Chronic diseases in self-employed French workers.
The objective of this study was to evaluate occupations associated with a high risk of specific chronic diseases in self-employed workers. For each occupational category and gender, the observed and expected numbers of prevalent cases for each chronic disease leading to exemption from copayments by the French National Health Insurance System in 2001 were compared using the age-specific self-employed population rates as a reference. Dramatic discrepancies were observed depending on occupational categories, specifically for diabetes mellitus, cardiovascular diseases, mental health disorders, chronic respiratory insufficiency, severe liver disorders, and connective tissue diseases. Based on this extremely large dataset, several known associations between occupations and specific diseases were confirmed; other potential associations observed require future investigation.


Interferon-alpha-mediated prevention of in vitro apoptosis of chronic lymphocytic leukemia B cells: role of bcl-2 and c-myc.
Chronic B lymphocytic leukemia cells (B-CLL), characterized by the accumulation in vivo of long-life span B cells, exhibit spontaneous programmed cell death or apoptosis when cultured in vitro. We show that interferon-alpha (IFN-alpha), although able to decrease in vivo the number of leukemic cells, protects chronic B lymphocytic leukemia cells from in vitro programmed cell death or apoptosis. This inhibition of spontaneous in vitro apoptosis of leukemic B cells was observed after 24-48 hr of culture with 100-1000 U of either Interferon-alpha 2a or 2b. The protective activity was observed in the majority of the patients tested (6 out of 8) independent of the amount of apoptosis observed. Furthermore, in contrast to IL-4, IFN-alpha did not up-regulate the expression of Bcl-2. This suggests that B-CLL cells can be prevented from undergoing apoptosis in vitro by at least two different mechanisms: one, triggered for instance by IL-4, is associated with Bcl-2 production and the second triggered by Interferon-alpha is Bcl-2 independent. To elucidate the pathways mobilized by Interferon-alpha we also studied the regulation of c-myc expression in our experimental system. We found that (i) induction of in vitro B-CLL apoptosis was not associated with up-regulation of c-myc, (ii) c-myc expression as assessed by mRNA and protein determinations was increased after in vitro or in vivo Interferon-alpha stimulation. Additional experiments using c-myc specific oligonucleotides demonstrated that when Interferon-alpha-mediated c-myc expression was decreased by 60%, the in vitro protective effect of Interferon-alpha was not modified. Thus our data show that in contrast to the situation in vivo, Interferon-alpha prevents spontaneous in vitro B-CLL cells apoptosis through a Bcl-2-independent pathway which is probably not related to c-myc up-regulation.


[Exploration of the experiment teaching of natural medicinal chemistry for undergraduates].
Natural medicinal chemistry is one of the important courses for students in pharmacy majors. Its experimental teaching focuses on fostering comprehensive experimental skills and innovative abilities of undergraduates. Liaoning University has explored ways to promote the experimental teaching of natural drug chemistry based on the graduate employment and practical teaching experience in the past decade. These explorations include three aspects, such as synchronizing experimental teaching with theoretical teaching, fostering students' awareness of experimental safety, and improving experimental teaching methods in natural drug chemistry experiments. The practices showed that the reform has achieved a good effect. A teaching system that can achieve the three expected aspects has been established, which improved the teaching effect and quality of natural medicinal chemistry experimental courses for undergraduates. Furthermore, these explorations may facilitate fostering pharmacy specialists who can meet the opportunities of developing Chinese medicine and natural drug research and meet the requirements of employment.


The effects of uni- and bilateral fatigue on postural and power tasks.
The aim of this study was to investigate the effects of unilateral and bilateral fatigue on both postural and power bipedal tasks. Ten healthy subjects performed two tasks: bipedal quiet standing and a maximal bipedal countermovement jumping before and after unilateral (with either the dominant or nondominant lower limb) and bilateral (with both lower limbs) fatigue. We employed two force plates (one under each lower limb) to measure the ground reaction forces and center of pressure produced by subjects during the tasks. To quantify the postural sway during quiet standing, we calculated the resultant center of pressure (COP) speed and COP area of sway, as well as the mean weight distribution between lower limbs. To quantify the performance during the countermovement jumping, we calculated the jump height and the peak force of each lower limb. We observed that both unilateral and bilateral fatigue affected the performance of maximal voluntary jumping and standing tasks and that the effects of unilateral and bilateral fatigue were stronger in the dominant limb than in the nondominant limb during bipedal tasks. We conclude that unilateral neuromuscular fatigue affects both postural and power tasks negatively.


Escherichia coli mastitis strains: In vitro phenotypes and severity of infection in vivo.
Mastitis remains a major infection of dairy cows and an important issue for dairy farmers and the dairy industry, in particular infections due to Escherichia coli strains. So far, properties specific to E. coli causing mastitis remain ill defined. In an attempt to better understand the properties required for E. coli to trigger mastitis, we used a range of in vitro assays to phenotypically characterize four E. coli strains, including the prototypical E. coli mastitis strain P4, possessing different relative abilities to cause mastitis in a mouse model. Our results indicate that a certain level of serum resistance might be required for colonization of the mammary gland. Resistance to neutrophil killing is also likely to contribute to a slower clearance of bacteria and higher chances to colonize the udder. In addition, we show that the four different strains do induce a pro-inflammatory response by mammary epithelial cells but with different intensities. Interestingly, the prototypical mastitis strain P4 actually induces the less intense response while it is responsible for the most severe infections in vivo. Altogether, our results suggest that different strategies can be used by E. coli strains to colonize the mammary gland and cause mastitis.


Basolateral sorting of the HIV type 2 and SIV envelope glycoproteins in polarized epithelial cells: role of the cytoplasmic domain.
In polarized epithelial cell lines, enveloped viruses are directionally released by asymmetric viral budding at specific plasma membrane domains. Previous studies have shown that HIV-1 budding and gp160 expression occur on basolateral membranes whereas the release of HIV-1 Gag particles, in the absence of the Env glycoproteins, is nonpolarized. We have examined the directional transport and surface expression of HIV-2 and SIV envelope glycoproteins using vaccinia virus recombinants in Vero C1008 polarized epithelial cells. Analogous to HIV-1 gp160, both HIV-2 and SIV surface glycoproteins were preferentially directed to basolateral membranes. Hence basolateral expression appears to be a common property of the glycoproteins of primate lentiviruses. To explore the role of the cytoplasmic domain in directing the HIV-2 and SIV Env glycoproteins to the basolateral surface, stop codons were introduced to mimic the natural cytoplasmic truncations observed following repeated passage of these viruses in culture. These truncated glycoproteins also were sorted to the basolateral domain, but at a lower efficiency than the full-length protein product. In contrast, when the entire cytoplasmic domain of the SIV Env glycoprotein was deleted, the tailless SIV mutant was preferentially expressed on the apical surface. These data indicate the presence of a basolateral sorting signal in the cytoplasmic domain of primate lentiviral glycoproteins.


Memory for activities for young, young-old, and old adults.
Adult age differences in memory for activities have frequently been reported. However, the age range of the older sample has varied from as young as 56 to as old as 89. The present memory for activities study distinguished between the performance of young-old adults (60 to 70) and old adults (71 to 82) in comparison to young adults (18 to 34). Nineteen tasks were administered over a 2-day period, and individuals were asked to recall them immediately or after a 24-h delay. Young-old adults' memory for activities was comparable to the young adults' for both immediate and delayed recall. Both the young and the young-old groups outperformed the old adults. The results suggest that researchers must consider the age of the individuals in the "old" group before drawing conclusions about adult age differences in memory for activities.


Renal blood flow and dynamic autoregulation in conscious mice.
Autoregulation of renal blood flow (RBF) occurs via myogenic and tubuloglomerular feedback (TGF) mechanisms that are engaged by pressure changes within preglomerular arteries and by tubular flow and content, respectively. Our understanding of autoregulatory function in the kidney largely stems from experiments in anesthetized animals where renal perfusion pressure is precisely controlled. However, normally occurring variations in blood pressure are sufficient to engage both myogenic and TGF mechanisms, making the assessment of autoregulatory function in conscious animals of significant value. To our knowledge, no studies have evaluated the dynamics of RBF in conscious mice. Therefore, we used spectral analysis of blood pressure and RBF and identified dynamic operational characteristics of the myogenic and TGF mechanisms in conscious, freely moving mice instrumented with ultrasound flow probes and arterial catheters. The myogenic response generates a distinct resonance peak in transfer gain at 0.31 +/- 0.01 Hz. Myogenic-dependent attenuation of RBF oscillations, indicative of active autoregulation, is apparent as a trough in gain below 0.3 Hz (-6.5 +/- 1.3 dB) and a strong positive phase peak (93 +/- 9 deg), which are abolished by amlodipine infusion. Operation of TGF produces a local maximum in gain at 0.05 +/- 0.01 Hz and a positive phase peak (62.3 +/- 12.3 deg), both of which are eliminated by infusion of furosemide. Administration of amlodipine eliminated both myogenic and TGF signature peaks, whereas furosemide shifted the myogenic phase peak to a slower operational frequency. These data indicate that myogenic and TGF dynamics may be used to investigate the effectiveness of renal autoregulatory mechanisms in conscious mice.


Effects of rAAV-mediated FGF-2 gene transfer and overexpression upon the chondrogenic differentiation processes in human bone marrow aspirates.
Application of genetically modified bone marrow concentrates in articular cartilage lesions is a promising approach to enhance cartilage repair by stimulating the chondrogenic differentiation processes in sites of injury. In the present study, we examined the potential benefits of transferring the proliferative and pro-chondrogenic basic fibroblast growth factor (FGF-2) to human bone marrow aspirates in vitro using the clinically adapted recombinant adeno-associated virus (rAAV) vectors to monitor the biological and chondrogenic responses over time to the treatment compared with control (lacZ) gene application. Effective, significant FGF-2 gene transfer and expression via rAAV was established in the aspirates relative to the lacZ condition (from ~ 97 to 36 pg rhFGF-2/mg total proteins over an extended period of 21 days). Administration of the candidate FGF-2 vector led to prolonged increases in cell proliferation, matrix synthesis, and chondrogenesis but also to hypertrophic and terminal differentiation in the aspirates. The present evaluation shows the advantages of rAAV-mediated FGF-2 gene transfer to conveniently modify bone marrow concentrates as a future approach to directly treat articular cartilage lesions, provided that expression of the growth factor is tightly regulated to prevent premature hypertrophy in vivo.


