The effects of age on neural correlates of recognition memory: An fMRI study.
Studies examining the effects of age on the neural correlates of recognition memory have yielded mixed results. In the present study, we employed a modified remember-know paradigm to compare the fMRI correlates of recollection and familiarity in samples of healthy young and older adults. After studying a series of words, participants underwent fMRI scanning during a test phase in which they responded "remember" to a test word if any qualitative information could be recollected about the study event. When recollection failed, participants signaled how confident they were that the test item had been studied. Young and older adults demonstrated statistically equivalent estimates of recollection and familiarity strength, while recognition memory accuracy was significantly lower in the older adults. Robust, age-invariant fMRI effects were evident in two sets of a priori defined brain regions consistently reported in prior studies to be sensitive to recollection and familiarity respectively. In addition, the magnitudes of 'familiarity-attenuation effects' in perirhinal cortex demonstrated age-invariant correlations with estimates of familiarity strength and memory accuracy, replicating prior findings. Together, the present findings add to the evidence that the neural correlates of recognition memory are largely stable across much of the healthy human adult lifespan.


The relationship between spinopelvic measurements and patient-reported outcome scores in patients with multiple myeloma of the spine.
Patients with multiple myeloma (MM) develop deposits in the spine which may lead to vertebral compression fractures (VCFs). Our aim was to establish which spinopelvic parameters are associated with the greatest disability in patients with spinal myeloma and VCFs. We performed a retrospective cross-sectional review of 148 consecutive patients (87 male, 61 female) with spinal myeloma and analysed correlations between spinopelvic parameters and patient-reported outcome scores. The mean age of the patients was 65.5 years (37 to 91) and the mean number of vertebrae involved was 3.7 (1 to 15). The thoracolumbar region was most commonly affected (109 patients, 73.6%), and was the site of most posterior vertebral wall defects (47 patients, 31.8%). Poorer Oswestry Disability Index scores correlated with an increased sagittal vertical axis (p = 0.006), an increased number of VCFs (p = 0.035) and sternal involvement (p = 0.012). Poorer EuroQol visual analogue scale scores correlated with posterior vertebral wall defects in the thoracolumbar region (p = 0.012). The sagittal vertical axis increased with the number of fractures and kyphosis in the thoracolumbar (p = 0.009) and lumbar (p < 0.001) regions. In MM, patients with VCFs have poorer clinical scores at presentation in the presence of sagittal imbalance. Outcome is particularly affected by multiple fractures in the thoracolumbar and lumbar regions and by failure to prevent kyphosis. Patients with MM should be screened for spinal lesions early. Cite this article: Bone Joint J 2016;98-B:1234-9.


A Novel Lamin A Mutant Responsible for Congenital Muscular Dystrophy Causes Distinct Abnormalities of the Cell Nucleus.
A-type lamins, the intermediate filament proteins participating in nuclear structure and function, are encoded by LMNA. LMNA mutations can lead to laminopathies such as lipodystrophies, premature aging syndromes (progeria) and muscular dystrophies. Here, we identified a novel heterozygous LMNA p.R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy (L-CMD) and lipodystrophy. In culture, the patient's skin fibroblasts entered prematurely into senescence, and some nuclei showed a lamina honeycomb pattern. C2C12 myoblasts were transfected with a construct carrying the patient's mutation; R388P-lamin A (LA) predominantly accumulated within the nucleoplasm and was depleted at the nuclear periphery, altering the anchorage of the inner nuclear membrane protein emerin and the nucleoplasmic protein LAP2-alpha. The mutant LA triggered a frequent and severe nuclear dysmorphy that occurred independently of prelamin A processing, as well as increased histone H3K9 acetylation. Nuclear dysmorphy was not significantly improved when transfected cells were treated with drugs disrupting microtubules or actin filaments or modifying the global histone acetylation pattern. Therefore, releasing any force exerted at the nuclear envelope by the cytoskeleton or chromatin did not rescue nuclear shape, in contrast to what was previously shown in Hutchinson-Gilford progeria due to other LMNA mutations. Our results point to the specific cytotoxic effect of the R388P-lamin A mutant, which is clinically related to a rare and severe multisystemic laminopathy phenotype.


Insights into blood feeding by schistosomes from a proteomic analysis of worm vomitus.
Whilst the schistosome tegument has been intensively studied there is little information about processes in the gut, the other major interface with the bloodstream, apart from the well characterised cascade of proteases involved in haemoglobin digestion. To gain insights into gut function we undertook a proteomic analysis of worm vomitus and performed in vitro erythrocyte feeding experiments. Additional to known gut constituents we identified two proline carboxypeptidases as well as enzymes capable of hydrolysing carbohydrate and ester linkages. Schistosome serpin and a2 macroglobulin protease inhibitors were also present. A series of "carrier proteins", principally lipid-binding saposins and cholesterol-binding NPC-2 were also detected, together with ferritins and calumenin that bind ferric iron and calcium, respectively. The presence of these lysosomal proteins and other lysosomal markers in the vomitus, plus observations on the cytology of the gut epithelium suggest that lysosomes directly secrete their contents into the gut lumen to digest incoming plasma constituents as well as haemoglobin. It is also likely that the carrier proteins function to sequester essential organic and inorganic nutrients for uptake into the epithelium. The feeding experiments indicate that erythrocytes are uncoated as they pass through the oesophagus, intersecting with its secretions, whilst the endocytosis of space-filling dextran into the gut epithelium provides a potential mechanism for carrier uptake by macropinocytosis.


Nanotopographical cues augment mesenchymal differentiation of human embryonic stem cells.
The production of bone-forming osteogenic cells for research purposes or transplantation therapies remains a significant challenge. Using planar polycarbonate substrates lacking in topographical cues and substrates displaying a nanotopographical pattern, mesenchymal differentiation of human embryonic stem cells is directed in the absence of chemical factors and without induction of differentiation by embryoid body formation. Cells incubated on nanotopographical substrates show enhanced expression of mesenchymal or stromal markers and expression of early osteogenic progenitors at levels above those detected in cells on planar substrates in the same basal media. Evidence of epithelial-to-mesenchymal transition during substrate differentiation and DNA methylation changes akin to chemical induction are also observed. These studies provide a suitable approach to overcome regenerative medical challenges and describe a defined, reproducible platform for human embryonic stem cell differentiation.


Resources for business continuity in disaster-based hospitals in the great East Japan earthquake: survey of Miyagi Prefecture disaster base hospitals and the prefectural disaster medicine headquarters.
To clarify advance measures for business continuity taken by disaster base hospitals involved in the Great East Japan Earthquake. The predisaster situation regarding stockpiles was abstracted from a 2010 survey. Timing of electricity and water restoration and sufficiency of supplies to continue operations were investigated through materials from Miyagi Prefecture disaster medicine headquarters (prefectural medical headquarters) and disaster base hospitals (14 hospitals) in Miyagi Prefecture after the East Japan earthquake. The number of hospitals with less than 1 day of stockpiles in reserve before the disaster was 7 (50%) for electricity supplies, 8 (57.1%) for water, 6 (42.9%) for medical goods, and 6 (42.9%) for food. After the disaster, restoration of electricity and water did not occur until the second day or later at 8 of 13 (61.5%) hospitals, respectively. By the fourth postdisaster day, 14 hospitals had requested supplies from the prefectural medical headquarters: 9 (64.3%) for electricity supplies, 2 (14.3%) for water trucks, 9 (64.3%) for medical goods, and 6 (42.9%) for food. The lack of supplies needed to continue operations in disaster base hospitals following the disaster clearly indicated that current business continuity plans require revision.


Novel nanoplex-mediated plant transformation approach.
Here, a rapid and easy transformation by electroporation technique for gene transfer in plants using cell penetrating amino nanocomplex (nanoplex) has been demonstrated in Nicotiana. Nanoplex was prepared using cell penetrating amino acids (CPAs) such as poly-L-lysine (PLL) and Argenine (Arg), in combination with the gold nanoparticles (AuNPs). PLLs-modified nanoplex with zeta potential of 34.2 ± 1.22 mV charge showed 63.3% efficiency for gene transformation in plant cells as compared to 60% when modified with Arg and the zeta potential was found to be 30.0 ± 0.83 mV; whereas, the transformation efficiency without nanoplex was found to be 6.6%. The findings indicate that the zeta potential of positively charged nanocomplex (AuNPs/CPAs/DNA/CPAs) increases the transformation efficiency because of their ability to protect the DNA from electroporation wave and endogenous enzyme damage. Transformation was confirmed by GUS assay and amplification of npt gene. This technique may open up new possibilities of gene transfer in plants, which will enable to produce large number of transgenic plants.


0.8 /spl mu/m CMOS implementation of weighted-order statistic image filter based on cellular neural network architecture.
In this paper, a very large scale integration chip of an analog image weighted-order statistic (WOS) filter based on cellular neural network (CNN) architecture for real-time applications is described. The chip has been implemented in CMOS AMS 0.8 /spl mu/m technology. CNN-based filter consists of feedforward nonlinear template B operating within the window of 3 /spl times/ 3 pixels around the central pixel being filtered. The feedforward nonlinear CNN coefficients have been realized using programmable nonlinear coupler circuits. The WOS filter chip allows for processing of images with 300 pixels horizontal resolution. The resolution can be increased by cascading of the chips. Experimental results of basic circuit building blocks measurements are presented. Functional tests of the chip have been performed using a special test setup for PAL composite video signal processing. Using the setup real images have been filtered by WOS filter chip under test.


Impact of intrinsic framework flexibility for selective adsorption of sarin in non-aqueous solvents using metal-organic frameworks.
Molecular modeling of mixture adsorption in nanoporous materials can provide insight into the molecular-level details that underlie adsorptive separations. Modeling of adsorption often employs a rigid framework approximation for computational convenience. All real materials, however, have intrinsic flexibility due to thermal vibrations of their atoms. In this article, we examine quantitative predictions of the adsorption selectivity for a dilute concentration of a chemical warfare agent, sarin, from bulk mixtures with aqueous and non-aqueous (methanol, isopropyl alcohol) solvents using metal-organic frameworks (MOFs). These predictions were made in MOFs approximated as rigid and also in MOFs allowed to have intrinsic flexibility. Including framework flexibility appears to have important consequences for quantitative predictions of adsorption selectivity, particularly for sarin/water mixtures. Our observations suggest the intrinsic flexibility of MOFs can have a nontrivial impact on adsorption modeling of molecular mixtures, especially for mixtures containing polar species and molecules of different sizes.


