A solid phase radioimmunoassay for prostatic acid phosphatase.
The sensitivity of a recently developed solid phase radioimmunoassay for human prostatic acid phosphatase was compared to that of an enzymatic method using p-nitrophenylphosphate as substrate. In 109 histologically verified untreated stages I to IV prostatic cancers and 200 men without such cancer the solid phase radioimmunoassay method demonstrated substantially greater sensitivity and specificity than the enzymatic technique. In the 109 prostatic malignancies the immunochemical method correctly classified 80 (73 per cent) versus 34 (31 per cent) for the p-nitrophenylphosphate enzymatic technique (p less than 10(-6). In 44 stages I and II cancers confined to the prostate the radioimmunoassay was abnormally elevated in 19 (43 per cent) with only 4 (9.1 per cent) enzymatic elevations (p less than 10(-3). In 65 stages III and IV extraprostatic cancers correct classifications were noted in 61 (94 per cent) of the radioimmunoassays and 30 (46 per cent) enzymatic tests (p less than 10(-6). The radioimmunoassay in 200 male controls yielded 11 (5.6 per cent) and the p-nitrophenylphosphate enzymatic test yielded 7 (3.5 per cent) falsely positive results. In 90 non-prostatic human cancer sera 85 (94.5 per cent) were correctly classified as negative by the radioimmunoassay for prostatic acid phosphatase versus 66 (73 per cent) as negative by the enzymatic method. These data are discussed in terms of the merits of a radioimmunochemical approach for the measurement of human serum prostatic acid phosphatase.


Oestrous cycle affects emergence from anaesthesia with dexmedetomidine, but not propofol, isoflurane, or sevoflurane, in female rats.
Although sex differences in anaesthetic sensitivity have been reported, what underlies these differences is unknown. In rodents, one source of variability in females is the oestrous cycle. Here we test the hypothesis that the oestrous cycle impacts emergence from general anaesthesia. Time to emergence was measured after isoflurane (2 vol% for 1 h), sevoflurane (3 vol% for 20 min), dexmedetomidine (50 μg kg-1 i.v., infused over 10 min), or propofol (10 mg kg-1 i.v. bolus) during proestrus, oestrus, early dioestrus, and late dioestrus in female Sprague-Dawley rats (n=24). EEG recordings were taken during each test for power spectral analysis. Serum was analysed for 17β-oestradiol and progesterone concentrations. The effect of oestrous cycle stage on return of righting latency was assessed using a mixed model. The association between righting latency and serum hormone concentration was tested by linear regression. Mean arterial blood pressure and arterial blood gases were assessed in a subset of rats after dexmedetomidine and compared in a mixed model. Oestrous cycle did not affect righting latency after isoflurane, sevoflurane, or propofol. When in the early dioestrus stage, rats emerged more rapidly from dexmedetomidine than in the proestrus (P=0.0042) or late dioestrus (P=0.0230) stage and showed reduced overall power in frontal EEG spectra 30 min after dexmedetomidine (P=0.0049). 17β-Oestradiol and progesterone serum concentrations did not correlate with righting latency. Oestrous cycle did not affect mean arterial blood pressure or blood gases during dexmedetomidine. In female rats, the oestrous cycle significantly impacts emergence from dexmedetomidine-induced unconsciousness. However, 17β-oestradiol and progesterone serum concentrations do not correlate with the observed changes.


Transcriptome analysis reveals modulation of differentially expressed genes in LPS-treated mouse macrophages (RAW264.7 cells) by grouper (Epinephelus coioides) Epinecidin-1.
The marine antimicrobial peptide Epinecidin (Epi)-1 has been shown to exert direct antimicrobial and immunomodulatory actions in teleost, mammalian and avian organisms. For instance, Epi-1 can suppress bacterial endotoxin lipolysachcharide (LPS)-induced proinflammatory cytokines in RAW264.7 murine macrophages. However, it remains unknown how Epi-1 might broadly affect non-activated and LPS-activated macrophages. To address this question, we performed a comparative transcriptomic analysis of non-treated and LPS-treated RAW264.7 cells in the presence and absence of Epi-1. Gene enrichment analysis was conducted on filtered reads, followed by GO and KEGG analyses. The results showed that Epi-1 treatment modulated pathways and genes associated with nucleoside binding, intramolecular oxidoreductase activity, GTPase activity, peptide antigen binding, GTP binding, ribonucleoside/nucleotide binding, phosphatidylinositol binding and phosphatidylinositol-4-phosphate binding. Based on the GO analysis results, we performed real-time PCR at different treatment times to compare expression levels of selected proinflammatory cytokines, anti-inflammatory cytokines, MHC, proliferation and differentiation genes. Epi-1 decreased expression of the proinflammatory cytokines, TNF-α, IL-6 and IL-1β, and it increased the anti-inflammatory cytokine TGFβ and Sytx1. MHC-associated genes, GM7030, Arfip1, Gpb11 and Gem, were induced by Epi-1, which is expected to enhance the immune response against LPS. Immunoglobulin-associated Nuggc was also upregulated by Epi-1. Finally, we found that Epi-1 downregulated the expression of host defense peptides CRAMP, Leap2 and BD3. Taken together, these findings suggest that Epi-1 treatment induces orchestrated changes in the transcriptome of LPS-stimulated RAW264.7 cells.


Selective impairment of contrast sensitivity in kittens exposed to periodic gratings.
1. Kittens were exposed to a periodic grating orientated vertically during the critical period of their life. 2. At the end of the critical period the amplitude of the response to drifting gratings was found to be reduced at the spatial frequency of exposure in multi-unit and in some single unit recordings at lateral geniculate level. 3. The contrast sensitivity measured with behavioural methods also showed a depression at the spatial frequency of exposure. 4. An analysis of the preferred stimulus orientation of cortical units in area 17 showed that all orientations were represented.


Occupational exposure and ovarian cancer risk.
Relatively little work has been done concerning occupational risk factors in ovarian cancer. Although studies conducted in occupational settings have reported positive associations, their usefulness is generally limited by the lack of information on important confounders. In a population-based case-control study, we assessed risk for developing epithelial ovarian cancer (EOC) associated with occupational exposure while accounting for important confounders. Participants were identified through provincial population-based registries. Lifetime occupational history and information on potential confounding factors were obtained through a self-administered questionnaire. Unconditional logistic regression and the likelihood ratio test were used to assess EOC risk with each occupation (or industry), relative to all other occupations (or industries), adjusting for potential confounders including body mass index, oral contraceptive use, menopausal hormone therapy, parity, age at first childbirth, age at menarche, age at menopause, family history of breast and ovarian cancer in mother and sister(s), tubal ligation, partial oophorectomy, and hysterectomy. Occupations and industries were coded according to the Canadian Standard Occupational Classification (SOC) and Standard Industrial Classification (SIC). Significant excess risk was observed for several groups of teaching occupations, including SOC 27, teaching and related (adjusted OR 1.77, 95% CI 1.15-2.81) and SOC 279, other teaching and related (adjusted OR 3.11, 95% CI 1.35-8.49). Significant excess was also seen for a four-digit occupational group SOC 4131, bookkeepers and accounting clerks (adjusted OR 2.80, 95% CI 1.30-6.80). Industrial sub-groups showing significant excess risk included SIC 65, other retail stores (adjusted OR 2.19, 95 % CI 1.16-4.38); SIC 85, educational service (adjusted OR 1.45, 95% CI 1.00-2.13); and SIC 863, non-institutional health services (adjusted OR 2.54, 95% CI 1.13-6.52). Our study found an elevated EOC risk for teaching occupations and is the first study to observe such an increased risk after adjustment for potential confounders. Further studies with more detailed assessment of the work environment and unique lifestyle characteristics may be fruitful in elucidating this etiology.


Hetero-interpenetrated metal-organic frameworks.
Interpenetrated metal-organic frameworks (MOFs) comprise two or more lattices that are mutually entangled. Interpenetration can be used to tune the structures and pore architectures of MOFs to influence, for example, their stability or interactions with guest molecules. The interpenetrating sublattices are typically identical, but hetero-interpenetrated MOFs, which consist of sublattices that are different from one another, have also been serendipitously produced. Here we describe a strategy for the deliberate synthesis of hetero-interpenetrated MOFs. We use the cubic α-MUF-9 framework as a host sublattice to template the growth of a second sublattice within its pores. Three different secondary sublattices are grown-two of which are not known as standalone MOFs-leading to three different hetero-interpenetrated MOFs. This strategy may serve to combine different properties into one material. We produce an asymmetric catalysis by allocating separate roles to the interpenetrating sublattices in a hetero-interpenetrated MOF: an achiral secondary amine on one sublattice provides the catalytic activity, while the chiral α-MUF-10 host imparts asymmetry to aldol and Henry reactions.


Pemphigus vulgaris involving the esophagus. A case report and review of the literature.
A case of pemphigus vulgaris confined to the oral cavity, larynx, and hypopharynx for two years with subsequent involvement of the entire esophagus is presented. Histopathology and direct immunofluorescence of the esophagus confirmed the diagnosis.


Relation of dreams to waking concerns.
To test that dreams are influenced by the pre-sleep waking emotional concerns of the sleeper and have an effect on waking adaptation, 20 depressed and 10 control subjects, who were all going through a divorce, were enrolled in a repeated measures study lasting 5 months. A Current Concerns test was administered on three occasions before nights when every REM period was interrupted to record recalled mental content. The degree of waking concern about the ex-spouse correlated significantly with the number of dreams in which the former partner appeared as a dream character. Those who were in remission at the follow-up evaluation had a higher percentage of well-developed dreams than those who remained depressed. Dreams of the former spouse reported by those in remission differed from those who remained depressed in the expression of dream affect and in the within-dream linkage among units of associated memory material. Dreams of the former spouse that are reported by those who are not in remission lack affect and connection to other memories.