Dll1 Can Function as a Ligand of Notch1 and Notch2 in the Thymic Epithelium.
T-cell development in the thymus is dependent on Notch signaling induced by the interaction of Notch1, present on immigrant cells, with a Notch ligand, delta-like (Dll) 4, on the thymic epithelial cells. Phylogenetic analysis characterizing the properties of the Dll4 molecule suggests that Dll4 emerged from the common ancestor of lobe- and ray-finned fishes and diverged into bony fishes and terrestrial organisms, including mammals. The thymus evolved in cartilaginous fishes before Dll4, suggesting that T-cell development in cartilaginous fishes is dependent on Dll1 instead of Dll4. In this study, we compared the function of both Dll molecules in the thymic epithelium using Foxn1-cre and Dll4-floxed mice with conditional transgenic alleles in which the Dll1 or Dll4 gene is transcribed after the cre-mediated excision of the stop codon. The expression of Dll1 in the thymic epithelium completely restored the defect in the Dll4-deficient condition, suggesting that Dll1 can trigger Notch signaling that is indispensable for T-cell development in the thymus. Moreover, using bone marrow chimeras with Notch1- or Notch2-deficient hematopoietic cells, we showed that Dll1 is able to activate Notch signaling, which is sufficient to induce T-cell development, with both the receptors, in contrast to Dll4, which works only with Notch1, in the thymic environment. These results strongly support the hypothesis that Dll1 regulates T-cell development via Notch1 and/or Notch2 in the thymus of cartilaginous fishes and that Dll4 has replaced Dll1 in inducing thymic Notch signaling via Notch1 during evolution.


The sooterkin doctor: the London career of John Maubray, MD (1700-1732), "andro-boethogynist".
Dr John Maubray (1700-1732) was one of the most prominent man-midwives of Georgian London. His emphasis on the importance of physical examination and a combination of theoretical and practical teaching seems to have foreshadowed later methods of training in midwifery. His espousal of the non-instrumental Deventerian system of obstetrics and his activities in the parish of St George's, Hanover Square in London, identified him with the dominant Whig party. Although he failed to acquire a major patron, his network of social connections enabled him to obtain charitable and public service appointments, culminating in his chairmanship of the Charitable Corporation.


Are professional handball players at risk for developing a glenohumeral internal rotation deficit in their dominant arm?
Overhead athletes, such as baseball players, have been shown to have adaptive changes in the shoulder range of motion (ROM) of their dominant arm. Professional handball players are a unique subtype of overhead athletes with very different demands from baseball players. The aim of this study was to determine if professional handball players demonstrate differences in shoulder ROM between their dominant and non-dominant arm and try to relate them with new variables. Fifty professional male handball players were included and completed a questionnaire regarding age at which they started to play, number of hours they practice a week, field position and arm dominance. ROM measurements were performed including forward flexion (FF), external rotation with the shoulder in abduction (ABER) and with adducted arm (ADER) and internal rotation with shoulder in abduction (IR). Statistical analysis was performed to determine differences in ROM between the dominant and non-dominant shoulder and if there is a relationship between these differences and shoulder load or field position. The dominant arm showed decreased internal rotation (47 vs. 56 degrees, p < 0.001) and increased external rotation both with the arm abducted (99 vs. 88 degrees, p < 0.001) and at the side (62 vs 57 degrees, p = 0.001). This was not correlated with shoulder load for any movement (FF, p = 0.980; ABER, p = 0.741; ADER, p = 0.803; IR, p = 0.085) but was dependent on field position with first line players showing the highest internal rotation deficit (13 degrees vs. 6-7 degrees in the other field positions, p = 0.013). This study showed that professional male handball players with a first line position have a significant risk for developing a glenohumeral internal rotation deficit, similar to the phenomenon seen in baseball pitchers.


Effects of a 10-month endurance-training program on performance of speeded perceptual-motor tasks.
This study investigated the effects of a 10-mo. endurance-training program (running) on speeded psychometric skills. On a weekly basis the experimental group of 36 subjects participated in one supervised and three unsupervised training sessions. The control group of 22 subjects engaged in no structural training activities during this period. Subjects' performance on a simple reaction-time task, a choice reaction-time task, and a letter-recognition task was assessed before and after the training intervention. Analysis indicated that a 20% improvement in aerobic fitness in the trained group was not accompanied by a significant improvement in psychometric performance. This result is discussed in terms of the relationship between aerobic fitness and cognitive performance. It is concluded that improved physical fitness is not necessarily accompanied by improved perceptual-motor skills.


Energy Requirement Assessment in Japanese Table Tennis Players Using the Doubly Labeled Water Method.
Total daily energy expenditure (TEE) and physical activity level (PAL) are important for adequate nutritional management in athletes. The PAL of table tennis has been estimated to about 2.0: it is categorized as a moderateactivity sport (4.0 metabolic equivalents [METs]) in the Compendium of Physical Activities. However, modern table tennis makes high physiological demands. The aims of the current study were to examine (1) TEE and PAL of competitive table tennis players and (2) the physiological demands of various types of table tennis practice. In Experiment 1, we measured TEE and PAL in 10 Japanese college competitive table tennis players (aged 19.9 ± 1.1 years) using the doubly labeled water (DLW) method during training and with an exercise training log and self-reported energy intake. TEE was 15.5 ± 1.9 MJ·day-1 (3695 ± 449 kcal·day-1); PAL was 2.53 ± 0.25; and the average training duration was 181 ± 38 min·day-1. In Experiment 2, we measured METs of five different practices in seven college competition players (20.6 ± 1.2 years). Three practices without footwork were 4.5-5.2 METs, and two practices with footwork were 9.5-11.5 METs. Table tennis practices averaged 7.1 ± 3.2 METS demonstrating similarities with other vigorous racket sports. In conclusion the current Compendium of Physical Activities underestimates the physiological demands of table tennis practice for competition; the estimated energy requirement should be based on DLW method data.


Unusual microtubule-dependent endocytosis mechanisms triggered by Campylobacter jejuni and Citrobacter freundii.
Bacterial invasion of six different human epithelial cell lines showed that some strains of the intestinal pathogen Campylobacter jejuni invaded intestinal cell lines at a level 10(2)-10(4) times higher than reported previously for other Campylobacter strains. Separately, urinary tract isolates of Citrobacter freundii triggered a high-efficiency invasion of bladder cells. Use of multiple inhibitors with known effects on eukaryotic cell structures/processes allowed us to define in these genetically distinct bacterial genera unusual bacterial invasion mechanisms that uniquely require microtubules but not microfilaments. Campylobacter jejuni strain 81-176 uptake into 407 intestinal cells and Citrobacter entry into T24 bladder cells was blocked by microtubule depolymerization and inhibitors of coated-pit formation but not by microfilament depolymerization. Inhibitors of endosome acidification had no significant impact on intracellular survival of Campylobacter jejuni or Citrobacter freundii, but monensin markedly reduced Citrobacter uptake. Epithelial cell invasion by both of these bacterial genera was dependent upon de novo bacterial protein synthesis but not upon de novo eukaryotic cell protein synthesis. In contrast to the T24 cell line-specific, strict microtubule-dependent uptake, Citrobacter entry into other cell lines was inhibited by both microtubule- and microfilament-depolymerization, suggesting that these bacteria encode two separate pathways for uptake (i, microtubule-dependent; ii, microfilament-dependent) that are cell line-specific and are recognized perhaps depending on the presence and abundance of appropriate eukaryotic receptors.


Lisinopril or Coreg CR in reducing cardiotoxicity in women with breast cancer receiving trastuzumab: A rationale and design of a randomized clinical trial.
Trastuzumab (TZB) is an established therapy for HER2-positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin-converting enzyme (ACE) inhibitors and β-blockers (BBs) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a BB during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo. We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to evaluate the effects of an ACE inhibitor (lisinopril) and a BB (carvedilol phosphate-extended release) on cardiotoxicity in patients with breast cancer who are receiving adjuvant or neoadjuvant TZB therapy. The primary objectives include (1) comparison of incidence of cardiotoxicity and (2) comparison of LVEF as a continuous variable in between the arms. Cardiotoxicity was defined as an absolute decrease in LVEF from baseline of ≥10% at follow-up or an absolute decrease of ≥5% in LVEF from baseline for individuals with <50% LVEF at follow-up. The target accrual is 468 participants, representing patients both with and without anthracycline exposure. The enrollment is completed. The trial is co-sponsored by University of South Florida and National Cancer Institute. The LVEF is being evaluated by echocardiography or multigated acquisition scan. If we can demonstrate that the use of an ACE inhibitor or a BB can reduce the degree of TZB-induced cardiotoxicity, it is hoped that patients will receive complete and uninterrupted TZB therapy for breast cancer without compromising cardiac function.


Spin Structure of K Valleys in Single-Layer WS_{2} on Au(111).
The spin structure of the valence and conduction bands at the K[over ¯] and K[over ¯]^{'} valleys of single-layer WS_{2} on Au(111) is determined by spin- and angle-resolved photoemission and inverse photoemission. The bands confining the direct band gap of 1.98 eV are out-of-plane spin polarized with spin-dependent energy splittings of 417 meV in the valence band and 16 meV in the conduction band. The sequence of the spin-split bands is the same in the valence and in the conduction bands and opposite at the K[over ¯] and the K[over ¯]^{'} high-symmetry points. The first observation explains "dark" excitons discussed in optical experiments; the latter points to coupled spin and valley physics in electron transport. The experimentally observed band dispersions are discussed along with band structure calculations for a freestanding single layer and for a single layer on Au(111).


