Influence of environmental factors on chronic prostatitis-like symptoms in young men: results of a community-based survey.
To investigate the influence of environmental factors on chronic prostatitis-like symptoms among young men in a community. Of 28,841 men aged 20 years dwelling in the community, a total of 16,321 men (response rate 56.6%) were included in this study. The National Institutes of Health Chronic Prostatitis Symptom Index was used to identify men with chronic prostatitis-like symptoms. The questionnaire also queried sociodemographic characteristics. The Korean Meteorological Administration provided information on the weather of the community. We determined the risk factors of chronic prostatitis-like symptoms among these environmental factors using univariate and multivariate analyses. Six percent of the men were identified as having significant prostatitis-like symptoms (perineal and/or ejaculatory pain and a total pain score of 4 or greater). The univariate logistic regression analysis indicated that education level, average duration of sunlight, and average temperature were risk factors for chronic prostatitis-like symptoms. As these variables increased, the scores of chronic prostatitis-like symptoms decreased. In the multivariate model used, the likelihood of chronic prostatitis-like symptoms varied by the final educational level, with middle school and high school graduates having 1.8 and 1.4-fold higher odds, respectively, than men attending college. In the same model, the average duration of sunlight was also an independent risk factor of chronic prostatitis-like symptoms (odds ratio 0.85; 95% confidence interval 0.77 to 0.95; P = 0.003), but the average temperature lost statistical significance. Our findings suggest that the community-based prevalence of chronic prostatitis-like symptoms may be high in young men. Higher education and a longer time in sunlight were associated with a decreased likelihood of chronic prostatitis-like symptoms.


CO2 induced seawater acidification impacts sea urchin larval development I: elevated metabolic rates decrease scope for growth and induce developmental delay.
Anthropogenic CO(2) emissions are acidifying the world's oceans. A growing body of evidence is showing that ocean acidification impacts growth and developmental rates of marine invertebrates. Here we test the impact of elevated seawater pCO(2) (129 Pa, 1271 μatm) on early development, larval metabolic and feeding rates in a marine model organism, the sea urchin Strongylocentrotus purpuratus. Growth and development was assessed by measuring total body length, body rod length, postoral rod length and posterolateral rod length. Comparing these parameters between treatments suggests that larvae suffer from a developmental delay (by ca. 8%) rather than from the previously postulated reductions in size at comparable developmental stages. Further, we found maximum increases in respiration rates of +100% under elevated pCO(2), while body length corrected feeding rates did not differ between larvae from both treatments. Calculating scope for growth illustrates that larvae raised under high pCO(2) spent an average of 39 to 45% of the available energy for somatic growth, while control larvae could allocate between 78 and 80% of the available energy into growth processes. Our results highlight the importance of defining a standard frame of reference when comparing a given parameter between treatments, as observed differences can be easily due to comparison of different larval ages with their specific set of biological characters.


Prognostic evaluation of intracranial metastasis in malignant melanoma.
Malignant melanoma (MM) is often reported as the third most common cause of intracranial metastasis (IM) after carcinoma of the breast and lung. Most patients with advanced MM will have widespread extracranial disease, but the majority will die from intracerebral spread. A retrospective review of 117 patients with documented IM from MM over the past 25 years was undertaken. Various factors (including age, race, sex distribution, primary lesions with Clark's level, Breslow's thickness, primary sites and staging at initial presentation, diagnosis of IM and its various treatment methods, survival data, and autopsy findings) were analyzed. Prognostic indicators were clarified from this analysis as a predictor of central nervous system (CNS) metastasis. An ideal treatment plan was also analyzed in order to predict a better survival. Fifty-eight percent of patients were male; 42% were female. Seventy-one percent of the primary lesions were of Clark's level IV and V, with mean Breslow's thickness of 3.5 mm. Median time interval between the initial diagnosis and development of IM was 3.5 years. Complete surgical resection of the intracranial lesion in the brain resulted in the longest mean survival of 10.3 months, whereas mean survival for the group with no treatment was only 3 weeks. Patients with primary lesions of the head and neck had the lowest mean survival of 3.3 months, whereas those whose primary sites were unknown had the longest mean survival of 7.5 months. One- and 2-year survival were 9% and 3%, respectively. All but one of the 30 patients at autopsy were found to have visceral metastasis, namely of the lung, liver, and bone. An aggressive search for metastasis should be undertaken in patients at high risk of developing CNS metastasis, e.g., male, head and neck primary, Clark's level IV and V, Breslow's thickness of > 3 mm, and presence of visceral metastases, mainly lung. A complete surgical resection should be attempted whenever possible, with adjunctive use of whole-brain irradiation, along with systemic chemotherapy for further control of recurrence and to prolong survival.


CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man.
Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value.


Influence of catfish skin mucus on trisodium phosphate inactivation of attached Salmonella Typhimurium, Edwardsiella tarda, and Listeria monocytogenes.
This study examined the antimicrobial effectiveness of trisodium phosphate (TSP) on Edwardsiella tarda, Listeria monocytogenes, and Salmonella Typhimurium attached to catfish skin with and without mucus. Salmonella Typhimurium and E. tarda attached more readily to catfish skin than did L monocytogenes. At high inoculum levels (10(7) CFU/ml), TSP treatments (at 2 to 6%) for 10 min reduced bacterial counts of E. tarda by >2.5 to >3.3 log10 CFU per skin sample for firmly attached cells and by 3.5 to 3.6 log10 CFU per skin sample for loosely attached cells. Counts of L. monocytogenes declined by 0.6 to >1.8 log10 CFU per skin sample for firmly attached cells and by 1.2 to 2.2 log10 CFU per skin sample for loosely attached cells. Counts of Salmonella Typhimurium were reduced by 3.6 to >3.8 log10 CFU per skin sample for firmly attached cells and by 3.5 to >3.8 log10 CFU per skin sample for loosely attached cells. Overall, counts of firmly attached bacteria on TSP-treated skins with mucus were higher than counts on skin without mucus. Firmly attached L. monocytogenes was more resistant to TSP than was firmly attached Salmonella Typhimurium or E. tarda. The presence of mucus on skins slightly decreased the antimicrobial effect of TSP Significant (P < 0.05) reduction in the numbers of all three bacteria can be achieved by treatment with 6% TSP for 10 min.


Purification and properties of the activating enzyme for iron protein of nitrogenase from the photosynthetic bacterium Rhodospirillum rubrum.
The oxygen-labile, activating enzyme for iron protein from the photosynthetic bacterium, Rhodospirillum rubrum, was purified 11,800-fold using a combination of chromatophore washing, DE52-cellulose chromatography, hydroxylapatite chromatography, reactive red-120 cross-linked agarose chromatography, reactive red-120 cross-linked agarose chromatography, and Sephadex G-75 gel filtration. Activating enzyme appeared homogeneous on silver-stained sodium dodecyl sulfate-polyacrylamide gels, and the staining intensity of the activating-enzyme band was correlated with the activating-enzyme activity observed in in vitro assays. Either formaldehyde fixation or higher acrylamide concentration was required to accurately assess the purity of activating enzyme on silver-stained gels. Activating enzyme was stable for 30 days at 4 degrees C. Dithiothreitol was a necessary component for the stability of partially purified activating enzyme. NaCl inhibited the coupled assay for activating enzyme. The pI of activating enzyme was determined to be 6.5. Activating enzyme is composed of a minimum of 336 amino acids and a minimum calculated Mr is 32,032. The Mr of activating enzyme was estimated to be 21,700 by analytical gel filtration and 32,800 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An absorption maximum at 280 nm was observed for the activating enzyme.


Reexamining trait rumination as a system of repetitive negative thoughts: A network analysis.
Rumination is strongly associated with risk, maintenance, and worsening of depressive and related symptoms, and it predicts poor treatment response and relapse. More work is needed to clarify the nature and malleability of rumination. We propose reexamining trait rumination as a system of interacting components ("nodes"). A regularized partial correlation network was first computed to estimate the functional relations among items from the Ruminative Responses Scale (RRS) (N = 403). We then tested whether items constitute multiple distinguishable sub-networks or communities, and if so, if particular items function as "bridges" connecting them. RRS items were not interchangeable, with network components varying widely in their centrality. We identified three communities of nodes and the nodes bridging these communities. Data were derived from a heterogeneous community sample and include items from a single measure. Thus, results should not be interpreted as definitive, but instead as hypothesis-generating and highlighting the utility of rethinking the conceptualization and measurement of rumination. Of the larger set of cognitive patterns forming the rumination construct, the high centrality nodes were largely passive and self-critical processes. Community detection analyses identified a sub-network largely comprising items from the RRS that have traditionally been labeled reflective pondering and adaptive; however, strong bridge nodes were also from this community. This implies that in isolation or at low levels such processes may not be problematic, but that their persistence or intensification could be associated with the activation of more maladaptive processes.


Adjuvant treatment of postmenopausal patients with high risk primary breast cancer. Results from the Danish adjuvant trials DBCG 77 C and DBCG 82 C.
The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients (tumor greater than 5 cm, positive axillary nodes, or invasion to skin/fascia) were randomized after total mastectomy and axillary sampling to postoperative radiotherapy (control) or to radiotherapy plus treatment with tamoxifen (TAM), 30 mg daily for 1 year. A total of 1,716 patients entered the study. At 8 years of follow-up, (7 years median time of observation), we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality, which is significant for patients less than 70 years of age. Retrospectively, an increased recurrence-free survival in TAM treated patients was significant in the following subgroups: tumor less than 5 cm, positive lymph nodes, anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein. In the subsequent trial (DBCG 82 C), 1,347 postmenopausal patients less than 70 years were randomized to one of the following 3 regimens: radiotherapy + tamoxifen, 30 mg daily for 1 year (TAM), TAM alone, or TAM + CMF (CMF i.v. day 1 every 4 weeks x 9). The survival is similar in the 3 groups at 4 years (2 years median time of observation).


Gated sodium-23 nuclear magnetic resonance images of an isolated perfused working rat heart.
Sodium-23 nuclear magnetic resonance images of phantoms and gated images of isolated perfused working rat hearts were obtained. By synchronizing the nuclear magnetic resonance process to the heartbeat, images were obtained at systole and at diastole.


