Word reading and picture naming in Italian.
Results from two separate norming studies of lexical access in Italian were merged, permitting a comparison of word-reading and picture-naming latencies and the factors that predict each one for an overlapping subsample of 128 common nouns. Factor analysis of shared lexical predictors yielded four latent variables: a frequency factor, a semantic factor, a length factor, and a final factor dominated by frication on the initial phoneme. Age of acquisition (AoA) loaded highly on the first two factors, suggesting that it can be split into separate sources of variance. Regression analyses using factor scores as predictors showed that word reading and picture naming are both influenced by the frequency/AoA factor. The semantics/AoA factor influenced only picture naming, whereas the length and frication factors influenced only word reading. Generalizability of these results to other languages is discussed, including potential effects of cross-language differences in orthographic transparency.


The sexual scripting of oral genital contacts.
There is evidence from a number of sources that contemporary cultural scenarios for sexual conduct are often very approving of oral genital sex. Two surveys of sexual conduct are analyzed to examine the changes in interpersonal sexual scripts for oral genital sex for cohorts of white and college-educated young people who entered young adulthood between 1928 and 1943 and 1963 to 1967. Males in the earlier cohort had an excess of fellatio during the premarital period from erotic contacts with prostitutes and transient partners. In contacts with potential marital partners and in marriage men and women had equivalent rates of oral sex indicating a greater sexual reciprocity in these affectional relationships. In the latter cohort male and female rates of oral sex before marriage are substantially greater than for the earlier period but are equivalent for the two genders. In both periods oral sex is most common among the coitally experienced and is initiated by males. Evidence is found for an increased amount of sexual activity unlinked to marriage, what might be labeled pre-premarital sex. Male participation in oral sex seems responsive to opportunity, lowered moral inhibition, and emotional commitment while females' participation seems more linked to features of the ongoing relationship. In a review of studies in the 1970s and 1980s a further major increase in the incidence of oral sex in the period before marriage can be found. From these data it appears that oral sex has become, over the last 50 years, part of the sexual scripts of many young people and is a common, though not necessarily a frequent, component of sexual relations in contemporary marriage.


Establishment of a transplantable tumor line (IP) derived from rat pulmonary carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats.
A transplantable tumor line (IP) was established in syngeneic rats from a spontaneous pulmonary carcinoma found in a male F344 rat aged 25 months. A tissue fragment of IP grew into a nodule, 2-3 cm in diameter, 2-3 weeks after implant, and IP has been serially passed through 26 generations. Lined by cuboidal or columnar epithelial cells, the primary tumor consisted of completely alveolar architecture. However, IP tumors developed various growth patterns such as glandular, acinar, trabecular, cord, and solid, and consisting of epithelial cells showing cellular atypia. Ultrastructurally, neoplastic cells had microvilli, basement membranes, and desmosomes, and occasional cells possessed dense cytoplasmic granules. Interestingly, it was shown by the immunohistochemistry, the RT-PCR method, and immunoradiometric assay that IP tumor cells produce parathyroid hormone-related protein (PTHrP). During a 3-week observation period after implant, IP-bearing rats showed severe emaciation, hypercalcemia, and hypophosphatemia, as well as an increase in osteoclastic areas and a decrease in shaft thickness of the femurs. These were considered to be due to a marked elevation of plasma PTHrP levels. Furthermore, IP-bearing rats developed calcification in various organs including the kidneys, lungs, and heart. These findings in IP-bearing rats were similar to those of humoral hypercalcemia of malignancy (HHM) reported in human cancer patients. PTHrP plays a central role in the development of HHM, but the mechanisms of HHM remain poorly understood. IP may become a useful model for studying the pathogenesis of HHM and the pathophysiological role of PTHrP.


Simultaneous AV nodal reentrant and ventricular tachycardias.
Simultaneous AV nodal reentrant and ventricular tachycardias were observed during the course of an electrophysiological study in a 51-year-old patient who suffered from recurrent attacks of sustained ventricular tachycardia. Occurrence of simultaneous tachycardias was facilitated by the fact that both tachycardias had a similar cycle length. Ventricular tachycardia was most probably initiated by AV nodal tachycardia previously induced by atrial extrastimulation following the administration of atropine.


Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by calicheamicin gamma 1 in human HL-60 cells.
The mechanism of calicheamicin gamma 1-mediated cytotoxicity was studied in human promyelocytic HL-60 leukemic cells. Calicheamicin gamma 1 caused an increase in poly(ADP-ribose) polymerase activity in HL-60 cells parallel to cell death. This effect of the drug correlated with a decrease in intracellular NAD+ level. 3-Aminobenzamide, an inhibitor of poly(ADP-ribosylation), prevented the calicheamicin gamma 1-triggered cytotoxicity in a dose-dependent manner. Simultaneous with the reversal of cytotoxicity, the addition of 3-aminobenzamide to drug-treated cells also inhibited the increase in poly(ADP-ribosylation) and the reduction in cellular NAD+ content. These results indicate that poly(ADP-ribosylation) activation and the subsequent perturbations in NAD(+)-dependent metabolic reactions are associated with the cytotoxic properties of the antitumor antibiotic calicheamicin gamma 1.


Esketamine: a glimmer of hope in treatment-resistant depression.
The motive of this article is to review the pharmacological and clinical aspects of esketamine (ESK), an NMDA-receptor antagonist approved recently by the FDA for treatment-resistant depression (TRD). PubMed/Medline database was searched using keywords 'esketamine' and 'depression', 'S-ketamine' and 'depression', and 'NMDA antagonist' and 'depression'. Individual trials were searched from ClinicalTrials.gov. We included English-language articles evaluating pharmacokinetics and pharmacodynamics of intranasal (IN) esketamine, along with clinical trial data related to its efficacy and safety in patients diagnosed with TRD. Compared to placebo, IN esketamine causes significant and rapid improvement in depression. Dizziness, vertigo, headache, increase in blood pressure are some of its common adverse effects. With the growing number of patients of TRD, additional effective and safe treatment is the need of the hour. Esketamine appears to be an effective therapy when combined with oral antidepressants in patients with TRD. It is of special value due to the rapid onset of its action. Long-term clinical studies are, however, needed to ascertain its safety profile.


Serum HBsAg changes in HBeAg positive chronic hepatitis B patients with continuous viral load reductions during treatment with adefovir or peg-interferon-alpha-2a.
Hepatitis B surface antigen (HBsAg) loss under antiviral therapy is rare in chronic hepatitis B patients and the dynamics of serum HBsAg in these patients are not available. The changes in serum HBsAg following treatment with adefovir (n=31) or peg-interferon-alpha-2a (n=23) were studied in hepatitis B e-antigen (HBeAg) positive chronic hepatitis B patients. Abbott Architect HBsAg assay was used to quantify serum HBsAg. HBsAg levels were significantly decreased during the first 12 weeks of treatment with median change of -397.0 IU/ml and -555.4 IU/ml, respectively for adefovir and peg-interferon-alpha-2a (p=0.005 and 0.001, respectively). Beyond 12 weeks, no further significant HBsAg reductions were found even in patients with sustained viral replication inhibition in either group. Three distinct patterns of HBsAg changes were observed in most patients in both treatment groups: biphasic pattern (rapid HBsAg reduction from baseline to week 12); assurgent pattern (higher HBsAg level at week 12 than at baseline); and wavy pattern (HBsAg reduction from baseline to week 12, followed by relapse at week 24 or week 28). These results might offer insights into the possible mechanism(s) underlying the unusual occurrences of HBsAg loss under antiviral therapy.


Correlation of the carcinogenic potential of di(2-ethylhexyl)phthalate (DEHP) with induced hyperplasia rather than with genotoxic activity.
It has been reported that in a long-term feeding study 12,000 ppm of di(2-ethylhexyl)phthalate (DEHP) in the diet produced hepatocellular carcinomas in male and female F-344 rats while 6000 ppm DEHP produced the same tumor type in male and female B6C3F1 mice. In terms of the actual numbers of animals with tumors DEHP produced a greater response in mice than rats. DEHP and its principal hydrolysis product, mono(2-ethylhexyl)phtalate (MEHP) produce multiple effects in the animal such as liver peroxisomal proliferation and hyperplasia. Accordingly, genotoxicity as DNA repair or unscheduled DNA synthesis (UDS) and cell replication as the percentage of cells undergoing scheduled DNA synthesis (SDS or S phase) were determined in mouse hepatocytes in vitro and in vivo in response to DEHP and MEHP. UDS and SDS were determined by autoradiographic quantitation of [3H]-thymidine incorporation in primary hepatocyte cultures treated directly or isolated from B6C3F1 male mice treated in vivo. No DNA repair was observed in mouse hepatocyte cultures treated with up to 1.0 mM DEHP or 0.5 mM MEHP. No DNA repair was observed in cultures from mice treated with up to 500 mg/kg DEHP 12, 24 or 48 h previously or from animals treated up to 28 days with 6000 ppm DEHP in the diet. At 24 h following treatment with 500 mg/kg DEHP, 3.1% of the hepatocytes were in S phase compared to control values of 0.2%. Administration of DEHP in the diet at 6000 ppm produced 9.2% of the cells in S phase at day 7 with the value returning to control levels by day 14. On day 28 of the feeding study the liver to body weight ratios had almost doubled in the group treated with DEHP compared to controls. No increase in the liver-specific enzyme alanine aminotransferase was seen in the serum following treatment with 500 mg/kg DEHP, indicating that the hyperplasia was due to mitogenic stimulation rather than regenerative hyperplasia in response to cytotoxicity. Increases in the endpoints relating to hyperplasia in response to DEHP were greater in the mouse than those that have been reported in the rat. Thus, the carcinogenic response of DEHP correlates better with induced hyperplasia rather than with genotoxicity.