Constant current sine wave transcutaneous nerve stimulation for the evaluation of peripheral neuropathy.
We have evaluated various forms of peripheral neuropathy with a new device which emits a constant sinusoid stimulus at varying frequencies to quantitate current perception thresholds (CPTs). In normal individuals, CPT measures increase with increasing stimulation frequency, are highest on the toe and lowest on the face. There is a significant effect of age and sex on threshold perception. In patients with neuropathy, there is a marked increase in thresholds on hands and feet, as well as a lesser but still significant increase of facial CPTs. Thresholds furthermore correlated with clinical severity in a group of patients with diabetic neuropathy. Facial thresholds were markedly elevated in the patients with moderate to severe neuropathy, suggesting that the device is sensitive to the systemic nature of peripheral neuropathy. The authors believe the device will be a useful tool in screening for sensory neurologic abnormalities.


[Clinical nuclear medicine in bone metastases].
(99m)Tc-hydroxymethylene diphosphonate is not directly to Calcium of the bone matrix, but is binding to hydroxyapatite within the bone matrix. Strontium-89 is a member of family II A of the periodic table, same as Calcium, and is incorporated into bone matrix directly. It is very important that the the regions of the pain from bone metastases are present in the site of the abnormal uptake by bone metastases.


Long-term outcome of intracoronary microstent implantation: lesion matched comparison with Palmaz-Schatz stent.
We performed a lesion matched comparison of AVE Microstent and Palmaz-Schatz stent implants with 6 month follow-up angiography to compare the occurrence of restenosis. Thirty-three pairs of lesions were matched for lesion location, ACC/AHA lesion type, reference diameter, lesion length, and angiographic descriptors. Age, sex, clinical profile, and indication for stenting were comparable. Quantitative coronary analysis before and after the procedure was comparable in the two groups but minimum lumen diameter (MLD) at follow-up was less with Microstent--2.01 +/- 1.01 mm than Palmaz-Schatz stent--2.43 +/- 0.96 mm (P = 0.05). Binary restenosis was present in 33% and 21% and was diffuse in 55% and 29% of the two groups, respectively. Typical angina at follow-up was more frequent with Microstent (36%) than Palmaz-Schatz stent (15%; P = 0.038). When implanted in lesions of similar complexity, Microstent yields similar post procedure angiographic results but smaller MLD at follow-up and more frequent angina than Palmaz-Schatz stent.


[Effect of different preparation crafts on the content of baicalin in shuanghuanglian (SHL) injection].
The content of baicalin is stable when baicalin is added quantitatively in preparation. The time of extraction of the effective components of SHL with alcohol and the concentration of alcohol have little effect on the content of baicalin. The components can be extracted once, and the content of alcohol is preferably 85%. The pH level has greater influence on the content of baicalin, and should be controlled between 7.0 to 8.0. 0.2% activated carbon is suitable in preparation.


Cloning and characterization of a gene for a 19 kDa fibrinogen-binding protein from Staphylococcus aureus.
Staphylococcus aureus has been shown to interact specifically with fibrinogen. Three different extracellular fibrinogen-binding proteins, two of which have coagulase activity, are produced by S. aureus strain Newman. The role of these fibrinogen-binding proteins during staphylococcal colonization and infection has not yet been fully elucidated. Here we describe the cloning, sequencing and expression of a gene for a 19 kDa fibrinogen-binding protein. This gene, called fib, encodes a 165-amino-acid polypeptide, including a 29-amino-acid signal sequence. The recombinant protein, which has an estimated molecular mass of 15.9 kDa, bound fibrinogen and was recognized by a polyclonal antiserum against the native Fib protein. Homologies between the Fib protein and the fibrinogen-binding domain of coagulase suggest that amino acids within this domain are involved in the binding to fibrinogen.


Some features of learning in the Morris water test in rats selected for responses to humans.
The characteristics of learning in the Morris water test were studied in gray rats subjected to prolonged selection for elimination (the tame strain) and enhanced (the aggressive strain) aggressivity towards humans. Blood corticosterone levels at different stages of learning were also estimated. Tame rats learned to locate the invisible platform better than aggressive rats. The time spent seeking the platform by aggressive rats increased because they spent more time at the periphery of the basin. The duration of vertical investigative activity while on the platform was greater in tame rats than in aggressive rats. Fixation of the memory trace was demonstrated by the observation that rats of both strains spent more time in the sector in which the platform had been located during the training period. Rats of the two strains showed essentially no difference in terms of the time spent seeking the platform when it was placed in the opposite sector. After one day of training, blood corticosterone was significantly lower in tame than in aggressive rats. On subsequent training days, hormone levels in tame animals increased and were no different from those in aggressive rats. It is suggested that decreased emotionality and stress reactivity facilitated the learning process in tame rats in the Morris water test.


Phenolic compounds and related enzymes are not rate-limiting in browning development of fresh-cut potatoes.
The effect of minimal processing on polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia-lyase (PAL), and phenolic compounds was studied in five potato cultivars (Agria, Cara, Liseta, Monalisa, and Spunta). Minimal processing caused an overall increase in PPO, POD, and PAL activities. The isoform pattern of PPO was the same for all of the cultivars before and after processing. No latent PPO was detected. The isoperoxidase pattern was approximately the same among cultivars. An increase in POD activity was related to the specific induction of an acidic isoperoxidase. PAL showed an induction pattern characterized by the presence of a maximum peak of activity after 4 days of processing for all of the cultivars. The sequence of browning susceptibility of potato cultivars was as follows: Monalisa > Spunta > Liseta > Cara > Agria. Browning development was only partially correlated to PAL activity (only during the first 4 days after wounding). However, this correlation could not explain the above sequence of browning susceptibility. Minimal processing caused an increase of chlorogenic acid, whereas tyrosine content remained unchanged. In summary, no significant correlation was found between either rate or degree of browning and any other biochemical and physiological attribute investigated (PPO, POD, hydrogen peroxide, ascorbic acid content, and initial phenolics content as well as total and individual phenolics accumulation).


Weak C-H acids as protonophores can carry hydrogen ions through lipid membranes and mitochondria: a case of o-carborane.
ortho-Carborane (1,2-C2B10H12) was found to be a carrier of protons in both mitochondrial and artificial lipid membranes, suggesting that this dicarborane can reversibly release hydrogen ions and diffuse through the membranes in neutral and anionic forms. Similar to conventional uncouplers (e.g. 2,4-dinitrophenol), o-carborane stimulated mitochondrial respiration and decreased the membrane potential at concentrations of tens of micromoles. Protonophoric activity of o-carborane was observed both by a fluorometric assay using pyranine-loaded liposomes and electrical current measurements across planar lipid bilayers. Substantial contribution of the proton flux to the o-carborane-mediated current was proved by a shift of the zero current voltage upon imposing a pH gradient across the membrane. Meta-carborane (1,7-C2B10H12) lacked the protonophoric activity in line with its reduced C-H acidity. The results suggest that weak C-H acids can exhibit protonophoric activity in the biological environment. The finding of a new class of protonophoric compounds is of substantial interest due to promising anti-obesity and anti-diabetic properties of uncouplers.


Diffusion-Weighted Imaging and Post-contrast Enhancement in Differentiating Optic Neuritis and Non-arteritic Anterior Optic Neuropathy.
Non-arteritic anterior ischaemic optic neuropathy (NAION) and optic neuritis (ON) may be difficult to distinguish early in their disease courses. Our goal was to determine if specific magnetic resonance imaging characteristics differentiate acute NAION from ON. Neuroradiologists, masked to diagnosis, reviewed the diffusion-weighted imaging (DWI) and post-contrast enhancement (PCE) characteristics of the optic nerve in 140 eyes. PCE and DWI signals of the optic disc alone did not discriminate between NAION and ON. After taking age and sex into consideration, only DWI and PCE of the intraorbital segment of the optic nerve differentiated the two, with ON having the increased likelihood of these findings. Isolated PCE without DWI signal at the optic disc, however, was 100% specific for NAION. This may be the most specific way to radiographically differentiate between NAION and ON in the acute setting.


HERC Ubiquitin Ligases in Cancer.
HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3-HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies.


Application of recurrence quantification analysis for early detection of lean blowout in a swirl-stabilized dump combustor.
Lean blowout (LBO) is a serious issue in modern gas turbine engines that operate in a lean (premixed) mode to follow the stringent emission norms. When an engine operates with a lean fuel-air mixture, the flame becomes unstable and is at times carried out of the combustion chamber by the unburnt flow. Thus, the sudden loss of the flame, known as lean blowout, leads to fatal accidents in aircrafts and loss of production in power plants. Therefore, an in-depth analysis of lean blowout is necessary as the phenomenon involves complex interactions between flow dynamics and chemical kinetics. For understanding the complex dynamics of this phenomenon, recurrence analysis can be a very useful method. In the current study, we observe a transition to LBO as the global fuel-air ratio is reduced from stoichiometric condition and perform recurrence quantification analysis (RQA) with the CH∗ chemiluminescence data obtained experimentally. The extent of fuel-air mixing is varied with an objective of developing some robust early predictors of LBO that would work over a wide range of premixing. We find some RQA measures, such as determinism, laminarity, and trapping time, which show distinctive signature toward LBO and thereby can be used as early predictors of LBO for both premixed and partially premixed flames. Our analysis shows that the computational time for laminarity and trapping time is relatively less. However, computational time for those measures depends upon the dynamics of the combustor, size of the data taken, and choice of recurrence threshold.


