Modern contraceptive utilization and associated factors among married pastoralist women in Bale eco-region, Bale Zone, South East Ethiopia.
Women who live in remote rural areas encounter different challenges against contraception and often deny the use of modern contraceptive methods. The predictors of modern contraceptive utilization by pastoralist women in the Bale eco-region could be specific and are not well known. Therefore, this study aims to assess modern contraceptive utilization and its determinants among married pastoralist women in Bale eco-region, Oromia regional state, South East Ethiopia. A community-based cross-sectional study was conducted from 20th November 2015 to 30th February 2016. A structured questionnaire was used to interview 549 married pastoralist women who were selected by multistage sampling technique. The data were analyzed by SPSS - 21 software, multivariate logistic regression analysis was used to identify predictors of modern contraceptive use at (P-value <0.05), and odds ratios with 95% confidence interval were used to assess the strength of associations between variables. The current modern contraceptive method use by married pastoralist women was (20.8%). Among the total users, (78.1%) use the injectable method. The common reasons for non-use of modern contraceptive methods includes: religious-opposition (55.9%), desire for more children (28.3%), fear of side effects (25.5%), and husband's opposition (17.5%). Couple discussion (AOR = 4.63, 95%CI: 2.15, 9.98), perceived husband's approval (AOR = 8.00, 95% CI: 3.52, 18.19), discussion with health extension worker (AOR = 5.99, 95% CI: 1.81, 19.85), and perceived cultural acceptability (AOR = 2.10, 95% CI: 1.09, 4.03) were the independent predictors of modern contraceptive use by married pastoralist women in Bale eco-region. The study identified lower modern contraceptive method utilization by pastoralist women, and the majority of the contraceptive users rely on short- acting contraceptive methods. The uncomplimentary perceptions towards religious and cultural acceptability of modern contraceptive method were among the major reasons for lesser utilization of the methods. Family planning programs should be tailored to actively involve pastoralist women, husbands, and religious leaders in pastoralist communities.


A risk score for unfavorable outcome in adults with bacterial meningitis.
To derive and validate a bedside risk score for adverse outcome in adults with bacterial meningitis. We derived a score for the risk for an unfavorable outcome (Glasgow Outcome Scale score 1-4) by performing logistic regression analyses of data from a prospective cohort study (Dutch Meningitis Cohort; N = 696). A key set of independent prognostic variables was selected from 22 potential predictors. A nomogram based on these key variables was constructed to facilitate use in clinical practice. To validate this nomogram, we used data from our randomized controlled trial on adjunctive dexamethasone therapy in adults with bacterial meningitis (European Dexamethasone Study; N = 301). Unfavorable outcome occurred in 237 of 696 episodes (34%) in the Dutch Meningitis Cohort; 143 patients (21%) died. In the analysis, 6 of 22 variables that are routinely available within 1 hour after admission were robust enough for inclusion in the final risk score: age, heart rate, Glasgow Coma Scale score, cranial nerve palsies, a cerebrospinal fluid leukocyte count less than 1,000 cells/mm3, and gram-positive cocci in cerebrospinal fluid Gram's stain. The concordance index for the risk score was 0.84 (95% confidence interval, 0.80-0.87) in the original cohort and 0.81 (95% confidence interval, 0.74-0.87) in the external validation cohort (European Dexamethasone Study). This bedside risk score can be used to identify patients with a high risk for unfavorable outcome in adults with bacterial meningitis within 1 hour after the initial presentation.


Willingness to pay for genetic testing for Alzheimer's disease: a measure of personal utility.
The increased availability of genetic tests for common, complex diseases, such as Alzheimer's disease (AD), raises questions about what people are willing to pay for these services. We studied willingness-to-pay for genetic testing in a study of AD risk assessment that included APOE genotype disclosure among 276 first-degree relatives of persons with AD. Seventy-one percent reported that they would ask for such testing from their doctor if it were covered by health insurance, and 60% would ask for it even if it required self-pay. Forty-one percent were willing to pay more than $100 for testing, and more than half would have been willing to pay for the test out of pocket. Participants who learned that they were APOE ε4 positive and those who had higher education were less likely to want testing if covered by insurance, possibly to avoid discrimination. This is the first report to examine willingness to pay for susceptibility genetic testing in a sample of participants who had actually undergone such testing. These findings reveal that some participants find valuable personal utility in genetic risk information even when such information does not have proven clinical utility.


Impact of enterprise digital transformation on capacity utilization: Evidence from China.
Based on empirical analysis of Chinese listed companies from 2010 to 2018, we demonstrate that enterprise digital transformation has a significant impact on improving capacity utilization. Digital transformation is a significant driving force behind enterprise-specific production and innovation. Furthermore, enterprise innovation and enterprise-specialized production play a mediating role in the impact of enterprise digital transformation on capacity utilization. Based on these baseline findings, heterogenous analysis reveals that the impact of digital transformation on capacity utilization is significant for firms with larger capital scales or poor governance and manufacturing abilities. However, it is less important for enterprises with small- and medium-sized capital scales or with more standardized governance, as well as non-manufacturing (service) enterprises.


The Expression of Perilipin Family Proteins can be used as Diagnostic Markers of Liposarcoma and to Differentiate Subtypes.
Objective: Liposarcoma is a mesenchymal malignant tumor characterized by adipocyte differentiation which is divided into four subtypes with different prognosis. Accurate histopathological diagnosis is essential for precise treatment. Perilipins, including PLIN1, PLIN2, PLIN3, PLIN4, PLIN5, is a family of lipid droplet-associated proteins that participate in lipid metabolism regulation. The role that perilipins play in sarcomas is not clear. This study aims to assess perilipins expression in subtypes of liposarcoma and various non-lipomatous sarcomas. Methods: A large set of 245 soft tissue sarcoma paraffin-embedded samples including 66 liposarcomas and 179 non-lipomatous sarcomas were collected for tissue microarray and immunohistochemistry to assess perilipins expression. Results: PLIN1 expression was shown in most liposarcomas (41/66) and was absent in non-lipomatous sarcomas (0/179). PLIN4 expression was shown in some liposarcomas (21/66) and was almost negative in non-lipomatous sarcomas (2/179). PLIN1 and PLIN4 expressions in liposarcoma were higher (both P<0.001) than those in non-lipomatous sarcoma. Both PLIN1 and PLIN4 also had a significant difference in liposarcoma subtypes (both P<0.001). PLIN2, PLIN3 and PLIN5 were widely expressed in liposarcomas, rhabdomyosarcomas, leiomyosarcomas, dermatofibrosarcoma protuberans, undifferentiated sarcomas, fibrosarcomas, Ewing's sarcomas and epithelioid sarcomas. PLIN2, PLIN3 and PLIN5 expressions were significantly different among non-lipomatous sarcoma (all P<0.01). Except for PLIN3, the expression of the other four perilipin members in liposarcoma was pairwise related. Conclusions: PLIN1 and PLIN4 can be used as diagnostic markers of liposarcoma and to differentiate liposarcoma subtypes. The combined application of whole perilipin family immunohistochemistry may help to distinguish differently differentiated sarcomas.


Surgical treatment of cervical spondylosis in patients 80 years of age and older-A retrospective observational study.
The older adult population in developed countries is rapidly increasing, as is the number of older adults with cervical spondylosis. Previous studies on the surgical outcomes of older adults with cervical spondylosis have reported contradictory results. This study aimed to compare the surgical outcomes in adults with cervical spondylosis who were <80 and ≥80 years old. We retrospectively investigated data from adults who underwent surgical treatment for cervical spondylosis between 2006 and 2016. The clinical outcomes and postoperative complications of patients who were <80 years old were compared to those of patients who were ≥80 years old. Of the 108 patients included in the study, 14 (13.0%) were ≥80 years old. The preoperative neurosurgical cervical spine score was significantly different between patients who were <80 (9.1 ± 2.4) and ≥80 (6.1 ± 2.1) years old (p < .001). The recovery rate was 58.2 ± 30.0% and 41.3 ± 24.7% in patients who were <80 and ≥80 years old, respectively (p = .05). However, the number of recovery points scored was 2.8 ± 2.0 and 3.4 ± 2.3 in patients who were <80 and ≥80 years old, respectively, which was not significantly different. Although 12 patients had medical comorbidities, they had no surgical complications. This study clarifies the benefits of surgical treatment for older adults with cervical spondylosis. Generally, older adults have lower recovery rates and are unlikely to experience full recovery; however, surgery for cervical spondylosis appears to improve patients' quality of life.


Detection of methadone and buprenorphine in urine samples from inmates of German prisons.
The use of non-prescribed opioid substitution drugs is a serious public health problem, involving general population as well as vulnerable populations such as prisoners. The estimation of the prevalence of opioid substitution drug misuse in prisoners is crucial to suggest strategies to contrast this phenomenon and reduce the associated morbidity and mortality. The present study aimed to provide an objective estimation of the prevalence of illicit use of methadone and buprenorphine in two German prisons. Urine samples were collected from inmates of Freiburg and Offenburg prisons at random times and tested for the detection of methadone, buprenorphine and their metabolites. Analyses were performed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. In total 678 inmates participated in this study. The participation rate was about 60% of all permanent inmates. Of the 675 samples suitable for the analysis, 70 samples (10.4%) tested positive for methadone, 70 samples (10.4%) for buprenorphine, and 4 samples (0.6%) for both drugs. At least 100 samples (14.8%) were not associated with reported prescribed-opioid substitution treatment (OST). Buprenorphine was the most common illicitly used drug. In one of the prisons, buprenorphine was brought in from the outside. The present cross-sectional experimental study was able to provide reliable information regarding the illicit use of opioid substitution drugs in prisons.


Structural and mutational analyses of the receptor binding domain of botulinum D/C mosaic neurotoxin: insight into the ganglioside binding mechanism.
Clostridium botulinum type D strain OFD05, which produces the D/C mosaic neurotoxin, was isolated from cattle killed by the recent botulism outbreak in Japan. The D/C mosaic neurotoxin is the most toxic of the botulinum neurotoxins (BoNT) characterized to date. Here, we determined the crystal structure of the receptor binding domain of BoNT from strain OFD05 in complex with 3'-sialyllactose at a resolution of 3.0Å. In the structure, an electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. Alanine site-directed mutagenesis showed the significant contribution of the residues surrounding the cleft to ganglioside recognition. In addition, a loop adjoining the cleft also plays an important role in ganglioside recognition. In contrast, little effect was observed when the residues located around the surface previously identified as the protein receptor binding site in other BoNTs were substituted. The results of cell binding analysis of the mutants were significantly correlated with the ganglioside binding properties. Based on these observations, a cell binding mechanism of BoNT from strain OFD05 is proposed, which involves cooperative contribution of two ganglioside binding sites.