Nicergoline inhibits human platelet Ca(2+) signalling through triggering a microtubule-dependent reorganization of the platelet ultrastructure.
Recently, we demonstrated that a pericellular Ca(2+) recycling system potentiates agonist-evoked Ca(2+) signalling and granule secretion in human platelets and hypothesized a role for the membrane complex (MC) in orchestrating the accumulation of Ca(2+) in the pericellular region. Previous work has demonstrated that treatment with high concentrations of nicergoline may disrupt the MC through an ability to trigger a re-organization of the dense tubular system. Experiments were therefore performed to assess whether nicergoline-induced changes in platelet ultrastructure affects thrombin-evoked Ca(2+) fluxes and dense granule secretion. Thrombin-evoked Ca(2+) fluxes were monitored in Fura-2- or Fluo-5N-loaded human platelets, or using platelet suspensions containing Fluo-4 or Rhod-5N K(+) salts. Fluorescence microscopy was utilized to monitor microtubule structure and intracellular Ca(2+) store distribution in TubulinTracker- and Fluo-5N-loaded platelets respectively. Dense granule secretion was monitored using luciferin-luciferase. Nicergoline treatment inhibited thrombin-evoked Ca(2+) signalling and induced alterations in the microtubule structure and the distribution of intracellular Ca(2+) stores in platelets. Nicergoline altered the generation and spreading of thrombin-induced pericellular Ca(2+) signals and almost completely prevented dense granule secretion. Stabilization of microtubules using taxol reversed most effects of nicergoline on platelet Ca(2+) signalling and partially reversed its effects on dense granule secretion. Nicergoline-induced alterations to platelet ultrastructure disrupt platelet Ca(2+) signalling in a manner that would be predicted if the MC had been disrupted. These data suggest that nicergoline may be a useful prototype for the discovery of novel MC-disrupting anti-thrombotics.


A validated LC/UV method for the determination of four adulterating drugs in herbal slimming capsules.
A simple LC/UV method for the simultaneous identification and quantification of Fluoxetine, Tiratricol, Benfluorex and Pseudoephedrine in slimming formulation is proposed. The method demonstrated effective in the analyses of herbal mixtures marketed in Italy as slimming capsules. Sixteen different herbal mixtures, selected among the most frequently compounded in Italian pharmacies, were tested as matrices. HPLC analyses were performed in a gradient mode on a C18 stationary phase The method was validated for accuracy, precision, linearity and selectivity. The limits of detection (LOD) were 3.4 μg/mL for Pseudoephedrine, 1.1 μg/mL for Triac, 0.9 μg/mL for Fluoxetine, and 0.8 μg/mL for Benfluorex. Repeatability and intermediate precision, expressed as percent of relative standard deviation, ranged from 3 to 7 and from 7 to 12, respectively. Given these limits, the developed method is proposed for the simple and cost effective screening of herbal products illegally adulterated with these four drugs known to enhance slimming effects.


Unbalanced inherited complex chromosome rearrangement involving chromosome 8, 10, 11 and 16 in a patient with congenital malformations and delayed development.
Complex chromosome rearrangements (CCR) are rare structural chromosome aberrations that can be found in patients with phenotypic abnormalities or in phenotypically normal patients presenting, however, recurrent miscarriages or infertility. Conventional karyotype generally allows their identification. However, molecular cytogenetic methods can reveal subtle rearrangements. We report, here, the identification of an unbalanced maternally inherited CCR in a boy with multiple congenital malformations and delayed development. High-resolution karyotype completed by molecular cytogenetic prompted us to precise the rearrangements. The healthy mother was found to carry a balanced de novo CCR that implicates four chromosomes (8, 10, 11 and 16), six breakpoints, three translocations and an insertion. The malsegregation of this CCR had led, in her son, to partial 10p12.3 to 10p14 deletion, a chromosomal region associated with the DiGeorge like phenotype.


The feasibility of hand-assisted laparoscopic aortic bypass using a low transverse incision.
Hand-assisted laparoscopy can be used to perform aortoiliac reconstructive procedures. This study aimed to evaluate the safety and feasibility of a hand-assisted aortofemoral bypass in patients with occlusive disease using a low abdominal transverse incision to reduce postoperative respiratory problems. In 18 patients, a modified Pfannenstiel incision was performed. A hand-assist device was inserted, and the aorta was exposed using transperitoneal laparoscopy. Tunneling was performed under laparoscopic control. The anastomosis was always performed proximally to the inferior mesenteric artery. In three patients, the proximal anastomosis had to be performed laparoscopically. The indication for surgery was occlusive disease in 16 patients and a combination of an aneurysm and aortoiliac occlusion in 2 patients. Conversion was required in one patient (1/18). In 13 patients (13/18), the total operating time did not exceed 180 min, and 61% of the patients (11/18) could be discharged by postoperative day 5. None of the patients died perioperatively (0/18). Complications were observed in six patients (6/18). Only one of these patients had respiratory problems (1/18). The remaining five patients had local complications such as wound healing problems. The anastomosis was sutured laparoscopically in three patients (3/18). Hand-assisted laparoscopy can be performed safely using a low transverse abdominal incision. In our experience this laparoscopic access can reduce the incidence of postoperative respiratory problems and incision-related complications.


Male circumcision uptake and its predictors among sexually active men aged 15-59 years living in the highest HIV prevalence region of Ethiopia: evidence from 2016 Ethiopia demographic and health survey.
Pieces of evidence showed that the Gambella region of Ethiopia has remained HIV hotspot area for successive years. However, the magnitude of male circumcision uptake and its associated factors are not well studied in this region. Hence, the aim of the current study is to assess the magnitude of male circumcision uptake and its predictors among sexually active men in the region using the 2016 Ethiopian Demographic and Health Survey Data. Data on 868 sexually active men residing in the Gambella region were extracted from the 2016 Ethiopian Demographic and health Survey. Descriptive statistics and logistic regression were respectively used to summarize descriptive data and measure the statistical associations. Adjusted odds ratio and confidence intervals were respectively used to measure statistical associations between variables and their statistical significances. The current study revealed that the overall prevalence of male circumcision uptake in the Gambella region was 61.2% (95% CI: 57.96,64.44). The results of multivariable logistic regression revealed that being Muslim (AOR = 9.54, 95% CI: 6.765.13.88), being Orthodox Christian (AOR = 8.5, 95%CI: 5.00-14.45), being from Poor household (AOR = 0.11, 95%CI: 0.06, 0.22), being from medium-income household (AOR = .33, 95%CI: 0.15, 0.73), listening to radio (AOR = .29, 95%CI: .16, .54), having comprehensive HIV knowledge (AOR = .44, 95%CI: .27, .71) and ever been tested for HIV (AOR = .27, 95%CI: .16,.46) were independently associated with male circumcision uptake. Despite all efforts made by different stakeholders to promote the provision of male circumcision in the Gambella region, its magnitude of uptake is still unacceptably low. The federal HIV prevention and Control Office and other stakeholders working on HIV prevention and control should give due emphasis to promoting HIV-related knowledge through community-based education and through religious leaders. Integrating and streamlining HIV-related education in the academic curricula, and expanding mass media coverage should also be given due consideration by the federal government and other stakeholders. The stakeholders should also give emphasis to strengthening and empowering poor sexually active men residing in the Gambella region.


Ubiquinone reduction in the photosynthetic reaction centre of Rhodobacter sphaeroides: interplay between electron transfer, proton binding and flips of the quinone ring.
This review is focused on reactions that gate (control) the electron transfer between the primary quinone Q(A) and secondary quinone Q(B) in the photosynthetic reaction centre of Rhodobacter sphaeroides. The results on electron and proton transfer are discussed in relation to structural information and to the steered molecular dynamics simulations of the Q(B) ring flip in its binding pocket. Depending on the initial position of Q(B) in the pocket and on certain conditions, the rate of electron transfer is suggested to be limited either by the quinone ring flip or by the charge-compensating proton equilibration between the surface and the buried Q(B) site.


Evaluation of pollution in Camichin estuary (Mexico): pro-oxidant and antioxidant response in oyster (Crassostrea corteziensis).
The physiological system of molluscs, particularly pro-oxidant and antioxidant mechanisms, could be altered by pollutants and induce disturbance on health status and productive parameters of aquatic organisms, such as oyster. Therefore, the aim of this study was to evaluate the chemical contamination in water (total metals and polycyclic aromatic hydrocarbons) and oxidative stress parameters in oysters (Crassostrea corteziensis) in Camichin estuary, located in Mexican Tropical Pacific. The results obtained showed the presence of arsenic, lead and zinc, as well as naphthalene, pyrene and benzo[a]pyrene in concentrations relatively higher than criteria established by local and international guidelines. Regarding the biomarkers of oxidative stress response (H2O2 and O2 concentration, catalase activity, lipid peroxidation, and hydroperoxide concentration), differences between oyster from estuary and control group were significant. These results indicate that these pollutants could be related with oxidative stress detected in oyster.


The effects of afterload reduction on myocardial carbon 11-labeled acetate kinetics and noninvasively estimated mechanical efficiency in patients with dilated cardiomyopathy.
With echocardiography and dynamic carbon 11-labeled acetate (C-11 acetate) positron emission tomographic imaging, C-11 acetate kinetics and a parameter that estimates mechanical ventricular efficiency (the work metabolic index) were defined in eight patients with dilated cardiomyopathy. The effect of afterload reduction with nitroprusside on these parameters was evaluated in six of these patients. Nitroprusside increased stroke work index but decreased the C-11 clearance rate. The work metabolic index determined noninvasively increased and correlated well with an invasive approach. The work metabolic index was inversely correlated with systemic vascular resistance. Nitroprusside shifted this relationship upward and to the left. This method of estimating efficiency is feasible and may represent a unique noninvasive approach for the evaluation of cardiac performance and responses to therapy.


Surgical management of ovarian carcinoma metastatic to the breast and axilla: A role for metastasectomy?
As patients with ovarian cancer are living longer, surgeons will be faced with the management of metastatic lesions amenable to resection more frequently. We present two patients with ovarian cancer metastatic to the breast who underwent resection for their metastases, but their outcomes differed significantly. After reviewing the literature, we propose that there can be definite benefit to resection in the appropriately selected patients and discuss factors to consider prior to proceeding with surgery.