Inhibition of glucose stimulated insulin secretion by neuropeptide Y is mediated via the Y1 receptor and inhibition of adenylyl cyclase in RIN 5AH rat insulinoma cells.
Neuropeptide Y (NPY) has been shown to inhibit insulin secretion from the islets of Langerhans. We show that insulin secretion in the insulinoma cell line RIN 5AH is inhibited by NPY. 125I-Peptide YY (PYY) saturation and competition-binding studies using NPY fragments and analogues on membranes prepared from this cell line show the presence of a single class of NPY receptor with a Y1 receptor subtype-like profile. Inhibition of insulin secretion in this cell line by NPY fragments and analogues also shows a Y1 receptor-like profile. Both receptor binding and inhibition of insulin secretion showed the same orders of potency with NPY > [Pro34]-NPY > NPY 3-36 >> NPY 13-36. The Y1 receptor antagonist, BIBP 3226, blocks NPY inhibition of insulin secretion from, and inhibits 125I-PYY binding to, RIN 5AH cells. Northern blot analysis using a Y1-receptor specific probe shows that NPY Y1 receptors are expressed by RIN 5AH cells. Y5 receptors are not expressed in this cell line. Neuropeptide Y inhibition of insulin secretion is blocked by incubation with pertussis toxin, implying that the effect is via a G-protein (Gi or Go) coupled receptor. Neuropeptide Y inhibits the activation of adenylyl cyclase by isoprenaline in RIN 5AH cell lysates, and the stimulation of cAMP by glucagon-like peptide-1 (7-36) amide (GLP-1). It also blocks insulin secretion stimulated by GLP-1, but not by dibutyryl cyclic AMP. Hence, we suggest that NPY inhibits insulin secretion from RIN 5AH cells via a Y1 receptor linked through Gi to the inhibition of adenylyl cyclase.


Bioactivity of select essential oil constituents against life stages of Anopheles arabiensis (Diptera: Culicidae).
Malaria is transmitted by infected female Anopheles mosquitoes, and An. arabiensis is a main malaria vector in arid African countries. Like other anophelines, its life cycle comprises of three aquatic stages; egg, larva, and pupa, followed by a free flying adult stage. Current vector control interventions using synthetic insecticides target these stages using adulticides or less commonly, larvicides. With escalating insecticide resistance against almost all conventional insecticides, identification of agents that simultaneously act at multiple stages of Anopheles life cycle presents a cost-effective opportunity. A further cost-effective approach would be the discovery of such insecticides from natural origin. Interestingly, essential oils present as potential sources of cost-effective and eco-friendly bioinsecticides. This study aimed to identify essential oil constituents (EOCs) with potential toxic effects against multiple stages of An. arabiensis life cycle. Five EOCs were assessed for inhibition of Anopheles egg hatching and ability to kill larvae, pupae and adult mosquitoes of An. arabiensis species. One of these EOCs, namely methyleugenol, exhibited potent Anopheles egg hatchability inhibition with an IC50 value of 0.51 ± 0.03 μM compared to propoxur (IC50: 5.13 ± 0.62 μM). Structure-activity relationship study revealed that methyleugenol and propoxur share a 1,2-dimethoxybenze moiety that may be responsible for the observed egg-hatchability inhibition. On the other hand, all five EOCs exhibited potent larvicidal activity with LC50 values less than 5 μM, with four of them; cis-nerolidol, trans-nerolidol, (-)-α-bisabolol, and farnesol, also possessing potent pupicidal effects (LC50 < 5 μM). Finally, all EOCs showed only moderate lethality against adult mosquitoes. This study reports for the first time, methyleugenol, (-)-α-bisabolol and farnesol as potent bioinsecticides against early life stages of An. arabiensis. This synchronized activity against Anopheles aquatic stages shows a prospect to integrate EOCs into existing adulticide-based vector control interventions.


Anterior cervical fusion assessment: surgical exploration versus radiographic evaluation.
Prospective clinical trial. The goal of this prospective study was to assess the reliability of plain radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) to detect a pseudarthrosis after an anterior cervical fusion compared with intraoperative exploration. Although anterior cervical fusions have been performed for >50 years, diagnosis of pseudarthrosis remains controversial, and even though various radiologic methods have been described to detect a pseudarthosis, no reports have compared these studies against the gold standard of intraoperative exploration to determine which is most accurate. All explorations were performed >6 months after the index procedure and studies were obtained within a month of surgery. Indications for reoperation were adjacent level disease and/or pseudarthrosis repair. All patients were thoroughly explored using a microscope, uncinate-to-uncinate exploration, and if necessary, removal of part of the corticalized graft. Radiologic studies were blindly and independently reviewed by 3 spine surgeons uninvolved in the care of the patients. Of the 14 patients included, 8 had pseudarthroses. Assessment of the agreement between intraoperative and radiographic findings revealed a mean Kappa statistic of 0.67 (range, 0.51-0.75, P < 0.05) for plain radiographs, 0.81 (range, 0.71-0.87, P < 0.05) for CT, and 0.48 (range, 0.32-0.71, P < 0.05) for MRI. When all studies were taken into consideration, the mean Kappa statistic increased to 0.85 (range, 0.71-1.00, P < 0.05). Assessment of paired interobserver reliability revealed a mean Kappa statistic of 0.46 (range, 0.31-0.55, P < 0.05) for plain radiographs, 0.82 (range, 0.73-0.87, P < 0.05) for CT, and 0.32 (range, 0.21-0.40, P < 0.05) for MRI. When all radiographic studies were taken into consideration, paired interobserver reliability had a mean Kappa statistic of 0.70 (range, 0.55-0.85, P < 0.05). Our results indicate that CT most closely agrees with intraoperative findings. We therefore recommend that CT be used in any study that relies on fusion status assessment. It is important to remember, however, that even CT is not 100% accurate.


Bias resulting from the use of 'assay sensitivity' as an inclusion criterion for meta-analysis.
Assay sensitivity has been proposed as a criterion for including psychiatric clinical outcome studies in meta-analyses. The authors assess the performance of assay sensitivity as a method for determining study appropriateness for meta-analysis by calculating expected standard drug vs placebo effect sizes for various combinations of high quality and flawed studies. In the absence of flawed studies, expected effect sizes are close to unbiased only when sample sizes are very large. In the presence of flawed studies, expected effect sizes tend to be substantially biased except under simultaneous conditions of high power, a large proportion of flawed studies, and a population standard vs placebo effect size of flawed studies considerably lower than that of high quality studies. The authors conclude that this method is not robust and can lead to serious bias. Unless it can be shown that specific conditions hold, assay sensitivity should not be used to make quality judgments of studies.


Spontaneous preterm delivery in primiparous women at low risk in Denmark: population based study.
To analyse trends in preterm delivery and the factors contributing to preterm delivery in Denmark. To construct a standard population at low risk (white European, 20-40 years of age, with a singleton spontaneous pregnancy) and describe the changes in this population so that time trends can be compared internationally. Population based study. 99.8% of all deliveries in Denmark, 1995-2004. Proportion of babies born at less than 37 weeks' completed gestation for each year in the overall population and in a standard population at low risk. Overall, the proportion of preterm deliveries increased by 22% from 1995 to 2004. During the same period, known risk factors for preterm delivery such as in vitro fertilisation, multiple pregnancies, and elective deliveries also increased, and logistic regression analyses showed that these factors were associated with an increased risk of preterm delivery. Spontaneous preterm deliveries in primiparous women at low risk rose 51% (from 3.8% to 5.7%) during this time compared with 20% (2.7% to 3.2%) in multiparous women at low risk. The overall proportion of preterm deliveries increased significantly from 1995 to 2004 and primiparity and multiple birth were the most important contributing factors. The rise in spontaneous preterm deliveries in the standard population of primiparous women at low risk was greater than in the total population.


Fungal L-asparaginase: Strategies for production and food applications.
L-asparaginase (L-asparagine amidohydrolase EC 126.96.36.199) is of great importance in pharmaceutical and food applications. This review aims to describe the production and use of fungal L-asparaginase focusing on its potential as an effective reducer of acrylamide in different food applications. Fungal asparaginases have been used as food additives and have gained importance due to some technical advantages, for example, fungi can grow using low-cost culture mediums, and the enzyme is extracellular, which facilitates purification steps. Research aimed at the discovery of new L-asparaginases, mainly those produced by fungi, have great potential to obtain cheaper enzymes with desirable properties for application in food aiming at the reduction of acrylamide.


[Wegener's granulomatosis as a clinical form of vasculitis].
A two cases Wegener's syndrome was described. The current knowledge concerning the role of neutrophils in pathogenesis of Wegener's syndrome is reviewed.


Matrix metalloproteinase 9 in mucosally invasive gastric cancer.
BACKGROUND: Matrix metalloproteinase 9 (MMP-9) facilitates tumor invasion and metastasis via basement membrane degradation. Control of MMP-9 production by cancer-stromal cell interactions in these processes has been observed.METHODS: We measured plasma MMP-9 concentrations, using a one-step sandwich enzyme immunoassay, and also immunohistochemically localized MMP-9 in patients with small gastric cancers limited to the mucosa. The cancers were classified as intraepithelial tumor (Tis) and T1 disease according to the tumor-node-metastasis (TNM) classification of the International Union Against Cancer.RESULTS: Patients with T1 disease had a higher positivity rate for and mean value of MMP-9 than patients with Tis disease. In T1 tumors, MMP-9 expression determined immunohistochemically, was greater in cells in cancer stroma than in cells in noncancerous stroma, a situation found in only a few Tis tumors.CONCLUSIONS: These results suggest that MMP-9 is related to the initial step of gastric cancer invasion.


Hospitals must be businesslike. Interview by Alan J. Appelbaum.
AHA's new chairman-elect designate believes that today's not-for-profit hospital is a business enterprise and that it might benefit by following a corporate model.


[Changes in the energy needs of the elderly: an often encountered cause of nutritional deficiencies and frailty].
Changes in the body composition of elderly people and diminished physical activity reduce the energy requirement and the daily energy intake. It is especially frail elderly people who run an increased risk of a poor nutritional condition which further enhances fragility. Frailty is often defined as the state of reduced physiologic reserve associated with increased susceptibility to disability. In frail elderly people energy requirement is often reduced. Studies have shown that when energy intake falls below a level of about 6.3 MJ, it is hard to obtain a diet with a sufficient supply of minerals and water soluble vitamins. It is especially the daily intake of vitamins of the B complex and of vitamin C that then prove insufficient. In addition, immobile elderly and elderly of 75 years and older are at risk for an inadequate vitamin D status. An adequate diet is one of the factors that may prevent frail health. Screening lists have been developed to quickly obtain information about the nutritional status of older adults. However, these lists still have to be adapted to the Dutch dietary pattern. Currently, a change of the body weight is the best warning of insufficient nutrition.


