaging. The objective of the study was to develop PLA/PEO ultrafine fibers containing phycocyanin to be used as pH indicators membranes for food packaging. The ultrafine fibers were formed by electrospinning process. The average diameter of 1318 nm was obtained for PLA/PEO ultrafine fibers with 2% (w·v-1) of phycocyanin and 921 nm for those developed with 3% (w·v-1) of the dye. PLA/PEO ultrafine fibers with 3% (w·v-1) of the phycocyanin presented the best responses regarding the perception of color change (ΔE). With the highest thickness (68.7 μm) of the ultrafine fibers developed from 3% (w·v-1) of phycocyanin, the ΔE value found was 18.85 to the variation of pH 3 to 4 and for variation from pH 5 to 6 the value of ΔE was 18.66. Thus, the use of PLA/PEO ultrafine fibers containing phycocyanin as pH indicator is an innovative application for intelligent packaging, since the color of pigment changes depending on pH variation.


Effects of histamine, granulocyte colony-stimulating factor and db-cAMP on the differentiation of HL-60 cells.
Histamine (10(-7) to 10(-3) M) dose-dependently decreased the incorporation of 3H-thymidine into HL-60 cells, starting from the third day of culture. Also, histamine 1 microM significantly induced the differentiation of HL-60 into cells having the morphological characteristics of mature neutrophils, as did db-cAMP and granulocyte colony-stimulating factor (G-CSF). Phosphorylation of proteins appeared at 60 kd and 120 kd was diminished. The phosphorylation profiles induced by G-CSF and db-cAMP were similar to that of histamine. In the case of db-cAMP, however, no phosphorylated band appeared at 120 kd.


Characteristics of the subject and interview influencing the test-retest reliability of the Diagnostic Interview for Children and Adolescents-Revised.
This paper reviews some of the characteristics of the informants as well as some of the attributes of the DICA-R interview that could influence the test-retest reliability in a sample of 109 psychiatric outpatients aged 7-17 years. Different regression models using reliability coefficients constructed from the kappa statistic were obtained. Of those characteristics evaluated in the children, a high level of psychological impairment proved to be significant when it came to predicting the lowest test-retest reliability of the answers; none of the subject-related characteristics were significant in the adolescent patient model. The attributes of the questions that proved to be significant when explaining the lower reliability obtained for the individual question in the children's model were the length of the questions (longest questions), the content (internalising), the presence of time concepts, comparison with the peer group, and the need to exercise judgement; in the adolescents' model, the significant attributes were found to be the internalising content, the presence of time concepts, evaluation concerning the impairment caused by the disorder, and the need to exercise judgement. In the group of children our results are in accordance with the original paper. Similar results were found with adolescents. These findings have implications for the development and revision of new interview schedules.


Long-term clinical course of proximal deep venous thrombosis and detection of recurrent thrombosis.
Symptomatic proximal deep vein thrombosis of lower extremities carries a high risk for recurrent venous thromboembolism that persists for many years. This risk is dependent on readily identifiable risk factors, being low after a trauma or a surgical intervention and higher in all the other patient categories. Moreover, postthrombotic sequelae will develop in one of every three patients, this risk being strongly related to the development of ipsilateral thrombosis. Although the optimal duration of anticoagulation in patients who experience an episode of proximal vein thrombosis is unknown, it seems reasonable to administer a short-term course of coumarin drugs to patients with thrombosis associated with transient risk factors, whereas a longer course (6 to 12 months) should be considered in patients with idiopathic thrombosis and in those with permanent risk factors. Indefinite anticoagulant therapy is a clinical judgement in the individual patient. The management of patients who develop clinical manifestations suggestive of recurrent ipsilateral venous thrombosis still represents a challenge for clinicians. Recent data suggest that these patients can be safely managed with the use of serial compression ultrasonography.


