Biofilms: Microbial Strategies for Surviving UV Exposure.
Biofilm communities are an ingenious form of protection of microbial cells which have been evolving for billion of years. In general, ultraviolet (UV) radiation presents poor penetration in the matrix of biofilms and only the first few top layers of microbial cells are exposed to its deleterious effects. For further protection against UV radiation, exposed cells can produce specialized compounds such as mycosporine-like amino acids and carotenoid pigments. In this chapter, the adaptation mechanisms presented by biofilms against UV radiation are presented, as well as the application of UV light to monitor and destroy biofilms in man made surfaces.


Mosquito surveillance in northwestern Italy to monitor the occurrence of tropical vector-borne diseases.
Mosquito-borne arboviruses (MBV) represent an important health problem, causing diseases and deaths both in human and animals mainly in tropical and subtropical countries. In recent years, they have emerged also in temperate regions where they have caused epidemics. Of mounting concern among public health authorities in Europe are zoonotic mosquito-borne viruses belonging to the Flavivirus genus. The aim of this study was to carry out active surveillance on mosquitoes in two regions of northwestern Italy (Liguria and Piedmont) to gain a better knowledge of the mosquito populations by identifying potential vectors of arboviruses and to investigate arbovirus infection. A network of 61 CO₂ CDC traps was placed in the study area; sampling was conducted from May to October 2011. A total of 46,677 mosquitoes was collected, identified to species level, and classified according to their vector competence. Mosquitoes collected from 16 traps, selected according to risk-based factors, were tested by biomolecular analysis to detect flavivirus infection. This study highlights the importance of entomological surveillance in northwestern Italy because most of the mosquitoes collected were found to have high vector competence. Moreover, the risk-based virological surveillance allowed to detect the presence of mosquito flavivirus RNA, phylogenetically closely related to the MMV Spanish isolate, in three pools and USUV RNA in one pool in new areas where it has not been reported previously. The availability of continuous data on mosquito populations provides invaluable information for use in cases of an epidemic emergency. Maintenance of this integrated system for the next years will provide stronger data that can inform the design of a risk-based surveillance for the early detection of the occurrence of outbreaks of tropical MBDs.


Vaso-vagal reactions in an ambulatory surgery center.
This prospective study was undertaken to determine the incidence and factors predisposing to vaso-vagal reactions during venous cannulation in an ambulatory surgery population. In 141 ambulatory surgery patients, signs and symptoms of a reaction together with mean arterial pressure and heart rate were recorded at 1-min intervals during and for 6 min after venous cannulation. Overall, 10.6% of patients were symptomatic (95% confidence interval [CI] 6%-17%). The incidence was 16.6% (95% CI 8.4%-24.9%) in patients < or = 40 yr and 33.3% (95% CI 6.7%-60.0%) with a prior fainting history. Young age, duration or number of attempts at venous cannulation, and fainting history were independently associated with increased risk of a reaction (P < 0.03-0.004 by multiple repression analysis). Minimum mean arterial pressure was less in symptomatic patients than in those who were asymptomatic (58 mm Hg +/- 11.3 SD versus 82 mm Hg +/- 14.3 SD, P < 0.0001). We conclude that reactions occur commonly, particularly in the young or in patients with a history of fainting. Reactions are typically associated with significant hypotension that may require treatment.


Pulse pressure and risk for myocardial infarction and heart failure in the elderly.
We sought to determine whether pulse pressure (PP), a measure of arterial stiffness, is an independent predictor of the incidence of coronary heart disease (CHD), congestive heart failure (CHF) and overall mortality among community-dwelling elderly. Current hypertension guidelines classify cardiovascular risk on the basis of elevated systolic blood pressure (SBP) or diastolic blood pressure (DBP) without considering their combined effects. Recent studies suggest that PP is a strong predictor of cardiovascular end points, but few data are available among community elderly. The study sample included 2,152 individuals age > or =65 years, who were participants in the Established Populations for Epidemiologic Study of the Elderly program, free of CHD and CHF at baseline and still alive at one year after enrollment. Blood pressure was measured at baseline. Incidence of CHD, incidence of CHF and total mortality were monitored in the following 10 years. There were 328 incident CHD events, 224 incident CHF events and 1,046 persons who died of any cause. Pulse pressure showed a strong and linear relationship with each end point. After adjusting for demographics, comorbidity and CHD risk factors, a 10-mm Hg increment in PP was associated with a 12% increase in CHD risk (95% confidence interval [CI], 2% to 22%), a 14% increase in CHF risk (95% CI, 5% to 24%), and a 6% increase in overall mortality (95% CI, 0% to 12%). While SBP and mean arterial pressure (MAP) also showed positive associations with the end points, PP yielded the highest likelihood ratio chi-square. When PP was entered in the model in conjunction with other blood pressure parameters (SBP, DBP, MAP or hypertension stage, respectively), the association remained positive for PP but became negative for the other blood pressure variables. The effect of PP persisted after adjusting for current medication use and was present in normotensive individuals and individuals with isolated systolic hypertension but not in individuals with diastolic hypertension. Elevated PP is a powerful independent predictor of cardiovascular end points in the elderly.


Reflection symmetry and mode transversality in microstructured fibers.
We investigate the influence of reflection symmetry on the properties of the modes of microstructured optical fibers. It is found that structures with reflection symmetry tend to support non-degenerate modes which are closer in nature to the analogous TE and TM modes of circular step-index fibers, as compared with fibers with only rotational symmetry. Reflection symmetry induces modes to exhibit smaller longitudinal components and transverse fields which are more strongly reminiscent of the radial and azimuthal modes of circular fibers. The tendency towards "transversality" can be viewed as a result of the interaction of group theoretical restrictions on the mode profiles and minimization of the Maxwell Hamiltonian.


Ultrastructure of the dorsal skins of hairless descendants derived from Mexican hairless dogs.
Ultrastructural characteristics of the dorsal skin of hairless descendants derived from Mexican hairless dogs (3-month-, 1-year- and 5-year-old) were investigated and compared with those of age-matched beagles. Except that beagles had no melanocytes in epidermis, there was no essential difference in ultrastructural characteristics of epidermis between hairless dogs and beagles. In the Stratum basale of epidermis of hairless dogs, a small number of melanocytes and a few Langerhans cell (LC)-like cells were observed among keratinocytes. Melanocytes contained many melanosomes and a few premelanosomes. LC-like cells were characterized by electron-lucent cytoplasm and lobulated nucleus and lacked melanin granules, tonofilaments and desmosomal attachments. Unlike LC in humans and rodents, these LC-like cells did not contain Birbeck granules. Although age-related ultrastructural changes of dorsal skin were generally not clear both in hairless dogs and in beagles, cells containing melanin granules were not infrequently observed among dermal collagen bundles in 5-year-old hairless dogs.


Aneurysmal fibrous histiocytoma.
Aneurysmal fibrous histiocytoma (AFH) is a type of fibrohistiocytic tumour. We present a case of a patient who presented with a skin papule on the thigh region. Histopathological examination following total excision of the lesion revealed an AFH. No sign of recurrence was present 6 months after surgery.


Cholinergic innervation of the guinea pig tympanic membrane.
While cholinergic nerve fibers of the parasympathetic system have been demonstrated in the middle ear mucosa, such innervation of the tympanic membrane has never been shown. Such fibers may prove important since the tympanic membrane may be one of the initial sites of effusion production, and since parasympathetic innervation is thought to be involved with middle ear effusion. To demonstrate cholinergic innervation, we have used modified direct thiocholine histochemical staining. Anesthetized Hartley guinea pigs were killed, and the tympanic bullae were removed intact, fixed in 4% paraformaldehyde, and then stained whole. Following staining, the tympanic membrane was dissected from each bulla and whole-mounted for light microscopy. Numerous acetylcholinesterase-positive fibers were observed on the tympanic membrane. Some fibers appeared to be vessel associated, although the majority did not. This suggests that these fibers may act on the mucosa or vasculature of the tympanic membrane and contribute to the pathogenesis of middle ear effusion.


Effects of the hydroxyl radical and hydrogen peroxide on tooth bleaching.
The mechanisms of bleaching of discolored coronal teeth using hydrogen peroxide (H2O2) were investigated. In a scanning-electron-microscopy study, the intertubular dentin and peritubular dentin were dissolved by high concentrations of H2O2, which is used for bleaching. The X-ray diffraction study showed that hydroxyapatite was not influenced by H2O2. In an electron-spin-resonance study, more hydroxyl radical (* OH) was detected as the H2O2 concentration was increased. When amino acids that are core components of dentin proteins, such as proline and alanine, were added to H2O2, the generation of * OH decreased, but there was no change when glycine was added. A nuclear-magnetic-resonance study showed that proline was degraded completely by H2O2, the structure of alanine changed slightly, and glycine was not affected by H2O2. It is suggested that H2O2 and * OH do not influence the inorganic tissue of dentin but attack the organic component of dentin. These facts suggest that * OH has the main role in tooth bleaching with H2O2.


Gastrointestinal damage caused by swallowing multiple magnets.
Swallowing multiple magnets is not uncommon worldwide and it frequently leads to serious consequences. However, most patients fail to receive timely and correct diagnosis and treatment. A literature search was performed to establish an algorithm for these accidents by the authors to identify relevant articles published from June 1987 to October 2010 in Google, Medline, ISI Web of Knowledge Ovid, CNKI, Korea Med and library document delivery, using search terms "magnet ingestion, " "fistula," and "perforation." A total of 149 patients with ingestion of magnetic foreign bodies from 20 countries and areas were identified. 22 of them were companioned with neurological and psychiatric disorders. Swallowing magnets occurred throughout childhood and adolescent, mostly ranging 2 to 4 years in age. Various gastrointestinal damages such as necrosis and intestinal perforation or fistula were encountered. Damage from swallowing multiple magnets carries a significant risk of morbidity and even mortality throughout childhood to adolescent worldwide. Older children and adults with neurological and psychiatric problems may be at high risk for such accidents. Early intervention is crucial.