Copper-catalyzed propargylation of diborylmethane.
A Cu/PPh3-catalyzed propargylic substitution reaction of diborylmethane is reported. Different substituted propargyl electrophiles can be employed in this reaction, and various synthetic valuable functional groups can be tolerated. Di-deuterated diborylmethane can also be used under these conditions and generates α-deuterated alkylboronic esters in good yield.


Obesity as an Effect Modifier in Sleep-Disordered Breathing and Postcardiac Surgery Atrial Fibrillation.
Because the interrelationships of objectively ascertained sleep-disordered breathing (SDB), postcardiac surgery atrial fibrillation (PCSAF), and obesity remain unclear, we aimed to further investigate the interrelationships in a clinic-based cohort. Patients with polysomnography and cardiac surgery (coronary artery bypass surgery and/or valvular surgery) within 3 years, from January 2009 to January 2014, were identified, excluding those with preexisting atrial fibrillation. Logistic models were used to determine the association of SDB (apnea hypopnea index [AHI] per 5-unit increase) and secondary predictors (central sleep apnea [CSA] [central apnea index ≥ 5] and oxygen desaturation index [ODI]) with PCSAF. Models were adjusted for age, sex, race, BMI, and hypertension. Statistical interaction and stratification by median BMI was performed. ORs and 95% CIs are presented. There were 190 patients who comprised the analytic sample (mean age, 60.6 ± 11.4 years; 36.1% women; 80% white; BMI, 33.3 ± 7.5 kg/m2; 93.2% had an AHI ≥ 5; 30% had PCSAF). Unlike unadjusted analyses (OR, 1.06; 95% CI, 1.01-1.1), in the adjusted model, increasing AHI was not significantly associated with increased odds of PCSAF (OR, 1.04; 95% CI, 0.98-1.1). Neither CSA nor ODI was associated with PCSAF. A significant interaction with median BMI was noted (P = .015). Effect modification by median BMI was observed; those with a higher BMI > 32 kg/m2 had 15% increased odds of PCSAF (OR, 1.15; 95% CI, 1.05-1.26; P < .003). SDB was significantly associated with PCSAF in unadjusted analyses, but not after taking into account obesity; those with both SDB and obesity may represent a vulnerable subgroup to target to reduce PCSAF and its associated morbidity.


Survival costs of reproduction in the blue tit (Parus caeruleus): a role for blood parasites?
One of the central tenets in life-history theory is that there is a trade-off between current and future reproduction (i.e. a cost of reproduction). The mechanism for this cost of reproduction is, however, largely unknown. One hypothesis is that the high workload during reproduction compromises resistance to parasites and that the resulting increase in parasitaemia has negative effects on the prospects of future survival. Although empirical evidence for a negative relationship between reproductive effort and parasite resistance exists, the causal relationships between reproductive effort, parasite resistance and future reproduction are still unclear. We use a path analytical approach to investigate whether a change in parasite resistance (as measured by intensities of infections by the blood parasite Haemoproteus) after manipulation of reproductive effort, translates into altered survival in female blue tits. Our results show a negative relationship between reproductive effort and parasite resistance, although evident only in first-year breeders. Moreover, we found survival costs of reproduction in first-year breeders. These costs were, however, not mediated by the blood parasite studied.


A novel radiation protection drape reduces radiation exposure during fluoroscopy guided electrophysiology procedures.
The purpose of this study was to evaluate a novel disposable lead-free radiation protection drape for decreasing radiation scatter during electrophysiology procedures. In recent years, there has been an exponential increase in the number of electrophysiology (EP) procedures exposing patients, operators and laboratory staff to higher radiation doses. The RADPAD was positioned slightly lateral to the incision site for pectoral device implants and superior to the femoral vein during electrophysiology studies. Each patient served as their own control and dosimetric measurements were obtained at the examiner's elbow and hand. Radiation badge readings for the operator were obtained three months prior to RADPAD use and three months after introduction. Radiation dosimetry was obtained in twenty patients: 7 electrophysiology studies, 6 pacemakers, 5 catheter ablations, and 2 implantable cardioverter-defibrillators. Eleven women and nine men with a mean age of 63 +/- 4 years had an average fluoroscopy time of 2.5 +/- 0.42 minutes per case. Mean dosimetric measurements at the hand were reduced from 141.38 +/- 24.67 to 48.63 +/- 9.02 milliroentgen (mR) per hour using the protective drape (63% reduction; p < 0.0001). Measurements at the elbow were reduced from 78.78 +/- 7.95 mR per hour to 34.50 +/- 4.18 mR per hour using the drape (55% reduction; p < 0.0001). Badge readings for three months prior to drape introduction averaged 2.45 mR per procedure versus 1.54 mR per procedure for 3 months post-initiation (37% reduction). The use of a novel radiation protection surgical drape can significantly reduce scatter radiation exposure to staff and operators during a variety of EP procedures.


Combination therapy versus gemcitabine monotherapy in the treatment of elderly pancreatic cancer: a meta-analysis of randomized controlled trials.
We aimed to compare the efficacy of combination therapy versus gemcitabine monotherapy in the treatment of elderly pancreatic cancer (PC) by using a meta-analysis. Databases were searched to identify relevant clinical trials. Hazard ratios (HRs) were used to estimate overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted by using Comprehensive Meta Analysis software (version 2.0). A total of 3,401 elderly PC patients from six randomized controlled trials were included for analysis. In comparison with gemcitabine alone, combination therapy in elderly PC patients did not significantly improve OS (HR 0.93, 95% CI: 0.82-1.06, p=0.29). Sub-group analysis according to treatment regimens showed that combined chemotherapy significantly improved OS in comparison with gemcitabine alone (HR 0.73, 95% CI: 0.56-0.94, p=0.016), while gemcitabine plus targeted agents did not improve OS (HR 1.02, 95% CI: 0.87-1.19, p=0.83). Additionally, gemcitabine plus nab-paclitaxel significantly improved PFS in elderly PC patients (HR 0.69, 95% CI: 0.52-0.91, p=0.009) in comparison with gemcitabine alone. No publication bias was detected by Begg's and Egger's tests for OS. The findings of this study suggest that combined chemotherapy, but not for gemcitabine plus targeted agents, could be recommended for elderly PC patients due to its survival benefits. Further studies are still needed to assess the treatment tolerance of combination chemotherapy in these patient populations.


Within-subjects assessment of the within-compound associations resulting from intermixed and blocked preexposure schedules.
Nonhungry rats received training consisting of intermixed presentations of a compound flavor and an element of that compound (AX, X, AX, X, . . .), and then a separate block of presentations of another compound (BX, BX, BX, . . .). Stimuli A and B were two odor solutions (almond and vanilla), and stimulus X was a highly concentrated solution of sucrose. After training, a state of hunger was induced in the rats, and their consumption levels of A and B alone were tested. We found higher test consumption of B than of A (Exp. 1). We interpreted these differences as indicating that the B-X association had become stronger than the A-X association as a result of the training. In Experiment 2, we demonstrated that the presence of X during training was necessary for that effect to appear (Exp. 2). These results give support to the recent proposal that within-compound associations are maintained better by blocked than by intermixed preexposure (Rodríguez & Alonso, 2014). We discuss the implications of this difference for explaining the intermixed-blocked perceptual-learning effect.


Dietary intake, food addiction and nutrition knowledge in young people with mental illness.
The aim of this study was to comprehensively assess dietary intake, nutrition knowledge and food addiction in young people with mental illness. This was a three-arm cross-sectional study of 16-25-year-olds attending community mental health services who met criteria for: (i) first-episode psychosis (FEP), (ii) ultra-high risk for psychosis (UHR) or (iii) depression/anxiety. Participants self-completed three validated questionnaires: (i) Australian Eating Survey, (ii) General Nutrition Knowledge Questionnaire-Revised and (iii) Yale Food Addiction Score Questionnaire. Thirty participants (mean age 19.7 ± 2.5 years) completed the study (10 per study arm); 43% of the energy intake was obtained from energy-dense, non-nutritious foods, higher than the recommended upper limit (<15%) and the levels reported in the general population (35%). Mean diet quality score was 33.5 ± 11.8 of 73. Mean food addiction symptom score was 3.3 ± 3.7. Prevalence of food addiction was 37%. Nutrition knowledge was lower in the FEP and UHR participants than the depression/anxiety group (48.2 ± 13.8 and 49.5 ± 8.2 of 88 respectively); however, this difference was not statistically significant. Unhealthy dietary intake was observed in the early stages of mental illness, likely seeding future poor physical health. Further research is needed on the role of food addiction in this population, including effective intervention techniques.


Femtosecond laser photoionization time-of-flight mass spectrometry of nitro-aromatic explosives and explosives related compounds.
The ultrafast laser-induced photoionization and photodissociation processes of the nitroaromatic containing explosive and explosive related compounds (ERCs) nitrobenzene (NB), 1,3-dinitrobenzene (DNB), m-nitrotoluene (MNT), 2,4-dinitrotoluene (DNT), and 2,4,6-trinitrotoluene (TNT) have been investigated at three laser wavelengths and power densities using a time-of-flight mass spectrometer. Examination of the mass spectra of these compounds reveals the enhanced formation of the molecular ion [M(+)] when ultraviolet (332 nm) and visible (495 nm) light is used relative to infrared (795 nm) radiation. In addition, at 795 nm and a power density of 3.5 x 10(14) W/cm(2), the presence of a competition between multiphoton ionization (MPI) and Coulomb explosion (CE) channels is revealed by peak shape analysis, and is thought to be operative under these conditions for all of the molecules investigated.


Transovarial biotransference of etoxazole through a terrestrial trophic web.
Transovarial transport is defined as the passage of chemicals from the maternal body to eggs within the ovaries. Little is known about the effects of transovarial transport on non-target species. This study evaluates etoxazole (a transovarial acaricidal compound) on a terrestrial trophic web consisting of a ubiquitous phytophagous mite, Tetranychus urticae Koch, and three species of predatory mites. Predatory mite females that consumed eggs laid by etoxazole-treated T. urticae also produced infertile eggs. There was a negative relationship between the proportion of etoxazole-treated T. urticae females and the instantaneous rate of predatory mite increase at the population level (r(2) = 0.86). Reduced fertility of etoxazole-treated T. urticae females continued for 18 days following application. Eggs laid by etoxazole-treated T. urticae females remained toxic to predatory mite females for 42 days after treatment. Transovarial transport could lead to magnification in the ecosystem by enhancing both bioavailability and movement of an active ingredient. The potential for enhancement of residual activity by terrestrial organisms and its significance once reaching the food web should be taken into account for new classes of acaricides and insecticides.