The relationship between inflammation, dyslipidemia and physical exercise: from the epidemiological to molecular approach.
Dyslipidemia and inflammation are frequently found in some diseases, such as obesity, type 2 diabetes mellitus, and cancer cachexia. Recent literature has identified that lipids have a pivotal role in the activation of inflammatory pathways, increasing the production of inflammatory cytokines, mainly tumor necrosis factor alpha, interleukin 6 and 1β. On the other hand, cytokines can promote disruption of lipid metabolism, in special cholesterol reverse transport, which is linked to development of atherosclerosis. With this in mind, acute and chronic exercise trainings have been pointed as important tools to counteract both dyslipidemia symptoms and systemic inflammation. Moreover, physical activity has been recommended in the prevention/treatment of the above mentioned outcomes by important health organizations around the world, mainly because it costs less and generates fewer side effects than isolated medicine. Despite the well-documented capacity of acute and chronic exercise training to counteract sustained disease-related immunometabolism, we have chosen to take a look from a current perspective in molecular pathways and in the field of epidemiology. The aim of the present review was therefore to discuss the results of dyslipidemia and inflammatory conditions with acute and chronic exercise training, which underlies the field of molecular pathways and epidemiology. The mechanisms underlying the response to the treatment are considered.


Homeopathy: what is it and is it of value in the care of patients with cancer?
The underlying principles of homeopathy include treating 'like with like' by remedies which are potentized by serial dilution and succussion. These distinguish homeopathy from other forms of alternative or complementary therapy. Conventional scientific wisdom dictates that homeopathy should have no effect above and beyond placebo but experiments on ultra-high dilutions of solutes together with some clinical data suggest the intriguing possibility that it might do in some circumstances. However, most clinical evidence comes from treating relatively minor self-limiting diseases and little comes from treating life-threatening disorders such as cancer. This paper explains the principles of homeopathy and reviews the data on its use in cancer care.


[Classification of lymphedema].
Classification of lymphedema is debated, because authors don't agree with the disordered physiology. Kinmonth divided all cases into primary and secondary lymphedema. Three types of primary lymphedema have been recognized: congenital, precox and tarda. Secondary lymphedema develops as a consequence of disruption or obstruction of the lymphatic pathways. Iatrogenic lymphedema are caused by surgery and/or radiation therapy. Post-infectious lymphedema are mainly caused by filariasis in tropical areas, and by cellulitis in occidental areas. Neoplastic disease (breast, prostatic cancer, Kaposi's sarcoma) are a major cause of secondary lymphedema. Less frequent etiologies are rheumatoid lymphedema, pathomimic lymphedema, pretibial myxoedema. Reduced lymphatic drainage is associated with severe chronic venous insufficiency and contributes to the leg swelling and the risk of infection.


What can we learn from the vaginal mesh story?
The use of vaginal mesh in prolapse surgery has created enormous controversy and unprecedented media interest; it has become the most emotive topic in urogynecology today. The US Food and Drug Administration 510(k) system allowed the proliferation of mesh products which were rapidly adopted by surgeons internationally. The importance of a firm understanding of the biomechanical properties of tissue and implants, surgical skill, patient selection, communication skills, informed consent, and high-quality research are all important lessons we can learn from the mesh story. These lessons need to be applied to all novel treatments in the field of urogynecology and beyond.


Depression in multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Prevalence of depression in MS is significant. Existence of mood disorders alters the patients' life quality. To determine the prevalence of depression in MS and establish the relationship between the severity of the disease, the onset of depression and their correlation with neuroimaging. Fifty patients with MS aged 20 to 50 years followed at the Neurology Department of Charles-Nicolle Hospital from 2008 to 2012 participated in this study. The evaluation included a neuropsychological assessment, physical examination with EDSS and MRI. Association between MS and depression is common and known. In our study, prevalence of depression was 65%. Coexistence of other psychiatric disorders was found in around 10% of patients. Mood disorder was inaugural in some cases and delayed in others. This suggests that depression in MS may be linked to the disease or a result of a functional disability process. Occurrence of depression was not directly related to disease severity in all cases studied. Depression is a possible manifestation of MS. This mood disorder is due to the demyelinating brain damage or to a genetic susceptibility. However, a fortuitous association cannot be excluded.


Cutaneous reactions with tenofovir disoproxil fumarate: a report of nine cases.
Adverse drug reactions causing the early discontinuation of therapy are common in patients with HIV infection. Hypersensitivity consisting mainly of a maculopapular rash on the face, extremities and trunk has been observed at a rate higher than expected in patients treated with tenofovir at our clinics. We therefore examined nine patients with suspected tenofovir hypersensitivity reactions in two indigent care HIV clinics. Type I and type IV hypersensitivity may be involved as immunological mechanisms.


The development of the extensor digitorium brevis muscle in progressive proximal muscular antrophies.
The development of the extensor digitorium brevis (EDB) muscle was studied in 39 healthy subjects, 27 patients with progressive proximal spinal muscular atrophy, 20 patients with limb-girdle muscular dystrophy and three with facioscapulohumeral muscular dystrophy. The EDB muscle is spared and usually hypertrophic in patients with muscular dystrophy, whereas it is often atrophic and weak in patients with spinal muscular atrophy. It is proposed that the degree of development of the EDB muscle can be used as a clinical sign in the differential diagnosis of progressive muscular atrophies.


[Use of induced sputum in the investigation of occupational asthma].
The diagnosis of occupational asthma relies mainly on the demonstration of changes in airway calibre and airway responsiveness after exposure to occupational agents in the laboratory or at the workplace. However, spirometry or peak expiratory flow measurements may be open to misinterpretation when they are not performed optimally. As in non-occupational asthma, airway inflammation is one of the main characteristics of occupational asthma. Induced sputum, a non invasive method to assess airway inflammation, has been successfully used in the management of asthma. This article reviews the studies that have investigated and characterized the changes in sputum cell counts occurring in subjects with occupational asthma after exposure to occupational agents in the laboratory or at the workplace in order to assess the place of induced sputum in the investigation of occupational asthma. It also reviews the use of induced sputum during the follow-up of workers with occupational asthma after removal from exposure. This article also describes a new condition identified thanks to the use of induced sputum : occupational eosinophilic bronchitis. In conclusion, induced sputum is a useful tool in the investigation of occupational asthma. Its use on a regular basis in the investigation of occupational asthma also allows for the possibility of diagnosis of overlooked conditions such as occupational eosinophilic bronchitis. Its role in the surveillance of workers at risk to develop occupational asthma remains to be determined.


[Proliferation inhibition of glioma cells by vitamin K2].
The antitumor effects of vitamin K2 were studied using three glioma cell lines: C6 (rat glioma cell), RBR17T and T98G (human glioma cell). The antitumor effects were estimated by count assay. The results was that vitamin K2 induced growth inhibition in a dose-dependent manner. The RBR 17T cells exposed to vitamin K2 for 72 hours resulted in oligonucleosomal DNA fragmentation and formed a ladder on agarose gel electrophoresis. Furthermore, the RBR17T cells exposed to vitamin K2 for 24 hours were significantly accumulated in the G0G1 phase of the cell cycle. Those results suggested that vitamin K2 can inhibit the proliferation of cells through the induction of cell cycle arrest and apoptosis for tumor cells. The combined treatment of vitamin K2 with ACNU or 5-FU or INF-beta or 1,25-dihydroxyvitamin D3 enhanced growth inhibition significantly. In conclusion, vitamin K2 can be a useful drug for the treatment of glioma.


Fine structural aspects on auditory hair cell degeneration in the budgerigar, Melopsittacus undulatus, as induced by kanamycin.
The effects of kanamycin, an antibiotic of the aminoglycoside group, on the auditory sensory epithelium of the budgerigar, Melopsittacus undulatus, were examined using both scanning and transmission electron microscopes. Results show that the threshold of the auditory brainstem response increased in birds treated with kanamycin 200 mg/kg for 49 days. While the auditory sensory epithelium of the normal budgerigar consists of short and tall hair cells, and supporting cells, following kanamycin administration, the middle to proximal region of the epithelium of the inner ear showed degenerative changes, with the other parts remaining apparently intact. In the damaged region, the short hair cells were flattened, and the tall ones became heterogeneous in shape. Both types of cells contained many dense bodies in their cytoplasm; they were rounded in shape and homogeneously dense. Severely degenerated tall hair cells also contained many large vacuoles with heterogeneous contents. Because the dense bodies and large vacuoles were positive for acid phosphatase reaction, they were respectively judged to be primary lysosomes and secondary lysosomes containing degenerating cell debris. Most supporting cells in the impaired region were lower in cytoplasmic electron density, and their apical surface became enlarged in area. Some flattened short hair cells were situated on the apical part of the swollen supporting cells. This finding suggests that the short hair cells are pressed toward the scala media by the supporting cells.


Vincristine-induced self-association of calf brain tubulin.
The vincristine-induced self-association of tubulin has been examined in a sedimentation velocity study as a function of free drug concentration in PG buffer (0.01 M NaPi and 10(-4) M GTP, pH 7.0) at 20 degrees C. Analysis of the weight-average sedimentation coefficient (S20,w) as a function of protein concentration showed a good fit with the model of an indefinite, isodesmic self-association mechanism. Analysis of the apparent association constants in terms of the Wyman linkage relations showed a good fit to mediation of the self-association by the binding of one ligand molecule. The intrinsic association constant for dimerization of the vincristine-liganded tubulin was found to be 3.8 X 10(5) M-1, and the intrinsic equilibrium constant for the binding of the self-association-linked vincristine molecule had a value of 3.5 X 10(4) M-1, consistent with that measured by fluorescence in our laboratory [Prakash, V., & Timasheff, S. N. (1983) J. Biol. Chem. 258, 1689-1697]. Both reactions are stronger in the presence of vincristine than of vinblastine, reflecting the oxidation of a -CH3 group to -CHO when going from the latter drug to the former one.