Radiocarbon concentration in tree-ring samples collected in the south-west Slovakia (1974-2013).
Radiocarbon measurements of tree-ring samples collected in Vysoká pri Morave were compared with tree-ring data of the Žlkovce monitoring station situated 5km south-east from the Jaslovské Bohunice Nuclear Power Plant (NPP). Radiocarbon concentrations in Vysoká pri Morave and in Žlkovce tree rings were decreasing exponentially with decay constants of 14.48±1.23 y and 17.96±1.97 y, respectively, in agreement with similar results obtained at other radiocarbon stations. The Suess effect, represented by a dilution in 14C levels by fossil fuel CO2 emissions, was observed in both tree-ring data sets. The Vysoká pri Morave 14C data were during 1974-1995 systematically lower by about 50‰ than the Schauinsland (Germany) clean air reference values due to a regional fossil-fuel impact. However, after 1996 the Vysoká pri Morave 14C data were closer to the Schauinsland data due to lower CO2 emissions as a result of closing some of the heavy industry technologies in the region.


Prevalence and determinants of metabolic syndrome in patients with schizophrenia: A systematic review and meta-analysis of Indian studies.
Several authors have studied prevalence of metabolic syndrome (Met-S) in schizophrenia patients. Studies conducted in Indian scenario have shown conflicting results. Community based studies reported extremely low prevalence of metabolic syndrome in contrast to hospital based studies reporting higher rates. In this systematic review we summarize results of studies conducted in India and discuss possible reasons for these discrepancies. Literature search was conducted with keywords metabolic, schizophrenia and India in PubMed, Google Scholar, and Science Direct database. Studies assessing prevalence of metabolic syndrome using IDF or NCEP-ATP III criteria, conducted in hospital and community setting were included. Fourteen studies conducted in hospital setting and two studies conducted in community were included for analysis. Pooled prevalence of Met-S in patients with schizophrenia was 29.83%. Pooled prevalence in community based studies was 10.81% significantly lower than in hospital based studies 33.05%. Overall meta-analysis of studies with case control design showed an OR 3.03 for prevalence in cases compared to controls. Except in one study conducted in a rural community, all other studies reported higher prevalence of Met-S in schizophrenia patients compared to controls. Drug-naïve patients had a pooled prevalence of 11.86%. In India, prevalence rates of Met-S in schizophrenia patients are comparable to the rates reported in western studies. Community based studies highlight a significantly lower prevalence compared to hospital studies. More community based studies will enhance our understanding of prevalence and determinants of Met-S in patients with schizophrenia.


Leiomyoma of the vagina: report of a case and literature review.
A case of a 63-year-old female with leiomyoma of the anterior vaginal wall is described. These tumors are slow in growth and solitary in number. Recurrence and sarcomatous change are only rarely seen. Treatment consists of surgical excision or enucleation.


The use of nonopioid drugs in management of chronic orofacial pain.
Although controversial, opioid analgesics have been prescribed for patients with chronic facial pain. Based primarily on survey data and a few well-controlled clinical trials, long-term opioid treatment provides adequate pain reduction in 41% to 100% of patients with chronic nonmalignant pain. However, only 25% of chronic facial pain patients reported adequate pain relief with chronic opioid treatment. Work, home, and school function are generally reestablished or maintained during chronic opioid treatment, but 25% to 38% of patients remain dysfunctional, and one study indicated that 20% of patients became dysfunctional during treatment. Chronic opioid treatment is associated with many transient side effects; constipation, dizziness, nausea, vomiting, itching, and fatigue have been reported in 5% to 42% of patients taking opioids over 1 year. Although survey studies suggest that the risks of addiction are low in typical patients, drug abuse rates up to 17.3% and prescription abuse rates up to 27.6% were reported within groups of chronic opioid users. Chronic opioid use induces analgesic tolerance and physical dependence, which may result in a serious abstinence syndrome in users and children born to users. Chronic opioid use also may induce harmful immune system changes, diminish cognitive and motor function, and produce nociceptive hyperexcitability. This article shows that the use of long-term opioids for chronic facial pain is not justified based on the available data. Despite these perceived problems, there is anecdotal evidence that chronic facial pain patients will respond positively to opioid analgesics. In our experience, the pain assessment scale and a modification of the World Health Organization's three-step analgesic ladder, which prescribes nonopioid analgesics, can be the starting point for the successful management of chronic facial pain.


Gold nanolabels for new enhanced chemiluminescence immunoassay of alpha-fetoprotein based on magnetic beads.
Gold'n'beads: A chemiluminescence immunoassay for the sensitive and rapid determination of AFP has been developed, employing bromophenol blue as a novel chemiluminescence enhancer by taking advantages of easy separation by magnetic beads and signal amplification by gold nanoparticles based on a sandwich-type immunoreaction (see scheme).A novel and sensitive chemiluminescence immunoassay (CLIA) has been developed by employing a new chemiluminescence (CL) enhancer, bromophenol blue (BPB), for the determination of alpha-fetoprotein (AFP) based on magnetic beads (MBs) and colloidal gold nanoparticles (AuNPs) modified with HRP-labeled anti-AFP antibodies. BPB, as a chemical indicator, was found to act as a novel and highly signal enhancer of the peroxidase-catalyzed CL reaction of luminol with hydrogen peroxide. After optimizing the CL reaction conditions, this new luminol-H(2)O(2)-HRP-BPB CL system was applied to a sandwich-type CLIA based on the magnetic separation and the amplification feature of AuNPs as HRP labels. A linear range was obtained when the concentrations of AFP were from 0.1 to 5.0 ng mL(-1) (R=0.9997) with the detection limit of 0.01 ng mL(-1) (3sigma), which is one order of magnitude lower than that obtained without using AuNPs, and much lower than that typically achieved by ELISA. The present method was successfully applied to the determination of AFP in human serum samples. The results indicated that this proposed protocol could be quite promising for the application in immunoassays.


Glutathione conjugation attenuates biological activities of 6-dehydroshogaol from ginger.
6-Dehydroshogaol (6-DHSG) is a bioactive α,β-unsaturated carbonyl compound isolated from fresh ginger with anti-inflammatory and phase II enzyme inducing activities. Here we describe the glutathione (GSH)-dependent metabolism and the effect of this metabolic transformation on the biological activities of 6-DHSG. Compared with other ginger compounds, such as 6-gingerol and 6-shogaol, 6-DHSG showed the most potent anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The biological activities of 6-DHSG were attenuated by sulfhydryl antioxidants such as glutathione (GSH) or N-acetyl cysteine (NAC), but not ascorbic acid (ASC). 6-DHSG was metabolised by GSH to form a GSH conjugate (GS-6-DHSG) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of glutathione-S-transferase (GST). GS-6-DHSG showed reduced biological activities compared with 6-DHSG in multiple biological assays. Together, these results indicate that GSH conjugation attenuates the biological activities of 6-DHSG and other α,β-unsaturated carbonyl compounds.


Multiplexed phase-space imaging for 3D fluorescence microscopy.
Optical phase-space functions describe spatial and angular information simultaneously; examples of optical phase-space functions include light fields in ray optics and Wigner functions in wave optics. Measurement of phase-space enables digital refocusing, aberration removal and 3D reconstruction. High-resolution capture of 4D phase-space datasets is, however, challenging. Previous scanning approaches are slow, light inefficient and do not achieve diffraction-limited resolution. Here, we propose a multiplexed method that solves these problems. We use a spatial light modulator (SLM) in the pupil plane of a microscope in order to sequentially pattern multiplexed coded apertures while capturing images in real space. Then, we reconstruct the 3D fluorescence distribution of our sample by solving an inverse problem via regularized least squares with a proximal accelerated gradient descent solver. We experimentally reconstruct a 101 Megavoxel 3D volume (1010×510×500µm with NA 0.4), demonstrating improved acquisition time, light throughput and resolution compared to scanning aperture methods. Our flexible patterning scheme further allows sparsity in the sample to be exploited for reduced data capture.


The hypothyroid rat as a model of increased sensitivity to dopamine receptor agonists.
Control and hypothyroid rats were challenged with a range of doses (0.5-4 mumol/kg) of either the nonselective dopamine agonist, apomorphine, or the selective D2 receptor agonist. LY 171555, and their stereotyped head-down sniffing (SHDS) responses measured. The dose-response curves for both agonists were shifted to the left in the hypothyroid rats compared to water-treated controls. Increasing doses of the selective D2 antagonist, raclopride, caused a parallel shift to the right in the LY 171555-induced SHDS dose-response curve. Schild analysis revealed a decreased sensitivity to raclopride in the hypothyroid animals. The selective D1 antagonist SCH 23390 was observed to decrease the maximal response elicited by LY 171555 in a dose-dependent manner and the hypothyroid rats were more sensitive to this effect. It was concluded that hypothyroid rats showed an apparent increased sensitivity to D2 receptor agonists and a decreased sensitivity to D2 antagonists. In addition, the facilitation effect of the D1 receptor on the D2 receptor appeared less tightly coupled in the hypothyroid rats.


A randomized, double-blind comparison of the antihypertensive efficacy and safety of once-daily losartan compared to twice-daily captopril in mild to moderate essential hypertension.
The antihypertensive efficacy and safety of losartan, a specific and selective angiotensin II (AII) receptor antagonist, was compared to captopril in patients with mild or moderate essential hypertension. This multinational, randomized trial consisted of a 4-week single-blind, placebo baseline period followed by a 12-week double-blind, parallel comparison of once-daily administration of losartan 50 mg or twice-daily administration of captopril 25 mg. After 6 weeks of treatment, the daily dosage was doubled in patients whose sitting diastolic blood pressure (SiDBP) remained > or = 90 mm Hg. Patients with essential hypertension having a mean trough SiDBP of 95-115 mm Hg after the placebo baseline period were randomized to losartan (N = 192) or captopril (N = 204) treatment. The primary efficacy variable was the mean change from baseline to Week 12 in trough SiDBP. Safety was assessed by recording spontaneously reported or observed adverse experiences and clinical laboratory measurements. After 12 weeks, both treatments produced clinically important reductions in trough SiDBP and sitting systolic blood pressure (SiSBP). These mean reductions (SiDBP, SiSBP) were significantly greater in the losartan group (-11.5 and -15.4 mm Hg, respectively) than in the captopril group (-9.3 and -12.2 mm Hg, respectively) (p = 0.010 for diastolic and p = 0.023 for systolic). The percentage of patients exhibiting an excellent (trough SiDBP < 90 mm Hg) or good (trough SiDBP > 90 mm Hg, with decrease of > or = 10 mm Hg) antihypertensive response to losartan and captopril therapy at Week 12 was comparable (60.0% and 54.7%, respectively). The percentage of patients reporting a clinical adverse experience considered drug-related by the investigator was 13% in the captopril group and 10% in the losartan group. The incidence of drug-related cough was 2.6% in the losartan group and 4.4% in the captopril group. Once daily administration of losartan 50 to 100 mg is an effective treatment for patients with essential mild to moderate hypertension. The antihypertensive efficacy of losartan 50/100 mg is significantly greater than that of twice daily captopril 25/50 mg. Both treatments were generally well-tolerated. The number of patients with the side effect of cough was higher following captopril.