A framework for automatic information quality ranking of diabetes websites.
Objective: When searching for particular medical information on the internet the challenge lies in distinguishing the websites that are relevant to the topic, and contain accurate information. In this article, we propose a framework that automatically identifies and ranks diabetes websites according to their relevance and information quality based on the website content. Design: The proposed framework ranks diabetes websites according to their content quality, relevance and evidence based medicine. The framework combines information retrieval techniques with a lexical resource based on Sentiwordnet making it possible to work with biased and untrusted websites while, at the same time, ensuring the content relevance. Measurement: The evaluation measurements used were Pearson-correlation, true positives, false positives and accuracy. We tested the framework with a benchmark data set consisting of 55 websites with varying degrees of information quality problems. Results: The proposed framework gives good results that are comparable with the non-automated information quality measuring approaches in the literature. The correlation between the results of the proposed automated framework and ground-truth is 0.68 on an average with p < 0.001 which is greater than the other proposed automated methods in the literature (r score in average is 0.33).


Electric field induced instability and pattern formation in thin liquid films.
Electrostatic field induced instability, morphology, and patterning of a thin liquid film confined between two electrodes with an air gap are studied on the basis of nonlinear 3D simulations, both for spatially homogeneous and heterogeneous fields. In addition to the spinodal flow resulting from the variation of field because of local thickness changes, a heterogeneous imposed field also moves the liquid from the regions of low field to high field, thus allowing a more precise control of pattern. Hexagonal packing of liquid columns is observed for a spatially homogeneous electric field, which is in accord with the e-field experiments on thin polymer films (Schaffer et al. Nature 2000, 403, 874). For a large liquid volume fraction in the gap, varphi > or = 0.75, the coalescence of columns causes a phase inversion, leading to the formation of air columns or cylindrical holes trapped in the liquid matrix (air-in-liquid dispersion). Locally ordered aligned patterns are formed by imposing a spatial variation of the electrostatic field by using a topographically patterned electrode. For example, multiple rows/lines of liquid columns are formed near the edge of a step-like heterogeneity of the electrode and annular rings of ordered columns or concentric ripples are formed around a heterogeneous circular patch. Simulations predict that the electrode pattern is replicated in the film only when the pattern periodicity, L(p), exceeds the instability length scale on the basis of the minimum interelectrode separation distance, L(p) > or = lambda(m)-d(min). Thus, the formation of secondary structures can be suppressed by employing an electrode with deep grooves and stronger field gradients, which produces almost ideal templating. The number density of the electric field induced patterns can be altered by tuning the mean film thickness (or the volume fraction of liquid in the gap), periodicity and depth (amplitude) of the grooves on the top electrode, and the applied voltage. The implications are in electrostatic lithography, pattern replication in soft materials, and the design and interpretation of thin film experiments involving electric fields.


Lung polymers in Z alpha1-antitrypsin deficiency-related emphysema.
Patients with alpha1-antitrypsin (alpha1-AT) deficiency are at risk of developing early-onset panlobular basal emphysema, which has been attributed to uncontrolled proteolytic activity within the lung. Severe genetic deficiency of alpha1-AT is most commonly due to the Z mutation (342Glu--> Lys), which results in a block in alpha1-AT processing within the endoplasmic reticulum of hepatocytes. The retained alpha1-AT forms inclusions, which are associated with neonatal hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. Our recent studies have shown that the accumulation of alpha1-AT is due to the Z mutation perturbing the structure of alpha1-AT to allow polymer formation, with a unique linkage between the reactive center loop of one alpha1-AT molecule and the A beta-pleated sheet of a second. The detection of loop-sheet polymers and other conformations of alpha1-AT in the lungs of patients with emphysema has been technically difficult. We show here that transverse urea-gradient-gel (TUG) electrophoresis and Western blot analysis may be used to characterize conformations of alpha1-AT in dilute samples of bronchoalveolar lavage fluid (BALF). This technique was used to demonstrate loop-sheet polymers in the lungs of patients with Z alpha1-AT-deficiency-related emphysema. Polymers were the predominant conformational form of alpha1-AT in BALF from the lungs of two of five Z homozygotes with emphysema, but were not detectable in any of 13 MM, MS, or MZ alpha1-AT controls. Because alpha1-AT loop-sheet polymers are inactive as proteinase inhibitors, this novel conformational transition will further reduce the levels of functional proteinase inhibitor in the lungs of the Z alpha1-AT homozygote, and so exacerbate tissue damage.


The efficacy and toxicity of combination therapy in rheumatoid arthritis. A meta-analysis.
To evaluate the efficacy and toxicity of combination therapy, compared with single second-line drug therapy, in rheumatoid arthritis. This study was a meta-analysis of published trials that evaluated combinations of full-dose second-line drugs and compared them with single second-line drugs at full dose. Using a random effects model, we summarized the difference between improvement with combination therapy and improvement with single-drug therapy. Five trials that met inclusion criteria, which contained 749 entering patients and 516 completing patients, were identified. The mean +/- SEM difference in improvement in tender joint count between combination and single-drug therapy at end of trial (24-52 weeks) was 2.4 +/- 0.7 joints (out of 60) (P < 0.001). At end of trial the difference between therapies in swollen joint counts was 1.0 +/- 1.2 joints (P = 0.42). The difference in grip strength improvement was 3.7 +/- 4.3 mm Hg (P = 0.40), and for erythrocyte sedimentation rate it was 3.4 +/- 3.1 mm/hour (P = 0.27). In general, the differences in efficacy between combination and single-drug therapy were clinically marginal. Nine percent more combination therapy-treated patients experienced side effect-related discontinuation of therapy than patients receiving single-drug therapy (P = 0.008). Combination therapy, as it has been used in recent clinical trials, does not offer a substantial improvement in efficacy, but does have higher toxicity than single drug therapy. These combination therapy regimens are not recommended for widespread use. Other more aggressive regimens with additional drugs or higher drug doses than have been studied might be more efficacious, but with an even higher rate of toxicity.


Modelling how plant cell-cycle progression leads to cell size regulation.
Populations of cells typically maintain a consistent size, despite cell division rarely being precisely symmetrical. Therefore, cells must possess a mechanism of "size control", whereby the cell volume at birth affects cell-cycle progression. While size control mechanisms have been elucidated in a number of other organisms, it is not yet clear how this mechanism functions in plants. Here, we present a mathematical model of the key interactions in the plant cell cycle. Model simulations reveal that the network of interactions exhibits limit-cycle solutions, with biological switches underpinning both the G1/S and G2/M cell-cycle transitions. Embedding this network model within growing cells, we test hypotheses as to how cell-cycle progression can depend on cell size. We investigate two different mechanisms at both the G1/S and G2/M transitions: (i) differential expression of cell-cycle activator and inhibitor proteins (with synthesis of inhibitor proteins being independent of cell size), and (ii) equal inheritance of inhibitor proteins after cell division. The model demonstrates that both these mechanisms can lead to larger daughter cells progressing through the cell cycle more rapidly, and can thus contribute to cell-size control. To test how these features enable size homeostasis over multiple generations, we then simulated these mechanisms in a cell-population model with multiple rounds of cell division. These simulations suggested that integration of size-control mechanisms at both G1/S and G2/M provides long-term cell-size homeostasis. We concluded that while both size independence and equal inheritance of inhibitor proteins can reduce variations in cell size across individual cell-cycle phases, combining size-control mechanisms at both G1/S and G2/M is essential to maintain size homeostasis over multiple generations. Thus, our study reveals how features of the cell-cycle network enable cell-cycle progression to depend on cell size, and provides a mechanistic understanding of how plant cell populations maintain consistent size over generations.


Kindlin-1 contributes to EGF-induced re-epithelialization in skin wound healing.
The commercial use of epidermal growth factor (EGF) is extensive and has been shown to be effective for skin wound healing in clinical practice. There is evidence to indicate that the topical administration of EGF significantly accelerates re-epithelialization by promoting keratinocyte mitogenesis and migration following acute injury; however, the mechanisms involved remain to be elucidated. Thus, in this study, we focused on Kindlin-1, a four-point-one, ezrin, radixin, moesin (FERM)-domain-containing adaptor protein, and report its contribution to EGF-induced re-epithelialization in skin wound healing. In tissue samples, the expression of Kindlin-1 was induced upon EGF treatment compared to that in the natural healing group. In immortalized human keratinocytes (HaCaT cells), we further proved that Kindlin-1 was necessary for mediating EGF-induced activation signals, including integrin β1 activation, focal adhesion kinase (FAK) phosphorylation and actin re-organization, which finally led to enhanced cell proliferation and migration. These results indicate that Kindlin-1 is essential in EGF-induced re-epithelialization in skin wound healing and provide additional rationale for the clinical application of EGF in the treatment of acute wounds.


CSB ablation induced apoptosis is mediated by increased endoplasmic reticulum stress response.
The DNA repair protein Cockayne syndrome group B (CSB) has been recently identified as a promising anticancer target. Suppression, by antisense technology, of this protein causes devastating effects on tumor cells viability, through a massive induction of apoptosis, while being non-toxic to non-transformed cells. To gain insights into the mechanisms underlying the pro-apoptotic effects observed after CSB ablation, global gene expression patterns were determined, to identify genes that were significantly differentially regulated as a function of CSB expression. Our findings revealed that response to endoplasmic reticulum stress and response to unfolded proteins were ranked top amongst the cellular processes affected by CSB suppression. The major components of the endoplasmic reticulum stress-mediated apoptosis pathway, including pro-apoptotic factors downstream of the ATF3-CHOP cascade, were dramatically up-regulated. Altogether our findings add new pieces to the understanding of CSB mechanisms of action and to the molecular basis of CS syndrome.