[Discovery of a new division system in brain and the regionalized drainage route of brain interstitial fluid].
Brain extracellular space (ECS) is a narrow, irregular space, which provides immediate living environment for neural cells and accounts for approximately 15%-20% of the total volume of living brain. Twenty-five years ago, as an interventional radiologist, the author was engaged in investigating early diagnosis and treatment of cerebral ischemic stroke, and the parameters of brain ECS was firstly derived and demonstrated during the study of the permeability of blood-brain barrier (BBB) and its diffusion changes in the cerebral ischemic tissue. Since then, the author and his team had been working on developing a novel measuring method of ECS: tracer-based magnetic resonance imaging (MRI), which could measure brain ECS parameters in the whole brain scale and make the dynamic drainage process of the labelled brain interstitial fluid (ISF) visualized. By using the new method, the team made a series of new findings about the brain ECS and ISF, including the discovery of a new division system in the brain, named regionalized ISF drainage system. We found that the ISF drainage in the deep brain was regionalized and the structural and functional parameters in different interstitial system (ISS) divisions were disparate. The ISF in the caudate nucleus could be drained to ipsilateral cortex and finally into the subarachnoid space, which maintained the pathway of ISF-cerebrospinal fluid (CSF) exchange. However, the ISF in the thalamus was eliminated locally in its anatomical division. After verifying the nature of the barrier structure between different drainage divisions, the author proposed the hypothesis of "regionalized brain homeostasis". Thus, we demonstrated that the brain was protected not only by the BBB, which avoided potential exogenous damage through the vascular system, but was also protected by an internal ISF drainage barrier to avoid potentially harmful interference from other ECS divisions in the deep brain. With the new findings and the proposed hypothesis, an innovative therapeutic method for the treatment of encephalopathy with local drug delivery via the brain ECS pathway was established. By using this new administration method, the drug was achieved directly to the space around neurons or target regions, overwhelming the impendence from the blood-brain barrier, thus solved the obstacles of low efficiency in traditional drug investigation. At present, new methods and discoveries developed by the author and his team have been widely applied in several frontier fields including neuroscience, new drug research and development, neurodevelopment aerospace medicine, clinical encephalopathy treatment,new neural network modeling and so on.


Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F.
Cell cycle progression initiated by interleukin-2 (IL-2) in T cells is critical for lymphoproliferation and an immune response. Phosphatidyl inositol 3-kinase (PI3K) is activated by IL-2. However, nuclear targets for PI3K are not known. Here we identify the cell cycle regulator E2F as an IL-2 target in T lymphocytes and PI3K as the critical signaling pathway. We eliminate both Stat5 and Raf/MEK pathways from E2F regulation. Protein kinase B (PKB) is activated by IL-2 via PI3K. The expression of an active PKB is sufficient to induce E2F activity. Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1. These results establish a crucial PI3K/PKB-mediated link between the IL-2 teceptor and the cell cycle machinery.


Substance abuse In Middle Eastern adolescents living in two different countries: spiritual, cultural, family and personal factors.
It is estimated that the percentage of students using illicit substances by sixth grade has tripled over the last decade not only in developed countries but in developing countries as well probably due to the transition to a more Western society. Although much has been done to understand the mechanisms underlying substance abuse, few studies have been conducted with minority ethnic and religious groups such as Middle Eastern Youth. The primary goal of this study was to determine whether there are differences in factors contributing to substance abuse in adolescents from Lebanon versus the U.S.A. and to decipher the role of spirituality, religion, and culture among other factors that may influence substance abuse. A correlational cross-sectional design was used with adolescents living in two different countries: Los Angeles, California and Beirut, Lebanon. Muslim adolescents had significantly less rates of alcohol and substance use than Christians in both Lebanon and Los Angeles. More years lived in the U.S.A. increases the likelihood of abuse for both Muslims and Christians. Attachment to God and family was negatively associated with substance abuse. These results among others facilitate a better understanding of the influence of culture, religion, family and personal factors on substance abuse. Culturally sensitive interventions could benefit from the findings of this pilot study.


[Obstetric outcomes in oxytocin-related and spontaneous deliveries--analysis of 2198 cases].
The aim of the work was to compare labour courses, ways of delivery, condition of the newborns in spontaneous and oxytocin-related labours and to analyse the indications for oxytocin administration. 2198 full-term deliveries (pregnant women qualified for elective caesarean section were excluded from the study) at the Provincial Hospital in Przemyśl, Poland. Labours with the adjunctive oxytocin infusion--1102 women. spontaneous labours (without oxytocin administration)--1096 women. The analysis of the compatibility of measured traits was carried out by the Chi2 test, p < 0.05 was assumed as statistically significant level. I. Indications for the oxytocin administration: secondary hypokinetic contractions of the uterus (642 labours--58.25%), premature rupture of membranes (176 labours - 15.97 %). II. Deliveries by caesarean section: 1. study group--187 women (16.97%). 2. control group--97 women (8.85%). Ch2 = 32.192; df = 1; p = 0.0000. III. Newborns after vaginal labours scored 7 or below according to the Apgar in the first minute after the delivery. 1. study group--35 newborns (8.7%); 2. control group--18 newborns (1.8%) ch2 = 5.493; df = 1; p = 0.0190. IV. Newborns hospitalised for over 48 hours: 1. study group--346 (31.39%); 2. control group--216 newborns (19.70%). Chi2 = 39.454; df = 1; p = 0.0000. (1) Hypokinetic uterine contractions were the most frequent indication for oxytocin administration during labour. (2) Oxytocin administration increases twice the risk of delivery by the caesarean section. (3) Newborns after vaginal oxytocin-related labours scored 7 or below on the Apgar score in the first minute after the birth when compared to the newborns after spontaneous labour. (4) Oxytocin administration during parturition elongates the time of newborns hospitalisation.