Sphingolipids involved in T1DM.


[Arterial surgery of the upper limb].
Arterial surgery of the upper limb represents 2.5% of peripheral vascular procedures in our center. From 1976 to 1989, 58 procedures were performed in 45 patients. There were 26 men and 19 women with average age of 52 years, ranging from 6 to 92 years. These patients were grouped in three categories according to etiology: 1) trauma; 2) acute non traumatic ischemia and 3) chronic ischemia. Sixteen patients (35.5%) were operated on for arterial trauma including three false aneurysms. Blunt trauma was the cause in 9 patients, penetrating in 6 and iatrogenic in one. Angioplasty and primary end to end anastomosis were used in 6, bypass in 4, simple ligation in 3, thrombectomy in 3. The outcome was excellent in 15/16 (93%). Non traumatic acute ischemia occurred in 16 patients (35.5%) and was due to emboli of cardiac origin in 92%. All patients were treated by thromboembolectomy. This group had a high mortality (5/16, 31%) because of associated medical conditions. The third group of 13 patients (29%) underwent surgery for chronic ischemia of the upper limb localized to the subclavian artery in 92%. They were treated with carotid subclavian bypasses in 9, other types of bypass in 3 and endarterectomy in 1. Excellent results were obtained in 10/13 (78%). Overall, satisfactory results were obtained in 90% of surviving patients. Operative mortality was 11.1% and the amputation rate was 13%.


Targeting phosphoinositide 3-kinase pathways in pancreatic cancer--from molecular signalling to clinical trials.
Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its silent nature and tendency for late discovery but also because of its persistent resistance to chemotherapy. At present there are very limited treatment alternatives for pancreatic cancer, hence the need to develop novel and more efficient drugs. It is well known that mutations in K-Ras oncogene accumulate early in the disease progression and occur in almost all of pancreatic ductal adenocarcinomas (PDAC). A key downstream target of the Ras family is phosphoinositide 3-kinase (PI3K), the enzyme responsible for generation of 3-phosphorylated phosphoinositides and activation of Akt (Protein Kinase B/Akt). The PI3K/Akt pathway is involved in inhibition of apoptosis and stimulation of cell proliferation and it is has been estimated that at least 50% of all cancer types are related to deregulation of this signalling pathway. In this review we will discuss how the PI3K/Akt/mTOR signaling network is altered in pancreatic cancer and further give an overview of preclinical and clinical studies where this pathway has been targeted.


A prospective study of egg consumption and risk of cardiovascular disease in men and women.
Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse. To examine the association between egg consumption and risk of CHD and stroke in men and women. Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994). A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer. Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire. We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and > or =1 per day (1.08) (P for trend = .75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and > or =1 per day (0.82) (P for trend = .95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend = .04], and among diabetic women, 1.49 [0.88-2.52; P for trend = .008]). These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.


Behçet disease-associated uveitis successfully treated with golimumab.
Over the past decade, the off-label use of biologic agents such as TNF-α antagonists, including infliximab and adalimumab, has improved the treatment armamentarium for refractory immune-mediated uveitis, with particular success in Behçet disease-associated uveitis. Golimumab is a novel fully human anti-TNF-α monoclonal antibody that has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, with very promising results. Herein, the authors present the use of GLM in a case of Behçet uveitis refractory to other TNF-α blockers. There are only two reports in the literature about the use of GLM in uveitis, describing four patients with JIA-associated uveitis and a case of idiopathic retinal vasculitis. To the authors' knowledge, this is the first report about the use of GLM in Behçet uveitis.


Cyclometalated cinchophen ligands on iridium(III): towards water-soluble complexes with visible luminescence.
Eight cationic heteroleptic iridium(III) complexes, [Ir(epqc)2(N^N)](+), were prepared in high yield from a cyclometalated iridium bridged-chloride dimer bearing two ethyl-2-phenylquinoline-4-carboxylate (epqc) ligands. Two X-ray crystallographic studies were undertaken on selected complexes (where the ancillary ligand N^N = 4,4'-dimethyl-2,2'-bipyridine and 4,7-diphenyl-1,10-phenanthroline) each confirming the proposed formulations, showing an octahedral coordination at Ir(III). In general, the complexes are luminescent (620-630 nm) with moderately long lifetimes indicative of phosphorescence. Hydrolysis of the ethyl ester moieties of the epqc ligands gave the analogous cinchophen-based complexes, which were water-soluble and visibly luminescent (568-631 nm). The spectroscopic and redox characterisation of the complexes was complemented by DFT and TD-DFT calculations, supporting the assignment of dominant (3)MLCT to the emissive character.


Reaction of cis- and trans-[PtCl2(NH3)2] with reduced glutathione inside human red blood cells, studied by 1H and 15N-[1H] DEPT NMR.
Reactions of cis- and trans-[PtCl2(NH3)2] with glutathione (GSH) inside intact red blood cells have been studied by 1H spin-echo nuclear magnetic resonance (NMR). Upon addition of trans-[PtCl2(NH3)2] to a suspension of red cells, there was a gradual decrease in the intensity of the resonances for free GSH, and new peaks were observed that were assignable to coordinated GSH protons in trans-[Pt(SG)Cl(NH3)2], trans-[Pt(SG)2(NH3)2], and possibly the S-bridged complex trans-[[NH3)2PtCl)2SG]+. Formation of trans-[Pt(SG)2(NH3)2] inside the cell was confirmed from the 1H NMR spectrum of hemolyzed cells, which were ultrafiltered to remove large protein molecules; the ABM multiplet of the coordinated GSH cys-beta CH2 protons was resolved using selective-decoupling experiments. Seventy percent of the total intracellular GSH was retained by the ultrafiltration membrane, suggesting that the mixed complex trans-[Pt(SG)(S-hemoglobin)(NH3)2] also is a major metabolite of trans-[PtCl2(NH3)2] inside red cells. The reaction of cis-[PtCl2(NH3)2] with intracellular GSH was slower; only 35% of the GSH had been complexed after a 4-hr incubation compared to 70% for the trans isomer. There was a gradual decrease in the intensity of the GSH 1H spin-echo NMR resonances, but no new peaks were resolved. This was interpreted as formation of high-molecular weight Pt:GSH and mixed GS-Pt-S(hemoglobin) polymers. By using a 15N-[1H] DEPT pulse sequence, we were able to study the reaction of cis-[PtCl2(15NH3)2] with red cells at concentrations as low as 1 mM. 15NH3 ligands were released, and no resonances assignable to Pt-15NH3 species were observed after a 12-hr incubation.


Floral MADS-box protein interactions in the early diverging angiosperm Aristolochia fimbriata Cham. (Aristolochiaceae: Piperales).
Floral identity MADS-box A, B, C, D, E, and AGL6 class genes are predominantly single copy in Magnoliids, and predate the whole genome duplication (WGD) events in monocots and eudicots. By comparison with the model species Arabidopsis thaliana, the expression patterns of B-, C-, and D-class genes in stamen, carpel, and ovules are conserved in Aristolochia fimbriata, whereas A-, E-class, and AGL6 genes have different expression patterns. Nevertheless, the interactions of these proteins that act through multimeric complexes remain poorly known in early divergent angiosperms. This study evaluates protein interactions among all floral MADS-box A. fimbriata proteins using the Yeast Two Hybrid System (Y2H). We found no homodimers and less heterodimers formed by AfimFUL when compared to AfimAGL6, which allowed us to suggest AGL6 homodimers in combination with AfimSEP2 as the most likely tetramer in sepal identity. We found AfimAP3-AfimPI obligate heterodimers and AfimAG-AfimSEP2 protein interactions intact suggesting conserved stamen and carpel tetrameric complexes in A. fimbriata. We observed a broader interaction partner set for AfimSEP2 than for its paralog AfimSEP1. We show conserved and exclusive MADS-box protein interactions in A. fimbriata in comparison with other eudicot and monocot model species in order to establish plesiomorphic MADS-box protein floral networks in angiosperms.


A new clue for the pathogenesis of hepatitis C virus infection: Activation of the MAPK/ERK signaling initiated by envelope protein 2.
Since cell signal transduction plays an important role in disclosing the nature of human diseases, the pathogenesis of viruses may result from the disturbance of intracellular signal cascades caused by viral proteins. Hepatitis C virus (HCV) is a main causative agent of severe human liver disorders worldwide. So far, the mechanisms of HCV pathogenicity remain unclear. Envelope protein 2 (E2) of HCV is thought to be responsible for initiating virus attachment to host cells, which is a prerequisite of HCV infection. We assume that some early events of HCV pathogenic effects may result from the interaction of HCV E2 protein with its cellular receptor (human CD81), which could regulate cell proliferation and differentiation. To test this hypothesis, the effects of HCV E2 protein on MAPK/ERK pathway in Molt-4 and U937 cells with or without human CD81 expression were investigated. The results showed that HCV E2 protein could specifically activate the MAPK/ERK pathway, and such activation was inhibited by monoclonal antibodies against CD81 or HCV E2, serum antibodies from HCV infected patients, and upstream MEK1 inhibitor PD98059. Moreover, HCV E2-driven MAPK/ERK or downstream transcription factor Elk-1 activation was completely blocked in the presence of PD98059. These findings strongly suggest that the regulation of transmembrane signaling by HCV E2 protein via its receptor(s) on host cells might contribute to the development of HCV-related diseases.


Differential release of human intestinal alkaline phosphatase in duodenal fluid and serum.
Human intestinal alkaline phosphatase (IAP) can be released by the enterocyte into duodenal fluid as a mixture of three isoforms. A proportion of the enzyme is associated with triple-layered membrane vesicles (vesicular IAP). Although, occasionally, free hydrophilic IAP dimers are present, the remaining enzyme usually consists of a mixture of hydrophobic IAP dimers and more complex hydrophobic IAP structures of larger size, both entities being identified as "intestinal variant" alkaline phosphatase (VAR IAP). The hydrophobicity of VAR IAP stems exclusively from its attached glycosyl-phosphatidylinositol (GPI) anchor. Both vesicular IAP and VAR IAP are converted to hydrophilic enzyme upon removal of the GPI tail by phospholipase D (PLD) present in duodenal fluid. The IAP released into the vascular bed consists mainly of VAR IAP; vesicular IAP is absent. The enzyme characteristics of VAR IAP partially purified from duodenal fluid and from serum are identical. In plasma, VAR IAP appears to associate with (lipo)protein complexes and is thus protected from further degradation by plasma PLD. Such complex formation may explain why, in the serum of a healthy reference population, VAR IAP was more abundant than hydrophilic dimeric IAP.