Systemic chemotherapy for urothelial transitional cell carcinoma: an overview of toxicity.
Chemotherapy for urothelial transitional cell carcinoma improves disease-related symptoms and overall survival. Unfortunately, many commonly used cytotoxic regimens affect normal as well as malignant tissue, resulting in toxicities that may require prompt medical diagnosis and management. This article reviews the reported toxicities of both single agent and combination chemotherapy regimens used to treat metastatic transitional cell carcinoma.


Internal jugular venous catheter-related bacteremia according to central and posterior accesses.
Although there are many studies about central venous catheter-related infection, we have not found any analysis of the incidence of internal jugular venous catheter-related bacteremia associated with different accesses. The objective of this study was to test whether the position of the internal jugular venous catheter, central or posterior, influences the incidence of bacteremia. A cohort study. A 12-bed polyvalent medical-surgical intensive care unit (ICU). Patients admitted to ICU between 1 May 2000 and 30 April 2004 who received one or more internal jugular venous catheters. A total of 1,483 patients were admitted to the polyvalent ICU, of whom 1,311 underwent central venous catheterization. A total of 547 patients received 684 internal jugular venous catheters, 169 by posterior and 515 by central access. There were no significant differences between central and posterior access patients in sex, age, APACHE II (14.1 +/- 5.0 vs. 13.9 +/- 5.2, p = 0.40), diagnosis, order of catheter insertion, use of mechanical ventilation, use of antimicrobials, use of total parenteral nutrition or use of pulmonary artery catheter. We found a higher incidence of internal jugular venous catheter-related bacteremia with central (4.8 per 1000 catheter-day) than with posterior (1.2 per 1000 catheter-day) access (odds ratio 3.9; 95% confidence interval 1.1-infinite; p = 0.03). Posterior access has a lower incidence of internal jugular venous catheter-related bacteremia than central access in non-severely ill patients (according to the low APACHE II score values of the study patients).


UV-radiation induces dose-dependent regulation of p53 response and modulates p53-HDM2 interaction in human fibroblasts.
We address here the effects of increasing fluencies of UV-radiation on stability, modifications, activity and HDM2-interactions of endogenous p53 tumor suppressor and on cellular damage response of human diploid fibroblasts. Low amounts of UVB/C-radiation induced a transient cell cycle arrest of the cells which correlated with rapid but transient increase in p53 levels. In contrast, high UV-fluency caused cell apoptosis and a slower but sustained increase in p53. Regulation of p53 target genes was highly dependent on the radiation dose used. Whereas low doses induced p21/Cip1/Waf1 and HDM2, high doses induced only GADD45 and BAX increasing the BAX:BCL-2 ratio. The levels of HDM2, a negative regulator of p53, increased only by the low dose of UVC and p53-HDM2 association was promoted. In the absence of HDM2-induction after the high dose of UV-radiation p53-HDM2-interaction was promoted, but HDM2 failed to downregulate p53. p53 site-specific modifications (Ser15, Ser33, Ser37, Lys382) varied kinetically and were dependent on the fluency of the radiation used. Maximal phosphorylation of p53 on Ser15 and Ser33 correlated with increased levels of HDM2-free p53. The results suggest that regulation of p53 and HDM2 by UV-radiation is highly dose-dependent and contributes to the outcome of the cellular response.


Pharmacologic targets for atrial fibrillation.
Despite advances in treatment, atrial fibrillation (AF) remains the most common arrhythmia in humans. Antiarrhythmic drug therapy continues to be a cornerstone of AF treatment, even in light of emerging non-pharmacologic therapies. Conventional antiarrhythmic drugs target cardiac ion channels and are often associated with modest AF suppression and the risk of ventricular proarrhythmia. Ongoing drug development has focused on targeting atrial-specific ion channels as well as novel non-ionic targets. Targeting non-ionic mechanisms may also provide new drugs directed towards the underlying mechanisms responsible for AF and possibly greater antiarrhythmic potency. Agents that act against these new targets may offer improved safety and efficacy in AF treatment.


Residue Phe266 in S5-S6 loop is not critical for Charybdotoxin binding to Ca2+-activated K+ (mSlo1) channels.
To gain insight into the interaction between the Charybdotoxin (ChTX) and BK channels. Site-directed mutagenesis was used to make two mutants: mSlo1-F266L and mSlo1-F266A. The two mutants were then expressed in Xenopus oocytes and their effects were tested on ChTX by electrophysiology experiments. We demonstrate an equilibrium dissociation constant Kd=3.1-4.2 nmol/L for both the mutants mSlo1-F266L and mSlo1-F266A similar to that of the wild-type mSlo1 Kd=3.9 nmol/L. The residue Phe266 does not play a crucial role in binding to ChTX, which is opposed to the result arising from the simulation of peptide-channel interaction.


RETRACTED: Polysaccharide from Angelica sinensis ameliorates high-fat diet and STZ-induced hepatic oxidative stress and inflammation in diabetic mice by activating the Sirt1-AMPK pathway.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief because of duplication of data already published in the following paper in Food & Function: “Protective effects of Angelica sinensis polysaccharide against hyperglycemia and liver injury in multiple low-dose streptozotocin-induced type 2 diabetic BALB/c mice” by Wang K et al. in Food Funct 2016; 7; 4889-4897. The following data are the same in both papers: 1 The results of liver slices of oil red O staining in JNB Figure 1 are the same as Figure 6 in Food & Function. 2 JNB Figures 1 A and B are the same as Figure 7 B in the paper in Food & Function. 3 JNB Table 1 is the same as data presented in Figures 6 A-D and parts of Figure 3 A in the paper in Food & Function.


A high-throughput dye-reducing photometric assay for evaluating microbial exoelectrogenic ability.
Exoelectrogenic bacteria (EEB) can transfer electrons to extracellular electron acceptors and have wide applications in environmental bioremediation and bioenergy generation. Thus, methods for effectively probing the exoelectrogenic ability of EEB are highly desirable. In this work, a simple but efficient photometric assay based on the extracellular reduction of high polar dyes was developed to evaluate the microbial exoelectrogenic ability. Methyl orange were proven to be used as a probe for evaluating the exoelectrogenic ability of EEB. Through monitoring the extracellular dye decolorization under anaerobic conditions, this plate-based photometric assay could rapidly measure the exoelectrogenic ability of various EEB. This approach was also able to evaluate the exoelectrogenic capacity of Shewanella oneidensis MR-1 wild-type strain and its Mtr mutants. Furthermore, the exoelectrogenic ability of mixed cultures in microbial fuel cells was correlated with the extracellular dye decolorization. Thus, this work is useful for the practical implementation of microbial exoelectrogenic ability evaluation.


Determination of selected parabens, benzophenones, triclosan and triclocarban in agricultural soils after and before treatment with compost from sewage sludge: A lixiviation study.
An accurate and sensitive method for the determination of selected EDCs in soil and compost from wastewater treatment plants is developed and validated. Five parabens, six benzophenone-UV filters and the antibacterials triclosan and triclocarban were selected as target analytes. The parameters for ultrasound-assisted extraction were thoroughly optimized. After extraction, the analytes were detected and quantified using ultra-high performance liquid chromatography tandem mass spectrometry. Ethylparaben (ring-(13)C6 labelled) and deuterated benzophenone (BP-d10) were used as internal standards. The method was validated using matrix-matched calibration and recovery assays with spiked samples. The limits of detection ranged from 0.03 to 0.40 ng g(-1) and the limits of quantification from 0.1 to 1.0 ng g(-1), while precision in terms of relative standard deviation was between 9% and 21%. Recovery rates ranged from 83% to 107%. The validated method was applied for the study of the behavior of the selected compounds in agricultural soils treated and un-treated with compost from WWTP. A lixiviation study was developed in both agricultural soil and treated soil and first order kinetic models of their disappearance at different depths are proposed. The application of organic composts in the soil leads to an increase of the disappearance rate of the studied compounds. The lixiviation study also shows the risk of pollution of groundwater aquifers after disposal or waste of these EDCs in agricultural soils is not high.


Lipid dynamics in LPS-induced neuroinflammation by DESI-MS imaging.
It is well-established that bacterial lipopolysaccharides (LPS) can promote neuroinflammation through receptor Toll-like 4 activation and induces sickness behavior in mice. This phenomenon triggers changes in membranes lipid dynamics to promote the intracellular cell signaling. Desorption electrospray ionization mass spectrometry (DESI-MS) is a powerful technique that can be used to image the distribution of lipids in the brain tissue directly. In this work, we characterize the LPS-induced neuroinflammation and the lipid dynamics in C57BL/6 mice at 3 and 24 h after LPS injection. We have observed that intraperitoneal administration of LPS (5 mg/kg body weight) induces sickness behavior and triggers a peripheral and cerebral increase of pro- and anti-inflammatory cytokine levels after 3 h, but only IL-10 was upregulated after 24 h. Morphological analysis of hypothalamus, cortex and hippocampus demonstrated that microglial activation was present after 24 h of LPS injection, but not at 3 h. DESI-MS revealed a total of 14 lipids significantly altered after 3 and 24 h and as well as their neuroanatomical distribution. Multivariate statistical analyzes have shown that ions associated with phosphatidylethanolamine [PE(38:4)] and docosatetraenoic acid [FA (22:4)] could be used as biomarkers to distinguish samples from the control or LPS treated groups. Finally, our data demonstrated that monitoring cerebral lipids dynamics and its neuroanatomical distribution can be helpful to understand sickness behavior and microglial activation after LPS administration.