Risk assessment of toxic and hazardous metals in paddy agroecosystem by biochar-for bio-membrane applications.
Toxic and carcinogenic metal (loid)s, such arsenic (As) and cadmium (Cd), found in contaminated paddy soils pose a serious danger to environmental sustainability. Their geochemical activities are complex, making it difficult to manage their contamination. Rice grown in Cd and As-polluted soils ends up in people's bellies, where it can cause cancer, anemia, and the deadly itai sickness. Solving this issue calls for research into eco-friendly and cost-effective remediation technology to lower rice's As and Cd levels. This research delves deeply into the origins of As and Cd in paddy soils, as well as their mobility, bioavailability, and uptake mechanisms by rice plants. It also examines the current methods and reactors used to lower As and Cd contamination in rice. Iron-modified biochar (Fe-BC) is a promising technology for reducing As and Cd toxicity in rice, improving soil health, and boosting rice's nutritional value. Biochar's physiochemical characteristics are enhanced by the addition of iron, making it a potent adsorbent for As and Cd ions. In conclusion, Fe-BC's biomembrane properties make them an attractive option for remediating As- and Cd-contaminated paddy soils. More efficient mitigation measures, including the use of biomembrane technology, can be developed when sustainable agriculture practices are combined with these technologies.


STEMI in an adolescent boy due to anomalous left main coronary artery arising from the right sinus of Valsalva: Case report and brief review of the literature.
Congenital anomalous origin of coronary artery is a rare cardiovascular malformation and the most common anomaly is the left circumflex (LCX) arising from the right sinus of Valsalva (RSV). Other forms include both coronary arteries from RSV, the left anterior descending coronary artery from RSV, and a single coronary artery from the left sinus of Valsalva. Despite being rare, anomalous origin of left main coronary artery (LMCA) from RSV carries a high risk of sudden cardiac death. Here, we report a case of 13-year-old boy with chest pain and acute extensive anterior ST-segment elevation myocardial infarction (STEMI) who was initially diagnosed as acute myocarditis in the emergency department. A bedside echocardiogram showed severe global hypokinesia of left ventricle (LV) and normal right ventricle (RV) function. Coronary computed tomography angiography (CCTA) examination showed LMCA originated from the RSV. The patient underwent coronary artery bypass grafting surgery and was discharged without complications. A timely correct diagnosis of an anomalous coronary artery is critical in symptomatic patients, CCTA plays an important role in clinical decision making.


Bloom syndrome ortholog HIM-6 maintains genomic stability in C. elegans.
Bloom syndrome is caused by mutation of the Bloom helicase (BLM), a member of the RecQ helicase family. Loss of BLM function results in genomic instability that causes a high incidence of cancer. It has been demonstrated that BLM is important for maintaining genomic stability by playing a role in DNA recombination and repair; however, the exact function of BLM is not clearly understood. To determine the mechanism by which BLM controls genomic stability in vivo, we examined the phenotypes caused by mutation of the C. elegans BLM helicase ortholog, HIM-6. We find that the loss of HIM-6 leads to genomic instability as evidenced by an increased number of genomic insertions and deletions, which results in visible random mutant phenotypes. In addition to the mutator phenotype, him-6 mutants have a low brood size, a high incidence of males, a shortened life span, and an increased amount of germ line apoptosis. Upon exposure to high temperature, him-6 mutants that are serially passed become sterile demonstrating a mortal germ line phenotype. Our data suggest a model in which loss of HIM-6 results in genomic instability due to an increased number of DNA lesions, which either cannot be repaired and/or are introduced by low fidelity recombination events. The increased level of genomic instability that leads to him-6(ok412) mutants having a shortened life span.


Nickel/zinc-catalyzed decarbonylative addition of anhydrides to alkynes: a DFT study.
Density functional theory (DFT) was used to investigate the nickel- or nickel(0)/zinc- catalyzed decarbonylative addition of phthalic anhydrides to alkynes. All intermediates and transition states were optimized completely at the B3LYP/6-31+G(d,p) level. Calculated results indicated that the decarbonylative addition of phthalic anhydrides to alkynes was exergonic, and the total free energy released was -87.6 kJ mol(-1). In the five-coordinated complexes M4a and M4b, the insertion reaction of alkynes into the Ni-C bond occurred prior to that into the Ni-O bond. The nickel(0)/zinc-catalyzed decarbonylative addition was much more dominant than the nickel-catalyzed one in whole catalytic decarbonylative addition. The reaction channel CA→M1'→T1'→M2'→T2'→M3a'→M4a'→T3a1'→M5a1' →T4a1'→M6a'→P was the most favorable among all reaction pathways of the nickel- or nickel(0)/zinc- catalyzed decarbonylative addition of phthalic anhydrides to alkynes. And the alkyne insertion reaction was the rate-determining step for this channel. The additive ZnCl2 had a significant effect, and it might change greatly the electron and geometry structures of those intermediates and transition states. On the whole, the solvent effect decreased the free energy barriers.


Surface distribution of heterogenous clathrin assemblies in resorbing osteoclasts.
Osteoclasts seeded on either glass coverslips or apatite pellets have at least two morphologically distinct substrate adhesion sites: actin-based adhesion structures including podosome belts and sealing zones, and adjacent clathrin sheets. Clathrin-coated structures are exclusively localized at the podosome belts and sealing zone, in both of which the plasma membrane forms a tight attachment to the substrate surface. When cultured on apatite osteoclasts can degrade the apatite leading to the formation of resorption lacunae. The sealing zone divides the ventral membrane into different domains, outside and inside of the sealing zones. The former facing the smooth-surfaced intact apatite contains relatively solitary or networks of larger flat clathrin structures; and the latter, facing the rough-surfaced degraded apatite in the resorption lacunae contain clathrin in various shapes and sizes. Clathrin assemblies on the membrane domain facing not only a resorption lacuna, or trails but also intact apatite indeed were observed to be heterogeneous in size and intensity, suggesting that they appeared to follow variations in the surface topography of the apatite surface. These results provide a detailed insight into the flat clathrin sheets that have been suggested to be the sites of adhesion and mechanosensing in co-operation with podosomes.


Mechanical properties, bone mineral content, and bone composition (collagen, osteocalcin, IGF-I) of the rat femur: influence of ovariectomy and nandrolone decanoate (anabolic steroid) treatment.
Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone resorption and/or stimulation of bone formation), the ultimate effect on mechanical properties, and the most effective dosage are not yet clear. To address these issues, dose-related effects of the long-term effect of ND on serum and bone biochemistry, bone mineral content, and bone mechanical properties in ovariectomized (OVX) rats (12 weeks old at the start of the experiment) were studied for 6 months. The results were compared with those obtained in age-matched, intact, and OVX rats. OVX caused in the femur a significant increase in net periosteal bone formation and net endosteal bone resorption of bone collagen content and torsional strength, and of serum alkaline phosphatase, osteocalcin, and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density and calcium/creatinine and phosphorus/creatinine in 24-hour urine were significantly reduced. Treatment of OVX rats with 1 mg ND/14 days resulted in a significant increase in periosteal bone formation, femur length, cortical and trabecular bone mineral content and density, torsion stiffness and strength, and bone IGF-I content, and a decrease in serum osteocalcin, urinary calcium/creatinine levels, and bone collagen content compared with OVX controls. The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment did not reverse all changes induced by OVS to the level of the intact controls. These results indicate that ND acts as an antiresorptive drug and as a home formation stimulating drug.(ABSTRACT TRUNCATED AT 250 WORDS)


Calibration of the Nuclear Associates 07-621 precision photometer.
The spectral response of the Nuclear Associates 07-621 photometer has been measured over an extended range (400-990 nm). The measurements reveal that the photometer shows large deviations from the standard CIE photopic response. In particular it has considerable excess response in the red (650-780 nm) and in the near infra red (780-990 nm). Although the instrument is claimed to have a photometric accuracy of +/- 7% this is only realised when measuring sources, such as tungsten lamps, which are rich in the red and near infra red regions of the spectrum. When used with sources, such as fluorescent lamps, which contain little radiation in the range 650-1200 nm it underestimates the light output by approximately 20%. As a consequence this photometer can only be used in radiology QA for such tasks as measuring view box luminance if the appropriate correction factor is used. This factor should be determined at the outset by comparing the Nuclear Associates 07-621 with a high quality photometer using the same type of light that is emitted by the boxes.


Regional investigation of lung function and microstructure parameters by localized 129 Xe chemical shift saturation recovery and dissolved-phase imaging: A reproducibility study.
To evaluate the reproducibility and regional variation of parameters obtained from localized 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to compare the results to 129 Xe dissolved-phase MR imaging. Thirteen healthy volunteers and 10 COPD patients were scanned twice using 129 Xe dissolved-phase imaging, CSSR, and ventilation imaging sequences. A 16-channel phased-array coil in combination with the regularized spectral localization achieved by sensitivity heterogeneity (SPLASH) method was used to perform a regional analysis of CSSR data. Lung function and microstructural parameters were obtained using Patz model functions and their reproducibility was assessed. The Patz model alveolar wall thickness parameter shows good reproducibility on a regional basis with a median coefficient of variation of 6.5% in healthy volunteers and 12.4% in COPD patients. Significant regional differences of lung function parameters derived from localized CSSR were found in healthy volunteers and correlations with spirometric indices were found. Localized 129 Xe CSSR provides reproducible estimates of alveolar wall thickness and is able to detect regional differences of lung microstructure.


Unusual cause of small intestine obstruction in a child: small intestine anisakiasis: report of a case.
Anisakiasis is caused by human infection by the anisakis larvae, a marine nematode found in undercooked or raw fish. Infection with the parasite Anisakis simplex is common in Japan and northern European countries. With the increased popularity of eating sushi and raw fish infection with anisakis is expected to rise. We present the case of a 14-year-old boy who had eaten sushi 3 days before the onset of symptoms and had small bowel obstruction caused by enteric anisakiasis. To the best of our knowledge this is the first reported case of intestinal anisakiasis presenting as a bowel obstruction in a child. Enteric anisakiasis is very rare, and its diagnosis is usually made after laparotomy. Nevertheless, when signs of acute abdomen develop after the ingestion of raw fish, such as sushi or sashimi, the possibility of enteric anisakiasis should be considered.