Primary care in the A & E department: meeting the challenge--a workshop series for A & E nurses.
Accident and emergency (A & E) departments lie at the interface between primary and secondary care. Patients who attend the accident and emergency department with primary care needs have traditionally been seen as 'inappropriate' and labelled in pejorative terms. Over the past few years, however, new models of care have emerged through research and practice development for meeting the needs of this group of patients in A & E. For effective service development there is a need to challenge and change the traditional A & E culture. This paper describes an educational approach towards changing clinical practice, by disseminating research and practice development initiatives through a workshop series. It aimed to disseminate research in a relevant manner to practitioners and to develop the primary care orientation of a number of A & E departments in England and Scotland. The workshop series sought to influence clinical practice by sharing the experience of researchers and practitioners in a supportive learning environment. The use of this approach offered a means of bridging the gap between research and practice development. The paper outlines the rationale for the workshop series, its structure, aims and objectives, and the reported progress in relation to change management and service provision identified by the participants. The workshop series proved to be an effective means of disseminating experience of research, practice development and change management.


Diagnostic accuracy of transbronchial biopsy in acute farmer's lung disease.
To evaluate whether transbronchial biopsy (TBB) is useful for the diagnosis of acute farmer's lung (FL) by calculating the likelihood ratios (LHRs) of (1) simple pathologic criteria and (2) an overall assessment of the biopsy specimens. Retrospective study in which a blinded analysis of 105 TBBs with adequate material from patients with parenchymal diseases (55 cases of FL matched with 50 control samples) was performed by two independent pathologists. Respiratory clinic of a university-affiliated referral center. Three pathologic criteria were first studied: (1) diffuse lymphocytic infiltration (LI); (2) focal LI; and (3) granulomas. Then, an overall assessment or the TBB was done. Four diagnostic categories were considered: (1) probable FL; (2) possible FL; (3) nonspecific; and (4) alternative diagnosis. LHRs favoring the diagnosis of FL were calculated for the pathologic criteria and for each diagnostic category. For both the pathologic criteria and the overall assessments, the interobserver agreement was fair. As a pathologic criterion, "diffuse LI" was better than "loosely formed granuloma" to discriminate FL from control samples (LHR, 9.1 [confidence interval, 2.2 to 37.0] vs 1.8 [confidence interval, 0.5 to 6.9]). After the overall assessment, as many as 48.6% of the TBBs were read as nonspecific. The LHRs of the four diagnostic categories were as follows: (1) probable FL: 1.1 (observer 1) and 2.6 (observer 2); (2) possible FL: 2.2 and 1.7; (3) nonspecific: 0.9 and 0.6; and (4) alternative diagnosis: 0.4 and 0.0. Hematoxylin-eosin-stained TBB specimen is of limited usefulness for the diagnosis of FL and should be reserved for patients with intermediate pretest probability of FL. Diffuse LI best discriminates FL from control samples and should be specifically sought.


Surgery to the external genitalia.
Surgery to the external genitalia is one of the most challenging chapters of reconstructive urology, due to the need to correct complex problems such as hypospadias or epispadias (isolated or associated to exstrophies). Although this specialty has shown a continuous technical advancement there is no consensus as to the most efficient surgical procedure or to the best strategy to treat these pathologies. The papers reviewed here reflect these statements and reinforce the idea that surgeons' good sense, allied with their experience in the area, are the factors that define the choice of the ideal surgical option for each case.


Molecular cloning and high-level expression of human polymerase beta cDNA and comparison of the purified recombinant human and rat enzymes.
The cDNA encoding the human polymerase beta from HeLa cells was PCR amplified and cloned, and its nucleotide sequence determined. The DNA sequence is identical to the polymerase beta cDNA sequence from Tera-2 cells. Three expression strategies were employed that were designed to maximize translation initiation of the polymerase beta mRNA in Escherichia coli and all yielded a high level of human polymerase beta. The recombinant protein was purified and its properties were compared with those of the recombinant rat enzyme. The domain structure and kinetic parameters (k(cat) and K(m)) were nearly identical. A mouse IgG monoclonal antibody to the rat enzyme (mAb-10S) was approximately 10-fold less reactive with the human enzyme than with the rat enzyme as determined by ELISA.


Halitosis: an overview of epidemiology, etiology and clinical management.
Halitosis is an unpleasant condition that causes social restraint. Studies worldwide indicate a high prevalence of moderate halitosis, whereas severe cases are restricted to around 5% of the populations. The etiological chain of halitosis relates to the presence of odoriferous substances in exhaled air, especially the volatile sulphur compounds (VSC) produced by bacteria. The organoleptic diagnosis is the gold standard and clinical management includes oral approaches, especially periodontal treatment and oral hygiene instructions, including the tongue. When oral strategies are not successful, referral to physicians is warranted.


Is clear speech tailored to counter the effect of specific adverse listening conditions?
The study investigated the perception of speech produced to counter the effects of adverse listening conditions. Participants completed a problem-solving task with an interlocutor in good listening conditions (NB) or with the interlocutor hearing them via a vocoder (VOC) or babble (BAB). Keywords extracted from recordings were presented in babble for initial consonant identification. BAB tokens were identified faster than VOC or NB tokens even though VOC and BAB tokens were rated as similarly clear. Acoustic measures showed clarifications to be global rather than specifically enhancing phonological contrasts. These results suggest that clear speaking styles are tailored to listeners' needs.


Homeostasis limits the development of mature CD8+ but not CD4+ thymocytes.
The involvement of a variety of clonal selection processes during the development of T lymphocytes in the thymus has been well established. Less information, however, is available on how homeostatic mechanisms may regulate the generation and maturation of thymocytes. To investigate this question, mixed radiation bone marrow chimeras were established in which wild-type T cell precursors capable of full maturation were diluted with precursors deficient in maturation potential because of targeted mutations of the RAG1 or TCR-alpha genes. In chimeras in which the majority of thymocytes are blocked at the CD4- CD8- CD25+ stage (RAG1 deficient), and only a small proportion of T cell precursors are of wild-type origin, we observed no difference in the maturation of wild-type CD4- CD8- CD25+ cells to the CD4+ CD8+ stage as compared with control chimeras. Therefore, the number of cell divisions occurring during this transition is fixed and not subject to homeostatic regulation. In contrast, in mixed chimeras in which the majority of thymocytes are blocked at the CD4+ CD8+ stage (TCR-alpha deficient), an increased efficiency of development of wild-type mature CD8+ cells was observed. Surprisingly, the rate of generation of mature CD4+ thymocytes was not affected in these chimeras. Thus, the number of selectable CD8 lineage thymocytes apparently saturates the selection mechanism in normal mice while the development of CD4 lineage cells seems to be limited only by the expression of a suitable TCR. These data may open the way to the identification of homeostatic mechanisms regulating thymic output and CD4/CD8 lineage commitment, and the development of means to modulate it.


Synthesis of 11H-pyridocarbazoles and derivatives. Comparison of their DNA binding and antitumor activity with those of 6H- and 7H-pyridocarbazoles.
The 8-methoxy- and 8-hydroxy-11H-pyrido[2,3-a]-, -[3,4-a]-, -[4,3-a]-, and [3,2-a]carbazoles were synthesized as potential DNA intercalating antitumor drugs. The structure of these compounds was confirmed by 1H NMR study including NOE experiments. The DNA binding properties of substituted and unsubstituted (8-H) heterocycles were determined by using their hydrochlorides or methiodides. These derivatives are able to bind to DNA with an affinity varying from 2.0 X 10(4) to 1.0 X 10(6) M-1, but most of them are unable to intercalate in contrast with the behavior of 6H- and 7H-pyridocarbazole analogues. The cytotoxicity of 11H-pyridocarbazoles, measured on L1210 cells in vitro, is much lower than those of 6H- and 7H-pyridocarbazole analogues.


Distributions of (137)Cs and (210)Pb in moss collected from Belarus and Slovakia.
In the present work, moss samples collected in Slovakia and Belarus were assayed with respect to gamma-emitting radionuclides. The results for (137)Cs and (210)Pb are discussed. Moss was used for the first time in Belarus, as a biological indicator of radioactive environmental pollution in consequence of the Chernobyl accident in 1986. In Belarus, the maximum activity of (137)Cs was observed in the Gomel region near Mazyr (6830 Bq/kg) and the minimum activity in the Vitebsyevsk Region near Luzhki-Yazno (5 Bq/kg). "Hot spots" were also observed near the towns Borisow and Yuratsishki. The results of measurements of (137)Cs in moss samples collected in 2000, 2006 and 2009 in the same localities of Slovakia are presented and compared with the results of air monitoring of (137)Cs carried out in Slovakia from 1977 until 2010. Measurements of the (210)Pb concentration in moss samples collected over the territory of Slovakia showed, that the median value exceed 2.3 times median value of (210)Pb obtained for Belarus moss. For that reason, the inhalation dose for man from (210)Pb and (137)Cs in Slovakia is more than twice as high as in Belarus, in spite of the initially very high (137)Cs exposure in the latter country.


Molecular characterization of the Anopheles gambiae 2L telomeric region via an integrated transgene.
A Drosophila P-element derivative (pUChsneo) integrated into the telomeric region of the left arm of the second chromosome of Anopheles gambiae was used to clone the proximally flanking An. gambiae sequences. Molecular analyses revealed that the pUChsneo construct was partially duplicated and had integrated into a subterminal minisatellite. This satellite has a repeat unit of 820 bp and is located exclusively at the tip of 2L. No sequence similarity to subterminal minisatellites from other dipterans was detected, but some structural features such as tandem subrepeats are shared. The end of the chromosome was mapped with respect to restriction sites in pUChsneo at approximately generation 100 after the integration event. Considering inevitable terminal nucleotide loss due to incomplete DNA replication, we conclude that the chromosome end must have undergone a dramatic elongation process since it was mapped in generation 23.