The action of fenfluramine andp-chloramphetamine on serotonergic mechanisms: A comparative study in rat brain nuclei.
A single injection of fenfluramine orp-chloroamphetamine (PCA) (100 μmol/kg intraperitoneally) decreases the serotonin (5HT) content and the tryptophan hydroxylase activity in various areas of the rat brain. Other reports have shown that a single injection of fenfluramine or PCA causes cytopathological changes in a serotonergic midbrain nucleus which was termed B9 by Dahlstrom and Fuxe (1). Despite this cytopathological change, fenfluramine fails to reduce the tryptophan hydroxylase activity in B9. In hippocampus the decrease of tryptophan hydroxylase elicited by fenfluramine persists for less than 21 days; in contrast PCA reduces the tryptophan hydroxylase activity in hippocampus, striatum, septal nuclei and B9 for longer than 21 days. Probably the decrease of tryptophan hydroxylase elicited by PCA in B9 is due to retrograde degeneration; the intensity and duration of the biochemical lesion elicited by fenfluramine and PCA in serotonergic terminals are a factor in determining the extent of the biochemical lesion in serotonergic cell bodies.


Combination docetaxel plus vitamin D(3) as an immune therapy in animals bearing squamous cell carcinomas.
Background tumor growth results in the mobilization of immune inhibitory CD34(+) progenitor cells. However, vitamin D(3) can differentiate the CD34(+) cells into immune stimulatory dendritic cells. This study determined if docetaxel treatment could increase the impact of the vitamin D(3) to generate dendritic cells. The murine squamous cell carcinoma model, SCC VII/SF, which is often used as a head and neck cancer model, was used to determine the immunological effects of two cycles of docetaxel plus vitamin D(3). Vitamin D(3) with or without docetaxel was similarly effective in reducing CD34(+) cell levels within the spleen, lymph nodes, and tumor. Dendritic cell levels were similarly enhanced in the lymph nodes by vitamin D(3) alone or combined with docetaxel. However, the combination treatment caused a prominent increase in intratumoral levels of active T cells, which was not observed by the individual treatments. Incorporating docetaxel treatment with vitamin D(3) differentiation-inducing treatment enhances intratumoral immune responsiveness.


Migraine: mimics, borderlands and chameleons.
Diagnostically, headache is the easy part of migraine. It is the surrounds of migraine--the aura, prodrome and postdrome--that can be most challenging, and confused with other pathologies. This article examines the definition and variants of migraine; alternative diagnoses for which migraine may be mistaken (mimics); conditions that lie between migraine and other diagnoses (borderlands) and the possible presentations of migraine posing as other conditions (chameleons). The focus is on adults, with only passing reference to children. Migraine is more often a chameleon than a mimic; and it is the careful history that usually makes the distinction. Given migraine's prevalence of 10-15%, relatively uncommon features of migraine occur quite often, in comparison with frequent manifestations of less common diseases. Thus, even rare or under-recognised presentations of migraine come into the differential diagnosis of many presentations.


Off to a slow start: under-development of the complement system in term newborns is more substantial following premature birth.
Complement represents a keystone to the innate immune system, with three activation pathways that utilise foreign microbial pattern recognition as well as activation by the host's specific antibodies. However, innate immunity is not synonymous with neonatal immunity. The complement system in healthy term (38-42 weeks gestation) newborns is under-developed and, with only a few exceptions (e.g. C7 and factor D), the circulating complement component concentrations are between 10 and 80% of adult levels. Complement activation is tightly regulated and the circulating regulator levels are also low relative to adults, sometimes at almost undetectable levels (e.g. C4b-binding protein). For premature newborns, these relative deficiencies are even more marked. Newborns are known to be more susceptible to infection, and the importance of complement, not only through its decreased ability to directly lyse bacteria with the common terminal pathway, but also its reduced ability to recruit (chemotaxis) innate and adaptive leukocytes to sites of microbial invasion and reduced ability to enhance phagocytosis (opsonisation) will be discussed. Complement also holds a key role in enhancing and directing refinement of the specific antibody response to pathogens (as an adjuvant) that likely plays a role in the well-known under-performance of the humoral immune response in newborns.


Strategies for optimized application of annular-phased-array systems in clinical hyperthermia.
A theoretical framework is presented for optimized heating of deep-seated tumours by phase and amplitude steering. The optimization problem for a specific tumour and perfusion case results in a functional dependency between power-level and maximum obtainable therapeutic efficiency. Different optimization criteria and strategies are outlined, which cause an increase of power or thermal dose in the tumour. Three tumour models (central pelvic tumour, eccentric abdominal tumour with or without necrosis) are analysed in detail. The simulation studies predict that appreciable parts of these tumours (50-100%) can be heated efficiently (42.5-43 degrees C) within the range of available and clinically tolerated power levels (1-5 kW/m), if tumour perfusion is less than 20-25 ml/100 g min. Some improvements are obtained by increasing the number of independent channels (from four to eight) and by the application of time-dependent (complementary) power-deposition patterns.


Inter-observer reliability of preoperative cardiopulmonary exercise test interpretation: a cross-sectional study.
Despite the increasing importance of cardiopulmonary exercise testing (CPET) for preoperative risk assessment, the reliability of CPET interpretation is unclear. We aimed to assess inter-observer reliability of preoperative CPET. We conducted a prospective, multi-centre, observational study of preoperative CPET interpretation. Participants were professionals with previous experience or training in CPET, assessed by a standardized questionnaire. Each participant interpreted 100 tests using standardized software. The CPET variables of interest were oxygen consumption at the anaerobic threshold (AT) and peak oxygen consumption (VO2 peak). Inter-observer reliability was measured using intra-class correlation coefficient (ICC) with a random effects model. Results are presented as ICC with 95% confidence interval, where ICC of 1 represents perfect agreement and ICC of 0 represents no agreement. Participants included 8/28 (28.6%) clinical physiologists, 10 (35.7%) junior doctors, and 10 (35.7%) consultant doctors. The median previous experience was 140 (inter-quartile range 55-700) CPETs. After excluding the first 10 tests (acclimatization) for each participant and missing data, the primary analysis of AT and VO2 peak included 2125 and 2414 tests, respectively. Inter-observer agreement for numerical values of AT [ICC 0.83 (0.75-0.90)] and VO2 peak [ICC 0.88 (0.84-0.92)] was good. In a post hoc analysis, inter-observer agreement for identification of the presence of a reportable AT was excellent [ICC 0.93 (0.91-0.95)] and a reportable VO2 peak was moderate [0.73 (0.64-0.80)]. Inter-observer reliability of interpretation of numerical values of two commonly used CPET variables was good (>80%). However, inter-observer agreement regarding the presence of a reportable value was less consistent.


MRP1 polymorphisms (T2684C, C2007T, C2012T, and C2665T) are not associated with multidrug resistance in leukemic patients.
One of the main problems in treating cancer patients is that cancer cells can develop drug resistance. Resistance to multiple anticancer drugs, so called multidrug resistance (MDR), most likely involves a nonspecific mode of resistance, through drug-efflux transporters. One of the most extensively studied genes involved in MDR is multidrug resistance protein 1 (MRP1). We investigated a possible association between the expression level of MRP1 and the occurrence of MDR in leukemic patients, and we tested the hypothesis that MRP1 polymorphisms are predictive of MDR in patients with acute leukemia. The mRNA level of MRP1 was determined in 111 patients with acute leukemia (including 52 patients with acute myeloid leukemia and 59 patients with acute lymphoblastic leukemia), by quantitative real-time PCR, to determine how it affected the response to chemotherapy. We typed T2684C, C2007T, C2012T, and C2665T MRP1 polymorphisms in 111 patients classified as either drug-resistant or drug-responsive. We found that high expression of MRP1 was associated with the MDR phenotype in both acute myeloid leukemia and acute lymphoblastic leukemia patients. There was no effect of a particular genotype on the expression level of the MRP1 gene. We found no significant differences in chemosensitivity among any of these genotypes.


Use of molecular biomarkers in FNA specimens to personalize treatment for thyroid surgery.
Accurate preoperative assessment of thyroid nodules with fine-needle aspiration biopsy (FNAB) continues to be a challenge, often resulting in unnecessary diagnostic surgical intervention. The detection of several novel gene mutations in differentiated thyroid cancer (DTC) over the last decade has led to the diagnostic use of these oncogenic alterations to improve FNAB sensitivity and specificity. Thyroid oncogene mutations including BRAF, RAS, and RET/PTC are reviewed. The potential benefit of using this panel on fine-needle aspiration (FNA) cytology samples will be described. Our use of ''reflexive'' molecular testing demonstrates its clinical value in conjunction with FNAB cytology, representing an application of personalized molecular medicine to guide appropriate surgical therapy.


Determination of reference values for plasma cystatin C and comparison with creatinine in premature infants.
Cystatin C (CysC) is a low-molecular-mass protein (13,343 dalton, 120 amino acids) belonging to the cystatin superfamily of reversible inhibitors of cysteine proteases. CysC appears to be eliminated from the circulation almost exclusively by glomerular filtration, which makes it a promising endogenous marker of renal function. CysC has been demonstrated to reflect glomerular filtration rate better than other low-molecular-weight proteins, including creatinine (Cr). We established reference values for serum CysC and compared them with Cr in 108 preterm infants by particle-enhanced nephelometric immunoassay. On the first day, serum CysC values ranged from 1.25 to 2.84 mg/L, significantly decreasing after 3 days of life. Cr levels determined simultaneously on the first day ranged from 0.05 to 1.12 mg/dl and were also significantly different from day 3 levels. Both CysC and Cr levels were independent of gender, birth weight, hemoglobin levels, and hydration state. Cr correlated negatively with gestational age (r = -0.25, p = 0.009), but not CysC. A significant correlation was found between CysC and Cr on day 1 (r = 0.21, p = 0.031), but no correlation was found according to day 3 blood samples (r = 0.19, p = 0.053). CysC is regarded as an alternative for assessing renal function in preterm neonates, but its advantages over Cr are not yet proven.


miR-30a inhibits the biological function of breast cancer cells by targeting Notch1.
miR-30a is situated on chromosome 6q.13 and is produced by an intronic transcriptional unit. However, its role in regulating the apoptosis, invasion and metastasis of breast cancer cells is not yet fully understood. The aim of this study was to research the biological function of miR‑30a and its direct target gene in breast cancer. The biological function of miR‑30a was determined by examining breast cancer cell growth, apoptosis, metastasis and invasion. In addition, Notch1 expression was measured by western blot analysis, and a luciferase reporter vector was constructed to identify the miR‑30a target gene. miR‑30a was found to be significantly downregulated in breast cancer cells. We also found that miR‑30a inhibited breast cancer cell viability, migration and invasion, and induced cell apoptosis. On the whole, our data indicate that miR‑30a attenuates the development of breast cancer by regulating the expression of the downstream target gene, Notch1.