Identification of CYP2C19*4B: pharmacogenetic implications for drug metabolism including clopidogrel responsiveness.
CYP2C19 is a principal enzyme involved in the bioactivation of the antiplatelet prodrug clopidogrel and common CYP2C19 loss-of-function alleles are associated with adverse cardiovascular events. To assess the impact of the CYP2C19*17 increased activity allele in the Ashkenazi Jewish (AJ) and Sephardi Jewish (SJ) populations and to determine the frequencies of additional variant alleles, 250 AJ and 135 SJ individuals were genotyped for CYP2C19*2-*10, *12-*17, *22 and P-glycoprotein (ABCB1) c.3435C>T. Importantly, CYP2C19*4, a loss-of-function allele, was identified in linkage disequilibrium with *17. This novel haplotype, designated CYP2C19*4B, significantly alters the interpretation of CYP2C19 genotyping when testing *17. Moreover, genotyping CYP2C19*17 changed the frequency of extensive metabolizers from ∼70 to ∼40%, reclassifying ∼30% as ultrarapid metabolizers. Combining CYP2C19 and ABCB1 identified ∼1 in 3 AJ and ∼1 in 2 SJ individuals at increased risk for adverse responses to clopidogrel. These data underscore the importance of including *4B and *17 when clinically genotyping CYP2C19.


Captopril in clinical hypertension. Changes in components of renin-angiotensin system and in body composition in relation to fall in blood pressure with a note on measurement of angiotensin II during converting enzyme inhibition.
The effect of the converting enzyme inhibitor captopril on arterial pressure, the components of the renin-angiotensin-aldosterone system, and body sodium and potassium content was studied in eight hypertensive patients with renal artery stenosis and, in conjunction with diuretics, in seven patients with hypertension unresponsive to previous treatment. Two hours after the first dose, captopril caused significant falls in systolic and diastolic pressures, plasma angiotensin II, and aldosterone, with converse increases in angiotensin I and both active and total renin; the initial fall in diastolic pressure was significantly related to the drop in plasma angiotensin II. The biochemical changes were sustained during prolonged treatment, even when diuretics were added. One untreated patient with renal artery occlusion had severe secondary aldosterone excess, was sodium and potassium depleted, and severely hyponatraemic and hypokalaemic; captopril restored blood pressure, plasma electrolyte concentrations, and exchangeable sodium and total body potassium to normal. In one man with renal artery stenosis and overall renal impairment captopril led to sodium retention, and blood pressure did not fall until a diuretic was added. In the remaining patients with renal artery stenosis, pretreatment renin, angio tensin II, and aldosterone concentrations were either normal or only modestly raised, and plasma electrolyte concentrations and body content of sodium and potassium were normal. Captopril alone controlled arterial pressure in all, three cases showing a gradual fall of pressure over the first six weeks of treatment; no significant changes in exchangeable sodium or total body potassium were seen. The group of patients with previously intractable hypertension were all controlled with a combination of captopril and diuretic.


EGFR gene regulation in colorectal cancer cells by garlic phytocompounds with special emphasis on S-Allyl-L-Cysteine Sulfoxide.
Colorectal cancer is one among the most common cancers in the world and a major cause of cancer related deaths. Similar to other cancers, colorectal carcinogenesis is often associated with over expression of genes related to cell growth and proliferation, especially Epidermal Growth Factor Receptor (EGFR). There is an increasing attention towards the plant derived compounds in prevention of colorectal carcinogenesis by downregulating EGFR. Among plants, garlic (Allium sativum L.) is emerging with anticancer properties by virtue of its organosulfur compounds. The present study was aimed to analyze the interaction ability of garlic compounds in the active region of EGFR gene by in silico molecular docking studies and in vitro validation. This was conducted using the Discovery studio software version 4.0. Among the tested compounds, s-allyl-l-cysteine-sulfoxide (SACS)/alliin showed higher affinity towards EGFR. Furthermore, wet lab analysis using cell viability test and EGFR expression analysis in colorectal cancer cells confirmed its efficacy as a potent anticancer agent.


Moment-to-moment within-person associations between acts of discrimination and internalized stigma in people living with HIV: An experience sampling study.
Internalized stigma related to HIV is associated with poorer outcomes for people living with HIV (PLWH). However, little is known about the association between experiences of daily acts of discrimination by others and the activation of internalized stigma, including factors that may moderate this association. One hundred nine men living with HIV responded to experience sampling method (ESM) questions 3 times a day for 7 days via smart-phones. ESM questions included experiences of recent acts of discrimination, internalized HIV stigma, avoidance coping with HIV, and recent social support. We also administered several traditional questionnaire measures assessing psychosocial constructs. In Hierarchical Linear Modeling analyses controlling for age, race, socioeconomic status, and time on antiretroviral therapy, experiencing discrimination predicted internalized stigma within-persons. Individuals higher on attachment-related avoidance, attachment-related anxiety, avoidance coping, perceived community stigma, and helplessness, and individuals lower on social support, had stronger associations between discrimination and current internalized stigma. Similarly, results from two state moderator variables supported our trait analyses: State-level (ESM) social support and avoidance coping were significant moderators. Thus, when PLWH experience incidents of discrimination due to HIV, this may lead to increased feelings of internalized stigma. We extend the literature by demonstrating that the associations between experienced and internalized stigma are not just at the generalized trait level, but also occur at the state-level, accounting for within person variability. Results provide implications for interventions aiming to modify maladaptive interpersonal traits as well as interventions to increase social support to reduce the impact of discrimination on PLWH.


Trade liberalization and the diet transition: a public health response.
Trade liberalization remains at the forefront of debates around globalization, particularly around the impact on agriculture and food. These debates, which often focus on how poorer countries can 'trade their way' out of poverty, pay limited attention to dietary health, especially in the light of the WHO's Global Strategy for Diet, Physical Activity and Health (2004), which warned that future health burdens will be increasingly determined by diet-related chronic diseases. This article examines the diet transition as the absent factor within debates on liberalizing trade and commerce. We describe the evolution of trade agreements, noting those relevant to food. We review the association between trade liberalization and changes in the global dietary and disease profile. We illustrate some of the complex linkages between trade liberalization and the 'diet transition', illustrated by factors such as foreign direct investment, supermarketization and cultural change. Finally, we offer three scenarios for change, suggesting the need for more effective 'food governance' and engagement by public health advocates in policy making in the food and agriculture arena.


The training environment of junior anaesthetic registrars learning epidural labour analgesia in Australian teaching hospitals.
Junior anaesthetic registrars perform epidural labour analgesia in many Australian hospitals, however data evaluating training and outcomes are scarce. We aimed to describe and evaluate training practices and environments provided for registrars who learn epidural labour analgesia in their first year of training. Twenty-nine registrars audited their epidurals, participated in semi-structured interviews and completed surveys for six months. The median (inter-quartile range) number of epidurals performed by each registrar was 17 (15-25). Fifty percent performed less than 20. Among 216 audited cases, complications were reported in 19% (dural puncture in 1.4%) and technical difficulties in 16%. Direct supervision was provided for a median (range) of 2.5 (6) epidurals per registrar and for a significantly higher proportion of epidurals performed in tertiary hospitals compared with district metropolitan and rural hospitals (35%, 6% and 22% respectively; P = 0.001). Registrars felt senior staff had supportive attitudes, however the onus for initiating supervision appeared to be with the registrars and responses to survey items addressing role clarity and access to supervision showed wide variation. Only 33% of registrars agreed that they received adequate training before their first epidural and 67% reported workplace stress. None received formal assessments designed to ensure adequate supervision and competency. These results suggest that current training practices for these trainees are inadequate and could be improved by audit and structured workplace learning and assessment activities. We have demonstrated the potential value of measuring a range of training outcomes and environmental factors and have provided baseline data for future research.


Post-translational modification and evoked release of two large surface proteins of sympathetic neurons.
Two high molecular weight glycoproteins, exposed on the surface of sympathetic neurons, are modified after they have been translated, glycosylated, and inserted in the plasma membrane. B1 (apparent Mr = 230,000 by electrophoresis in sodium dodecyl sulfate) and B3 (Mr approximately 200,000) are each modified to give proteins of lower apparent molecular weight: B2 (Mr approximately 215,000) and B4 (Mr approximately 185,000). B1 and B3 are derived from two precursors, P1 (Mr approximately 210,000) and P3 (Mr approximately 185,000) which are nonsialylated, mannose-rich proteins not exposed on the cell surface. In unstimulated cells, B1 and B3 are converted to B2 and B4 with a half-life of 4 to 6 hr. In cells which have been treated chemically to evoke the release of neurotransmitter, the modification appears to be accelerated, and B2 and B4 are shed into the medium in soluble form (S2 and S4). This evoked release of protein is calcium dependent and is detected only in conditions which favor the rapid release of neurotransmitter. In the absence of exogenous calcium, however, transmitter release can be evoked without the accompanying release of protein. Thus the release of protein is not an essential step of transmitter release, but may follow it. B1, its precursor, and derivatives are immunologically related to the NILE (nerve growth factor-inducible, large external) glycoprotein of pheochromocytoma PC12 cells (McGuire, J. C., L. A. Greene, and A. V. Furano (1978) Cell 15: 357-365). B3 does not cross-react with B1 or NILE antigenically, but otherwise is synthesized, processed, and released in a similar manner.