Zwitterionic sulfobetaine-grafted poly(vinylidene fluoride) membrane with highly effective blood compatibility via atmospheric plasma-induced surface copolymerization.
Development of nonfouling membranes to prevent nonspecific protein adsorption and platelet adhesion is critical for many biomedical applications. It is always a challenge to control the surface graft copolymerization of a highly polar monomer from the highly hydrophobic surface of a fluoropolymer membrane. In this work, the blood compatibility of poly(vinylidene fluoride) (PVDF) membranes with surface-grafted electrically neutral zwitterionic poly(sulfobetaine methacrylate) (PSBMA), from atmospheric plasma-induced surface copolymerization, was studied. The effect of surface composition and graft morphology, electrical neutrality, hydrophilicity and hydration capability on blood compatibility of the membranes were determined. Blood compatibility of the zwitterionic PVDF membranes was systematically evaluated by plasma protein adsorption, platelet adhesion, plasma-clotting time, and blood cell hemolysis. It was found that the nonfouling nature and hydration capability of grafted PSBMA polymers can be effectively controlled by regulating the grafting coverage and charge balance of the PSBMA layer on the PVDF membrane surface. Even a slight charge bias in the grafted zwitterionic PSBMA layer can induce electrostatic interactions between proteins and the membrane surfaces, leading to surface protein adsorption, platelet activation, plasma clotting and blood cell hemolysis. Thus, the optimized PSBMA surface graft layer in overall charge neutrality has a high hydration capability and the best antifouling, anticoagulant, and antihemolytic activities when comes into contact with human blood.


Prenatal diagnosis and outcome of a ruptured aneurysm arising from the left atrium.
Prenatal diagnosis of a fetal cardiac aneurysm or diverticula is rare. We report what we believe to be the first case of an atrial wall aneurysm diagnosed as ruptured or leaking by fetal pericardiocentesis. Spontaneous resolution of the anomaly was observed in the third trimester with delivery of a vigorous newborn at term. The infant did not require surgical intervention after birth and has done well at follow-up examinations.


Clinical audit of anaesthesia practice and adverse peri-operative events at Parkland Memorial Hospital, Dallas, Texas.
A study was undertaken to compare the quantity and nature of adverse event data collected during two equivalent time periods in 1990-1991 and 1991-1992 respectively. During the first period adverse event data were collected and reviewed sporadically, critical incidents were not specifically identified and no formal mechanism for regular presentation of these data existed. During the second period a new and detailed data collected from was introduced. The resulting data were analysed and presented to trainee and senior anaesthetists during formal clinical education sessions. Adverse incident reporting was significantly increased during the later period. Unsafe clinical practices and common errors were also more easily identified.


Fowler syndrome-a clinical, radiological, and pathological study of 14 cases.
We report on 14 fetuses from 10 families with the autosomal recessive syndrome of proliferative vasculopathy and hydranencephaly-hydrocephaly (Fowler syndrome). In four families sibs were affected and in six the parents were consanguineous. Antenatal ultrasonography showed hydrocephaly in all except two fetuses, but hydranencephaly was diagnosed in only one case. Postural abnormalities were seen in 10 fetuses and structural brain abnormalities were suspected in 3. At autopsy the cerebral cortex appeared as a translucent membranous structure (hydranencephaly) in most fetuses. However, in one case, the ventricles were dilated but the cortical mantle was relatively well preserved. Histology of the brain showed the characteristic glomeruloid vascular proliferation of Fowler syndrome in all cases, but with variable extent of involvement of the central nervous system. Dystrophic calcification and necrosis were always present. Extra-cranial anomalies included micrognathia (10 fetuses), cleft palate (1 fetus), cystic hygroma (2 fetuses), joint contractures (12 fetuses), and pterygia (11 fetuses). The typical proliferative vasculopathy was never observed outside the central nervous system and karyotypes were normal in the 10 fetuses studied. Fowler syndrome should be considered in the differential diagnosis of lethal multiple pterygium syndrome, fetal akinesia, and hydrocephalus in addition to classical hydranencephaly. Autopsy and study of the brain are essential to differentiate autosomal recessive Fowler syndrome from other causes of hydrocephaly and hydranencephaly, which may have a lower recurrence risk.


A diagnostic approach to developmental specific learning disorders.
Children and adolescents who are not doing well in school are often referred to physicians for evaluation. Many of these children have average or above-average intelligence but are academically frustrated, low achievers. Parents state that although they are convinced that their child is bright, he or she does not seem to learn, and does not behave acceptably in school and at home. Results of the usual pediatric and neurologic examinations are frequently unrevealing. In evaluating children who are doing poorly in school, the clinician must determine whether the child has a developmental specific learning disorder and whether primary affective illness, disturbed vigilance, or hyperactivity complicates the picture. Children who are intelligent but failing in school frequently manifest either one or several of these conditions. Although there are reasonably well-established criteria for affective illness in children, clinically useful criteria for evaluating the variety of childhood learning problems have not been available. We present criteria for the diagnosis of developmental specific learning disorders and briefly mention some aspects of management and treatment. We also describe a primary disorder of vigilance that becomes manifest in school, worsening the learning and performance process, which is further worsened by affective illness.


Changes in plasma orexin-A levels in sevoflurane-remifentanil anesthesia in young and elderly patients undergoing elective lumbar surgery.
Delayed emergence from general anesthesia frequently occurs in elderly patients, but the reason is not clear. Orexin has been shown to be involved in arousal from general anesthesia. In this study, we examined plasma orexin-A levels in both elderly and young patients during the anesthesia arousal cycle. We recruited 41 patients scheduled for elective lumbar surgery and eventually evaluated 34 patients. Patients were divided into a young group (age 30-55, N = 16) and an elderly group (age 65-77, N = 18). Anesthesia with sevoflurane-remifentanil was titrated to maintain the Bispectral Index between 45 and 65. The times from stopping anesthesia to eyes opening and extubation were recorded. Arterial blood was collected, and plasma orexin-A was determined by radioimmunoassay at the following 4 time points: preanesthesia (T0), 1 hour after anesthesia induction (T1), emergence (5 minutes after tracheal extubation) (T2), and 30 minutes after tracheal extubation (T3). The times from stopping anesthesia to eyes opening and tracheal extubation were both significantly longer in the elderly group than in the young group (P = 0.004, P = 0.01, respectively). Basal (T0) orexin-A levels were higher in the elderly group than in the young group (T0, 26.13 ± 1.25 vs 17.9 ± 1.30 pg/mL, P < 0.0001). Plasma orexin-A levels did not change during induction of anesthesia in either group but significantly increased at T2 (vs T0, P <0.0001) in both elderly (35.0 ± 1.7 pg/mL) and young (29.2 ± 1.9 pg/mL) groups. Orexin-A levels were significantly higher in the elderly than in the young group at T1, T2, and T3. Plasma orexin-A levels are not responsible for the delayed emergence from general anesthesia in elderly patients.


A retrospective study of the effect of fibrinogen levels during fresh frozen plasma transfusion in patients with traumatic brain injury.
The association between traumatic brain injury (TBI) and coagulopathy is well established. While coagulopathy prophylaxis in TBI involves replenishing coagulation factors with fresh frozen plasma (FFP), its effectiveness is controversial. We investigated the relationship between plasma fibrinogen concentration 3 h after initiating FFP transfusion and outcomes and evaluated the correlation with D-dimer levels at admission. We retrospectively examined data from 380 patients with severe isolated TBI with blood samples collected a maximum of 1 h following injury. Plasma fibrinogen and D-dimer concentrations were obtained at admission, and plasma fibrinogen concentration was again assessed 3-4 h following injury. The patients were divided into two groups based on whether or not they received FFP transfusion. Patients were also divided into subgroups according their fibrinogen level: ≥ 150 mg/dL (high-fibrinogen subgroup) or < 150 mg/dL (low-fibrinogen subgroup) 3 h after injury. Demographic, clinical, radiological and laboratory data were compared between these subgroups. Glasgow Outcome Scale (GOS) scores at discharge and 3 months after injury were significantly lower in the FFP transfusion group than in the FFP non-transfusion group. Among patients who received FFP, GOS scores at discharge and 3 months after injury were significantly higher in the high-fibrinogen subgroup than in the low-fibrinogen subgroup. Elevated admission D-dimer predicted subsequent fibrinogen decrease. In FFP transfusion, fibrinogen level ≥ 150 mg/dL 3 h after injury was associated with better outcomes in TBI patients. Assessing the admission D-dimer and tracking the fibrinogen are crucial for optimal coagulopathy prophylaxis in TBI patients.


From lecture to learning tasks: use of the 4C/ID model in a communication skills course in a continuing professional education context.
This article describes the use of four-component instructional design (4C/ID), a model to plan educational interventions for complex learning. This model was used to design a continuing education course on communication skills for health professionals in a context that is hierarchical and communal. The authors describe the 4C/ID model and provide an example of its application in designing the course. In the 4C/ID model, learning tasks serve as the backbone of the course, with lectures and other supportive information organized around them. The 4C/ID model is different from traditional models that base the course on lectures on different topics and connect part-task assignments to these topics. The use of the 4C/ID model to develop the educational intervention moves the paradigm from lectures to learning tasks to better prepare learners for real practice.


Quantitative measurements of the volume and surface area of the radial head.
We investigated the hypothesis that a quantitative 3-dimensional computed tomography (Q3DCT) modeling technique based on anatomical and demographic data that can measure size, shape, and proximal articular surface area can be used to develop formulas that could predict the volume and proximal surface area of the intact radial head in patients with fractures of the radial head. We used a consecutive series of 50 computed tomography scans with a slice thickness of 1.25 mm or less obtained in patients with fracture of the distal humerus, but no injury to the radial head, to create 3-dimensional models. The volume and proximal articular surface area of the radial head were measured, and predictive formulas based on anatomical measurements and gender were calculated using multiple linear regression. There were significant correlations between total radial head volume and proximal radial head articular surface area for height, weight, radial head diameter, radial neck diameter, coronoid diameter, and gender. Multiple linear regression modeling resulted in formulas that could account for 89% of the variation in radial head volume and 75% of the variation in proximal articular surface area. The volume and proximal articular surface area of the radial head can be estimated based on anatomical measurements and gender. This may lead to better estimates of lost fragments when it is not possible to directly model the fractured radial head and computed tomography scan of the opposite limb is not available.