Isolation of etiological agent of hydropericardium syndrome in chicken embryo liver cell culture and its serological characterization.
The virus causing hydropericardium syndrome was isolated in chicken embryo liver (CEL) cell culture from livers obtained from naturally infected broilers. The cytopathic effects characterized by rounding and degeneration of cells were visible 36 hr post infection in first passage. At 4th passage level, the infectivity titre was 5.24 log10 TCID50/ml. In May-Grunwald and Giemsa stained cells, basophilic intranuclear inclusions ('bird eye' inclusion), typical of aviadenovirus infection, were observed. The specificity of inclusion was confirmed by indirect immunofluorescence. Various serological tests, such as agar gel precipitation test, counter immuno electrophoresis, micro serum neutralization test and enzyme linked immunosorbent assay were also standardized to confirm the isolation of etiological agent of hydropericardium syndrome in CEL cell culture and to diagnose the disease in poultry.


Ligation of a patent ductus arteriosus under fentanyl anesthesia improves protein metabolism in premature neonates.
Although surgical ligation effectively reverses the cardiopulmonary failure associated with patent ductus arteriosus (PDA), previous findings have suggested that such surgery itself elicits a catabolic response in premature neonates. Therefore, the authors sought to quantitatively assess whether PDA ligation under fentanyl anesthesia aggravated or improved the protein metabolism of premature neonates. Seven ventilated, premature neonates (birth weight 815 +/- 69 g) underwent PDA ligation with standardized fentanyl anesthesia (15 microg/kg) on day-of-life 8.4 +/- 1.2 and were studied immediately pre- and 16 to 24 hours postoperatively while receiving continuous total parenteral nutrition (TPN). Whole-body protein kinetics were calculated using intravenous 1-[13C]leucine, and skeletal muscle protein breakdown was measured from the urinary 3-methylhistidine to creatinine ratio (MH:Cr). Whole-body protein breakdown (10.9 +/- 1.2 v8.9 +/- 0.8 g/kg/d, P < .05), turnover (17.4 +/- 1.2 v 15.4 +/- 0.8 g/kg/d, P< .05), and MH:Cr (1.95 +/- 0.20 v 1.71 +/- 0.16 micromol:mg, P< .05) decreased significantly after operation. This resulted in a 60% improvement in protein balance (1.6 +/- 0.8 v 2.6 +/- 0.6 g/kg/d, P = 0.08) postoperatively. Because of decreased whole-body protein breakdown, whole-body protein turnover, skeletal muscle protein breakdown, and increased protein accrual, surgical PDA ligation under fentanyl anesthesia promptly improves the protein metabolism of premature neonates enduring the stress of a PDA.


Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells.
The functional role of interleukin-22 (IL22) in chronic inflammation is controversial, and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic colitis and probed mechanisms of IL22-mediated regulation of colonic epithelial cells. To investigate the functional role of IL22 in chronic colitis and how it regulates colonic epithelial cells, we employed a three-dimentional mini-gut epithelial organoid system, in vivo disease models and transcriptomic datasets in human IBD. As well as inducing transcriptional modules implicated in antimicrobial responses, IL22 also coordinated an endoplasmic reticulum (ER) stress response transcriptional programme in colonic epithelial cells. In the colon of patients with active colonic Crohn's disease (CD), there was enrichment of IL22-responsive transcriptional modules and ER stress response modules. Strikingly, in an IL22-dependent model of chronic colitis, targeting IL22 alleviated colonic epithelial ER stress and attenuated colitis. Pharmacological modulation of the ER stress response similarly impacted the severity of colitis. In patients with colonic CD, antibody blockade of IL12p40, which simultaneously blocks IL12 and IL23, the key upstream regulator of IL22 production, alleviated the colonic epithelial ER stress response. Our data challenge perceptions of IL22 as a predominantly beneficial cytokine in IBD and provide novel insights into the molecular mechanisms of IL22-mediated pathogenicity in chronic colitis. Targeting IL22-regulated pathways and alleviating colonic epithelial ER stress may represent promising therapeutic strategies in patients with colitis. NCT02749630.


