Borrelia burgdorferi in ticks of the Canton Tessin (Switzerland).
In the northern Alps it is hard to find an Ixodes ricinus population which does not harbour Borrelia burgdorferi. The infection rates range from 5 to 34% for adults and nymphs to 3.1% for larvae. This study shows that the infection rates on the southern side of the Alps are similar, at 25% for adults, 36.2% for nymphs and 3.2% for larvae. With respect to tick species other than I. ricinus, we did not succeed in finding any spirochetes in Dermacentor marginatus, Haemaphysalis punctata, Ixodes hexagonus, Rhipicephalus sanguineus.


Prediction of standing height among Israeli older adults: results from a national survey.
An accurate measurement of full height while standing is sometimes not possible among older adults, in particular among the frail elderly. For such cases, the use of knee height (KH) and ulna bone length (UL) has been suggested for standing height estimation. Studies have shown that predictive equations of height were ethnic-specific. This study attempted to develop representative equations to predict standing height based on KH, UL and waist circumference (WC) for older adult Israeli women and men. A random sample of 1500 older adults (aged 74.48 ± 6.09 years old). Participants were interviewed in their homes and measurements of Standing height, KH, UL and WC were taken. A quadratic regression analysis, for each sex separately, was performed to predict standing height based on age, KH, UL and WC. The adjusted r (2) standing height prediction equations were 0.51 and 0.67 for women and men, respectively. The prediction of the standing height of frail elderly Israelis, by KH, UL, WC and age, may be an alternative method when actual standing height is difficult or not possible to measure.


Implantable diagnostic monitors in the early assessment of syncope and collapse.
The implantable diagnostic monitor, or loop recorder (ILR) is a subcutaneous monitor capable of continuous ECG monitoring up to 3 years. It is an elegant investigative tool for the assessment of patients with recurrent, unexplained syncope in whom an arrhythmic cause needs to be excluded, and is now increasingly utilised very early in the diagnostic work-up of these patients, in line with current guidelines. This review examines the evidence underpinning these recommendations as well as the relevant clinical trials evaluating the use of the ILR in syncope. Continued research will be needed to validate its role as a first line investigation in a sub-select of syncopal patients, especially with the addition of remote monitoring capabilities.


IgG from patients with antiphospholipid syndrome binds to platelets without induction of platelet activation.
The clinical manifestations of the antiphospholipid syndrome (APLS) include arterial and venous thrombosis, thrombocytopenia and fetal loss, but the pathogenic mechanisms remain unclear. It has been hypothesized that platelet activation by autoantibody may be a pathogenic mechanism. We studied IgG binding, microparticle (mp) formation and P-selectin expression by flow cytometry in normal platelets after incubation in serum from 11 patients with antiphospholipid antibodies and that from 10 normal healthy subjects. Levels of platelet-associated IgG were significantly higher after incubation in patient sera (mean 17.2, range 2.0-75.0%) compared with normal sera (mean 2.0, range 1.2-3.7%, P<0.05). Incubation of normal platelets in serum led to increased microparticle formation (P<0.01) and P-selectin expression (P < 0.05), compared with unstimulated platelets. There was no significant difference, however, between microparticle formation nor P-Selectin expression induced by patient serum (mp 3.0 (1.6-5.0)%; P-selectin 8.0 (4.0-16.6)%) versus normal serum (mp 3.2 (2.1-4.5)%; P-selectin 10.1 (4.0-15.6); median (range)). Pre-activation of platelets with sub-threshold ADP concentrations or thrombin receptor activator peptide resulted in a small increase in microparticle formation, but there was still no significant difference between the effects of patient and control sera. Despite the presence of platelet membrane binding IgG in serum from 5/11 patients with antiphospholipid antibodies, there was no evidence for associated enhanced platelet-activating ability. This study supports antiplatelet reactivity in antiphospholipid syndrome, but not a direct platelet-activating role for platelet-directed autoantibodies.


Withdrawal of statins and risk of subarachnoid hemorrhage.
Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH. We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date. During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.


Chronic hypoxia increases staurosporine sensitivity of pulmonary artery smooth muscle to endothelin-1.
Endothelins (ET) have been implicated in the pathogenesis of hypoxia-induced pulmonary hypertension. We evaluated the contribution of protein kinase C (PKC) to the ET-1 response of isolated endothelium-denuded extralobar pulmonary artery (PA) from rats exposed to chronic hypoxia (10% O2-90% N2, 1 ATM, 14 days or 28 days) or air. Hypoxia increased hematocrit (Hct [% above air control]: at 14 days, by 28+/-2%; after 28 days to 33+/-2%) and the mass ratio of right ventricle over left ventricle plus septum (RV/LV+S [% above air control]: at 14 days, by 54+/-1%; after 28 days to 114+/-13%), an index of right ventricle hypertrophy. Hypoxic exposure for 14 days and 28 days decreased PA sensitivity to ET-1 (change in EC50: 14 days, four-fold; 28 days, two-fold vs. air controls) and transiently decreased the magnitude of maximum ET-1-induced contraction (Emax [% decrease from control]: 14 days, 53+/-6%; 28 days, 23+/-6%). Staurosporine, a PKC inhibitor, decreased ET-1 sensitivity of PA from 0, 14, and 28 days air-exposed rats by four- to nine-fold without affecting Emax. However, staurosporine markedly decreased hypoxic PA sensitivity to ET-1 (change in EC50: 14 days, 1700-fold; 28 days, 55-fold vs. hypoxic controls) and decreased Emax (% decrease from hypoxic control: 14 days, 38+/-6%; 28 days, 59+/-7%). In conclusion, hypoxic exposure time-dependently varies the responsiveness of PA smooth muscle to ET-1 and may modulate the contribution of PKC activation.


Development of a reaction-limited model of dissolution: application to official dissolution tests experiments.
A reaction-limited model for drug dissolution is developed assuming that the reaction at the solid-liquid interface is controlling the rate of dissolution. The dissolution process is considered as a bidirectional chemical reaction of the undissolved drug species with the free solvent molecules, yielding the dissolved species of drug complex with solvent. This reaction was considered in either sink conditions, where it corresponds to the unidirectional case and the entire amount of the drug is dissolved, or reaching chemical equilibrium, which corresponds to saturation of the solution. The model equation was fitted successfully to dissolution data sets of naproxen and nitrofurantoin formulations measured in the paddle and basket apparatuses, respectively, under various experimental conditions. For comparative purposes these data were also analyzed using three functions based on the diffusion layer model. All functions failed to reveal the governing role of saturation solubility in the dissolution process associated with the diffusion layer model when the conditions for the valid estimation of saturation solubility, established theoretically in this study, were met by the experimental set up employed. Overall, the model developed provides an interesting alternative to the classic approaches of drug dissolution modeling, quantifying the case of reaction-limited dissolution of drugs.


Asymptomatic metastasis to cricoid from prostate carcinoma: an incidental finding detected on 18F-choline PET/CT.
Metastases to the larynx from prostate carcinoma are rare. We describe a case of asymptomatic prostate carcinoma metastasis to the right cricoid cartilage detected on 18F-fluorocholine PET/CT. This was histologically proven on open biopsy and the patient was offered local radiotherapy.


13-week subchronic toxicity study with morpholine oleic acid salt administered to B6C3F1 mice.
The effect of subchronic administration of morpholine oleic acid salt (MOAS) was studied in B6C3F1 mice. The dose levels of MOAS used were 0%, 0.15%, 0.3%, 0.6%, 1.25%, and 2.5% in drinking water. Reduced weight gains were noted in both sexes in the 2.5% group as compared to controls, but reductions were not significant. Water consumption values showed a dose-related tendency for a decrease in both females and males. Urine analysis showed significant elevation of specific gravity in the males in the 0.6%, 1.25%, and 2.5% groups and the females in the 1.25% and 2.5% groups. Significant elevation of plasma urea nitrogen was observed in males of the 1.25% and 2.5% groups and in females of the 0.6%, 1.25%, and 2.5% groups. The relative weight of the kidneys showed a dose-dependent increase that was statistically significant for the 1.25% and 2.5% MOAS groups in both sexes. Except for cloudy swelling of the proximal tubules of the kidneys in mice on the 2.5% regimen, no treatment-related histopathological alterations were observed in organs of either sex.


Thermal tolerance and repair of thermal damage by cultured cells.
Exposure of hamster cells to 42.5 degrees C for long periods leads to the development of thermal tolerance; the slope of the survival curve become shallower after about 3.5 to 4 hours. If two 4-hour exposures at 42.5 degrees C are separated by various periods of time, thermal tolerance is eliminated by 20 hours. Prolonged exposure at 42.5 degrees C offers considerable protection from subsequent treatments to acute hyperthermia at 45 degrees C indicate or in conditioned medium or balanced salt solution failed to reveal any evidence of repair of potentially lethal damage.


Circulation of eastern equine encephalitis, western equine encephalitis, Ilhéus, Maguari and Tacaiuma viruses in equines of the Brazilian Pantanal, South America.
Neutralizing antibodies to EEE (6.7%), WEE (1.2%), ILH (26.6%), MAG (28.2%) and TCM (15.7%) viruses were found in sera of 432 equines of the Brazilian Pantanal, area where undiagnosed horse deaths are frequently observed. A 4-fold rise in CF titer to EEE virus was detected in acute and convalescent sera of an encephalitis horse sacrificed in 1992. Antibodies to EEE, ILH, MAG and TCM viruses were detected in horses less than 2 years old indicating recent circulation of these viruses in the Pantanal. The evidence of recent equine encephalitis associated with rising CF titer to EEE warrants a more intensive study with attempts to isolate virus from horses with clinical manifestations of encephalitis.


Isolated basilar artery occlusion associated with a clivus fracture.
Most vascular injuries to the brain secondary to blunt head trauma involve the internal carotid circulation. A case of isolated basilar occlusion secondary to a clival fracture is described and compared to three other cases in the literature.