Decompressive L5 Transverse Processectomy for Bertolotti's Syndrome: A Preliminary Study.
Bertolotti's syndrome is a spinal disorder characterized by abnormal enlargement of the transverse process of the most caudal lumbar vertebra. The L5 transverse process may be enlarged either unilaterally or bilaterally and may articulate or fuse with the sacrum or ilium. Pseudoarticulation between the transverse process of the L5 and the alar of the sacrum can cause buttock pain and leg pain. In addition, the L4 exiting nerve root could be compressed by an enlarged L5 transverse process. The authors could have obtained satisfactory results from the selected cases of Bertolotti's syndrome by applying a selective transverse processectomy of the L5. The objective of this study is to determine the effectiveness of L5 transverse processectomy for symptomatic Bertolotti's syndrome. A retrospective study. A total of 256 patients with Bertolotti's syndrome who had severe buttock pain and unilateral or bilateral radiating leg pain were selected. The correct diagnosis was made based on imaging studies which included computed tomography (CT), plain x-rays, and magnetic resonance imaging (MRI). The final diagnosis was made by confirming pain relief from anesthetic block. A total of 87 patients were classified into 2 groups: group A included 50 patients whose pain was relieved by block into the pseudoarticulation and group B included 37 patients whose pain was relieved by block into the L4 exiting nerve root. A total of 61 cases (group A: 39 cases, group B: 22 cases) were selected as pure L5 transverse processectomy. The primary outcome measures were reduction in pain scores and improvement in quality of life. Among 61 patients, there were 19 men and 42 women. The mean age of the patients was 53.2 ± 12 years (group A: 57.8 ± 14 years [16 - 86 years], group B: 53.4 ± 14 years [27 - 77 years]). The mean follow-up period was 6.5 months. The patients' mean visual analog scale (VAS) prior to surgery was 7.54 ± 0.81 (group A: 7.59 ± 0.93, group B: 7.50 ± 0.86), and the mean postoperative VAS was 2.86 ± 1.67 (group A: 3.82 ± 1.59, group B: 2.05 ± 1.00). According to Macnab's criteria, 12 patients showed excellent results (group A: 3, group B: 9), 41 patients showed good results (group A: 11, group B: 30), 6 patients showed fair results (group A: 5, group B: 1), and 2 patients showed poor results (group A: 2, group B: 0). Thus, satisfactory results were achieved in 86.89% of the cases. In patients with Bertolotti's syndrome, pseudoarticulation as well as L4 nerve root compression can be the source of buttock pain and lower extremity pain. Bisectional cutting of the L5 transverse process and decompression of the L4 nerve root could be an optimal treatment for Bertolotti's syndrome, and it may be easily approached by the paraspinal approach. This is a retrospective study and only offers one-year follow-up data for patients with Bertolotti's syndrome who have undergone L5 transverse process resection.Key words: Bertolotti's syndrome, pseudoarticulation, L5 transverse processectomy, paraspinal approach.


Patient information: community pharmacy needs and perspectives.
Providing complete and understandable information to patients about medicines is considered an integral component of high-quality medical and pharmaceutical care. With such information, not only can the level of general health increase, but costs associated with noncompliance, including polypharmacy and hospitalization, can decrease. Although patient information leaflets (PILs) have been available since the 1970s, their use is more relevant today because of the counseling requirements of the Omnibus Budget Reconciliation Act of 1990. A national survey of community pharmacists was conducted to determine their attitudes toward this patient education strategy. Results demonstrate that pharmacists believe PILs benefit patients, but that PILs need revision in terms of readability, understandability, and standardization.


Oral health considerations in older women receiving oral bisphosphonate therapy.
Recent reports of bisphosphonate-related osteonecrosis of the jaw (BRONJ) have increased awareness of oral health in patients receiving osteoporosis therapy. This study describes the demographic, oral health, and clinical characteristics of a contemporary population of women aged 50 and older undergoing oral bisphosphonate treatment who returned a mailed questionnaire pertaining to dental symptoms. The study, as previously reported, was conducted within Kaiser Permanente Northern California, a large, integrated healthcare delivery system. The cohort included 7,909 women with bisphosphonate exposure of at least 1 year, with a subset of 923 women reporting dental symptoms who underwent clinical examination. Overall, the average age was 71 ± 9; 70% were white, and 74% had at least some college education. Nearly two-thirds had received oral bisphosphonate therapy for 3 or more years. Most reported daily tooth brushing, 85% had had a dental examination in the past year, 22% reported denture use, and 6% reported moderate to severe periodontal disease. Oral healthcare patterns varied according to age and race and ethnicity. Five hundred seven (6.4%) women reported a tooth extraction in the prior year, of whom two developed BRONJ (0.4%). Tori or exostoses were found in 28% of examined participants with dental symptoms; these were predominantly in the lingual mandible and palate, with palatal BRONJ occurring in 1.6% of symptomatic participants with palatal tori. In summary, among older women with bisphosphonate exposure, oral health varied according to patient characteristics, and BRONJ occurred more frequently after tooth extraction or on palatal tori. These data support efforts to optimize oral health and to identify risk factors for BRONJ in older individuals receiving bisphosphonate drugs.


Predicting Model of Lymph Node Metastasis Using Preoperative Tumor Grade, Transvaginal Ultrasound, and Serum CA-125 Level in Patients With Endometrial Cancer.
The purpose of this study was to evaluate the predicting model for lymph node metastasis using preoperative tumor grade, transvaginal sonography (TVS), and serum cancer antigen 125 (CA-125) level in patients with endometrial cancer. Between January 2000 and February 2013, we identified 172 consecutive patients with surgically staged endometrial cancer. Transvaginal sonography was performed by an expert gynecologic radiologist in all patients. All patients had complete staging surgery including total hysterectomy with bilateral pelvic and para-aortic lymphadenectomy and were staged according to the 2009 International Federation of Gynecology and Obstetrics classification. Various clinicopathologic data were obtained from medical records and were retrospectively analyzed. Of 172 patients, 138 patients presented with stage I (118 IA and 20 IB), 12 had stage II, 18 had stage III (2 IIIA, 1 IIIB, 8 IIIC1, and 7 IIIC2), and 2 had stage IV diseases. Most patients had endometrioid adenocarcinoma (88.4%), and others (12.6%) had nonendometrioid histology. Eighteen patients (10.5%) were found to have lymph node metastasis. Deep myometrial invasion on preoperative TVS (≥50%), high serum CA-125 level (≥ 35 IU/mL), preoperative grade 2 or 3 tumors were significant preoperative factors predicting lymph node metastasis. There was no significant association between preoperative histology and lymph node metastasis. We calculated the simple model predicting lymph node metastasis based on preoperative tumor grade, TVS findings, and CA-125 level using logistic regression analysis. The sensitivity and specificity of this model were 94% and 57%, respectively (area under the curve, 0.84; 95% confidence interval [CI], 0.74-0.93; P < 0.01). Preoperative tumor grade, myometrial invasion on preoperative TVS, and CA-125 can accurately predict lymph node metastasis in patients with endometrial cancer. The current study suggests the possibility that TVS could be positively used for preoperative evaluation strategy in the low-resource countries instead of expensive imaging modalities such as magnetic resonance imaging or positron emission tomography-computed tomography.


Cochlear inner hair cells: effects of transient asphyxia on intracellular potentials.
Intracellular potentials were recorded from inner hair cells in the guinea pig cochlea. Transient asphyxia was induced by interrupting respiration for brief periods. Asphyxia caused a hyperpolarization of the resting membrane potential (resting Em). The hyperpolarization averaged 2.9 mV for 30 s asphyxias and 5.7 mV for 45 s asphyxias. The membrane potential recovered quickly after normal ventilation was resumed. Asphyxia also induced a rapid and profound decrease of the d.c. receptor potential in response to moderate intensity tone bursts at the characteristic frequency of the inner hair cell. At maximal depression, the receptor potential was reduced about 60% for a 30 s asphyxia and 100% for a 45 s asphyxia. The receptor potential recovered slowly after normal ventilation was resumed. A similar percent reduction and time course of recovery were observed for the a.c. receptor potential. In recordings from the same animals, the round window compound action potential (CAP) was as severely depressed by asphyxia as the hair cell receptor potentials. The time course of recovery for the CAP was similar to the slow recovery of the d.c. receptor potential. In contrast, the round window cochlear microphonics (CM) and the endolymphatic potential (EP) were affected less by asphyxia and recovered quickly after ventilation was resumed. Frequency tuning curves (FTCs) for the d.c. receptor potential were measured during the period of maximal receptor potential depression. These FTCs showed decreased tip sensitivity and a decrease in sharpness of tuning, as measured by the Q10. These changes were fully reversible. Low frequency (tail) segments of the FTCs were much less affected by asphyxia. The inner hair cell FTC changes during asphyxia were compared with neural FTC changes reported by other investigators. The similarities lead us to the conclusion that the inner hair cell and the auditory neural response to sound are equally sensitive to asphyxia.


Effects of (+)-HA-966, CGS-19755, phencyclidine, and dizocilpine on repeated acquisition of response chains in pigeons: systemic manipulation of central glycine sites.
The effects of i.m. injections of (+)-HA-966, a glycine-site antagonist at the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, its enantiomer (-)-HA-966, the competitive glutamate antagonist CGS-19755, the uncompetitive glutamate antagonists phencyclidine and dizocilpine, and the micro opioid agonist morphine were evaluated in a repeated acquisition task in pigeons. All of the drugs produced dose-dependent decreases in rates of responding. The NMDA receptor and channel blockers and (+)-HA-966 appeared to have a greater effect on acquisition than did morphine at doses that did not fully suppress responding. The rate suppression and learning impairment produced by a large dose of (+)-HA-966 (100 mg/kg) were completely prevented by coadministration of the glycine-site agonist D-serine (560 mg/kg) but not by its enantiomer, L-serine (1000 mg/kg). D-Serine, however, produced incomplete antagonism of the effects of dizocilpine and phencyclidine and failed to alter those of CGS-19755. These findings provide evidence that reducing the activity of the NMDA subtype of the glutamate receptor through pharmacological action at any of three sites produces similar decrements in acquisition, and those produced through antagonism of the glycine site are differentially sensitive to the glycine-site agonist D-serine.