Severe acute gastritis associated with Helicobacter pylori infection.
We describe the case of a young female referred to our unit because of acute upper abdominal symptoms. Upper gastrointestinal endoscopy showed a gastric picture resembling lymphoma or acute non-steroidal anti-inflammatory drug gastropathy (deep, large and irregular ulcers), but the clinical history and the histological examination of gastric biopsies were consistent only with acute gastritis Helicobacter pylori-correlated. The patient was treated with omeprazole and antibiotics with complete recovery. As the patient's cat had suffered from an acute gastrointestinal distress two weeks earlier, a case of zoonosis was hypothesized and an upper gastrointestinal endoscopy was performed also on the cat. Unfortunately, we were not able to detect Helicobacter pylori in the cat gastric mucosa, but only urease-producing spiral microorganisms. Possible sources of infection and pathogenetic mechanisms of the severe gastritis are discussed.


Properties of chalconaringenin and rutin isolated from cherry tomatoes.
Fresh cherry tomatoes cv. 'Susanne' contain more of the two flavonoids chalconaringenin (CN) and rutin than lycopene. Therefore some properties including antioxidant behavior of the flavonoids were studied. The two flavonoids were extracted from peel and isolated by use of different chromatographic methods. Molecular absorbtivities were found to be 26907 for CN and 20328 abs M(-1) cm(-1) for rutin. Both compounds exhibited properties as antioxidants through several assays, and rutin was found to be the strongest antioxidant except in one assay. None of the assays revealed pro-oxidative effects. As naringenin rather than CN is frequently reported as a tomato constituent, the stability of CN was investigated in order to detect potential ways of isomerization during sample preparation. CN isomerized slowly both under UVB radiation and in alkaline solutions. Thus, such factors do not explain the occurrence of naringenin in tomato samples. The deficiency in reports on CN may be explained by the similarity in chromatographic behaviors of CN and naringenin, and due to the fact that they have same molecular weights.


Detection of amplifiable messenger RNA in the serum of patients with lung cancer.
Recently, in addition to the detection of circulating tumor cells in peripheral blood of patients with solid tumors, the presence of free circulating nucleic acids in the plasma and serum has also been described. We have focused on the possibility of isolating and amplifying intact extracellular, tumor-related mRNA from the plasma/serum of patients with lung cancer. For this purpose, we established several RT-PCR-based amplification systems for the detection of a panel of five different genes. The expression of these genes was either shown to be restricted to lung tissue or associated with malignancy. We examined two small groups of 18 patients with lung cancer before and during chemotherapy, respectively. The message for beta-actin (control for integrity of the RNA) was detected in all of the analyzed sera from the control group and patients with lung cancer. Analysis of CK-19 expression was positive in the majority of tumor patients, but positive results were also shown in all of the control sera. The expression of MAGE-2 and TTF-1 genes was not observed in any of the patients in either the lymphocyte preparations or serum samples. Expression of the PGP 9.5 gene was observed in the cells of all 18 patients, but mRNA in the serum was only detectable in one case. The hnRNP-B1 mRNA was detectable in 14/18 sera, and Her2/neu-specific mRNA could be amplified from the serum of 7/18 patients. Combining the last two markers, we were able to detect all patients with a malignant lung tumor.


Children's knowledge and affective response to AIDS.
Given the urgency of the AIDS crisis, the current emphasis is on prevention of the disease. School-age children may be considered a vulnerable population at risk for future development of HIV infection. Prevention needs to involve educational programs founded on children's knowledge and beliefs about AIDS. Scant literature exists on children's cognition and affective response to AIDS. In this study, 58 school-age children were interviewed to determine their attitudes, beliefs, and emotional response to AIDS. Findings indicate that, in this sample, children had little specific knowledge of AIDS etiology, transmission, or treatment. They expressed negative emotional response to the discussion of AIDS. Health educational programs need to be designed to target children's need for accurate AIDS information that reflects their developmental stage.