Isoform-specific phosphoinositide 3-kinase inhibitors as therapeutic agents.
The phosphoinositide 3-kinase (PI3K) family of enzymes consists of several closely related isoforms that are thought to have distinct biological roles. Until now, researchers have been frustrated by poor selectivity of the available pharmacological inhibitors, which are unable to distinguish adequately the activities of different PI3K isoforms. Recently published patent specifications describe new PI3K inhibitors, including several that are selective for the PI3Kdelta isoform. There is now cautious optimism that isoform-selective PI3K inhibitors will provide new avenues for therapeutic applications in a range of diseases.


Understanding health care provider barriers to hospital affiliated medical fitness center facility referral: a questionnaire survey and semi structured interviews.
The purpose of this study is to understand health care provider barriers to referring patients to Medical Fitness Center Facilities within an affiliated teaching hospital system using referral of diabetic services as an example. The aims of this study include: (1) to assess health care providers' awareness and use of facilities, (2) to determine barriers to referring patients to facilities, (3) identify current and needed resources and/or changes to increase referral to facilities. A 20-item electronic survey and requests for semi-structured interviews were administered to hospital system directors and managers (n = 51). Directors and managers instructed physicians and staff to complete the survey and interviews as applicable. Perceived barriers, knowledge, utilization, and referral of patients to Medical Fitness Center Facilities were collected and examined. Descriptive statistics were generated regarding practice characteristics, provider characteristics, and referral. Of the health care providers surveyed and interviewed (n = 25) 40% indicated verbally suggesting use of facilities, 24% provided a flyer about the facilities. No respondents indicated that they directly referred patients to the facilities. However, 16% referred patients to other locations for physical activity - including their own department's management and prevention services. 20% do not refer to Medical Fitness Center Facilities or any other lifestyle programs/locations. Lack of time (92%) and lack of standard guidelines and operating procedures (88%) are barriers to referral. All respondents indicated a strong ability to refer patients to Medical Fitness Center Facilities if given education about referral programs available as well as standard clinical guidelines and protocol for delivery. The results of this study indicate that, although few healthcare providers are currently referring patients to Medical Fitness Center Facilities, health care providers with an affiliated Medical Fitness Center Facility not only want clinical standard guidelines, protocol, and training to refer patients to Medical Fitness Center Facilities, but believe they have the ability to increase referral if given these tools. The Medical Fitness Association has a unique opportunity to bridge health care providers to Medical Fitness Center Facilities by developing clinical practice guidelines in cooperation with the American Diabetes Association.


Assessment of Paramedic Ultrasound Curricula: A Systematic Review.
Prehospital ultrasound is being applied in the field. The purpose of this systematic review is to describe evidence pertaining to ultrasound curricula for paramedics specifically, including content, duration, setting, design, evaluation, and application. Electronic searches of MEDLINE, Embase, CINAHL, and the Cochrane Center Register of Controlled Trials were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary literature describing acute care ultrasound curricula for paramedics were included. Two authors independently extracted data and assessed quality using 2 validated tools. Twelve studies with 187 paramedics were included. Curricula duration varied, with effective curricula teaching focused assessment with sonography for trauma (FAST) in 6 to 8 hours and pleural ultrasound in 25 minutes. FAST, pleural, and fracture-detection ultrasound are being applied in the field by paramedics; however, no literature exists describing application to detect cardiac standstill. Curricula combined didactic and hands-on components including simulation and evaluated competency using sensitivity and specificity of paramedic-performed ultrasound. Paramedic ultrasound curricula in FAST and pleural ultrasound is feasible and time effective with successful application. Although fracture detection ultrasound is being used by the special operations forces, no comprehensive curriculum was described. Curricula designed to detect cardiac standstill have been too short, and successful application by paramedics has not been shown.


Excision and end-to-end anastomotic urethroplasty in the management of post-traumatic urethral stricture disease: experience and challenges in a Nigerian teaching hospital.
The study aims to assess the outcome of excision and end-to-end anastomotic urethroplasty in the management of post traumatic urethral stricture in at one of the teaching hospitals in Nigeria. All cases of post traumatic urethral stricture disease managed by excision and end to end anastomosis between January 2000 and December 2006 were retrospectively studied. The data collected included the patients age, cause of stricture, location, length and the outcome of surgery. A total of 47 patients excision and end to end anastomotic urethroplasty were carried out during the period. Twenty patients (42.6%) had bulbar stricture and 27 (57.4%) had pelvic fracture urethral distraction stricture involving the posterior urethra. There was a 100% success rate in the 20 patients with bulbar urethral stricture at a minimum follow up of 1 year while the success rate for the 27 patients with posterior urethral stricture was 70.4%. Complications included one case each of perineal wound infection and of urethrocutaneous fistula which were managed conservatively. Excision and end to end anastomotic urethroplasty gives excellent results for the treatment of short segment post traumatic bulbar strictures and should be used as the primary treatment for such strictures.


Advancing patient-centricity in Medical Affairs: A survey of patients and patient organizations.
Current guidance on advancing patient-centricity in Medical Affairs is insufficient. A framework was previously proposed from a Medical Affairs perspective, without direct patient input, featuring five focus areas: medical strategy; medical communication; evidence generation; patient engagement; and patient care experience. We conducted a literature review to evaluate and provide background on those focus areas. Consequently, two new focus areas were identified: digital health and patient medical education. Because the patient perspective provides an important value-add, we consulted on the seven priority areas identified with patient and patient organizations through questionnaires. The gathered responses implied that they were accurately prioritized to increase patient-centricity. However, this must be tested on a larger sample size to validate its feasibility.


Pharmacological blockade of PCAF ameliorates osteoarthritis development via dual inhibition of TNF-α-driven inflammation and ER stress.
Epigenetic mechanisms have been reported to play key roles in osteoarthritis (OA) development. P300/CBP-associated factor (PCAF) is a member of the histone acetyltransferases, which exhibits a strong relationship with endoplasmic reticulum (ER) stress and transcription factor nuclear factor kappa B (NF-κB) signals. Salidroside, a natural histone acetylation inhibitor, showed its anti-inflammatory and anti-apoptotic effects in lipopolysaccharide (LPS)-stimulated microglia cells in our previous study. However, whether Sal has a protective effect against OA remains unknown, and its relationships to PCAF, NF-κB, and the ER stress pathway should be explored further. We identified the role of PCAF in the pathogenesis of OA and determined the chondroprotective effect of Sal on both tumor necrosis factor alpha (TNF-α)-treated human chondrocytes and a destabilized medial meniscus (DMM) mouse OA model. We found increased PCAF expression in human OA cartilage and TNF-α-driven chondrocytes. Meanwhile, silencing of PCAF attenuated nuclear p65 and C/EBP homologous protein levels in chondrocytes upon TNF-α stimulation. Furthermore, Sal was found to specifically bind to the inhibitory site of the PCAF protein structure, which subsequently reversed the TNF-α-induced activation of NF-κB signal and ER stress-related apoptosis in chondrocytes. In addition, the protective effect of Sal and its inhibitory effects on PCAF as well as inflammatory- and ER stress-related markers were also observed in the mouse DMM model. Pharmacological blockade of PCAF by Sal ameliorates OA development via inhibition of inflammation and ER stress, which makes Sal a promising therapeutic agents for the treatment of OA.


Electrochemical profile for calcium ions in the stria vascularis: cellular model of calcium transport mechanism.
The d.c. potential and the Ca2+ concentration in the stria vascularis of the chincilla were measured using double-barreled Ca2+-selective microelectrodes with fine tips. The impalement of the microelectrode through the stria vascularis indicated two or three regions showing low Ca2+ concentrations. The first region with a low Ca2+ concentration, presumably corresponding to the basal cell, showed a Ca2+ concentration of 2.5 +/- 1.9 microM. The low Ca2+ region, adjacent to the endolymph, showed 0.31 +/- 0.15 microM and presumably corresponds to the marginal cell. In contrast, the Ca2+ concentrations in the spiral ligament, intrastrial space and endolymph were 1.6 +/- 0.2 mM, 0.75 +/- 0.12 mM, and 17 +/- 7 microM, respectively. Based upon the electrochemical profile for Ca2+ ions, we hypothesize mechanisms of cellular Ca2+ transport where Ca2+ ions from perilymph are accumulated into endolymph via the action of Ca2+-ATPase located in apical membranes of both the basal and marginal cells.


Segmental testicular infarction: report of seven new cases and literature review.
Segmental testicular infarction is a relatively rare acute or subacute condition which is infrequently thought of in the differential diagnosis for testicular pain. However, missing or misdiagnosing this entity on clinical evaluation and/or imaging has significant implications for patients as they may undergo unnecessary surgery for suspected testicular torsion or tumor. Knowledge and recognition of the features of segmental testicular infarction on ultrasound and MRI will aid in the diagnosis of this disease early in the patient's course. The common imaging features of segmental testicular infarction and the clinical literature are reviewed, with an emphasis on ultrasound, utilizing seven recent cases from three institutions.


Factors associated with number of treatment interviews of patients from a barrio neighborhood mental health service: a cross-validation.
Demographic and treatment variables were, for a second time, found associated with number of treatment interviews completed by lower socioeconomic patients of a barrio area neighborhood mental health service. Of the eight variables that originally differentiated patients with respect to number of interviews, six remained significant on cross-validation. The longer staying patients were characterized by: young adult age range; disrupted marital status; self-referral; using psychotropic medication; major and secondary problems of anxiety and depression.


THE SOCIAL ECONOMICS OF ADOLESCENT BEHAVIOR AND MEASURING THE BEHAVIORAL CULTURE OF SCHOOLS.
Schools are thought to have an important impact on adolescent behaviors, but the mechanisms are not well understood. We hypothesize that there are measurable constructs of peer- and teacher-related extrinsic motivations for adolescent behaviors and sought to develop measures of school culture that would capture these constructs. We developed several survey items to assess school behavioral culture and collected self-reported data from a sample of adolescents age 14-17 attending high school in low income neighborhoods of Los Angeles. We conducted exploratory and confirmatory factor analysis to inform the creation of simple-summated multi-item scales. We also conducted a cultural consensus analysis to identify the existence of shared pattern of responses to the items among respondents within the same school. From 1159 adolescents, six factors were identified: social culture regarding popular (Cronbach's alpha=0.84) and respected (alpha=0.83) behaviors, teacher support (alpha=0.86) and monitoring of school rules (alpha=0.85), valued student traits (alpha=0.67) and school order (alpha=0.68). Cultural consensus analysis identified a shared pattern of responses to the items among respondents at 8 of the 13 schools. School academic performance, which is based on standardized test results, is strongly correlated with social culture regarding popular behaviors (Pearson's correlation coefficient r=0.64), monitoring of school rules (r= 0.71), and school order (r= 0.83). The exploratory and confirmatory factor analyses did not support a single, overall factor that measures school culture. However, the six identified sub-scales might be used individually to examine school influence on academic performance and health behaviors.