Percutaneous versus surgical closure of secundum atrial septal defects: a systematic review and meta-analysis of currently available clinical evidence.
To summarise data from studies comparing surgical (SC) versus percutaneous closure (PC) of atrial septal defects (ASDs). Electronic databases, journals and major international conference proceedings were systematically searched for pertinent clinical studies comparing the two methods of closure (percutaneous and surgical) published up to December 2008, including only those reporting on more than 20 patients. Primary endpoints: occurrence of death and of total and major early complications. Thirteen original studies (3,082 patients) were included. All studies were non-randomised. One death was reported in the surgical group (0.08%; 95% C.I. 0-0.23%). Analysis of postprocedural complications showed a 31% rate (95% CI 21-41%) in SC patients and a 6.6% rate (95% CI 3.9-9.2%) in PC subjects. The adjusted OR for SC vs. PC total complications was 5.4 (95% CI 2.96-9.84; p<0.0001), significantly in favour of PC. The postprocedural major complication rate was 6.8% (95% CI 4-9.5%) in SC patients and 1.9% (95% CI 0.9-2.9%) in PC patients. The adjusted OR for SC vs. PC major complications was 3.81 (95% CI 2.7-5.36; p=0.006), again favouring PC. The largest cohort to date of patients with secundum ASD shows that treatment by a percutaneous approach has a significantly lower rate of either total or major early postprocedural complications compared to surgery.


Characterization of a factor from the U937 cell line that enhances the toxicity of human eosinophils to Schistosoma mansoni larvae.
A factor produced by lipopolysaccharide-stimulated human monocytes, monocyte-derived eosinophil cytotoxicity-enhancing factor (M-ECEF), increases the ability of human eosinophils to kill larvae of Schistosoma mansoni. In order to purify this monokine, a continuous cell line was sought as a generator of source material. It was found that high titers of an ECEF-like activity could be obtained from the U937 cell line cultured in serum-free medium. Production of this activity was optimal when cells were cultured with PMA for 2 days and were further treated with LPS for 2 days. PMA and LPS alone did not enhance eosinophil cytotoxicity and could be separated completely from U937-ECEF activity by reversed-phase HPLC. Thus, the activity was not due to carry-over of these two stimuli. U937-ECEF was compared with M-ECEF by a number of analytical methods. ECEF from both sources was resistant to several denaturing treatments but was sensitive to proteases or to reduction and alkylation. U937-ECEF exhibited activity profiles similar, if not identical, to those of M-ECEF when subjected to molecular sizing HPLC in the presence of 8 M urea, isoelectric focusing, and reversed-phase HPLC. The activity has apparent m.w. of 17,000 and 32,000, isoelectric points ranging from 3.8 to 5.1, and one or more reversed-phase HPLC retention times, depending on the method of sample preparation. These results demonstrate certain physical characteristics of M-ECEF, show that the U937 cell line is an appropriate source for the purification of M-ECEF, and provide information that will allow the design of a purification strategy. Although it appears that tumor necrosis factor (TNF) or a TNF-like molecule is a component of M-ECEF, a major component of M-ECEF is different from TNF as judged by the 1) physical characteristics of M-ECEF, 2) low direct toxicity of M-ECEF to L929 cells, 3) comparative stability of M-ECEF to heat treatment, and 4) inability of an anti-TNF monoclonal antibody to remove M-ECEF activity.


Biomechanical analysis of the keratoconic cornea.
Keratoconus is a non-inflammatory disease characterized by irregular thinning and gradual bulging of the cornea, which results in distortion of the corneal surface that causes blurred vision. We conducted three-dimensional finite element (FE) simulations to analyze the biomechanical factors contributing to the distorted shape of a keratoconic cornea. We assumed orthotropic linear elastic tissue mechanical properties, and simulated localized tissue thinning (reduction from 0.5 mm to 0.35 or 0.2 mm). We analyzed tissue deformations, stresses and theoretical dioptric power maps predicted by the models, for intraocular pressure (IOP) of 10, 15 20 and 25 mmHg. The analyses revealed that three factors affect the shape distortion of keratoconic corneas: (i) localized thinning, and (ii) reduction in the tissue's meridian elastic modulus or (iii) reduction in the shear modulus perpendicular to the corneal surface, whereas thinning showed the most predominant effect. Maximal stress levels occurred at the centers of the bulged regions, at the thinnest points. The IOP levels had little influence on dioptric power in the healthy cornea, but a substantial influence in keratoconic conditions. The present FE studies allowed characterization of the biomechanical interactions in keratoconus, toward understanding the aetiology of this poorly studied malady.


Induction of collagen mineralization by a bone sialoprotein--decorin chimeric protein.
The observation that hydroxyapatite (HA) formation from metastable solutions can be induced by nucleating proteins such as bone sialoprotein (BSP) suggests a possible treatment for bone defects. The introduction of a mixture of nucleating protein and type I collagen should result in a defect becoming filled with a mineralized collagenous matrix that is biologically and mechanically compatible and capable of being remodeled. To create a nucleating protein that would interact with collagen fibrils, we combined the putative collagen-binding site of mouse decorin with one of two putative HA-nucleating sites of pig BSP. The resulting chimeric protein induced the formation of HA crystals in a steady-state agarose gel system and bound with high affinity to fibrillar type I collagen. The addition of chimeric protein to collagen gels perfused with low concentrations of calcium and phosphate resulted in the deposition of large, apparently needle-shaped HA crystals on the surface of collagen fibrils. These findings suggest that the BSP-decorin chimeric protein could be capable of inducing the mineralization of collagen in vivo.


Childhood experiences of violence in perpetrators as a risk factor of intimate partner violence: a systematic review.
Perpetrators' experiences of violence during childhood are considered a risk factor for intimate partner violence (IPV). The objective of this study is to systematically review the characteristics and quality of papers which analyse the association between being battered during childhood, witnessing marital violence as a child within the family of origin and having an absent or rejecting father and the occurrence of IPV. Nine scientific databases were consulted (1960-2004). After applying the exclusion criteria, 10 studies were analysed. Variables are sample characteristics, directionality/study design, IPV and perpetrators' childhood measurements, findings, limitations and interventions. All the studies found an association. Conflict Tactics Scale was the main tool used to measure the IPV. Different instruments were used to measure violent childhood experiences in men as an exposure. Recall bias (seven papers) and retrospective data (four papers) were reported as the main methodological limitations. Despite these, 50% of the studies proposed treatments/preventive measures. Our findings support the results of previous studies, implying that action recommendations within IPV prevention are still not evidence based. Methodological problems of the papers reviewed should be solved to obtain more useful data. Scientific evidence about the aetiology of IPV should be increased to guide effective prevention programmes.


Symptomless cyst formation at the location of a biloma resolved with a single aspiration: case report.
A biloma is an encapsulated bile collection outside the biliary tree. The underlying causes include iatrogenic, traumatic, and spontaneous injury of the biliary tree. Its diagnosis is based upon clinical history, imaging studies, and needle aspiration with chemical analysis of the fluid. Biloma usually presents as a simple or septated cyst or a cyst with internal contents. The symptomatic biloma if left untreated may result in significant morbidity and even mortality. In past reports, the mainstay of management relied on bile flow diversion and/or bile drainage to achieve elimination of bile as well as complete resolution of the cyst. We report on a 58-year-old woman with a 9.0 x 5.4 cm cyst between the right liver and the upper role of the kidney after wedge resection for a hepatoma in the right lobe. She suffered from abdominal pain and fever. A single percutaneous needle aspiration with chemical analysis confirmed the diagnosis of biloma and relieved her symptoms. The biloma vanished immediately. However, a recurrent symptomless cyst was detected at the same site 6 months later. Its content was proven to be clear transudate, and it was left untreated. If a biloma has no communication with the biliary tree, and the proximal biliary tree has neither stricture nor stones, percutaneous aspiration alone may achieve resolution.


[Development of novel laboratory technology--Chairmen's introductory remarks].
The theme of the 58th annual meeting is, "Mission and Challenge of Laboratory Medicine". This symposium is named, "Development of Novel Laboratory Technology" and is held under the joint sponsorship of the Japanese Society of Clinical Chemistry and the Japanese Electrophoresis Society. Both societies have superior skills at developing methodology and technology. The tools used in the lectures are a carbon nanotube sensor, immunochromatography, direct measurement using polyanions and detergents, epigenomic analysis and fluorescent two-dimensional electrophoresis. All of the lectures will be very helpful and interesting.


Influence of sympathetic vascular regulation on heart-rate scaling structure: spinal cord lesion as a model of progressively impaired autonomic control.
Estimation of self-similarity is a promising tool for quantifying alterations in cardiovascular dynamics. To evaluate the as yet unexplored influence of sympathetic vascular regulation on the scaling exponent, namely on the parameter characterizing self-similarity, we studied patients with a spinal cord injury as a model of progressively impaired vascular control. We considered 24 able-bodied subjects (AB) and 23 paraplegics with increasing lesion levels: between T(12) and L(4) (n=7); T(5) and T(11) (n=9); and C(6) and T(4) (n=7). We recorded the heart rate in three conditions characterized by increasing sympathetic activation: supine (SUP), sitting (SIT) and exercise (EXE). We calculated the scaling exponent by detrended fluctuation analysis (H(DFA)). Sympathetic activation had different effects on H(DFA), depending on the lesion level. H(DFA) tended to decrease in AB from SUP (0.85+0.02; mean+SEM) and SIT (0.84+0.02) to EXE (0.79+0.02). It remained constant in the T(12)-L(4) group (0.92+0.04, 0.94+0.05 and 0.94+0.04, respectively), while it increased significantly in the T(5)-T(11) group (0.88+0.07, 0.94+0.05, 1.00+0.08) and increased even more in the C(6)-T(4) group (0.83+0.07, 0.91+0.05, 1.06+0.06). Results suggest that heart-rate self-similarity depends on vascular sympathetic control, because it is altered by spinal-cord lesions, even when cardiac neural control is intact.