Management of patent foramen ovale and stroke.
Paradoxical embolization is a rare but well-recognized cause of stroke. Some studies have suggested a link between patent foramen ovale (PFO) and a higher risk of ischemic stroke through this mechanism. PFO is more commonly seen in patients with cryptogenic stroke, but a clear causative relationship between the two is not well established. Other anatomic features associated with a PFO could increase the risk of a recurrent stroke, including an atrial septal aneurysm (ASA), a large PFO, and spontaneous right-to-left shunt at rest. An underlying hypercoagulable state should be ruled out if a PFO is found in a patient with a stroke or transient ischemic attack who has no other identifiable source. Options for secondary prevention in these patients include antiplatelet therapy, anticoagulation, and surgical or endovascular closure. Studies have not shown any advantage of warfarin over aspirin. Surgical closure is a less favorable option because of its high perioperative risks. To date, retrospective studies show variable results of endovascular closure for prevention of stroke. Several randomized prospective studies currently under way are expected to conclusively answer this question. Until these data is available, antiplatelet therapy remains the first-line treatment and endovascular closure should be considered in selected cases.


Interpreting the electronic fetal monitor. Strategies for management.
Electronic fetal monitoring offers the practitioner involved in the intrapartum care of women a mechanism to validate the fetus' physiologic adaptation to the labor and delivery experience. Utilizing a predetermined framework for constant assessment of fetal well-being will assist the clinician in the bedside management of these patients. This pathway of reassurance for fetal evaluation is an effective tool in the intrapartum observations of the fetus. If the fetus can demonstrate his physiologic well-being, labor may continue. However, if there are no signs of reassurance, immediate delivery of the fetus should be considered.


Quality of Care for Transcatheter Aortic Valve Implantation: Development of Canadian Cardiovascular Society Quality Indicators.
Transcatheter aortic valve implantation (TAVI) is a relatively new procedure to treat aortic stenosis in patients at high surgical risk, and it is becoming increasingly available in Canada. Variation exists in the clinical care, program coordination, evaluation, and funding across provinces and centres. As a part of the Canadian Cardiovascular Society (CCS) quality initiative, the TAVI Quality Indicator (QI) Working Group was established in 2014 to develop a set of indicators to measure quality of care for Canadians undergoing TAVI for aortic stenosis. The TAVI QI Working Group is composed of expert clinical and government agency representatives. The group developed consensus agreements for the selection of the first iteration of measurable structure, process, and outcome indicators reflective of the quality of care for patients undergoing TAVI. The objectives of the project are to develop quality indicators with the eventual goal of standardizing TAVI quality reports across Canada and to support local and national quality assurance, as well as engage multiple stakeholders to build a national strategy for the evaluation of quality of care.


Absorption, distribution and metabolism of propyl anthranilate.
Analysis of the gut contents of rats killed at intervals after dosage with propyl anthranilate or anthranilic acid suggested that both acid and ester were absorbed rapidly; the chief site of absorption was the stomach. Not more than a trace of the ester was hydrolysed in the stomach but of the dosed ester detected in the small intestine (less than 7%) a considerable proportion, increasing with time after dosing was present as anthranilic acid. Measurement of the level of radioactivity in the blood after administration of 14C-labelled propan-1-ol, propyl anthranilate or anthranilic acid showed that the alcohol was absorbed more rapidly than either the ester or acid. Unchanged propyl anthranilate was readily detected in the blood of rats dosed with the ester and some unhydrolysed ester was excreted in the urine. The level of radioactivity of the organs of rats 2 h and 4 h after administration of the 14C-labelled compounds was measured. Velocity constants for the excretion of 14CO2 by rats dosed with 14C-labelled propyl anthranilate were significantly lower than those found for rats dosed with [14C]propan-1-ol indicating a limiting step in the metabolism of the propyl moiety of the ester which did not occur in the metabolism of propan-1-ol. The urinary metabolites of anthranilic acid excreted by rabbits and rats dosed with the acid were qualitatively the same as those excreted by these species after dosing with propyl anthanilate; some quantitative differences were however, observed.


Resuscitation after severe hypoxia in a young child: temporary isoelectric EEG and loss of BAEP components.
EEG and multimodality evoked potentials are currently used to ascertain brain death. We have observed electrocerebral silence (ECS) and loss of wave IV and V in BAEP in a 28-month-old child, 2 h after resuscitation from severe hypoxia, followed by reappearance of EEG activity and of waves IV and V (latencies and amplitudes within normal range) 18 h later. Temporary loss of EEG activity has been observed occasionally, while rapid reoccurrence of BAEP waves IV and V was unexpected and in contrast to the common observation, that rostro-caudal loss of BAEP waves is irreversible. This observation suggests that temporary loss of BAEP waves IV and V may occur and that caution is necessary in the interpretation of BAEP recorded immediately after a resuscitation.


Broncholithiasis: its detection by computed tomography in patients with recurrent hemoptysis of unknown etiology.
Broncholithiasis is often not diagnosed by conventional roentgenography and fiberoptic bronchoscopy. Demonstrated here and three such cases of "recurrent hemoptysis of unknown etiology,". The broncholith in each case was clearly demonstrated only by the thoracic computed tomography (CT). We stress that CT is an extremely useful modality in the diagnosis of broncholithiasis and that the true incidence of broncholithiasis could be greater than was previously believed.


Lives Interrupted: Navigating Hardship During COVID-19 Provides Lessons in Solidarity and Visibility for Mobile Young People in South Africa and Uganda.
We examine data from young women and men in South Africa and young female sex workers in Uganda to explore the inequalities and hardships experienced during the COVID-19 pandemic and investigate the opportunities and ability presented to navigate in a virtual world to build an inclusive supportive future for young people on the move. We argue that against the backdrop of a fragile past, young people who see their today disturbed, tomorrow reshaped and their futures interrupted, need support to interact with their social environment and adjust their lives and expectations amidst the changing influences of social forces.


Identification of human homologues of the mouse mammary tumor virus receptor.
Human breast tumors contain DNA sequences with high homology to the Mouse Mammary Tumor Virus (MMTV) env gene. env encodes the membrane glycoprotein that binds to the MMTV receptor (Mtvr) in mouse tissues and is required for infection. If humans become infected with MMTV, identification of a human Mtvr might shed light on the mechanism of infection. Here, we identified two human genes, Mtvr1 and Mtvr2, encoding proteins highly related to the mouse receptor. Mtvr-related sequences were also detected in other mammalian species. Thus, zoonotic transmission of MMTV is a real possibility given the existence of highly homologous MMTV receptors.


Determination of the dissociation constants of ropinirole and some impurities and their quantification using capillary zone electrophoresis.
Ropinirole, 4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one, is a potent anti-Parkinson's disease drug developed by SmithKline Beecham Pharmaceuticals. Capillary zone electrophoresis (CZE) was used for the determination of the dissociation constants of ropinirole and five structurally related impurities, potentially formed during its synthesis and for separation and quantification of these substances. The dissociation constants obtained from the CZE measurements were confirmed by UV spectrophotometry for some of the test compounds, obtaining a good agreement between the values. Careful optimization of the running buffer composition permitted base-line resolution of the six compounds in a borate buffer containing acetonitrile and magnesium sulfate (a 100 mM borate buffer containing 30 mM MgSO4 and 20 vol.% of acetonitrile). It was shown that CZE can determine the level of these impurities, down to a level of 0.05% of the main component within 15 min.


Barrett's Adenocarcinomas are frequently underdiagnosed as "high grade intraepithelial neoplasia".
Relevant guidelines require that a primary histological diagnosis of high-grade intraepithelial neoplasia (HGIEN) in Barrett's oesophagus, be submitted to a second opinion by an expert gastroenterological pathologist. To date, however, no pertinent study of the outcome of such second-opinion diagnoses has been published. Between 2001 and 2005, histological slides from 275 patients with the primary diagnosis HGIEN underwent a second-opinion review. The resulting diagnoses were checked by follow-up in 207 of these patients (75.3 %). The second-opinion diagnosis no IEN (n = 27) was confirmed in 85.2 % of the cases, 7.4 % had LGIEN, 3.7 % had HGIEN or a well-differentiated Barrett's adenocarcinoma (BCA) (1 patient, each). In the single patient with the second-opinion diagnosis LGIEN, endoscopic resection revealed a well-differentiated BCA, Follow-up examinations confirmed the second-opinion diagnosis BCA in 5 out of 12 patients, in 1 patient no IEN was found, and 6 patients had a BCA. The second-opinion diagnosis BCA was confirmed by follow-up-examinations in 145 patients (86.8 %), in 12 patients (7.2 %) follow-up revealed HGIEN and in 10 no neoplasia. The results of this study show that the demand for a second opinion from an expert gastroenterological pathologist is justified, and also that BCA is frequently underdiagnosed as HGIEN.


Impact of Tumor Growth Speed of Primary Lesions on the Clinical Outcomes of Appendicular Skeletal Metastases.
This study aimed to investigate the clinical influence of the growth speed of primary lesions on appendicular skeletal metastases to provide an optimal treatment strategy for the metastases. Fifty-seven patients who underwent surgery for appendicular skeletal metastases between 2008 and 2020 were included. According to the growth speed of primary lesions, the patients were divided into the S group (slow-to-moderate, n=34) and the R group (rapid, n=23), and the outcomes were investigated. The period from diagnosis of skeletal metastases to pathological fracture (PF) was shorter in the R group than in the S group (p=0.24). The overall survival of the S group was significantly better than that of the R group (p=0.02). The appendicular skeletal metastases of the primary tumor with rapid growth speed have a high risk of PFs developed early from the diagnosis of skeletal metastases, and the prognosis may be poor.


Retrograde signaling via axonal transport through signaling endosomes.
Neurons extend axons far from cell bodies, and retrograde communications from distal axons to cell bodies and/or dendrites play critical roles in the development and maintenance of neuronal circuits. In neurotrophin signaling, the retrograde axonal transport of endosomes containing active ligand-receptor complexes from distal axons to somatodendrite compartments mediates retrograde signaling. However, the generality and specificity of these endosome-based transportations called "signaling endosomes" remain to be elucidated. Here, I summarize the discovery of semaphorin3A signaling endosomes, the first example other than neurotrophins to regulate dendritic development via AMPA receptor GluA2 localization in dendrites. The molecular components of Sema3A and neurotrophin signaling endosomes are distinct, but partially overlap to regulate specific and common cellular events. Because receptors are transported back to the cell bodies, neurons must replenish receptors on the growth cone surface to ensure continued response to the target-derived ligands. Recent findings have demonstrated that retrograde signaling endosomes also induce anterograde delivery of nascent receptors in neurotrophin signaling. The coupling between anterograde and retrograde axonal transport via signaling endosomes therefore plays a critical role in regulating proper neuronal network formation.


