Can the bias of self-reported sitting time be corrected? A statistical model validation study based on data from 23 993 adults in the Norwegian HUNT study.
Despite apparent shortcomings such as measurement error and low precision, self-reported sedentary time is still widely used in surveillance and research. The aim of this study was threefold; (i) to examine the agreement between self-reported and device-measured sitting time in a general adult population; (ii), to examine to what extent demographics, lifestyle factors, long-term health conditions, physical work demands, and educational level is associated with measurement bias; and (iii), to explore whether correcting for factors associated with bias improves the prediction of device-measured sitting time based on self-reported sitting time. A statistical validation model study based on data from 23 993 adults in the Trøndelag Health Study (HUNT4), Norway. Participants reported usual sitting time on weekdays using a single-item questionnaire and wore two AX3 tri-axial accelerometers on the thigh and low back for an average of 3.8 (standard deviation [SD] 0.7, range 1-5) weekdays to determine their sitting time. Statistical validation was performed by iteratively adding all possible combinations of factors associated with bias between self-reported and device-measured sitting time in a multivariate linear regression. We randomly selected 2/3 of the data (n = 15 995) for model development and used the remaining 1/3 (n = 7 998) to evaluate the model. Mean (SD) self-reported and device-measured sitting time were 6.8 (2.9) h/day and 8.6 (2.2) h/day, respectively, corresponding to a mean difference of 1.8 (3.1) h/day. Limits of agreement ranged from - 8.0 h/day to 4.4 h/day. The discrepancy between the measurements was characterized by a proportional bias with participants device-measured to sit less overestimating their sitting time and participants device-measured to sit more underestimating their sitting time. The crude explained variance of device-measured sitting time based on self-reported sitting time was 10%. This improved to 24% when adding age, body mass index and physical work demands to the model. Adding sex, lifestyle factors, educational level, and long-term health conditions to the model did not improve the explained variance. Self-reported sitting time had low validity and including a range of factors associated with bias in self-reported sitting time only marginally improved the prediction of device-measured sitting time.


New method for measuring QRS duration using high-frequency electrocardiography.
Definition of QRS onset and offset is a basic problem in electrocardiography. Current techniques rely either on subjective estimates or on computer algorithms using QRS derivative or spatial vector velocity parameters. We developed a spectral method based on the observation that the QRS complex, unlike the P wave, PR segment, or ST-T complex is comprised of significant frequencies greater than 50 Hz. Accordingly, we adapted a microprocessor-based electrocardiograph (ECG) system with a signal-averaging program to reduce noise and a 50-300 Hz digital filter. Leads I and aVF were simultaneously acquired by computer in 40 subjects with a wide range of QRS duration (55.5-161 ms). Excellent correlation (r = 0.98) was noted between high-frequency QRS duration measurement and careful visual determinations made at high gain and expanded time scale. The high-frequency ECG appears to provide an objective physiological definition of the QRS complex based on spectral content not on morphology or slope.


White Matter Abnormalities in Children with HIV Infection and Exposure.
Background: Due to changes in guidelines and access to treatment, more children start combination antiretroviral therapy (ART) in infancy. With few studies examining the long-term effects of perinatal HIV infection and early ART on neurodevelopment, much is still unknown about brain maturation in the presence of HIV and ART. Follow-up studies of HIV infected (HIV+) children are important for monitoring brain development in the presence of HIV infection and ART. Methods: We use diffusion tensor imaging (DTI) to examine white matter (WM) in 65 HIV+ and 46 control (HIV exposed uninfected (HEU) and HIV unexposed uninfected (HU)) 7-year-old children. This is a follow up of a cohort studied at 5 years, where we previously reported lower fractional anisotropy (FA) in corticospinal tract (CST) and mean diffusivity (MD) increases in inferior/superior longitudinal fasciculi (ILF/SLF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in HIV+ children compared to uninfected controls. In addition, we also found a difference in FA related to age at which ART was initiated. Results: At 7 years, we found two regions in the left IFOF and left ILF with lower FA in HIV+ children compared to controls. Higher MD was observed in a similar region in the IFOF, albeit bilaterally, as well as multiple clusters bilaterally in the superior corona radiata (SCR), the anterior thalamic radiation (ATR) and the right forceps minor. Unlike at 5 years, we found no impact on WM of ART initiation. In HEU children, we found a cluster in the right posterior corona radiata with higher FA compared to HU children, while bilateral regions in the CST demonstrated reduced MD. Conclusions: At age 7, despite early ART and viral load (VL) suppression, we continue to observe differences in WM integrity. WM damage observed at age 5 years persists, and new damage is evident. The continued observation of regions with lower FA and higher MD in HIV+ children point to disruptions in ongoing white matter development regardless of early ART. Lastly, in HEU children we find higher FA and lower MD in clusters in the CST tract suggesting that perinatal HIV/ART exposure has a long-term impact on WM development.


Importance of dam BW change and calf birth weight in double-muscled Belgian Blue cattle and its relationship with parity and calving interval.
Factors affecting calving interval (CI) in double-muscled Belgian Blue (DMBB) beef cows were investigated with regard to the BW yield (BWY) of the cow-calf pair, using 834 CI records from 386 females with parities 1 to 6. The effect of parity and CI on BWY was also studied. Cow-calf pair BWY was defined as calf birth weight plus dam BWY per CI. CI (mean±s.e.: 404±1.9 days) was affected by parity, calving season, suckling and calf birth weight/dam weight. Primiparous cows had a shorter CI than cows with three or more calvings (P<0.05), with an intermediate CI for second-calf cows. Spring calvings resulted in a shorter CI than summer and autumn calvings, with intermediate values for winter calvings. Suckling dams had longer CIs than non-suckling dams. There were interactions (P<0.05) between calving season and suckling, and between calving season and mating system. Shortest CIs were observed for spring calvings in case of non-suckling and for summer calvings in case of suckling. Longest CIs were observed for autumn calvings in case of natural service (NS) and for winter calvings in case of artificial insemination (AI). Calf birth weight/dam weight of 6% to 10% resulted in shorter CI than a ratio of <6% (P<0.05). Body condition and mating system (NS v. AI) did not affect CI. Daily cow-calf pair BWY was affected by parity (P<0.001) and CI (P=0.013), with a tendency for an interaction (P=0.094). Daily cow-calf pair BWY did not differ for CIs of <12 to 16 months in primiparous cows and was lowest for a CI of 13 to 15 months in second-calf cows, whereas the effect of CI was more variable in older cows. Dam contribution to cow-calf pair BWY was larger than calf birth weight in first- and second-calf cows, and increased with increasing CI. Dam contribution to cow-calf pair BWY was smaller than calf birth weight in older cows, varying from 0.2 to 1.0 depending on CI. A short CI is advised for DMBB cows because of a larger BWY and more efficient nutrient utilisation.


Replication of in vitro tobravirus recombinants shows that the specificity of template recognition is determined by 5' non-coding but not 3' non-coding sequences.
Natural recombinant tobacco rattle tobravirus (TRV) isolates contain sequences from a different tobravirus, pea early browning virus (PEBV). To characterize the sequence requirements for viable recombinant formation hybrid cDNA clones of RNA2 of PEBV and TRV were assembled. Inclusion of 320 nt from the 5' terminus of PEBV or 335 nt from the 5' terminus of TRV in the hybrid RNAs was sufficient to permit their replication by, respectively, PEBV RNA1 or TRV RNA1 regardless of the origin of the 3' terminal region. However, PEBV RNA1 but not TRV RNA1 was sometimes able to support low level replication of RNA2 containing the heterologous 5' terminal region. In vitro translation of PEBV transcripts containing 5' noncoding region deletions supported the hypothesis that in vivo the PEBV coat protein (CP) is expressed from a subgenomic RNA and that, therefore, in the recombinants the CP subgenomic promoter probably is recognized by the replicase of the heterologous virus.


Far-infrared spectroscopic characterization of explosives for security applications using broadband terahertz time-domain spectroscopy.
Broadband terahertz time-domain spectroscopy (THz-TDS) has been used to measure the far-infrared (FIR) vibrational spectra of several commonly used pure explosives, including 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), 1,3-dinitrato-2,2-bis(nitratomethyl)propane (PETN), and two types of plastic explosive, SEMTEX and SX2. A number of distinct absorption peaks, originating from FIR-active vibrational modes of these polycrystalline energetic materials, were observed in the frequency range 0.3-7.5 THz (10-250 cm(-1)). In addition, the temperature-dependent FIR vibrational spectra of PETN were measured between 4 K and 296 K with several well-resolved absorption peaks observed across this temperature range. We find that as the temperature is reduced, the observed absorption peaks resolve into narrower features and shift towards higher frequencies. The temperature dependence of the spectra is explained in terms of the anharmonicity of the vibrational potentials of crystalline compounds, and an empirical fit is given to describe the peak shift with temperature.


MultiTab: A Novel Portable Device to Evaluate Multisensory Skills.
To infer spatial-temporal features of an external event we are guided by multisensory cues, with intensive research showing an enhancement in the perception when information coming from different sensory modalities are integrated. In this scenario, the motor system seems to also have an important role in boosting perception. With the present work, we introduce and validate a novel portable technology, named MultiTab, which is able to provide auditory and visual stimulation, as well as to measure the user's manual responses. Our preliminary results indicate that MultiTab reliably induces multisensory integration in a spatial localization task, shown by significantly reduced manual response times in the localization of audiovisual stimuli compared to unisensory stimuliClinical relevance- The current work presents a novel portable device that could contribute to the clinical evaluation of multisensory processing as well as spatial perception. In addition, by promoting and recording manual actions, MultiTab could be especially suitable for the design of rehabilitative protocols using multisensory motor training.