A new paraneoplastic encephalomyelitis autoantibody reactive with the axon initial segment.
Serum from a patient with paraneoplastic encephalomyelitis (PEM) and small cell lung cancer (SCLC) showed high titer immunohistochemical staining of the axon initial segment (AIS) on rat and human brain sections. EM studies showed that the antigen was localized in close proximity of the microtubules in the AIS. Double labeling experiments and absence of staining at the nodes of Ranvier excluded the previously identified betaIV spectrin as autoantigen. Screening a rat hippocampal cDNA library resulted in the isolation of ubiquitin-conjugating enzyme E2E1 (UBE2E1). However, blocking and elution experiments excluded UBE2E1 as the AIS autoantigen.


Studying the social construction of cancer-related fatigue experience: the heuristic value of Ethnoscience.
Patients' lived experience of illness and health is receiving increased attention in the medical field. Understanding patients' perspective and experiences is an undoubted asset for efficient health interventions and improved clinical concordance. Patients' experiences of care and cure, however, are influenced by the cultural setting in which these experiences take place. This implies that health interventions should be "ecological" and attuned to the specific sociocultural context of the patients. Our research group is conducting a cross-cultural qualitative study aimed ad exploring how fatigue (a symptom very common in cancer) is perceived and manifested by patients in different countries (Canada, Thailand, England and Italy). In order to achieve this, the study was design according to the method of Ethnoscience, that appeared to us the best suited to explore the meanings that patients attribute to their state and the linguistic patterns they use to describe it. In this paper we will describe in details the process of Ethnoscience and will discuss the heuristic value of this research approach. Ethnoscience was an effective research strategy for exploring how beliefs and values shape symptoms and the behavioural manifestations of cancer related fatigue. This paper discusses the heuristic value of Ethnoscience and its applicability to the study of health relate topics, particularly those where issues of social construction are important. Ethnoscience is a promising and innovative research approach, able to cast light on the way people experience and make sense of their illness.


Surgical and oncological safety of nipple-sparing mastectomy in an Asian population.
Nipple-sparing mastectomy (NSM) allows for excellent postmastectomy reconstruction aesthetics and is used for both therapeutic and risk-reducing purposes. Reservations regarding the potential for locoregional recurrence and concerns about nipple-areolar complex (NAC) necrosis remain amongst many surgeons. We review the surgical and oncological outcomes after NSM in our institution. All NSM cases at the National Cancer Centre Singapore and Singapore General Hospital between 2005 and 2015 were reviewed. Tumour characteristics, reconstruction methods, surgical and oncological outcomes are described. A total of 139 NSMs were performed for 130 patients. The median age was 46 years (range 21-66). The use of NSM increased from 2% of all breast reconstructions in 2005 to 37% in 2015. The majority (n = 119; 86%) were for cancer treatment and 20 (14%) for risk-reducing purposes. Among those performed for cancer, patients mainly had early stage breast cancer (n = 106, 89%). Autologous reconstruction (n = 111, 80%) was most common. Early complications requiring surgical intervention occurred in 24 (17%) NSMs, including 9 partial/complete flap loss and 2 complete NAC loss. Smoking, previous breast radiation and periareolar incision were all not associated with a higher re-intervention rate (p = 0.93, 0.41 and 0.91, respectively). Median follow-up was 43 months (range 5-145). Five patients (4%) developed local recurrence, including 2 NAC recurrences. The 2- and 5-year overall survival rate is 97 and 90%, respectively. NSM is an oncologically safe procedure in selected patients with acceptable low complication rates.


The PI3K/Akt1-FoxO1 Translocation Pathway Mediates EXf Effects on NIT-1 Cell Survival.
EXf, a glucagon-like peptide 1 (GLP-1) receptor agonist, stimulates β-cell proliferation and reduces apoptosis in diabetic animal models, but the underlying mechanisms are not fully understood. We constructed a FoxO1-GFP fusion protein expression plasmid and transiently transfected it into NIT-1 cells to investigate whether FoxO1 mediates EXf effects on NIT-1 cell survival. Our results showed that EXf could increase cell viability by inhibiting apoptosis and stimulating proliferation, and it could also promote the translocation of the FoxO1-GFP fusion protein from the nucleus to the cytoplasm in NIT-1 cells. However, the above effects of EXf were suppressed by the inhibitor of PI3K. Comparative transcription analysis showed up-regulation of igf-1r, irs-2, pI3k, akt1 and pdx-1 in NIT-1 cells after EXf treatment. Moreover, the up-regulation of PI3K and phosphorylation of Akt1 upon EXf treatment was confirmed by Western blot, both phenomena were abrogated by wortmannin, an inhibitor of PI3K. In summary, FoxO1 may mediate the effects of EXf on NIT-1 cell survival by activating the PI3K/Akt1 pathway.


Chronic obstructive pulmonary disease history assessment in Spain: a multidimensional chronic obstructive pulmonary disease evaluation. Study methods and organization.
This present paper describes the method and the organization of the study known as the COPD History Assessment In SpaiN (CHAIN), whose main objective is to evaluate the long-term natural history of a chronic obstructive pulmonary disease (COPD) patient cohort from a multidimensional standpoint and to identify clinical phenotypes, in comparison with another non-COPD control cohort. CHAIN is a multicenter, observational study of prospective cohorts carried out at 36 Spanish hospitals. Both cohorts will be followed-up during a 5-year study period with complete office visits every 12 months and telephone interviews every 6 months in order to evaluate exacerbations and the vital state of the subjects. The recruitment period for cases was between 15 January 2010 and 31 March 2012. At each annual visit, information will be collected on: (i) clinical aspects (socio-economic situation, anthropometric data, comorbidities, smoking, respiratory symptoms, exacerbations, quality of life, anxiety-depression scale, daily life activities, treatments); (ii) respiratory function (spirometry, blood gases, hyperinflation, diffusion, respiratory pressures); (iii) BODE index (main study variable); (iv) peripheral muscle function, and (v) blood work-up (including IgE and cardiovascular risk factors). In addition, a serum bank will be created for the future determination of biomarkers. The data of the patients are anonymized in a database with a hierarchical access control in order to guarantee secure information access. The CHAIN study will provide information about the progression of COPD and it will establish a network of researchers for future projects related with COPD.


Establishing Feasibility of Early Palliative Care Consultation in Pediatric Hematopoietic Stem Cell Transplantation.
Children and adolescents undergoing hematopoietic stem cell transplantation (HSCT) encounter a number of distressing physical symptoms and existential distress but may not be afforded timely access to palliative care services to help ameliorate the distress. This feasibility study investigated the acceptability and outcomes of early palliative care consultation to promote comfort in this population. A longitudinal, descriptive cohort design examined both provider willingness to refer and willingness of families to receive palliative care interventions as well as satisfaction. Feasibility was demonstrated by 100% referral of eligible patients and 100% of patient and family recruitment (N = 12). Each family received 1 to 3 visits per week (ranging from 15 to 120 minutes) from the palliative care team. Interventions included supportive care counseling and integrative therapies. Families and providers reported high satisfaction with the nurse-led palliative care consultation. Outcomes included improvement or no significant change in comfort across the trajectory of HSCT, from the child and parental perspective. Early integration of palliative care in HSCT is feasible and acceptable to families and clinicians.


Effects of feeding diets containing increasing content of corn distillers dried grains with solubles to grower-finisher pigs on growth performance, carcass composition, and pork fat quality.
Crossbred pigs (n = 512) with an average initial BW of 22.1 +/- 0.54 kg were used to evaluate growth performance, carcass characteristics, and pork fat quality of grower-finisher pigs fed corn-soybean meal diets containing increasing content of distillers dried grains with solubles (DDGS). One of 4 dietary treatments was randomly assigned to each pen within sex. Dietary treatment and sex were the main factors in a 3-phase feeding program (BW = 22 to 53 kg, 53 to 85 kg, and 85 to 115 kg). Dietary treatments consisted of a corn-soybean meal control, or a corn-soybean meal diet containing 10, 20, or 30% DDGS. Overall, increasing the dietary DDGS content had no effect on ADG (P = 0.74), but ADFI was linearly reduced and G:F was linearly increased (P < 0.01). Dressing percentage, LM marbling and firmness, and belly firmness were linearly reduced (P < 0.01), but percentage of fat-free lean was linearly increased (P < 0.05) with increasing dietary DDGS. Subjective LM color score (P = 0.65), drip loss (P = 0.37), and ultimate pH of LM (P = 0.21) were not influenced by dietary DDGS. Japanese color scores for backfat (P = 0.41) and belly fat (P = 0.85) were similar among dietary treatments (P = 0.41). Feeding an increasing content of DDGS linearly increased (P < 0.05) PUFA concentration, particularly linoleic acid (C18:2), in belly fat, backfat, and LM intramuscular fat, but the increase in LM intramuscular fat was smaller in magnitude (P < 0.05) than in backfat and belly fat. Pigs fed an increasing content of DDGS had a linear increase (P < 0.05) in the iodine value of backfat, belly fat, and LM intramuscular fat of 58.4 to 72.4, 61.5 to 72.3, and 54.8 to 57.7, respectively. Oxidation of LM intramuscular fat measured on d 0, 14, 21, and 28 of storage was not affected by dietary treatment. Taste tests for LM showed no effects of diet on flavor, off-flavor (P = 0.36), tenderness (P = 0.66), juiciness (P = 0.58), and overall acceptability (P = 0.52) scores. Similarly, bacon flavor (P = 0.88), off-flavor, crispiness, and overall liking scores were not affected by increasing dietary DDGS, but bacon fattiness (P < 0.01) and tenderness (P < 0.05) scores were linearly reduced. These results showed no negative effects on growth performance or dressing percentage when growing-finishing pigs were fed diets containing up to 30% DDGS, but fat quality may not meet the standards of all pork processors when feeding diets containing more than 20% DDGS.