[Leaching of copper ore of the Udokanskoe deposit at low temperatures by an association of acidophilic chemolithotrophic microorganisms].
Pure cultures of indigenous microorganisms Acidithiobacillus ferrooxidans strain TFUd, Leptospirillum ferrooxidans strain LUd, and Sulfobacillus thermotolerans strain SUd have been isolated from the oxidation zone of sulfide copper ore of the Udokanskoe deposit. Regimes of bacterial-chemical leaching of ore have been studied over a temperature range from -10 to +20 degrees C. Effects of pH, temperature, and the presence of microorganisms on the extraction of copper have been shown. Bacterial leaching has been detected only at positive values of temperature, and has been much more active at +20 than at +4 degrees C. The process of leaching was more active when the ore contained more hydrophilic and oxidized minerals. The possibility of copper ore leaching of the Udokanskoe deposit using sulfuric acid with pH 0.4 at negative values of temperature and applying acidophilic chemolithotrophic microorganisms at positive values of temperature and low pH values was shown.


The use of urodynamic studies to assess the effect of pharmacological agents with particular references to alpha-adrenergic blockade.
A method of studying the effect of drugs on the lower urinary tract is described, using cord-injured patients with detrusor hyperreflexia. In this study 19 patients received intravenous phentolamine. This alpha-adrenergic blockade produced a significant reduction in the maximum voiding detrusor pressure, voided volumes and peak flow rates with no reduction of outflow tract obstruction.


Comparison of diarrhea induced by ingestion of fructooligosaccharide Idolax and disaccharide lactulose: role of osmolarity versus fermentation of malabsorbed carbohydrate.
Whether carbohydrate malabsorption causes diarrhea probably depends on the balance between the osmotic force of the carbohydrate and the compensatory capacity of the colon to dispose of the carbohydrate by bacterial fermentation. The present study evaluated the specific role of the osmolarity by comparing the severity of diarrhea after ingestion of two nonabsorbable carbohydrates, the fructooligosaccharide Idolax and the disaccharide lactulose. Both carbohydrates are readily fermented by the colonic flora but differ in osmolarity, the osmotic force being twice as high for lactulose as for Idolax. Twelve subjects were given increasing doses (0, 20, 40, 80, 160 g/d) of Idolax and lactulose in a crossover design. Every dose level was administered for three days with intervals of one week. Stools were collected on the third day to determine 24-hr volume, concentrations of short-chain fatty acids, L- and D-lactate, residues of Idolax or lactulose, sodium, potassium, pH, osmolarity, and in vitro productions of organic acids. Measured by short-chain fatty acid and lactate formation in a fecal incubation system, the fermentation of Idolax and lactulose was identical and very rapid compared with a range of reference carbohydrates. A laxative effect of both Idolax and lactulose was demonstrated. The increment in fecal volume as a function of the dose administered was twice as high for lactulose (slope of the regression line = 7.3, r = 0.64, P< 10(-5)) as for Idolax (slope = 3.7, r = 0.51, P<10(-3)), i.e., isosmolar doses of lactulose and Idolax had the same effect on fecal volume. The variation in fecal volume was substantial (lactulose 80 g/day: 110-1360 g/day; Idolax 160 g/day: 130-1440 g/day). High responders had earlier and larger fecal excretions of the saccharide compared with low-responders. Fecal volume in carbohydrate-induced diarrhea is proportional to the osmotic force of the malabsorbed saccharide, even though all or the majority of the saccharide is degraded by colonic bacteria. The capacity to modify the diarrhea varies considerably from person to person and is associated with colonic saccharide disposal, whereas the variation in response to isosmolar amounts of different saccharides is small within the same individual.


Predicting carcinogenicity with short-term tests: biological models and operational approaches.
This paper illustrates the basic biological models that have had an influence on the development and deployment of short-term assays for carcinogens. A tentative description of such a conceptual framework is provided with the use of methods for the quantitative analysis of information. This picture is contrasted with the results of a series of statistical mathematical analyses carried out on real genotoxicity data bases. The resulting evidence indicates that the biological models derived from basic laboratory research are not adequate or sufficient to interpret the operational performances of short-term assays. Obviously these models are of great importance, but, this observed discrepancy suggests the need for articulated approaches, with particular emphasis on analytical tools able to interpret the complexity of these systems. In particular, the multivariate data analysis methods are indicated as suitable for the description of large and complex bodies of data, and the identification of typologies and regularities. A number of applications of such methods are also presented. The conclusion is that biological models and operational approaches have to interact on the same level. The operational approach should indicate whether the conceptual framework of the experimenter is adequate to describe the experimental situation and possibly point to new relationships and trends, as well as to practical solutions.


Do antidromic latency jumps indicate axonal branching in nigrostriatal and hypothalamo-neurohypophysial neurons?
Neurons in many brain regions exhibit discontinuous decreases in antidromic latency with small increases in stimulating current. We used an electrophysiological test requiring a single stimulating electrode to determine whether these 'latency jumps' are due to shifts in the site of spike initiation to the same or different axon branches. Latency jumps in response to stimulation of the striatal terminal fields of substantia nigra, pars compacta neurons represent spike initiation on different branches while those seen in paraventricular neurons with pituitary stalk stimulation usually reflect a change in site on a single branch.


Serum urate level and cancer.
Histograms of the serum uric acid level of cancer patients (n = 501) and healthy controls (n = 15150) are compared. The statistical evaluation of the data yields significantly lower uric acid levels for cancer patients than for healthy persons (P less than 0.0001 for males, P less than 0.001 for females). These results support the theory that reactive species of oxygen (singlet oxygen and oxygen radicals) play an important role during carcinogenesis.


Case report: a diagnostically challenging conjunctival mass caused by the Epstein-Barr virus.
We present a paediatric case of infectious mononucleosis in a 13-year old, manifesting with follicular conjunctivitis and a conjunctival mass in one eye with no evidence of leucocytosis on the blood count. The diagnosis was confirmed following surgical excision and biopsy. The case represented a diagnostic challenge due to its atypism and given the steady increase in the prevalence of EBV-related ocular diseases in the last years, this report can serve as an example to prompt earlier serological tests to identify the aetiology in similar cases. This is important because EBV can be treated with acyclovir early in the active viral phase.


Significance of non-standardized magnetic resonance imaging abnormalities and subsequent targeted prostate cancer biopsy for pathologists: A retrospective observational study.
Prostate biopsy is essential in diagnosing prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) and magnetic resonance imaging (MRI)-transrectal ultrasound fusion-guided biopsy are also useful for diagnosis. However, the burden of implementing and maintaining these techniques should be considered. Therefore, we investigated the significance of non-standardized pre-biopsy MRI abnormalities (conditions not in accordance with PI-RADS) and subsequent targeted biopsy. We collected clinicopathological data, including the presence or absence of MRI abnormalities, through biopsies from January 2017 to February 2022 at the Kanagawa Cancer Center and performed statistical analyses. We enrolled in 1086 cases: MRI abnormalities were observed in 861 cases (79.3%). In these 861 cases, the adenocarcinoma detection rate, number of positive cores, and length of the highest Grade Group (GG) lesions were significantly higher. In the multivariate analysis, MRI abnormalities were the most significant factor for detecting adenocarcinoma of ≥GG 2 (odds ratio: 4.52, 95% confidence interval: 3.08-6.63). Targeted biopsy showed a higher percentage of positive cores with ≥GG2 and longer highest GG lesion lengths than systematic biopsy. Furthermore, the highest GG was upgraded in 109 of 788 cases by targeted biopsy. However, several adenocarcinomas (125/788; 15.9%) could not be detected using only targeted biopsy. Non-standardized MRI abnormalities are powerful predictors of cancer and grading. Targeted biopsies based on MRI abnormalities provide several benefits. Owing to the relatively low implementation hurdle, these biopsies may serve as a bridge until the ideal approaches are popularized if the limitations are well understood.


Spermatocyte chromosome alterations in mice inoculated with antirabies vaccine and tetanus toxoid separately and in combination.
The genotoxic potential of antirabies vaccine (ARV) and tetanus toxoid (TT) inoculated separately and in combination was evaluated by spermatocyte chromosome analysis in mice. Adult males were vaccinated with a dose of 1 ml/kg ARV once daily for 7 days, or with a dose of 1 ml/kg TT once only, or with both (TT being administered along with the last dose of ARV). Spermatocytes were analyzed over 1-6 post-vaccination weeks for numerical and structural changes as well as for univalent formation. Controls were age matched non-vaccinated males. Significantly high incidences of structural aberrations from wk 4 onwards and at wk 6 following inoculation of ARV and TT, respectively, suggested susceptibility of stem cells to the vaccines. Combined vaccination (ARV plus TT) showed an additive effect. Occurrence of univalents involving autosomes as well as sex chromosomes was very common in all the vaccinated groups, the sex chromosomes being prevalently involved. Structural aberrations showed a positive correlation with time, while univalent formation showed a negative correlation. It appears that factors for clastogenicity and univalent formation are different for both the vaccines.


Does Induction with Misoprostol Impact the Small for Gestational Age Neonate?
To compare outcomes in small for gestational age neonates induced with misoprostol to other cervical ripening agents. We hypothesized that misoprostol use will demonstrate no significant difference in outcomes compared with alternative agents. Small for gestational age neonates (<10th percentile for gestational age) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) sponsored Consortium on Safe Labor database were analyzed. Neonates induced with misoprostol ± oxytocin (n = 451) were compared with neonates induced with prostaglandin E2 ± oxytocin and/or mechanical dilation ± oxytocin (n = 663). Primary outcomes included intrapartum fetal distress, cesarean section for fetal distress, cesarean section for any reason, neonatal intensive care unit admission, low 5-minute Apgar, and composite neonatal morbidity. Multiple logistic regression was used to calculate adjusted odds ratios (aORs). Data were analyzed using SAS. Small for gestational age neonates induced with misoprostol ± oxytocin compared with alternative agents had decreased low 5-minute Apgar scores (aOR 0.27 [0.10-0.71]). No significant differences were demonstrated among very small for gestational age neonates (<5th percentile for gestational age). Our results suggest that misoprostol does not increase risk of adverse outcomes in small for gestational age neonates; however, prospective studies are warranted to further assess optimal cervical ripening agents in this population.