Arthroscopic Single-Row Versus Double-Row Suture Bridge Technique for Rotator Cuff Tears in Patients Younger Than 55 Years: A Prospective Comparative Study.
When arthroscopic rotator cuff repair is performed on a young patient, long-lasting structural and functional tendon integrity is desired. A fixation technique that potentially provides superior tendon healing should be considered for the younger population to achieve long-term clinical success. Hypothesis/Purpose: The purpose was to compare the radiological and clinical midterm results between single-row and double-row (ie, suture bridge) fixation techniques for arthroscopic rotator cuff repair in patients younger than 55 years. We hypothesized that a double-row technique would lead to improved tendon healing, resulting in superior mid- to long-term clinical outcomes. Cohort study; Level of evidence, 2. A consecutive series of 66 patients younger than 55 years with a medium to large full-thickness tear of supraspinatus and infraspinatus tendons who underwent arthroscopic single-row or double-row (ie, suture bridge) repair were enrolled and prospectively observed. Thirty-four and 32 patients were assigned to single-row and double-row groups, respectively. Postoperatively, tendon integrity was assessed by MRI following Sugaya's classification at a minimum of 12 months, and clinical outcomes were assessed with the Constant score and the University of California, Los Angeles (UCLA) score at a minimum of 2 years. Mean follow-up time was 46 months (range, 28-50 months). A higher tendon healing rate was obtained in the double-row group compared with the single-row group (84% and 61%, respectively [ P < .05]). Although no difference in outcome scores was observed between the 2 techniques, patients with healed tendon demonstrated superior clinical outcomes compared with patients who had retorn tendon (UCLA score, 34.2 and 27.6, respectively [ P < .05]; Constant score, 94 and 76, respectively [ P < .05]). The double-row repair technique potentially provides superior tendon healing compared with the single-row technique. Double-row repair should be considered for patients younger than 55 years with medium to large rotator cuff tears.


ACOG Committee Opinion No. 565: Hormone therapy and heart disease.
Menopausal hormone therapy should not be used for the primary or secondary prevention of coronary heart disease at the present time. Evidence is insufficient to conclude that long-term estrogen therapy or hormone therapy use improves cardiovascular outcomes. Nevertheless, recent evidence suggests that women in early menopause who are in good cardiovascular health are at low risk of adverse cardiovascular outcomes and should be considered candidates for the use of estrogen therapy or conjugated equine estrogen plus a progestin for relief of menopausal symptoms. There is some evidence that lends support to the "timing hypothesis," which posits that cardiovascular benefit may be derived when estrogen therapy or hormone therapy is used close to the onset of menopause, but the relationship of duration of therapy to cardiovascular outcomes awaits further study. Clinicians should encourage heart-healthy lifestyles and other strategies to reduce cardiovascular risk in menopausal women. Because some women aged 65 years and older may continue to need systemic hormone therapy for the management of vasomotor symptoms, the American College of Obstetricians and Gynecologists recommends against routine discontinuation of systemic estrogen at age 65 years. As with younger women, use of hormone therapy and estrogen therapy should be individualized based on each woman's risk-benefit ratio and clinical presentation.


Functional interactions between mu opioid and alpha 2A-adrenergic receptors.
Adrenergic and opioid receptors belong to the rhodopsin family of G-protein coupled receptors, couple to analogous signal transduction pathways, and affect the nociceptive system. Although a number of previous studies have reported functional interactions between these two receptors, the basis for this has not been well explored. We propose that direct receptor-receptor interactions could account, in part, for opioid-adrenergic cross-talk. In this report, we have addressed this using biophysical, biochemical, and pharmacological studies. We show that mu opioid and alpha2A adrenergic receptors reside in close proximity in live cells using the bioluminescence resonance energy transfer assay. These receptors colocalize to proximal dendrites in primary hippocampal neurons. mu-alpha2A Receptor complexes can be isolated from heterologous cells or primary neurons coexpressing these receptors. In these cells, the activation of either mu or alpha2A receptor leads to a significant increase in the level of immunoprecipitable mu-alpha2A complexes, whereas activation of both receptors leads to a significant decrease. The implications of these effects on signaling were examined using the agonist-mediated increase in G-protein activity and mitogen-activated protein kinase activity. We find that activation of either mu or alpha2A receptors leads to an increase in the extent of signaling, whereas activation of both receptors leads to a decrease. The increase in signaling by individual ligands and decrease by a combination of ligands is also seen in primary spinal cord neurons endogenously expressing these receptors. Taken together, these results suggest that physical associations between mu and alpha2A receptors could play a role in the functional interactions between these receptors.


Prognostic and predictive impact of metastatic organ involvement on maintenance therapy in advanced metastatic colorectal cancer: Subgroup analysis of patients treated within the PanaMa trial (AIO KRK 0212).
Despite molecular selection, patients (pts) with RAS wildtype mCRC represent a heterogeneous population including diversity in metastatic spread. We investigated metastatic patterns for their prognostic and predictive impact on maintenance therapy with 5-fluorouracil/folinic acid ± panitumumab. The study population was stratified according to (1) number of involved metastatic sites (single vs multiple organ metastasis), liver-limited disease vs (2) liver metastasis plus one additional site, and (3) vs liver metastasis plus ≥two additional sites. Kaplan-Meier method and Cox regressions were used to correlate efficacy endpoints. Single organ metastasis was observed in 133 pts (53.6%) with 102 pts (41.1%) presenting with liver-limited disease, while multiple organ metastases were reported in 114 pts (46.0). Multiple compared to single organ metastases were associated with less favorable PFS (HR 1.48, 95% CI 1.13-1.93; P = .004) and OS (HR 1.37, 95% CI 0.98-1.93; P = .068) of maintenance therapy. While metastatic spread involving one additional extrahepatic site was not associated with clearly impaired survival compared to liver-limited disease, pts with liver metastasis plus ≥two additional sites demonstrated less favorable PFS (HR 1.92, 95% CI 1.30-2.83; P < .001), and OS (HR 2.38, 95% CI 1.51-3.76; P < .001) of maintenance therapy. Pmab-containing maintenance therapy appeared active in both pts with multiple (HR 0.58; 95% CI, 0.39-0.86; P = .006) as well as to a lesser numerical extent in pts with single organ metastasis (HR 0.83; 95% CI, 0.57-1.21; P = .332; Interaction P = .183). These data may support clinical decisions when EGFR-based maintenance therapy is considered.


"Pain is one piece of a complex jigsaw puzzle" - experiences of raising a child with cerebral palsy who has pain.
Purpose: To explore experiences of parenting a child with CP and pain.Method: Fourteen mothers and one father of children (9-16) with CP were included. All children had pain regularly, but the frequency and intensity of their pain experiences varied. Their motor function varied from GMFCS level I to V. Cognitive abilities varied from normal to moderate cognitive deficits. All children could express themselves verbally. Semi structured individual interviews were carried out, and results were developed using inductive thematic analysis.Results: The analysis resulted in the main theme "My child's pain is just one piece of a complex jigsaw puzzle". The main theme was developed by four mutually exclusive, but related themes: "My child's struggle burdens me", "Pain and CP direct our everyday life", "I want to be in control, but cannot always be" and "We are the only ones who understand the complexity".Conclusion: Parents of children with CP experience pain as one aspect of a bigger picture. They need help and support to cope with their child's pain, and professional helpers need to address the complexity pain is a part of.IMPLICATIONS FOR REHABILITATIONParents of children with cerebral palsy (CP) experience their child's pain as one piece in a jigsaw puzzle, and counseling needs to address the complexity rather than the separate parts of the picture.Health professionals should support parents in evaluation and management of their child's pain, as a feeling of competence in pain management is important to reduce parental stress.Health professionals should inform themselves about the life situation of parents whose child with CP has pain, and encourage them to seek practical support and apply for relevant support schemes that can make their everyday life easier.Parents of children with CP should be encouraged to take part in a diagnosis-specific support group, where they can meet with others in a similar situation, in order to reduce their feeling of being alone with their challenges.


Discriminative host sanction together with relatedness promote the cooperation in fig/fig wasp mutualism.
Sanctioning or punishing is regarded as one of the most important dynamics in the evolution of cooperation. However, it has not been empirically examined yet whether or not such enforcement selection by sanctioning or punishing and classical theories like kin or reciprocity selection are separate mechanisms contributing to the evolution of cooperation. In addition, it remains largely unclear what factors determine the intensity or effectiveness of sanction. Here, we show that in the obligate, interspecific cooperation between figs and fig wasps, the hosted figs can discriminatively sanction cheating individuals by decreasing the offspring development ratio. Concurrently, the figs can reward the cooperative pollinators with a higher offspring development ratio. This sanction intensity and effectiveness largely depend on how closely the host and symbiont are related either in terms of reciprocity exchange or genetic similarity as measured by the reciprocal of the foundress number. Our results imply that in asymmetric systems, symbionts might be forced to evolve to be cooperative or even altruistic through discriminative sanction against the noncooperative symbiont and reward to the cooperative symbiont by the host (i.e. through a game of 'carrot and stick').


Multiple mandibular exostoses: a rare case report.
Multiple maxillary and mandibular exostoses are common localized overgrowths of the bone. They are non-neoplastic and are thought to be reactive or developmental in origin. These exostoses need to be accurately distinguished from the other more diagnostically significant lesions, notably from the exosteal osteomas. The aetiology of exostosis has been investigated by different authors, but no consensus has been reached so far. We are reporting a rare case of an otherwise healthy 38 year old female with multiple exostoses in the mandibular anterior region, which correlated both clinically and radiographically.