Characterization of Enterobius vermicularis in a human population, employing a molecular-based method from adhesive tape samples.
Human infection with the parasitic nematode Enterobius vermicularis occurs worldwide, particularly in children. Although its prevalence may exceed 35% in some parts of the world, molecular studies of E. vermicularis in humans are limited. The aim of the present study was to investigate the genetic variation within E. vermicularis in a human population. For this purpose, 77 adhesive tape samples taken from Greek children infested with E. vermicularis were tested. New primers were designed to amplify a segment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of E. vermicularis from adhesive tape samples. Thirty-six amplicons were sequenced and eleven different haplotypes were identified. All sequences clustered within the type previously characterized (type B), only reported to date from captive chimpanzees. To the best of our knowledge, this is the first study of E. vermicularis genotypes from a human population.


Relationship between pericardial pressure and lymphatic pericardial fluid transport in sheep.
We investigated the relationship between pericardial pressure and the volumetric lymphatic clearance rate of pericardial fluid in sheep. A single catheter perfusion system was established to deliver tracer to the pericardial cavity and control pericardial pressure. In addition, catheters were placed into the thoracic duct and into the jugular vein at the base of the neck. (125)I-human serum albumin (HSA) was administered into the pericardial perfusate to serve as the lymph flow marker and its concentration monitored in the effluent from the outflow end of the perfusion system. (131)I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, estimates of total pericardial clearance into lymphatics increased significantly as pericardial pressures were elevated in 2. 5 cm H(2)O increments from 2.5 to 12.5 cm H(2)O (P = 0.018). Pericardial lymph transport ranged from 0.89 +/- 0.10 to 3.09 +/- 0. 66 ml/h at 2.5 and 12.5 cm H(2)O pericardial pressure, respectively. The majority of transport occurred through mediastinal vessels with a small proportion (10.3 to 23.9%) being cleared into lymphatics leading to the thoracic duct. We conclude that lymphatic pericardial fluid transport increases approximately 3.5-fold over a pericardial pressure range that encompasses the transition between the shallow and steep portions of the pericardial pressure-volume relationship.


Paying Attention or Paying Too Much in Medicare Part D.
We study whether people became less likely to switch Medicare prescription drug plans (PDPs) due to more options and more time in Part D. Panel data for a random 20 percent sample of enrollees from 2006--2010 show that 50 percent were not in their original PDPs by 2010. Individuals switched PDPs in response to higher costs of their status quo plans, saving them money. Contrary to choice overload, larger choice sets increased switching unless the additional plans were relatively expensive. Neither switching overall nor responsiveness to costs declined over time, and above-minimum spending in 2010 remained below the 2006 and 2007 levels.


Unintended outcomes of medicaid drug cost-containment policies on the chronically mentally ill.
Cost-containment policies frequently focus on reducing drug expenditures, although prescription drug costs are a relatively small proportion of total health care expenditures. Data show that very few drug cost-containment policies can selectively reduce unneeded care while maintaining essential care. In the early 1980s, the New Hampshire Medicaid program introduced a drug-payment limit (a "cap") that set the number of reimbursable medications a patient could receive per month at 3. Analyses reviewed in this article indicate that New Hampshire's drug cap, while in effect, reduced the use of prescription drugs among the elderly and the mentally ill but increased hospital and nursing home admissions, partial hospitalizations, distribution of psychoactive medications by community mental health centers, and use of emergency mental health services. Vulnerable populations are most likely to experience adverse effects from hastily-applied drug cost-containment policies, and resulting compensatory measures may create more expenses than the policy removes.


Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1.
The Notch genes encode single-pass transmembrane receptors that transduce the extracellular signals responsible for cell fate determination during several steps of metazoan development. The mechanism by which extracellular signals affect gene transcription and ultimately cell fate decisions is beginning to emerge for the Notch signalling pathway. One paradigm is that ligand binding to Notch triggers a Presenilin1-dependent proteolytic release of the Notch intracellular domain from the membrane, resulting in low amounts of Notch intracellular domain which form a nuclear complex with CBF1/Su(H)/Lag1 to activate transcription of downstream targets. Not all observations clearly support this processing model, and the most rigorous test of it is to block processing in vivo and then determine the ability of unprocessed Notch to signal. Here we report that the phenotypes associated with a single point mutation at the intramembranous processing site of Notch1, Val1,744-->Gly, resemble the null Notch1 phenotype. Our results show that efficient intramembranous processing of Notch1 is indispensable for embryonic viability and proper early embryonic development in vivo.


Post-receptorial mechanisms underlie functional disregulation of beta2-adrenergic receptors in lymphocytes from Multiple Sclerosis patients.
Increased density of beta2-adrenergic receptors has been demonstrated on peripheral blood mononuclear cells (PBMCs) from Multiple Sclerosis (MS) patients. In this study we found that isoproterenol reduces T-cell proliferation and IFNgamma secretion in PBMCs cultures from healthy controls and IFNbeta-treated but not untreated MS patients. Reduced expression levels of G protein coupled receptor kinase (GRK)2/3 (p < 0.05) and increased isoproterenol-induced cAMP accumulation (p < 0.0001) were found in PBMCs from all MS patients. Dibutyryl cAMP reduced the proliferation of PBMCs from all subgroups but in a slighter manner in untreated MS patients. We conclude that signalling through beta2-adrenergic receptors is chronically up-regulated but functionally uncoupled to immunoregulatory functions of lymphocytes from MS patients. Disregulation downstream the cAMP-associated signalling may underlie such a phenomenon.


[The effect of strontium-89 therapy in a patient with cholangiocellular carcinoma].
A 77-year-old man was diagnosed as having cholangiocellular carcinoma. The patient underwent partial right hepatectomy in June 2008, and multiple bone metastases occurred approximately 9 months after surgery. He refused salvage chemotherapy and radiation therapy. Although he had been treated with opiate analgesics, he was unable to sit up owing to severe pain in the left ilium. He was hospitalized because of buttock pain and left leg numbness. Even a combination of fentanyl patch, gabapentin, and subarachnoid block was ineffective in controlling pain. Strontium-89 (89Sr) therapy was successful in eliminating the intractable pain, and there were no serious side effects during therapy. The patient was discharged from the hospital, and he received palliative care at home for a short period.


Interpersonal communications and telemedicine: hypotheses and methods.
Demonstration interviews between a psychiatrist who has used videolinks for a range of clinical interactions and a simulated patient facilitate a better understanding of interpersonal communication, both face to face and mediated. This might allow users to be trained to maximize the use of the available communications technology and provide a source of more rational reassurance for the technophobic professional.


Cancer incidence and mortality after treatment with folic acid and vitamin B12.
Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk. To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials. Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007. Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721). Cancer incidence, cancer mortality, and all-cause mortality. During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B(12) vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B(12) vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B(12) vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12). Vitamin B(6) treatment was not associated with any significant effects. Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods. clinicaltrials.gov Identifier: NCT00671346.


Cellular and segmental distribution of Ca2(+)-pump epitopes in rat intestine.
We used a monoclonal antibody (5F10) specific for the human erythrocyte plasma membrane Ca(++)-pump to demonstrate the presence and distribution of Ca(++)-pump epitopes in rat intestine. In paraffin embedded tissue sections, antibody 5F10 binds to epitopes in the basolateral membranes of absorptive cells in rat duodenum and portions of jejunum but not ileum. Western blot analysis of intestinal mucosal proteins with antibody 5F10 shows binding of antibody to major bands of Mr approximately 135,000 and Mr approximately 72,000, and to lesser bands of Mr approximately 125,000 and Mr approximately 27,000. This pattern was seen in mucosal homogenates of rat duodenal and jejunal cells and to a lesser extent in ileal cells. The Mr approximately 135,000 band corresponds to the molecular weight of Ca(++)-pumps in other tissues. The other bands correspond in size to known proteolytic fragments of the Ca(++)-pump. Slot-blot analysis of nitrocellulose immobilized mucosal homogenates shows binding of 5F10 to be greatest in duodenum and least in ileum. Ca(++)-transport studies by the everted gut sac technique show a correlation between vitamin D induction of active Ca(++)-transport and the segmental distribution of Ca(++)-pump epitopes.


Pressure sores: adopting the principles of risk management.
This article examines the continuing problem of pressure sores in the NHS from a purchasing and a providing manager's perspective. Risk management and the need for clinical effectiveness in treatment and prevention strategies are discussed. Reporting systems are advocated as a means to estimate risk and to form a store of information that will enable a response to made when problem areas are identified. Nursing advice and input into the contracting process is vital. The need for purchasers and NHS managers to work together to ensure that effective interventions are implemented to reduce both the financial burden on the NHS and the physiological insult offered to patients is stressed.


Towards a general theory of driver behaviour.
Taylor [Taylor, D.H., 1964. Drivers' galvanic skin response and the risk of accident. Ergonomics 7, 439-451] argued that drivers attempt to maintain a constant level of anxiety when driving which Wilde [Wilde, G.J.S., 1982. The theory of risk homeostasis: implications for safety and health. Risk Anal. 2, 209-225] interpreted to be coupled to subjective estimates of the probability of collision. This theoretical paper argues that what drivers attempt to maintain is a level of task difficulty. Naatanen and Summala [Naatanen, R., Summala, H., 1976. Road User Behaviour and Traffic Accidents. North Holland/Elsevier, Amsterdam, New York] similarly rejected the concept of statistical risk as a determinant of driver behaviour, but in so doing fell back on the learning process to generate a largely automatised selection of appropriate safety margins. However it is argued here that driver behaviour cannot be acquired and executed principally in such S-R terms. The concept of task difficulty is elaborated within the framework of the task-capability interface (TCI) model, which describes the dynamic interaction between the determinants of task demand and driver capability. It is this interaction which produces different levels of task difficulty. Implications of the model are discussed regarding variation in performance, resource allocation, hierarchical decision-making and the interdependence of demand and capability. Task difficulty homeostasis is proposed as a key sub-goal in driving and speed choice is argued to be the primary solution to the problem of keeping task difficulty within selected boundaries. The relationship between task difficulty and mental workload and calibration is clarified. Evidence is cited in support of the TCI model, which clearly distinguishes task difficulty from estimates of statistical risk. However, contrary to expectation, ratings of perceived risk depart from ratings of statistical risk but track difficulty ratings almost perfectly. It now appears that feelings of risk may inform driver decision making, as Taylor originally suggested, but not in terms of risk of collision, but rather in terms of task difficulty. Finally risk homeostasis is presented as a special case of task difficulty homeostasis.