Changes in biochemical and functional parameters for men during exercise.
Benefits of physical activity are undeniable. The aim of the present research was to determine the effects of physical activity and age on cholesterol and glucose levels in the blood, as well as changes in the functional parameters of the cardiovascular system, during stepwise increases in physical load for men employed in the same place, but with different levels of physical activity. The subjects were 95 military officers who were divided into groups according to the level of physical activity of their occupation, with veloergometry used as physical load. Cholesterol and glucose levels in the blood were taken as biochemical indices. The results showed that occupational physical activity had a positive effect on biochemical and cardiovascular functional parameters before, during, and after the physical load. Only the cardiovascular rate (systolic blood pressure) in older subjects was significantly higher than that of the younger persons; for all other parameters, age had no effect at all.


F-18 FDG uptake in subcutaneous panniculitis-like T-cell lymphoma.
A 41-year-old male presented to an outside institution complaining of a lump under the skin of his right abdomen. CT scan reported ill-defined densities with streaky inflammatory changes in the anterior abdominal wall. Excisional biopsy of the subcutaneous adipose tissues of the right anterior abdominal wall was consistent with subcutaneous panniculitis-like T-cell lymphoma. Flow cytometry demonstrated CD3+ and CD8+ population. On immunohistochemistry, most lymphoid cells were positive for CD3, CD45RO, CD5, and CD8 and negative for CD10, CD43, CD4, CD20, and CD56. The MIB-1 proliferative index was 30%. Bone marrow biopsy revealed no evidence of lymphomatous involvement.


Catalytic Asymmetric Decarboxylative Michael Addition To Construct an All-Carbon Quaternary Center with 3-Alkenyl-oxindoles.
The first highly enantioselective asymmetric decarboxylative addition of β-keto acids with 3-alkenyl-oxindoles bearing an all-carbon quaternary stereocenter have been developed. The relevant products were acquired in 49-98% yields with 88-98% enantioselectivities in the presence of 0.04-1.0 mol % of chiral rhodium catalyst. The comprehensive practicability of this method was proven in the preparation of the key intermediate, which can be easily transformed into analogues of physovenine and physostigmine.


The integrin alpha 6 beta 4 and the biology of carcinoma.
The integrin family of adhesion receptors plays a major role in epithelial organization and function. Moreover, the altered expression and function of specific integrins most likely contributes significantly to carcinoma progression. The integrin alpha 6 beta 4, the focus of this review, is a receptor for several members of the laminin family and is preferentially expressed at the basal surface of most epithelia, where it contributes to basement membrane interactions. Mounting evidence suggests that the alpha 6 beta 4 integrin plays a key role in carcinoma cell biology. Several histopathological studies have established a correlation between alpha 6 beta 4 integrin expression and tumor progression. The importance of alpha 6 beta 4 expression in tumors in underscored by the findings that invading fronts of several carcinomas are enriched in the expression of alpha 6 beta 4 integrin ligands, such as laminin-1 and laminin-5. The participation of the alpha 6 beta 4 integrin in invasion is supported further by in vitro functional studies using carcinoma cells that have been transfected with the beta 4 cDNA. The mechanisms by which alpha 6 beta 4 contributes to tumor progression are probably related to its mechanical and signaling properties and are currently under intense study.


Morphological damage induced by Escherichia coli lipopolysaccharide in cultured hepatocytes: localization and binding properties.
Lipopolysaccharides (LPS) from Gram-negative bacteria are considered to be the responsible agents for the induction of endotoxic shock, affecting the liver as a target organ. In this study, the cell morphology and some biochemical properties of 24 h-culture-hepatocyte monolayers treated with Escherichia coli 0111:B4 lipopolysaccharide, were observed. Cell morphology was observed by scanning electron microscopy and immunofluorescence methods. LPS interaction induced an increase in rounded cells with diminished adhesion capacity. As biochemical parameters, albumin synthesis and 2-deoxyglucose uptake were measured. LPS decreased the hexose uptake in a dose-dependent manner. Binding of (14C)LPS to cultured hepatocytes showed that LPS binds to non-specific constituents of the membrane bilayer.


[Effects of electroacupuncture combined with compound Salviae Miltiorrhizae tablet on the expressions of brain derived neurotrophic factor and vascular endothelial growth factor in hippocampus CA1 of chronic cerebral ischemia rats].
To observe the effects of electroacupuncture (EA) combined with Compound Salviae Miltiorrhizae Tablet (CSMT) on the expressions of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in hippocampus CA1 of chronic cerebral ischemia (CCI) rats. Totally 50 Sprague-Dawley rats were randomly divided into the normal control group, the model group, the CSMT group, the EA group, and the EA +CSMT groups, 10 in each group. The CCI model was prepared by permanent bilateral common carotid arteries occlusion. One week after modeling, CSMT at 0.75 g/kg was given to rats in the EA + CSMT group and the CSMT group by gastrogavage, once daily, for 5 successive weeks. EA at Baihui (DU20) and Dazhui (DU14) was performed to rats in the EA group and the EA + CSMT group, lasting for 30 min, once daily, for 5 successive weeks. The expressions of BDNF and VEGF in the hippocampus CA1 area were detected by immunohistochemical assay and image analysis. Compared with the normal control group, the number of positively expressed BDNF and VEGF neurons and their expression intensity in the hippocampus CA1 of the model group obviously decreased (P < 0.01). Compared with the model group, the number of positively expressed BDNF and VEGF neurons and their expression intensity in the hippocampus CA1 of the CSMT group, the EA group, and the EA + CSMT groups obviously increased (P < 0.01, P < 0.05). The number of positively expressed BDNF and VEGF neurons and their expression intensity were obviously higher in the EA + CSMT group than those of the CSMT group and the EA group (P < 0.01). EA combined with CSMT could significantly increase the expressions of BDNF and VEGF in the hippocampus CA1 of CCl rats. Besides, their effects were significantly higher than those of the CSMT group or the EA group.


Non-communicable diseases in the Western Area District, Sierra Leone, before and during the Ebola outbreak.
Setting: Twenty-seven peripheral health units, five secondary hospitals and one tertiary hospital, Western Area District, Sierra Leone. Objectives: To describe reporting systems, monthly attendances and facility-based patterns of six non-communicable diseases (NCDs) in the pre-Ebola and Ebola virus disease outbreak periods. Design: A cross-sectional study using programme data. Results: Reporting was 89% complete on the six selected NCDs pre-Ebola and 86% during the Ebola outbreak (P < 0.01). Overall, marked declining trends in NCDs were reported during the Ebola period, with a monthly mean of 342 cases pre-Ebola and 164 during the Ebola outbreak. The monthly mean number of cases per disease in the pre-Ebola and Ebola outbreak periods was respectively 228 vs. 85 for hypertension, 43 vs. 27 for cardiovascular diseases, 36 vs. 18 for diabetes and 25 vs. 29 for peptic ulcer disease; this last condition increased during the outbreak. There were higher proportions of NCDs among females during the Ebola outbreak compared with the pre-Ebola period. Except for peptic ulcer disease, the number of patients with NCDs declined by 25% in peripheral health units, 91% in the secondary hospitals and 70% in the tertiary hospital between the pre-Ebola and the Ebola outbreak periods. Conclusion: Comprehensive reporting of NCDs was suboptimal, and declined during the Ebola epidemic. There were decreases in reported attendances for NCDs between the pre-Ebola and the Ebola outbreak periods, which were even more marked in the hospitals. This study has important policy implications.


Corticosteroids as effectors of lipid polymorphism of dielaidoylglycerophosphoethanolamine. A study using 31P NMR and differential scanning calorimetry.
The influence of corticosteroids on the lipid polymorphism of dielaidoylglycerophosphoethanolamine was studied by 31P NMR spectroscopy and differential scanning calorimetry. Both techniques evidenced two transitions in the pure lipid samples. The first one corresponded to the gel----liquid crystalline phase transition. It occurred at a temperature of 38.9 degrees C, as measured by differential scanning calorimetry and at 35-40 degrees C as detected by 31P NMR. The second transition corresponded to the bilayer----hexagonal HII phase transition. It occurred at 64.2 degrees C as measured by differential scanning calorimetry and at 60 degrees C as detected by NMR. Addition of corticosteroids led to different specific effects on the bilayer----hexagonal HII phase transition, according to their chemical structure. These effects appear to be the result of low amounts of incorporated steroids, according to binding studies (partition coefficient values range between 5 and 54). The presence of a conjugated 3-keto group in the steroid molecule (progesterone) promoted a downward shift in the bilayer----hexagonal HII phase transition temperature by about 6 -7 degrees C as compared to the 3 beta-OH-bearing compound (pregnenolone), which did not exhibit any appreciable effect. No change in the delta H of transition could be measured. The presence of the 21-OH group (like in deoxycorticosterone) induced the formation of a structure, characterized by an isotropic lineshape of the 31P NMR spectrum at temperatures where the 'hexagonal' type of lineshape is present, without steroid. The transition from the bilayer to this other structure occurred at a slightly higher temperature than the bilayer----hexagonal HII phase transition. It corresponded to a peak in differential scanning calorimetry scans with a delta H of 2.1 kJ X mol-1. The presence of the 17 beta-OH group as present in 17 beta-OH-progesterone and 11-deoxycortisol suppressed the two former effects. These compounds had no influence on the bilayer----hexagonal HII phase HII phase transition. The additional presence of the 11 beta-OH group like in corticosterone and cortisol, evoked a stabilization of the bilayer organization as the bilayer----hexagonal HII phase transition temperature is shifted upward by about 10 degrees C. This was accompanied by a decrease of the delta H to 0.8 kJ X mol-1. Besides this, the corticosteroids did not affect to a large extent the gel----liquid crystalline phase transition: a general slight downward shift of the transition temperature and a small broadening of the transition were observed without significant change in the delta H.(ABSTRACT TRUNCATED AT 400 WORDS)


[The corneal wound healing and the extracellular matrix].
The cornea is the first refractive element of the eye. The transparency of the cornea results from the regularly arranged collagen fibrils, forming lamellar structure and the leucin rich proteoglycans, which make interactions between the fibrils. The adult cornea consists mainly of fibril-forming collagens. The cornea has less amount of fibril associated and non-fibrillar collagens. The main proteoglycans of the cornea are keratan-sulfate proteoglycans and it also contains dermatan-sulfate proteoglycans. Disorders of the proteoglycan synthesis lead to the disruption of the unique pattern and result in thicker collagen fibrils. The abnormal structure of the extracellular matrix can generate corneal disorders and the loss of corneal transparency. Furthermore, proteoglycans and collagens have an important role in wound healing. In injury the keratocytes produce higher amounts of collagens and proteoglycans mediated by growth factors. Depending on the ratio of the cells and growth factors the extracellular matrix returns to normal or corneal scar tissue develops.