Use of a Closure Device for the Management of Inadvertent Placement of a Central Venous Catheter in the Carotid Artery: A Case Report and Literature Review.
The placement of a central venous catheter (CVC) is a common intervention in hospitalized patients. Several adverse events have been reported in this "blind" procedure when it is performed without the aid of ultrasound, including artery catheterization, which although uncommon, is a serious complication. Potential treatment options include manual compression, open surgical repair, and endovascular treatment. A 62-year-old critically ill patient with accidental arterial catheterization of the right common carotid artery (CCA) during placement of CVC is presented. The catheter was removed successfully with the use of a Perclose-ProGlide closure device. A systematic literature review was performed to identify similar cases treated with the same technique. This case presents an alternative minimally invasive treatment option, using a Perclose Proglide (Abbott) closure device for the removal of a misplaced CVC in the right CCA. Although this is an off-label use of the device it can be an effective alternative treatment option, especially in unstable patients.


X-ray microtomography: 3-dimensional imaging of teeth for computer-assisted learning.
X-ray microtomography (XMT), a miniaturised form of computed tomography, has been used to generate 3-dimensional volume data sets of the X-ray absorption of human teeth in vitro, with a resolution of approximately 40 microns (cubic voxel sidelength). Examples are presented of images relevant to dental morphology, cariology, and cavity preparation and restoration. Applications of XMT imaging to dental education are discussed in the context of new approaches to visual learning through computer-assisted methods.


Immune stimulation for the treatment of papilloma.
There is no curative therapy for recurrent respiratory papillomatosis. Unmethylated dinucleotides of cytosine and guanine (CpG) are potent immune stimulants that have shown efficacy against tumors as monotherapy, as vaccine adjuvants, and in combination with chemotherapies. We examined the therapeutic effect of CpG oligodeoxynucleotides in the treatment of papillomavirus in a cottontail rabbit model (CRPV). Twenty rabbits were infected with CRPV; 10 were treated with 11 weekly CpG inoculations while treatment control rabbits received intralesional saline solution. Eight rabbits (4 treatment, 4 control) were rechallenged with CRPV 17 weeks after the initial viral challenge and monitored for new papilloma development. Papillomas developed in all 20 rabbits (100%) within 4 weeks of infection. The diagnosis was confirmed histologically. There was no difference in the average tumor burden between the treatment and control groups after 11 weeks of CpG treatments or after 9 additional weeks of observation. There was no difference between the groups in papilloma size at the site of the injections, nor was there eradication of papillomas at remote sites in either group. No new papillomas developed in any of the 8 animals that were rechallenged. We have reproduced an effective mammalian papilloma model for preclinical immunotherapeutic testing. Despite the potency of CpG in triggering host immunity, CpG oligodeoxynucleotide did not show a therapeutic effect against the large papilloma burdens tested in this study. The lack of effect suggests that either enhanced papilloma antigen presentation or targeting of immune-evasive mechanisms used by the papillomas is needed to treat bulky disease with an immunotherapeutic strategy.


Echocardiographic Assessment of Ischaemic Mitral Regurgitation, Mechanism, Severity, Impact on Treatment Strategy and Long Term Outcome.
The commonest mitral regurgitation etiologies are degenerative (60%), rheumatic post-inflammatory, 12%) and functional (25%). Due to the large number of patients with acute MI, the incidence of ischaemic MR is also high. Ischaemic mitral regurgitation is a complex multifactorial disease that involves left ventricular geometry, the mitral annulus, and the valvular/subvalvular apparatus. Ischaemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. The objective of this study is to determine the role of echocardiography in detecting and assessment of mitral regurgitation mechanism, severity, impact on treatment strategy and long term outcome in patients with myocardial infarction during the follow up period of 5 years. Also one of objectives to determine if the absence or presence of ischaemic MR is associated with increased morbidity and mortality in patients with myocardial infarction. The study covered 138 adult patients. All patients were subjected to echocardiography evaluation after acute myocardial infarction during the period of follow up for 5 years. The patients were examined on an ultrasound machine Philips iE 33 xMatrix, Philips HD 11 XE, and GE Vivid 7 equipped with all cardiologic probes for adults and multi-plan TEE probes. We evaluated mechanisms and severity of mitral regurgitation which includes the regurgitant volume (RV), effective regurgitant orifice area (EROA), the regurgitant fraction (RF), Jet/LA area, also we measured the of vena contracta width (VC width cm) for assessment of IMR severity, papillary muscles anatomy and displacement, LV systolic function ± dilation, LV regional wall motion abnormality WMA, LV WMI, Left ventricle LV remodeling, impact on treatment strategy and long term mortality. We analyzed and follow up 138 patients with previous (>16 days) Q-wave myocardial infarction by ECG who underwent TTE and TEE echocardiography for detection and assessment of ischaemic mitral regurgitation (IMR) with baseline age (62 ± 9), ejection fraction (EF 41±12%), the regurgitant volume (RV) were 42±21 mL/beat, and effective regurgitant orifice area (EROA) 20±16 mm(2), the regurgitant fraction (RF) were 48±10%, Jet/LA area 47±12%. Also we measured the of vena contracta width (VC width cm) 0,4±0,6 for assessment of IMR severity. During 5 years follow up, total mortality for patients with moderate/severe IMR-grade II-IV (54.2±1.8%) were higher than for those with mild IMR-grade I (30.4±2.9%) (P<0.05), the total mortality for patients with EROA ≥20 mm(2)(54±1.9%) were higher than for those with EROA <20 mm(2)(27.2±2.7%) (P<0.05), and the total mortality for patients with RVol ≥30 mL (56.8±1.7%) were higher than for those with RVol<30ml (29.4±2.9%) (P<0.05). After assessment of IMR and during follow up period 64 patients (46%) underwent CABG alone or combined CABG with mitral valve repair or replacement. In this study, the procedure of concomitant down-sized ring annuloplasty at the time if CABG surgery has a failure rate around 24% in terms of high late recurrence rate of IMR during the follow period especially after 18-42 months. The presence of ischaemic MR is associated with increased morbidity and mortality. Chronic IMR, an independent predictor of mortality with a reported survival of 40-60% at 5 years. Ischaemic mitral regurgitation has important prognosis implications in patients with coronary heart disease. Recognizing the mechanism of valve incompetence is an essential point for the surgical planning and for a good result of the mitral repair. It is important that echocardiographers understand the complex nature of the condition. Despite remarkable progress in reparative surgery, further investigation is still necessary to find the best approach to treat ischaemic mitral regurgitation.


Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies.
Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown to induce thyroid dysfunction in some cancer patients. The purpose of the present study was to evaluate the incidence and risk factors of this adverse autoimmune response. Triiodothyronine, thyroxine and thyrotropin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopathy (69 patients); rIL-2 was administered intravenously in 5-day cycles (18 x 10(6)-24 x 10(6) IU.m-2.day-1) either alone in 79 cases or in combination with autologous bone marrow transplantation in 26 cases, with interferon-gamma in 37 cases, with tumor necrosis factor-alpha in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was present upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9%) patients exhibited peripheral hypothyroidism, out of which four exhibited biphasic thyroiditis. Another five (3.4%) patients developed transient hyperthyroidism. Anomaly could not be classified in three patients. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abnormalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoimmune antibodies. Antithyroid antibodies were detected in 60.9% of patients with this complication. Thyroid-stimulating antibodies were never detected.(ABSTRACT TRUNCATED AT 250 WORDS)


Attraction of Aphidius ervi (Hymenoptera: Braconidae) and Aphidoletes aphidimyza (Diptera: Cecidomyiidae) to Sweet Alyssum and Assessment of Plant Resources Effects on their Fitness.
The green peach aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) is one of the most economically important aphid species affecting crops worldwide. Since many natural enemies of this aphid have been recorded, biological control of this pest might be a viable alternative to manage it. Selected plant species in field margins might help to provide the natural enemies with food sources to enhance their fitness. This study aimed to investigate if sweet alyssum, Lobularia maritima (L.) (Brassicaceae), is a potential food source for the parasitoid Aphidius ervi Haliday (Hymenoptera: Braconidae) and the predator Aphidoletes aphidimyza (Rondani) (Diptera: Cecidomyiidae), and whether this flower could contribute to enhance the biological control of M. persicae. Volatiles produced by alyssum, with and without flowers, attracted both natural enemies. This attractiveness to alyssum flowers was disrupted when compared with peach shoots recently infested with a relatively low number of aphids. When aphids were absent, parasitoids exposed to alyssum survived longer than those that fed on a sugar solution or on water. In the case of the predator, alyssum flowers did not benefit longevity since the nectaries were inaccessible to females. However, our results provide evidence that A. aphidimyza would be able to feed on nectar if accessible. The floral resource did not improve the reproductive capacity of the two natural enemies, but the 10% sugar solution increased the egg load of the predator. Provision of other sugar resources, such as flowers with exposed nectaries and extra floral nectar may also be a viable option to improve the biological control of M. persicae.


The epidemiology of physical activity and physical function in older people.
A primary goal of studies of successful aging is to identify the modifiable factors related to the plasticity of higher physical function; however, little is known about the relationship between habitual physical activity (especially that of lower- to moderate-intensity) and the maintenance of day-to-day functioning in older people. The purpose of this paper is to address the question of how patterns of physical activity translate into altered physical function among healthy older populations. In this paper, physical activity is classified as a behavior, whereas physical function is classified as performance, comprised of a series of increasingly integrated steps. Recent data from several epidemiologic studies suggest that physical activity is associated with the maintenance of more basic components of physical function, as well as with higher-order task or goal-oriented functions in healthy older people. Moreover, higher levels of physical activity appear to be associated with better functioning, even in those with already-existing chronic disease. Recent CDC/ACSM health recommendations call for incorporating at least 30 min of any activity into the daily schedule. Therefore, regular participation in activities of moderate intensity (such as walking, gardening, house/yard work) should be encouraged among the general older community.