Impact of a male-only weight loss maintenance programme on social-cognitive determinants of physical activity and healthy eating: A randomized controlled trial.
To examine the effect of a gender-tailored, Social Cognitive Theory (SCT)-based weight loss maintenance (WLM) intervention on men's physical activity and healthy eating cognitions and behaviours in the 12 months after completing a weight loss programme. A two-phase, assessor-blinded, randomized controlled trial. Ninety-two overweight/obese men (mean [SD] age: 49.2 years [10.1], BMI: 30.7 [3.3] kg/m(2) ) who lost at least 4 kg after completing the 3-month SCT-based SHED-IT Weight Loss Program were randomly allocated to receive (1) the SCT-based SHED-IT WLM Program; or (2) no additional resources (self-help control group). The 6-month gender-tailored SHED-IT WLM Program was completely self-administered and operationalized SCT behaviour change principles to assist men to increase moderate-to-vigorous physical activity (MVPA) and decrease energy-dense, nutrient-poor (discretionary) food consumption after initial weight loss. After randomization (WLM baseline), men were reassessed at 6 months (WLM post-test) and 12 months (6-month WLM follow-up). SCT cognitions (e.g., self-efficacy, goal setting), MVPA, and discretionary food consumption were assessed with validated measures. Following significant improvements in cognitions, MVPA and discretionary food consumption during the weight loss phase, intention-to-treat, linear mixed models revealed no significant group-by-time differences in cognitions or behaviours during the WLM phase. Initial improvements in MVPA and some cognitions (e.g., goal setting, planning, and social support) were largely maintained by both groups at the end of the study. Dietary effects were not as strongly maintained, with the intervention and control groups maintaining 57% and 75% of the Phase I improvements in discretionary food intake, respectively. An additional SCT-based WLM programme did not elicit further improvements over a self-help control in the cognitions or behaviours for MVPA or discretionary food intake of men who had lost weight with a SCT-based weight loss programme. Statement of contribution What is already known on this subject?Weight regain after weight loss (WL) is common. As successful weight loss maintenance (WLM) requires sustained improvements in cognitions and behaviours, health psychology can contribute to intervention development. However, little research has examined the utility of psychological theory in the context of a WLM randomised controlled trial. What does this study add? A theory-based WL program improved men's physical activity and dietary behaviours and cognitions. Men who also received a theory-based WLM program did not show further improvements in physical activity or dietary cognitions and behaviours compared to those that did not.


Ridge preservation with the use of deproteinized bovine bone mineral.
The aim was to examine the tissue composition of extraction sockets that had been grafted with deproteinized bovine bone mineral and allowed to heal for 6 months. Twenty-five subjects with one tooth each scheduled for extraction and replacement with dental implants were recruited. The assigned teeth were carefully removed. The site/patient was thereafter allocated to a test or a control group. In the test group patients, Bio-Oss(®) Collagen was placed to fill the fresh extraction socket while in the controls no grafting was performed. After about 6 months of healing, a biopsy was sampled from the center of the extraction site. The specimens were decalcified, embedded in paraffin, sectioned, and stained in HTX. The proportions occupied by mineralized bone, osteoid, bone marrow, fibrous tissue, and Bio-Oss(®) particles were determined by morphometric point counting. Mineralized bone made up 57.4 ± 12.4% of the control sites (C) and 48.9 ± 8.5% of the T1 sites (graft material not included). The amount of bone marrow (C: 7.1 ± 6.1%, T1: 2.1 ± 3.1%) and osteoid (C: 7.3 ± 4.9%, T1: 1.9 ± 2.1%) was about five times greater in the control than in the test sites. Fibrous tissue comprised 23.1 ± 16.3% (C) and 40.0 ± 11.9% (T1). I n the T2 sites (graft material included), the percentage mineralized bone was 39.9 ± 8.6 while the proportions of bone marrow and osteoid were 1.8 ± 2.5% and 1.6 ± 1.8%. Fibrous tissue occupied 32.4 ± 9.2% and Bio-Oss(®) particles 19.0 ± 6.5% of the T2 sites. Placement of the biomaterial in the fresh extraction socket retarded healing. The Bio-Oss(®) particles were not resorbed but became surrounded by new bone. This may explain why grafted extraction sites may fail to undergo dimensional change.


Sodium and lithium interactions with the Na+/Dicarboxylate cotransporter.
The two-electrode voltage clamp was used to study the currents associated with transport of succinate by the cloned Na+/dicarboxylate cotransporter, NaDC-1, expressed in Xenopus oocytes. The presence of succinate induced inward currents which were dependent on the concentrations of succinate and sodium, and on the membrane potential. At -50 mV, the K0.5succinate was 180 microM and the K0.5Na+ was 19 mM. The Hill coefficient was 2.3, which is consistent with a transport stoichiometry of 3 Na+:1 divalent anion substrate. Currents were induced in NaDC-1 by a range of di- and tricarboxylates, including citrate, methylsuccinate, fumarate, and tricarballylate. Although Na+ is the preferred cation, Li+ was also able to support transport. The K0.5succinate was approximately 10-fold higher in Li+ compared with Na+. In the presence of Na+, however, Li+ was a potent inhibitor of transport. Millimolar concentrations of Li+ resulted in decreases in apparent succinate affinity and in the Imaxsuccinate. Furthermore, lithium inhibition under saturating sodium concentrations showed hyperbolic kinetics, suggesting that one of the three cation binding sites in NaDC-1 has a higher affinity for Li+ than Na+. We conclude that NaDC-1 is an electrogenic anion transporter that accepts either Na+ or Li+ as coupling cations. However, NaDC-1 contains a single high affinity binding site for Li+ that, when occupied, results in transport inhibition, which may account for its potent inhibitory effects on renal dicarboxylate transport.


Trait self-control is predicted by how reward associations modulate Stroop interference.
Although cognitive control is commonly identified as the basis of self-controlled behavior, correlations found between trait self-control and laboratory measures of cognitive control such as Stroop interference are typically low. Based on the notion that self-control requires the ability to refrain from rewarded behaviors, and inspired by the recent finding that Stroop interference is modulated by reward associations, we propose the idea that the modulation of interference by reward associations (MIRA) is a cognitive marker of trait self-control. Two independent samples of participants completed (1) a modified Stroop task designed to assess MIRA and (2) two common measures of trait self-control: the Brief Self-Control Scale (BSCS) and the Barratt Impulsiveness Scale (BIS-11). MIRA was strongly correlated with the BSCS and moderately correlated with two of the three subscales of the BIS-11. MIRA thus appears to reflect a cognitive endophenotype of individual differences in self-control, and perhaps of related mental disorders.


Subretinal neovascularization developing after prophylactic argon laser photocoagulation of atrophic macular scars.
Two patients who had lost central vision in one eye due to a histoplasmic disciform macular scar received prophylactic argon laser photocoagulation to one or more atrophic lesions (histo spots) in the second macula in an effort to reduce the risk of developing active neovascularization in the second eye. Despite this prophylactic treatment, both patients developed a choroidal neovascular membrane from the photocoagulation scar.


Examination of the problems confronting those with epilepsy.
This paper reports the findings of two studies using similar numbers of patients with epilepsy, but differing referral bases and investigative tools. It demonstrates that people with epilepsy still experience major problems in the areas of emotional adjustment and stability, personal relationships, and employment.


A general strategy to create RNA aptamer sensors using "regulated" graphene oxide adsorption.
Aptamers have been used as molecular recognition elements for sensor development in combination with graphene oxide (GO), a nanomaterial with properties including fluorescence quenching, and selective adsorption of single-stranded nucleic acids. However, previous sensor designs based on aptamer-GO adsorption have not demonstrated wide applicability, and few studies have explored the potential of RNA aptamers. Herein, we present a new sensing strategy based on "regulated" GO adsorption that can accommodate various RNA aptamers. First, adsorption of a fluorophore-labeled RNA aptamer to GO results in fluorescence quenching due to close proximity of the fluorophore to GO. The addition of a complementary, "blocking" DNA strand (BDNA) that hybridizes to the 3'-end of the aptamer, weakens aptamer-GO interaction, and enables increased fluorescent signal generation upon the addition of target, as the sensing system becomes completely separated from GO. Our findings can be applied toward different aptamers, and adapted to enhance generality of existing sensing applications.


Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis.
We performed a case-control study to assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV), GB virus C/hepatitis G virus (HGV), TT virus, alcohol intake, and tobacco smoking as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis. We prospectively recruited 174 patients with a first diagnosis of HCC admitted to the main hospitals in Brescia, North Italy. On the basis of histological, clinical, and radiological criteria, the presence of cirrhosis was established in 142 cases, excluded in 21 cases, and remained undefined in 11 cases. Among the HCC cases without cirrhosis, a histological picture of normal liver was found in a single patient, chronic viral hepatitis was found in 11 patients, alcoholic hepatitis was found in 5 patients, nonspecific reactive hepatitis was found in 3 patients, and hemochromatosis was found in 1 patient. As controls, we also included 610 subjects unaffected by hepatic diseases and admitted to the same hospitals as cases. The odds ratios for having HCC according to positivity for HCV RNA, HBsAg and/or HBV DNA, and alcohol intake > 80 g/day (95% confidence interval) were as follows, in the presence and absence of cirrhosis, respectively: (a) 33.5 (17.7-63.4) and 19.7 (6-64.8) for HCV RNA; (b) 17.6 (9.0-34.4) and 20.3 (5.7-72.6) for HBsAg; and (c) 5.5 (3.1-9.7) and 4.6 (1.5-13.8) for alcohol intake. No association was found with HGV or TT virus infections or tobacco. This study has shown that most HCC cases arising in the area are due to HBV, HCV, or alcohol intake, in both the presence and absence of cirrhosis.