A case of giant skull base chondroma.
Intracranial chondroma is a rare benign tumor. Here, we present the case of a 29-year-old female who was afflicted with left eye blindness and ptosis. Brain computerized tomography and magnetic resonance imaging revealed the presence of a giant calcified mass accompanied by a solid mass in the middle and posterior fossa. A differential diagnosis regarding chordoma, chondrosarcoma, and other chondroid tumors based on radiologic information was inconclusive. The lesion was resected completely under a microscope using a combined pterional and subtemporal approach. The pathologic report confirmed the diagnosis of chondroma. No evidence of neurological worsening was observed. The tumor had a calcified mass with mature hyaline cartilage surrounded by a thick fibrous capsule. We dissected the periphery of the tumor mass and removed it via aspiration. It was readily distinguished from normal brain parenchymal tissue. The large calcified mass at the center of the tumor had relatively high vascularity, and a high-speed drill and various rongeurs were used to remove the tumor.


Design and Control of a Single-Leg Exoskeleton with Gravity Compensation for Children with Unilateral Cerebral Palsy.
Children with cerebral palsy (CP) experience reduced quality of life due to limited mobility and independence. Recent studies have shown that lower-limb exoskeletons (LLEs) have significant potential to improve the walking ability of children with CP. However, the number of prototyped LLEs for children with CP is very limited, while no single-leg exoskeleton (SLE) has been developed specifically for children with CP. This study aims to fill this gap by designing the first size-adjustable SLE for children with CP aged 8 to 12, covering Gross Motor Function Classification System (GMFCS) levels I to IV. The exoskeleton incorporates three active joints at the hip, knee, and ankle, actuated by brushless DC motors and harmonic drive gears. Individuals with CP have higher metabolic consumption than their typically developed (TD) peers, with gravity being a significant contributing factor. To address this, the study designed a model-based gravity-compensator impedance controller for the SLE. A dynamic model of user and exoskeleton interaction based on the Euler-Lagrange formulation and following Denavit-Hartenberg rules was derived and validated in Simscape™ and Simulink® with remarkable precision. Additionally, a novel systematic simplification method was developed to facilitate dynamic modelling. The simulation results demonstrate that the controlled SLE can improve the walking functionality of children with CP, enabling them to follow predefined target trajectories with high accuracy.


Nanoencapsulation for drug delivery.
Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology.


Incident analysis occurrence related to potentially dangerous medicines distributed in teaching hospital.
To analyze the reports of incidents related to potentially hazardous medications distributed at a teaching hospital in the interior of São Paulo. A descriptive, retrospective study with a quantitative approach of data from the analysis of pharmacovigilance notifications that occurred between January 2009 and December 2014, from tables and graphs, showing the absolute/relative frequencies. From 786 reports of pharmacovigilance, 188 were related to potentially hazardous medicines, 36.7% of which were ineffective, 32.44% were technical complaints, 15.95% were adverse reactions, 7.44% were phlebitis, 5.13% were extravasation , 1.06% dispensing error, 0.53% administration error and 0.53% medication error. The professionals who most notified were nurses. The most commonly reported pharmacological groups were drugs with action on the nervous system (35.63%). The analysis showed that there were a significant number of reports and the need to adopt strategies to ensure greater patient safety.


The landscape of fear as an emergent property of heterogeneity: Contrasting patterns of predation risk in grassland ecosystems.
The likelihood of encountering a predator influences prey behavior and spatial distribution such that non-consumptive effects can outweigh the influence of direct predation. Prey species are thought to filter information on perceived predator encounter rates in physical landscapes into a landscape of fear defined by spatially explicit heterogeneity in predation risk. The presence of multiple predators using different hunting strategies further complicates navigation through a landscape of fear and potentially exposes prey to greater risk of predation. The juxtaposition of land cover types likely influences overlap in occurrence of different predators, suggesting that attributes of a landscape of fear result from complexity in the physical landscape. Woody encroachment in grasslands furnishes an example of increasing complexity with the potential to influence predator distributions. We examined the role of vegetation structure on the distribution of two avian predators, Red-tailed Hawk (Buteo jamaicensis) and Northern Harrier (Circus cyaneus), and the vulnerability of a frequent prey species of those predators, Northern Bobwhite (Colinus virginianus). We mapped occurrences of the raptors and kill locations of Northern Bobwhite to examine spatial vulnerability patterns in relation to landscape complexity. We use an offset model to examine spatially explicit habitat use patterns of these predators in the Southern Great Plains of the United States, and monitored vulnerability patterns of their prey species based on kill locations collected during radio telemetry monitoring. Both predator density and predation-specific mortality of Northern Bobwhite increased with vegetation complexity generated by fine-scale interspersion of grassland and woodland. Predation pressure was lower in more homogeneous landscapes where overlap of the two predators was less frequent. Predator overlap created areas of high risk for Northern Bobwhite amounting to 32% of the land area where landscape complexity was high and 7% where complexity was lower. Our study emphasizes the need to evaluate the role of landscape structure on predation dynamics and reveals another threat from woody encroachment in grasslands.


Interactive effects of metals and carbon nanotubes in a microcosm agrosystem.
Agricultural soils are exposed to multiple contaminants through the use of agrochemicals or sewage sludge, introducing metals, nanomaterials and others. Among nanomaterials, carbon nanotubes (CNTs) are known for their large surface area and adsorption capabilities, possibly modifying other element behavior. However, to date, very little is known about the impacts of such interactions in agrosystems. In this study, we aimed at understanding the transfer and toxicity of contaminants (Cd, Pb, Zn and CNTs) in microcosms including native soil bacteria, earthworms and lettuce. After a 6 week exposure, no effect of the addition of CNTs to metal contaminated soils was detected on bacterial concentration or earthworm growth. However, in lettuce, an interactive effect between CNTs and metals was highlighted: in the soil containing the highest metal concentrations the addition of 0.1 mg kg-1 CNTs led to a biomass loss (-22%) and a flavonoid concentration increase (+27%). In parallel, the addition of CNTs led to differential impacts on elemental uptake in lettuce leaves possibly related to the soil organic matter content. For earthworms, the addition of 10 mg kg-1 CNTs resulted in an increased body elemental transfer in the soil with the higher organic matter content (Pb: + 34% and Zn: + 25%).


[Desflurane Anesthesia in a Morbidly Obese Patient with Severe Obstructive Sleep Apnea].
A 33-year-old morbidly obese patient (body mass index = 59.5 kg x m(-2)) with severe obstructive sleep apnea was scheduled to undergo osteosynthesis of right radial, ulnar and femoral fractures under general anesthesia. Awake intubation under conscious sedation using fantanyl and midazolam was performed by the Pentax-AWS Airwayscope. By using desflurane under continuous infusion of remifentanil 0.2-0.5 μg x kg(-1) x min(-1), BIS values were maintained between 40 and 60 during the surgery. Although duration of surgery was long (430 minutes), the times from discontinuation of the anesthetic drug to eye opening and extubation were 82 seconds and 8.5 minutes, respectively. Respiratory depression was minimal during postoperative period. In this case desflurane was safely used in a morbidly obese patient with severe obstructive sleep apnea.


Varenicline and abnormal sleep related events.
To assess adverse drug reaction reports of "abnormal sleep related events" associated with varenicline, a partial agonist to the α4β2 subtype of nicotinic acetylcholine receptors on neurones, indicated for smoking cessation. Twenty-seven reports of "abnormal sleep related events" often associated with abnormal dreams, nightmares, or somnambulism, which are known to be associated with varenicline use, were identified in the World Health Organisation (WHO) Global Individual Case Safety Reports Database. Original anonymous reports were obtained from the four national pharmacovigilance centers that submitted these reports and assessed for reaction description and causality. These 27 reports include 10 of aggressive activity occurring during sleep and seven of other sleep related harmful or potentially harmful activities, such as apparently deliberate self-harm, moving a child or a car, or lighting a stove or a cigarette. Assessment of these 17 reports of aggression or other actual or potential harm showed that nine patients recovered or were recovering on varenicline withdrawal and there were no consistent alternative explanations. Thirteen patients experienced single events, and two had multiple events. Frequency was not stated for the remaining two patients. The descriptions of the reports of aggression during sleep with violent dreaming are similar to those of rapid eye movement sleep behavior disorder and also nonrapid eye movement (NREM) sleep parasomnias in some adults. Patients who experience somnambulism or dreams of a violent nature while taking varenicline should be advised to consult their health providers. Consideration should be given to clarifying the term sleep disorders in varenicline product information and including sleep related harmful and potentially harmful events.


Robotic Assistance System for Cone-Beam Computed Tomography-Guided Percutaneous Needle Placement.
The study aimed to evaluate a new robotic assistance system (RAS) for needle placement in combination with a multi-axis C-arm angiography system for cone-beam computed tomography (CBCT) in a phantom setting. The RAS consisted of a tool holder, dedicated planning software, and a mobile platform with a lightweight robotic arm to enable image-guided needle placement in conjunction with CBCT imaging. A CBCT scan of the phantom was performed to calibrate the robotic arm in the scan volume and to plan the different needle trajectories. The trajectory data were sent to the robot, which then positioned the tool holder along the trajectory. A 19G needle was then manually inserted into the phantom. During the control CBCT scan, the exact needle position was evaluated and any possible deviation from the target lesion measured. In total, 16 needle insertions targeting eight in- and out-of-plane sites were performed. Mean angular deviation from planned trajectory to actual needle trajectory was 1.12°. Mean deviation from target point and actual needle tip position was 2.74 mm, and mean deviation depth from the target lesion to the actual needle tip position was 2.14 mm. Mean time for needle placement was 361 s. Only differences in time required for needle placement between in- and out-of-plane trajectories (337 s vs. 380 s) were statistically significant (p = 0.0214). Using this RAS for image-guided percutaneous needle placement with CBCT was precise and efficient in the phantom setting.