CSF N-CAM in neuroleptic-naïve first-episode patients with schizophrenia.
An increased concentration of neural cell adhesion molecule (N-CAM) 105-115 kDa has been reported in patients with schizophrenia in both CSF and in post-mortem brain samples. To determine whether increased N-CAM is integral to the disease process or, alternatively, results from early treatment, CSF N-CAM was measured in a blind study of first episode (FE) patients, who were either neuroleptic-naïve (NN) or neuroleptic-treated (NT, < 100 mg Haldol equivalents), multi-episode (ME) patients, and controls. Overall, the FE patients displayed lower N-CAM concentrations as compared to controls (p = 0.043). This decrease in N-CAM in FE patients was seen only in the FE-NT group as compared to both controls (p = 0.0006). The FE-NT group also showed a lower CSF N-CAM compared to that in the FE-NN (p = 0.025) group. No difference in CSF N-CAM between the FE-NN and control group was found. ME patients showed an increased N-CAM as compared with FE patients (p = 0.018), but not as compared to controls (p = 0.93). Neuroleptic-naïve first-episode patients do not display a phenotypic increase in N-CAM. Thus, N-CAM is altered in first-episode patients following acute neuroleptic treatment and withdrawal, as compared to neuroleptic-naïve first-episode patients.


Activities of Antioxidant and Proteolytic Systems and Biomarkers in the Fat Body and Hemolymph of Young Apis mellifera Females.
The proteolytic and antioxidant systems are important components of humoral immunity, and these biomarkers indicate the immune status. These compounds are synthesized in the bees' fat body and released into the hemolymph. Their functions maintain the organism's homeostasis and protect it against adverse environmental factors (including pathogens). We determined the activities of acidic, neutral, and alkaline proteases and their inhibitors, as well as superoxide dismutase (SOD), catalase (CAT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and the level of total antioxidant potential (TAC). These compounds were investigated in the fat body and hemolymph in the females with increased reproductive potential, i.e., queens and rebels, and in normal (non-reproductive sterile non-rebel) workers. The phenoloxidase (PO) activities were determined in the hemolymph. The normal workers had higher activities of proteases and their inhibitors, SOD and CAT, in the fat body and hemolymph, compared to the queens and rebels. The protease inhibitors were not usually active in the queens. As we predicted, the rebels revealed values between those of the queens and normal workers. The highest activities of proteases and antioxidants were identified in the fat body from the third tergite in comparison with the sternite and the fifth tergite. These results are important for oxidative stress ecology and give a better understanding of the functioning of the fat body and the division of labor in social insects.


Neurotoxicity of silver nanoparticles stabilized with different coating agents: In vitro response of neuronal precursor cells.
Silver nanoparticles (AgNPs) represent one of the most abundant biocidal nanomaterials contained in more than 30% of nano-enabled consumer products and 75% of nanomedical products. The cumulative exposure of the general population may therefore reach critical and potentially hazardous levels. Due to data gaps on AgNP effects in humans, it is urgent to further evaluate their possible toxicity, particularly in vulnerable systems like the nervous one. As AgNPs may cross the blood brain and placental barriers, this study evaluated the in vitro effect of different AgNPs on neuronal precursor cells. For this purpose, 10 nm-sized AgNPs were stabilized with five different coating agents rendering a neutral, positive and negative surface charge. Murine neural stem cells (mNSCs) were used as cellular model to test AgNP neurotoxicity by evaluating the range of toxicity endpoints including cellular viability, apoptosis induction, oxidative stress response, cellular and mitochondrial membrane damages, DNA damage, inflammation response, and neural stem cell regulation. Our results clearly showed that the neurotoxic potential of AgNPs was not dependent on their surface charge or coating agents used for their surface stabilization. All AgNP types exhibited significant toxicity in neuronal precursor cells at an in vitro dose of 5 mg Ag/L or lower.


[Microflora of the nasal cavity and its sensitivity to antibiotics in patients with chronic rhinitis treated by cryotherapy].
Cryotherapy is used in treatment of chronic rhinitis and pharyngitis. The effect of cryotherapy on the qualitative and quantitative composition of the microflora was studied. Staphylococci prevailed in the rhinitis patients, streptococci, Clebsiella and Neisseria being registered more rarely. The staphlococcal isolates were highly sensitive to monomycin, neomycin, erythromycin and levomycetin. The results of the dynamic study showed that the flora composition did not significantly change during cryotherapy and the sensitivity level of the staphylococcal isolates to the antibodies remained unchanged.


Risky attitudes towards road use in pre-drivers.
Motor vehicle accidents are one of the principal causes of adolescent disability or mortality and male drivers are more likely to be involved in road accidents than female drivers. In part such associations between driver age and sex have been linked to differences in risky behaviour (e.g. speed, violations) and individual characteristics (e.g. sensation seeking, deviant behaviour). The aim of this research is to determine whether associations between risky road user behaviour and individual characteristics are a function of driver behaviour or whether they are intrinsic and measurable in individuals too young to drive. Five hundred and sixty-seven pre-driver students aged 11-16 from three secondary schools completed questionnaires measuring enthusiasm for speed, sensation seeking, deviant behaviour and attitudes towards driver violations. Boys reported more risky attitudes than girls for all measures. Associations between sensation seeking, deviant behaviour and attitudes towards risky road use were present from early adolescence and were strongest around age 14, before individuals learn to drive. Risky attitudes towards road use are associated with individual characteristics and are observed in adolescents long before they learn to drive. Safe attitudes towards road use and driver behaviour should be promoted from childhood in order to be effective.


Regulation of glutathione in inflammation and chronic lung diseases.
Oxidant/antioxidant imbalance, a major cause of cell damage, is the hallmark for lung inflammation. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extra-cellular protective antioxidant against oxidative stress, which plays a key role in the control of signaling and pro-inflammatory processes in the lungs. The rate-limiting enzyme in GSH synthesis is glutamylcysteine ligase (GCL). GSH is essential for development as GCL knock-out mouse died from apoptotic cell death. The promoter (5'-flanking) region of human GCL is regulated by activator protein-1 (AP-1) and antioxidant response element (ARE), and are modulated by oxidants, phenolic antioxidants, growth factors, inflammatory and anti-inflammatory agents in various cells. Recent evidences have indicated that Nrf2 protein, which binds to the erythroid transcription factor (NF-E2) binding sites, and its interaction with other oncoproteins such as c-Jun, Jun D, Fra1 and Maf play a key role in the regulation of GCL. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many chronic inflammatory lung diseases. Knowledge of the mechanisms of GSH regulation could lead to the pharmacological manipulation of the production and/or gene transfer of this important antioxidant in lung inflammation and injury. This article describes the role of AP-1 and ARE in the regulation of cellular GSH biosynthesis and assesses the potential protective and therapeutic role of glutathione in oxidant-induced lung injury and inflammation.


No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19.
The use of hydroxychloroquine (HCQ), with or without concurrent administration of azithromycin (AZM), for treatment of COVID-19 has received considerable attention. The purpose of this study was to determine whether HCQ administration is associated with improved mortality in COVID-19 patients. We conducted a retrospective analysis of data collected during the care process for COVID-19 positive patients discharged from facilities affiliated with a large healthcare system in the United States as of April 27, 2020. Patients were categorized by treatment with HCQ (in addition to standard supportive therapy) or receipt of supportive therapy with no HCQ. Patient outcomes were evaluated for in-hospital mortality. Patient demographics and clinical characteristics were accounted for through a multivariable regression analysis. A total of 1669 patients were evaluated (no HCQ, n = 696; HCQ, n = 973). When adjusting for patient characteristics, receipt of AZM, and severity of disease at admission, there was no beneficial effect of receipt of HCQ on the risk of death. In this population, there was an 81% increase in the risk of mortality among patients who received HCQ at any time during their hospital stay versus no HCQ exposure (OR: 1.81, 95% CI: 1.20-2.77, p = 0.01). In this retrospective analysis, we found that there was no benefit of administration of HCQ on mortality in COVID-19 patients. These results support recent changes to clinical trials that discourage the use of HCQ in COVID-19 patients.


Global variation in young adult central nervous system tumor incidence by region, age, and sex from 1988 to 2012.
Central nervous system (CNS) tumors result in tremendous morbidity and mortality. Incidence of CNS tumors in young adults is less studied. It is unknown how young adult CNS tumor incidence has changed globally in recent decades. We used Cancer Incidence in Five Continents (CI5) data (1988-2012) to estimate incidence rates (IR), average annual percent change in incidence (AAPC; 95% confidence intervals [95% CI]), and male-to-female incidence rate ratios (IRR; 95% CI) by six histologies and age at diagnosis (20-29years, 30-39years). Tumors were classified as astrocytic, medulloblastoma, ependymal, oligodendroglial, meninges, and other embryonal. Geographic regions were defined using the United Nations Statistics Division geoscheme. There were 78,240 CNS tumor cases included. 20-29-year-old (yo) rates were lower than 30-39 yo in most regions for astrocytic, oligodendroglial and ependymal tumors. Globally, astrocytic tumor incidence decreased (20-29 yo AAPC: - 0.70; 95% CI: - 1.32, - 0.08) while incidence increased for oligodendroglial (20-29 yo AAPC: 3.03; 95% CI: 1.57-4.51; 30-39 yo AAPC: 2.67; 95% CI: 0.79-4.58), ependymal (20-29 yo AAPC: 1.16; 95% CI: 0.31-2.03; 30-39 yo AAPC: 2.29; 95% CI: 1.14-3.46), medulloblastoma (30-39 yo AAPC: 0.6; 95% CI: 0.04-1.24) and tumors of the meninges (20-29 yo AAPC: 1.55; 95% CI: 0.04-3.07). There was a 20-40% male incidence excess in all histologies except for meninge tumors (30-39 yo IRR: 0.71; 95% CI: 0.61, 0.84). Incidence of oligodendroglial and ependymal tumors increased globally in 20-39 yo suggesting better diagnoses or changes in risk factors. Males had a higher incidence of CNS tumors for most tumors studied and in most regions.


A phase II study of celecoxib, gemcitabine, and cisplatin in advanced pancreatic cancer.
Pancreatic cancer is amongst the most chemoresistant malignancies. Expression of the cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to therapy. A Phase II study was undertaken to determine the effect of gemcitabine by fixed-dose rate infusion (FDR), cisplatin and the COX-2 inhibitor, celecoxib, on the 6-month survival rate in patients with metastatic pancreatic cancer. The eligibility criteria included a pathologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas. No prior gemcitabine therapy was allowed. Patients received a combination of gemcitabine 1,000 mg/m(2) over 100 minutes, cisplatin 35 mg/m(2) I.V. on days 1 and 8, and celecoxib continuously at a daily dose of 800 mg. Cycles were repeated every 21 days. Twenty-two patients with metastatic pancreas cancer were enrolled (median age, 59.5 years; M:F, 13:9). The median number of cycles was 2 per patient. The median survival time was 5.8 months (90% CI, 3.6-7.6 months). The probability of survival at 6 months was 46% (90% CI, 27-62%). The major toxicity was neutropenia with grade 3 or 4 toxicities seen in 65% of patients. The addition of celecoxib to gemcitabine (by FDR) and cisplatin did not appear to increase activity of the chemotherapy doublet in patients with advanced pancreatic cancer. Celecoxib alone may not be sufficient to sensitize pancreatic cancer to the effects of conventional cytotoxic therapy.