Strong cooperative enhancement of two-photon absorption in double-strand conjugated porphyrin ladder arrays.
We present the two-photon absorption (2PA) spectra of a series of conjugated porphyrin oligomers containing N = 2, 4, 8, and ca. 13 monomer units, meso-meso connected with butadiyne linkers. We demonstrate that, in the coplanar double-strand arrays, self-assembled upon addition of 4,4'-bipyridyl, the conjugation length increases dramatically, leading to very strong cooperative enhancement of 2PA. We analyze the scaling of 2PA in both the double-strand and rotationally free single-strand arrays and show how the effective conjugation length in both cases is linked to the observed 2PA properties. By introducing a "conjugation signature" for the 2PA strength, we show that, in double-strand arrangement, the conjugation embraces the whole molecule up to the tetramer level, whereas in single-strand arrangement, it is always less than N, except for N = 2, but keeps increasing until N = 8. Our finding of extremely strong 2PA cross section, sigma2 approximately 105 GM, in double-strand oligomers peaking at 1.3 mum can find use for signal processing in fiber-optic devices.


Enzyme Purification Improves the Enzyme Loading, Self-Propulsion, and Endurance Performance of Micromotors.
Enzyme-powered micro- and nanomotors make use of biocatalysis to self-propel in aqueous media and hold immense promise for active and targeted drug delivery. Most (if not all) of these micro- and nanomotors described to date are fabricated using a commercially available enzyme, despite claims that some commercial preparations may not have a sufficiently high degree of purity for downstream applications. In this study, the purity of a commercial urease, an enzyme frequently used to power the motion of micro- and nanomotors, was evaluated and found to be impure. After separating the hexameric urease from the protein impurities by size-exclusion chromatography, the hexameric urease was subsequently characterized and used to functionalize hollow silica microcapsules. Micromotors loaded with purified urease were found to be 2.5 times more motile than the same micromotors loaded with unpurified urease, reaching average speeds of 5.5 μm/s. After comparing a number of parameters, such as enzyme distribution, protein loading, and motor reusability, between micromotors functionalized with purified vs unpurified urease, it was concluded that protein purification was essential for optimal performance of the enzyme-powered micromotor.


Fragmentation of Rest/Activity Patterns in Community-Based Elderly Individuals Predicts Incident Heart Failure.
Heart failure has previously been linked to sleep disorders that are often associated with frequent disturbances to human rest/activity patterns. We tested whether fragmentation of sustained rest/activity patterns derived from actigraphic recordings at baseline predicts incident heart failure in community-based elderly individuals. We studied 1099 community-based elderly adults participating in the Rush Memory and Aging Project who had baseline motor activity monitoring up to 11 days and were followed annually for up to 14 years. Fragmentation was assessed using previously validated indexes, derived from the probability of transitions once sustained rest or activity has been established. Heart failure was recorded via a clinical interview during the annual follow-up. Cox proportional hazards models were constructed to examine the relationship between rest fragmentation index and incident heart failure. Covariates grouped in terms of demographics, lifestyle factors and co-morbidities and cardiovascular risk factors/diseases were included. Increased rest fragmentation (but not activity fragmentation) was associated with higher risk for incident heart failure. Specifically, a subject with a rest fragmentation at the 90th percentile showed a 57% increased risk of developing incident heart failure compared to a subject at the 10th percentile in this cohort. This effect was equivalent to that of being over a decade older. These observations were consistent after adjusting for all covariates. Increased rest fragmentation, a potential surrogate for sleep fragmentation, is independently associated with a higher risk of developing heart failure in community-based elderly adults during up to 14 years of follow-up. Further work is required to examine the specific contributions from daytime napping versus nighttime sleep periods in the elderly, as well as the underlying autonomic and cardio-dynamic pathways that may explain the effects on heart function.


Antibacterial activity of cefditoren against major community-acquired respiratory pathogens recently isolated in Italy.
In this study we evaluated the in vitro activities of cefditoren--a broad-spectrum oral cephalosporin--and other comparator agents against 2,396 fresh isolates from community-acquired respiratory tract infections, collected from 6 clinical Italian microbiology laboratories. On penicillin-susceptible pneumococci and Streptococcus pyogenes, cefditoren demonstrated to be the most active antibiotic (MIC(90)values of 0.03 and 0.06 mg/L respectively), showing only a slight decrease in potency on penicillin-intermediate and resistant pneumococci (MIC(90)value 0.5 mg/L, 1.0 mg/L respectively). All the other comparators displayed MIC(90 )values of 4 - 8 mg/L for penicillins and of 4 to >64 mg/L for the oral cephalosporins. Cefditoren and levofloxacin were the most active against MSSA (MIC(90)0.5 mg/mL). Cefditoren displayed a uniformly potent inhibitory activity (MIC(90)of 0.03 mg/L) against all strains of Haemophilus influenzae, regardless of their ampicillin resistance (mediated or not by beta-lactamase production), while against Moraxella catarrhalis MIC(90)values were higher against beta-lactamase-positive (0.25 mg/L). Cefditoren was active also against Klebsiella pneumoniae and Escherichia coli : in this case its activity was comparable with that of levofloxacin. In conclusion, cefditoren, due to its potent activity, is a new effective therapeutic option for the treatment of respiratory tract infections.


A Pragmatic Test for Detecting Association between a Dichotomous Trait and the Genotypes of Affected Families, Controls and Independent Cases.
The efficient analysis of hybrid designs [e.g., affected families, controls, and (optionally) independent cases] is attractive because it should have increased power to detect associations between genetic variants and disease. However, the computational complexity of such an analysis is not trivial, especially when the data contain pedigrees of arbitrary size and structure. To address this concern, we developed a pragmatic test of association that summarizes all of the available evidence in certain hybrid designs, irrespective of pedigree size or structure. Under the null hypothesis of no association, our proposed test statistic (POPFAM+) is the quadratic form of two correlated tests: a population-based test (e.g., wQLS), and a family-based test (e.g., PDT). We use the parametric bootstrap in conjunction with an estimate of the correlation to compute p-values, and we illustrate the potential for increased power when (1) the heritability of the trait is high; and, (2) the marker-specific association is driven by the over-representation of risk alleles in cases, and by the preferential transmission of risk alleles from heterozygous parents to their affected offspring. Based on simulation, we show that type I error is controlled, and that POPFAM+ is more powerful than wQLS or PDT alone. In a real data application, we used POPFAM+ to analyze 43 genes of a hybrid epilepsy study containing 85 affected families, 80 independent cases, 234 controls, and 118 reference samples from the International HapMap Project. The results of our analysis identified a promising epilepsy candidate gene for follow-up sequencing: malic enzyme 2 (ME2; min p < 0.0084).


A social perspective on need and demand for orthodontic treatment.
In addition to needs fostered by actual physical disabilities resulting from malocclusion, need and demand for orthodontic treatment may develop entirely apart from any consideration of health needs. In fact, improvement of physical function is not the primary motivation of many persons who receive orthodontic care. A variety of social factors are related to perceived needs for acceptable dentofacial appearance and to public demand for orthodontic services. Since early times human teeth have been the object of mutilations to satisfy sociocultural expectations. The mutilation, and even removal of teeth, to achieve dental cultural norms in, so-called, primitive societies may appear barbaric to an ethnocentric society. However, a significant sociocultural need can be met equally by the African or Brazilian who has had teeth filed to a point and by the Western adolescent who having had four teeth surgically removed to provide space in the arch then undergoes two years of orthodontic therapy to reposition and straighten the remaining teeth. From a sociological point of view, the need and desire of members of a society to achieve a culturally acceptable body image constitutes neither frivolity nor luxury. If children's teeth do not naturally meet the norm for esthetic dental appearance, the response of families to sociocultural expectations and pressures produces a culturally valid need for orthodontic intervention. Other social factors affecting perceived need and demand for orthodontic care are socioeconomic, desire for upward social mobility, and social change with regard to public attitudes toward the availability of dental health services and the increasing removal of financial barriers. Potential changes in present US orthodontic practice may be required if care is to be delivered to significantly larger segments of the population.


Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion.
Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.


Correlation of titer, preservation method, and storage of Mycoplasma gallisepticum F strain and the immune response in chickens.
The F strain of Mycoplasma gallisepticum (MG) was used either fresh or after lyophilization or freezing at -60 C to vaccinate young leghorn chickens. Vaccine stored either frozen or lyophilized for 22 months was also used. Each vaccine preparation was given at dosages ranging from 10(5) to 10(9) colony-forming units/ml. All dosage levels of MG significantly (P less than 0.05) reduced air-sac lesion scores after aerosol challenge with the R strain of MG at 6 weeks postvaccination, regardless of the method of vaccine preservation or storage.


Potential of patellar height measurement methods in predicting recurrent patellar dislocation incidence: a case-control study.
Recurrent patellar dislocation (RPD) is a multifactorial disease that affects young and active people. Patellar height measurements are used clinically to screen and diagnose knee conditions. However, there are no known studies that have assessed and compared the performance of patellar height indices for predicting the incidence of RPD, which could be used to recommend surgical treatment after primary patellar dislocation. This case-control study aimed to determine if the patellar height index could be used to predict the incidence of RPD, and to identify the optimal method in terms of its diagnostic ability for RPD. Altogether, 133 patients (52 patients with RPD [Group R] and 81 sex- and age-matched controls [Group C]) were enrolled in this study. The Insall-Salvati (IS), Blackburne-Peel (BP), Caton-Deschamps (CD), and modified IS (mIS) methods were used to measure the patellar height index. The intra-observer and inter-observer reliabilities of these four methods were determined using intraclass correlation coefficients. A receiver operating characteristic curve analysis was performed to evaluate the predictive ability of each index and identify the cut-off values that indicated significantly increased risk of RPD. Patient demographics were similar between the two groups. The inter-observer and intra-observer reliabilities were good for all four methods. In patients with RPD, the mean index values for the four methods were significantly higher than those in the matched controls. The area under the curve (AUC) values for IS, BP, CD, and mIS were 0.91 (standard error [SE], 0.03; 95% confidence interval [CI], 0.84-0.96), 0.72 (SE, 0.05; 95% CI, 0.63-0.81), 0.86 (SE, 0.03; 95% CI, 0.79-0.92), and 0.96 (SE, 0.01; 95% CI, 0.94-0.99), respectively. Patellar height indices had high predictive performance for the incidence of RPD. The mIS method had the highest AUC.