Differentiation of human embryonic stem cells into smooth muscle cells in adherent monolayer culture.
Smooth muscle cell (SMC) plays critical roles in many human diseases, an in vitro system that recapitulates human SMC differentiation would be invaluable for exploring molecular mechanisms leading to the human diseases. We report a directed and highly efficient SMC differentiation system by treating the monolayer-cultivated human embryonic stem cells (hESCs) with all-trans retinoid acid (atRA). When the hESCs were cultivated in differentiation medium containing 10microM RA, more than 93% of the cells expressed SMC-marker genes along with the steadily accumulation of such SMC-specific proteins as SM alpha-actin and SM-MHC. The fully differentiated SMCs were stable in phenotype and capable of contraction. This inducible and highly efficient in vitro human SMC system could be an important resource to study the mechanisms of SMC phenotype determination in human.


Substrate and method dependent inhibition of three ABC-transporters (MDR1, BCRP, and MRP2).
Drug transport and drug-drug interactions (DDI) with human ABC transporters are generally investigated in mammalian cell lines or inverted membrane vesicles from insect cells (Sf9) overexpressing the transporter of interest. In this study, we instead used membrane vesicles from human embryonic kidney cells (HEK293) overexpressing wild type MDR1/Pgp (ABCB1), BCRP (ABCG2), and MRP2 (ABCC2) with the aim to study the concentration dependent inhibition of shared and prototypic probe substrates. We first investigated 15 substrates and identified estrone-17-beta-glucorinide (E17G) as shared substrate. Nine specific and general inhibitors were then studied using E17G and prototypic probe substrates. The results were compared with those previously obtained in Sf9 vesicles and cell lines of canine (MDCKII) and human (Saos-2) origin. For the majority of inhibitors, Ki values differed <10-fold between E17G and probe substrates. Significant differences in Ki values were observed for about one third of the inhibitors. The transport inhibition potencies in HEK293 vesicles were in good agreement with those obtained in Sf9 vesicles. Large differences were found in the inhibition potencies observed in the vesicular systems compared to the cellular systems. Nevertheless, the rank order correlations between the different experimental systems were generally good. Our study provides further information on substrate dependent inhibition of ABC-transporters, and suggests that simple ranking of compounds can be used as a tier one approach to bridge results obtained in different experimental systems.


Inhibition of heat-induced phosphorylation of stathmin by the bioflavonoid quercetin.
Effects of quercetin on heat-induced phosphorylation of stathmin in JURKAT cells were examined. Two-dimensional electrophoresis of stathmin showed that heat shock increases mono- and diphosphorylation of stathmin. Monophosphorylation induced by heat shock was inhibited by the presence of 0.1 mM quercetin, but not by the presence of 0.1 microM staurosporine. Immunoblot analysis of phosphorylated stathmin showed that heat-induced phosphorylation at Ser-38 was inhibited by quercetin but not by staurosporine. Quercetin enhanced heat-induced tyrosine phosphorylation of MAP kinase. These observations indicate that quercetin inhibits heat-induced phosphorylation at Ser-38 of stathmin but mitogen-activated protein (MAP) kinase is not involved in its phosphorylation.


Does Implant Design Affect Implant Primary Stability? A Resonance Frequency Analysis-Based Randomized Split-Mouth Clinical Trial.
The purpose of this study was to assess implant stability in relation to implant design (conical vs. semiconical and wide-pitch vs narrow-pitch) using resonance frequency analysis. Twenty patients with bilateral edentulous maxillary premolar region were selected. In one hemiarch, conical implants with wide pitch (group 1) were installed; in the other hemiarch, semiconical implants with narrow pitch were installed (group 2). The implant allocation was randomized. The implant stability quotient (ISQ) was measured by resonance frequency analysis immediately following implant placement to assess primary stability (time 1) and at 90 days after placement (time 2). In group 1, the mean and standard deviation ISQ for time 1 was 65.8 ± 6.22 (95% confidence interval [CI], 55 to 80), and for time 2, it was 68.0 ± 5.52 (95% CI, 57 to 77). In group 2, the mean and standard deviation ISQ was 63.6 ± 5.95 (95% CI, 52 to 78) for time 1 and 67.0 ± 5.71 (95% CI, 58 to 78) for time 2. The statistical analysis demonstrated significant difference in the ISQ values between groups at time 1 (P = .007) and no statistical difference at time 2 (P = .54). The greater primary stability of conical implants with wide pitch compared with semiconical implants with narrow pitch might suggest a preference for the former in case of the adoption of immediate or early loading protocols.


Calculation of gyrotropy coefficients in media with low-pitch helical structures.
Chiral smectic liquid crystals are known for their huge optical activity due to the precession of the anisotropic dielectric tensor around the helicoidal axis. For an oblique direction of the propagating wave, the helix acts as a grating which splits an incident beam in different directions as long as the pitch is not too small with respect to the light wavelength. When the pitch of the helix is smaller than the wavelength, the effect of the helix is a renormalization of the gyrotropic coefficients (g_{⊥} and g_{∥}) of the resulting uniaxial medium. We report here on a method to compute these coefficients in that limit. Resolution of the Maxwell equations, using a perturbative approach, gives expressions for g_{⊥} and g_{∥} as a power development of the ratio (p/λ). The various terms of these developments coincide with the approximate expressions of these coefficients known in the literature.


Assessment of left-ventricular mass and remodeling in obese adolescents: M-mode, 2D or 3D echocardiography?
Although there have been several studies about the impact of obesity on left-ventricular mass (LVM) and remodeling and their influence on cardiovascular morbidity and mortality, no studies are available on the best echocardiographic technique to study them. In addition, the role of systemic hypertension on LVM in obese adolescents has not been adequately investigated. To compare LVM and remodeling pattern assessed by M-mode, two-dimensional (2D) and three-dimensional (3D) echocardiography in obese adolescents, and to correlate LVM with 24-h ambulatory blood pressure measurements. We studied 120 adolescents: 86 obese patients by M-mode, 2D and 3D echocardiography and 34 normal individuals by echo and magnetic resonance imaging (MRI). In normal individuals LVM was assessed by 3D echo and had the strongest correlation to MRI. In obese adolescents left-ventricular geometry was abnormal in 27 patients (31%) by 3D echo, in 21 patients (24%) by 2D echo and in 43 patients (50%) by M-mode. Mean SBP was significantly related to relative wall thickness, body mass index (BMI) and LVM/h evaluated by 3D echo [r=0.52 (P<0.0001), r=0.36 (P=0.004) and r=0.28 (P=0.03), respectively]. However, at a multivariate analysis, BMI showed a stronger correlation with LVM/h assessed by 3D compared to mean SBP (r=0.44 and P=0.001 vs. r=0.26, P=0.1). In young patients LVM assessed by 3D echo had the strongest correlation to MRI compared to 2D and M-mode echo. In obese adolescents, 3D echo showed left-ventricular remodeling in 31% with LVM more significantly correlated with BMI compared to mean SBP.


No influence of single intravenous doses of omeprazole on theophylline elimination kinetics.
The influence of single intravenous doses of omeprazole on the pharmacokinetics of intravenously administered theophylline was studied in eight healthy male volunteers. In a partially randomized three-period crossover design, an IV infusion of theophylline (400 mg over 30 min) was combined with IV omeprazole (either 40 mg over 2.5 min or 80 mg over 5 min) or with IV placebo (over 2.5 min). Theophylline and omeprazole plasma concentrations were measured over 24 hours after the start of the infusions and pharmacokinetic parameters were calculated. The theophylline plasma concentration-time profiles after omeprazole coadministration were virtually identical to the corresponding profile after placebo administration. For each of the pharmacokinetic parameters of theophylline, the 90% confidence intervals of the omeprazole coadministrations were within the 80 to 120% bioequivalence range with respect to the placebo coadministration. Omeprazole plasma concentrations indicated a biexponential decline in most subjects, with a more rapid elimination after the 40-mg than after the 80-mg dose (P less than .01). Doubling the dose caused an almost three-fold increase of AUC resulting in a difference in clearance (P less than .02), whereas the volume of distribution was similar. The results of this study indicate that the metabolism of theophylline is not affected by single intravenous doses of omeprazole. The nonlinear pharmacokinetics of omeprazole are ascribed to saturation of its main metabolizing enzyme, S-mephenytoin hydroxylase.


Exploration of the therapeutic potential of the antiestrogen RU 58668 in breast cancer treatment.
The recently described pure antiestrogen RU 58668 displayed potent antiproliferative activities in vitro on several ER+ human mammary cell lines, stimulated either by estradiol or by endogenous or exogenous growth factors. Moreover, when administered to nude mice it proved to be the only antiestrogen to induce regression (at least 10 weeks) of estradiol-stimulated MCF-7 tumors, whereas tamoxifen only stabilized the tumor volume for 4 to 8 weeks. So the first purpose of this work was to study the effect of RU 58668 for 6 months and to evaluate its activity on tumors which escaped from the tamoxifen treatment. On the other hand, we looked for its effect on models more related to frequently described clinical observations, such as the overexpression of an oncogene or the implication of autocrine or paracrine growth factors. Long-term studies of RU 58668 on the estradiol-stimulated MCF-7 model showed that this compound induced a shrinking of tumor volumes for at least 25 weeks (3 to 6 times longer than the stabilization induced by tamoxifen) and was able to reduce the volume of tumors which escaped from, or even were stimulated by, tamoxifen. On models of spontaneously growing tumors, where the overexpression of an oncogene or the production of growth factors was involved, RU 58668 induced the same tumor shrinking that was previously observed on estradiol- or tamoxifen-stimulated models. Finally, when MCF-7 cells were injected in the uteri, a spontaneous tumor take was observed (in about 80-90% of the animals), leading to a more than twofold increase in uterus weight. This growth is largely stimulated by estradiol and tamoxifen. On this model, histological examination showed that only 30% of the animals receiving RU 58668 displayed tumoral microfoci. These studies suggest that RU 58668 may be used for the treatment of ER+ patients which are primarily resistant to or which escaped from tamoxifen treatment. Its preventive activity on tumor take also suggests its use as an adjuvant to prevent the development of metastases.