Absence of immunodominant anti-Gag p17 (SL9) responses among Gag CTL-positive, HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele.
According to a number of previous reports, control of HIV replication in humans appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses. During the chronic phase of HIV-1 infection, up to 75% of the HIV-infected individuals who express the histocompatibility leukocyte Ag (HLA)-A*0201 recognize the Gag p17 SLYNTVATL (aa residues 77-85) epitope (SL9). However, the role of the anti-SL9 CD8 CTL in controlling HIV-1 infection remains controversial. In this study we determined whether the pattern of SL9 immunodominance in uninfected, HLA-A*0201 HIV vaccine recipients is similar to that seen in chronically HIV-infected subjects. The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immunoassays, including peptide:MHC tetramer binding, IFN-gamma ELISPOT, and cytokine flow cytometry. Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a detectable anti-SL9 response. These findings strongly suggest that the pattern of SL9 epitope immunodominance previously reported among chronically infected, HLA-A*0201-positive patients is not recapitulated in noninfected recipients of Gag-containing canarypox-based candidate vaccines and may be influenced by the relative immunogenicity of these constructs.


Clinical characteristics of ectopic thyroid in Korea.
Ectopic thyroid is a rare entity and can occur at any location in the midline position. A role for the ectopic thyroid in the pathogenesis of hypothyroidism and nongoitrous cretinism has been emphasized. To assess the clinical characteristics of an ectopic thyroid by analyzing 49 cases reported in Korea. This study was a retrospective review of 19 cases who were diagnosed by thyroid scan at our institutions together with 30 cases reported in the Korean medical literature, found using KoreaMed. Most cases of ectopic thyroid were diagnosed in patients aged between 1 and 29 years; it was more common in females (43 patients). A lingual thyroid was found in 23 patients, a sublingual thyroid in 17 patients, combined type in 7 patients, a prelaryngeal thyroid in 1 patient, and an intratracheal thyroid in 1 patient. Only four cases had the thyroid gland in the normal position. The chief complaints at presentation were palpable mass in 20 patients, growth retardation in 10 patients, and a lump sensation in the throat in 6 patients. Twenty-six of 42 patients (61.9%) had hypothyroidism, and 16 patients (38.1%) had euthyroidism. As for the treatment modalities, 18 of 26 patients with hypothyroidism and 4 of 16 patients with normal thyroid function received thyroid hormone medication; 3 of 26 patients with hypothyroidism and 8 of 16 patients with euthyroidism underwent resection of the ectopic thyroid. Our study suggests that radionuclide thyroid scanning and function testing may be useful not only for the diagnosis of an ectopic thyroid but also before deciding on the therapeutic modality; patients should be followed up to detect changes in thyroid function and malignant transformation.


Modelling the sorption behaviour of perfluoroalkyl carboxylates and perfluoroalkane sulfonates in soils.
A simple parametric model was developed to predict the sorption of perfluoroalkyl substances (PFASs) in soils. Initially, sorption and desorption solid-liquid distribution coefficients (Kd and Kd,des respectively) of eight PFASs (five perfluoroalkyl carboxylates, PFCAs, and three perfluoroalkane sulfonates, PFSAs) in seven soils with organic carbon (OC) content ranging from 1.6 to 41% were quantified using batch experiments. The information obtained helped to fill the gaps in a literature-based database of Kd values of PFASs, which was lacking data on soils with high OC content. The overall dataset finally comprised 435 entries. Normalized sorption coefficients for the soil OC and mineral fraction contents (KOC and KMIN respectively) were deduced for each PFAS by correlating the corresponding Kd values obtained under a wide range of experimental conditions with the fraction of organic carbon (fOC) of the soils. Furthermore, the sorption mechanisms in each phase were shown to depend mainly on PFAS chain length. The dependence of KOC and KMIN values on PFAS chain length defined the basic equations to construct the model for predicting PFAS sorption, applicable to both PFCAs and PFSAs with chain lengths ranging from 3 to 11 fluorinated carbons. The validation of the proposed model confirmed its ability to predict the Kd of PFASs based only on the soil OC and silt+clay contents and PFAS chain length. Therefore, it can be used in the first stages of a risk assessment process aiming at estimating the potential mobility of PFASs in soils after a contamination event. SYNOPSIS: This study develops a new parametric model to predict the sorption of perfluoroalkyl substances (PFASs) in soils.


Partial differential equation models in the socio-economic sciences.
Mathematical models based on partial differential equations (PDEs) have become an integral part of quantitative analysis in most branches of science and engineering, recently expanding also towards biomedicine and socio-economic sciences. The application of PDEs in the latter is a promising field, but widely quite open and leading to a variety of novel mathematical challenges. In this introductory article of the Theme Issue, we will provide an overview of the field and its recent boosting topics. Moreover, we will put the contributions to the Theme Issue in an appropriate perspective.


[Mitoxantrone-cytarabine-etoposide induction therapy in children with acute myeloid leukemia: a single-center study of complications and clinical outcomes].
To investigate the complications and clinical outcome of children with acute myeloid leukemia (AML) undergoing mitoxantrone-cytarabine-etoposide (MAE) induction therapy. A total of 170 children with AML were given MAE induction therapy, and the complications and remission rate were analyzed after treatment. The male/female ratio was 1.33:1 and the mean age was 7.4 years (range 1-15 years). Leukocyte count at diagnosis was 29.52×109/L [range (0.77-351)×109/L]. Of all children, 2 had M0-AML, 24 had M2-AML, 2 had M4-AML, 48 had M5-AML, 3 had M6-AML, 7 had M7-AML, 69 had AML with t(8;21)(q22;q22), and 15 had AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22). The most common complication was infection (158/170, 92.9%). Among these 158 patients, 22 (13.9%) had agranulocytosis with pyrexia (with no definite focus of infection), and 136 (86.1%) had definite focus of infection (including bloodstream infection). Other complications included non-infectious diarrhea, bleeding, and drug-induced hepatitis. Treatment-related mortality was observed in 10 children, among whom 8 had severe infection, 1 had multiple organ failure, and 1 had respiratory failure. Remission rate was evaluated for 156 children and the results showed a complete remission rate of 85.3%, a partial remission rate of 4.5%, and a non-remission rate of 10.3%. Induction therapy with the MAE regimen helps to achieve a good remission rate in children with AML after one course of treatment. Infection is the main complication and a major cause of treatment-related mortality.


One-Step Fabrication of AgNPs Embedded Hybrid Dual Nanofibrous Oral Wound Dressings.
In the dental medical field, an infection of opened oral tissues by bacteria give rise to serious periodontal disease (PD) after trauma or various oral surgery such as third molar extraction, oral implant, and unexpected trauma. However, progress for bioactive improvement, a prevention of oral tissue contamination, has been currently limitation. Therefore, an innovative research is extremely important and needed for immediately inhibition of bacteria. In this study, we designed a biocompatible oral wound dressing as co-electrospun nanofiber to combine gelatin (GE) and polyurethane (PU) containing silver nanoparticle (AgNPs) to enhance antibacterial activity targeting to periodontal bacteria. Prior to an electrospinning (ELSP), AgNPs was directly synthesized by silver nitrate with capping agent within dimethylformamide (DMF) for use as an ELSP solvent. The fabricated products were cross-linked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) followed by characterized via theoretical analysis. In results, AgNPs were not only perfectly synthesized without a reduction agent, but also electrospun nanofiber (EN) containing AgNPs was well fabricated with the modulation of AgNPs levels. Additionally, the presence of AgNPs within the fiber strand was clearly shown. In the antibacterial test, the developed oral wound dressing showed excellent antibacterial activity as increasing content of the AgNPs. All of tests clearly confirmed that our strategy may suggest a useful paradigm as oral wound dressing to prevent of a bacterial infection as means to oral wound dressing of gingiva and periodontal tissues for obviation of periodontitis.


[Alcohol and sudden death: a survey on alcohol-related deaths at tokyo Metropolitan Medical Examiner's Office (1989)].
Seven thousand three hundred seventy-six sudden or violent manner of deaths were inspected or autopsied at Tokyo Metropolitan Medical Examiner's Office in 1989. Out of these victims, 693 (9.4%) victims were regarded as heavy drinkers on the basis of the drinking habits and the autopsy reports and 196 (2.7%) victims without past problem drinking were thought to be drunk at death from the family statements or the blood alcohol analysis. The total 889 (12.1%) alcohol-related cases (autopsy was performed on the 489 cases) were studied from epidemiological and etiological viewpoints. The average age of the alcohol-related victims (male: 811, female: 78) was 52 +/- 11 years. In middle-aged (45-54 years) men, 34% of the all sudden or violent deaths were alcohol-related. About half of the alcohol-related victims were living alone and jobless and they often died at home, particularly in the bed. In the alcohol-related victims, the blood alcohol concentration (BAC) analysis revealed that the average BAC of female was significantly higher than that of male. (2.12 +/- 1.73 mg/ml vs. 1.33 +/- 1.75, P < 0.01). This difference may be associated with sex difference in ethanol metabolism, body composition and drinking habits. Among the major causes of the alcohol-related deaths, alcoholic liver diseases accounted for 226 (25%), gastro-intestinal bleedings for 115 (13%), cardiovascular diseases for 105 (12%) and violent deaths (e.g., acute alcohol intoxication, falls, traffic accidents, suicide) for 329 (37%). By histopathological examination of the liver, about 30% of the alcoholic liver disease cases showed mainly fatty metamorphosis and 48% showed liver cirrhosis. Only 12% of the cirrhotics had either jaundice or ascites, suggesting hepatic failure. Alcoholic cardiomyopathy was suspected in only 11 cases. In conclusion, many people, particularly middle-aged men, lose their lives due to heavy drinking and there are many pathologically unexplainable sudden deaths of alcoholics.


Chest trauma and its impact on the release of vasoactive mediators.
Every year, major chest injury is involved in 56% of deaths in trauma victims. Blunt chest trauma apparently plays a crucial role in trauma-induced death of multiply injured patients. Therefore, the aim of this study was to evaluate the impact of different types of injuries, including lung tissue damage, on the release of various prostanoids. In a prospective study, the release of arachidonic acid (AA) metabolites was estimated in patients suffering blunt chest trauma alone, i.e., single thoracic injury, and in multiple injured patients including blunt chest trauma. The results were compared with those of patients suffering from single long bone fractures of the leg without additional injury. The plasma concentrations of the AA metabolites, prostacyclin, thromboxane, prostaglandin F2 alpha, and prostaglandin M were determined immediately after admission and in hourly and daily intervals thereafter. Despite clearly different injury scores, elevated levels of circulating AA metabolites were found in the plasma in all patients. This study reveals that any trauma increases significantly the release of prostanoids into the peripheral blood without regard to the impact of tissue damage. This phenomenon is, however, most pronounced following lung injury. On the basis of these results we suggest that there is a specific impact of those mediators in blunt chest trauma. The prostanoids apparently are suitable to describe and even to monitor the extent of thoracic trauma, thus giving additional information in some respect to the individual outcome.