Disparities in the recording of Parkinson's disease on death certificates.
Although little is known regarding potential socioeconomic or racial bias in the recording of Parkinson's disease (PD) on death certificates, studies of incidence, prevalence, and the etiology of PD frequently rely on this type of data. A national population-based survey was linked to death certificate data to investigate the concordance of PD reported on death certificates for persons reporting PD during life. Logistic regression was used to identify independent factors associated with differential reporting of PD at death. Among decedents with PD reported during life, 54.8% had PD recorded on the death certificate. Nearly 70% of persons in higher income categories had PD recorded at death compared to 35.4% for those earning $10,000 or less. Age and gender adjusted odds of having PD recorded at death was 2.3 (1.1-3.9), for those with an annual income of $35,000 or more. Income differences remain significant in multivariable models after controlling for age, gender, race, census region, family size, rural residence, and number of chronic medical conditions. In conclusion, this study found socioeconomic bias in the reporting of PD at death. This bias is large enough to confound death certificate-based investigations of incidence, prevalence, and risk factors that differ across socioeconomic strata.


Protective immunity to Brugia malayi larvae in BALB/c mice: potential of this model for the identification of protective antigens.
Protective immune responses against the infective larvae of Brugia malayi have been demonstrated in BALB/c mice. Various factors governing resistance to reinfection have been examined to provide baseline data for use of this model in studies of immunoprophylaxis. Parasites that established following a primary infection survived for approximately 10 days, following which numbers declined rapidly to a low level. Resistance was evidenced by a more rapid clearance of secondary infection parasites. The degree of immunity expressed was not related to the route of administration of the initial infection (subcutaneous, intravenous, intramuscular, or intraperitoneal). However, both the level of resistance and the rapidity of its expression were dependent on dose, with as few as 2 larvae stimulating measurable immunity. Sensitization with living male or female adult worms, fourth stage larvae or microfilariae of B. malayi, or infective larvae of B. pahangi conferred substantial resistance to larval challenge. Significant levels of immunity were also induced by dead B. malayi larvae (46%) and their aqueous extracts (76%), but not with the corresponding insoluble fraction. We suggest that this experimental system is ideally suited to aid in the identification of putative protective antigens in brugian filariasis.


Working memory capacity and the scope and control of attention.
Complex span and visual arrays are two common measures of working memory capacity that are respectively treated as measures of attention control and storage capacity. A recent analysis of these tasks concluded that (1) complex span performance has a relatively stronger relationship to fluid intelligence and (2) this is due to the requirement that people engage control processes while performing this task. The present study examines the validity of these conclusions by examining two large data sets that include a more diverse set of visual arrays tasks and several measures of attention control. We conclude that complex span and visual arrays account for similar amounts of variance in fluid intelligence. The disparity relative to the earlier analysis is attributed to the present study involving a more complete measure of the latent ability underlying the performance of visual arrays. Moreover, we find that both types of working memory task have strong relationships to attention control. This indicates that the ability to engage attention in a controlled manner is a critical aspect of working memory capacity, regardless of the type of task that is used to measure this construct.


Cancer-related fatigue: a survey of health practitioner knowledge and practice.
This study aims to identify the current practices of health professionals in the assessment and treatment of cancer-related fatigue (CRF). Health professionals working with oncology clients participated in an electronic survey distributed via professional associations and oncology societies. One hundred twenty-nine professionals from nursing, medical, and allied health disciplines participated in an electronic survey. Overall, there was a perception that CRF was inadequately managed at some facilities. Routine fatigue screening processes in the workplace were reported by more than half of participants; however, less than one quarter used a clinical guideline or conducted in-depth CRF assessments. Awareness of interventions for CRF varied amongst participants with one quarter able to list five appropriate interventions for cancer-related fatigue. Access to services for managing fatigue was inconsistent across service types, with post-treatment triage a high priority for CRF in some organisations yet not others. Participants identified a need for improved guidelines, enhanced expertise and better access to services for people with CRF. There is a need for further education in CRF management for a range of health disciplines in oncology and additional resources to facilitate translation of CRF guidelines into clinical practice.


Prefrontal cortex activation during story encoding/retrieval: a multi-channel functional near-infrared spectroscopy study.
Encoding, storage and retrieval constitute three fundamental stages in information processing and memory. They allow for the creation of new memory traces, the maintenance and the consolidation of these traces over time, and the access and recover of the stored information from short or long-term memory. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that measures concentration changes of oxygenated-hemoglobin (O2Hb) and deoxygenated-hemoglobin (HHb) in cortical microcirculation blood vessels by means of the characteristic absorption spectra of hemoglobin in the near-infrared range. In the present study, we monitored, using a 16-channel fNIRS system, the hemodynamic response during the encoding and retrieval processes (EP and RP, respectively) over the prefrontal cortex (PFC) of 13 healthy subjects (27.2 ± 2.6 years) while were performing the "Logical Memory Test" (LMT) of the Wechsler Memory Scale. A LMT-related PFC activation was expected; specifically, it was hypothesized a neural dissociation between EP and RP. The results showed a heterogeneous O2Hb/HHb response over the mapped area during the EP and the RP, with a O2Hb progressive and prominent increment in ventrolateral PFC (VLPFC) since the beginning of the EP. During the RP a broader activation, including the VLPFC, the dorsolateral PFC and the frontopolar cortex, was observed. This could be explained by the different contributions of the PFC regions in the EP and the RP. Considering the fNIRS applicability for the hemodynamic monitoring during the LMT performance, this study has demonstrated that fNIRS could be utilized as a valuable clinical diagnostic tool, and that it has the potential to be adopted in patients with cognitive disorders or slight working memory deficits.


Deep Serratus Plane Catheter for Management of Acute Postthoracotomy Pain After Descending Aortic Aneurysm Repair in a Morbidly Obese Patient: A Case Report.
Regional procedures for postthoracotomy pain control have classically focused on paravertebral blocks and thoracic epidurals; however, these techniques may be challenging in an increasingly obese population and contraindicated with numerous anticoagulant and antiplatelet agents. While less studied, truncal blocks allow analgesic intervention for this growing patient cohort. This case report describes placement of a deep serratus anterior plane catheter in an intubated, morbidly obese patient with a lumbar drain who failed extubation secondary to acute postthoracotomy pain. The serratus plane catheter facilitated extubation and adequate analgesia without prohibiting anticoagulant use or interfering with the monitoring of spinal cord function.


Sedation in gastrointestinal endoscopy: an anesthesiologist's perspective.
Sedation is required to treat an ever increasing number of patients for medical diagnostic or therapeutic procedures, in particular in gastrointestinal endoscopy. Due to the apparent ease of administration of sedative techniques, and due to the shortage of anesthetic staff in many Western countries, sedation is being carried out more and more frequently by non-anesthesiologist doctors or even paramedical staff. Due to its pharmacokinetic properties, propofol has become the preferred sedative drug used by non-anesthesiologists. However, uncritical use of propofol by nonqualified persons might result in much higher complications rates and even fatal events. Several guidelines have been published with common issues, but also some significant differences. Whether they contribute to improved patient safety or not will depend on the practical application and interpretation of these guidelines. Although further evaluation is needed, computer-assisted systems might contribute to the safe administration of propofol through a better control of the level of sedation.


The law of patient consent. Its relevance to chiropractors and osteopaths.
In 1992, the High Court of Australia handed down a decision on consent to medical treatment. The case had widespread media publicity, and caused consternation among many members of the medical profession. This article explains the law on consent to treatment by health practitioners and considers the relevance of the law for chiropractors and osteopaths.


Delayed imitation of lipsmacking gestures by infant rhesus macaques (Macaca mulatta).
Human infants are capable of accurately matching facial gestures of an experimenter within a few hours after birth, a phenomenon called neonatal imitation. Recent studies have suggested that rather than being a simple reflexive-like behavior, infants exert active control over imitative responses and 'provoke' previously imitated gestures even after a delay of up to 24 h. Delayed imitation is regarded as the hallmark of a sophisticated capacity to control and flexibly engage in affective communication and has been described as an indicator of innate protoconversational readiness. However, we are not the only primates to exhibit neonatal imitation, and delayed imitation abilities may not be uniquely human. Here we report that 1-week-old infant rhesus macaques (Macaca mulatta) who show immediate imitation of a lipsmacking gesture also show delayed imitation of lipsmacking, facilitated by a tendency to refrain from lipsmacking toward a still face during baseline measurements. Individual differences in delayed imitation suggest that differentially matured cortical mechanisms may be involved, allowing some newborns macaques to actively participate in communicative exchanges from birth. Macaque infants are endowed with basic social competencies of intersubjective communication that indicate cognitive and emotional commonality between humans and macaques, which may have evolved to nurture an affective mother-infant relationship in primates.


Effects of copolymer component on the properties of phosphorylcholine micelles.
Zwitterionic polymers have unique features, such as good compatibility, and show promise in the application of drug delivery. In this study, the zwitterionic copolymers, poly(ε-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) with disulfide (PCL-ss-PMPC) or poly(ε-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) or without disulfide (PCL-PMPC) and with different block lengths in PCL-ss-PMPC, were designed. The designed copolymers were obtained by a combination of ring-opening polymerization and atom transferring radical polymerization. The crystallization properties of these polymers were investigated. The micelles were prepared based on the obtained copolymers with zwitterionic phosphorylcholine as the hydrophilic shell and PCL as the hydrophobic core. The size distributions of the blank micelles and the doxorubicin (DOX)-loaded micelles were uniform, and the micelle diameters were <100 nm. In vitro drug release and intracellular drug release results showed that DOX-loaded PCL-ss-PMPC micelles could release drugs faster responding to the reduction condition and the intracellular microenvironment in contrast to PCL-PMPC micelles. Moreover, in vitro cytotoxicity evaluation revealed that the designed copolymers possessed low cell toxicity, and the inhibiting effect of DOX-loaded phosphorylcholine micelles to tumor cells was related to the components of these copolymers. These results reveal that the reduction-responsive phosphorylcholine micelles with a suitable ratio of hydrophilic/hydrophobic units can serve as promising drug carriers.