Diagnostic value of flecainide testing in unmasking SCN5A-related Brugada syndrome.
Provocation tests with sodium channel blockers are often required to unmask ECG abnormalities in Brugada syndrome (BrS). However, their diagnostic value is only partially established, while life-threatening ventricular arrhythmias during these tests were reported. We aimed to establish sensitivity, specificity, and safety of flecainide testing, and to predict a positive test outcome from the baseline ECG. We performed 160 tests with flecainide in subjects determined to be at risk for BrS. P wave width, PQ duration, QRS width, S wave amplitude and duration in leads II-III, in addition to ST morphology and J point elevation in V1-V3 were measured before and after flecainide administration. Moreover, leads were positioned over the third intercostal space (V1(IC3)-V2(IC3)). Flecainide tests were considered positive if criteria from the First Consensus Report on BrS were fulfilled. In 64 cases, the test was positive, while 95 were negative (1 test was prematurely interrupted). The sensitivity and specificity, calculated in SCN5A-positive probands and their family members, were 77% and 80%, respectively. Baseline ECGs exhibited significant group differences in P, PQ, and QRS duration, J point elevation (leads V1-V2 and V1(IC3)-V2(IC3)), and S duration in II, but an attempt to predict the outcome of flecainide testing from these baseline ECG parameters failed. No malignant arrhythmias were observed. Flecainide testing is a valid and safe tool to identify SCN5A-related BrS patients. Baseline ECGs do not predict test outcomes, but point to conduction slowing as a core mechanism in BrS.


Whey protein-polysaccharide blended edible film formation and barrier, tensile, thermal and transparency properties.
Films made from different protein (P) or polysaccharide (PS) materials have widely different properties. The objective of this study was to determine whether whey protein isolate (WPI)-PS blended films possess a combination of properties intermediate and possibly superior to WPI or PS film alone. Oxygen permeability (OP) and tensile strength (TS) for PS-WPI blended films were intermediate between the OP and TS properties of pure methycellulose (MC), hydroxypropylmethylcellulose (HPMC) or sodium alginate (SA) film and pure WPI film. Starch-WPI blends gave the weakest films. Water vapor permeability values for all pure and blended films were similar. Blended films made of MC, HPMC or SA with WPI had lower transparency than pure MC, HPMC, SA or WPI films. Differential scanning calorimetry thermograms obtained from the blended films exhibited a single glass transition temperature (T(g) ) at an intermediate value between the T(g) values of the pure films. Whether properties of PS-WPI blended films are intermediate to properties of the pure PS and WPI film depends on the particular PS and specific property. In the case of MC or HPMC with WPI, the blended films reflect the higher TS of the PS and lower OP of the WPI.


Exporting obesity: US farm and trade policy and the transformation of the Mexican consumer food environment.
Obesity has reached epidemic proportions, in the United States as well as among its trade partners such as Mexico. It has been established that an "obesogenic" (obesity-causing) food environment is one influence on obesity prevalence. To isolate the particular role of NAFTA, the North American Free Trade Agreement, in changing Mexico's food environment, we plotted the flow of several key products between the United States and Mexico over the 14-year NAFTA period (1994-2008) and situated them in a broader historical context. Key sources of USDA data include the Foreign Agricultural Service's Global Agricultural Trade System, its official repository for current and historical data on imports, exports and re-exports, and its Production, Supply, and Distribution online database. US export data were queried for agricultural products linked to shifting diet patterns including: corn, soybeans, sugar and sweeteners, consumer-oriented products, and livestock products. The Bureau of Economic Analysis' Balance of Payments and Direct Investment Position Data in their web-based International Economic Accounts system also helped determine changes in US direct investment abroad from 1982 to 2009. Directly and indirectly, the United States has exported increasing amounts of corn, soybeans, sugar, snack foods, and meat products into Mexico over the last two decades. Facilitated by NAFTA, these exports are one important way in which US agriculture and trade policy influences Mexico's food system. Because of significant US agribusiness investment in Mexico across the full spectrum of the latter's food supply chain, from production and processing to distribution and retail, the Mexican food system increasingly looks like the industrialized food system of the United States.


Novobiocin blocks the Drosophila heat shock response.
In the studies reported here we show that the antibiotic novobiocin, an in vitro inhibitor of topoisomerase II, blocks the Drosophila heat shock response. If novobiocin is added prior to induction, there is no detectable expression of the Drosophila heat shock genes. Moreover, analysis of the chromatin organization of the 87A7 heat shock locus indicates that the antibiotic prevents the structural alterations which normally accompany heat induction. When novobiocin is added after induction, transcription appears to be rapidly turned off, and the chromatin organization of the 87A7 locus is "fixed" in an "active" configuration. Novobiocin also prevents the re-establishment of the pre-induced 87A7 chromatin organization which occurs during recovery from heat shock. We have also presented data suggesting that this antibiotic blocks transcription at 25 degrees C. These findings raise the possibility that topoisomerase II may be required in eukaryotes for both gene activation and deactivation.


Epidemiology of human and animal trichinellosis in Italy since its discovery in 1887.
The epidemiology of trichinellosis in Italy is characterised by a sylvatic cycle present only on the mainland. The domestic cycle probably never existed, though a domestic focus occurred on the island of Sicily between 1933 and 1946. The red fox is the main reservoir, with the prevalence of infection ranging from 0.0% in lowlands to 60% in the Alps. The main etiological agent is Trichinella britovi. Trichinella pseudospiralis has been detected in two birds. From 1948 to March 2000, trichinellosis was diagnosed in 1,347 persons, who acquired the infection in 21 outbreaks.


Pharmacokinetics of talinolol is modified by barnidipine: implication of P-glycoprotein modulation.
Concomitant administration of P-glycoprotein substrates and inhibitors may cause pharmacokinetic drug interactions leading to increased concentrations associated with serious side effects and toxicities. Barnidipine is a longacting calcium-channel blocker and potent inhibitor of P-glycoprotein in vitro, and talinolol is a beta-blocker and probe substrate of P-glycoprotein. This study was designed to investigate the effects of single and repeated oral doses of barnidipine on talinolol pharmacokinetics in rats. In the single-dose study, talinolol (20 mg/kg) alone and with barnidipine at low (1 mg/kg) and high doses (10 mg/kg) were orally administered to rats. In the repeated-dose study, rats were treated with barnidipine (1 mg/kg/day) or vehicle only for four days, then with talinolol (20 mg/kg, on day 5). Blood samples were collected at 0.5, 1, 2, 4, 6 h following last dose and plasma talinolol levels were determined by HPLC. Compared to the control, Cmax of talinolol elevated 10% (p=0.79) and 110% (p<0.05); plasma AUC0-6h increased 33% (p=0.41) and 46% (p<0.05) following low and high single doses of barnidipine co-administration, respectively. In the repeated-dose study, Cmax and AUC0-6h of talinolol increased 131% (p<0.05) and 130% (p<0.05) respectively, following co-administration of a low barnidipine dose. Double-peaks were observed when single or repeated low doses of barnidipine were co-administered. There may be coupling between occurrence of double-peak phenomenon and P-glycoprotein inhibition. Increment of talinolol bioavailability upon low and high doses of barnidipine co-administration may be due to P-glycoprotein inhibition. The higher increase of talinolol plasma AUC0-6h due to the repeated doses of barnidipine may be explained by downregulation of P-glycoprotein.


Aerosol fabrication of hollow mesoporous silica nanoparticles and encapsulation of L-methionine as a candidate drug cargo.
Hollow spherical nanoparticles with ordered mesoporous silica shells were fabricated by evaporation-induced self-assembly using (NH(4))(2)SO(4) and cetyltrimethyl ammonium bromide (CTAB) as templates. The model drug, L-methionine, was encapsulated within the spherical void at high loadings by repeated crystallization.


Psoriasis and the pregnant woman: what are the key considerations?
Pregnancy is characterized by multiple physiologic changes. During the entire gestational period, both mother and infant are vulnerable to a variety of external and internal factors. Maternal disease, use of certain medications, drugs, alcohol, smoking, and radiation exposure can have devastating effects on the fetus. Pregnancy-related complications in women with psoriasis can be caused by both the disease and the treatment. The response of the maternal placenta to psoriasis-induced inflammation and comorbid conditions, such as obesity, hypertension, and depression, may also influence the pregnancy. Herein, we review the relationship between psoriasis and undesirable pregnancy outcomes.


Assistance of intraoperative microvascular Doppler in the surgical obliteration of spinal dural arteriovenous fistula: cases description and technical considerations.
Intraoperative microvascular Doppler may be valuable in assisting in the surgical obliteration of dural arteriovenous fistula of the spinal cord. It enables identification, through flow spectrum analysis, of the anatomic components and haemodynamic features of this type of vascular malformation. In two cases, intraoperative microvascular Doppler was used to assist in the surgical obliteration of dural arteriovenous fistula of the spinal cord. The fistulas were identified prior to the dura opening, and for this only minimally invasive surgery was required. Direct recordings of the arterialised draining vein and the nidus of the fistula demonstrated a pathological spectrum caused by the arterial supply and the disturbed venous outflow in which a high-resistance flow pattern and low diastolic flow resembling an arterial-like flow velocity were observed. The fistulas were obliterated by interruption of the draining vein, and Doppler measurements provided information on flow velocity changes in the medullary veins from an arterial to a venous pattern. The absence of any residual flow in the draining vein confirmed successful haemodynamic treatment. Intraoperative microvascular Doppler recording is valuable assistance in surgical closure of spinal arteriovenous fistula.


[Toxicity of benzhydrylurea under experimental conditions].
Benzhydrylurea, which displays an anticonvulsant action and is of low acute toxicity in capable after a 3-month administration to rats to inhibit the growth of male-rats, intensify the excretion of protein with the urine, raise the blood sugar level (with its single administration--to reduce), provoke dystrophic changes in the liver, kidneys and central nervous system. Following a 1--3-week introduction of the substance guinea pigs and cats demonstrate hemorrhagic erosions in the stomach and small intestine (but not rabbits, dogs and rats), the appearance of pathological forms of erythrocytes, while guinea pigs suffer from leucopoietic disorders.


Randomized double-blind, placebo-controlled clinical trial of a selective 5-lipoxygenase inhibitor (AA-861) for the prevention of seasonal allergic rhinitis.
In a randomized, double-blind, parallel group trial conducted in eight European centres, the 5-lipoxygenase inhibitor AA-861 was administered orally, starting 2 weeks before the pollen season and continuing for 8 weeks; after the start of the season escape medication was permitted if necessary. Patients were enrolled who had a previous history of pollen allergy, confirmed by skin prick tests and/or relevant allergen-specific immunoglobulin E to pollen. Daily symptoms scores were recorded on diary cards and assessments were made by the investigator during the study period. Better global improvement ratings were achieved using AA-861, as assessed both by the investigators and the patients. The total nasal symptoms scores and activities of daily living were also improved compared to placebo. No significant adverse reactions were encountered.