Insertion of Group II Intron-Based Ribozyme Switches into Homing Endonuclease Genes.
Fungal mitochondrial genomes act as "reservoirs" for homing endonucleases. These enzymes with their DNA site-specific cleavage activities are attractive tools for genome editing, targeted mutagenesis and gene therapy applications. Herein, we present strategies where homing endonuclease open reading frames (HEases ORFs) are interrupted with group II intron sequences. The ultimate goal is to achieve in vivo expression of HEases that can be regulated by manipulating the splicing efficiency of the HEase ORF-embedded group II introns. That addition of exogenous magnesium chloride (MgCl2) appears to stimulate splicing of nonnative group II introns in Escherichia coli and the addition of cobalt chloride (CoCl2) to the growth medium antagonizes the expression of HEase activity (i.e., splicing). Group II introns are potentially autocatalytic self-splicing elements and thus can be used as molecular switches that allow for temporal regulated HEase expression. This should be useful in precision genome engineering, mutagenesis, and minimizing off-target activities.


Prevalence and Correlates of HIV Infection Among Sex Workers in Papua New Guinea: First Results from the Papua New Guinea and Australia Sexual Health Improvement Project (PASHIP).
The primary objective of this study was to estimate the individual and combined impacts of socio-demographic and sexual behaviours on HIV diagnosis among 523 female sex workers who participated in the Papua New Guinea and Australia Sexual Health Improvement Project. Logistic regression models were used to identify the factors associated with HIV positivity. We estimated their population level impacts in order to quantify the proportion of HIV seropositivity is attributed to these factors. Less than 40 % of women consented to get tested for HIV. HIV prevalence was 7 % (95 % CI 4-11 %); lack of education and knowledge/awareness of HIV accounted for ~70 % of the HIV diagnoses. A major obstacle is lack of interest for testing. Our study underscored the major challenges in this culturally, linguistically heterogeneous country. The epidemic in Papua New Guinea requires targeted prevention interventions among those at highest risk of acquiring or transmitting infection.


Challenging heterosexism in college health service delivery.
The empowerment and affirmation of lesbian, bisexual, and gay students is long overdue. This article explores how human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), substance abuse, violence and hate-related crimes, suicide, and heterosexism all adversely affect the physical and emotional health of nonheterosexual college students. College health services must expand their current scope and practice and assume a leadership role in combating all forms of oppression by actively incorporating and addressing the unique health issues and needs of the lesbian, bisexual, and gay population. This article provides a brief overview of the relevant healthcare issues for lesbians, bisexuals, and gays; examples of heterosexism in college health services; and recommendations for institutional and personal and professional change.


Composition methods for four-port couplers in photonic integrated circuitry.
Planar photonic integrated circuits based on four-port couplers offer enhanced sophistication and functionality. Each four-port coupler is characterized by sixteen signal coupling coefficients governed by ten energy constraints. The ability to generate the constrained sixteen coupling coefficients is needed in the analysis of the four-port coupler. However, the energy constraint equations are nonlinear and cumbersome to solve directly. We introduce two techniques to reduce these signal coupling coefficients to a set of six free parameters. Hence we can characterize all possible couplers in terms of their sixteen constrained coupling coefficients, or either of two sets of six free parameters. This reduction in parameters has significant ramifications for the design, specification, and empirical characterization of these useful building blocks.


[Changes in the lymphoid tissue and in the level of corticosteroids in staphylococcal intoxication and infection].
A complex quantitative study of changes of proliferative processes in lymphatic vessels on the one hand and changes of the level of corticosteroids in the peripheral blood in staphylococcal intoxication and infection in the same rats on the other hand has been carried out. In the work H3-thymidine has been used. The comparison of the obtained morphological data with the dynamics of the change in the corticosteroid level shows that the decay of lymphocytes, the devastating of light centers and the cortical substance of lymph nodes, an abrupt lowering of the amount of DNA-synthesizing and mitotically dividing cells take place in the period associated with a release of a great amount of corticosteroids into the blood. The drop of their level to control values goes in parallel with increasing the amount of DNA-synthesizing and mitotically dividing cells. The obtained data suggest that the leading role in those changes of the lympoid tissue which had been described by a number of authors in infectional processes is played by corticosteroids.


Calcium deposits on glyceryl methyl methacrylate and hydroxyethyl methacrylate contact lenses.
Five patients wore a hydroxyethyl methacrylate (HEMA) lens on one eye and a glyceryl methyl methylcrylate (GMA) lens on the other eye. The eye with the GMA lens remained comfortable longer than the other eye. The GMA lens is less likely to acquire calcium deposits and continues to be wearable longer than the HEMA lens.


Sensing the Airs: The Cultural Context for Breathing and Breathlessness in Uruguay.
The sensory experience of breathing, particularly the sensation of breathlessness in the case of chronic obstructive pulmonary disease (COPD), is a rich though understudied topic in medical anthropology. Fieldwork in Uruguay made it clear to me that to study the sensorial experience of breathlessness, I would also have to study the widely shared cultural conceptualizations and practices surrounding air, breath, and health. In this article, I illustrate ethnographically how the experience of breathing and breathlessness is closely tied to perceptions of air outside the body - in particular humidity, temperature change, wind, and contamination. In conceptualizing breath as the mechanism and air the medium for environmental embodiment, I bring together sensorial medical anthropology, anthropology of the body, and the anthropology of wind and climate. My findings, in light of similar findings across contexts, suggest that a body transformed by COPD is hyperperceptive and hypersensitive to changes in air.


Effectiveness of Stretching on Posterior Shoulder Tightness and Glenohumeral Internal-Rotation Deficit: A Systematic Review of Randomized Controlled Trials.
Posterior shoulder tightness (PST) and glenohumeral internal-rotation deficit (GIRD) can contribute to shoulder pain suffered by athletes engaged in overhead sporting activities. Stretching is a common intervention to resolve PST and GIRD, but it has weak evidence of effectiveness to date. This systematic review aimed to collect and synthesize effectiveness data from English- and Japanese-language randomized controlled trials (RCTs) investigating stretching interventions for PST and GIRD. 7 English databases and 3 Japanese databases were searched from inception until December 5, 2015. Only English- and Japanese-language RCTs were considered. Risk of bias in the included studies was assessed using the Physiotherapy Evidence Database scale. Data were synthesized qualitatively. Eight English-language and 2 Japanese-language papers of low to high quality were included. There was moderate evidence for positive immediate and short-term effects of cross-body stretch on PST and GIRD in asymptomatic young subjects. Moderate evidence was found to suggest that active sleeper stretch might not be more effective than no intervention to improve PST and GIRD in the short term. Cross-body stretch can be effective to improve PST and GIRD in asymptomatic young subjects immediately or in the short term. Further study with methodological rigor is necessary to investigate the long-term effectiveness of stretching interventions on PST and GIRD in symptomatic patients.


Merosesquiterpenoids and ten-membered macrolides from a soft coral-derived Lophiostoma sp. fungus.
One new merosesquiterpenoid, craterellin D (1), along with one known analog, craterellin A (2), and five known ten-membered macrolides, 3-7, were isolated from a soft coral-derived Lophiostoma sp. fungus. The absolute configuration of 1 was established based on biogenetic consideration with the co-isolated analog 2, whose configuration was determined by modified Mosher's method and single-crystal X-ray diffraction analysis using CuKα radiation. The absolute configuration of 3 was determined by X-ray diffraction analysis using CuKα radiation. Compounds 2 and 3 showed antibacterial activities against Bacillus cereus with a MIC value of 3.12 μM.


Lead poisoning.
While lead is a very old poison whose toxicity was known to the ancient Greeks, new information about mechanisms and effects of lead toxicity is continually being discovered. Family practitioners should be alert to the possibility of lead poisoning and the situations in which it occurs. Symptoms may be non specific and careful questioning of patients or their parents may be required to identify possible exposure.


Hydrogen Sulfide and T-Type Ca2+ Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion.
Hydrogen sulfide (H2S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H2S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Cav3.2 T-type Ca2+ channels mediate some of the biological activity of H2S, we focus on the role of the H2S/Cav3.2 pathway in regulating the neuronal and neuroendocrine function. In the neuronal system, H2S regulates the activity of various ion channels including Cav3.2. Exogenous and endogenous H2S enhances the Cav3.2 channel activity, promoting somatic and visceral pain signaling. The H2S/Cav3.2 pathway also facilitates neuritogenesis or neuronal differentiation. Interestingly, endogenous H2S formed by CSE regulates secretory function by enhancing Cav3.2 channel activity in neuroendocrine-differentiated prostate cancer cells or carotid glomus cells. Key Messages: The H2S/Cav3.2 pathway may serve as therapeutic targets for treatment of intractable pain, neuronal injury, androgen-independent prostate cancer, cardiovascular diseases, etc.


[Frontal giant cell glioblastoma: radio-induced tumor? Case report and literature review].
The current WHO classification recognizes two distinct variants of glioblastoma multiforme (GBMs): giant cell glioblastoma (GCG) and gliosarcoma, based on histological heterogeneity. Unlike conventional GBMs, GCGs preferentially occur in younger individuals and are associated with a better prognosis, a few reports documenting prolonged survival up to 17 years after diagnosis. However, transformation to gliosarcoma is possible and has been already reported. Radio-induced glioblastoma, which meets Cahan's criteria for radio-induced tumor, is very rare; the first case was published by Kleriga et al. We report a rare case observed in a 46-year-old man with a past history of right nose leiomyosarcoma treated 40 years earlier by surgery and interstitial and external beam radiation. At admission, the patient presented left hemiparesis revealing a right frontal GCG confirmed by pathology after cranial surgery. We describe this case firstly because of its rare histological variety and discuss its clinical, radiological, histopathological, therapeutic and prognostic characteristics with literature data. Secondly, because of its occurrence 40 years after external radiotherapy, which could suggest the hypothesis of radio-induced glioblastoma.