Polarization dependent photocurrent in the Bi2Te3 topological insulator film for multifunctional photodetection.
Three dimensional Z2 Topological insulator (TI) is an unconventional phase of quantum matter possessing insulating bulk state as well as time-reversal symmetry-protected Dirac-like surface state, which is demonstrated by extensive experiments based on surface sensitive detection techniques. This intriguing gapless surface state is theoretically predicted to exhibit many exotic phenomena when interacting with light, and some of them have been observed. Herein, we report the first experimental observation of novel polarization dependent photocurrent of photodetectors based on the TI Bi2Te3 film under irradiation of linearly polarized light. This photocurrent is linearly dependent on both the light intensity and the applied bias voltage. To pursue the physical origin of the polarization dependent photocurrent, we establish the basic TI surface state model to treat the light irradiation as a perturbation, and we adopt the Boltzmann equation to calculate the photocurrent. It turns out that the theoretical results are in nice qualitative agreement with the experiment. These findings show that the polycrystalline TI Bi2Te3 film working as a multifunctional photodetector can not only detect the light intensity, but also measure the polarization state of the incident light, which is remarkably different from conventional photodetectors that usually only detect the light intensity.


Assessing 3 Outbreak Detection Algorithms in an Electronic Syndromic Surveillance System in a Resource-Limited Setting.
We evaluated the performance of X-bar chart, exponentially weighted moving average, and C3 cumulative sums aberration detection algorithms for acute diarrheal disease syndromic surveillance at naval sites in Peru during 2007-2011. The 3 algorithms' detection sensitivity was 100%, specificity was 97%-99%, and positive predictive value was 27%-46%.


Smoking-induced metabolic disorders: a review.
Smoking is the leading avoidable cause of cardiovascular mortality worldwide. The aim of this report is to briefly review the existing evidence regarding smoking and cardiovascular risk, and to analyze in greater detail the links between tobacco use and metabolic disorders. The evidence so far shows that smoking dose-dependently increases the risk of impaired glucose tolerance, the incidence of type 2 diabetes mellitus and abdominal-type obesity. Although smokers have a lower body mass index than do nonsmokers, recent data show that they have higher waist-to-hip ratios and waist circumferences, established risk factors for cardiovascular disorders-in particular, for coronary heart disease. We propose that smoking may lead not only directly, but also indirectly via these metabolic risk factors, to cardiovascular disorders. As both weight and waist circumference may increase on stopping smoking, further studies are needed to assess whether the post-smoking weight increase and potential changes in waist-to-hip ratio (or waist circumference) have consequences that may reduce the benefits of smoking cessation.


Structural basis for KCTD-mediated rapid desensitization of GABAB signalling.
The GABAB (γ-aminobutyric acid type B) receptor is one of the principal inhibitory neurotransmitter receptors in the brain, and it signals through heterotrimeric G proteins to activate a variety of effectors, including G-protein-coupled inwardly rectifying potassium channels (GIRKs)1,2. GABAB-receptor signalling is tightly regulated by auxiliary subunits called KCTDs, which control the kinetics of GIRK activation and desensitization3-5. However, the mechanistic basis for KCTD modulation of GABAB signalling remains incompletely understood. Here, using a combination of X-ray crystallography, electron microscopy, and functional and biochemical experiments, we reveal the molecular details of KCTD binding to both GABAB receptors and G-protein βγ subunits. KCTDs associate with the receptor by forming an asymmetric pentameric ring around a region of the receptor carboxy-terminal tail, while a second KCTD domain, H1, engages in a symmetric interaction with five copies of Gβγ in which the G-protein subunits also interact directly with one another. We further show that KCTD binding to Gβγ is highly cooperative, defining a model in which KCTD proteins cooperatively strip G proteins from GIRK channels to induce rapid desensitization following receptor activation. These results provide a framework for understanding the molecular basis for the precise temporal control of GABAB signalling by KCTD proteins.


Higher Lung and Heart Doses Decrease Early and Long-Term Survival, Respectively, in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation.
Cardiopulmonary toxic effects may reduce the efficacy of postoperative radiation therapy (PORT) in patients with non-small cell lung cancer (NSCLC). However, few studies have examined whether the heart and lung doses affect overall survival (OS). We investigated the correlation of heart and lung doses with OS in patients with NSCLC undergoing PORT. This retrospective analysis included 307 patients with NSCLC undergoing PORT. The total dose was 50 Gy. Landmark analyses were performed at 36 months, with hazard ratios (HRs) calculated separately for events occurring up to 36 months (early survival) and after 36 months (long-term survival). Stabilized inverse probability of treatment weighting (sIPTW) was performed to balance the characteristics of the high- and low-dose groups. We performed sensitivity analyses at 24 and 48 months. The median follow-up period was 67.42 months. Heart doses were significantly correlated with long-term survival (HR, 1.14; P = .015) but not with early survival (HR, 0.97; P = .41) or whole survival (HR, 1.02; P = .58). Lung doses were marginally significantly correlated with early survival (HR, 1.03; P = .07) but not with long-term survival (HR, 1.00; P = .85) or whole survival (HR, 1.02; P = .12). Higher heart and lung doses were associated with decreased long-term and early survival, respectively, before and after sIPTW. Landmark analyses at 24 and 48 months showed consistent results. For patients with NSCLC undergoing PORT, a higher heart dose was associated with decreased long-term survival, whereas a higher lung dose was associated with decreased early survival.


Update of treatment for Gaucher disease.
Gaucher disease (GD), the most common lysosomal disorders, is a rare autosomal recessive hereditary disease that is caused by deficiency of glucosylceramidase. For now, there are five approved therapies for GD, which are used to treat thousands of patients with GD. Despite success of approved therapies, many unresolved issues attract academic institutions and industry to develop potential therapies to resolve them. This paper updated the latest information about approved therapies and potential curative therapies.


Somatic Mutation: What Shapes the Mutational Landscape of Normal Epithelia?
Epithelial stem cells accumulate mutations throughout life. Some of these mutants increase competitive fitness and may form clones that colonize the stem cell niche and persist to acquire further genome alterations. After a transient expansion, mutant stem cells must revert to homeostatic behavior so normal tissue architecture is maintained. Some positively selected mutants may promote cancer development, whereas others inhibit carcinogenesis. Factors that shape the mutational landscape include wild-type and mutant stem cell dynamics, competition for the niche, and environmental exposures. Understanding these processes may give new insight into the basis of cancer risk and opportunities for cancer prevention. Recent advances in sequencing have found somatic mutations in all epithelial tissues studied to date. Here we review how the mutational landscape of normal epithelia is shaped by clonal competition within the stem cell niche combined with environmental exposures. Some of the selected mutant genes are oncogenic, whereas others may be inhibitory of transformation. Discoveries in this area leave many open questions, such as the definition of cancer driver genes, the mechanisms by which tissues constrain a high proportion of oncogenic mutant cells, and whether clonal fitness can be modulated to decrease cancer risk.


Relationship between vertebral fracture prevalence and abdominal aortic calcification in women with rheumatoid arthritis.
Vertebral fracture assessment (VFA)-detected abdominal aortic calcification (AAC) has been validated as an indicator of increased risk of vertebral fractures (VFs) in other populations but this relationship in rheumatoid arthritis (RA) is unclear. We assess the prevalence of AAC on VFA scans and its potential relationship with prevalent VFs in a cohort of RA women. We enrolled 250 women with RA. VFA images, and scans of the lumbar spine and proximal femur were obtained using dual-energy x-ray absorptiometry. The presence/severity of VFs and AAC were carried out using validated approaches. AAC was detected in 95 of 250 (38%) eligible subjects and 83 (33.2%) had at least one VF. Significantly subjects with VFs had a higher AAC score (3.4 ± 3.8 versus 0.7 ± 1.4; p˂0.001) and higher prevalence of AAC than those without VFs (65% versus 26%; P˂0.001). The group with VFs tended to be older, had more menopausal women, and lower lumbar spine and total hip BMD than those without VF. They also had a long-standing disease and high DAS 28-CRP, a great steroid cumulative dose, and a high prevalence of rheumatoid factor (RF). In multivariate analyses, a significant association was noted between prevalent VFs and age of patients, RA disease activity, presence of densitometric osteoporosis, RF, and VFA-detected AAC, whereas there was no significant association with steroid cumulative dose and disease duration. VFA is a convenient tool for the diagnosis of VFs and AAC. In this cohort, VFA-detected AAC was independently associated with prevalent VFs.


Toxicological aspects of the interesterified-fat from processed foods: Influences on opioid system and its reward effects in rats.
Considering the high consumption of processed foods, interesterified fat (IF) has been used to replace trans fat, since it may harm nervous system functions. Opioids are intensely used to alleviate pain, and have a highly addictive potential. Therefore, their improper use is related to addiction, tolerance, and withdrawal syndrome. Wistar rats received soybean oil (SO) or IF during gestation, lactation and post-weaning until pups' adolescence. On post-natal day 39, animals received morphine (4 mg/kg i.p.) in the conditioned place preference (CPP) paradigm. SO group showed morphine preference during drug withdrawal, while IF group showed no preference or withdrawal symptoms, but higher sensitivity to thermal stimuli than SO group. Morphine contidioning increased dopamine 1 receptor (D1R) and NMDAR: N-methyl-d-aspartate receptor (NMDAR) immunoreactivity in the hippocampus of SO, whereas these molecular changes were not observed in IF group. Regardless of morphine conditioning, IF group showed increased Kappa opioid receptor (KOR) immunoreactivity in the spinal cord, evidencing a negative correlation with thermal sensitivity. The chronic consumption of IF-rich foods during earlier periods of life may affect opioid neurotransmission, resulting in loss of rewarding effects related to this system.