Dental injuries in mountain biking--a survey in Switzerland, Austria, Germany and Italy.
Mountain biking is considered an extreme sport, causing not only head and neck injuries, but also injuries to every part of the body. Using standardised interview, the aim of this work was to survey the frequency of dental injuries in mountain biking, as well as the behaviour of athletes after experiencing dental trauma, depending on their intensity level. Furthermore, habits of wearing helmets and mouthguards as well as knowledge about the tooth rescue kit were investigated. A total of 423 male mountain bikers from Germany, Italy, Austria and Switzerland were surveyed for this study, including 50 juniors from Switzerland. 27 athletes (5.7%) had endured tooth accidents in mountain biking. Only 246 (52%) were aware of the fact that avulsed teeth can be replanted, and only 30 individuals knew about the tooth rescue kit (6.3%). 71.9% (n=340) were familiar with mouthguards; however, only 21 individuals (4.4%) used mouthguards while mountain biking. The results show that where mountain biking is concerned, more information about prevention is required.


Factors Influencing Habitual Physical Activity in Parkinson's Disease: Considering the Psychosocial State and Wellbeing of People with Parkinson's and Their Carers.
Participating in habitual physical activity (HPA) may slow onset of dependency and disability for people with Parkinson's disease (PwP). While cognitive and physical determinants of HPA are well understood, psychosocial influences are not. This pilot study aimed to identify psychosocial factors associated with HPA to guide future intervention development. Sixty-four PwP participated in this study; forty had carer informants. PwP participants wore a tri-axial accelerometer on the lower back continuously for seven days at two timepoints (18 months apart), measuring volume, pattern and variability of HPA. Linear mixed effects analysis identified relationships between demographic, clinical and psychosocial data and HPA from baseline to 18 months. Key results in PwP with carers indicated that carer anxiety and depression were associated with increased HPA volume (p < 0.01), while poorer carer self-care was associated with reduced volume of HPA over 18 months (p < 0.01). Greater carer strain was associated with taking longer walking bouts after 18 months (p < 0.01). Greater carer depression was associated with lower variability of HPA cross-sectionally (p = 0.009). This pilot study provides preliminary novel evidence that psychosocial outcomes from PwP's carers may impact HPA in Parkinson's disease. Interventions to improve HPA could target both PwP and carers and consider approaches that also support psychosocial wellbeing.


Effects of ensiling on the digestibility and utilization of whole oilseeds by wethers.
Two digestion and N metabolism trials were conducted with 35-kg wethers to assess the feeding value of whole cottonseed or soybeans ensiled with corn silage in 3.6-m3 concrete silos (1.8 x 1.4 m). Dietary treatments for the cottonseed trial were ensiled whole cottonseed, untreated whole cottonseed, and 21 or 13% cottonseed meal in a basal diet of corn silage. There were no differences among treatments for DM and ADF intakes. Including ensiled or whole cottonseed in rations decreased digestibility of DM and ADF. Digestibility of CP was similar for the 21% cottonseed meal and whole cottonseed treatments. Nitrogen retention was similar for all treatments. Treatments for the soybean trial were ensiled whole soybeans, untreated whole soybeans, and 4 or 14% soybean meal. Lambs fed 14% soybean meal consumed more DM and ADF than those fed whole soybeans. Dry matter and ADF digestibilities were similar for all diets. Lower CP intakes resulted in less retained N for lambs fed whole soybean diets compared with those fed 14% soybean meal. Ensiling soybeans did not affect digestibilities of DM, CP, or ADF, or N retention. Ensiled whole soybeans or whole cottonseed may be fed to wethers as an alternative to separate feeding of oilseed meals with little effect on intake, CP digestibility, or N retention.


Integration is the art of decomposition.
A growing demand for integrating stand-alone information systems with an HIS can be observed. Different forms of integration can be distinguished: technical integration, user interface integration, and integration of the information service. The integration of the information service appears to be especially difficult. An integrated information service can only be achieved when the applications use each other's information services. We will discuss three approaches for letting applications belonging to another system utilize the necessary information service of a host system. The first approach makes use of the user interface, and the necessary information service has to be extracted from the service to a user. Another, often used, approach is the extension of the applications with coupling modules. The coupling modules communicate messages and translate them into the context of the application. The applications are modified scarcely and the coupling modules have to supply the necessary information services. When the coupling problem is more complex (e.g., a larger set of data is to be exchanged interactively), a growing effort will be needed for these adapting modules. A better approach is to split the application into building blocks. Applications are composed of building blocks. The application, which should deliver the integrated information service, is also composed of such building blocks. The building blocks are designed to offer information services that can be used by other systems as well. If we succeed in decomposing the applications into suitable building blocks, an integrated information service could be more easily achieved.


Preventing White Adipocyte Browning during Differentiation In Vitro: The Effect of Differentiation Protocols on Metabolic and Mitochondrial Phenotypes.
Mitochondrial dysfunction in white adipose tissue is strongly associated with obesity and its metabolic complications, which are important health challenges worldwide. Human adipose-derived stromal/stem cells (hASCs) are a promising tool to investigate the underlying mechanisms of such mitochondrial dysfunction and to subsequently provide knowledge for the development of treatments for obesity-related pathologies. A substantial obstacle in using hASCs is that the key compounds for adipogenic differentiation in vitro increase mitochondrial uncoupling, biogenesis, and activity, which are the signature features of brown adipocytes, thus altering the white adipocyte phenotype towards brown-like cells. Additionally, commonly used protocols for hASC adipogenic differentiation exhibit high variation in their composition of media, and a systematic comparison of their effect on mitochondria is missing. Here, we compared the five widely used adipogenic differentiation protocols for their effect on metabolic and mitochondrial phenotypes to identify a protocol that enables in vitro differentiation of white adipocytes and can more faithfully recapitulate the white adipocyte phenotype observed in human adipose tissue. We developed a workflow that included functional assays and morphological analysis of mitochondria and lipid droplets. We observed that triiodothyronine- or indomethacin-containing media and commercially available adipogenic media induced browning during in vitro differentiation of white adipocytes. However, the differentiation protocol containing 1 μM of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone prevented the browning effect and would be proposed for adipogenic differentiation protocol for hASCs to induce a white adipocyte phenotype. Preserving the white adipocyte phenotype in vitro is a crucial step for the study of obesity and associated metabolic diseases, adipose tissue pathologies, such as lipodystrophies, possible therapeutic compounds, and basic adipose tissue physiology.


Mammaglobin, a breast-specific gene, and its utility as a marker for breast cancer.
The mammaglobin gene encodes a 10-kDa glycoprotein that is distantly related to a family of proteins that includes rat estramustine binding protein (EMBP)/prostatein and human Clara cell 10-kDa protein (CC10)/uteroglobin. Among normal adult tissues, mammaglobin mRNA expression has been detected only in the mammary gland. As an initial step to determine mammaglobin's clinical utility as a breast tumor marker, we evaluated the frequency and specificity with which mammaglobin expression could be detected in primary breast tumors, metastatic breast tumors, and breast tumor cells present in the peripheral circulation. Approximately 80% of all primary and metastatic breast tumors examined were strongly immunopositive for mammaglobin protein, and staining was independent of tumor grade. Among peripheral stem cell collections from breast cancer patients, mammaglobin mRNA could be detected in 60% of cases. Recent work has identified the secreted mammaglobin protein in the sera of some breast cancer patients using both Western blot and ELISA. This study demonstrates that the detection of mammaglobin protein and mRNA in clinical samples may be a useful marker for primary, metastatic, and occult breast cancer.


Evaluating the impact of high- and low-fidelity instruction in the development of auscultation skills.
A principal justification for the use of high-fidelity (HF) simulation is that, because it is closer to reality, students will be more motivated to learn and, consequently, will be better able to transfer their learning to real patients. However, the increased authenticity is accompanied by greater complexity, which may reduce learning, and variability in the presentation of a condition on an HF simulator is typically restricted. This study was conducted to explore the effectiveness of HF and low-fidelity (LF) simulation for learning within the clinical education and practice domains of cardiac and respiratory auscultation and physical assessment skills. Senior-level nursing students were randomised to HF and LF instruction groups or to a control group. Primary outcome measures included LF (digital sounds on a computer) and HF (human patient simulator) auscultation tests of cardiac and respiratory sounds, as well as observer-rated performances in simulated clinical scenarios. On the LF auscultation test, the LF group consistently demonstrated performance comparable or superior to that of the HF group, and both were superior to the performance of the control group. For both HF outcome measures, there was no significant difference in performance between the HF and LF instruction groups. The results from this study suggest that highly contextualised learning environments may not be uniformly advantageous for instruction and may lead to ineffective learning by increasing extraneous cognitive load in novice learners.


Iridoid glucosides from Veronica pectinata var. glandulosa.
A new highly oxygenated iridoid glucoside, urphoside B (1) was isolated from the Veronica pectinata var. glandulosa together with seven known iridoid glucosides, aucubin, catalpol, veronicoside, catalposide, verproside, amphicoside and 6-O-veratroyl catalpol. The planar as well as the stereo structures of the isolated compounds were determined by means of extensive 1D- and 2D-NMR spectroscopy and confirmed by HR-Mass.


eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health.
eIF3, a multi-subunit complex with numerous functions in canonical translation initiation, is known to interact with 40S and 60S ribosomal proteins and translation elongation factors, but a direct involvement in translation elongation has never been demonstrated. We found that eIF3 deficiency reduced early ribosomal elongation speed between codons 25 and 75 on a set of ∼2,700 mRNAs encoding proteins associated with mitochondrial and membrane functions, resulting in defective synthesis of their encoded proteins. To promote elongation, eIF3 interacts with 80S ribosomes translating the first ∼60 codons and serves to recruit protein quality-control factors, functions required for normal mitochondrial physiology. Accordingly, eIF3e+/- mice accumulate defective mitochondria in skeletal muscle and show a progressive decline in muscle strength. Hence, eIF3 interacts with 80S ribosomes to enhance, at the level of early elongation, the synthesis of proteins with membrane-associated functions, an activity that is critical for mitochondrial physiology and muscle health.