Regulation of immune response by P2X7 receptor.
The P2X7 receptor is an ATP-gated cation channel that is widely expressed in cells of the immune system. Signal transduction is accompanied by fast influx of Ca2+ and Na+, and efflux of K+. This receptor differs from other members of the P2X family in its relatively low affinity for ATP, the presence of a long C-terminal region that contains several protein-protein interaction motifs, and the activation of two membrane conductance states following receptor ligation. In the immune system, this receptor has been implicated in the processing and release of cytokines such as IL-1 beta, and in the initiation of cell death via both apoptotic and necrotic pathways. As such, it has been proposed to function as a major regulator of inflammation. Consistent with this hypothesis, inactivation of this receptor in mice modulates disease pathogenesis in several animal models of inflammatory and autoimmune diseases. Loss-of-function polymorphisms have also been noted in the human population, and there is accumulating evidence that these polymorphisms are linked to certain diseases. In this article, we review the current status of research in this field, with particular emphasis on the signaling pathways activated by this receptor, the mechanisms involved in the initiation of cell death, and associations with disease states in mice and humans.


Neuroimmune interactions in Alzheimer's disease-New frontier with old challenges?
The perceived role of the immune system in neurodegenerative diseases has undergone drastic changes over time. Initially considered as a passive bystander, then condemned as a mediator of neurodegeneration and now established as an important player in the pathogenetic cascade, neuroimmune interactions have come a long way to arrive center stage in Alzheimer's disease research. Despite major breakthroughs in recent years, basic questions remain unanswered as conflicting data describe immune overactivation, inadequate response or exhaustion of the immune system in neurodegenerative diseases. Furthermore, difficulties in translating in vitro and in vivo studies in model systems to the complex human disease condition with multiple overlapping pathologies and the long disease duration in patients suffering from neurodegenerative diseases have hampered progress. Development of novel, advanced model systems, as well as new technologies to interrogate existing disease models and valuable collections of human tissue samples, including brain tissue in parallel with improved imaging and biomarker technologies are guiding the way to better understand the role of the immune system in Alzheimer's disease with hopes for more effective interventions in the future.


Rheological properties of concentrated skim milk: influence of heat treatment and genetic variants on the changes in viscosity during storage.
Heat treatment during manufacturing of milk powder is one of the most important tools for manipulation of its functional properties, and it is the basis of the classification of these proteins into low-, medium-, and high-heat types. Slight differences in the sequences of the major proteins in milk (genetic variants) seem to have also a significant effect in milk powder processing (U.S. patent). Therefore, the effects of high-temperature storage and heat treatment on skim milk of defined genetic variants of beta-lactoglobulin (beta-LG) were measured. The samples had 45% total solids, the temperature of aging was 50 degrees C, and the heat treatment was 90 degrees C for 10 min prior to evaporation. Measurements on shear rate and on apparent viscosity were determined for each sample. During storage of the concentrated milk, the apparent viscosity and yield values increased markedly, and the age-dependent increase in viscosity in heat-treated concentrated skim milks was much more pronounced than in those prepared from unheated skim milks. The increase in apparent viscosity and yield value with storage time was notably different for milks containing different genetic variants. Unheated concentrated milks containing the B variant of beta-LG showed the most rapid increase in apparent viscosity with storage time, whereas the viscosity increase was slowest in the concentrate containing the A variant. In contrast, heat-treated concentrated milks containing the A variant of beta-LG showed the most rapid increase in viscosity with storage time, whereas the viscosity increase was slowest in the concentrate containing the AB variant. The changes in apparent viscosity of concentrated milk were largely reversible under high shear during the early stages of storage, but samples stored for a long time showed irreversible changes in apparent viscosity. Particle size analysis confirmed irreversible aggregation and fusion of casein particles during storage.


[Is papilloma of the esophagus a preneoplastic lesion? Study of 33 cases].
The etiology of esophagus papilloma is much debated: some authors attach greater importance to irritation factors, while others give preference to the viral hypothesis and suggest that this disease could eventually lead to squamous cell carcinoma of the esophagus. To verify the viral hypothesis, we reviewed the histological slides of the 33 cases of esophageal papilloma diagnosed in our Institute of Pathology between 1973 and 1988. We evaluated the histological diagnosis using Winckler's criteria. HPV typing was done using probes of HPV DNA types 6-11, 16-18, 31-33-35 applied to paraffin sections according to the in-situ hybridization method. Clinical and endoscopic data of 15 cases (from the CHUV) are reviewed. Oncological data was provided by the Vaud Cantonal Tumor Register. No patient in our series fulfilled all the histological criteria set by Winckler to diagnose an HPV condition. Viral DNA 31-33-35 was found in a small minority of the papillomas. The clinical impact of esophageal papilloma on epidermoid carcinogenesis is nil.


Availability of the HRSA competitive grants preview--HRSA. General notice.
HRSA announces the availability of the HRSA Competitive Grants Preview publication for Fall 1997. This edition of the Preview is a comprehensive review of HRSA's Fiscal Year 1998 programs. The purpose of the Preview is to provide the general public with a single source of program and application information related to the Agency's annual grant planning review. The Preview is designed to replace multiple Federal Register notices which traditionally advertised the availability of HRSA's discretionary funds for its various programs. In this edition of the Preview, HRSA's programs which provide funding for loan repayments and scholarships to individuals have been included in the section "Additional HRSA Programs." It should be noted that other program initiatives responsive to new or emerging issues in the health care area and unanticipated at the time of publication of the Preview, may be advertised through the Federal Register mechanism from time-to-time. Deadlines or other requirements appearing in the Federal Register are not changed by this notice. The Preview contains a description of competitive and additional programs scheduled for review in Fiscal Year 1998 and includes instructions on how to access the Agency for information and receive application kits for all programs announced. Specifically, the following information is included in the Preview: Program Title, Legislative Authority, Purpose, Eligibility, Estimated Amount of Competition, Estimated Number of Awards, Funding Priorities and/or Preferences, Projected Award Date, Application Deadline, Application Kit Availability, Catalog of Federal Domestic Assistance (CFDA) program identification number, and programmatic contact.


The disparity between homologous chromosomes during DNA replication.
When the patterns of replicating chromosome bands of homologous chromosomes within a diploid cell during DNA synthesis phase are compared, the frequency of disparity (i.e. a band present on only one homologue) is less than expected on the basis of chance. This could be taken as implying some "link" between homologues which constrains their programmes of replication to keep in step. This paper develops a model showing that the observed disparities can be accommodated within a framework of homologue independence. Differences between cells in the time of appearance of bands lead in any sample to the summation of an infinitude of binomial distributions and hence to over-dispersion. The model fits observed data for bands replicating in euchromatic and heterochromatic chromosome regions obtained from Syrian hamster fibroblast cells growing in vitro.


[Prosthetic radial head for type III Masson fractures].
The treatment of type III Masson radius head fractures is variable; there is not a clear solution. This study addresses the course of patients treated with radius head replacement for type III Masson fractures at ISSEMYM Medical Center, Ecatepec, Mexico. Four male patients were included; mean age was 34.5 years (range 28-41). The mechanism of injury was direct contusion; 3 of the elbows were left (75%) and one was right (25%). A bipolar uncemented prosthesis was used. According to Broberg and Morrey functional assessment criteria, patients had an excellent course. The mean time elapsed after surgery is 13 months. We concluded that the radius head prosthesis for type III Masson fractures is a good alternative. Patients may start rehabilitation right away, unlike what occurs with other surgical techniques.


The many facets of speech production and its complex effects on phonological processing.
In our commentary, we discuss two additional points about developmental speech production. First, we suggest that more precision is needed to accurately describe 'speech production' processes, and we suggest that hierarchical constructs from the adult literatures on articulatory phonology and speech motor control may be applicable to infants as well. Second, we discuss the implications from data that indicate that the effects of production are subject to task-, attentional-, linguistic-, and experience-related demands.


Inheritance of porcine receptors for enterotoxigenic Escherichia coli with fimbriae F4ad and their relation to other F4 receptors.
Enteric Escherichia coli infections are a highly relevant cause of disease and death in young pigs. Breeding genetically resistant pigs is an economical and sustainable method of prevention. Resistant pigs are protected against colonization of the intestine through the absence of receptors for the bacterial fimbriae, which mediate adhesion to the intestinal surface. The present work aimed at elucidation of the mode of inheritance of the F4ad receptor which according to former investigations appeared quite confusing. Intestines of 489 pigs of an experimental herd were examined by a microscopic adhesion test modified in such a manner that four small intestinal sites instead of one were tested for adhesion of the fimbrial variant F4ad. Segregation analysis revealed that the mixed inheritance model explained our data best. The heritability of the F4ad phenotype was estimated to be 0.7±0.1. There are no relations to the strong receptors for variants F4ab and F4ac. Targeted matings allowed the discrimination between two F4ad receptors, that is, a fully adhesive receptor (F4adRFA) expressed on all enterocytes and at all small intestinal sites, and a partially adhesive receptor (F4adRPA) variably expressed at different sites and often leading to partial bacterial adhesion. In pigs with both F4ad receptors, the F4adRPA receptor is masked by the F4adRFA. The hypothesis that F4adRFA must be encoded by at least two complementary or epistatic dominant genes is supported by the Hardy-Weinberg equilibrium statistics. The F4adRPA receptor is inherited as a monogenetic dominant trait. A comparable partially adhesive receptor for variant F4ab (F4abRPA) was also observed but the limited data did not allow a prediction of the mode of inheritance. Pigs were therefore classified into one of eight receptor phenotypes: A1 (F4abRFA/F4acR+/F4adRFA); A2 (F4abRFA/F4acR+/F4adRPA); B (F4abRFA/F4acR+/F4adR-); C1 (F4abRPA/F4acR-/F4adRFA); C2 (F4abRPA/F4acR-/F4adRPA); D1 (F4abR-/F4acR-/F4adRFA); D2 (F4abR-/F4acR-/F4adRPA); E (F4abR-/F4acR-/F4adR-).