Overexpression of the crgA gene abolishes light requirement for carotenoid biosynthesis in Mucor circinelloides.
This work describes the isolation and characterization of crgA, a Mucor circinelloides gene, which has a dominant-positive effect on light-regulated carotenogenesis. The crgA gene was originally identified in a transformation experiment as a 3'-truncated open reading frame which caused carotenoid overaccumulation in the dark. The complete cloning and sequencing of crgA revealed that its putative product presented several recognizable structural domains: a RING-finger zinc binding domain near the N-terminus, a putative nuclear localization signal, two stretches of acidic amino acids, glutamine-rich regions and a putative isoprenylation motif. The expression of exogenous copies of the complete crgA gene or two different 3'-truncated versions, produced a similar dominant-positive effect on the light-inducible carotenogenesis of M. circinelloides. The presence of these exogenous sequences also caused a missregulation of the endogenous crgA gene, resulting in its overexpression. Collectively, these observations suggest that crgA is involved in the regulation of carotenoid biosynthesis by light.


Broadband homonuclear chemical shift correlation at high MAS frequencies: a study of tanh/tan adiabatic RF pulse schemes without 1H decoupling during mixing.
At high magic angle spinning (MAS) frequencies the potential of tanh/tan adiabatic RF pulse schemes for 13C chemical shift correlation without 1H decoupling during mixing has been evaluated. It is shown via numerical simulations that a continuous train of adiabatic 13C inversion pulses applied at high RF field strengths leads to efficient broadband heteronuclear decoupling. It is demonstrated that this can be exploited effectively for generating through-bond and through-space, including double-quantum, correlation spectra of biological systems at high magnetic fields and spinning speeds with no 1H decoupling applied during the mixing period. Experiments carried out on a polycrystalline sample of histidine clearly suggest that an improved signal to noise ratio can be realised by eliminating 1H decoupling during mixing.


Molecular mechanisms of adenosine-induced apoptosis in human HepG2 cells.
To investigate effects of adenosine on cell proliferation and apoptosis in human HepG2 cells. HepG2 cells were incubated in the presence of adenosine (0.1-5 mmol/L) for 12-48 h, and the effect of adenosine on cell proliferation was evaluated by using 3-(4,5-dimethyl-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Hoechst 33342 fluorescent staining, dUTP-fluorescein isothiocyanate (FITC) fluorescence and flow cytometric analysis techniques were used to observe cell apoptosis. The effects of adenosine receptor (A1, A2a, A3 and nonspecific receptor) antagonists (8-cpt, DMPX, MRS1191, and theophylline) and an adenosine transporter protein inhibitor (dipyridamole) on adenosine-induced cell apoptosis were observed. Mitochondrial membrane potential was analyzed using DePsipher fluorescent staining, and caspase activity was detected using a Fluorometric assay kit and a fluorescence microplate reader. Adenosine significantly reduced cell viability in a dose- and time-dependent manner. The cytotoxicity of adenosine was related to the induction of cell apoptosis. Four adenosine receptor antagonists had no effect on cell apoptosis. However, dipyridamole significantly reduced the percentage of adenosine-induced apoptotic cells from 27.3% to 7.1% (P<0.05). At 48 h after treatment, 3 mmol/L adenosine increased caspase-3 activity 3.5-fold; dipyridamole markedly decreased caspase-3 activity 1.6-fold, and decreased apoptotic cell numbers. When HepG2 cells were treated with 3 mmol/L adenosine, mitochondrial membrane potential and the activity of caspase-8 or -9 remained unchanged. Our results suggest that adenosine-induced apoptosis in HepG2 cells is related to intracellular events rather than cell surface receptors, and that a caspase-3 cascade activation is required, which is not mediated via a mitochondrial pathway.


Annexin A2 regulates a disintegrin and metalloproteinase 17-mediated ectodomain shedding of pro-tumor necrosis factor-α in monocytes and colon epithelial cells.
Understanding the mechanism of tumor necrosis factor (TNF)-α shedding is important because TNF-α triggers inflammatory bowel disease development. A disintegrin and metalloproteinase (ADAM) 17 is a key enzyme for the shedding of not only the type 1 membrane-anchored protein, amphiregulin, but also the type 2 protein, TNF-α. However, the detailed mechanism by which ADAM17 cleaves type 1 and 2 membrane-anchored proteins is unclear. Annexin (ANX) A2 is involved in ADAM17-mediated amphiregulin shedding. In this study, we examined whether ANX A2 is involved in TNF-α shedding. We prepared U937, HT29, and HCT116 cells overexpressing alkaline phosphatase (AP)-tagged proTNF-α and depleted ADAM17 and ANX A2. We assessed TNF-α release and shedding by measuring the TNF-α release concentration and AP activities in conditioned media after interleukin-1β or 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation by enzyme-linked immunosorbent assay and AP assay, respectively. A direct association of ANX A2 with ADAM17 was examined with immunoprecipitation and Western blotting. Enzyme-linked immunosorbent assay and AP assay showed interleukin-1β-induced TNF-α shedding in HCT116 and HT29 cells and TPA-induced TNF-α release in U937 cells. KB-R7785 and ADAM17 depletion significantly blocked TNF-α shedding by TPA. ANX A2 depletion significantly inhibited TNF-α shedding by interleukin-1β and TPA. In contrast, ANX A2 depletion did not abrogate ADAM17-mediated amphiregulin and heparin-binding epidermal growth factor-like growth factor shedding. ANX A2 was directly associated with ADAM17. ANX A2 was closely associated with ADAM17 and played an important role in TNF-α shedding by TPA. Inhibition of ANX A2 might be a new therapeutic strategy for prevention of TNF-α shedding during inflammatory bowel disease inflammation.