Nurses' attitudes towards older people and working with older patients: an explanatory model.
To establish an explanatory model of registered nurses' attitudes towards older people and working with older patients. Increasing demands for health-care from an ageing population will require a higher proportion of nurses who have positive attitudes towards older people and like working with older patients. A convenience sample of registered nurses (n = 579; 79.3% response rate) attending continuing professional education courses within a large university in London was surveyed from October to December 2011. Registered nurses expressed positive attitudes towards older people and 89.7% reported positive attitudes towards working with older patients. The variables of self-ageing anxiety, attitudes towards health-care resource allocation, knowledge of ageing, ethnic group, job title, attitudes towards older patients and interaction between ethnic group and attitudes towards working with older patients explained 42.6% of the variance in attitudes towards older people. Factors, including attitudes towards older people, self-ageing anxiety, commitment to nursing, attitudes towards health-care resources allocation among older people and clinical specialty explained 16.7-34.3% of the variance in attitudes towards older patients. The models identified several related factors that may help in the selection and management of nurses for caring older people. Our findings highlight the importance of investing in continuing education related to gerontological nursing and the ageing process so that there is a growing pool of registered nurses who wish to care for older patients.


Effect of copper and lead on two consortia of phototrophic microorganisms and their capacity to sequester metals.
The roles of consortia of phototrophic microorganisms have been investigated in this paper to determine their potential role to tolerate or resist metals and to capture them from polluted cultures. With this purpose, two consortia of microorganisms: on one hand, Geitlerinema sp. DE2011 (Ge) and Scenedesmus sp. DE2009 (Sc) (both identified in this paper by molecular biology methods) isolated from Ebro Delta microbial mats, and on the other, Spirulina sp. PCC 6313 (Sp) and Chroococcus sp. PCC 9106 (Ch), from Pasteur culture collection were polluted with copper and lead. In order to analyze the ability of these consortia to tolerate and capture metals, copper and lead were selected, because both have been detected in Ebro Delta microbial mats. The tolerance-resistance to copper and lead for both consortia was determined in vivo and at cellular level by Confocal Laser Scanning Microscopy (CLSM-λscan function). The results obtained demonstrate that both consortia are highly tolerant-resistant to lead and that the limits between the copper concentration having cytotoxic effect and that having an essential effect are very close in these microorganisms. The capacity of both consortia to capture extra- and intracellular copper and lead was determined by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) respectively, coupled to an Energy Dispersive X-ray detector (EDX). The results showed that all the microorganisms assayed were able to capture copper extracellularly in the extrapolymeric substances, and lead extra- and intracellularly in polyphosphate inclusions. Moreover, the studied micro-organisms did not exert any inhibitory effect on each other's metal binding capacity. From the results obtained in this paper, it can be concluded that consortia of phototrophic microorganisms could play a very important role in biorepairing sediments polluted by metals, as a result of their ability to tolerate or resist high concentrations of metals and to bioaccumulate them, extra- and intracellulary.


Religiosity, sexual behaviors, and sexual attitudes during emerging adulthood.
The current study examined associations between religiosity and sexual behaviors and attitudes during emerging adulthood. Two hundred and five emerging adults completed surveys about five aspects of their religiosity (group affiliation, attendance at religious services, attitudes, perceptions of negative sanctions, and adherence to sanctions) and their sexual behaviors (abstinence, age of onset, lifetime partners, condom use) and attitudes (conservative attitudes, perceived vulnerability to HIV, and condom-related beliefs). Associations were found between the measures of religiosity and sexuality, although the patterns differed by measures used. Religious behavior was the strongest predictor of sexual behavior. Many aspects of religiosity were associated with general sexual attitudes, which was not the case for perceived vulnerability to HIV and condom-related beliefs. The findings support reference group theory and highlight the importance of considering the specific constructs of religiosity and sexuality assessed in studies of these topics.


Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury.
Traumatic brain injury (TBI) often produces cognitive impairments by primary or secondary neuronal loss. Stem cells are a potential tool to treat TBI. However, most previous studies using rodent stem or progenitor cells failed to correlate cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is undetermined. This study therefore characterized phenotypic differentiation, neurotrophic factor expression and release and functional outcome of grafting hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate parasagittal fluid percussion TBI followed by ipsilateral hippocampal transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs were treated in vitro for 7 days with our previously developed priming procedure. Significant spatial learning and memory improvements were detected by the Morris water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological analyses revealed that hNSCs survived and differentiated mainly into neurons in the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA. This is the first direct demonstration of the release of a neurotrophic factor in conjunction with stem cell grafting. In conclusion, human fetal neural stem cell grafts improved cognitive function of rats with acute TBI. Grafted cells survived and differentiated into neurons and expressed and released GNDF in vivo, which may help protect host cells from secondary damage and aid host regeneration.


Auxin-sensitive elements from promoters of tobacco GST genes and a consensus as-1-like element differ only in relative strength.
We have investigated the cis-acting potential of several as elements (20-bp as-1/ocs-like sequences) in both yeast and plant cells. These TGACG[N7]TGACG-resembling elements were surprisingly similar with respect to their ability to confer inducibility by auxins and related compounds to a heterologous TATA box in stably transformed plant cells. Both in plant cells and in yeast it was found that differences between as elements were of a quantitative nature. A strong element based on the consensus sequence for as elements conferred the highest level of gene expression. The rather aberrant as elements present in the promoters of auxin-inducible gst genes Nt103 and Nt114 of tobacco were much weaker cis-acting elements. The ability of an element to drive reporter gene expression was found to correlate with the extent to which proteins present in (nuclear) extracts of yeast and plant cells bound to it. The cloned transcription factor TGA1a was shown to be a very good candidate to be the factor that mediates the in vivo regulation of gene expression via as elements. The physiological significance of gene activation by active and inactive auxins is discussed.


Epidermal growth factor receptor-related protein inhibits cell growth and induces apoptosis of BxPC3 pancreatic cancer cells.
Dysregulation of the epidermal growth factor receptor (EGFR) signaling network has been frequently reported in pancreatic cancer. Inhibition of EGFR was associated with antitumor effects in both in vitro and in vivo studies of pancreatic cancer. We have previously reported the isolation and characterization of an EGFR-related protein (ERRP), which seems to be a negative regulator of EGFR. In the present investigation, we tested our hypothesis whether recombinant ERRP could be an effective inhibitor of growth of BxPC3 pancreatic cancer cells. Cell growth and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptosis ELISA assay, respectively, in the presence and absence of recombinant ERRP in BxPC3 cells. To evaluate activation of EGFR and its downstream signaling events, levels of phospho-EGFR, phospho-AKT, and phospho-extracellular signal-regulated kinase (phospho-ERK) were determined by Western blot analysis. NF-kappaB activity was measured by electrophoretic mobility shift assay. Our data show, for the first time, that ERRP inhibits the growth of BxPC3 cells in a dose- and time-dependent manner. The EGF or transforming growth factor (TGF)-alpha-induced stimulation of cell growth and activation of EGFR was also inhibited by ERRP. These changes were accompanied by a concomitant attenuation of activation of mitogen-activated protein (MAP) kinases, AKT, and NF-kappaB. ERRP also induced apoptosis as evidenced by increased poly(ADP-ribose) polymerase cleavage and reduction in procaspase3. From these results, we conclude that ERRP is a potent inhibitor of growth of BxPC-3 pancreatic cancer cells, which could be due to attenuation of EGFR cellular signaling processes. We also suggest that ERRP could be a potential therapeutic agent for pancreatic cancer.


The pattern of subjective anxiety during in-session exposures over the course of cognitive-behavioral therapy for clients with social anxiety disorder.
Exposure-based therapies are efficacious treatments for social anxiety disorder (i.e., Gould et al., 1997). Much of the theory behind these treatments is derived from Foa and colleagues' (Foa, Huppert, & Cahill, 2005; Foa & Kozak, 1986) work on emotional processing. However, there has been little research examining individual differences in emotional processing patterns within and between treatment sessions among clients with social anxiety disorder. This study utilized longitudinal data analytic methods to examine changes in subjective anxiety during the first 3 exposure sessions in group and individual cognitive-behavioral therapy for social anxiety disorder. The results of this study provide preliminary evidence that, although anxiety generally decreases across exposures, some individuals experience considerable fluctuations in anxiety during a single exposure. Although anxiety during the first exposure was not significantly related to outcome, the relationship between anxiety during exposure and outcome became stronger during subsequent exposures. Overall, this study highlights the need to conduct more fine-grained analyses to better understand the mechanisms underlying exposure-based therapies for social anxiety disorder.


Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease: a randomized phase II study.
This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.


Monitoring bacterial indicators and pathogens in cattle feedlot waste by real-time PCR.
Quantitative microbial health risk assessment requires accurate enumeration of pathogens in hazard-containing matrices as part of the risk characterization process. As part of a risk management-oriented study of cattle feedlot waste contaminants, we investigated the utility of quantitative real-time PCR (qPCR) for surveying the microbial constituents of different faecal wastes. The abundance of Escherichia coli and enterococci were first estimated in five cattle feedlot waste types from five localities. Bacteria were quantified using two culture methods and compared to the number of genome copies detected by qPCR targeted at E. coli and Enterococcus faecalis. Bacterial numbers detected in the different wastes (fresh faeces, pen manure, aged manure, composted manure, carcass manure compost) ranged from 10-(7) to 10(2)g(-1) (dry weight). Both indicator groups were detected by qPCR with a comparable sensitivity to culture methods across this range. qPCR measurements of E. coli and E. faecalis correlated well with MPN and spread plate data. As a second comparison, we inoculated green fluorescent protein (GFP) labeled reference bacteria into manure samples. GFP labeled E. coli and Listeria monocytogenes were detected by qPCR in concentrations corresponding to between 18% and 71% of the initial bacterial numbers, compared to only 2.5-16% by plating. Our results supported our selection of qPCR as a fast, accurate and reliable system for surveying the presence and abundance of pathogens in cattle waste.