Developmental stages in human embryos: revised and new measurements.
The staging of human embryos, as distinct from seriation, depends on a morphological scheme devised by Streeter and completed by O'Rahilly, who proposed the term Carnegie stages. To avoid misconceptions and errors, and to place new findings in perspective, it is necessary to summarize the essentials of the Carnegie system: (1) Twenty-three stages cover the embryonic period, i. e. the first 8 postfertilizational weeks of development. (2) The system is based on internal as well as external features, and the use of only external criteria is subject to serious limitations. For example, precise delineation of stages 19-23 and of the embryonic-fetal transition depends on histological examination. (3) Prenatal measurements are not an integral component of the staging system, and hence a stage should never be assigned merely on the basis of embryonic length. A 20-mm embryo, for example, could belong to any of three stages. Measurements, however, are important for the assessment of age, and very few measurements are available for staged embryos. Presented here and based on accurate staging are the maximum diameter of the chorionic sac, the crown-heel length, the greatest length exclusive of the lower limbs, the biparietal diameter, the head circumference, the length of the hindbrain, the total length of the brain, and the lengths of the limbs as well as of their segments, including the foot length. (4) Prenatal ages are also not an integral part of the staging system and hence a stage should never be assigned merely on the basis of prenatal age. Ages, however, are of clinical importance and their estimate has been rendered more precise by accurate timing of fertilization followed by ultrasonography. Prenatal age is postfertilizational and hence some 2 weeks less than the postmenstrual interval. The term gestational age is ambiguous and should be discarded. Presented here is a new graph showing proposed estimates of age in relation to stages and based on current information.


Optogenetic Control of Ras/Erk Signaling Using the Phy-PIF System.
The Ras/Erk signaling pathway plays a central role in diverse cellular processes ranging from development to immune cell activation to neural plasticity to cancer. In recent years, this pathway has been widely studied using live-cell fluorescent biosensors, revealing complex Erk dynamics that arise in many cellular contexts. Yet despite these high-resolution tools for measurement, the field has lacked analogous tools for control over Ras/Erk signaling in live cells. Here, we provide detailed methods for one such tool based on the optical control of Ras activity, which we call "Opto-SOS." Expression of the Opto-SOS constructs can be coupled with a live-cell reporter of Erk activity to reveal highly quantitative input-to-output maps of the pathway. Detailed herein are protocols for expressing the Opto-SOS system in cultured cells, purifying the small molecule cofactor necessary for optical stimulation, imaging Erk responses using live-cell microscopy, and processing the imaging data to quantify Ras/Erk signaling dynamics.


Cerebellar and hindbrain motion in Chiari malformation with and without syringomyelia.
The pathogenesis of syringomyelia associated with Chiari malformation type I (CM-I) is unclear. Theories of pathogenesis suggest the cerebellar tonsils may obstruct CSF flow or alter pressure gradients, or their motion might act as a piston to increase CSF pressure in the spinal subarachnoid space. This study was performed to measure cerebellar tonsillar and hindbrain motion in CM-I and assess the potential contributions to syrinx formation. Sixty-four CM-I patients and 25 controls were retrospectively selected from a clinical database, and all subjects had undergone cardiac-gated cine balanced fast-field echo MRI. There were a total of 36 preoperative CM-I scans, which consisted of 15 patients with and 21 patients without syringomyelia. Nineteen patients underwent paired pre- and postoperative imaging. Anteroposterior (AP) and superoinferior (SI) movements of the tip of the cerebellar tonsils, obex, fastigium of the fourth ventricle, pontomedullary junction, and cervicomedullary junction were measured. The distance between the fastigium and tip of the tonsils was used to calculate tonsillar tissue strain (Δi/i0). CM-I patients had significantly greater cerebellar tonsillar motion in both the AP and SI directions than controls (AP +0.34 mm [+136%], p < 0.001; SI +0.49 mm [+163%], p < 0.001). This motion decreased after posterior fossa decompression (AP -0.20 mm [-33%], p = 0.001; SI -0.29 mm [-36%]; p < 0.001), but remained elevated above control levels (AP +56%, p = 0.021; SI +67%, p = 0.015). Similar trends were seen for all other tracked landmarks. There were no significant differences in the magnitude or timing of motion throughout the hindbrain between CM-I patients with and without syringomyelia. Increased tonsillar tissue strain correlated with Valsalva headaches (p = 0.03). Cerebellar tonsillar motion may be a potential marker of CM-I and may have use in tailoring surgical procedures. The lack of association with syringomyelia suggests that tonsillar motion alone is not the driver of syrinx formation. Tonsillar tissue strain may play a part in the pathophysiology of Valsalva headaches.


Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase outside of sialic acid biosynthesis: modulation of sialyltransferase and BiP expression, GM3 and GD3 biosynthesis, proliferation, and apoptosis, and ERK1/2 phosphorylation.
Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase (GNE) beyond controlling flux into the sialic acid biosynthetic pathway by converting UDP-GlcNAc to N-acetylmannosamine are described in this report. Overexpression of recombinant GNE in human embryonic kidney (HEK AD293) cells led to an increase in mRNA levels for ST3Gal5 (GM3 synthase) and ST8Sia1 (GD3 synthase) as well as the biosynthetic products of these sialyltransferases, the GM3 and GD3 gangliosides. Conversely, down-regulation of GNE by RNA interference methods had the opposite, but consistent, effect of lowering ST3Gal5 and ST8Sia1 mRNAs and reducing GM3 and GD3 levels. Control experiments ensured that GNE-mediated changes in sialyltransferase expression and ganglioside biosynthesis were not the result of altered flux through the sialic acid pathway. Interestingly, exogenous GM3 and GD3 also changed the expression of GNE and led to reduced ST3Gal5 and ST8Sia1 mRNA levels, demonstrating a reciprocating feedback mechanism where gangliosides regulate upstream biosynthetic enzymes. Cellular responses to the GNE-mediated changes in ST3Gal5 and ST8Sia1 expression and GM3 and GD3 levels were investigated next. Conditions that led to reduced ganglioside production (e.g. short hairpin RNA exposure) stimulated proliferation, whereas conditions that resulted in increased ganglioside levels (e.g. recombinant GNE and exogenous gangliosides) led to reduced proliferation with a concomitant increase in apoptosis. Finally, changes to BiP expression and ERK1/2 phosphorylation consistent with apoptosis and proliferation, respectively, were observed. These results provide examples of specific biochemical pathways, other than sialic acid metabolism, that are influenced by GNE.


Congenital orbital teratoma.
A case of congenital orbital teratoma is described in which there was no organized eye only microscopic evidence of ocular tissues within the disorganized teratoma. A baby boy presented at birth with a 10-x-8-cm mass extruding from the left orbit. Magnetic resonance imaging (MRI) showed a mixed cystic-solid orbital mass containing areas of calcification and deforming the bony orbit around its margins. There was no organized eye and no intracranial extension. The eye was removed with reconstruction of the eyelids. Histopathology showed representation from all three germ cell layers consistent with a teratoma. There was no organized eye, but some disorganized ocular structures within the teratoma. Follow-up has been uneventful. Neonatologists and pediatricians should be aware of the possible diagnoses in a newborn presenting with an orbital mass, so that early definitive surgery can be performed with preservation of the globe where possible.


Treatment for lupus nephritis.
Cyclophosphamide, in combination with corticosteroids has been used to induce remission in proliferative lupus nephritis, the most common kidney manifestation of the multisystem disease, systemic lupus erythematosus. Cyclophosphamide therapy has reduced mortality from over 70% in the 1950s and 1960s to less than 10% in recent years. Cyclophosphamide combined with corticosteroids preserves kidney function but is only partially effective and may cause ovarian failure, infection and bladder toxicity. Several new agents, including mycophenolate mofetil (MMF), suggest reduced toxicity with equivalent rates of remission. This is an update of a Cochrane review first published in 2004. To assess the benefits and harms of different immunosuppressive treatments in biopsy-proven proliferative lupus nephritis. For this update, we searched the Cochrane Renal Group's Specialised Register (up to 15 April 2012) through contact with the Trials' Search Coordinator using search terms relevant to this review. Randomised controlled trials (RCTs) and quasi-RCTs comparing any treatments for biopsy-proven lupus nephritis in both adult and paediatric patients with class III, IV, V +III and V +IV lupus nephritis were included. All immunosuppressive treatments were considered. Data were abstracted and quality assessed independently by two authors, with differences resolved by discussion. Dichotomous outcomes were reported as risk ratio (RR) and measurements on continuous scales reported as mean differences (MD) with 95% confidence intervals (CI). We identified 50 RCTs involving 2846 participants. Of these, 45 studies (2559 participants) investigated induction therapy, and six studies (514 participants), considered maintenance therapy.Compared with intravenous (IV) cyclophosphamide, MMF was as effective in achieving stable kidney function (5 studies, 523 participants: RR 1.05, 95% CI 0.94 to 1.18) and complete remission of proteinuria (6 studies, 686 participants: RR 1.16, 95% CI 0.85 to 1.58). No differences in mortality (7 studies, 710 participants: RR 1.02, 95% CI 0.52 to 1.98) or major infection (6 studies, 683 participants: RR 1.11, 95% CI 0.74 to 1.68) were observed. A significant reduction in ovarian failure (2 studies, 498 participants: RR 0.15, 95% CI 0.03 to 0.80) and alopecia (2 studies, 522 participants: RR 0.22, 95% CI 0.06 to 0.86) was observed with MMF. In maintenance therapy, the risk of renal relapse (3 studies, 371 participants: RR 1.83, 95% CI 1.24 to 2.71) was significantly higher with azathioprine compared with MMF. Multiple other interventions were compared but outcome data were relatively sparse. Overall study quality was variable. The internal validity of the design, conduct and analysis of the included RCTs was difficult to assess in some studies because of the omission of important methodological details. No study adequately reported all domains of the risk of bias assessment so that elements of internal bias may be present. MMF is as effective as cyclophosphamide in inducing remission in lupus nephritis, but is safer with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse with no increase in clinically important side effects. Adequately powered trials with long term follow-up are required to more accurately define the risks and eventual harms of specific treatment regimens.