[Morgagni hernia in childhood].
We report six cases of Morgagni hernia diagnosed and operated on in our pediatric surgical unit during a 14-year period. Four children were younger than 1 year and two between 1 and 2 years. Predominance in males was found. Associated congenital pathology was present in 3 children (Down's syndrome, diaphragmatic relaxation, criptorquidia and pyelo-ureteral stenosis). Predominant clinical features were respiratory infections and vomiting. In only one patient clinical onset was with respiratory distress. Plain chest x-ray was the most used diagnostic procedure. In all cases barium enema was performed to confirm the clinical diagnosis. Most frequent surgical approach was a midline supra-umbilical laparotomy. Diaphragmatic defect was left sided in 3 children and right-sided in the other 3. Transverse colon and liver were the most frequent herniated viscera. Postoperative follow-up showed no complications or recidives.


Recovery of circulating haemopoietic progenitor cells in the early phase of haemopoietic reconstitution after autologous and allogeneic bone marrow transplantation.
The recovery of circulating haemopoietic progenitor cells was evaluated serially in seven patients for 3-4 weeks after bone marrow transplantation (two autologous and five allogeneic) as treatment for leukaemia. Eight normal healthy volunteers were used as controls. CFU-G (colony forming unit-granulocyte) was found to be the earliest progenitor cell to recover at a mean interval of 16 +/- 1 (SE) days post-transplantation. A lag of 7 days was found before circulating CFU-GM (colony forming unit-granulocyte, monocyte) reappeared, while BFU-E (burst forming unit-erythroid) were detectable in only two patients in the first 4 weeks. The peak level of circulating progenitors was very low, 28 +/- 8/ml, compared with a mean level of 619 +/- 235/ml in eight normal individuals. This pattern of circulating progenitor cell recovery post-transplantation was consistently seen in all patients. CFU-G reappeared significantly earlier than CFU-GM suggesting that early granulocytic recovery after bone marrow transplantation is mediated by proliferation of mature progenitors committed to the granulocytic lineage, whereas later reconstitution is accompanied by the emergence of CFU-GM.


HA-1A. A human monoclonal antibody for the treatment of gram-negative sepsis.
HA-1A is a human monoclonal IgM antibody that binds to endotoxin. The results of the clinical trials of HA-1A demonstrate that HA-1A reduces mortality among patients with sepsis and gram-negative bacteremia. Secondary endpoints, including resolution of organ failure, discharge from intensive care unit, and discharge from the hospital, support the beneficial effects of the antibody. The antibody is well tolerated with rare side effects, including hypotension and urticarial rash. No anti-HA-1A antibodies have been detected.


The effects of different materials of protective gloves on thermoregulatory responses.
The effects of two kinds of protecting gloves for pesticide spraying made of different materials on thermoregulatory responses during exercise were studied at ambient temperature of 28 degrees C and relative humidity of 60% in six healthy females, aged 19. One kind of gloves was made of polyurethane (A) and the other of Goretex (B) with cotton lining in each glove. Both kinds of gloves had almost the same volume. Main results of the experiment were summarised as follows: (1) during the exercise an increase of rectal temperature was inhibited more effectively in B than in A; (2) skin temperature of hand was significantly lower in B than in A; (3) absolute humidity and temperature inside the gloves were significantly lower during the period from the gripping bar exercise to the end of the experiment; (4) the number of contractions by the handgrip exercise performed immediately after the second turning of the screw was significantly smaller in A than in B. The findings presented suggest that the gloves made of Goretex material could reduce thermal strain during intermittent work in warm environmental conditions.