Poly(alizarin red)/graphene modified glassy carbon electrode for simultaneous determination of purine and pyrimidine.
In this work, a poly(alizarin red)/Graphene composite film modified glassy carbon electrode (PAR/Graphene/GCE) was prepared for simultaneous determination of four DNA bases (guanine, adenine, thymine and cytosine) without any pretreatment. The morphology and interface property of PAR/Graphene films were examined by scanning electron microscopy and electrochemical impedance spectroscopy. The PAR/Graphene/GCE exhibited excellent electrocatalytic activity toward purine (guanine and adenine) and pyrimidine (thymine and cytosine) in 0.1 M phosphate buffer solution (pH 7.4). Under optimum conditions, differential pulse voltammetry was used to detect the oxidation of purine and pyrimidine. The results showed that PAR/Graphene/GCE exhibited well-separated peaks, low detection limit, high sensitivity and wide linear range for simultaneous detection of purine and pyrimidine. The proposed sensor also has good stability and reproducibility. Furthermore, the modified electrode was applied for the detection of DNA bases in a fish sperm DNA sample with satisfactory results.


Prevention of bone loss by hormone replacement therapy is probably not due to stimulation of calcitonin secretion.
Weekly fasting serum calcitonin levels and biochemical indices of bone metabolism were measured in 13 postmenopausal women being given hormone replacement therapy over a period of 8 weeks. All of the biochemical indices except urinary hydroxyproline creatinine ratios fell significantly, indicating that the treatments were effective in reducing bone turnover. Calcitonin levels fell significantly and, within the individual, levels were positively correlated with adjusted calcium levels. These findings do not support the theory that estrogen conserves bone by stimulating calcitonin secretion.


Incidence of fracture through metastases in long bones.
A knowledge of the incidence of fractures through metastases of various sizes in long bones is important when considering prophylactic internal fixation. The notes and X-rays of 66 consecutive patients with 100 metastases in long bones were analysed. Fractures are highly unlikely to occur (2.3 per cent) when less than 50 per cent of the cortex is destroyed and most likely to occur (80 per cent) when over 75 per cent of the cortex is destroyed.


Mapping of a new target region of allelic loss to a 2-cM interval at 22q13.1 in primary breast cancer.
Allelic losses on chromosome arm 22q are frequently observed in human meningiomas and in carcinomas of the colon, ovary, and breast. Among 140 primary breast cancers we examined for loss of heterozygosity (LOH) at 16 polymorphic loci on the long arm of chromosome 22, 56 (40%) showed LOH for at least one locus. Eleven of these tumors had retained heterozygosity for markers proximal to the NF2 locus but showed LOH for markers distal to NF2. Deletion mapping indicated a new common region of deletion, 2-cM in extent, at q13.1 between Interleukin 2 receptor beta (IL2RB) and D22S279. Our results raise the possibility that one or more tumor suppressor genes associated with breast cancer may exist at 22q13.1. Comparison of these results with clinicohistological data indicated that allelic losses on 22q tend to occur more frequently in tumors of malignant histological types.


Human colonic substance P-producing cells are a separate population from the serotonin-producing enterochromaffin cells.
Human colonic mucosa was immunostained with antibodies against substance P to identify the endocrine cells containing this peptide in the mucosal glands. Dual immunohistochemical and histochemical studies were also carried out to determine whether these cells are enterochromaffin cells and contain serotonin as claimed in the literature. The results obtained indicate that the normal human colonic substance P-producing cells are not argentaffin cells, nor do they contain serotonin. In addition, they are also negative both for several silver and for other techniques commonly used to identify digestive endocrine cells. They are positive, however, with the argyrophilic technique of Churukian-Schenk. It is concluded, therefore, that the substance P-producing cells of the human colonic mucosa are not a subpopulation of the enterochromaffin cells, but constitute a distinct and independent cell type.


High dose methotrexate with and without BCG therapy in advanced head and neck malignancy.
Twenty-three patients with advanced recurrent head and neck carcinoma were randomized to receive either high dose methotrexate with calcium leucovorin rescue (HDMTX) or HDMTX in combination with bacilli Calmette Guerin (HDMTX/BCG). An additional eight patients were treated with escalating doses of HDMTX ranging from 1 to 7 g of methotrexate. Of 12 patients receiving HDMTX, one complete response and two partial responses were noted. Of 11 patients in the HDMTX/BCG group, one complete response and two partial responses were observed. Only one partial response was noted in eight patients receiving escalating doses of the drug. Responses were brief and no significant difference in response duration was seen in any particular group. Toxicities in all groups were tolerable. BCG did not improve response rate, median duration of response, or median survival in these patients. Reported experiences with high dose methotrexate have been reviewed and again, responses to "high dose methotrexate" were found to be of brief duration. Despite acceptable toxicity, the brief duration of response and cost of such therapy raises serious question on the usefulness of chemoimmunotherapy utilizing high dose methotrexate with leucovorin rescue and BCG in the management of advanced recurrent carcinomas of the head and neck region.


Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings.
Oxidative stress is involved in the aetiology of defective embryo development. Reactive oxygen species (ROS) may originate from embryo metabolism and/or embryo surroundings. Embryo metabolism generates ROS via several enzymatic mechanisms. The relative contribution of each source seems different depending on the species, the stage of development, and the culture conditions. Several exogenous factors and culture conditions can enhance the production of ROS by embryos. ROS can alter most types of cellular molecules, and also induce development block and retardation. Multiple mechanisms of embryo protection against ROS exist, and these have complementary actions. External protection, present in follicular and tubal fluids, mainly comprises non-enzymatic antioxidants such as hypotaurine, taurine and ascorbic acid. Internal protection mainly comprises antioxidant enzymes: superoxide dismutase, glutathione peroxidase and gamma-glutamylcysteine synthetase. Transcripts encoding for these enzymes are present in the oocyte, embryo and oviduct. It may be important that these transcripts are stored during oocyte maturation in order to allow the embryo to acquire the aptitude to develop. It is now common to add antioxidant compounds to culture media. Nevertheless, maintaining the pro-oxidant-antioxidant equilibrium in embryos through such supplementation is a complex problem. Further studies are necessary to limit oxidative stress during embryo culture.


Ultrastructural study of the equine cecum during onset of laminitis.
The morphologic and pathologic changes which occurred within the cecal mucosa of 4 horses during the onset of laminitis were determined from cecal biopsy materials obtained via a cecal fistula; the laminitis was induced with carbohydrate overload. The cecal epithelial mucosa specimens were obtained at 0 (base line), 24, 32, 48, and 72 hours after horses were given carbohydrate overload, and these were fixed and subsequently photographed. Changes in the cecal epithelium were examined by transmission electron and scanning electron microscopies. These histopathologic changes indicated that the mucosal barrier was substantially damaged by the carbohydrate overload.


Preparation and testing of goat anti--thymocyte globulin.
This study details methods of production, purification and testing of large volumes of uniformly potent, non-toxic, anti-human thymocyte globulin (ATG). Plasma from 70 goats immunised with human thymic lymphocytes was fractionated by ammonium sulphate precipitation to its IgG component. Contaminating antibodies were removed by absorption methods. After fractionation and absorption, ATG retained its ability to inhibit the formation of rosettes by human lymphocytes with sheep red blood cells. Antibodies to human glomerular basement membrane were not detected in any tested preparation. Tests performed on monkeys, mice and rabbits revealed low toxicity.


Penile enlargement surgery.
Aesthetic surgery to improve the appearance of the penis, scrotum, and pubic region has successfully evolved. Penile lengthening is performed by releasing the suspensory ligament of the penis followed by use of penile weights. Girth is increased by wrapping a dermal-fat graft around the penile circumference. The choice of surgery is determined by the patient's anatomy and desires.


Effect of the RF cavity temperature on low-energy injection at HLS.
The resonant frequency shift caused by the temperature of the RF cavity at the Hefei Light Source has been measured and the results analysed. The effect of this frequency shift on low-energy injection with a low cavity voltage is discussed, and a new injection mode is proposed.


Clinical experience with combined reconstruction of the anterior cruciate and anterolateral ligaments of the knee in sportsmen.
Rupture of the anterior cruciate ligament (ACL) is one of the most common sports injuries of the knee joint. Today, we have a large number of approaches to arthroscopic reconstruction of the anterior cruciate ligament that lead to successful outcomes and allow the patients to return to a significant level of activity post-operatively. Nevertheless, the return to competitions rate stays relatively low. The functional state is thought to be dependent on rotational and anteroposterior stability of the knee. These data encourage search for methods of additional stabilization of the knee joint, one of them being extra-articular tenodesis, or reconstruction of anterolateral ligament of the knee. To evaluate medium-term results of combined simultaneous arthroscopic reconstruction of anterior cruciate ligament and anterolateral ligament of the knee joint in sportsmen and to access the probability of return to competitions. The surgeries were performed in 2014-2015 in 50 patients who fulfilled the entry criteria: 20 patients (including 10 professional sportsmen) underwent arthroscopic ACL reconstruction together with reconstruction of anterolateral ligament-group 1 (main group), and 30 patients (including 10 professional sportsmen) underwent arthroscopic ACL reconstruction-group 2 (control group). Group 1: All patients of group 1 were able to return to the pre-operative sports level in two years after the surgery. The mean Tegner Lysholm score was 72.6 ± 6.45 (hereinafter, SE-standard error) before the surgery and 97.4 ± 1.18 after the surgery. The mean IKDC score was 63.1 ± 4.8% before the surgery and 96.3 ± 1.8% after the surgery. Group 2: 20 of 30 patients (66.7%) returned to the pre-operative level of activity and returned to competitions (if they were professional sportsmen) in a year after the surgery. Five of ten patients (50%) (professional sportsmen) returned to competitions. Fifteen of 20 patients (75%) (amateur sportsmen) also returned to competitions. The mean pre-operative Tegner Lysholm score was 69.6 ± 3.5, and the mean post-operative score was 92.1 ± 3.9. The mean pre-operative IKDC score was 73.4 ± 3.2%, and the mean post-operative score was 90.3 ± 3.7%. The results of the study show that more patients with higher functional demands and more professional sportsmen returned to sports. Despite the results of our and other foreign studies, a need remains for studies that will compare outcomes of ALL reconstruction with the same surgical technique in homogenous groups of patients.