Positron emission tomography imaging as a key enabling technology in drug development.
The use of positron emission tomography (PET) in drug development has become more common in the pharmaceutical industry in recent years. One of the biggest challenges to gaining acceptance of this technology is for project teams to understand when to use PET. This chapter reviews the usage of PET in drug development in the context of target, mechanism and efficacy biomarkers. Examples are drawn from a number of therapeutic areas, but we also show that the relative penetration of this technology beyond CNS and oncology applications has been relatively small. However, with the increasing availability of PET and development of novel radiotracers it is expected that the utilization will be much broader in future years, with the additional expectation that the use of PET as an efficacy biomarker will also become more evident.


Middle Pleistocene handaxes from the Korean Peninsula.
We present four biface assemblages from an archaeologically poorly known region of the Old World: Middle Pleistocene Korea. The handaxes are derived from a series of Middle Pleistocene localities in the Imjin/Hantan River Basins (IHRB) in Korea. The best known of these localities is Chongokni, although a number of equally important sites in the IHRB have been discovered and excavated over the course of the past two decades (e.g., Kumpari, Chuwoli, and Kawoli). Reanalysis of the age of the Chongokni deposits suggests a hominin occupation between 350-300 ka. Comparative study of the IHRB handaxes with the well-known bifacial implements from Olorgesailie (Kenya) and Hunsgi-Baichbal (India) indicates that the often-noted "thick" trait of the East Asian handaxes differs at a statistical level across the various regions of the Old World. The finds from the IHRB sites, and the Chinese sites of Bose and Dingcun that contain handaxes-like implement, question the validity of the Movius Line sensu stricto. However, why East Asian Middle Pleistocene hominins did not consistently produce more refined bifaces across broader regional and/or temporal facies, remains open to question. Thus, the absence of similar sites in wider areas of Early and Middle Pleistocene East Asia suggests that the Movius Line sensu lato is still supportable and warrants additional detailed cross comparative studies of the stone toolkits east and west of the line.


Fava's Anger Attacks Questionnaire: evaluation of the French version in depressed patients.
The prevalence, symptomatology and correlates of anger attacks were studied in 103 depressed French patients, using a French version of the Anger Attacks Questionnaire. The prevalence of anger attacks during the previous month was 46.7%, and the most frequently reported symptoms were feeling of panic (85.1%), tachycardia (83.7%), and feeling out of control (81.3%). The occurrence of anger attacks was significantly associated with intensity of loss of control, and history of panic attacks. There was no significant association with age, gender, severity of depression or anxiety, history of suicidal attempts or mood disorder. Three weeks of treatment with serotoninergic antidepressants induced a significant decrease in anger attack prevalence.


Doctors' working hours and time spent on patient care in the period 1994 - 2014.
There is always a keen interest in the qualitative and quantitative aspects of doctors’ working hours. In this study developments are described in terms of total weekly working hours and time spent on direct patient care from 1994 to 2014 by doctors working in different job categories and medical disciplines in Norway. All data has been obtained from LEFO’s reference panel of doctors, a near representative sample of approximately 1 600 practising doctors who have been followed up with questionnaires every second year since 1994. In the course of this period, doctors have come off the panel as they retired and new young doctors have been included in replacement. Questions relating to how they spend their time have always featured in the questionnaire. This article is based on data from 1994, 2000, 2006, 2010 and 2014. Response rates were between 67 and 95 %. From 1994 to 2014, total weekly working hours remained the same for all categories of doctors, except those working in academia. Time spent on direct patient care has fallen, but not significantly, for general practitioners, specialists working in private practice and doctors working in academia and administration. Meanwhile, community medical officers and hospital doctors have seen their time spent on patient care fall significantly over the 20-year period. There is however great variation, particularly between the different medical disciplines in hospitals. Differences and changes in the amount of time spent by doctors on direct patient care are caused by both structural and cultural factors relating to the working situation, and not least by a considerable increase in the number of hospital doctors.


Is there a role for gut microbiota in type 1 diabetes pathogenesis?
Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by insufficient insulin production due to the destruction of insulin secreting β-cells in the Langerhans islets. A variety of factors, including chemicals, viruses, commensal bacteria and diet have been proposed to contribute to the risk of developing the disorder. In the last years, gut microbiota has been proposed as a main factor in T1D pathogenesis. Several alterations of gut microbiota composition were described both in animal model and in humans. The decrease of Firmicutes/Bacteroides ratio was the most frequent pattern described, in particular, in human studies. Furthermore, Bacteroides, Clostridium cluster XIVa, Lactobacillus, Bifidobacterium, and Prevotella relative abundances were different in healthy and affected subjects. Dysbiosis would seem to increase intestinal permeability and thus promote the development of a pro-inflammatory niche that stimulates β-cell autoimmunity in predisposed subjects. Preliminary studies on animal models were realized to investigate the role of gut microbiota modulation as therapy or prevention approach in predisposed animals: promising and stimulating results have been reported. Key message Dietary antigens and microbiota-derived products might act as triggers of T1D by causing a pro-inflammatory and metabolic dysfunctional environment.


Incidence of schizophrenia among ethnic minorities in the Netherlands: a four-year first-contact study.
There is only one previous report on the first-contact incidence of schizophrenia among immigrants in the Netherlands, which was based on a small number of cases, particularly for second generation immigrants. We conducted another two-year first-contact incidence study in the same geographical area, combined the data of both studies and compared risks over all four years. The incidence of schizophrenia was increased for all first generation non-Western immigrants. The risk was particularly high for second generation immigrants: the age- and gender-adjusted incidence rate ratio was 5.8 (95% CI, 2.9-11.4) for Moroccans, 2.9 (1.6-5.0) for Surinamese, 2.3 (1.0-5.4) for Turks, and 3.5 (1.8-6.8) for immigrants from other non-Western countries.


Thoracic spinal cord intramedullary aspergillus invasion and abscess.
Invasive central nervous system aspergillosis is a rare form of fungal infection that presents most commonly in immunocompromised individuals. There have been multiple previous reports of aspergillus vertebral osteomyelitis and spinal epidural aspergillus abscess; however to our knowledge there are no reports of intramedullary aspergillus infection. We present a 19-year-old woman with active acute lymphoblastic leukemia who presented with several weeks of fevers and bilateral lower extremity weakness. She was found to have an intramedullary aspergillus abscess at T12-L1 resulting from adjacent vertebral osteomyelitis and underwent surgical debridement with ultra-sound guided aspiration and aggressive intravenous voriconazole therapy. To our knowledge this is the first reported case of spinal aspergillosis invading the intramedullary cavity. Though rare, this entity should be included in the differential for immunocompromised patients presenting with fevers and neurologic deficit. Early recognition with aggressive neurosurgical intervention and antifungal therapy may improve outcomes in future cases.


Immunology in Malaysia--a review.
Immunology is a discipline that traverses all branches of clinical medicine. Thus since about ten years ago major hospitals in Malaysia established routine clinical immunology services particularly in the diagnosis of autoimmune/connective tissue disorders. More recently these laboratories have ventured into basic research in Dengue Haemorrhagic Fever, Leukaemia Immunology, Nasopharyngeal Cancer and Leprosy. The rationale for these projects together with early results from them are discussed.


Environmental salinity regulates receptor expression, cellular effects, and circulating levels of two antagonizing hormones, 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3, in rainbow trout.
In freshwater-adapted rainbow trout, intestinal cells (enterocytes) possess receptors for 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] in the basolateral membrane, and respond to treatment with 1,25(OH)(2)D(3) with increased intracellular calcium concentrations. No receptors are found for the antagonizing hormone 24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)] at the enterocyte basolateral membrane, and it has no effect on enterocyte calcium homeostasis. After acclimation to seawater, however, the enterocyte membrane receptors for 1,25(OH)(2)D(3) are down-regulated and specific binding for 24,25(OH)(2)D(3) appears, which is further up-regulated with time spent in seawater. This shift in receptor expression is concurrent with an increased sensitivity of the enterocytes to 24,25(OH)(2)D(3) and a decreased sensitivity to 1,25(OH)(2)D(3). This results in a partial inhibition of intracellular calcium uptake, which would be beneficial when inhabiting a calcium-rich environment like seawater.


Recurrent group A streptococcal carriage in a health care worker associated with widely separated nosocomial outbreaks.
Nine postpartum infections (five bacteremias, three cases of endometritis without bacteremia, and one infected episiotomy site) caused by an M-nontypable, T-28 strain of group A Streptococcus occurred during a 9-week period in 1987. Seven cases were cared for by one obstetrician, who was also present in the delivery suite when the remaining patients delivered. This individual was found to be an anal carrier of group A Streptococcus with the same M and T types. During the cluster, the attack rate for vaginal deliveries performed by this individual was 18% (6 of 34 patients). The individual was treated with penicillin V (500 mg four times a day for 10 days), rifampin (600 mg twice a day for 5 days), and hexachlorophene showers. Surveillance cultures of the physician were negative 1 week, 1 month, and 3 months after completion of therapy. No additional cases were identified among the next 210 vaginal deliveries performed by this individual. Fourteen months after therapy, four new cases occurred during 2 days. The physician was found to be heavily colonized once again with the original strain of group A Streptococcus and was treated with rifampin (600 mg twice a day) and oral vancomycin (250 mg four times a day) for 7 days. An open-ended regimen of penicillin V (250 mg/day) and periodic surveillance cultures was begun. During the next 19 months, this physician performed 275 vaginal deliveries, one of which resulted in an M-nontypable, T-28 group A streptococcal infection, at a time when the physician's surveillance cultures were negative. It is unclear how long a colonized health care worker who causes nosocomial group A streptococcal disease must be treated or monitored, but there is some risk after more than a year. Long-term surveillance or prophylaxis may be useful in some circumstances.