Mitochondrial function and coronary flow reserve improvement after autologous myoblast patch transplantation for ischaemic cardiomyopathy: a case report.
Autologous myoblast patch (AMP) transplantation has resulted in good clinical outcomes for end-stage ischaemic cardiomyopathy, but the mechanisms behind them are unclear. Herein, we report the relationship between mitochondrial function and coronary flow reserve (CFR) before and after AMP transplantation. The patient was a 73-year-old man who underwent coronary artery bypass grafting (CABG). At that time, the left ventricular ejection fraction (LVEF) was 53%, but it declined to 25% after 6 years. He was diagnosed with ischaemic cardiomyopathy (ICM). Coronary flow reserve in NH3-positron emission tomography (NH3-PET) was impaired to 1.69. In Tc-99m MIBI scintigraphy, the washout rate (WR) was 17%, suggestive of impaired mitochondrial function. He was not a candidate for heart transplantation, and we performed AMP transplantation 6 years after CABG. One year after AMP transplantation, LVEF, CFR, and Tc-99m MIBI WR improved to 36%, 2.07, and 7%, respectively. The Tc-99m MIBI WR improved especially in the anterolateral region, and the CFR increased in almost all segments. In this case, AMP transplantation for ICM improved cardiac function, CFR, and mitochondrial function. The mitochondrial transfer from the transplanted myoblasts to the damaged myocardium may have contributed to the mitochondrial function improvement. This probably induced myocardial energy metabolism recovery and decreased oxygen demand. AMP transplantation also has the potential to improve microvascular dysfunction, due to angiogenesis induction. These effects can lead to improved prognoses of ICM after AMP transplantation, highlighting its potential to cure refractory heart failure.


Ratiometric nanothermometer based on an emissive Ln3+-organic framework.
Luminescent thermometers working at the nanoscale with high spatial resolution, where the conventional methods are ineffective, have emerged over the last couple of years as a very active field of research. Lanthanide-based materials are among the most versatile thermal probes used in luminescent nanothermometers. Here, nanorods of metal organic framework Tb0.99Eu0.01(BDC)1.5(H2O)2 (BDC = 1-4-benzendicarboxylate) have been prepared by the reverse microemulsion technique and characterized and their photoluminescence properties studied from room temperature to 318 K. Aqueous suspensions of these nanoparticles display an excellent performance as ratiometric luminescent nanothermometers in the physiological temperature (300-320 K) range.


Functional plasticity in the respiratory drive to thoracic motoneurons in the segment above a chronic lateral spinal cord lesion.
A previous neurophysiological investigation demonstrated an increase in functional projections of expiratory bulbospinal neurons (EBSNs) in the segment above a chronic lateral thoracic spinal cord lesion that severed their axons. We have now investigated how this plasticity might be manifested in thoracic motoneurons by measuring their respiratory drive and the connections to them from individual EBSNs. In anesthetized cats, simultaneous recordings were made intracellularly from motoneurons in the segment above a left-side chronic (16 wk) lesion of the spinal cord in the rostral part of T8, T9, or T10 and extracellularly from EBSNs in the right caudal medulla, antidromically excited from just above the lesion but not from below. Spike-triggered averaging was used to measure the connections between pairs of EBSNs and motoneurons. Connections were found to have a very similar distribution to normal and were, if anything (nonsignificantly), weaker than normal, being present for 42/158 pairs, vs. 55/154 pairs in controls. The expiratory drive in expiratory motoneurons appeared stronger than in controls but again not significantly so. Thus we conclude that new connections made by the EBSNs following these lesions were made to neurons other than α-motoneurons. However, a previously unidentified form of functional plasticity was seen in that there was a significant increase in the excitation of motoneurons during postinspiration, being manifest either in increased incidence of expiratory decrementing respiratory drive potentials or in an increased amplitude of the postinspiratory depolarizing phase in inspiratory motoneurons. We suggest that this component arose from spinal cord interneurons.


Psychiatric epidemiology.
In this paper, some of the basic concepts of epidemiology are presented. Their applicability to psychiatry is outlined, and the definitions of terms are given. Various methods of epidemiological investigation are discussed. The background for the development of recent prevalence studies, including advances in diagnostic methods and case ascertainment, are given in some detail, and some recent results are presented. Additional areas of investigation are discussed more briefly.


[Effects of sex hormones on bladder function and structure: experiment with ovariectomized female rats].
To investigate the effects of sex hormones on bladder and mechanism thereof. Sixty mature female SD rats underwent bilateral ovariectomy and then randomly divided into 6 groups: low dose estrogen group (OVX + E group) treated with estradiol benzoate 0. 25 mg/kg injected intramuscularly qod, high dose estrogen group (OVX + E 1 mg group) treated with estradiol benzoate 1 mg/kg, progesterone (P) group, treated with P 1 mg, OVX + E + P group treated with estradiol benzoate 0.25 mg/kg + progesterone 1 mg, d androgen group (OVX + T group) treated with testosterone propionate 3 mg/kg, and untreated ovariectomized group (OVX group) receiving no medication. Another 10 rats underwent sham operation. Four weeks later the rats were killed with their bladders and urethras taken out to undergo light and electron microscopy. The thickness of bladder wall of the OVX group was (0.97 +/- 0.11) mm, significant thinner than that of the sham operation group [(1.10 +/- 0.1) mm, P < 0.05)]. The thickness levels of bladder walls of the OVX + E and OVX + T groups were (1.23 +/- 0.12) mm and (1.26 +/- 0.12 mm) respectively, both significantly thicker than that of the OVX group (both P < 0.01). Wider spaces between the detrusor muscle fascicles and degeneration of detrusor muscle cells were seen in the bladder walls of the OVX group, and such phenomena were milder in the OVX + E and OVX + T groups, however, wider spaces between the detrusor muscle fascicles could be seen in the OVX + E + P group too. The hypertrophic effect on the detrusor muscle of the OVX + E 1 mg group was weaker than that of the OVX + E group, a lot of cytoplasmic vacuoles was seen in the 2 groups treated with E, especially the OVX + E 1 mg group. The bladder structure of the OVX + P group was similar to that of the OVX group. Endogenous testosterone level as well as estrogen level can significantly affect the bladder structure with a hypertrophic effect on bladder detrusor muscle. But higher doze of estrogen also has some unexpected effects which may destroy bladder structure. In addition, progesterone can compromise the effect of estrogen.


[Historicity and the epistemological condition of psychoanalysis: filiation and orthopraxis].
The very particular epistemological condition of psychoanalysis (that of a "psychology" closely tied to "metapsychology") is well evidenced in the genesis and historical development of this "new science"; so intrinsically tied to Freud's personality that it requires a personal and guaranteed transmission: a "filiation". Indeed, from this epistemological situation, as well as from the clinical character of psychoanalytical interpretation, was been the deontological necessity for a societal institution that attests to the orthodoxy of psychoanalytical praxis: an "ortho-praxis". This yields a body of problems specific to the scientific historiography of psychoanalysis, to the extent that the diversity of heuristic conditions of historians, whether psychoanalysts or non-psychoanalysts, although effective, does not always ensure a privilege or natural advantage. The epistemological analysis of such a body of problems--starting from the notions of "chronicle" and "history" in general--lead, nonetheless, to the exclusion of relativism and historiographic solipsism.


[Participation of serotonin in the mechanisms of the formation of trigeminal motor nucleus].
The formation of trigeminal motor nucleus (TMN) was studied in the early postnatal period in 21 female Wistar rats which received the serotonin biosynthesis inhibitor para-chloro-phenylalanine at prenatal Day 16 (the period of serotoninergic system formation). It was shown that the serotonin deficit during the prenatal period in rats resulted in the changes of TMN structural organization. In the early postnatal period, the delay of neuropil development, the reduction of cell body size with the partial loss of Nissl substance in some of the neurons, the presence of degenerating neurons with the signs of hyperchromatosis in all the parts of the nucleus, especially in TMN ventromedial part, were detected. At later stages, the destruction of motoneurons became slower, though some of them had morphological abnormalities. With the increase of the postnatal age (by Day 20) the number of motor neurons decreased, apparently, as a result of the gradual intensification of cell death. Simultaneously with the motor neuron degeneration in TMN parts studied, the astrocytic gliosis was observed.


Treatment of seafood processing wastewater using upflow microbial fuel cell for power generation and identification of bacterial community in anodic biofilm.
Tubular upflow microbial fuel cell (MFC) utilizing sea food processing wastewater was evaluated for wastewater treatment efficiency and power generation. At an organic loading rate (OLR) of 0.6 g d(-1), the MFC accomplished total and soluble chemical oxygen demand (COD) removal of 83 and 95%, respectively. A maximum power density of 105 mW m(-2) (2.21 W m(-3)) was achieved at an OLR of 2.57 g d(-1). The predominant bacterial communities of anode biofilm were identified as RB1A (LC035455), RB1B (LC035456), RB1C (LC035457) and RB1E (LC035458). All the four strains belonged to genera Stenotrophomonas. The results of the study reaffirms that the seafood processing wastewater can be treated in an upflow MFC for simultaneous power generation and wastewater treatment.


Characterization of a novel anther-specific gene encoding a leucine-rich repeat protein in petunia.
In Petunia x hybrida 'Fantasy Red', a leucine-rich repeat (LRR) gene referred to as PhLRR, was identified in a flower bud cDNA library. The open reading frame sequence of PhLRR was 1251 bp, encoding a putative 46.2-kDa protein of 416 amino acids. The PhLRR protein showed high similarity to members of polygalacturonase inhibitor proteins (PGIPs), contained 11 conserved LRR domains, and was an extracellular localization protein. Phylogenetic analysis showed that PhLRR belonged to the same PGIPs subfamily as SHY, indicating that PhLRR may be involved in the development of pollen-like SHY. Expression analysis revealed that PhLRR was abundantly expressed during early stages of flower bud and anther development, while it was not detected in any other examined organs, such as sepals, petals, pistils, roots, stems, leaves, or open flowers. Furthermore, many cis-acting elements (such as AGAAA and GTGA) related to anther-specific gene expression were identified in the PhLRR gene promoter region, indicating that the promoter is also anther-specific. These results suggested that PhLRR is a novel anther-specific gene that may be essential for the early development of anthers.