Momordin I, an inhibitor of AP-1, suppressed osteoclastogenesis through inhibition of NF-kappaB and AP-1 and also reduced osteoclast activity and survival.
Osteoclasts originating from hematopoietic precursor cells differentiate into multinucleated cells through multiple steps. The essential roles of NF-kappaB and AP-1 in osteoclast differentiation have been clearly demonstrated in numerous studies. c-Fos, a component of AP-1 transcription factor, plays a key role in osteoclast differentiation. Recently, we found a strong inhibitor of AP-1 transcriptional activity, named momordin I, based on the structure of oleanolic acid glycosides and originally isolated from Ampelopsis radix. So, we hypothesized that momordin I might be able to regulate osteoclast formation, activity, and survival. Here, we report the ability of momordin I to suppress osteoclastogenesis in a co-cultured system and a RANKL-induced osteoclast precursor system. Momordin I remarkably inhibited the activation of NF-kappaB as well as AP-1 in RANKL-induced RAW264.7 cells, in which momordin I appeared to target IkappaB degradation and c-Fos expression, respectively, but not MAPK signaling pathways. The ability of momordin I to change the ratio of RANKL and OPG in primary osteoblasts was partially responsible for the reduction of osteoclast formation. Furthermore, pit formation on dentin slices was suppressed by momordin I with stimulating actin ring disruption. Our results also showed that momordin I highly shortened osteoclast lifespan and induced osteoclast apoptosis. In conclusion, the present results demonstrate for the first time that momordin I is a potent inhibitor of osteoclast differentiation via the reduction of NF-kappaB and AP-1, and also suppresses osteoclast function and survival.


Evaluation on scolicidal efficacy of propolis.
Propolis is a resinous material collected by bees from various plants. It has antimicrobial, antioxidative, immunostimulative, and regenerative properties. We determined the scolicidal effect of propolis in different concentrations and various exposure times. Tubes containing Echinococcus granulosus protoscoleces were supplemented with different concentrations of ethyl alcohol extract of propolis. At the end of the incubation times, viability of protoscoleces was assessed by trypan blue exclusion test. We also applied 5 ml of 1 microg/ml propolis intraperitoneally for determination of side effects and mortality rates. We determined that 1 microg/ml concentration of propolis killed all of the protoscoleces at the end of the 3rd minute. In the in vivo part of the study, intraperitoneal application of propolis did not cause any side effects or mortality. We concluded that this natural agent can be used as a potent scolicidal agent after studies which will determine in vivo efficacy and the effects on liver and biliary tree when injected directly into the common bile duct.


Transcranial direct current stimulation (tDCS) relieved itching in a patient with chronic neuropathic pain.
Itching is often called the second modality of nociception besides pain, and affects many chronic pain patients. This case report presents a first note on beneficial effects of transcranial direct current stimulation (tDCS) on itching associated with chronic neuropathic pain in a patient diagnosed with syringomyelia. tDCS is a novel noninvasive neuromodulatory method with promising therapeutic potential in pain and symptom management. The primary mechanism of tDCS is subthreshold modulation of the neuronal resting membrane potential that induces a polarity-dependent modification of N-Methyl-D-aspartate receptor function that plays a role in neuroplasticity. The patient, a 46-year-old white male diagnosed with syringomyelia 2 decades ago, continuously reported weakness in the arms and dyesthesias including pain and itch that fluctuated in severity. Pharmacological treatment with baclofen, duloxetine, and bupropion was partially helpful; however, did not prevent flares of pain and other dysesthesias, including itch. The patient underwent 3 tDCS treatment courses consisting of 20 minutes of tDCS on 5 consecutive days at each course over 13 months. Although there was no change in pain intensity or quality during or after tDCS, the treatment resulted in a reduction in itch to a mild, tolerable intensity that persisted for 3 to 4 months after each course, before returning to the pretreatment level. The patient has agreed to a plan of care that will incorporate neurostimulation every 4 to 6 months, as long as its effectiveness continues. This case provides a rationale for future studies of neuromodulatory treatments for itch, and indicates a potential clinical use of neuromodulation in patients with unrelieved itching.


Utilization of bacteriophages as molecular label.
We proof that nanomaterials can be successfully marked with relatively small amounts of purified bacteriophages acting as a molecular bar code label. Bacteriophages are DNA protected by a proteinous hull. The DNA fraction of the bacteriophages particle offers a nearly unlimited potential to encode information into the label. The information included in the molecular label can be read using PCR driven amplification. We show, how bacteriophage particles are easily applied to label a nanoscaled bulk material e.g., multi walled carbon nanotubes.


Mean arterial pressure: a better marker of stroke in patients with uncontrolled hypertension in rural areas of China.
The purpose of this study was to compare the association of pulse pressure (PP) and mean arterial pressure (MAP) with stroke in uncontrolled hypertensive subjects. A total of 9,901 uncontrolled hypertensive subjects were included in a cross-sectional study in 62 villages of Fuxin county of Liaoning Province, China. Among the 9,901, 406 cases of ischemic stroke and 145 cases of cerebral hemorrhage were identified. Older age, male gender, increased SBP, higher DBP, and history of hyperlipemia were positively associated with both ischemic stroke and cerebral hemorrhage by multivariate logistic regression analysis. However, the odds rations (ORs) of drinking for ischemic stroke and cerebral hemorrhage were 0.407 (95%CI: 0.304-0.544) and 0.595 (95%CI: 0.377-0.940), respectively. An increase of 10 mmHg of MAP had ORs of 1.430 (95%CI: 1.332-1.535) for ischemic stroke and 1.359 (95%CI: 1.220-1.514) for cerebral hemorrhage. The OR of PP (per 10 mmHg increase) for ischemic stroke was 1.085 (95%CI: 1.026-1.148). Subjects with the fourth quartile of PP and MAP had ORs of 1.555 (95%CI: 1.127-2.146) ischemic stroke and 5.127 (95%CI: 3.452-7.616) for cerebral hemorrhage, with the first quartile as the reference group. The OR of the fourth quartile of MAP for cerebral hemorrhage was 5.935 (95%CI: 2.932-12.012). There was no significant association between PP and cerebral hemorrhage. In sensitivity analysis, ORs of standard MAP for ischemic stroke were higher than those of PP in each stratified age subgroup. Increased MAP and PP were significant markers of ischemic stroke and cerebral hemorrhage was only associated with increased MAP. MAP was more closely associated with stroke than PP in patients with uncontrolled hypertension.


Oral anticoagulants vs antiplatelets in cryptogenic stroke with potential cardiac emboli: Meta-analysis.
The best antithrombotic strategy for cryptogenic stroke with potential cardiac emboli is not known. The objective of this study was to conduct a meta-analysis to evaluate the efficacy and safety of oral anticoagulants (OACs) vs. antiplatelet therapies in these patients METHODS: Pubmed, EMBASE, CENTRAL and clinicaltrials.gov were searched from January 1980 to April 2021 to identify trials comparing OACs versus antiplatelet therapies in patients with cryptogenic stroke and potential cardiac emboli (patent foramen ovale, moderate-severe left atrial enlargement, heart failure with reduced ejection fraction). Relative risk (RR) with 95% confidence (CI) was used as a measure of the effect of OACs versus antiplatelet therapies on recurrent ischemic stroke and major bleeding. We computed a random-effect estimate based on the Mantel-Haenszel method for a given outcome. We identified 6 studies derived from 5 trials with 2282 patients. Pooled results from 6 studies showed that compared with antiplatelet therapies, OACs were associated with a lower risk of recurrent ischemic stroke (RR 0.61, 95% CI 0.41 to 0.91, P=0.02). Only 3 studies of cryptogenic stroke with patent foramen ovale reported a major bleeding endpoint and pooled results from random-effects model showed that OACs compared with antiplatelet therapies were associated with a non-significantly increased risk of major bleeding (RR 1.61, 95% CI 0.76 to 3.40, P=0.21). OACs compared with antiplatelet therapies were associated with a reduced recurrent ischemic stroke risk and OACs might be a viable non-procedural alternative in patients with cryptogenic stroke and potential cardiac emboli.


Porphyromonas gingivalis minor fimbriae are required for cell-cell interactions.
Two distinctive types of fimbriae have been identified in Porphyromonas gingivalis. In this report, we demonstrate that minor fimbriae are involved in P. gingivalis autoaggregation and colonization. A mutant with a deficiency in minor fimbriae can bind to a saliva-coated surface but does not form microcolonies as the wild-type strain does.


Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression.
Suicidal behavior has been associated with reduced central serotonergic function. Because selective serotonin reuptake inhibitors (SSRIs) enhance serotonergic function, the authors studied the efficacy of an SSRI, paroxetine, in the prevention of recurrent suicidal behavior. They conducted a 1-year double-blind study comparing paroxetine (40 mg/day) and placebo in 91 patients who had recently attempted suicide for at least a second time. None of the patients had experienced a major depressive episode or had any other major DSM-III-R axis I diagnoses. At least one cluster B personality disorder was present in 74 patients. With adjustment for the number of previous suicide attempts, paroxetine showed significant efficacy in the prevention of recurrent suicidal behavior. Among the patients who had attempted suicide fewer than five times, 12 (36%) in the placebo group (N = 33) and five (17%) in the paroxetine group (N = 30) made a subsequent suicide attempt. Paroxetine was also significantly more effective in patients who met fewer than 15 criteria for cluster B personality disorders than in those who met more than 15 criteria. Overall, paroxetine was not significantly different from placebo in its effect on depressive mood, hopelessness, and anger. However, the data suggest that paroxetine may have some temporary effect in reducing anger. This study indicates that enhancing serotonergic function with an SSRI may reduce suicidal behavior in a subgroup of patients who have attempted suicide more than once but who do not suffer from major depression.