Evidence-based pain management and palliative care in issue four for 2004 of the Cochrane Library.
The Cochrane Library of Systematic Reviews is published quarterly. Issue four for 2004 of the library was published in October 2004. The Cochrane Library now contains 2170 complete reviews, 1500 protocols of reviews and 4918 one-page summaries of systematic reviews published in the general medical literature. In addition there are citations of 427.807 randomised controlled trials, 18 methodology reviews and 5968 cited papers in the Cochrane methodology register. The health technology assessment database contains 4395 citations. In this edition of the Library issued in October 2004, there were 96 new reviews of which 12 have potential relevance for practitioners in pain and palliative medicine. Regular readers will note that the format of the citation has changed with the move to publication of the Cochrane Library by John Wiley & Sons. Citations will probably change again in the future as currently there is no indication of the date when a review was first published.


Comparative punting kinematics and pelvic fin musculature of benthic batoids.
Although the majority of batoid elasmobranchs, skates and rays, are benthically associated, benthic locomotion has been largely overlooked in this group. Only skates have been previously described to perform a form of benthic locomotion termed "punting." While keeping the rest of the body motionless, the skate's pelvic fins are planted into the substrate and then retracted caudally, which thrusts the body forward. In this study, we demonstrate that this form of locomotion is not confined to the skates, but is found across a range of phylogenetically and morphologically diverse batoid species. However, only the clearnose skate, Raja eglanteria, and the lesser electric ray, Narcine brasiliensis, performed "true punting," in which only the pelvic fins were engaged. The yellow stingray, Urobatis jamaicensis, and the Atlantic stingray, Dasyatis sabina, performed "augmented punting," in which pectoral fin movement was also used to generate thrust. Despite this supplemental use of pectoral fins, the augmented punters failed to exceed the punting capabilities of the true punters. The urobatid and the true punters all punted approximately half their disc length per punt, whereas the dasyatid punted a significantly shorter distance. The skate punted significantly faster than the other species. Examination of the pelvic fin musculature revealed more specialized muscles in the true punters than in the augmented punters. This concordance of musculature with punting ability provides predictive power regarding the punting kinematics of other elasmobranchs based upon gross muscular examinations. In contrast to previous assumptions, our results suggest that benthic locomotion is widespread among batoids.


Etomidate as a sole agent for endotracheal intubation in the prehospital air medical setting.
Etomidate is an anesthetic agent with rapid onset, short duration of action, a generally stable hemodynamic profile, and cerebroprotective effects. It is used in the hospital setting to facilitate emergency endotracheal intubation. This helicopter EMS used etomidate as an intubating agent without paralytics for 2 years. Intubations performed by the helicopter crew using etomidate alone were reviewed. Intubation was classified as successful or unsuccessful. Successful intubations requiring three or more attempts or repeated doses of etomidate were interpreted as difficult. Fifty patients received etomidate to facilitate orotracheal intubation. Etomidate was the sole agent in 44 of these cases. Mean age was 31 years (range 4-79); 35 patients (80%) were men. Most patients (79%) were victims of blunt trauma. The mean dose of etomidate was 0.5 mg/kg (range 0.3-1.1). Hemodynamic parameters remained stable. Intubation was successful in 39 patients (89%). Intubation was difficult in seven patients (16%) and unsuccessful in five (11%). Masseter muscle spasm was noted in three of the five patients for whom intubation was unsuccessful. Other complications included emesis in eight patients and seizure-like activity in one patient. Etomidate can be used to facilitate emergency endotracheal intubation in the prehospital air medical setting, with a success rate of 89%. At the doses used in the study, hemodynamic parameters remained stable, but intubation was difficult or unsuccessful in 27% of patients. Masseter muscle spasm, which may represent orofacial myoclonus or inadequate relaxation, is common in patients who cannot be intubated with etomidate. Etomidate is recommended as a sole agent for facilitating intubation only when rapid sequence intubation with paralysis is contraindicated or otherwise undesirable.


[Long-term outcome of 52 patients with chronic periaortitis treated with steroids, immunosuppressive therapy and(or) tamoxifen.].
The study aims to assess the therapeutic benefit of medicine treatment in chronic periaortitis. A retrospective study of 52 patients with chronic periaortitis treated at Peking Union Medical College Hospital. Summarize clinical features, level of acute-phase reactants, extent of ureteral obstruction, level of renal function, size of mass with repeated follow-up CT scanning during the period of therapy. The most prominent symtom was back or abdominal pain. 76.92% had ureteral obstruction, with 26.92% had a progressive renal failure. After a period of treatment, 95.35% were significant to complete resolution of symptoms. There was also a remarkable decrease in ESR and C-reactive protein a median treatment of 4 weeks. Creatinine decreased significantly (P = 0.002) in patients with progressive renal failure. 66.67% was successfully removed the ureteric stents. CT scanning showed 75% mass regression after a median of 6 months. The clinical manifestations of chronic periaortitis is nonspecific, which often leads to a delayed diagnosis and the late complications. Chronic periaortitis is very effectively treated by a combination of steroids and immunosuppressive therapy and(or) tamoxifen, with excellent long-term outcome and relatively fewer disease relapse.


Cryptosporidium parvum: oocysts purification using potassium bromide discontinuous gradient.
Cryptosporidium parvum oocysts were purified using a discontinuous potassium bromide density gradient, composed by three solutions of 6, 16 and 28% (w/v) KBr in Tris-EDTA buffer. Fecal samples containing oocysts were washed to diminish interfering lipids and applied to the gradient. After centrifugation, oocysts can be easily aspirated from a clear band, diluted and washed by centrifugation in phosphate buffer to remove residual KBr. This method allows the purification of large amounts of highly purified C. parvum oocysts, using low cost reagents and a standard table-top centrifuge.


[Scanography and chemonucleolysis of herniated discs. Value and limitations in 20 cases].
Scanography explorations were conducted before and after chemonucleolysis in 20 patients with sciatica from herniated discs. The scanner can improve the selection of patients for this new type of medical treatment by detecting adverse factors: stenosed discs, excluded hernias, narrow canals, stenosis of the lateral recesses. The diagnostic precision of scanography can be demonstrated by comparison of results with those obtained by discography. Following chemonucleolysis, however, intravenous injection of a contrast medium and a high resolution programme are necessary to obtain specific information from scanography.


Molecular cloning and expression of a functional snake venom serine proteinase, with platelet aggregating activity, from the Cerastes cerastes viper.
The venoms of Viperidae snakes contain numerous serine proteinases that have been recognized to possess one or more of the essential activities of thrombin on fibrinogen and platelets. Among them, a platelet proaggregant protein, cerastocytin, has been isolated from the venom of the Tunisian viper Cerastes cerastes. Using the RACE-PCR technique, we isolated and identified the complete nucleotide sequence of a cDNA serine proteinase precursor. The recombinant protein was designated rCC-PPP (for C. cerastes platelet proaggregant protein), since its deduced amino acid sequence is more than 96% identical to the partial polypeptide sequences that have been determined for natural cerastocytin. The structure of the rCC-PPP cDNA is similar to that of snake venom serine proteinases. The expression of rCC-PPP in Escherichia coli system allowed, for the first time, the preparation and purification of an active protein from snake venom with platelet proaggregant and fibrinogenolytic activities. Purified rCC-PPP efficiently activates blood platelets at nanomolar (8 nM) concentrations, as do natural cerastocytin (5 nM) and thrombin (1 nM). It is able to clot purified fibrinogen and to hydrolyze alpha-chains. Thus, rCC-PPP could be therefore considered a cerastocytin isoform. By comparison with other snake venom serine proteinases, a Gly replaces the conserved Cys(42). This implies that rCC-PPP lacks the conserved Cys(42)-Cys(58) disulfide bridge. A structural analysis performed by molecular modeling indicated that the segment of residues Tyr(67)-Arg(80) of rCC-PPP corresponds to anion-binding exosite 1 of thrombin that is involved in its capacity to induce platelet aggregation. Furthermore, the surface of the rCC-PPP molecule is characterized by a hydrophobic pocket, comprising the 90 loop (Phe(90)-Val(99)), Tyr(172), and Trp(215) residues, which might be involved in the fibrinogen clotting activity of rCC-PPP.


Analysis of the Early Results of 693 Patients Undergoing Valvular Reoperation Between 1993 and 2011.
The study aim was to identify factors affecting early mortality in valvular reoperations. Between January 1993 and December 2011, a total of 693 patients who had undergone valvular reoperations due to problems with previously implanted mechanical and biological valves, new valve degeneration or valve failure after a reconstructive procedure was included in the study. Factors affecting early mortality were identified by the examination of preoperative and perioperative data, using multivariate analysis. The average age of the patients was 44.9 years. For all patients, overall hospital mortality was 15.9%, while hospital mortality rates were 12.9% and 35.3% for elective operation and urgent/emergency treatment, respectively. Factors affecting early mortality in the multivariate analysis were longer total perfusion time (>120 min, p = 0.001), emergency or urgent treatment (p = 0.001), and the presence of preoperative renal failure (p = 0.001). Mortality for elective patients in valvular reoperations was within an acceptable range. Total mortality was dependent on a high mortality level of emergency/urgency of the cases. The use of a well-defined protocol in valvular reoperations may decrease hospital mortality.


Pneumomediastinum in labour -- probably not caused by a lumbar epidural anaesthesia.
We describe a case of pneumomediastinum and subcutaneous emphysema during labour. The patient had previously received an epidural anaesthesia to alleviate labour pain. We found several reports of subcutaneous emphysema and pneumomediastinum (or pneumothorax) possibly caused by or related to epidural anaesthesia use, but conclude that the epidural anaesthesia was probably not a cause in our case.