[Performance evaluation of X-ray CT using visible scintillation light].
We proposed a new method of performance evaluation for X-ray CT using visible scintillation light and examined its usefulness in this study. When we scanned a plastic scintillator disk in a gantry opening of the X-ray CT, we could observe visible scintillation light. The rotation of the light-emitting area of the disk corresponded to that of the X-ray tube. We were able to record the scintillation light by digital video camera. By analyzing the area of visible scintillation light, the rotation speed of the X-ray tube, angular spread of the X-ray beam, uniformity of the incident X-rays, and change in X-ray energy were measured. No other method is available to obtain the above parameters of X-ray CT during a single CT scan. In the measurements of the uniformity of incident X-rays and change of X-ray energy, our method showed good accuracy in detecting the attenuation caused by the couch between the X-ray tube and the plastic scintillator disc. The proposed method is inexpensive and easy-to-use. We conclude that the method is a useful tool for performance evaluation as well as a maintenance tool for X-ray CT.


Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study.
The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities.


Poor work design begets poor work design: Capacity and willingness antecedents of individual work design behavior.
Few studies have systematically considered how individuals design work. In a replication study (N = 211, Study 1), we showed that students naturally tend to develop simplified, low variety work. In 2 further simulation studies, we quantitatively assessed participants' work design behaviors via 2 new measures ("enriching task allocation" and "enriching work strategy selection"). As a comparison measure, we assessed individuals' tendency to choose individualistic rather than work design strategies ("person-focused strategy selection"). We then investigated how work design behaviors are affected by capacity (professional expertise, explicit knowledge, job autonomy) and willingness (life values). For a sample of human service professionals (N = 218, Study 2), participants scored higher on enriching task allocation and enriching work strategy selection if they had expertise as an industrial/organizational psychologist and if they had high autonomy in their own job. Explicit knowledge about work design predicted lower scores on person-focused strategy selection, and mediated the effects of professional expertise on this outcome. Individuals high in openness values scored higher on enriching work strategy selection, and those high in conservation values scored lower on enriching task allocation. These findings were replicated in Study 3 among working professionals (N = 602). We then showed that openness to change values predicted enriching work strategy selection via the more proximal processes of valence (valuing intrinsic work characteristics) and affect (positive affect when enriching others' work). This article opens up a new area of inquiry: how and why individuals design work for others in the way they do. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Contamination, suffering and womanhood: Lay explanations of breast cancer in Central Vietnam.
Breast cancer has become the most frequent cancer among women in Vietnam, claiming over 6000 lives a year. In this article we investigate how laypeople explain the causes of this pressing health issue based on an ethnographic study conducted in the Central region of Vietnam in 2019, including hospital observation, interviews with 33 breast cancer patients and focus groups with 21 laypeople. Our findings show that their knowledge of causation is mediated through historical social contexts of warfare, a rapacious market economy, poverty, and cultural configurations of gender roles. Contamination of the environment and food, use of chemicals, failure to follow postpartum practices, breast ailments, and worry are understood to be immediate determinants of breast cancer. These popular accounts are unlikely to recognize biomedical narratives of breast cancer risk that focus upon individual responsibility and lifestyle factors because they may not reflect the lived realities of women. We emphasise the implications for public awareness campaigns to meaningfully engage with the situated social and cultural specificities of breast cancer.


Azide-tagged sphingolipids: new tools for metabolic flux analysis.
Several diseases involve alterations in sphingolipid metabolism, so the development of tools for the analysis of sphingolipid metabolic fluxes is of interest. In this work, ω-azidosphingolipids 1-3 have been synthesized and tested as tracers in live cells. The synthesis starts from (S)-Garner's aldehyde and uses bromide or tosyloxy precursors for the introduction of the azido group into the sphingoid base. Studies in HGC-27 cells showed that probes 1-3 compete with the natural metabolites and are incorporated into sphingolipid pathways without affecting cell viability. The reactivity and bioorthogonality of the terminal azido group have been exploited by means of click reactions with different azadibenzocyclooctyne tags. This allows the mass spectrometric characterization of azidosphingolipidomes in pooled samples from different cell populations after independent treatments, providing proof of concept of the applicability of this technology in sphingolipid metabolic flux analysis.


The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions.
1. Little information is available about the pharmacokinetic interactions of anticancer drugs in man. However, clinically significant drug interactions do occur in cancer chemotherapy, and it is likely that important interactions have not been recognized. 2. Specific cytochrome P450 (CYP) enzymes have been recently shown to be involved in the metabolism of several essential anticancer agents. In particular, enzymes of the CYP3A subfamily play a role in the metabolism of many anticancer drugs, including epipodophyllotoxins, ifosphamide, tamoxifen, taxol and vinca alkaloids. CYP3A4 has been shown to catalyse the activation of the prodrug ifosphamide, raising the possibility that ifosphamide could be activated in tumour tissues containing this enzyme. 3. As examples of recently found, clinically significant interactions, cyclosporin considerably increases plasma doxorubicin and etoposide concentrations. Although cyclosporin and calcium channel blockers may influence the pharmacokinetics of certain anticancer agents by inhibiting their CYP3A mediated metabolism, it is more likely that these P-glycoprotein inhibitors inhibit P-glycoprotein mediated drug elimination. 4. Appropriate caution should be exercised when combining P-glycoprotein inhibitors and potential CYP3A inhibitors with cancer chemotherapy.


Dinitrogen oxide detection for process failure early warning systems.
A number of experiments were conducted in order to establish whether the concentration of N2O in the off-gas from an activated sludge pilot plant could be used as a indicator for monitoring the nitrification process and as an early indication of ammonia appearing in the plant effluent. A strong correlation was found between ammonia shock loads and the concentration of N20 in the off-gas from the aeration tank for ammonia shock loads and dissolved oxygen depletion. When subjecting the experimental setup to doses of a nitrification inhibitor (allylthiourea) a similar pattern was seen with a correlation between nitrite build up in the aeration tank and concentration increase of N2O in the off-gas from the aeration tank. The results from this work suggest the concentration and the changes in the concentration of N2O in the exhaust gas from a nitrifying process may be a useful parameter for monitoring nitrifying activated sludge processes.


Kinanthropometric and performance characteristics of elite and non-elite female softball players.
The purpose of the present study was to compare the kinanthropometric and performance characteristics of elite and non-elite female softball players. A total forty elite and non-elite level female softball players were selected from the different colleges affiliated to the Guru Nanak Dev University, Amritsar, for the present study. The height of subjects was measured by using the standard anthropometric rod. Weight was measured with portable weighing machine. Widths and diameters of body parts were measured by using digital caliper. Girths and lengths were taken with steel tape. Skinfold thickness measurements were taken using the Slimguide skinfold caliper. All subjects were also assessed for performance tests i.e. vertical jump, 50m sprint, medicine ball throw, 10×4m shuttle run and reaction time. Independent samples t-test reveals that elite female softball players were significantly taller (P<0.05) than the non- elite players. The elite female softball players also had significantly greater biacromial (P<0.05), bi- illiocristal (P<0.05) and bicondylar femur (P<0.05) diameters and forearm circumference (P<0.05) as compared to non-elite female softball players. The non-elite female softball players were found to have significantly greater thigh circumference (P<0.05), triceps (P<0.05) and subscapular (P<0.05) skinfold thicknesses than the elite female softball players. The non-elite players were also found to have significantly higher percentage body fat (P<0.05) than the elite players. In performance tests, the elite players were found to have significantly better reaction time (P<0.05), speed (P<0.05) and agility (P<0.05) as compared to non-elite female softball players. The elite female softball players had significantly greater kinanthropometric characteristics, body composition and performance characteristics than the non-elite female softball players.


The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.
There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that Nm OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of Ng genital tract infection. We found that immunization with the licensed Nm OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the Ng bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with Ng OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several Ng surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized Ng PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50 titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that Nm OMVs confer cross-species protection against gonorrhea, and implicate several Ng surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.


Carbon nanoparticles induce ceramide- and lipid raft-dependent signalling in lung epithelial cells: a target for a preventive strategy against environmentally-induced lung inflammation.
Particulate air pollution in lung epithelial cells induces pathogenic endpoints like proliferation, apoptosis, and pro-inflammatory reactions. The activation of the epidermal growth factor receptor (EGFR) is a key event responsible for signalling events involving mitogen activated protein kinases specific for these endpoints. The molecular events leading to receptor activation however are not well understood. These events are relevant for the toxicological evaluation of inhalable particles as well as for potential preventive strategies in situations when particulate air pollution cannot be avoided. The current study therefore had the objective to elucidate membrane-coupled events leading to EGFR activation and the subsequent signalling cascade in lung epithelial cells. Furthermore, we aimed to identify the molecular target of ectoine, a biophysical active substance which we described to prevent carbon nanoparticle-induced lung inflammation. Membrane signalling events were investigated in isolated lipid rafts from lung epithelial cells with regard to lipid and protein content of the signalling platforms. Using positive and negative intervention approaches, lipid raft changes, subsequent signalling events, and lung inflammation were investigated in vitro in lung epithelial cells (RLE-6TN) and in vivo in exposed animals. Carbon nanoparticle treatment specifically led to an accumulation of ceramides in lipid rafts. Detailed analyses demonstrated a causal link of ceramides and subsequent EGFR activation coupled with a loss of the receptor in the lipid raft fractions. In vitro and in vivo investigations demonstrate the relevance of these events for carbon nanoparticle-induced lung inflammation. Moreover, the compatible solute ectoine was able to prevent ceramide-mediated EGFR phosphorylation and subsequent signalling as well as lung inflammation in vivo. The data identify a so far unknown event in pro-inflammatory signalling and contribute to the understanding of particle cell interaction and therefore to risk identification and risk assessment of inhalable xenobiotics. Moreover, as this cellular reaction can be prevented by the well tolerated substance ectoine, a molecular preventive strategy for susceptible persons against airway inflammation is proposed.


Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus.
A previously undescribed coronavirus (CoV) is the etiologic agent responsible for severe acute respiratory syndrome (SARS). Using a panel of contiguous cDNAs that span the entire genome, we have assembled a full-length cDNA of the SARS-CoV Urbani strain, and have rescued molecularly cloned SARS viruses (infectious clone SARS-CoV) that contained the expected marker mutations inserted into the component clones. Recombinant viruses replicated as efficiently as WT virus and both were inhibited by treatment with the cysteine proteinase inhibitor (2S,3S)-transepoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester. In addition, subgenomic transcripts were initiated from the consensus sequence ACGAAC in both the WT and infectious clone SARS-CoV. Availability of a SARS-CoV full-length cDNA provides a template for manipulation of the viral genome, allowing for the rapid and rational development and testing of candidate vaccines and therapeutics against this important human pathogen.


[Acute hemodynamic effects of biventricular and left ventricular pacing in chronic pacemaker-dependent patients with advanced heart failure].
The beneficial hemodynamic effects of cardiac resynchronization in patients with intraventricular conduction delay have been demonstrated. The potential hemodynamic effects of cardiac resynchronization to compensate the pacing-induced left ventricular conduction delay in chronically paced heart failure patients are not as well established. The aim of the study was to evaluate the acute hemodynamic effects of biventricular and left ventricular pacing in chronically paced patients with advanced heart failure. Fourteen consecutive pacemaker or defibrillator patients with permanent atrial fibrillation and AV block (11 male, 3 woman, mean age: 68 +/- 7 years) were enrolled in this study. There were 5 ischemic (36%) and 9 nonischemic (64%) patients (mean left ventricular ejection fraction: 19 +/- 5%; mean end-diastolic left ventricular diameter: 71 +/- 11 mm). In all patients a right ventricular and left ventricular (via coronary sinus) pacing lead was placed. The aortic and left ventricular hemodynamic measurements were performed using a two-channel micro-tip catheter. The measurements of the aortic pulse pressure (APP) and (dP/ dtmax) were performed during right ventricular apical pacing (RVP), left ventricular (LVP), and biventricular pacing (BVP) (70 bpm). Compared to RVP, LVP and BVP increased APP and dP/dtmax (35.8 +/- 4.2 vs 43.3 +/- 4.5 and 41.2 +/- 4 mmHg; p < 0.001) and (758 +/- 56 vs 967 +/- 60 and 961 +/- 62 mmHg/s; p < 0.001). LVP and BVP showed a comparable hemodynamic response. The hemodynamic effects were not related to the width of the paced QRS complex. Every patient showed improved hemodynamics during LVP and BVP unrelated to the underlying heart disease and to the baseline level of left ventricular dysfunction. BVP and LVP pacing acutely improve contractile left ventricular function in chronically paced patients with advanced heart failure.


Role of robot-assisted pelvic surgery.
The purpose of this study was to assess the current role of robot-assisted urological surgery in the female pelvis. The recently published English literature was reviewed to evaluate this role, with special emphasis on reconstructive procedures. These included colposuspension for genuine female stress urinary incontinence, repair of female genitourinary fistulas, ureterosciatic hernias, sacrocolpopexy for vault prolapse, ureterolysis and omental wrap for retroperitoneal fibrosis, ureteric reimplantation, and bladder surgery. To date, a wide spectrum of urogynecological reconstructive procedures have been performed with the assistance of the surgical robot and have been reported worldwide. Currently, a number of female pelvic ablative and reconstructive procedures are technically feasible with the aid of the surgical robot. While the role of robot-assisted surgery for bladder cancer, ureterolysis, ureteric reimplantation, repair of genitourinary fistulas, colposuspension, and sacrocolpopexy is nearly established among urologists, other procedures, such as myomectomy, simple hysterectomy, trachelectomy, and Wertheim's hysterectomy, are still evolving with gynecologists. The advantages of robot assistance include better hand-eye coordination, three-dimensional magnified stereoscopic vision with depth perception, intuitive movements with increased precision, and filtering of hand tremors. For most of the currently performed procedures in selected patients, the robot-assisted surgical outcomes appear to be relatively superior as compared to an open and purely laparoscopic surgical procedure.


Classification algorithms enhance the discrimination of glaucoma from normal eyes using high-definition optical coherence tomography.
To evaluate the diagnostic performance of classification algorithms based on Linear Discriminant Analysis (LDA) and Classification And Regression Tree (CART) methods, compared with optic nerve head (ONH) and retinal nerve fiber layer (RNFL) parameters measured by high-definition optical coherence tomography (Cirrus HD-OCT) for discriminating glaucoma subjects. Consecutive glaucoma subjects (Training data = 184; Validation data = 102) were recruited from an eye center and normal subjects (n = 508) from an ongoing Singaporean Chinese population-based study. ONH and RNFL parameters were measured using a 200 × 200 scan protocol. LDA and CART were computed and areas under the receiver operating characteristic curve (AUC) compared. Average RNFL thickness (AUC 0.92, 95% confidence interval [CI] 0.91, 0.93), inferior RNFL thickness (AUC 0.92, 95% CI 0.91, 0.93), vertical cup-disc ratio (AUC 0.91, 95% CI 0.90, 0.92) and rim area/disc area ratio (AUC 0.90, 95% CI 0.86, 0.93) discriminated glaucoma better than other parameters (P ≤ 0.033). LDA (AUC 0.96, 95% CI 0.95, 0.96) and CART (0.98, 95% CI 0.98, 0.99) outperformed all parameters for diagnostic accuracy (P ≤ 0.005). Misclassification rates in LDA (8%) and CART (5.6%) were found to be low. The AUC of LDA for the validation data was 0.98 (0.95, 0.99) and CART was 0.99 (0.99, 0.994). CART discriminated mild glaucoma from normal better than LDA (AUC 0.94 vs. 0.99, P < 0.0001). Classification algorithms based on LDA and CART can be used in HD-OCT analysis for glaucoma discrimination. The CART method was found to be superior to individual ONH and RNFL parameters for early glaucoma discrimination.


Density-dependent survival varies with species life-history strategy in a tropical forest.
Species coexistence in diverse communities likely results from multiple interacting factors. Mechanisms such as conspecific negative density dependence (CNDD) and varying life-history strategies related to resource partitioning are known to influence plant fitness, and thereby community composition and diversity. However, we have little understanding of how these mechanisms interact and how they vary across life stages. Here, we document the interaction between CNDD and life-history strategy, based on growth-mortality trade-offs, from seedling to adult tree for 47 species in a tropical forest. Species' life-history strategies remained consistent across stages: fast-growing species had higher mortality than slow-growing species at all stages. In contrast, mean CNDD was strongest at early life stages (i.e. seedling, sapling). Fast-growing species tended to suffer greater CNDD than slow-growing species at several, but not all life stages. Overall, our results demonstrate that coexistence mechanisms interact across multiple life stages to shape diverse tree communities.


Wear Performance of Calcium Carbonate-Containing Knee Spacers.
Articulating spacers should be wear-resistant and load-bearing to avoid prolonged immobilization of the patient and to reduce morbidity. However, due to the articulation of both components, a release of cement wear particles is to be expected. The aim of this study was to investigate the wear performance of a new spacer cement that contains calcium carbonate as a radio-opaque substance, in comparison to an established barium sulphate-containing spacer material, and also to characterize the amount, morphology, and size distributions of the released cement particles in detail. Force-controlled simulation was carried out on an AMTI knee simulator. The test parameters were in accordance with the standard ISO 14243-1 with a 50% reduced axial force. Tests were run for 500,000 cycles at a frequency of 1 Hz. For wear analysis, photographic documentation of the wear scars, gravimetric wear measurements and wear particle analysis were performed. The barium sulphate spacer material showed a total articular wear of 375.53 ± 161.22 mg. For the calcium carbonate-containing cement, reduced articular wear of 136.32 ± 37.58 mg was determined. Isolated cement wear particles of the barium sulphate-containing cement had a diameter of 0.429 ± 0.224 μm and were significantly larger compared to the calcium carbonate-containing cement (0.380 ± 0.216 μm, p = 0.02). The calcium carbonate-containing cement showed better wear performance in terms of gravimetric wear and particle release. Thus, calcium carbonate seems to be a promising material as a radio-opaque substrate in cement spacers.


Diagnostic value of microtympanometry in primary care.
To determine the reliability, validity, and feasibility of a new hand held microtympanometer. Comparison of microtympanometry by two independent observations of a general practitioner and a nurse, and against a validated reference instrument. Primary care health centre of a school for the deaf in the United States. 111 schoolchildren receiving a regular check up. Tympanometry with the Grason Stadler 28, classified with a slightly modified Jerger's classification. Interobserver reliability was 0.95 (Cohen's kappa). Results of microtympanometry were highly comparable with results of the reference instrument (likelihood ratio of positive results, 161.2). The microtympanometer could be used in general practice: it is hand held, child friendly, easy to handle, and accurate.