Prevention and control of infection.
Foal septicemia is a major cause of neonatal morbidity and mortality. In order to improve success rates, earlier diagnosis and treatment are essential. This article stresses methods to prevent and treat infections in the compromised equine neonate.


Further studies on antitumour responses induced by short-term pretreatment with syngeneic tumour cells.
The ability of s.c. injected tumour cells to specifically inhibit the growth of similar cells injected i.v. 2 days later has been confirmed. The capacity of tumour cells to elicit this effect varies form tumour to tumour. Furthermore, it is more readily achieved with cultured than with freshly excised tumour cells. The superior effect elicited by cultured tumour cells was not overcome by treating them with trypsin or pronase. The protection achieved was impaired in T-cell-depleted mice and mice which had been irradiated (400 rad) prior to pretreatment. In contrast, it was not affected by administration of silica, sodium aurothiomolate or cortisone acetate. The results imply that T-cell-dependent responses are involved in the protection conferred by pre-injecting tumour cells shortly before i.v. challenge.


Energy analysis of PDT using thermography during the treatment of basal cell carcinoma.
The changes in tissue temperature of basal cell carcinoma lesions were investigated during photodynamic therapy in order to better understand the effects and mechanisms of PDT in tissue. In this study, the monitoring of 40 lesions of basal cell carcinoma was performed during photodynamic therapy. The lesion region becomes thermally evident throughout the procedure, and there is an improved contrast of the lesion edges after the end of the irradiation. The comparison between thermal and fluorescence images showed a correlation between the PpIX evidenced through widefield fluorescence and the temperature gradient of the thermal images after the procedure, indicating that thermography is a potential diagnostic tool to evaluate the selective response of PDT. A model was created to calculate the amount of light energy converted to heat, tissue damage, and other energy transfer processes involved in the PDT. Using this model, it was shown that most of the energy conversion was in photodynamic action (48.7% and 48.3%, in first and second session, respectively), followed by the energy ratio attributable to blood perfusion (37.2%). This is evidence that photodynamic therapy does not generate a significant thermal component, an important aspect of the study of its mechanisms.


Impact of two different types of exercise training on AMPH addiction: Role of hippocampal neurotrophins.
Amphetamine (AMPH) abuse results in neurobehavioral alterations related to the reward circuit. The hippocampus plays a role in cognition, reward, and drug addiction. There are no pharmacological approaches to prevent AMPH relapse. Physical exercise has been studied as a non-pharmacological promising influence to attenuate reward symptoms related to addictive drugs. This study aimed to compare the effects of non-weight-loaded and weight-loaded physical exercise on behavioral (relapse, memory and anxiety) and hippocampal molecular parameters associated with AMPH addiction in Wistar rats. Male rats were subjected to the AMPH-Conditioned Place Preference (CPP) paradigm. After 8-conditioning days, they were subjected to swimming physical exercise protocol (without or with weight-load). Behavioral evaluations were performed to assess the influence of both exercise protocols in addiction parameters, including relapse after AMPH reconditioning, working memory, locomotor activity, and anxiety-like symptoms. Subsequently, protein levels of Brain-Derived Neurotrophic Factor (BDNF) and pro-BDNF ex-vivo assays were carried out in samples of the hippocampus of the animals. AMPH relapse and anxiety-like behaviors were reduced only in rats subjected to non-weight-loaded exercise. Hippocampal BDNF and pro-BDNF immunoreactivity were increased in non-weight-loaded exercise rats. Behavioral and molecular analyses were not modified in rats subjected to weight-loaded exercise. These findings demonstrate that non-weight-loaded exercise was more effective against relapse and anxiety-like behavior induced by AMPH. Non-weight-loaded exercise upregulated the hippocampal immunocontent levels in rats.


Cigarette smoking behaviors and beliefs in persons living with HIV/AIDS.
To measure biopsychosocial domains related to tobacco use in persons living with HIV/AIDS (PLWHAs). Cross-sectional interview study of 60 PLWHA smokers randomly selected from an HIV clinic. Participants averaged 14.4 cigarettes daily. Sixty-five percent were moderately or highly nicotine dependent, and most were motivated to quit. Substance use and depression were very common. Most reported that smoking helped them cope with depression, anxiety, and anger. Twenty-seven percent thought (mistakenly) that smoking raised their T-cell counts and/or helped fight infections. Referrals to quitlines or cessation programs were uncommon. Smoking among PLWHAs is a challenging problem requiring targeted intervention strategies.


Cerebral blood flow in patients with subarachnoid haemorrhage studied with an intravenous isotope technique. Its clinical significance in the timing of surgery of cerebral arterial aneurysm.
The cerebral blood flow state has been evaluated in a series of 207 patients suffering from subarachnoid haemorrhage and with proved arterial aneurysms. Particular interest was focussed on 160 in grade I or II according to Botterell. An intravenous isotope method was used with 131-I Hippuran or 99-Tc pertechnetate as indicators. 133 of the 160 patients were operated on. 78 were also examined postoperatively. The radioactivity was recorded by two gamma detectors place bilaterally over the skull. The heights of the curves were taken as an index of the cerebral blood flow. Transit time was determined by dividing the area of the curve by its height. The results showed that even patients with no or slight neurological symptoms could have a depressed cerebral blood flow. Alterations in the blood flow seemed to precede a change in the clinical picture. Postoperatively, most patients had a further decrease in flow, but some others remained unchanged or even improved. With a normal or only slightly disturbed cerebral blood flow in the preoperative period, the morbidity and mortality of intracranial aneurysm surgery was estimated at 8%. For patients with a low preoperative blood flow value, i.e. more than a 40% reduction, the morbidity and mortality was much higher, about 30%. The results indicate that an analysis of the cerebral blood flow status represents an additional diagnostic parameter of great clinical significance, increasing the possibility of predicting to outcome of the operative treatment of an intracranial arterial aneurysm.


[Characterization of patients who died of invasive pneumococcal disease in the child population of Bogota, Colombia].
Streptococcus pneumoniae (S. pneumoniae), also known as pneumococcus, is one of the main bacteria associated with mortality in children under 2 years of age, with a morbidity and mortality incidence that varies according to demographics and exposure to risk, or protective factors. To describe the child mortality due to invasive pneumococcal disease (IPD) between 2008 -2014 (6 years), in 8 Medical Centres in Bogotá, Colombia. Descriptive observational case series of patients who died of IPD, aged 28 days to 18 years, in 8 tertiary care institutions in Bogota, Colombia. The study period was from 1 January 2008 to 15 January 2014. 239 patients. A total of 239 registered cases of IPD were reviewed, showing a mortality of 8% (n 18). The mean age of patients that died was 43.7 months, with an age range from 2 to 176 months (14 years), with 66% of the cases being male. Serotypes were identified in 8 patients, finding: 6A, 6B, 10A, 14, 18C, 23B, 23F, and 35B. The most common clinical presentation of the cases was meningitis with mortality of 33% (6 cases), followed by bacteraemia without focus in 28% (5 cases), and pneumonia with 27% (5 cases). Combined clinical situations were presented, such as pneumonia and meningitis in 11% (2 cases). Two of the patients had clearly documented risk factors for IPD (asplenia and chronic respiratory disease). IPD mortality is particularly high in children under 2 years in male patients, especially when presented with a meningeal focus (44%). Serotyping was not possible in all patients who died, since no strain isolated was sent to the National Institute of Health. Continuous and systematic vigilance is required to evaluate the impact of vaccination and possible changes in the pattern of presentation of disease.


[Personality, school-achievement and behavior disorders].
In the framework of the Basle Adolescence-Study, students with indications of behaviour disorders were the subject of a special analysis. The greater part of them belonged to the lower social class and frequented the intellectually less demanding branches of the school system. Even where this was not the case their personality profile showed the characteristics of the lower class populations. The theoretical base of the "labelling approach" could be verified. School and Counselling Service proved to be efficacious parts of the system of social control.


Giant aneurysms: A gender-specific complication of Kawasaki disease?
Kawasaki disease (KD) is a pediatric vasculitis of unknown origin. Its main complication is the development of coronary artery aneurysms (CAA) with giant CAA at the end of the spectrum. In this cohort study, we evaluated the association between patient characteristics and the development of giant CAA based on z-scores. Multivariable, multinomial logistic regression analysis was used to identify variables associated with giant CAA. A total of 301 KD patients, comprising 216 patients without enlargement, 45 with small-sized, 19 with medium-sized, and 21 with giant CAA with all echocardiographies at our center were retrospectively included. Remarkably, 95% of patients with giant CAA were boys. In addition to 'no/late intravenous immunoglobulin (IVIG) treatment', 'male gender' (OR 16.23, 95% CI 1.88-140.13), 'age<1 year' (OR 7.49, 95% CI 2.29-24.46), and 'IVIG re-treatment (9.79, 95% CI 2.79-34.37)' were significantly associated with an increased risk of giant CAA, with patients without enlargement as reference. Compared to patients with medium-sized CAA, 'IVIG re-treatment' was significantly associated with giant CAA. The majority of giant CAA continued to increase in size during the first 40 days. We identified risk factors associated with an increased risk of giant CAA. The difference in variables between the giant CAA group and the other CAA subgroups suggests a separation between patients with the treatment-resistant giant CAA and the other IVIG-responsive patients, in which gender may be factored as a most relevant genetic trait. The increase in size during the first 2 months indicates the need for repeated echocardiography.