Evaluation of a new semiquantitative immunodot assay for the screening of specific IgE.
The Immunodot CMG is a new, simple assay for the semiquantitative screening of specific IgE. It does not necessitate any particular equipment. It consists of two nitrocellulose strips on which either five indoor or five outdoor allergens are bound. In the present evaluation, 82 serum samples from allergic patients were tested with the first strip and 101 with the second. The results were compared with those obtained with the CAP System (Kabi Pharmacia). A version using undiluted serum and a short incubation time (short version) appeared to be more sensitive than a long version using serum diluted 1:5. In most cases, the results agreed with those of the CAP System. Discordant results were found in 2-9% of the cases according to the allergen, and were most often negative with Immunodot CMG and positive with the CAP System, indicating a slightly lower sensitivity for the new test. When compared to the CAP System, the Immunodot CMG showed a sensitivity of 84.5% and a specificity of 94%. Readings were found to be reproducible and easy to perform with the naked eye. Our results showed that the Immunodot CMG test is comparable to the CAP System, which is slightly more sensitive but requires much more elaborate and expensive equipment.


Comparison of social support, depression and anger in diabetic and cardiac patients.
To explore the role of social support, depression and anger in diabetic and cardiac patients. The cross-sectional study was conducted from April to September 2015 at three public-sector hospitals in Punjab, Pakistan, and comprised cardiac and people with diabetes from outpatient departments. Data was collected using the Siddiqui-Shah depression scale, the interpersonal support evaluation list and the Trait anger and expression scale. Data was analysed using SPSS 21. Of the 200 patients, 101(50.5%) were cardiac and 99(49.5%) were diabetic. Among the cardiac patients, 51(50.5%) were males and 50(49.5%) were females, while the corresponding number among the diabetics were 50(50.5%) and 49(50.5%). Cardiac patients exhibited higher level of depression and received more social support than the diabetic patients (p<0.05). Low social support was a significant negative predictor of anger and depression among diabetic and cardiac patients (p<0.05). Social support was found to be a significant factor in the treatment of diabetes and cardiac diseases.


"The best and most practical philosophers": Seamen and the authority of experience in early modern science.
Within the historiography of early modern science, trust and credibility have become synonymous with genteel identity. While we should not overlook the cultural values attached to social hierarchy and how it shaped the credibility of knowledge claims, this has limitations when thinking about how contemporaries regarded the origins of that knowledge and its location in different types of workers and skillsets. Using the example of seamen in the circles of the Royal Society, this article employs the category of experience, and by extension expertise, to illustrate how recognized forms of knowledge and skill acted as routes to credibility and authority in early modern science. It argues that, within the experimental community, the seaman's authority derived from their direct experience of novel and remote phenomena and the cumulative effect of their wider experience. The accumulated experience they acquired from frequent practice, observation, and exposure translated into a form of "expertness" that rendered seamen trustworthy and credible observers and thinkers. The gentlemanly trust model does not accommodate nor acknowledge the ways the seaman's direct and accumulated experience (and that of many other professional groups) were recognized and valued in inquiry and discourse. The article therefore sets out a new model for understanding trust, credibility, and authority in early modern science that can take us beyond a restrictive mono-model that locates trust in one sociocultural category to highlight the multiple, and sometimes competing, claims to epistemological authority.


Maintenance of the celiac trunk with the left-sided liver allograft for in situ split-liver transplantation.
It has been shown that in situ split-liver transplantation (SLT) expands the cadaveric donor pool, decreases recipient waiting time, and decreases pretransplant morbidity. However, the technique as previously described requires a microvascular left hepatic artery anastomosis. In an attempt to decrease the incidence of hepatic artery thrombosis and to increase collaboration among transplant teams, in the current report, we describe a modification of the in situ SLT technique that maintains the celiac trunk with the left-sided liver allograft. Twelve in situ split-liver procurements resulted in 24 segmental liver allografts; 11 right trisegments, 11 left lateral segments, 1 right lobe, and 1 left lobe. The common bile duct and main portal vein were maintained with the right-sided liver allograft in all cases. The right hepatic artery was divided, and the celiac trunk was maintained with the left-sided liver allograft in nine cases. In one case the left hepatic artery was divided and the celiac trunk was maintained with the right-sided allograft. Two of the 12 donors had a completely replaced left hepatic artery originating from the left gastric artery, which was divided at its origin from the celiac trunk. When the celiac trunk was maintained with the left-sided allografts, arterial reconstruction of the right-sided allograft was performed with an external iliac arterial interposition graft. Nineteen of the 24 split-liver allografts were transplanted at our center. The remaining five liver allografts were shared with regional liver transplant centers. In this series, 1-year actuarial patient and allograft survival rates are 100% and 96%, respectively. Hepatic artery thrombosis (HAT) did not occur in any patient receiving a left-sided split allograft in which the celiac trunk or left gastric artery was maintained; in addition, HAT did not occur in any of the right-sided allografts. HAT did occur immediately after transplantation in the one patient who was transplanted with a left lateral segment without the celiac trunk. This allograft was salvaged by early thrombectomy and interposition grafting. One patient required retransplantation, owing to portal vein thrombosis. Hepatic venous outflow obstruction did not occur in any of the patients. Two patients required reexploration in the posttransplant period because of arterial anastomotic site bleeding, and one of the left lateral segment allograft recipients had a cut-surface bile leak, which was managed nonoperatively. All of the patients are alive and well, including the five patients who received their transplants at other centers, with a median follow-up of 10 months (range, 1-27 months). In summary, our data demonstrate that maintaining the celiac trunk with the left-sided allograft in SLT provides excellent early survival results with low complication rates. This technical modification obviates the need for a left hepatic artery microvascular anastomosis and should lower the incidence of hepatic artery thrombosis in the small-caliber left hepatic artery. We have also shown that this technique allows sharing among liver transplant centers without compromise in patient or allograft survival rates. It is hoped that this modification in SLT will increase the number of livers split, and will promote sharing among transplant centers to truly optimize the number of liver allografts available from the cadaveric pool.


The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke Patients.
To investigate whether transcranial direct-current stimulation (tDCS) can improve cognition in stroke patients. Forty-five stroke patients (20 males and 25 females, average age: 62.7 years) with cognitive dysfunction were included in this prospective, double-blinded, randomized case-control study. All patients were right-handed and the mean elapsed time after stroke was 39.3 days. Three different treatments groups were used: (1) anodal stimulation of the left anterior temporal lobe, (2) anodal stimulation of the right anterior temporal lobe, and (3) sham stimulation. tDCS was delivered for 30 minutes at 2 mA with 25 cm(2) electrodes, five times/week, for a total of 3 weeks, using a Phoresor II Auto Model PM 850 (IOMED(®)). The evaluation of cognitive impairment was based on a Computerized Neuropsychological Test (CNT), Korean Mini-Mental State Examination (K-MMSE). The Korean version of the Modified Barthel Index (K-MBI) was used to assess activities of daily living functionality. These evaluations were conducted in all patients before and after treatment. Each group included 15 patients. Pre-treatment evaluation showed no significant differences between the three groups for any of the parameters. There was significant improvement in the verbal learning test on the CNT in the left anodal stimulation group (P < 0.05). There were, however, no significant differences in the K-MMSE or K-MBI scores among the three groups. These results demonstrated the beneficial effects of anodal tDCS on memory function. Thus, tDCS can successfully be used as a treatment modality for patients with cognitive dysfunction after stroke.


Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions in vitro.
Human melanoma cell lines that express high constitutive levels of the metastasis-associated marker intercellular adhesion molecule 1 (ICAM-1) were found to secrete interleukin 1 (IL-1) in vitro. Experiments with neutralizing antibodies showed that this cytokine was responsible for their expression of ICAM-1 but not that of two other progression/metastasis markers, Muc-18 and Gp IIb/IIIa. The IL-1 present in melanoma-conditioned medium induced the expression of vascular cell adhesion molecule 1, endothelial-leukocyte adhesion molecule 1, and ICAM-1 on human umbilical vein endothelial cells (ECs) in culture and increased the rate at which melanoma cells and ECs adhered to each other. IL-1-producing melanoma lines adhered significantly more rapidly to ECs than did non-IL-1-producing lines, and this enhancement was reduced by prior incubation of the melanoma cells with neutralizing anti-IL-1 antibodies. Similarly, endothelial cells treated with conditioned medium from IL-1-producing melanoma lines adhered significantly more rapidly to melanoma cells than did ECs treated with medium from non-IL-1-producing melanoma lines, and this enhancement was abolished by addition of anti-IL-1 antibodies to EC cultures in conditioned medium. Blocking antibodies to endothelial vascular cell adhesion molecule 1, endothelial-leukocyte adhesion molecule 1, and ICAM-1 failed to inhibit melanoma-EC adhesion, but an antibody to tumor cell GpIIb/IIIa did block adhesion by up to 44%. The ability to secrete IL-1 could increase the metastatic potential of melanoma cells by stimulating tumor cell-EC adhesion.


Strategies in haploidentical stem cell transplantation in adults.
Haploidentical related donors are alternative stem cell sources for patients without human leukocyte antigen (HLA)-matched related or unrelated donors. Immediate access to the donor, availability for patients with rare haplotypes, ease of stem cell procurement, and lack of a requirement for a physical cord blood bank or an extensive HLA database render this type of hematopoietic stem cell transplantation particularly attractive despite the high histoincompatibility barrier between the recipient and the haploidentical graft. In this review, we answer the following questions: 1) What are the current transplant strategies used to overcome the histoincompatibility barrier in haploidentical stem cell transplantation and their clinical results? 2) How should we choose the donor when there is more than one available haploidentical donor? 3) How does transplantation from haploidentical donors compare to that from umbilical cord blood? None declared.