Meningothelial cells participate in immunological processes in the cerebrospinal fluid.
Meningothelial cells (MECs) form the innermost layer of the meningeal sheath and as such are in direct contact with the cerebrospinal fluid (CSF) likely influencing CSF composition. The CSF space is a site of active immunological processes. To investigate an immunological role of MECs, cytokine and chemokine secretion, phagocytotic and pinocytotic activity by MECs was analyzed following stimulation with lipopolysaccharide, phorbol ester or rotenone. Secretion of IL-6 and IL-8 by MECs increased in a dose dependent manner after stimulation concomitant with NF-κB activation. In addition, phagocytotic clearance by MECs was enhanced suggesting an immunological role for MECs in the CSF compartment and pointing to a possible connection to neurodegenerative processes.


Microdialysis in the estimation of interstitial myocardial neuropeptide Y release.
The purpose of this study was to investigate the feasibility of cardiac microdialysis for the in vivo estimation of cardiac interstitial peptide concentrations, and, to determine the changes in neuropeptide Y release in myocardial tissue during experimental brain death in pigs. Using a specifically designed concentric flexible probe, perfused with Ringer solution containing 0.5% of bovine serum albumin at a flow rate of 2 microliters/min, allowed us to obtain a 23 +/- 2% relative recovery rate in vitro. Based on these in vitro recovery data, a regional study of the kinetics of interstitial NPY levels following brain death was obtained by monitoring the changes in NPY dialysate levels recorded from dialysis probes implanted into the right and left ventricular walls of the beating heart in vivo. Basal dialysate NPY levels determined by radioimmunoassay were of 95.2 +/- 7.0 and 93.2 +/- 9.1 pmol/l in left and right ventricle, respectively. Brain death was followed by a sustained 2 h increase in NPY dialysate levels in both ventricles (peak levels: 173.2 +/- 30.9 pmol/l in left ventricle, and 149.7 +/- 23.9 pmol/l in right ventricle), which then returned to control levels. We conclude that cardiac microdialysis is a simple and promising new tool for evaluating the role of peptides in cardiovascular regulation.


Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease.
Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence. We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status. A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all P < .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P < .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years). Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered.


Cytokine-induced functional suppression of microencapsulated rat pancreatic islets in vitro.
It is likely that inflammatory cytokines are released near microencapsulated islets in vivo. Rates of insulin release or glucose oxidation were measured after culture of microencapsulated rat islets with interleukin (IL)-1beta and tumor necrosis factor-(TNF-alpha). Their ability to recover from IL-1beta-induced suppression was also investigated. Microencapsulated islets were suppressed after exposure to IL-1beta, which was potentiated by TNF-alpha. After exposure to lower IL-1beta concentrations, microencapsulated islets had similar oxidation rates as corresponding controls. At higher concentrations, microencapsulated islets were more suppressed than nonencapsulated islets. Microencapsulated and control islets were able to recover from suppression after exposure to 2.5 U/ml of IL-1beta. Microencapsulation using the present alginate/poly-L-lysine/alginate capsules does not protect islets against the detrimental effects of IL-1beta and TNF-alpha. Indeed, microencapsulated islets seem to be more susceptible to suppression at higher concentrations of IL-1beta. However, after exposure to a lower concentration of IL-1beta, microencapsulated islets can recover.


A Rare Case of Muco-epidermoid Carcinoma Parotid in a 6-Year-Old Girl and Review of Literature.
Mucoepidermoid carcinoma (MEC) is the commonest malignant salivary gland tumor affecting the parotid gland in adults and children. In children and adolescents, there is a peak incidence in the second decade. We came across a 6-year-old girl with intermediate-grade MEC parotid gland, which is very unusual below 10 years of age. A global literature search revealed only 3 other similar cases in children below 10 years of age. She presented with a 2-year history of left parotid gradually increasing hard swelling involving the overlying skin and underlying sternocleidomastoid muscle which was confirmed on a contrast-enhanced computed tomography (CECT) scan of the face and neck as well as a core biopsy to be a MEC left parotid. The patient underwent a left radical parotidectomy sacrificing the main trunk of the facial nerve while carefully preserving its distal branches along with a left selective neck dissection (SND) followed by facial reanimation using primary neurorrhaphy. Histopathology confirmed an intermediate-grade MEC pT4aN2bMx with close deep lobe margin warranting adjuvant radiotherapy. Albeit very rare, salivary gland neoplasms may occur in children in the first decade of life. Appropriate planning regarding oncological resection with/without facial reanimation, appropriate rehabilitation followed by adjuvant treatment based on histopathology ensures a good prognosis.


No evidence of plasticity in hair follicles of recipients after allogeneic hematopoietic stem cell transplantation.
Here we show in a prospective quantitative study of 115 patients after allogeneic hematopoietic stem cell transplantation that hair follicles remain exclusively of recipient type despite full whole blood donor-type chimerism. Our data indicate that unmanipulated hematopoietic donor stem cells do not contribute directly to reconstitution even in an organ at highest need for repair.


Effect of glutamate receptor antagonists on suckling-induced prolactin release in rats.
The aim of the present study was to investigate the role of endogenous excitatory amino acid receptors in suckling- induced prolactin (PRL) elevation. Glutamate is known to be the dominant excitatory neurotransmitter and may act simultaneously on different glutamatergic receptor subtypes. MK-801 (dizocilpine) is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA), while GyKI 52466 is an antagonist of the R,S-alpha-amino- 3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/ kainate receptor subtypes. Using the combination of the two receptorsubtype antagonists, we tested the hypothesis that parallel blockade of more than one subtype is more effective. Low-dose MK-801 (0.033 mg/kg) had no effect on suckling-induced PRL elevation after 4 h of separation. When injected alone, 10 mg/kg of GyKI 52466 was also ineffective, but in combination with low-dose MK-801 it efficiently diminished the sucklinginduced PRL elevation while lactation proceeded. The same dose of GyKI 52466 combined with 0.2 mg/kg of MK-801 (a combination that in other studies was able to block the foot-shock-induced PRL elevation) was more effective. Simultaneous blockade of the two ionotropic glutamate receptors with 0.2 mg/kg of MK-801 and 10 mg/kg of GyKI 52466 caused a decline in plasma PRL concentration of continuously suckling mothers. We conclude that the endogenous glutamatergic system has an important role in suckling-induced PRL elevation and in the maintenance of constantly high PRL levels in lactating mothers. Furthermore, the NMDA and AMPA/kainate receptor subtypes can interact with each other in this process.


Brain functional network abnormality extends beyond the sensorimotor network in brachial plexus injury patients.
Brachial plexus injury (BPI) is a type of severe peripheral nerve trauma that leads to central remodeling in the brain, as revealed by functional MRI analysis. However, previously reported remodeling is mostly restricted to sensorimotor areas of the brain. Whether this disturbance in the sensorimotor network leads to larger-scale functional remodeling remains unknown. We sought to explore the higher-level brain functional abnormality pattern of BPI patients from a large-scale network function connectivity dimension in 15 right-handed BPI patients. Resting-state functional MRI data were collected and analyzed using independent component analysis methods. Five components of interest were recognized and compared between patients and healthy subjects. Patients showed significantly altered brain local functional activities in the bilateral fronto-parietal network (FPN), sensorimotor network (SMN), and executive-control network (ECN) compared with healthy subjects. Moreover, functional connectivity between SMN and ECN were significantly less in patients compared with healthy subjects, and connectivity strength between ECN and SMN was negatively correlated with patients' residual function of the affected limb. Functional connectivity between SMN and right FPN were also significantly less than in controls, although connectivity between ECN and default mode network (DMN) was greater than in controls. These data suggested that brain functional disturbance in BPI patients extends beyond the sensorimotor network and cascades serial remodeling in the brain, which significantly correlates with residual hand function of the paralyzed limb. Furthermore, functional remodeling in these higher-level functional networks may lead to cognitive alterations in complex tasks.


Hypertensive disorders of pregnancy in Greece.
Unique population data on the incidence of hypertension during pregnancy was obtained during the 1983 Greek National Perinatal Survey. Of the 9915 women delivering in April who had their blood pressures measured during pregnancy, only 3.0% had a diastolic pressure of over 90 mmHg. The data can be compared with 11.6% of 15,744 women delivering in the United Kingdom in one week of April 1970 and for whom data on antepartum blood pressures were available (p less than 0.0001). Corresponding rates for proteinuric pre-eclampsia were 0.7 and 3.1% (p less than 0.0001). In Greece, there was no consistent variation with parity but a strong trend with advancing maternal age. The perinatal mortality rate among pregnancies with diastolic pressures of 91 mmHg and more was 6%, three times the national rate. Such cross-cultural comparisons of hypertension in pregnancy form a valuable basis on which to develop hypotheses to explain the aetiology of this condition.


Long-term impaired memory following predatory stress in mice.
Brief exposure of mice to unavoidable predatory stimuli is associated with behavioral and neurochemical changes consistent with increased anxiety and produces short-term impaired learning restored by acute fluoxetine treatment, but not by diazepam. The present study investigated long-lasting changes induced by a unique unavoidable cat exposure in BALB/c mice on learning abilities using learning tests (radial maze, spatial configuration of objects recognition test). Results from the group comparison showed that predatory exposure induced significant learning disabilities in the radial maze (16 to 22 days poststressor) and in the spatial configuration of objects recognition test (26 to 28 days poststressor). These findings indicate that memory impairments may persist for extended periods beyond a predatory stress. This animal model of unique exposure of mice to unavoidable predatory stimuli has proven to be a useful model for the study of reactions to traumatic stress.