Disseminated corticolimbic neuronal degeneration induced in rat brain by MK-801: potential relevance to Alzheimer's disease.
Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors by MK-801 induces neuronal degeneration in the posterior cingulate/retrosplenial cortex and other corticolimbic regions although damage in the latter has not been adequately characterized. This disseminated corticolimbic damage is of interest since NMDA hypofunction, the mechanism that triggers this neurodegenerative syndrome, has been postulated to play a role in the pathophysiology of Alzheimer's disease (AD). Several histological methods, including electron microscopy, were used to evaluate the neurotoxic changes in various corticolimbic regions of rat brain following MK-801 or a combination of MK-801 plus pilocarpine. We found that MK-801 triggers neuronal degeneration in a widespread pattern similar to that induced by phencyclidine and that females showed more damage than males. The neurotoxic reaction involved additional brain regions when muscarinic receptors were hyperactivated by administering pilocarpine with MK-801. Ultrastructural evaluation revealed that a major feature of the neurotoxic action involves degeneration of dendritic spines which entails loss of synaptic complexes. The ultrastructural appearance of degenerating neurons was generally inconsistent with an apoptotic mechanism, although evidence equivocally consistent with apoptosis was observed in some instances. The cell death process evolved relatively slowly and was still ongoing 7 days posttreatment. Relevance of these results to AD is discussed.


A biological approach to assembling tissue modules through endothelial capillary network formation.
To create functional tissues having complex structures, bottom-up approaches to assembling small tissue modules into larger constructs have been emerging. Most of these approaches are based on chemical reactions or physical interactions at the interface between tissue modules. Here we report a biological assembly approach to integrate small tissue modules through endothelial capillary network formation. When adjacent tissue modules contain appropriate extracellular matrix materials and cell types that support robust endothelial capillary network formation, capillary tubules form and grow across the interface, resulting in assembly of the modules into a single, larger construct. It was shown that capillary networks formed in modules of dense fibrin gels seeded with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs); adjacent modules were firmly assembled into an integrated construct having a strain to failure of 117 ± 26%, a tensile strength of 2208 ± 83 Pa and a Young's modulus of 2548 ± 574 Pa. Under the same culture conditions, capillary networks were absent in modules of dense fibrin gels seeded with either HUVECs or MSCs alone; adjacent modules disconnected even when handled gently. This biological assembly approach eliminates the need for chemical reactions or physical interactions and their associated limitations. In addition, the integrated constructs are prevascularized, and therefore this bottom-up assembly approach may also help address the issue of vascularization, another key challenge in tissue engineering.


Distributed Bragg reflector structures based on PT-symmetric coupling with lowest possible lasing threshold.
A new approach towards the design of optimized distributed Bragg reflector (DBR) structures is proposed by taking advantage of recent developments related to the concept of parity-time (PT) in optics. This approach is based on using unidirectional gratings that provide coupling between co-propagating modes. Such couplers with PT symmetric gratings can provide co-directional mode coupling occurring only in one direction. This specific coupling property is achieved through a combined contribution of superimposed index and gain/loss modulations with same grating periodicity, but shifted with respect to one another by a quarter periods. Based on the transfer matrix approach, the transmission and reflection properties of the structure are modeled. One of the unique characteristics of the structure is very low lasing threshold. Such low threshold can be achieved by 100% reflectivity of the both Bragg grating mirrors, and by releasing the amplified signal in one single direction through a PT symmetric grating assisted co-directional coupler. Besides the lasing applications, the proposed structure can be implemented as an optical memory unit of replicating any input optical waveform.


Short-term potentiation phenomena in the rat limbic forebrain.
Several types of short-term postactivation potentiation (PAP) effect were examined in limbic forebrain pathways in the chronic rat. We tested 9 different stimulation sites and 1-3 target sites for each stimulation site. All pathways showed PAP effects following activation by single electrical pulses or pulse trains. Using exponential curve fitting procedures, we found that the decay curves could be best fitted by one, or a sum of 2-3, exponential curves. On the basis of time constants, these curves fell into 4 different categories: facilitation (tau = 80 ms), augmentation (tau = 7s), potentiation 1 (tau = 70s), and potentiation 2(tau = 6.5 min). The latter component was the one most reliably generated in the chronic preparation. Frequency facilitation (facilitation during a stimulation train) was also examined and it appeared to be based upon a mechanism similar to that underlying paired pulse facilitation. Evidence is presented that facilitation and augmentation may be based on the the same mechanism. The possibility that the remaining components involve different mechanisms is discussed.


Anti-cancer effect of clofazimine as a single agent and in combination with cisplatin on U266 multiple myeloma cell line.
Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. CLF (10μM, 24h) treatment resulted up to 72% growth suppression on a panel of hematological cell lines. Dose-response study conducted on U266 MM cell line revealed an IC50 value of 9.8±0.7μM. CLF also showed a synergistic inhibition effect in combination with cisplatin. In mechanistic assays, CLF treatment caused mitochondrial membrane depolarization, change in cell membrane asymmetry and increase in caspase-3 activity; indicating to an intrinsic apoptosis mechanism. This study provides new evidence for the anticancer effect of CLF on U266 cell line. Further in vivo and clinical studies are warranted to evaluate its therapeutic potential for MM treatment.


150-μm Spatial Resolution Using Photon-Counting Detector Computed Tomography Technology: Technical Performance and First Patient Images.
The aims of this study were to quantitatively assess two new scan modes on a photon-counting detector computed tomography system, each designed to maximize spatial resolution, and to qualitatively demonstrate potential clinical impact using patient data. This Health Insurance Portability Act-compliant study was approved by our institutional review board. Two high-spatial-resolution scan modes (Sharp and UHR) were evaluated using phantoms to quantify spatial resolution and image noise, and results were compared with the standard mode (Macro). Patients were scanned using a conventional energy-integrating detector scanner and the photon-counting detector scanner using the same radiation dose. In first patient images, anatomic details were qualitatively evaluated to demonstrate potential clinical impact. Sharp and UHR modes had a 69% and 87% improvement in in-plane spatial resolution, respectively, compared with Macro mode (10% modulation-translation-function values of 16.05, 17.69, and 9.48 lp/cm, respectively). The cutoff spatial frequency of the UHR mode (32.4 lp/cm) corresponded to a limiting spatial resolution of 150 μm. The full-width-at-half-maximum values of the section sensitivity profiles were 0.41, 0.44, and 0.67 mm for the thinnest image thickness for each mode (0.25, 0.25, and 0.5 mm, respectively). At the same in-plane spatial resolution, Sharp and UHR images had up to 15% lower noise than Macro images. Patient images acquired in Sharp mode demonstrated better delineation of fine anatomic structures compared with Macro mode images. Phantom studies demonstrated superior resolution and noise properties for the Sharp and UHR modes relative to the standard Macro mode and patient images demonstrated the potential benefit of these scan modes for clinical practice.


Saline-filled breast implants: a Plastic Surgery Educational Foundation multicenter outcomes study.
In 1993, the Plastic Surgery Educational Foundation commissioned the senior author (Cunningham) to design an 11-center retrospective cohort outcomes study to obtain physician- and patient-reported data on saline-filled breast implants. Data were obtained from 504 patients with 995 saline-filled breast implants placed between January 1, 1980 and December 31, 1989, with a mean follow-up of 6 years. Most (93.8 percent) saline-filled breast implants were placed for breast augmentation. Of the 504 patients, 104 (20.6 percent) required reoperation for open capsulotomy or for replacement or removal of a deflated implant. Complications occurred in 22 patients (4.4 percent), with hematoma being most common. Implant deflation occurred in 55 implants (5.5 percent) and affected 51 patients (10.1 percent) but was underreported by chart abstraction alone. Risk factors for implant deflation included underfilling the implant by more than 25 cc (odds ratio 3.3, p = 0.0400), the use of model 1800 saline-filled breast implants (odds ratio 3.1, p = 0.0010), intraluminal antibiotics (odds ratio 2.6, p = 0.0183), and intraluminal steroids (odds ratio 2.4, p = 0.0711). Based on 44 of 55 saline-filled breast implants with known deflation dates, actuarial survival is 95.7 to 98.0 percent at 5 years and 90.2 to 95.2 percent at 10 years (95 percent confidence interval). Significant periprosthetic capsular contracture affected 103 patients (20.4 percent) during follow-up. Risk factors for capsular contracture included omitting intraluminal antibiotics (odds ratio 16.7, p = 0.0001), omitting intraluminal steroids (odds ratio 12.5, p = 0.0001), submammary placement of the saline-filled breast implant (odds ratio 7.8, p = 0.0001), and use of antibiotics in the implant pocket (odds ratio 6.1, p = 0.0001). Overall patient satisfaction with saline-filled breast implants was rated as high by 94.2 percent, and 94.8 percent of patients would choose saline-filled breast implants again. Dissatisfaction with their saline-filled breast implants was more frequent in patients with significant breast firmness (odds ratio 22.9, p = 0.0001), those undergoing prophylactic mastectomy (odds ratio 8.2, p = 0.0005), and those desiring smaller implants (odds ratio 6.9, p = 0.0001). In conclusion, saline-filled breast implants are a safe alternative to silicone gel-filled breast implants and demonstrate a high rate of patient satisfaction. Underfilling of saline-filled breast implants should be avoided because it contributes to deflation. Although intraluminal antibiotics and steroids protect against capsular contracture, they also contribute to saline-filled breast implant deflation. The incidence of capsular contracture is decreased by placing the saline-filled breast implant in the subpectoral position. Finally, patients should be aware of the possible need for reoperations related to their implants.


Increased BNip3 and decreased mutant p53 in cisplatin-sensitive PDT-resistant HT29 cells.
We have reported previously the isolation of three photodynamic therapy (PDT)-resistant human colon carcinoma HT29 cell lines that show increased expression of the Hsp27 and BNip3 protein and a decreased expression of the mutant p53 protein compared to parental HT29 cells. Since mutant p53 and increased expression of Hsp27 have been associated with resistance to various chemotherapeutic agents, whereas BNip3 is a potent inducer of apoptosis, we were interested in determining whether these PDT-resistant cells were cross-resistant to other cytotoxic agents. We report here that the PDT-resistant HT29 cell lines showed a significant increase in cisplatin sensitivity and an increase in both spontaneous and cisplatin-induced apoptosis compared to parental HT29 cells. In addition, the cisplatin sensitivity of the PDT-resistant HT29 variants and several other clonal variants of HT29 cells correlated with increased BNip3 and decreased mutant p53 protein levels, but not Hsp27 protein levels.