Cancer-testis antigen MAGEC2 promotes proliferation and resistance to apoptosis in Multiple Myeloma.
Cancer-testis antigens belonging to the MAGE family of genes, such as MAGEC2, are commonly and specifically expressed in Multiple Myeloma (MM) and are associated with a more aggressive clinical course and chemotherapy resistance. MAGEC2 is thought to be an excellent candidate for cancer immunotherapy; however, the biological role of MAGEC2 in MM has remained unclear. We investigated the biological role of MAGEC2 in myeloma cells determining the effect of MAGEC2 knockdown on proliferation and apoptosis. Loss of MAGEC2 resulted in reduced proliferation, viability, and anchorage-independent growth of myeloma cells irrespective of the functional status of TP53 (p53). The anti-proliferative effect of MAGEC2 silencing was due to a decrease of cells in the S phase, cell cycle delay at both G0/G1 and/or G2/M, and an increase in the sub-G0/G1 diploid population related to apoptotic cell death. Importantly, overexpression of short hairpin (sh)RNA-refractory MAGEC2 rescued the anti-proliferative effect of mRNA knockdown and protected cells from apoptotic cell death. Our findings support a TP53-independent role of MAGEC2 in promoting the survival of myeloma cells suggesting that MAGEC2-specific immunotherapies have the potential to eradicate the most malignant cells within the myeloma tumour bulk leading to durable clinical responses.


Influence of clinical and laboratory variables on faecal antigen ELISA results in dogs with canine parvovirus infection.
False negative faecal canine parvovirus (CPV) antigen ELISA results in dogs with CPV infection are common, but the factors that lead to these false negative results are still unknown. The aim of this study was to investigate whether dogs with a false negative faecal CPV antigen ELISA result have milder clinical signs and laboratory changes, a lower faecal virus load, higher faecal and serum CPV antibody titres and a faster recovery than dogs with a positive result. Eighty dogs with CPV infection, confirmed by the presence of clinical signs and a positive faecal CPV polymerase chain reaction (PCR), were assigned to two groups according to their faecal antigen ELISA result. Time until presentation, severity of symptoms, laboratory parameters, faecal virus load, faecal and serum antibody titres, and CPV sequencing data were compared between both groups. In 38/80 dogs that were hospitalised until recovery, the time to recovery, mortality, and the course of the disease were compared between dogs with positive and negative faecal antigen ELISA results. Of the 80 dogs included, 41 (51.3%) had a false negative faecal antigen ELISA result. ELISA-negative dogs had a significantly shorter time until presentation, lower frequency of defaecation, lower faecal virus load, and higher serum antibody concentrations than ELISA-positive dogs. Laboratory changes, CPV shedding, and outcomes were not associated with faecal antigen ELISA results. In conclusion, low faecal CPV load and antibodies binding to CPV antigen in faeces are likely to be important reasons for false negative faecal antigen ELISA results. Dogs with clinical signs of CPV infection should be retested by faecal PCR.


Avoiding the problem state bottleneck by strategic use of the environment.
We investigated whether environmental support can be used to circumvent the problem state bottleneck in human multitasking. Previously, it was shown that people can only maintain a single chunk of information in their problem state resource, the central part of working memory. Consequently, when the problem state resource was required by multiple tasks concurrently, performance decreased. This phenomenon was termed the problem state bottleneck. To investigate whether the environment can be used to circumvent this bottleneck, we conducted an experiment with two main conditions. In the No-Support condition we replicated an earlier experiment that indicated the existence of the problem state bottleneck. In the Support condition we presented external cues, reducing the load on the problem state resource. To support the results of the experiment we present a computational cognitive model. The experiment and model indicated that the problem state bottleneck can be avoided by using external cues. However, subjects only used external cues when this led to faster behavior. These results were interpreted in the light of the Soft Constraints Hypothesis, which states that humans always follow the fastest strategy possible, as opposed to the most accurate strategy.


[The adaptive response of B cells to the action of cytotoxic preparations in culture. II. Immunoglobulin interaction with adriamycin and ethidium bromide].
The binding of adriamycin and ethidium bromide coupled to sepharose beads with intracellular and serum immunoglobulins is detected. These drugs do not bind with Fab and Fc fragments of immunoglobulin. The binding of ethidium bromide to immunoglobulins is competitive. Possible adaptive features of this phenomenon are discussed.


[Lupus erythematosus. 4. Investigation of the oral cavity: a) The antibody picture in studies of oral lesions, b) Immunopathology, c) S.L.E. and Sjogren syndrome; d) L.E. and collagen disease, e) The importance of oral lesions in L.E].
The AA. in this note IV report the most recent acquisitions about hematology, serology and immunopathologic findings; describe the association and the overlap between oral lesions in Lupus Erythematosus and other diseases. Finally analysed the importance of establishing the diagnosis of oral manifestations of Lupus Erythematosus.


Drug hypersensitivity syndrome induced by sulfasalazine: A case report.
Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality. A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC). The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results. The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines. Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red. This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.


Neuroendocrine carcinoma in the nasal cavity of ten dogs.
Neuroendocrine (NE) carcinoma was diagnosed in 10 dogs. In six cases examined by cephalometric radiography and computerized tomography, a large mass was seen to fill the nasal cavity. Histopathologically, sheets, nests or ribbons of neoplastic cells were separated by delicate or thick fibrovascular stroma. The neoplastic cells were round, oval, or spindle-shaped; cytoplasmic granules and hyperchromatic nuclei with prominent nucleoli were present. Neoplastic cells were invariably immunohistochemically positive for cytokeratin (CK) AE1/AE3, neuron-specific enolase, chromogranin A and vasoactive intestinal polypeptide. Eight dogs were positive for S100 protein, seven for synaptophysin, five for protein gene product 9.5, two for somatostatin, and one for Leu-7. Immunolabelling gave negative results for CK 8, CK 19, calcitonin, calcitonin gene-related polypeptide, neurofilaments, serotonin, gastrin and glial fibrillary acidic protein. Ultrastructurally, the neoplastic cells contained a large number of round, membrane-bounded, densely-cored granules corresponding to neurosecretory granules. These observations were consistent with the neuroendocrine nature of the carcinomas.


New-onset versus chronic atrial fibrillation in acute myocardial infarction: differences in short- and long-term follow-up.
Atrial fibrillation (AF) occurs commonly in patients with acute myocardial infarction (AMI) and has been established as a marker of adverse prognosis. There are only few clinical trials that investigate differences between new-onset and chronic AF in AMI. We hypothesize that chronic AF is associated with an increased rate of adverse short- and long-term outcomes. In a single center study, over a period of 28 months, 375 consecutive patients with AMI were included [337 patients without AF (89.9%) and 38 with AF (10.1%)]. As much as 16 patients had new-onset AF (42.1%) and 22 had chronic AF (57.9%). Patients with severe coronary artery disease develop AF more often in AMI, and the existence of AF was associated with a poor prognosis. Compared to patients with new-onset AF, chronic AF was more frequently associated with advanced age (75 vs. 70 years, p not significant), reduced left ventricular ejection fraction (44.8 vs. 54.0%, p < 0.05) and NSTEMI (63.6 vs. 36.4%, p < 0.05). Only chronic AF resulted in increased in-hospital death (18.2 vs. 0.0%; p < 0.005) at the 2-year follow-up, 14 patients with AF died (63.6%), predominantly due to cardiovascular reasons. Our results indicate that patients with chronic AF had a higher incidence of in-hospital death than those with new-onset AF or without. Chronic AF includes a group of older and sicker patients than their counterparts with new-onset AF. Understanding these findings may ultimately lead to better care of patients with this arrhythmia to prevent the development of the underlying atrial substrate in chronic AF patients and to improve their otherwise worse prognosis.


Application of bipolar membrane electrodialysis for simultaneous recovery of high-value acid/alkali from saline wastewater: An in-depth review.
With the development of comprehensive utilization of high-salinity wastewater, salt resources regeneration has been considered as the fundamental requirement for process sustainability and economic benefits. As one of the potential candidates, bipolar membrane electrodialysis (BMED) was rapidly developed in recent years for the treatment of saline wastewater. Different from other methods directly obtaining salts or condensed wastewater, BMED could utilize and convert the dissolved waste salt into higher-value acid and alkali simultaneously, which has various advantages including outstanding environmental effects and economic benefits. In this review, the recent applications of BMED for waste salt recovery and high-value acid/alkali generation from saline wastewater were systematically outlined. Based on the summary above, the economy analysis of BMED was further reviewed from the roles of desalination and resources recovery. In addition, the BMED-based processes integrated with in-situ utilization of the generated acid/alkali resources were discussed. Furthermore, the influence of operating factors on BMED performance were outlined. Finally, the strategies for improving BMED performance were concluded. Furthermore, the future application and prospects of BMED was presented. This work would provide guidance for the applications of bipolar membrane electrodialysis in saline wastewater treatment and the high-value conversion of salt resources into acids and alkalis.


Self-induced orbital emphysema as a presenting sign of Munchausen's syndrome.
A bizarre case of severe, debilitating pneumo-orbit resulting in proptosis, blindness, and eventual exenteration of the right eye and threatening the same fate for the left eye was worked up painstakingly for over 10 years before a final diagnosis of Munchausen's syndrome was uncovered. Five days after the diagnosis was made and appropriate management was instituted the severely proptotic left eye had returned to normal and the patient was discharged for out-patient psychiatric follow-up. A discussion of the differential diagnosis of pneumo-orbit is presented and Munchausen's syndrome, the final diagnosis in this case, is discussed from both an historical and psychiatric perspective.


[Butoctamide enhancement of the antitumor activity of 6-mercaptopurine on Ehrlich solid tumors in mice (author's transl)].
Effects of butoctamide (N-(2-ethylhexyl)-3-hydroxybutyramide, L-2) on the antitumor activity of 6-mercaptopurine (6-MP) against Ehrlich solid tumors in mice were investigated. No change was observed in tumor growth after either oral or intraperitoneal administration of butoctamide (100 mg/kg/day X 7). This drug increased the activity of a low dose of 6-MP (2.5 approximately 10 mg/kg/day. i.p., X 7), but did not change the activity of a high dose of 6-MP (40 approximately 80 mg/kg/day, i.p., X 7). The antitumor activity of thioinosine (6-MP riboside) was similarly increased by administration of butoctamide (100 mg/kg/day, i.p., X 7). On the other hand, concomitant administration of butoctamide with cyclophosphamide, methotrexate, mitomycin C or adriamycin had no effect on the activity of these anticancer drugs. In butoctamide (100 mg/kg/day, i.p., X 7)-treated mice, the antitumor activities of a single administration of 6-MP and cyclophosphamide were not increased. Butoctamide stimulated the hypoxanthine-guanine phosphoribosyltransferase activity and inhibited the xanthine oxidase activity of mouse liver, to a certain degree as compared to controls. Butoctamide may promote conversion from 6 MP to thioinosinic acid monophosphate to a biologically active state, rather than to thiouric acid or hypoxanthine which would be inactive.