Effects of a Lifestyle Intervention in Routine Care on Short- and Long-Term Maternal Weight Retention and Breastfeeding Behavior-12 Months Follow-up of the Cluster-Randomized GeliS Trial.
Postpartum weight retention (PPWR) is associated with an increased risk for maternal obesity and is discussed to be influenced by breastfeeding. The objective was to evaluate the effect of a lifestyle intervention delivered three times during pregnancy and once in the postpartum period on PPWR and on maternal breastfeeding behavior. In total, 1998 participants of the cluster-randomized "healthy living in pregnancy" (GeliS) trial were followed up until the 12th month postpartum (T2pp). Data were collected using maternity records and questionnaires. Data on breastfeeding behavior were collected at T2pp. At T2pp, mean PPWR was lower in women receiving counseling (IV) compared to the control group (C) (-0.2 ± 4.8 kg vs. 0.6 ± 5.2 kg), but there was no significant evidence of between-group differences (adjusted p = 0.123). In the IV, women lost more weight from delivery until T2pp compared to the C (adjusted p = 0.008) and showed a slightly higher rate of exclusive breastfeeding (IV: 87.4%; C: 84.4%; adjusted p < 0.001). In conclusion, we found evidence for slight improvements of maternal postpartum weight characteristics and the rate of exclusive breastfeeding in women receiving a lifestyle intervention embedded in routine care, although the clinical meaning of these findings is unclear.


Difference in the heat sensitivity of DNA-dependent protein kinase activity among mouse, hamster and human cells.
To examine the heat sensitivity of DNA-dependent protein kinase (DNA-PK) activity in a variety of cultured mouse, hamster and human cell lines. Eight cell lines, which have been routinely used in our laboratory, were examined. Cells were heated at 44.0 +/- 0.05 degrees C and DNA-PK activity was measured by a DNA-pull-down assay followed by gel-electrophoresis. Cellular sensitivity to hyperthermia and/or X-ray was evaluated by a colony formation assay. In mouse FSA1233 and FM3A cells, DNA-PK activity dropped to 15-16% of unheated control after 20 min of heating. In Chinese hamster V79 and CHO-K1 cells, kinase activity did not change appreciably after 20 min treatment but decreased to 60-70 and 22-23% after 40 or 60 min treatment, respectively. However, even after 180 min treatment, DNA-PK activity remained almost intact in human MOLT-4, MKN45 and A7 cells, and decreased only slightly in U937 cells. Hyperthermic radiosensitization was seen even in human cells but, as a trend, it was small compared with rodent cells. The heat sensitivity of DNA-PK was clearly different among mouse, hamster and human cells. The results suggested a possibility that the role of DNA-PK inactivation in hyperthermic radiosensitization might be variable, depending on cells, and would reinforce the warning that the direct extrapolation of data from rodent cells might lead to overestimation of the effectiveness of hyperthermia on human cancer.


Gut microbiota depletion from early adolescence alters adult immunological and neurobehavioral responses in a mouse model of multiple sclerosis.
Emerging evidence indicates that gut microbiota interacts with immune and nervous systems in the host and plays a critical role in the pathogenesis of multiple sclerosis (MS) and many psychiatric disorders such as depression and anxiety. The aim of this study was to explore the influence of gut bacterial depletion from early adolescence on adult immunological and neurobehavioral responses in mice with experimental-autoimmune-encephalomyelitis (EAE). We used an animal model of gut microbiota depletion induced by antibiotics from weaning to adulthood to assess clinical signs, cognitive function and depression-and anxiety-related symptoms in non-EAE and EAE-induced mice. We measured levels of interferon (IFN)-γ, interleukin (IL)-17A and IL-10 in serum, and BDNF, IL-1β and tumor necrosis factor (TNF)-α) in the hippocampus. Antibiotic-treated mice displayed a significant delay in the onset of clinical symptoms of EAE. However, a higher severity of EAE was found between days 19-22 post-immunization in antibiotics-treated mice, while a reduction in the clinical signs of MS was observed at days 24-25 post-immunization. Antibiotic administration decreased IFN-γ and IL-17A levels and increased IL-10 in serum of EAE-induced mice. Antibiotic treatment significantly decreased hippocampal BDNF and enhanced learning and memory impairments in EAE-induced mice. However, no significant changes were found in non-EAE mice. Non-EAE and EAE mice treated with antibiotics exhibited increased anxiety-related behaviors, whereas depression-related symptoms and increased hippocampal TNF-α and IL-1β were only observed in EAE-induced mice treated with antibiotics. This study supports the view that depletion of gut microbiota by antibiotics from weaning profoundly impacts adult immunological and neurobehavioral responses.


Genetic status and timing of a weevil introduction to Santa Cruz Island, Galapagos.
Successful invasive species can overcome or circumvent the potential genetic loss caused by an introduction bottleneck through a rapid population expansion and admixture from multiple introductions. We explore the genetic makeup and the timing of a species introduction to Santa Cruz Island in the Galápagos archipelago. We investigate the presence of processes that can maintain genetic diversity in populations of the broad-nosed weevil Galapaganus howdenae howdenae. Analyses of combined genotypes for 8 microsatellite loci showed evidence of past population size reductions through moment and likelihood-based estimators. No evidence of admixture through multiple introductions was found, but substantial current population sizes (N0 298, 95% credible limits 50-2300), genetic diversity comparable with long-established endemics (Mean number of alleles = 3.875), and lack of genetic structure across the introduced range (F ST = 0.01359) could suggest that foundations are in place for populations to rapidly recover any loss of genetic variability. The time estimates for the introduction into Santa Cruz support an accidental transfer during the colonization period (1832-1959) predating the spurt in human population growth. Our evaluation of the genetic status of G. h. howdenae suggests potential for population growth in addition to our field observations of a concurrent expansion in range and feeding preferences towards protected areas and endemic host plants.


Effect of capsaicin on the rabbit urinary bladder. What is the function of sensory nerves that contain substance P?
The sensory innervation of the rabbit urinary bladder was studied using local application of the specific sensory neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). This agent has its major effect by damaging small diameter unmyelinated sensory nerves. The drug produced a 51% reduction in the bladder content of the neuropeptide substance P. It therefore appears that a substantial proportion of the bladder's content of the peptide is to be found in capsaicin-sensitive sensory nerves. Cystometrograms carried out before and after treatment with capsaicin were similar; this suggests that capsaicin-sensitive sensory nerves may not be of importance in the afferent limb of the micturition reflex. In vitro muscle strip studies demonstrated a small reduction in the sensitivity of the detrusor muscle to electrical stimulation of its intramural nerves. It is possible that in vitro intramural nerve stimulation leads to release of neurotransmitters from sensory as well as motor nerves. It is proposed that small diameter sensory nerves in the bladder wall may have a role in the transmission of the sensation of pain and in the triggering of inflammatory reactions rather than forming the afferent limb of the micturition reflex.


Cryptococcal meningitis causing obstructive hydrocephalus in a patient on fingolimod.
Cryptococcosis is a recognised opportunistic infection in immunocompromised patients. The long-term adverse effect profile of fingolimod, an immunomodulating agent approved for use in multiple sclerosis in 2010, is only just emerging. We report the first case to our knowledge of a patient presenting with obstructive hydrocephalus secondary to cryptococcal meningitis in the setting of fingolimod therapy. Extensive posterior fossa leptomeningeal inflammation with associated cerebellar oedema resulted in effacement of the fourth ventricle and obstructive hydrocephalus requiring urgent ventriculostomy. Induction, consolidative and maintenance antifungal therapy was prescribed and subsequent conversion to a ventriculoperitoneal shunt was successful in relieving the patient's ventriculomegaly. Awareness of these rare, novel and life-threatening complications of fingolimod-associated immunocompromise is critical as the use of such drugs is expected to rise.


Stability limits for the supercooled liquid and superheated crystal of Lennard-Jones particles.
We have studied the limits of stability in the first order liquid-solid phase transition in a Lennard-Jones system by means of the short-time relaxation method and using the bond-orientational order parameter Q6. These limits are compared with the melting line. We have paid special attention to the supercooled liquid, comparing our results with the point where the free energy cost of forming a nucleating droplet goes to zero. We also indirectly estimate the dimension associated to the critical nucleus at the spinodal, expected to be fractal according to mean field theories of nucleation.


Molecular characterization of breast cancer cell lines by clinical immunohistochemical markers.
Breast cancer is the leading cause of cancer mortality in females worldwide. Studies based on gene expression profiles have identified different breast cancer molecular subtypes, such as luminal A and B cells, cancer cells that are estrogen receptor (ER) and/or progesterone receptor (PR) positive, human epidermal growth factor 2 (HER2)-enriched cells, cancer cells that exhibit an overexpression of the oncogene HER2, and triple-negative cells, cancer cells that are negative for ER, PR and HER2 expression. Immunohistochemistry is the most common type of method used for the identification of these molecular subtypes, through the identification of specific cell receptors. The present study aimed to evaluate the ER, PR and HER2 receptor expression in human breast cancer cell lines, and to classify the corresponding molecular subtype comparing two alternative methods. In the present study, a panel of human mammary carcinoma cell lines: BT-20; Hs578T; MCF-7; MCF-7/AZ; MDA-MB-231; MDA-MB-468; SKBR3; and T47D were used. Immunohistochemical and immunocytochemistry assays were used to characterize the breast cancer subtypes of these cell lines according to the expression of ER, PR and HER2 receptors. The results revealed the molecular characterization of this panel of breast cancer cell lines, using the differential expression of classical and clinically used markers in concordance with previous studies. In addition, these data are important for additional in vitro studies of these specific receptors.


A longitudinal study of energy and nitrogen excretion by fasted cockerels.
An experiment was conducted in which the energy and nitrogen voided by cockerels during the final 48 hr of each of 14 72-hr fasts, 28 days apart, were measured. There were 12 Single Comb White Leghorn cockerels of each of two strains aged 150 days at the time of the first excreta collection and 12 birds from each of two meat-type strains aged 268 days at the first collection. Birds that died during the experiment were replaced by similar birds maintained under comparable conditions. Both excreta energy (FE + UE) and excreta nitrogen (FN + UN) varied among time periods and among birds and appeared to be related to metabolic body size. Similar patterns were observed when the FE + UE data were corrected to zero nitrogen balance (FEn + UEn ). There was a significant (P less than .01) quadratic relationship between ambient temperature and FE + UE, FN + UN, and FEn + UEn with higher excreta outputs being associated with either low or high temperatures. Frequently, but not inevitably, higher FE + UE and FN + UN were observed prior to death. The FE + UE was significantly (P less than .01) correlated with FN + UN. In general, the estimated regression coefficient relating energy to nitrogen output was similar to the value, based upon the energy content of chicken urine, used to correct FE + UE to FEn + UEn . However, the analyses indicated that the correction factor may vary among birds or over time and may be related to metabolic body weight. To what extent this variability can be defined and incorporated into metabolic energy assays requires further investigation.