Successful Treatment of a Lichenoid-Like Granulomatous Reaction to Purple Tattoo Pigment With Intralesional Kenalog.
Tattoo reactions can be clinically challenging to diagnose and treat. We present a case of a biopsy-proven granulomatous reaction to purple tattoo ink that clinically mimicked lichen planus. This reaction was successfully treated with one course of intralesional kenalog (ILK), with no recurrence six months after treatment. To our knowledge, this is the first report of a granulomatous tattoo reaction appearing clinically like lichen planus, and one of the few reports of a reaction to purple tattoo pigment. It highlights the importance of biopsying tattoo-related dermatoses prior to treatment in order to confirm the diagnosis. It also illustrates how a minimally invasive technique utilizing ILK to treat a granulomatous tattoo reaction can result in excellent dermatologic, cosmetic, and symptomatic outcomes. Based on this therapeutic success, we believe treatment with ILK injections should be attempted before more invasive modalities such as excision or laser therapy.


The Molecular Profile of Rhadinorhynchus dorsoventrospinosus Amin, Heckmann, and Ha 2011 (Acanthocephala: Rhadinorhynchidae) from Vietnam.
Of the 46 known species of Rhadinorhynchus Lühe, 1911, only 6 species, including Rhadinorhynchus dorsoventrospinosus Amin, Heckmann, and Ha, 2011, have dorsal and ventral, as well as lateral, trunk spines in the posterior field of trunk spines. The other 5 species are Rhadinorhynchus erumei Gupta and Fatima, 1981, Rhadinorhynchus adenati (Golvan and Houin, 1964) Golvan, 1969, Rhadinorhynchus lintoni Cable and Linderoth, 1963, Rhadinorhynchus pacificus Amin, Rubtsova, and Ha, 2019, and Rhadinorhynchus multispinosus Amin, Rubtsova, and Ha, 2019. These 5 species are distinguished from R. dorsoventrospinosus by differences in proboscis hook armature, trunk spine organization, and egg size. The distinction of R. dorsoventrospinosus is further demonstrated by its molecular description. We amplified the 18S and ITS1+5.8S+ITS2 rDNA region and cytochrome c oxidase subunit 1 (COI) gene for this study. Unfortunately, no ITS1+5.8S+ITS2 gene sequences are available for comparison with other species of the genus Rhadinorhynchus. Therefore, phylogenetic trees generated from sequences of the 18S nuclear region and COI gene were analyzed for the phylogenetic position of isolates of R. dorsoventrospinosus. Rhadinorhynchus dorsoventrospinosus has been validated as a species based on comparisons of morphological (original description) and molecular features (this paper). The additional genetic data will be useful as more species are described and as more genetic material becomes available to improve taxon sampling in the genetic analysis.


[Distal femoral periprosthetic fractures: classification and therapy].
Periprosthetic fracture is one of the most serious complication of total knee arthroplasty. In our retrospective clinical study we designed our classification with rules for treatment of those fractures. During the last thirty years we treated 53 distal femoral periprosthetic fractures in our orthopaedic department. In our clinical study we reviewed our group of distal femoral periprosthetic fractures with on the basis of X-ray findings, the treatment method used and treatment outcomes. According to our findings we divided distal femoral periprosthetic fractures into six groups: Type I Nondisplaced fractures, 5.7%; treatment failure rate, 33%. Type II a Fractures with lateral comminution (the most often type of fractures), 37.7%; treatment failure rate, 20%. Type II b Fractures with medial comminution, 7.5%; treatment failure rate, 60%. Type II c Fractures above TKA (the second most often type), 34%; treatment failure rate, 18%. Type II d Comminuted fractures, 5.7%; treatment failure rate, 18%. Type IIIFractures with loosening of TKA, 9.4%; treatment failure rate, 20%. For the treatment of fractures we used various methods according to the type of fracture: Plate osteosynthesis in 32 cases, with failure in seven. Three failures in IIa group due to incorrect osteosynthesis with condylar plate, treated by reosteosteosynthesis with same implant. One in IIb group treated primarily with cement plomb, after second failure treated with revision total knee arthroplasty. Two failures in IIc group, treated by reosteosynthesis with spongioplasty using the same implant. One failure in III group solved with revision TKA. Intramedullary nail in nine cases , with failure in two. One failure in IIb group treated by reosteosynthesis with condylar plate and cement plombage. One in IIc group due to infection, solved with extraction of material and second stage revision TKA. Conservative treatment in three cases,with failure in two. One in I group treated with condylar plate. One in IId group solved with revision TKA. Miniosteosynthesis in three cases, with failure in two.One failure in IIa group treated with condylar plate, one in IIb group treated with intramedullary nail and additional hydroxyapatite plombage. Revision total knee arthroplasty in five cases with no failure. Extraction of TKA, external fixation, and arthrodesis in 1 case with no failure. The rules for treatment of distal femoral periprosthetic fractures are not definite yet. For fractures above TKA is recommended nail osteosynthesis; for fractures at the level of femoral component is preferable to use osteosynthetic material, condylar plate or LCP. Bone grafts, bone cement, and artificial bone are used to augment osteosynthesis in comminuted fractures. Fractures at the site of loosening are indicated for revision TKA. According to our results: Type I: Conservative treatment possible. Osteosynthesis with condylar plate is recommended. Type IIa: Indication for condylar plate osteosynthesis. Type IIb: The most problematic group. Osteosynthesis with condylar plate with augmentation or condylar plate placed from medial side. Type IIc: Plate osteosynthesis possible, intramedullary nail is recommended. Type IId: Osteosynthesis with augmentation is possible in some cases; revision TKA is recommended. Type III: Indication for revision TKA.


A framework for ontology-based question answering with application to parasite immunology.
Large quantities of biomedical data are being produced at a rapid pace for a variety of organisms. With ontologies proliferating, data is increasingly being stored using the RDF data model and queried using RDF based querying languages. While existing systems facilitate the querying in various ways, the scientist must map the question in his or her mind to the interface used by the systems. The field of natural language processing has long investigated the challenges of designing natural language based retrieval systems. Recent efforts seek to bring the ability to pose natural language questions to RDF data querying systems while leveraging the associated ontologies. These analyze the input question and extract triples (subject, relationship, object), if possible, mapping them to RDF triples in the data. However, in the biomedical context, relationships between entities are not always explicit in the question and these are often complex involving many intermediate concepts. We present a new framework, OntoNLQA, for querying RDF data annotated using ontologies which allows posing questions in natural language. OntoNLQA offers five steps in order to answer natural language questions. In comparison to previous systems, OntoNLQA differs in how some of the methods are realized. In particular, it introduces a novel approach for discovering the sophisticated semantic associations that may exist between the key terms of a natural language question, in order to build an intuitive query and retrieve precise answers. We apply this framework to the context of parasite immunology data, leading to a system called AskCuebee that allows parasitologists to pose genomic, proteomic and pathway questions in natural language related to the parasite, Trypanosoma cruzi. We separately evaluate the accuracy of each component of OntoNLQA as implemented in AskCuebee and the accuracy of the whole system. AskCuebee answers 68 % of the questions in a corpus of 125 questions, and 60 % of the questions in a new previously unseen corpus. If we allow simple corrections by the scientists, this proportion increases to 92 %. We introduce a novel framework for question answering and apply it to parasite immunology data. Evaluations of translating the questions to RDF triple queries by combining machine learning, lexical similarity matching with ontology classes, properties and instances for specificity, and discovering associations between them demonstrate that the approach performs well and improves on previous systems. Subsequently, OntoNLQA offers a viable framework for building question answering systems in other biomedical domains.


Obesity-related asthma in children and adolescents.
There is substantial epidemiological and experimental evidence of an obesity-related asthma phenotype. Compared to children of healthy weight, children with obesity are at higher risk of asthma. Children with obesity who have asthma have greater severity and poorer control of their asthma symptoms, more frequent asthma exacerbations, and overall lower asthma-related quality of life than children with asthma who have a healthy weight. In this Review, we examine some of the latest evidence on the characteristics of this phenotype and its main underlying mechanisms, including genetics and genomics, changes in airway mechanics and lung function, sex hormone differences, alterations in immune responses, systemic and airway inflammation, metabolic dysregulation, and modifications in the microbiome. We also review current recommendations for the treatment of these children, including in the management of their asthma, and current evidence for weight loss interventions. We then discuss initial evidence for potential novel therapeutic approaches, such as dietary modifications and supplements, antidiabetic medications, and statins. Finally, we identify knowledge gaps and future directions to improve our understanding of asthma in children with obesity, and to improve outcomes in these susceptible children. We highlight important needs, such as designing paediatric-specific studies, implementing large multicentric trials with standardised interventions and outcomes, and including racial and ethnic groups along with other under-represented populations that are particularly affected by obesity and asthma.


Biofabrication to build the biology-device interface.
The last century witnessed spectacular advances in both microelectronics and biotechnology yet there was little synergy between the two. A challenge to their integration is that biological and electronic systems are constructed using divergent fabrication paradigms. Biology fabricates bottom-up with labile components, while microelectronic devices are fabricated top-down using methods that are 'bio-incompatible'. Biofabrication--the use of biological materials and mechanisms for construction--offers the opportunity to span these fabrication paradigms by providing convergent approaches for building the bio-device interface. Integral to biofabrication are stimuli-responsive materials (e.g. film-forming polysaccharides) that allow directed assembly under near physiological conditions in response to device-imposed signals. Biomolecular engineering, through recombinant technology, allows biological components to be endowed with information for assembly (e.g. encoded in a protein's amino acid sequence). Finally, self-assembly and enzymatic assembly provide the mechanisms for construction over a hierarchy of length scales. Here, we review recent advances in the use of biofabrication to build the bio-device interface. We anticipate that the biofabrication toolbox will expand over the next decade as more researchers enlist the unique construction capabilities of biology. Further, we look forward to observing the application of this toolbox to create devices that can better diagnose disease, detect pathogens and discover drugs. Finally, we expect that biofabrication will enable the effective interfacing of biology with electronics to create implantable devices for personalized and regenerative medicine.