Monoclonal antibodies against human low density lipoprotein. Stoichiometric binding studies using Fab fragments.
Because of its physical properties, apolipoprotein B (apo B) has remained poorly characterized. In an attempt to elucidate apo B structure, the Fab fragments of 3 different monoclonal anti-human apo B antibodies were tested in a quantitative assay for their binding to human low density lipoprotein (LDL). In each case the assay gave a linear Scatchard plot with a maximum of 1 Fab fragment bound to a single LDL particle. This result favors an LDL model containing a single large Mr apo B protein, which is not composed of multiple, identical, small Mr subunits.


A case of cardiac arrest due to postpartum hemorrhage treated with hysterectomy and extracorporeal membrane oxygenation.
Although extracorporeal membrane oxygenation is relatively contraindicated in patients with severe disseminated intravascular coagulation (DIC), it can be safely introduced by providing adequate anti-DIC therapy.


Molecular epidemiology of pancreatic cancer.
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Currently there is no early diagnostic test and no effective treatment options for this deadly disease. Prevention of pancreatic cancer is difficult because little is known about its etiology. The main modifiable risk factors for pancreatic cancer include cigarette smoking and dietary factors. Information from molecular epidemiological study of pancreatic cancer is very limited. DNA adducts derived from exposure to polycyclic aromatic hydrocarbon, aromatic amines, and heterocyclic amines have been detected in human pancreatic tissues. DNA damages derived from oxidative stress and lipid peroxidation are also present in the pancreas. No study has demonstrated a main effect of carcinogen-metabolizing genes and DNA repair genes on the risk of pancreatic cancer thus far. However, significant effects of these genes have been observed among individuals with known carcinogen exposure, such as smoking. A number of environmental and lifestyle factors, such as smoking, alcohol, coffee consumption, and exposure to organochlorine or hydrocarbon solvent, have been associated with the frequency and spectrum of K-ras mutation in pancreatic tumors. Dietary folate intake and serum levels of folate have been associated with the risk of pancreatic cancer among male smokers. These findings demonstrate the potential of the molecular epidemiology approach in understanding the etiology of pancreatic cancer. Further efforts should be made to understand the interactive relationship between genetic and environmental factors in the etiology of pancreatic cancer, which will in turn be important in identifying the high-risk population for the primary prevention of this deadly disease.


T cell factor 4 is a pro-catabolic and apoptotic factor in human articular chondrocytes by potentiating nuclear factor κB signaling.
T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors are downstream effectors of Wnt/β-catenin signaling, which has been implicated in the development and progression of osteoarthritis (OA). This study aimed to investigate the role of TCF/LEF transcription factors in human articular chondrocytes. Primary human osteoarthritic cartilage predominantly expressed TCF4 and to a lesser extent, LEF1 and TCF3 mRNA. Overexpression of TCF4, but not of TCF3 or LEF1, induced MMP-1, -3, and -13 expression and generic MMP activity in human chondrocytes. This was due to potentiating NF-κB signaling by a protein-protein interaction between TCF4 and NF-κB p65 activating established NF-κB target genes such as MMPs and IL-6. LEF1 competed with TCF4 for binding to NF-κB p65. IκB-α was able to counteract the effect of TCF4 on NF-κB target gene expression. Finally, we showed that TCF4 mRNA expression was elevated in OA cartilage compared with healthy cartilage and induced chondrocyte apoptosis at least partly through activating caspase 3/7. Our findings suggest that increased TCF4 expression may contribute to cartilage degeneration in OA by augmenting NF-κB signaling.


Three-dimensional evaluation of secondary alveolar bone grafting using a 3D- navigation system based on computed tomography: a two-year follow-up.
Secondary bone grafting is widely used in the closure of oronasal fistulas and reconstruction of maxillary defects. It often fails from lack of physiological stress or inadequate covering of the transplanted bone with surrounding tissue. The aim of this study was to assess the exact bone volume after secondary alveolar bone grafting over a period of two years using a navigation system based on computed tomography (CT). We examined 20 patients with complete unilateral cleft lip and palate (UCLP) who had been treated by secondary bone grafting during late mixed dentition. CT scans of the upper jaw were taken immediately preoperatively, and 1 and 2 years postoperatively. The cleft defects and the bony bridges were marked on the monitor. The software of the navigation system created three-dimensional models showing the amount and site of bone resorption. The mean bone loss after one and two years was 51% and 52%, respectively. There was a significant correlation between the size of the cleft and the success of the alveolar bone grafting (p=0.01). When the teeth adjacent to the cleft were missing the amount of bone lost was 95% after the first year. There was also significant bone loss in the buccopalatine direction. Three-dimensional reconstruction of the bony bridges with a navigation system accurately shows the amount of bone within the cleft site. This method is definitely superior to conventional two-dimensional orthopantomography.


Stretch-induced, steady-state force enhancement in single skeletal muscle fibers exceeds the isometric force at optimum fiber length.
Stretch-induced force enhancement has been observed in a variety of muscle preparations and on structural levels ranging from single fibers to in vivo human muscles. It is a well-accepted property of skeletal muscle. However, the mechanism causing force enhancement has not been elucidated, although the sarcomere-length non-uniformity theory has received wide support. The purpose of this paper was to re-investigate stretch-induced force enhancement in frog single fibers by testing specific hypotheses arising from the sarcomere-length non-uniformity theory. Single fibers dissected from frog tibialis anterior (TA) and lumbricals (n=12 and 22, respectively) were mounted in an experimental chamber with physiological Ringer's solution (pH=7.5) between a force transducer and a servomotor length controller. The tetantic force-length relationship was determined. Isometric reference forces were determined at optimum length (corresponding to the maximal, active, isometric force), and at the initial and final lengths of the stretch experiments. Stretch experiments were performed on the descending limb of the force-length relationship after maximal tetanic force was reached. Stretches of 2.5-10% (TA) and 5-15% lumbricals of fiber length were performed at 0.1-1.5 fiber lengths/s. The stretch-induced, steady-state, active isometric force was always equal or greater than the purely isometric force at the muscle length from which the stretch was initiated. Moreover, for stretches of 5% fiber length or greater, and initiated near the optimum length of the fiber, the stretch-enhanced active force always exceeded the maximal active isometric force at optimum length. Finally, we observed a stretch-induced enhancement of passive force. We conclude from these results that the sarcomere length non-uniformity theory alone cannot explain the observed force enhancement, and that part of the force enhancement is associated with a passive force that is substantially greater after active compared to passive muscle stretch.


Fast recovery with etanercept in patients affected by polymyalgia rheumatica and decompensated diabetes: a case-series study.
We enrolled nine consecutive patients affected by newly diagnosed polymyalgia rheumatica and decompensated diabetes mellitus. All patients were treated with etanercept (25 mg twice weekly) and prednisone and were followed up to 1 year. At the sixth-month follow-up, etanercept and prednisone were withdrawn. Patients were seen at regular intervals (days 0, 30, 60, 90, 150, 180) and the following variables determined: erythrocytes sedimentation rate, C-reactive protein, fasting serum glucose, pain measured by visual analog scale, and the Health Assessment Questionnaire. Our results indicate that etanercept might have some steroid-sparing effects, but controlled investigations are needed to support etanercept use in clinical practice for this kind of patients.


The influence of diastolic and systolic function on exercise performance in heart failure due to dilated cardiomyopathy or ischemic heart disease.
Peripheral adaptations and ventricular abnormalities influence physical performance in chronic heart failure. However, the role of the heart in determining exercise capacity has not been completely elucidated. To define cardiac determinants of exercise capacity in patients with dilated cardiomyopathy. In 101 patients with heart failure (NYHA class II-III) due to primary or ischemic dilated cardiomyopathy we measured peak exercise oxygen consumption (Pvo2), left ventricular ejection fraction (EF), left and right atrial and ventricular cavity dimensions, mitral and tricuspid flows. Patients were subdivided in class A (Pvo2 > 20 ml/min per kg; n = 44), class B (Pvo2 16-20 ml/min per kg; n = 42) and class C (Pvo2 < 16 ml/min per kg; n = 15). Left ventricular diastolic and systolic dimensions, left atrial diameter, right atrial and ventricular areas were greater in class C than in class B and A; EF was lower in class C than in the other two classes; mitral peak flow velocity at early diastole (PFVE) and the ratio between early and late peak flow velocity (PFVE/PFVA) were higher in class C; mitral and tricuspid deceleration time (DT) in class B and A significantly exceeded those in class C. Peak vo2 was correlated with left and right ventricular dimensions, left atrial diameter, EF, mitral PFVE and PFVE/PFVA, mitral and tricuspid DT. Left ventricular EF, DT of the mitral valve and left ventricular diastolic diameter were independent predictors of peak vo2 at multivariate analysis. In patients with dilated cardiomyopathy Pvo2 is related to left and right ventricular dimensions, left and right ventricular filling pattern and EF. Both systolic and diastolic dysfunction influence functional capacity.


Cerebrospinal fluid growth-associated protein 43 levels in patients with progressive and stable mild cognitive impairment.
Cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) is prominently elevated in Alzheimer's disease (AD) dementia patients in comparison to normal controls. CSF GAP-43 levels in mild cognitive impairment (MCI) individuals who have different clinical trajectories need to be studied. We examined 137 cognitively normal (CN) controls, 218 stable MCI patients (sMCI), 99 progressive MCI (pMCI) patients, and 120 AD dementia patients. Associations between the CSF GAP-43 levels and the four diagnosis groups were evaluated with multiple-variable linear regression. The relationships between CSF GAP-43 and core CSF biomarkers were assessed by Spearman correlations. Cox regression analysis was performed to assess the values of GAP-43 in predicting MCI conversion. We examined associations between baseline CSF GAP-43 levels and longitudinal cognitive function, hippocampal volumes, and brain glucose metabolism using linear mixed-effects models. CSF GAP-43 was elevated in the pMCI and AD groups in comparison to the CN group and in the pMCI and AD groups in comparison to the sMCI group. CSF GAP-43 significantly predicted conversion from MCI to AD. CSF GAP-43 was a significant predictor of cognitive decline, hippocampal atrophy, and brain hypometabolism over time. Furthermore, elevated CSF GAP-43 levels were associated with accelerated deterioration in cognition and neurodegeneration. CSF GAP-43 is increased in the predementia stage of AD, and it may enhance the neurodegenerative process. Future efforts on pharmacological interventions targeting synaptic dysfunction could be promising in AD treatment.