Isocitrate dehydrogenase mutation hot spots in acute lymphoblastic leukemia and oral cancer.
Isocitrate dehydrogenase (IDH) encodes a nicotinamide adenine dinucleotide phosphate+-dependent enzyme for oxidative decarboxylation of isocitrate and has an essential role in the tricarboxylic acid cycle. Mutations of IDH1 and IDH2 have been identified in patients with glioma, leukemia, and other cancers. However, the incidence of IDH mutations in acute myeloid leukemia in Taiwan is much lower than that reported in Western countries. The reason for the difference is unknown and its clinical implications remain unclear. Acute lymphoblastic leukemia (ALL) is a heterogenous hematopoietic malignancy. Oral squamous cell carcinoma (OSCC) results from chronic carcinogen exposures and is highly prevalent in trucking workers, especially in southern Taiwan. Subtypes of both diseases require specific treatments, and molecular markers for developing tailored treatments are limited. High-resolution melting (HRM) analysis is now a widely used methodology for rapid, accurate, and low-cost mutation scanning. In this study, 90 adults with OSC and 31 children with ALL were scanned by HRM analysis for IDH1 and IDH2 mutation hot spots. In ALL, the allele frequency was 3.23% in both IDH1 and IDH2. In OSCC, the allele frequency was 2.22% in IDH2. A synonymous mutation over pG313 (c.939A > G) of IDH2 was found in both pediatric ALL and adult OSCC. Therefore, we concluded that mutations of IDH are uncommon in ALL and OSCC and are apparently not a major consideration when selecting treatment modalities.


MicroRNA-744 inhibited cervical cancer growth and progression through apoptosis induction by regulating Bcl-2.
Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumor progressions, including cervical cancer. Aberrant miR-744 expression has been indicated in many growth of tumor, the mechanism of miR-744 inhibits both the proliferation and metastatic ability for cervical cancer remains unclear. Accumulating evidences reported that Bcl-2 signal pathway plays an important role in the cellular process, such as apoptosis, cell growth and proliferation. The goal of this study was to identify miR-744 that could inhibit the growth, migration, invasion, proliferation and metastasis of gastric cancer through targeting Bcl-2 expression. Real-time PCR (RT-qPCR) was used to quantify miR-744 expression in vitro and vivo experiments. The biological functions of miR-744 were determined via cell proliferation. Our study indicated that miR-744 targeted on Bcl-2, which leads to the inactivation of apoptosis signaling and the cell proliferation of cervical cancer cells, ameliorating cervical cancer growth and progression. In addition, both up-regulation of miR-744 and down-regulation of Bcl-2 could stimulate Caspase-3 expression, promoting apoptosis of cervical cancer cells. Therefore, our research revealed the mechanistic links between miR-744 and Bcl-2 in the pathogenesis of cervical cancer through modulation of Caspase-3, leading to the inhibition of cervical cancer cell growth. And targeting miR-744 could be served as a novel strategy for future cervical cancer therapy clinically.


Giant lumbar pseudomeningocele after revision lumbar laminectomy: a case report and review of the literature.
Incidental durotomy is a relatively common complication of spine surgery. Prevalence ranges from 3 to 5% in primary and 7 to 17% in revision procedures. Despite this relatively common occurrence the subsequent development of pseudomeningoceles following lumbar spine surgery is reported to be between 0.07 and 2%. Giant pseudomeningoceles (GP) are rare and therefore we report our experience with a case. We report a case of an iatrogenic GP post revision lumbar surgery that extended 19 cm in length. The patient underwent revision L3-S1 laminectomy, laminotomy, excision of pseudomeningocele and successful direct dura repair. Postoperatively, a subcutaneous seroma persisted. This was managed with surgical exploration and prolonged drainage. This led to reduction of the seroma and symptomatic improvement for the patient. Incidental durotomy is a relatively common complication of spine surgery and if the durotomy is not addressed at the time of an operation a pseudomeningocele may develop. A pragmatic approach for GP is to individualise management based upon symptoms. Although GP are rare, prevention is likely the best approach. We outlined a structured approach to the management of an incidental dural leak that formed the largest reported pseudomeningocele reported to date.


Synthesis of methyl 5-S-alkyl-5-thio-D-arabinofuranosides and evaluation of their antimycobacterial activity.
The emergence of drug resistant tuberculosis necessitates a search for new antimycobacterial compounds. The antigen 85 (ag85) complex is a family of mycolyl transferases involved in the synthesis of trehalose-6,6'-dimycolate and the mycolated hexasaccharide motif found at the terminus of the arabinogalactan in mycobacterium. Enzymes involved in the synthesis of cell wall structures like these are potential targets for the development of new antiinfectives. To potentially inhibit the ag85 complex, methyl 5-S-alkyl-5-thio-arabinofuranoside analogues were designed based on docking studies with ag85C derived from Mycobacterium tuberculosis. The target arabinofuranosides were then synthesized and the antibacterial activity evaluated against Mycobacterium smegmatis ATCC 14468. Two of the compounds, 5-S-octyl-5-thio-alpha-d-arabinofuranoside (8) and 5-S-octyl-5-thio-beta-d-arabinofuranoside (11), showed MICs of 256 and 512microg/mL, respectively. Attempts to directly evaluate acyltransferase inhibitory activity of the arabinofuranosides against ag85C are also described. In conclusion, a new class of antimycobacterial arabinofuranosides has been discovered.


Clinical evaluation of a fully-automated parenchymal analysis software for breast cancer risk assessment: A pilot study in a Finnish sample.
To assess the association between breast cancer risk and mammographic parenchymal measures obtained using a fully-automated, publicly available software, OpenBreast. This retrospective case-control study involved screening mammograms of asymptomatic women diagnosed with breast cancer between 2016 and 2017. The 114 cases were matched with corresponding healthy controls by birth and screening years and the mammographic system used. Parenchymal analysis was performed using OpenBreast, a software implementing a computerized parenchymal analysis algorithm. Breast percent density was measured with an interactive thresholding method. The parenchymal measures were Box-Cox transformed and adjusted for age and percent density. Changes in the odds ratio per standard deviation (OPERA) with 95% confidence intervals (CIs) and the area under the ROC curve (AUC) for parenchymal measures and percent densities were used to evaluate the discrimination between cases and controls. Differences in AUCs were assessed using DeLong's test. The adjusted OPERA value of parenchymal measures was 2.49 (95% CI: 1.79-3.47). Parenchymal measures using OpenBreast were more accurate (AUC = 0.779) than percent density (AUC = 0.609) in discriminating between cases and controls (p < 0.001). Parenchymal measures obtained with the evaluated software were positively associated with breast cancer risk and were more accurate than percent density in the prediction of risk.


Stepwise multivariate discriminant analysis (SMDA) for paired and unpaired biomedical data using microcomputers.
It may be necessary in biostatistics to discriminate between individuals and groups. The discriminant analysis is used for this purpose. The discriminant procedure has been programmed for microcomputers. The program has been written in a generic BASIC in order to make the procedure user-friendly. To have such a software package implemented on a personal computer may greatly facilitate the use of this complex analysis in biomedicine.


Establishment of a bioluminescent Renca cell line for renal carcinoma research.
Luciferase modification of tumour cells enables early and non-invasive imaging to detect tumour growth in situ and could provide sensitive and effective detection of carcinoma during research and therapy. Renca cells, a murine renal carcinoma cell line, were infected with lentivirus expressing luciferase to obtain Renca-luc. The proliferation, invasion, and migration of Renca and Renca-luc cell lines were compared using colorimetric, Boyden chamber, and wound-healing assays. Orthotopic tumour models were established in BALB/c mice using Renca and Renca-luc cells, and tumour growth in vivo was detected using bioluminescence imaging and magnetic resonance imaging (MRI). Intensity of luciferase signals from Renca-luc was positively correlated with cell number. Bioluminescence signal was detected 1 day after the establishment of the renal carcinoma model using Renca-luc and was significantly increased after 7 days. Tumour size at 7 days following the establishment of renal carcinoma models using Renca and Renca-luc was determined using MRI. The presence of renal model tumours was confirmed by histological staining. The expression of luciferase did not affect Renca cell characteristics in vitro or tumour growth in vivo. Luciferase labelling could provide a sensitive and non-invasive evaluation method for immunological and tumour therapy of renal carcinomas.


Genome sequences of two Antarctic strains of Pseudomonas prosekii: insights into adaptation to extreme conditions.
Pseudomonas prosekii is a recently described species isolated exclusively from James Ross Island close to the Antarctic Peninsula at 64° south latitude. Here, we present two P. prosekii genome sequences and their analyses with respect to phylogeny, low temperature adaptation, and potential biotechnological applications. The genome of P. prosekii P2406 comprised 5,896,482 bp and 5324 genes (GC content of 59.71%); the genome of P. prosekii P2673 consisted of 6,087,670 bp and 5511 genes (GC content of 59.50%). Whole genome sequence comparisons confirmed a close relationship between both investigated strains and strain P. prosekii LMG 26867T. Gene mining revealed the presence of genes involved in stress response, genes encoding cold shock proteins, oxidative stress proteins, osmoregulation proteins, genes for the synthesis of protection molecules, and siderophores. Comparative genome analysis of P. prosekii and P. aeruginosa PAO1 highlighted differences in genome content between extremophile species and a mesophilic opportunistic pathogen.


Genome Sequence of Pseudomonas sp. Strain ST1, Isolated from Olive (Olea europaea L.) Knot Galls in Croatia.
We report the genome sequence of a Pseudomonas sp. strain isolated from olive knot galls. The genome size is 6.101 Mbp with a G+C content of 58%. A total of 6,137 coding DNA sequences (CDS) were predicted, including 52 tRNA and 4 rRNA genes.


[Thrombosis of the superficial dorsal vein of the penis (penile Mondor's phlebitis). The interest of Doppler examination].
Thrombosis of the superficial dorsal vein of the penis (TSDVP) is a frequent and benign pathology that is often underestimated. A patient consulted for acute erectile dysfunction and pain in the base of the penis due to a TSDVP, which was treated with non-steroidal anti-inflammatory agents and anticoagulants and was followed-up by Doppler ultrasound examination of the penis. Essentially clinical, the diagnosis of TSDVP can benefit from Doppler ultrasound of the penis in difficult cases, because it is a useful tool for correct diagnosis and therapeutic management of the pathology.


Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction.
Paraquat (PQ) was demonstrated to induce dopaminergic neuron death and is used as a Parkinson's disease (PD) mimetic; however, its mechanism remains contradictory. Alternatively, minocycline is a second-generation tetracycline and is undergoing clinical trials for treating PD with an unresolved mechanism. We thus investigated the molecular mechanism of minocycline in preventing PQ-induced cytotoxicity. In this study, minocycline was effective in preventing PQ-induced apoptotic cell death, which involves the cleavages of poly (ADP-ribose) polymerase (PARP) and caspase 3 and increased fluorescence intensity of annexin V-FITC. In addition, PQ also quickly induced alterations of unfolded protein responses (UPRs) and subsequently dysfunction of the mitochondria (such as the decrease in membrane potential and increase in membrane permeability and superoxide formation). Finally, the mechanism of minocycline in preventing PQ-induced apoptosis might be mediated by attenuating endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which respectively results in caspase-12 activation and the release of H2O2, HtrA2/Omi, and Smac/Diablo. Thus, minocycline could possibly be used to treat other neurodegenerative disorders with similar pathologic mechanisms.


Metastasis suppressors: functional pathways.
Metastasis is a complex process and a major contributor of death in cancer patients. Metastasis suppressor genes are identified by their ability to inhibit metastasis at a secondary site without affecting the growth of primary tumor. In this review, we have conducted a survey of the metastasis suppressor literature to identify common downstream pathways. The metastasis suppressor genes mechanistically target MAPK, G-protein-coupled receptor, cell adhesion, cytoskeletal, transcriptional regulatory, and metastasis susceptibility pathways. The majority of the metastasis suppressor genes are functionally multifactorial, inhibiting metastasis at multiple points in the cascade, and many operate in a context-dependent fashion. A greater understanding of common pathways/molecules targeted by metastasis suppressor could improve metastasis treatment strategies.


Material properties of trabecular bone structures.
The transplantation of human allograft for restoration and filling of cortical bone defects is well known. Our aim was an experimental investigation of the mechanical stability of the often used femoral head spongiosa depending on the caliber and extent of the allograft. To evaluate the orientation of the trabecular structures of the femoral head and relate this data to its mechanical properties, morphometric studies were combined with mechanical tests of cancellous bone specimens. The mechanical examination of the allograft was done following the compression test according to DIN 50106. We examined 36 human unfixed hip joint spongiosa cylinders with a height of 11 mm and a diameter of 24 mm. We took three specimens from each femoral head. We compressed the allograft at a constant velocity of 0.017 mm/sec. We calculated the maximum compression strength, the yield point and the Young's modulus. We also examined 12 parallelepipedic specimens with (17 x 17 x 51 mm) for morphometric analysis and loading in the direction of the primary compressive group (PCG), as well as perpendicular loading and at an angle of 45 degrees. We found divergent mechanical stabilities. None of the femoral heads showed comparable compressive strength. There was no position dependency of the strength of the samples. No relation between optical appearance and strength was found. We found a value for the lower compressive strength, which can be used for calculation as a basic value for safe constructions. Furthermore we tested the well known dependence of strength on the direction of the trabecular structure. We found a strong relationship between strength and load direction on the preferred direction of the trabecular structure. The sole recommendation resulting from our investigations is to rely on the lowest compressive strength for all preoperative planning. Relying on higher compressive strength by using the theoretical predicted areas of higher strength is hazardous since we found no correlation between position of sampling and strength. The size of our samples is important, because of the fact that different sizes of the samples might cause different failure mechanisms in the samples. The preparation of the femoral head spongiosa should be done according to the primary compressive group of the trabecular structure.


Clinico-microbiological analysis of toxigenic clostridium difficile from hospitalised patients in a tertiary care hospital, Mangalore, Karnataka, India.
Prevalence of Clostridium difficile, an anaerobic, Gram-positive, spore-forming bacillus, is very much underestimated in India. The present study was intended to assess the burden of toxigenic C. difficile in hospitalised patients with clinically significant diarrhoea and analysis of their clinical picture. This cross-sectional study was conducted in a tertiary care teaching hospital, South India, from January 2012 to December 2014. Stool samples were collected consecutively from 563 inpatients from various wards. The prevalence of toxigenic C. difficile was determined by toxigenic culture and a two-step algorithm. The clinical spectrum of these patients was also analysed. Associated pathogens were identified using standard procedures. Statistical analysis was done by frequency, percentage, Chi-square test and z-test. Out of the 563 stool samples analysed, the prevalence of toxigenic C. difficile was 12.79% and that of non-toxigenic C. difficile was 10.83%. The prevalence of toxigenic C. difficile among oncology patients was highly significant (HS). Antibiotic treatment, prolonged hospital stay and underlying diseases/conditions were the risk factors which were HS, and fever was the significant clinical feature among the patients. Escherichia coli was the predominant associated pathogen isolated (18.47%). The presence of toxigenic C. difficile in our locality is a matter of concern. Constant supervision, appropriate treatment and preventive measures are crucial in controlling C. difficile infection.


Different cell death mechanisms are involved in leprosy pathogenesis.
Leprosy is a chronic granulomatous disease that remains a serious public health problem in developing countries. According to the Madrid classification, leprosy presents in four clinical forms: two immunologically unstable forms (indeterminate and borderline) and two stable polar forms (tuberculoid and lepromatous). In leprosy, the relationship of cell death to clinical disease outcome remains unclear. Therefore, we investigated the extent of autophagy and different cell death mechanisms-such as apoptosis, necroptosis, and pyroptosis-in cutaneous lesions of patients with leprosy, as well as the role of these mechanisms in clinical disease progression. This cross-sectional analytical study included 30 patients with a confirmed diagnosis of leprosy, with 10 patients in each of the following groups: lepromatous (LL), tuberculoid (TT), and indeterminate (II) leprosy groups. For histopathological analysis, skin samples were subjected to haematoxylin-eosin staining and immunostaining for apoptotic and necroptotic markers. The results indicated that FasL expression was much higher in the LL form than in the TT and II forms. Similar results (higher expression in the LL form than in the TT and II forms) were observed for caspase 8, RIP1, and RIP3 expressions. MLKL, BAX, and caspase 3 expression levels were highest in the LL form, especially in globular foamy macrophages. Beclin-1 expression was highest in the TT form but was low in LL and II forms. Caspase 1 expression was highest in the LL form, followed by that in the TT and II forms. In conclusion, our study elucidates the role of different cell death mechanisms in the pathophysiology of various forms of leprosy and suggests measures that may be used to control the host response to infection and disease progression.


Enhancers: five essential questions.
It is estimated that the human genome contains hundreds of thousands of enhancers, so understanding these gene-regulatory elements is a crucial goal. Several fundamental questions need to be addressed about enhancers, such as how do we identify them all, how do they work, and how do they contribute to disease and evolution? Five prominent researchers in this field look at how much we know already and what needs to be done to answer these questions.


What are pre-service teachers like? Analysis of their psychosocial profile.
Modern society is becoming increasingly interested in people who are emotionally competent and who have the psychosocial skills required to be successful within the current social environment. However, no studies have been published on the assessment of the role of Emotional Intelligence (EI) on mental health if we assume the possible mediation of resilience and personality factors in the case of pre-service teachers. Therefore, the aim of the study was to analyse the mediating role of resilience and personality factors in the relationship between EI and mental health of 1,022 pre-service teachers enrolled in different educational degrees. The results found support the mediating role of resilience in the relationship between emotional intelligence and mental health; nevertheless, this was not the case when personality traits were analysed. Furthermore, it has been found that EI and resilience positively affect mental health of university students. Practical implications of this study are oriented towards an advance within the emerging trend of deepening the EI and resilience constructs among mental health care providers. Only if we understand the complex interactions between the constructs which determine people will it be possible to develop educational and health programmes responding to current needs.


Does an encounter with the ambulatory clinical pharmacist in the transitional setting play a role in clinic attendance and patient engagement?
Patient engagement is an important aspect in improving patient outcomes. However, there is a paucity of literature regarding patient engagement in a nonresearch health care setting and the impacts of ambulatory clinical pharmacist interventions. Patient engagement has several definitions making it challenging to assess, but attendance to initial primary care provider (PCP) visits is an important aspect of patient engagement. The study objective was to assess if improved patient engagement, defined as attendance to an initial PCP visit, was associated with differences in services provided or pharmacist participation during postdischarge clinic appointments. The site of this study was the Johns Hopkins After Care Clinic (JHACC), an interdisciplinary postdischarge, safety net clinic in Baltimore, MD. Through an interdisciplinary health care team including pharmacists, patients received comprehensive care to assist with postacute disease-state management and transitions of care. Initial PCP visit attendance after a postacute visit in a high-risk population was evaluated for differing service delivery factors between groups who attended and did not attend their initial PCP visit. Descriptive statistics and chi-square tests were used for analysis. Patients were statistically significantly more likely to engage in primary care when clinical pharmacy specialists participated in their JHACC appointment (P = 0.02). Medication education and disease-state counseling improved initial PCP visit attendance, both of which are key pharmacist activities. This study suggests ambulatory clinical pharmacy specialists' roles in an interdisciplinary clinic model correlates with increased attendance to initial PCP visits, a surrogate for patient engagement. Disease-state education and medication education are both important activities in improving this measure; however, additional research is necessary to determine specific pharmacist interventions associated with patient engagement. As research in patient engagement continues, the positive effects of pharmacist involvement in this area could support their value in ambulatory care services.


Chemokine production during hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. Individuals with HP develop lymphocytic alveolitis,granuloma formation, and fibrosis. HP is categorized as a Th1 disease, and granuloma formation is dependent on T cells and the Th1 cytokine IFN-gamma. We therefore hypothesized that the IFN-gamma-inducible chemokines IP-10, Mig, and I-TAC, which are frequently associated with Th1 diseases, would play an important role in the pathogenesis of disease. We analyzed the expression of multiple chemokines in the lungs of wild-type (WT) and IFN-gamma-knockout (GKO) mice exposed to the particulate antigen Saccharopolyspora rectivirgula (SR). Our results demonstrate the production of IP-10, Mig, and I-TAC in WT mice during the development of HP, whereas GKO mice have reduced levels of IP-10 and no Mig or I-TAC mRNA in the lungs in response to SR exposure. The production of these chemokines is associated with an influx of CXCR3+/CD4+ T cells into lungs of WT mice, which is reduced in GKO mice. These results suggest that IFN-gamma mediates the recruitment of CXCR3+/CD4+ T cells into the lung via production of the chemokines IP-10, Mig, and I-TAC, resulting in granuloma formation.