Fourier synthesis image reconstruction by use of one-dimensional position-sensitive detectors.
An improvement of Fourier synthesis optics for hard x-ray imaging is described, and the basic performance of the new optics is confirmed through numerical simulations. The original concept of the Fourier synthesis imager utilizes nonposition-sensitive hard x-ray detectors coupled to individual bigrid modulation collimators. The improved concept employs a one-dimensional position-sensitive detector (such as a CdTe strip detector) instead of the second grid layer of each bigrid modulation collimator. This improves the imaging performance in several respects over the original design. One performance improvement is a two-fold increase in the average transmission, from 1/4 to 1/2. The second merit is that both the sine and cosine components can be derived from a single grid-detector module, and hence the number of imaging modules can be halved. Furthermore, it provides information along the depth direction simultaneously. This in turn enables a three-dimensional imaging hard x-ray microscope for medical diagnostics, incorporating radioactive tracers. A conceptual design of such a microscope is presented, designed to provide a field of view of 4 mm and a spatial resolution of 400 microm.


Consumer acceptance of fresh blueberries in bio-based packages.
Instrumental analyses have shown that non-vented bio-based containers made from poly(lactic acid) (PLA) have the capability to enhance blueberry shelf life as compared with commercial vented petroleum-based clamshell containers. However, consumer preference has not been explored so far. In this study, two sensory evaluations, triangle and paired preference tests, were performed after storing fruit in both containers at 3 and 10 degrees C for 7 and 14 days. In addition, physicochemical analyses were performed after each tasting in order to correlate instrumental findings with consumer preference. The results of the triangle test showed the capability of the consumer to differentiate (P < or = 0.001) between blueberries from different packages at both storage temperatures. A consumer preference for flavour, texture, external appearance and overall quality (P < or = 0.001) of blueberries packaged in PLA containers was observed in the paired comparison test. The instrumental analyses showed that blueberries in the PLA packages exhibited a weight loss below the limit for marketable life, a stable soluble solid content and titratable acidity and no fungal growth during storage. Consumers distinguished between blueberries from different packages and preferred those packaged in the PLA containers. The instrumental analyses showed that the usable life of the berries was extended in the PLA containers. A correlation between consumer preference and instrumental evaluations was found.


Cathodoluminescence applied to the study of human glomerulonephritis.
The cathodoluminescence (CL) emission of fluorescent species submitted to electron beam irradiation in a scanning electron microscope may be used to reveal the localisation of the emitter at microscopic level. This technique has been applied to the study of human renal biopsies with membraneous glomerulonephritis. Cryosections of biopsies were stained with specific antibody, labelled either by fluorescein or by rhodamine. Rhodamine exhibited a stronger luminescence and a greater resistance to the 'beam effect' than fluorescein. We obtained CL panchromatic pictures of sections labelled with rhodamine at enlargements up to X15 000, without noticeable quenching of emission.


Focal activities and re-entrant propagations as mechanisms of gastric tachyarrhythmias.
Gastric arrhythmias occur in humans and experimental animals either spontaneously or induced by drugs or diseases. However, there is no information regarding the origin or the propagation patterns of the slow waves that underlie such arrhythmias. To elucidate this, simultaneous recordings were made on the antrum and the distal corpus during tachygastrias in open abdominal anesthetized dogs using a 240 extracellular electrode assembly. After the recordings, the signals were analyzed, and the origin and path of slow wave propagations were reconstructed. Several types of arrhythmias could be distinguished, including (1) premature slow waves (25% of the arrhythmias), (2) single aberrant slow waves (4%), (3) bursts (18%), (4) regular tachygastria (11%), and (5) irregular tachygastria (10%). During regular tachygastria, rapid, regular slow waves emerged from the distal antrum or the greater curvature, whereas, during irregular tachygastria, numerous variations occurred in the direction of propagation, conduction blocks, focal activity, and re-entry. In 12 cases, the arrhythmia was initiated in the recorded area. In each case, after a normal propagating slow wave, a local premature slow wave occurred in the antrum. These premature slow waves propagated in various directions, often describing a single or a double loop that re-entered several times, thereby initiating additional slow waves. Gastric arrhythmias resemble those in the heart and share many common features such as focal origin, re-entry, circular propagation, conduction blocks, and fibrillation-like behavior.


Visual disorders associated with cerebral palsy.
School children severely afflicted with cerebral palsy, but unselected in regard to their visual status. have been studied. Of 120 children examined only 24 (20%) had normal eyes or ocular adnexae. Squint was found in 52.5% of the children and significant refractive errors in 50%. There was also a high incidence of strabismic and anisometropic amblyopia (15%) and visual field defects (11%). A number of other ocular abnormalities were found, the majority of which were not amenable to any form of treatment. Early identification of treatable ocular defects and their treatment along conventional lines is emphasised. It is also important to identify untreatable defects that may have a bearing on the child's education. These children need all the help available, and visual function should be at its best. A diagnosis of cerebral palsy has usually been made by the time such a child reaches 18 months of age. In view of the high incidence of ocular defects a full ophthalmological assessment should be part of the routine assessment of the child.


Older and Newer Strategies for the Pharmacological Management of Agitation in Patients with Bipolar Disorder or Schizophrenia.
The management of acute agitation in patients with bipolar disorder or schizophrenia is a multifaceted and dynamic task, which presents unique and complex challenges to healthcare providers. To ascertain and describe which medications are best to use in patients with agitation, affected by bipolar disorder or schizophrenia. Selective review of current literature and guidelines referred to the treatment of agitation in individuals affected with bipolar disorder or schizophrenia Results: When possible, the pharmacologic management of agitation should be preceded by a in-depth evaluation of the possible causes of the agitation. The use for of first and second-generation antipsychotic medications, of benzodiazepines and of the newer inhaled antipsychotic loxapine, is reviewed and commented. The mainstay of medication treatment of acute agitation should be based on a thotough assessment cause. If agitation is due to delirium or to another physial condition, an attempt to address the underlying causes should be always considered. When agitation is primarily due to schizophrenia or bipolar disorder, antipsychotics and/or benzodiazepines are usually the mainstay of treatment. Newer inhaled formulation of loxapine has shown ability to rapidly reduce the agitation in mild to moderate patients with schizophrenia or bipolar disorder, with a decrease in agitation that was evident since the first assessment, 10 minutes after the first dose.


Cation ordering and flexibility of the BO₄²⁻ tetrahedra in incommensurately modulated CaEu₂(BO₄)₄ (B = Mo, W) scheelites.
The factors mediating cation ordering in the scheelite-based molybdates and tungstates are discussed on the basis of the incommensurately modulated crystal structures of the CaEu2(BO4)4 (B = Mo, W) red phosphors solved from high-resolution synchrotron powder X-ray diffraction data. Monoclinic CaEu2(WO4)4 adopts a (3 + 1)-dimensionally modulated structure [superspace group I2/b(αβ0)00, a = 5.238 73(1)Å, b = 5.266 35(1) Å, c = 11.463 19(9) Å, γ = 91.1511(2)°, q = 0.56153(6)a* + 0.7708(9)b*, R(F) = 0.050, R(P) = 0.069], whereas tetragonal CaEu2(MoO4)4 is (3 + 2)-dimensionally modulated [superspace group I4₁/a(αβ0)00(-βα0)00, a = 5.238 672(7) Å, c = 11.548 43(2) Å, q1 = 0.55331(8)a* + 0.82068(9)b*, q2 = -0.82068(9)a* + 0.55331(8)b*, R(F) = 0.061, R(P) = 0.082]. In both cases the modulation arises from the ordering of the Ca/Eu cations and the cation vacancies at the A-sublattice of the parent scheelite ABO4 structure. The cation ordering is incomplete and better described with harmonic rather than with steplike occupational modulation functions. The structures respond to the variation of the effective charge and cation size at the A-position through the flexible geometry of the MoO4(2-) and WO4(2-) tetrahedra demonstrating an alternation of stretching the B-O bond lengths and bending the O-B-O bond angles. The tendency towards A-site cation ordering in scheelites is rationalized using the difference in ionic radii and concentration of the A-site vacancies as parameters and presented in the form of a structure map.


Clinical teaching performance improvement of faculty in residency training: A prospective cohort study.
The purpose of this study is to investigate how aspects of a teaching performance evaluation system may affect faculty's teaching performance improvement as perceived by residents over time. Prospective multicenter cohort study conducted in The Netherlands between 1 September 2008 and 1 February 2013. Nine hundred and one residents and 1068 faculty of 65 teaching programs in 16 hospitals were invited to annually (self-) evaluate teaching performance using the validated, specialty-specific System for Evaluation of Teaching Qualities (SETQ). We used multivariable adjusted generalized estimating equations to analyze the effects of (i) residents' numerical feedback, (ii) narrative feedback, and (iii) faculty's participation in self-evaluation on residents' perception of faculty's teaching performance improvement. The average response rate over three years was 69% for faculty and 81% for residents. Higher numerical feedback scores were associated with residents rating faculty as having improved their teaching performance one year following the first measurement (regression coefficient, b: 0.077; 95% CI: 0.002-0.151; p = 0.045), but not after the second wave of receiving feedback and evaluating improvement. Receiving more suggestions for improvement was associated with improved teaching performance in subsequent years. Evaluation systems on clinical teaching performance appear helpful in enhancing teaching performance in residency training programs. High performing teachers also appear to improve in the perception of the residents.