Comparison of serologic methods for the diagnosis of Mediterranean spotted fever.
During summer Mediterranean spotted fever (MSF) is prevalent in the subcostal part of Croatia (North Dalmatia) as well as in other areas of the Mediterranean coast. We compared the specificity and sensitivity of complement fixation (CF), latex agglutination (Latex-R. conorii), microimmunofluorescence (micro-IF) and enzyme-linked immuno assay (ELISA) for detection and measuring antibodies against Rickettsia conorii in 78 sera from 46 patients with/or suspected Mediterranean spotted fever. The seroreactivity with SFG antigens containing the Rickettsia conorii-antigen(s) as a common determinant, was positive in all four serological tests suggesting that Rickettsia conorii was the probable causative agent of infection in our patients.


Dynamic determination of kinetic parameters, computer simulation, and probabilistic analysis of growth of Clostridium perfringens in cooked beef during cooling.
The objective of this research was to develop a new one-step methodology that uses a dynamic approach to directly construct a tertiary model for prediction of the growth of Clostridium perfringens in cooked beef. This methodology was based on simultaneous numerical analysis and optimization of both primary and secondary models using multiple dynamic growth curves obtained under different conditions. Once the models were constructed, the bootstrap method was used to calculate the 95% confidence intervals of kinetic parameters, and a Monte Carlo simulation method was developed to validate the models using the growth curves not previously used in model development. The results showed that the kinetic parameters obtained from this study accurately matched the common characteristics of C. perfringens, with the optimum temperature being 45.3°C. The results also showed that the predicted growth curves matched accurately with experimental observations used in validation. The mean of residuals of the predictions is -0.02logCFU/g, with a standard deviation of only 0.23logCFU/g. For relative growths <1logCFU/g, the residuals of predictions are <0.4logCFU/g. Overall, 74% of the residuals of predictions are <0.2logCFU/g, 7.7% are >0.4logCFU/g, while only 1.5% are >0.8logCFU/g. In addition, the dynamic model also accurately predicted four isothermal growth curves arbitrarily chosen from the literature. Finally, the Monte Carlo simulation was used to provide the probability of >1 and 2logCFU/g relative growths at the end of cooling. The results of this study will provide a new and accurate tool to the food industry and regulatory agencies to assess the safety of cooked beef in the event of cooling deviation.


Arteriovenous shunt in the management of severe asthma.
Arteriovenous shunt is described as a possible method to achieve vascular access in selected chronically ill patients with poor peripheral veins and, in the case of acute exacerbation, a prompt demand for access to the venous blood flow. Three patients with severe bronchial asthma are described, in whom arteriovenous shunts have been of great value.


Improving communication within the interdisciplinary team monitoring young women with onco-gynecological pathology in Romania.
The quality of medical care, as well as the application of effective treatments in the management of patients with gynecologic neoplasm, is of great importance. Finding new and efficient ways of communication between the doctors involved in the multidisciplinary team for the management of the disease, from the diagnosis to the reintegration into society, would help improve the quality of comprehensive patient care. The objective of the study was to assess the collaboration of family physicians with specialists treating patients suffering from gynecologic cancer, in order to improve the relationship between them via electronic communication. We conducted a descriptive, transversal study on 353 family physicians and 37 specialist doctors from Romania, between January and June 2015. For statistical data analysis, R for Data Analysis and Graphics version 3.2.1 was used. Most of the family physicians and specialist doctors believed that they provided the best care that they could, but consider that a multidisciplinary approach using online communication methods, in which doctors collaborate among each other, is needed. Finding a simple, efficient and modern means of communication is essential in order to increase the efficiency of medical care overall.


[Arterial involvement in Behçet's disease].
Ten cases of Behçet's disease with arterial lesions were observed in a series of 500 patients over a period of 12 years. The majority of patients were male (9/10) aged between 24 and 36 years with a mean of 30 +/- 5 years. The first group (3 cases) presented with thrombosis of the radial and superficial femoral arteries, the second group (4 cases) presented with aneurysm of the subclavian artery, common and external iliac arteries, brachiocephalic trunk and abdominal aorta and the third group (3 cases) had a combination of thrombosis and aneurysm of the pulmonary, external iliac and renal arteries.


Rapid-rate transcranial magnetic stimulation and hemispheric language dominance: usefulness and safety in epilepsy.
We performed rapid-rate transcranial magnetic stimulation (r-TMS) in 14 epileptic patients, using a coil centered over nine different positions on each side of the scalp and while the subjects counted aloud. We obtained lateralized speech arrest, concordant with the site of manual preference, in only seven patients. There was transitory homonymous hemianopia (one patient), brief jerking of one arm (two patients), and affective (crying) reaction (three patients) after the end of a train of stimuli. In our experience, r-TMS is not as sensitive as previously reported for determination of hemispheric language dominance and may have undesirable side effects.


A case study of disseminated histoplasmosis linked to common variable immunodeficiency.
Histoplasma capsulatum, a ground fungus, can infect humans, normally in endemic areas; the resulting disease can be asymptomatic or it can have a benign development, but in rare cases it can develop into a serious clinical condition and can even be fatal. Its most characteristic initial location is in the lungs, resembling tuberculosis, often accompanied by mediastinitis and an exuberant fibrotic response. The spread of this infection can be caused by the concomitance of another illness that alters the immunological balance. Sometimes such an association is not clear. Therefore, disseminated histoplasmosis is defined as a clinical condition where the fungus is present in more than one location. Common variable immunodeficiency is characterized by a generalized failure in the synthesis of antibodies, leading the affected individuals to present recurrent infections, especially those caused by encapsulated bacteria, most often involving the respiratory tract. We studied a serious case of disseminated histoplasmosis, accompanied by common variable immunodeficiency, observed at the Infirmary of the department of Medical Practice of the Federal University at Paraná Hospital das Clínicas.


Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population.
gamma-Glutamyl carboxylation, a reaction essential for the activity of vitamin K-dependent proteins, requires the concerted actions of gamma-glutamyl carboxylase (GGCX), vitamin K 2, 3-epoxide reductase complex 1 (VKORC1), and the chaperone calumenin (CALU). We evaluated the contribution of genetic polymorphisms in VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals and geno-typed 9 representative single-nucleotide polymorphisms in 3655 Japanese individuals representative of the general population. The mean activity of protein C in women bearing the GG genotype of GGCX 8016G>A (130.8% +/- 1.5%, n = 156) was significantly greater (P = .002) than that of individuals with either the AG (126.8% +/- 0.7%, n = 728) or the AA (125.4% +/- 0.6%, n = 881) genotype, after adjusting for confounding factors. The GGCX 8016G>A change leads to the substitution of Gin for Arg at amino acid residue 325 (Arg 325 Gln). This effect was comparable to that of a previously defined polymorphism in the protein C promoter. Mean protein S activity was influenced by the VKORC1 3730G>A and CALU 20943T>A genotypes, after adjusting for confounding factors. Thus, polymorphisms in genes involved in the vitamin K-dependent gamma-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population.


AQP8 transports NOX2-generated H2O2 across the plasma membrane to promote signaling in B cells.
H2O2 acts as a second messenger in key signaling circuits, transiently modulating tyrosine phosphatases and kinases. We investigated its origin, membrane transport, and functional role during B cell activation and differentiation. Our data identified NADPH-oxidase 2 as the main source of H2O2 and aquaporin 8 as a transport facilitator across the plasma membrane. On aquaporin 8 silencing, inducible B lymphoma cells responded poorly to TLR and BCR stimulation. Their differentiation was severely impaired, as demonstrated by retarded onset of IgM polymerization, low amounts of IgM secretion, and prolonged BCR expression on the cell surface. A silencing-resistant aquaporin 8 rescued responsiveness, confirming that the import of H2O2 across the membrane is essential for B cell activation. The addition of exogenous catalase to primary B splenocytes severely impaired the tyrosine phosphorylation induced by BCR cross-linking, as did the absence of NOX2 in a murine model of chronic granulomatous disease. Importantly, re-expression of gp91phox through gene therapy restored the specific B cell signaling deficiency in NOX2-/- cells. Thus, efficient induction of B cell activation and differentiation requires intact H2O2 fluxes across the plasma membrane for signal amplification.


Pharmacokinetics of two randomized trials evaluating the safety and efficacy of indinavir, saquinavir and lopinavir in combination with low-dose ritonavir: the MaxCmin1 and 2 trials.
Our objective was to identify possible differences in protease inhibitor plasma concentrations between and within three protease inhibitor regimens (indinavir, saquinavir and lopinavir all in combination with low-dose ritonavir) and to relate these differences to safety and efficacy. Data originated from pre-defined pharmacokinetic substudies within two randomized 48-week trials evaluating the safety and efficacy of three protease inhibitor regimens. At weeks 4 and 48, plasma was collected and minimum drug plasma concentrations, C(min), were obtained. Out of 656 randomized patients, 283 patients had available C(min) at week 4. Indinavir, saquinavir and lopinavir C(min) were high when combined with low-dose ritonavir. No significant difference in the proportion of patients experiencing treatment failure could be found according to the C(min) within any treatment arm. A saquinavir C(min) > 2000 ng/ml was associated with an increased risk of gastrointestinal grade 3 or 4 adverse events and higher total cholesterol. Overall, there were no changes in C(min) from week 4 to week 48 in patients who remained on therapy. No association between treatment failure and the C(min) could be demonstrated. Associations between high C(min) and toxicity were identified in the saquinavir arm; therefore, dose reductions may be appropriate in certain patients with C(min) several times above the minimum effective concentration.