Multidose drug dispensing and discrepancies between medication records.
The objective of this study was to investigate whether implementation of multidose drug dispensing (MDD) for elderly outpatients is associated with a change in the number of discrepancies in the medication record at the general practitioners (GPs) and at the community home-care services. A controlled follow-up study with paired design of patients' medication records was performed during implementation of MDD. Medication records from the home care units and from the GPs were reviewed, and the discrepancies were noted. The discrepancies were rated into four classes based upon the potential harm, and a risk score system was applied, giving the potentially most harmful discrepancies the highest score. Medication records from 59 patients with a mean age of 80 years were included. The number of discrepancies was reduced from 203 to 133 (p<0.001), and the total risk score decreased from 308 to 181 (p<0.001) after the implementation of MDD. For both drugs subject to MDD and drugs not suitable for MDD, the reductions in discrepancies were significant (39% and 31% reduction respectively). Calculated health risk due to discrepancies between the medication records from the home-care service and from the GPs decreased during the time of implementation of the MDD system. It seems likely that most of the positive effect was caused by the change in routines and enhanced focus on the medication process rather than by MDD per se.


Candidate circulating biomarkers for the cardiovascular disease continuum.
The early identification of susceptibility to adverse cardiovascular outcomes and risk stratification amongst asymptomatic individuals, as well as amongst those with overt disease continues to be one of the major priorities of clinically-orientated research in the field of atherothrombosis. Available data from epidemiological studies indicate that traditional risk factors do not fully explain the predisposition to cardiovascular disease, its dynamics in different population groups and treatment responses. The pressing need for the development and clinical implementation of new markers of atherothrombotic disease has fuelled rapidly expanding research into cardiac biomarkers. This review outlines the main principles of biomarker qualification that have entered clinical practice, as well as an overview of the development of targeted biomarkers across the cardiovascular "continuum". We discuss in detail the evidence from epidemiological and clinical studies advocating the potential clinical use of the most promising candidate plasma biomarkers (more specifically, C-reactive protein, coagulation and inflammatory mediators and natriuretic peptides). Such an application of biomarkers to aid clinical risk assessment would be important in our efforts to improve risk stratification of subjects at risk of cardiovascular events.


Rotavirus infections and vaccines: burden of illness and potential impact of vaccination.
Rotaviruses are the most common cause of severe gastroenteritis in children. By 5 years of age virtually every child worldwide will have experienced at least one rotavirus infection. This leads to an enormous disease burden, where every minute a child dies because of rotavirus infection and another four are hospitalized, at an annual societal cost in 2007 of $US2 billion. Most of the annual 527 000 deaths are in malnourished infants living in rural regions of low and middle income countries. In contrast, most measurable costs arise from medical expenses and lost parental wages in high income countries. Vaccines are the only public health prevention strategy likely to control rotavirus disease. They were developed to mimic the immunity following natural rotavirus infection that confers protection against severe gastroenteritis and consequently reduces the risk of primary healthcare utilization, hospitalization and death. The two currently licensed vaccines--one a single human strain rotavirus vaccine, the other a multiple strain human-bovine pentavalent reassortant rotavirus vaccine--are administered to infants in a two- or three-dose course, respectively, with the first dose given at 6-14 weeks of age. In various settings they are safe, immunogenic and efficacious against many different rotavirus genotypes. In high and middle income countries, rotavirus vaccines confer 85-100% protection against severe disease, while in low income regions of Africa and Asia, protection is less, at 46-77%. Despite this reduced efficacy in low income countries, the high burden of diarrheal disease in these regions means that proportionately more severe cases are prevented by vaccination than elsewhere. Post-licensure effectiveness studies show that rotavirus vaccines not only reduce rotavirus activity in infancy but they also decrease rates of rotavirus diarrhea in older and unimmunized children. A successful rotavirus vaccination program will rely upon sustained vaccine efficacy against diverse and evolving rotavirus strains and efficient vaccine delivery systems. The potential introduction of rotavirus vaccines into the world's poorest countries with the greatest rates of rotavirus-related mortality is expected to be very cost effective, while rotavirus vaccines should also be cost effective by international standards when incorporated into developed countries immunization schedules. Nonetheless, cost effectiveness in each country still depends largely on the local rotavirus mortality rate and the price of the vaccine in relation to the per capita gross domestic product.


Ultrasound-guided needle positioning in sensory nerve conduction study of the sural nerve.
To evaluate the usefulness of ultrasound imaging to improve the positioning of the recording needle for nerve conduction studies (NCS) of the sural nerve. Orthodromic NCS of the sural nerve was performed in 44 consecutive patients evaluated for polyneuropathy. Ultrasound-guided needle positioning (USNP) was compared to conventional "blind" needle positioning (BNP), electrically guided needle positioning (EGNP), and to recordings with surface electrodes (SFN). The mean distance between the needle tip and the nerve was 1.1 mm with USNP compared to 5.1 mm with BNP (p<0.0001). The mean amplitude of the sensory nerve action potential (SNAP) was 21 microV with USNP and 11 microV with BNP (p<0.0001). Compared to BNP, nerve-needle distances and SNAP amplitudes did not improve with EGNP. SNAP amplitudes recorded with SFN were significantly smaller than with BNP, EGNP and USNP. Ultrasound increases the precision of needle positioning markedly, compared to conventional methods. The amplitude of the recorded SNAP is usually clearly greater using USNP. In addition, USNP is faster, less painful and less dependent on the patient. USNP is superior to BNP, EGNP, and SFN in accurate measurement of SNAP amplitude. It has a potential use in the routine near-nerve needle sensory NCS of pure sensory nerves.


Variables associated with health-related quality of life in a Brazilian sample of patients from a tertiary outpatient clinic for depression and anxiety disorders.
Health-related quality of life (HRQOL) assessment tools have been broadly used in the medical context. These tools are used to measure the subjective impact of the disease on patients. The objective of this study was to evaluate the variables associated with HRQOL in a Brazilian sample of patients followed up in a tertiary outpatient clinic for depression and anxiety disorders. Cross-sectional study. Independent variables were those included in a sociodemographic questionnaire and the Hospital Anxiety and Depression Scale (HADS) scores. Dependent variables were those included in the short version of the World Health Organization Quality of Life (WHOQOL-BREF) and the scores for its subdomains (overall quality of life and general health, physical health, psychological health, social relationships, and environment). A multiple linear regression analysis was used to find the variables independently associated with each outcome. Seventy-five adult patients were evaluated. After multiple linear regression analysis, the HADS scores were associated with all outcomes, except social relationships (p = 0.08). Female gender was associated with poor total scores, as well as psychological health and environment. Unemployment was associated with poor physical health. Identifying the factors associated with HRQOL and recognizing that depression and anxiety are major factors are essential to improve the care of patients.


O6 -methylguanine DNA methyltransferase gene promoter methylation in high-grade gliomas: a review of current status.
Assessment of promoter methylation of the O 6 -methylguanine DNA methyltransferase (MGMT) gene has recently gained importance in molecular profiling of high-grade gliomas. It has emerged not only as an important prognostic marker but also as a predictive marker for response to temozolomide in patients with newly diagnosed glioblastoma. Further, recent studies indicate that MGMT promoter methylation has strong prognostic relevance even in anaplastic (grade III) gliomas, irrespective of therapy (chemotherapy or radiotherapy). This article provides an overview of its use as a predictive and prognostic biomarker, as well as the methods employed for its assessment and use in therapeutic decision making.


Benefits of lipid-lowering therapy in patients with type 2 diabetes mellitus.
The incidence of type 2 diabetes mellitus is expected to increase dramatically over the next decade. Patients with type 2 diabetes are at a much greater risk for cardiovascular disease (CVD) than are nondiabetic individuals. Consequently, the treatment of CVD risk factors is a healthcare priority in this patient population. Dyslipidemia is a major cardiovascular (CV) risk factor in patients with type 2 diabetes, and it is characterized by elevated triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, and a preponderance of small, dense low-density lipoprotein (LDL) particles. Subgroup analyses of clinical trial data suggest that treatment of the entire range of lipid abnormalities may reduce CV risk in this patient population. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are the best therapy for LDL cholesterol reduction. A number of statin trials have shown significant CV risk reduction through LDL cholesterol lowering in subgroups of patients with diabetes. The recently published Collaborative Atorvastatin Diabetes Study (CARDS), a placebo-controlled trial conducted solely in patients with type 2 diabetes, terminated 2 years earlier than its anticipated length owing to the significant reduction in number of CV events observed in patients randomized to receive low-dose atorvastatin versus placebo. These results suggest that low-dose statin therapy with atorvastatin results in significant reduction of CV events in patients with type 2 diabetes without prior CVD or high LDL cholesterol levels. Based on this evidence, patients with type 2 diabetes may be candidates for statin therapy regardless of LDL cholesterol level and in the absence of a previous CV event.


N-acetylcysteine protects against fluoride-induced oxidative damage in primary rat hepatocytes.
Fluoride induces the overproduction of free radicals, which might in turn affect various biochemical parameters. Therefore, the aim of this study was to elucidate the role of N-acetylcysteine (NAC) in decreasing fluoride-induced oxidative stress. The fluoride intoxicated (0.002; 0.082; 0.164mmol/l) rat hepatocytes was pre-treated (60min) and simultaneously treated with NAC (1mmol/l). The resulting levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and intracellular reduced glutathione (GSH) were measured along with the total antioxidant status (TAS) to determine whether NAC treatment reduced cell damage and/or the antioxidant state. These results suggest that NAC pre-treatment provides protection against fluoride-induced oxidative stress in hepatocytes.