Achilles tendinitis in running athletes.
Achilles tendinitis is an injury that commonly affects athletes in the running and jumping sports. It results from repetitive eccentric load-induced microtrauma that stresses the peritendinous structures causing inflammation. Achilles tendinitis may be classified histologically as peritendinitis, tendinosis, or partial tendon rupture. Training errors are frequently responsible for the onset of Achilles tendinitis. These include excessive running mileage and training intensity, hill running, running on hard or uneven surfaces, and wearing poorly designed running shoes. Biomechanical abnormalities that predispose to Achilles tendinitis include gastrocnemius-soleus muscle weakness or inflexibility and hindfoot malalignment with foot hyperpronation. The initial treatment should be conservative with relative rest, gastrocnemius-soleus rehabilitation, cryotherapy, heel lifts, nonsteroidal anti-inflammatory drugs, and correction of biomechanical abnormalities. Surgery is recommended only for persons with chronic symptoms who wish to continue running and have not benefited from conservative therapy.


Chronic ramelteon treatment in a mouse model of Alzheimer's disease.
Prior research has reported beneficial effects of melatonin in rodent models of Alzheimer's disease (AD). This study evaluated the effect of ramelteon (Rozerem, a melatonin receptor agonist) on spatial learning & memory and neuropathological markers in a transgenic murine model of AD (the B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mouse strain; hereafter 'AD mice'). Three months of daily ramelteon treatment (~3mg/kg/day), starting at 3 months of age, did not produce an improvement in the cognitive performance of AD mice (water maze). In contrast to wild-type control mice, AD mice did not show any evidence of having learned the location of the escape platform. The cortex and hippocampus of AD mice contained significant quantities of beta-amyloid plaques and PARP-positive (poly ADP ribose polymerase) cells, indicating apoptosis. Six months of ramelteon treatment, starting at 3 months of age, did not produce any change in these neuropathological markers. The ability of long term melatonin treatment to improve cognition and attenuate neuropathology in AD mice did not generalize to this dosage of ramelteon.


Humor modulates the mesolimbic reward centers.
Humor plays an essential role in many facets of human life including psychological, social, and somatic functioning. Recently, neuroimaging has been applied to this critical human attribute, shedding light on the affective, cognitive, and motor networks involved in humor processing. To date, however, researchers have failed to demonstrate the subcortical correlates of the most fundamental feature of humor-reward. In an effort to elucidate the neurobiological substrate that subserves the reward components of humor, we undertook a high-field (3 Tesla) event-related functional MRI study. Here we demonstrate that humor modulates activity in several cortical regions, and we present new evidence that humor engages a network of subcortical regions including the nucleus accumbens, a key component of the mesolimbic dopaminergic reward system. Further, the degree of humor intensity was positively correlated with BOLD signal intensity in these regions. Together, these findings offer new insight into the neural basis of salutary aspects of humor.


Social distance towards schizophrenia in health professionals.
The stigma and prejudice of the public regarding psychiatric disorders are a long-standing social problem. However, health professionals are more likely to have negative attitudes and label people with mental health conditions. This study aimed to investigate how self-rated familiarity and literacy about schizophrenia are related to social distancing towards schizophrenia patients among health professionals in Taiwan. This study used a cross-sectional questionnaire survey and invited respondents to complete the survey either electronically or in a pencil/paper format. Respondents included health professionals in different disciplines and students under medical placements. The survey instrument consists of three parts: sociodemographic information, the 18-item Social Distance Scale for schizophrenia, and the 19-item Schizophrenia Experience and Knowledge Questionnaires. Data were analyzed using linear regression models to explore sociodemographic factors, self-rated familiarity, and literacy total scores about social distance, attitude, and opinions towards schizophrenia. In total, 420 health professionals completed the questionnaire, of which 24.5% were physicians, 36.0% nurses, 6.7% pharmacists, and 28.6% interns. The majority of respondents (n = 360, 85.7%) had contact experience with schizophrenia patients, and approximately 60% rated their experience as a positive impression. Although 62.9% of respondents had received psychiatric education or training, 86% believed that such education/training was insufficient. Moreover, over half of the respondents did not have confidence in their knowledge of schizophrenia. Older age, being married, and having more working experience were associated with high social distance, a negative attitude, and high prejudice. More familiarity with schizophrenia was associated with low social distance, a positive attitude, and less prejudice. A high literacy score was associated with a positive attitude and less prejudice, but no significant correlation was observed with social distance (β ± SE = -0.26 ± 0.14, p = .057). Among respondents who rated their past contact experiences as negative, neither familiarity nor literacy was associated with social distance. High levels of self-rated familiarity and high literacy about schizophrenia were associated with low social distance, a positive attitude, and less prejudice towards schizophrenia among health professionals. Therefore, sufficient education and training are imperative to increase familiarity and knowledge of schizophrenia. Appropriate education could be implemented from different perspectives, including communication skills, resources of social support, and topics to reduce stigma and prejudice.


Immunization of calves against salmonellosis.
Salmonella typhimurium bacterins, containing adequate antigenic mass, protected calves against clinical signs of salmonellosis and death. Protection against salmonellosis was correspondingly reduced when the bacterin was diluted 1:10 and 1:100. A mouse protection test revealed that 17 of 18 (94%) of the S typhimurium-containing bacterin serials produced in 1977 stimulated adequate immunity.


Efficacy of gamma knife surgery for control of peritumoral oedema associated with metastatic brain tumours.
To evaluate the efficacy of gamma knife surgery (GKS) for the control of peritumoral oedema associated with metastatic brain tumours. A retrospective study of 280 consecutive metastatic brain tumours-100 from lung cancers, 100 from breast cancers and 80 from renal-cell carcinomas, associated with peritumoral oedema. The peritumoral oedema index was measured as A*B*C, where A (cm) was the maximum diameter of peritumoral oedema on the axial image, B (cm) was the maximum diameter perpendicular to A, and C (cm) was the maximum diameter on the coronal image. The oedema index of the renal cancer metastases was significantly larger than those of lung and breast cancer metastases (p<0.01). The oedema index of the renal cancer metastases at final imaging was also larger than those of lung (p<0.05) and breast (p<0.01) cancer metastases. The delivered marginal dose (22 Gy or more) was significantly correlated with tumour growth control by multivariate analysis (p = 0.03). Primary site (renal or not renal: p<0.01) and delivered marginal dose (25Gy or more: p = 0.04) were significantly correlated with control of peritumoral oedema by multivariate analysis. Brain oedema around metastatic brain tumours from renal-cell carcinomas was more extensive at the time of GKS and at final imaging compared with lung and breast cancer metastases. This paper suggests that the optimal doses for tumour growth control and brain oedema control may differ for metastatic brain tumours from renal-cell carcinomas.


Diphenhydramine overdose detected early by integration of toxidrome and electrocardiography and treated with venoarterial extracorporeal membrane oxygenation: a case report.
Drug overdose can lead to a range of symptoms, including potentially life-threatening cardiac arrhythmias. However, identifying the specific causative drug upon admission can be challenging in many cases. The toxidrome approach is a method that utilizes toxidromes, which are collections of findings obtained from physical examination and ancillary tests, that may be caused by a specific toxin. In this particular case, a man presented with an unknown drug overdose that caused symptoms indicative of anticholinergic effects and abnormal electrocardiogram (ECG) findings. The ECG revealed an R wave in lead aVR, S waves in leads I and aVL, and wide QRS tachycardia with a Brugada pattern. Shortly after arrival, the patient developed cardiac arrest due to a lethal arrhythmia. Prompt initiation of venoarterial extracorporeal cardiopulmonary membrane oxygenation (VA-ECMO) was performed. Fortunately, the patient achieved full neurological recovery, and the overdosed drug was identified as diphenhydramine. When diagnosing and treating drug overdose caused by an unidentified substance, diphenhydramine toxicity should be considered when an anticholinergic toxidrome is present and a Brugada pattern is observed on the ECG. VA-ECMO demonstrates potential as a viable treatment option when initial interventions prove ineffective.


Effects of barrier perches and density on broiler leg health, fear, and performance.
Deterioration of footpad and hock condition and increased stress are important welfare concerns in high-density broiler production. It has been argued that environmental enrichment may help address these issues. We hypothesized that increasing environmental complexity by providing access to barrier perches across a range of densities should improve footpad and hock health, reduce leg fluctuating asymmetry (FA), and mitigate fear in broilers without compromising bird performance. In this study, 2,088 one-day-old broiler chicks were randomly assigned to one of the following barrier and density treatment combinations over 4 replications: simple barrier, complex barrier, or no barrier (control) and low (8 birds/m(2)), moderate (13 birds/m(2)), or high (18 birds/m(2)) density. In wk 7, data were collected on average tibia width and length, FA of tibia width and tibia length, footpad and hock lesions, tonic immobility, feed conversion, final BW, and mortalities. Broilers at higher densities had more severe footpad (P < 0.0001) and hock lesions (P < 0.0001). Their tibias were also longer (P < 0.0001) and less symmetric in length (P < 0.05). The tibias of birds in complex barrier pens were more symmetric in length compared with controls (P < 0.05). Barrier treatment had no effect on hock lesions, although there was a trend for simple barriers to reduce the severity of footpad lesions compared with the control treatment (P = 0.089). Birds kept in simple barrier pens were more susceptible to tonic immobility induction (P < 0.05). Final BW, feed conversion, and mortalities were neither affected by stocking density nor by barrier inclusion. In conclusion, this study shows a negative effect of high density on broiler footpad health and FA. Although barrier perches did not appear to reduce fearfulness, the improvement in footpad health suggests that simple barriers may provide key welfare benefits to broiler chickens.