Expression, subunit composition, and function of AMPA-type glutamate receptors are changed in activated microglia; possible contribution of GluA2 (GluR-B)-deficiency under pathological conditions.
Microglia express AMPA (α-amino-hydroxy-5-methyl-isoxazole-4-propionate)-type of glutamate (Glu) receptors (AMPAR), which are highly Ca(2+) impermeable due to the expression of GluA2. However, the functional importance of AMPAR in microglia remains to be investigated, especially under pathological conditions. As low expression of GluA2 was reported in some neurodegenerative diseases, GluA2(-/-) mice were used to show the functional change of microglial AMPARs in response to Glu or kainate (KA). Here we found that Glu-induced currents in the presence of 100 μM cyclothiazide, an inhibitor of AMPAR desensitization, showed time-dependent decrease after activation of microglia with lipopolysaccharide (LPS) in GluA2(+/+) microglia, but not in GluA2(-/-) microglia. Upon activation of microglia, expression level of GluA2 subunits significantly increased, while expression of GluA1, A3 and A4 subunits on membrane surface significantly decreased. These results suggest that nearly homomeric GluA2 subunits were the main reason for low conductance of AMPAR in activated microglia. Increased expression of GluA2 in microglia was also detected partially in brain slices from LPS-injected mice. Cultured microglia from GluA2(-/-) mice showed higher Ca(2+) -permeability, consequently inducing significant increase in the release of proinflammatory cytokine, such as TNF-α. The conditioning medium from KA-treated GluA2(-/-) microglia had more neurotoxic effect on wild type cultured neurons than that from KA-treated GluA2(+/+) microglia. These results suggest that membrane translocation of GluA2-containing AMPARs in activated microglia has functional importance and thus, dysfunction or decreased expression of GluA2 may accelerate Glu neurotoxicity via excess release of proinflammatory cytokines from microglia.


Morphometric effects of use and disuse on peripheral nerve.
Rat peripheral nerve was evaluated morphometrically following hemicordotomy, tenectomy, or both to assess the effects of disuse and hyperactivity on the peripheral nervous system. Hemicordotomy resulted in an increase in diameter of nerve fibers supplying both "fast" and "slow" skeletal muscles in hypoactive and hyperactive limbs. Nerve fiber atrophy occurred only in nerve to "fast" muscle following disuse induced by hemicordotomy and tenectomy. The possible role of "motor nerve growth factor" or altered axoplasmic flow in bringing about these morphologic changes in peripheral nerve is discussed.


The oxazolidinones: past, present, and future.
The success of linezolid stimulated significant efforts to discover new agents in the oxazolidinone class. Over a dozen oxazolidinones have reached the clinic, but many were discontinued due to lack of differentiated potency, inadequate pharmacokinetics, and safety risks that included myelosuppression. Four oxazolidinones are currently undergoing clinical evaluation. The Trius Therapeutics compound tedizolid phosphate (formerly known as torezolid phosphate, TR-701, DA-7218), the most advanced, is in phase 3 clinical trials for acute bacterial skin and skin structure infections. Rib-X completed two phase 2 studies for radezolid (Rx-01_667, RX-1741) in uncomplicated skin and skin structure infections and community-acquired pneumonia. Pfizer and AstraZeneca have each identified antitubercular compounds that have completed phase 1 studies: sutezolid (PNU-100480, PF-02341272) and AZD5847 (AZD2563), respectively. The oxazolidinones share a relatively low frequency of resistance largely due to the requirement of mutations in 23S ribosomal RNA genes. However, maintaining potency against strains carrying the mobile cfr gene poses a challenge for the oxazolidinone class, as well as other 50S ribosome inhibitors that target the peptidyl transferase center.


Prognostic Value of Galectin-3 after Left Atrial Appendage Occlusion for Predicting Peri-Device Leakage.
Echocardiographic detection of residual peri-device leakage (PDL) after percutaneous left atrial appendage occlusion (LAAO) is crucial for managing anticoagulation. Galectin-3, a protein involved in tissue-foreign body interactions, may hold significance in understanding PDL and cardiac tissue remodeling after LAAO. This study aimed to analyze galectin-3 serum levels in relation to PDL using a novel echo-morphological classification. LAAO eligible patients were included in the study. Galectin-3 serum levels were measured before LAAO, at 45 days (45D), and at 6 months (6M) after the procedure. Transesophageal echocardiography was used to assess LAAO success. A new echo-morphological classification categorized the degree of LAAO into three different types (A: homogenous echodensity, indicating completely thrombosed device; B: inhomogeneous echolucencies (<50% of device); and C: partially thrombosed device with echolucencies > 50%). Among 47 patients, complete LAAO was achieved in 60% after 45D and in 74% after 6M. We observed a significant increase and distribution of serum levels of galectin-3 [ng/mL] after 45D among the three types (baseline: 13.1 ± 5.8 ng/mL; 45D: 16.3 ± 7.2 ng/mL (Type A) vs. 19.2 ± 8.6 ng/mL (Type B) vs. 25.8 ± 9.4 ng/mL (Type C); p = 0.031), followed by a drop in galectin-3 for Types A and B after 6M toward and below the baseline levels (6M: 8.9 ± 3.1 ng/mL (Type A) vs. 12.4 ± 5.5 ng/mL (Type B)), whereas Type C persisted in showing elevated galectin-3 levels compared to all other types (6M: 17.5 ± 4.5 ng/mL (Type C); p < 0.01). Increased galectin-3 serum levels after LAAO likely reflect the transition from thrombus formation to fibrotic scar development in the LAA lumen. Successful occlusion is associated with a time-restricted decrease in galectin-3 levels after 6 months, while relevant PDL leads to persistently elevated levels, making galectin-3 a potential predictor of occlusion success.


One step construction of Agrobacterium-Recombination-ready-plasmids (OSCAR), an efficient and robust tool for ATMT based gene deletion construction in fungi.
Increasing availability of genomic data and sophistication of analytical methodology in fungi has elevated the need for functional genomics tools in these organisms. Previously we reported a method called DelsGate for rapid preparation of deletion constructs for protoplast-mediated fungal transformation systems, which is based on Gateway® technology. However, over the past several years Agrobacteriumtumefaciens-mediated transformation (ATMT) has become the preferred genetic transformation method for an increasing number of fungi. Therefore, we developed a method for One Step Construction of Agrobacterium-Recombination-ready-plasmids (OSCAR), to rapidly create deletion constructs for ATMT systems. The OSCAR methodology involves PCR amplification of the upstream and downstream flanks of the gene of interest, using gene specific primers each with a 5' extension containing one of four different attB recombination sites, modified from the Invitrogen MultiSite Gateway® system. Amplified gene flanks are then mixed with specifically designed marker and binary vectors and treated with BP clonase, generating the deletion construct in a single cloning step. The entire process of deletion construct preparation can be accomplished in just 2days. Using OSCAR we generated eight targeted deletion constructs and used two of them to generate deletion mutants in Verticillium dahliae by ATMT. In summary, OSCAR methodology combines PCR and Gateway® technology to rapidly and robustly generate precise deletion constructs for fungal ATMT and homologous gene replacement.


Improvement of the cardiovascular effect of methyldopa by complexation with Zn(II): Synthesis, characterization and mechanism of action.
the antihypertensive drug α-methyldopa (MD) stands as one of the extensively used medications for managing hypertension during pregnancy. Zinc deprivation has been associated with many diseases. In this context, the synthesis of a Zn coordination complex [Zn(MD)(OH)(H2O)2]·H2O (ZnMD) provide a promising alternative pathway to improve the biological properties of MD. ZnMD was synthesized and physicochemically characterized. Fluorescence spectral studies were conducted to examine the binding of both, the ligand and the metal with bovine serum albumin (BSA). MD, ZnMD, and ZnCl2 were administered to spontaneous hypertensive rats (SHR) rats during 8 weeks and blood pressure and echocardiographic parameters were determined. Ex vivo assays were conducted to evaluate levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO). Cross-sectional area (CSA) and collagen levels of left ventricular cardiomyocytes were also assessed. Furthermore, the expression of NAD(P)H oxidase subunits (gp91phox and p47phox) and Superoxide Dismutase 1 (SOD1) was quantified through western blot analysis. The complex exhibited a moderate affinity for binding with BSA showing a spontaneous interaction (indicated by negative ΔG values) and moderate affinity (determined by affinity constant values). The binding process involved the formation of Van der Waals forces and hydrogen bonds. Upon treatment with MD and ZnMD, a reduction in the systolic blood pressure in SHR was observed, being ZnMD more effective than MD (122 ± 8.1 mmHg and 145 ± 5.6 mmHg, at 8th week of treatment, respectively). The ZnMD treatment prevented myocardial hypertrophy, improved the heart function and reduced the cardiac fibrosis, as evidenced by parameters such as left ventricular mass, fractional shortening, and histological studies. In contrast, MD did not show noticeable differences in these parameters. ZnMD regulates negatively the oxidative damage by reducing levels of ROS and lipid peroxidation, as well as the cardiac NAD(P)H oxidase, and increasing SOD1 expression, while MD did not show significant effect. Moreover, cardiac nitric oxide levels were greater in the ZnMD therapy compared to MD treatment. Both MD and ZnMD have the potential to be transported by albumin. Our findings provide important evidence suggesting that this complex could be a potential therapeutic drug for the treatment of hypertension and cardiac hypertrophy and dysfunction.


Isolation and Characterization of an Escherichia albertii Strain Producing Three Different Toxins from a Child with Diarrhea.
Here, we report a bacterium-isolated as the sole pathogen from a child with diarrhea-harboring eae and 2 different cytolethal distending toxin genes (cdt) that are homologous to Escherichia coli cdt-I and cdt-II. The bacterium was originally identified as atypical E. coli by conventional biochemical testing, but was finally identified as E. albertii by multilocus sequence analysis, which is the only method that can currently differentiate E. albertii from E. coli. The Shiga toxin 2f (stx2f) genes were also detected in the strain. Production of these 3 toxins was confirmed by western blotting and/or a cytotoxicity assay using eukaryotic cell lines. This is the first report showing the biological activity of CDT-I, CDT-II, and Stx2f in E. albertii.