Looking for high energy density compounds among polynitraminecubanes.
Based on fully optimized geometric structures at DFT-B3LYP/6-311G** level, we calculated electronic structures, heats of formation, strain energies, bond dissociation energies and detonation performance (detonation velocity and detonation pressure) for a series of polynitraminecubanes. Our results have shown that energy gaps of cubane derivatives are much higher than that of triaminotrinitrobenzene (TATB), which means that cubane derivatives may be more sensitive than TATB. Polynitraminecubanes have high and positive heats of formation, and a good linear relationship between heats of formation and nitramine group numbers was presented. As the number of nitramine groups in the molecule increases, the enthalpies of combustion values are increasingly negative, but the specific enthalpy of combustion values decreases. It is found that all cubane derivatives have high strain energies, which are affected by the number and position of nitramine group. The calculated bond dissociation energies of C-NHNO(2) and C-C bond show that the C-C bond should be the trigger bond in the pyrolysis process. It is found that detonation velocity (D), detonation pressure (P) and molecule density (ρ) have good linear relationship with substituented group numbers. Heptanitraminecubane and octanitraminecubane have good detonation performance over 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX), and they can be regarded as potential candidates of high energy density compounds (HEDCs). The results have not only shown that these compounds may be used as HEDCs, but also provide some useful information for further investigation.


Contribution of family social support to the metabolic control of people with diabetes mellitus: A randomized controlled clinical trial.
This randomized controlled clinical trial aimed to evaluate the contribution of family social support to the clinical/metabolic control of people with type 2 diabetes mellitus. Diabetes mellitus is a chronic disease that requires continuous care in order for individuals to reach glycemic control, the primordial goal of treatment. Family social support is essential to the development of care skills and their maintenance. However, there are few studies that investigate the contribution of family social support to diabetes control. The study was developed between June 2011 and May 2013, and included 164 people who were randomized using simple randomization. The intervention group differed from the control group in that it included a family caregiver, who was recognized by the patient as a source of social support. The educational interventions received by people with diabetes mellitus were used as the basis of the education provided through telephone calls to patients' family members and caregivers, and their purpose was to encourage dialogue between the patients and their relatives about the topics related to diabetes. Regarding the clinical impact, the results showed that there was a greater reduction in blood pressure and glycated hemoglobin in the intervention group than in the control group, showing a positive effect on the control of the disease. Families should be incorporated into the care of people with diabetes mellitus and especially in health care programs, in particular those that can promote different forms of social support to strengthen the bond between family members.


GABAergic inhibition and modifications of taste responses in the cortical taste area in rats.
Using multibarrel electrodes, recordings were made in the cortical taste area (CTA), specifically in the granular and dysgranular parts of the insular cortex (areas GI and DI), of urethane-anesthetized rats. The effects of an iontophoretic application of gamma-aminobutylic acid (GABA) and bicuculline methiodide (BMI), a specific antagonist to the GABA(A) receptor, were tested. GABA decreased background discharges in ca. 69% of 509 neurons in both areas, and in ca. 58% of 64 taste neurons. BMI antagonized the inhibitory action of GABA in CTA neurons and facilitated background discharges in ca. 51% of the 390 neurons tested, including ca. 69% of the 52 taste neurons, which indicates that CTA neurons have GABA(A) receptors to receive inhibitory inputs from interneurons. In both areas, the effects of BMI (6-20 nA) on taste responses of the 85 CTA neurons (49 and 36 in areas GI and DI, respectively) to the four basic taste stimuli were examined: 65 neurons were recognized in the absence of BMI, whereas 20 only in the presence of the drug. BMI increased taste responses in 25 of the former group and changed the type of their response profiles in 25 including 12 neurons whose responses were increased. It also changed the best stimulus in 34 neurons. The drug affected the receptive fields in almost all cases examined (n = 23) and increased the size in 78.2% when the value for all four basic taste stimuli were totaled. New receptive fields were uncovered by BMI in varying regions of the oral cavity depending on the taste stimulus. But the drug decreased taste responses in several neurons (n = 8). These findings indicate that the GABAergic inhibitory system apparently contributes to modifying or selecting taste information in both areas of the CTA.


Sudden unexpected death in epilepsy: from the lab to the clinic setting.
Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in a patient with epilepsy. Sudden unexpected death in epilepsy is probably the most common cause of epilepsy-related deaths. Many predisposing and initiating factors may coexist and contribute to SUDEP, but the mechanisms are poorly understood. Cardiac and respiratory deregulation seems to have a major role in SUDEP. Here, we review several advances in understanding the mechanisms involved in SUDEP.


Taste conditioning effects of buprenorphine in morphine-naive and morphine-experienced rats.
Male Sprague-Dawley rats were injected daily with saline (morphine-naive rats) or 20 mg kg-1 morphine (morphine-experienced rats), starting 15 days before the experiment. Subsequent taste conditioning indicated that 0.1 mg kg-1 buprenorphine significantly decreased 0.025% saccharin consumption in morphine-naive, but not in morphine-experienced rats. A 10 mg kg-1 dose of morphine gave similar results, while d-amphetamine (0.75 mg kg-1) was consistently aversive. It was concluded that morphine experience selectively blocks the aversive effects of buprenorphine in rats; thus it possibly increases the potential for buprenorphine abuse.


Developmental competence of bovine oocytes after specific inhibition of MPF kinase activity: effect of estradiol supplementation and follicle size.
In the bovine, the concentration of 17beta-estradiol (E2) in the follicular fluid of the dominant follicle is high, indicating a possible role of E2 on the cytoplasmic maturation that occurs before the LH surge. The aim of this study was to investigate the role of E2 on the developmental competence of bovine oocytes originating from different sized follicles and temporarily maintained at the germinal vesicle stage with roscovitine (ROS). First, the efficiency of ROS to inhibit germinal vesicle breakdown (GVBD) in oocytes harvested from small (3-4 mm diameter) and medium (5-8 mm diameter) sized follicles was demonstrated. Next, the effect of E2 during temporary inhibition of GVBD by ROS on the subsequent nuclear maturation was evaluated. Oocytes from small and medium sized follicles were cultured in the presence of ROS, FSH and with or without E2 for 24 h. After this period, oocytes were cultured for another 24 h with FSH but without ROS and E2, after which the nuclear stages and the developmental competence of oocytes were assessed. In conclusion, it is demonstrated that exposure to E2, during temporary inhibition of the GVBD with ROS, affected neither nuclear nor cytoplasmic maturation of oocytes originating from small and medium sized follicles. It might be that in vivo, the increase of E2 during follicle growth is more related to selection of the dominant follicle than to the cytoplamsic maturation of the oocyte as such.


The effects of long-term low-dose cyclosporin A treatment on muscles and tendons: an experimental study.
Limited studies report that patients receiving immunosuppressive therapy, including cyclosporin A (CsA), face muscle and/or tendon pathologies. The current study aimed (i) to investigate if CsA cause changes in the microscopic structure of striated muscle tissues and tendons after long-term low-dose therapy and (ii) to examine if the vehicle of CsA, Cremophor EL, or steroid administration might cause additional effects. Twenty-four adult female Sprague-Dawley rats weighing 230-300 g were divided at random into four groups. Group 1 served as the control. Groups 2-4 received CsA intraperitoneally for 2.5 months: Group 2 received the oral form of CsA, Group 3 received the intravenous form of CsA, which contains Cremophor EL, and Group 4 received the intravenous form of CsA and prednisolone. Samples from the Achilles tendons and triceps surae muscles were examined at light microscope level. Focal necrotic areas, enlargement of connective tissue and increase in mononuclear cells were clear on muscles in the experimental groups. No morphologic effects were observed on tendons. Long-term low-dose CsA therapy causes focal microscopic changes in muscles but not in tendons. No additional effects were demonstrated with Cremophor EL or steroids. It should be noted that muscle tissue damage after trauma or surgeries in patients receiving CsA might be more dramatic due to the pathologic changes already caused by CsA, as supported by several case reports.


ArRAnging the hindbrain.
The retinoic acid (RA)-dependent mechanisms that orchestrate the development of the hindbrain have been the focus of intense studies over the last decade. A wide range of model systems and experimental approaches have been used to provide important insights into hindbrain patterning. A recent paper could help to unify seemingly disparate observations across species and experimental approaches. Specification of the entire caudal hindbrain is fully dependent on retinoic acid, and specification of individual rhombomeres (r) follows a strict rostrocaudal sequence at precise developmental time windows. Progressively higher RA signalling is necessary for assigning more posterior territories. Complete RA deficiency results in the caudal hindbrain assuming an r4-like identity, which is postulated to be the hindbrain ground state.


Molecular phylogenetic studies on the origin of biodiversity in Lake Baikal.
Lake Baikal is host to some 2500 metazoan species, maybe more, the majority of which are endemic. When studies of the lake shifted from purely descriptive work to a more analytical approach in the second half of this century, the question of the origin of its fauna became central and is still one of the main challenges to researchers of Baikalian biodiversity. Current research is investigating whether biodiversity can be explained by a few adaptive radiations since the Miocene, whether it results from the accumulation of diversity throughout the whole history of the Baikalian rift zone (about 70 million years) or whether it stems from even older events.


Hierarchical Mesoporous Metal-Organic Frameworks for Enhanced CO2 Capture.
Hierarchical porous materials are promising for catalyst, separation and sorption applications. A ligand-assisted etching process is developed for template-free synthesis of hierarchical mesoporous MOFs as single crystals and well-intergrown membranes at 40 °C. At 223 K, the hierarchical porous structures significantly improve the CO2 capture capacity of HKUST-1 by more than 44 % at pressures up to 20 kPa and 13 % at 100 kPa. Even at 323 K, the enhancement of CO2 uptake is above 25 % at pressures up to 20 kPa and 7 % at 100 kPa. The mesoporous structures not only enhance the CO2 uptake capacity but also improve the diffusion and mass transportation of CO2 . Similarly, well-intergrown mesoporous HKUST-1 membranes are synthesized, which hold the potential for film-like porous devices. Mesoporous MOF-5 crystals are also obtained by a similar ligand-assisted etching process. This may provide a facile way to prepare hierarchical porous MOF single crystals and membranes for wide-ranging applications.


Occlusal relationship in patients with pain-dysfunction symptoms in the temporomandibular joints.
A total of 135 patients (thirty-three males, 102 females) seeking treatment for pain and dysfunction of the TMJ were divided into five subgroups using the clinical dysfunction index of Helkimo. No relation could be found between the number of occluding molars and premolars and the severity of the symptoms nor the evolution of the complaints. A weak correlation was found between the outcome of the treatment with the occlusal splint and occlusal adjustment, and the above mentioned occlusal parameters (r = 0.47).


Synthesis of fructooligosaccharides from Aspergillus niger commercial inulinase immobilized in montmorillonite pretreated in pressurized propane and LPG.
Commercial inulinase from Aspergillus niger was immobilized in montmorillonite and then treated in pressurized propane and liquefied petroleum gas (LPG). Firstly, the effects of system pressure, exposure time, and depressurization rate, using propane and LPG, on enzymatic activity were evaluated through central composite design 2³. Residual activities of 145.1 and 148.5% were observed for LPG (30 bar, 6 h, and depressurization rate of 20 bar min⁻¹) and propane (270 bar, 1 h, and depressurization rate of 100 bar min⁻¹), respectively. The catalysts treated at these conditions in both fluids were then used for the production of fructooligosaccharides (FOS) using sucrose and inulin as substrates in aqueous and organic systems. The main objective of this step was to evaluate the yield and productivity in FOS, using alternatives for enhancing enzyme activity by means of pressurized fluids and also using low-cost supports for enzyme immobilization, aiming at obtaining a stable biocatalyst to be used for synthesis reactions. Yields of 18% were achieved using sucrose as substrate in aqueous medium, showing the potential of this procedure, hence suggesting a further optimization step to increase the process yield.


Caring for transgender patients with epilepsy.
Approximately 25 million individuals older than age 15 identify as transgender, representing about 0.3-0.9% of the world's population. The aim of this paper is to identify and describe important medical and social considerations facing transgender persons with epilepsy. We performed literature searches on the following terms: transgender AND epilepsy, transgender AND neurology, gender dysphoria AND epilepsy, gender dysphoria AND neurology. We also performed literature searches for common feminizing or masculinizing treatment regimens, and searched for interactions of those treatment regimens with antiepileptic drugs (AEDs) and with seizures. There are multiple bidirectional interactions between AEDs and the commonly used treatments for aligning external sex characteristics with identified gender. The scope of the transgender population with epilepsy remains to be elucidated. Transgender patients with epilepsy face significant social and medical challenges. Interactions between medical gender-affirming treatments and AEDs are common, and management must depend on knowledge of these interactions to provide appropriate treatment.


Mentally handicapped adolescents: their use of leisure.
An investigation into national provision for leisure-time activities for severely mentally handicapped adolescents and a survey of 214 families yielded the information that although national provision appeared to be reasonably comprehensive, this was not reflected in the restricted use of leisure locally. The young people involved in the survey mainly participated in solitary, passive activities which were family orientated with the exception of attendance at Special clubs. It is suggested that the following factors contribute to this present state of affairs: Firstly, the attitude of patients who have so fully accepted their role as sole providers of care and recreation that they are unaware of the long-term consequences or "problems" in this area; Secondly, it is suggested that the lack of local friendships outside the school environment restricts the development of social activities; Thirdly, that lack of basic skills further restricts the choice of activities open to these young people.


Hypertension screening in a salami factory: a worksite hypertension study.
The prevalence, awareness and control of hypertension are important epidemiological research topics worldwide. The screening of hypertension in a workplace has some special aspects. We have screened the employees in a Hungarian salami factory (Pick Salami Factory, Szeged, Hungary) for hypertensives. In a cross-sectional survey, the blood pressure (BP) was measured with an instrument meeting accepted measuring principles (BP-TRU BP) and a questionnaire was filled. In all, 1012 factory workers were screened (600 male and 412 female) and 25.7% of the workers proved to be hypertensives. Of these, 61.5% of the hypertensive employees were aware that their BP is high. Among the treated hypertensives, 21.9% were controlled. These results suggest that the efficacy of the management of hypertension in Hungary cannot be solely responsible for the high cardiovascular morbidity and mortality. The improvement of the management of hypertension should decrease the cardiovascular risk in the hypertensive population. The worksite screening and follow-up of hypertension seem to be logical health service solutions. This has been proven to be cost-effective.


Il-12: keeping cell-mediated immunity alive.
Interleukin (IL)-12 has dominated the field of cell-mediated immunity since its discovery more than 10 years ago, and clearly plays an essential role in the development of Th1 cells under a variety of conditions. Recent studies now indicate that the importance of IL-12 is not limited to initiating an immune response, but may contribute to maintaining immunity. Thus, Th1 responses rapidly wane in the absence of IL-12, leading to a loss in protective immunity against intracellular pathogens, such as Leishmania and Toxoplasma. Determining how IL-12 maintains Th1 cells, and consequently cell-mediated immunity, will provide new insights useful in controlling the immune response, and may thus influence the design of new vaccines and immunotherapies.


Human T cell leukemia virus type I-induced disease: pathways to cancer and neurodegeneration.
Retroviral infection is associated with a number of pathologic abnormalities, including a variety of cancers, immunologic diseases, and neurologic disorders. Shortly after its discovery in 1980, human T cell leukemia virus type I (HTLV-I) was found to be the etiologic agent of both adult T cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurologic disease characterized by demyelinating lesions in both the brain and the spinal cord. Approximately 5-10% of HTLV-I-infected individuals develop either ATL or HAM/TSP. Interestingly, the two diseases have vastly different pathologies and have rarely been found to occur within the same individual. While a number of host and viral factors including virus strain, viral load, and HLA haplotype have been hypothesized to influence disease outcome associated with HTLV-I infection, the relative contributions of such factors to disease pathogenesis have not been fully established. Recent research has suggested that the route of primary viral infection may dictate the course of disease pathogenesis associated with HTLV-I infection. Specifically, mucosal exposure to HTLV-I has been associated with cases of ATL, while primary viral infection based in the peripheral blood has been correlated with progression to HAM/TSP. However, the cellular and molecular mechanisms regulating disease progression resulting from primary viral invasion remain to be elucidated. Although a variety of factors likely influence these mechanisms, the differential immune response mounted by the host against the incoming virus initiated in either the peripheral blood or the mucosal compartments likely plays a key role in determining the outcome of HTLV-I infection. It has been proposed that the route of infection and size of the initial viral inoculum allows HTLV-I to infect different target cell populations, in turn influencing the breadth of the immune response mounted against HTLV-I and affecting disease pathogenesis. A model of HTLV-I-induced disease progression is presented, integrating information regarding the role of several host and viral factors in the genesis of both neoplasia and neurologic disease induced following HTLV-I infection, focusing specifically on differential viral invasion into the bone marrow (BM) and the influence of this event on the virus-specific CD8(+) cytotoxic T lymphocyte (CTL) response that is initiated following HTLV-I infection.


Nonsurgical removal of a kinked right coronary catheter.
Cardiac catheterization is a commonly performed procedure affording valuable data. Catheter related complications such as catheter knotting, fracture, and collapse have been reported. Occasionally surgery is needed to extricate an entrapped catheter when nonsurgical means are unsuccessful. We describe a case of kinking of a right coronary catheter during transfemoral coronary arteriography, so that the catheter could not be withdrawn. A simple, nontraumatic method facilitated removal of the kinked catheter and permitted completion of the procedure, obviating the need for surgery.


Gains and losses of the XII-VII component of the "baby-sitter" procedure: a morphometric analysis.
The classic hypoglossal transfer to the facial nerve is invariably followed by complications caused by tongue atrophy. In 1984, Terzis introduced the "baby-sitter" procedure which involved a formal cross-facial procedure, in addition to partial neurectomy of the hypoglossal nerve, and an end-to-side coaptation with the ipsilateral facial nerve. This reported study provides, for the first time, quantification of the number of hypoglossal motor fibers needed to successfully restore eye sphincter function, using an end-to-side coaptation with preservation of the tongue. Thirty adult Sprague-Dawley rats were divided into six groups: control, denervated, perineurial window, 20 percent partial neurectomy (PN), 40 percent PN, and 80 percent PN. The procedure involves interposing a nerve graft (saphenous) between the partially severed XII nerve and the upper zygomatic branch of the facial nerve. Evaluation of the behavioral data (blink reflex) revealed good-to-superb return of the blinking mechanism in the 40 percent group, without significant tongue atrophy. Electrophysiologic data in the 40 percent neurectomy group demonstrated superiority to the other groups. Quantitative axonal morphometry of the coaptation sites and graft, as well as motor end-plates of the orbicularis oculi muscle and tongue showed the 40 percent partial neurectomy group to be the optimal group.


Learning curve of the Inoue technique of percutaneous mitral balloon valvuloplasty.
There is controversy as to whether the double-balloon or the Inoue technique of percutaneous mitral balloon valvuloplasty (PMBV) provides superior immediate and long-term results. This study was undertaken to analyze the effect of the learning curve of the Inoue technique of PMBV in the immediate and long-term outcome of PMBV. The learning curve of Inoue PMBV was analyzed in 233 Inoue PMBVs divided into 2 groups: "early experience" (n = 100) and "late experience" (n = 133). The results of the overall Inoue technique were compared with those of 659 PMBVs performed with the double-balloon technique. Baseline clinical and morphologic characteristics between early and late experience Inoue groups were similar. Post-PMBV mitral valve area (1.89 +/- 0.56 vs 1.69 +/- 0.57 cm(2); p = 0.008) and success rate (60% vs 75.9%; p = 0.009) were significantly higher in the late experience Inoue group. Furthermore, there was a trend for less incidence of severe post-PMBV mitral regurgitation > or = 3+ in the late experience group (6.8% vs 12%; p = 0.16). Although the post-PMBV mitral valve area was larger with the double-balloon technique (1.94 +/- 0.72 vs 1.81 +/- 0.58 cm(2); p = 0.01), the success rate (71.3% vs 69.1%; p = NS), incidence of > or = 3+ mitral regurgitation (9% vs 9%), in-hospital complications, and long-term and event-free survival were similar with both techniques. In conclusion, there is a significant learning curve of the Inoue technique of PMBV. Both the Inoue and the double-balloon techniques are equally effective techniques of PMBV because they resulted in similar immediate success, in-hospital adverse events, and long-term and event-free survival.