Synthesis, duplex-forming ability, enzymatic stability, and in vitro antisense potency of oligonucleotides including 2'-C,4'-C-ethyleneoxy-bridged thymidine derivatives.
We synthesized thymidine derivatives of 2'-C,4'-C-ethyleneoxy-bridged 2'-deoxyribonucleic acids with an 8'-methyl group ((R)-Me-EoDNA and (S)-Me-EoDNA) and without any substituent (EoDNA). Oligonucleotides including these EoDNAs showed high hybridization abilities with complementary RNA and excellent enzymatic stabilities compared with natural DNA. Moreover, the in vitro antisense potency of oligonucleotides with these EoDNAs and our recently reported methylene-EoDNAs was investigated and compared with that of LNA, which is a practical chemical modification for oligonucleotide-therapeutic agents. The results showed that EoDNAs and methylene-EoDNAs could be promising candidates for antisense technology.


Environmental temperature effects on adipose tissue growth in a hibernator.
Obligate hibernators express circannual patterns of body mass and hibernation, which persist under constant laboratory conditions. Brown adipose tissue (BAT) is important for thermogenesis during arousals from hibernation, whereas white adipose tissue (WAT) serves as energy storage and thermal insulation. The goal of this study was to investigate the effects of environmental temperature on BAT and WAT. We hypothesized that changes to environmental temperature would not influence the pattern of mass gain or BAT and WAT volume in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). To test this, we housed animals at thermoneutral 25°C (warm-housed) or 5°C (cold-housed), with the same photoperiod (12 h light:12 h dark) over an entire year. Throughout the year we measured the volume and water:fat ratio of WAT and BAT using magnetic resonance imaging (MRI). We found no evidence of torpor in the warm-housed animals, indicating that this species might not be an obligate hibernator, as previously assumed. Regardless of ambient temperature, BAT volume increased prior to winter, then decreased in late winter with no change in water:fat ratio. By contrast, both body mass and WAT volume of cold-housed animals declined throughout the winter and recovered after hibernation, but thermoneutral housing produced no circannual pattern in body mass, even though WAT volume declined in late winter. Cold exposure appears to be a primary regulator for WAT but BAT may exhibit an endogenous circannual rhythm in terms of depot volume.


Effects of high-intensity interval training on physical capacities and substrate oxidation rate in obese adolescents.
To investigate the effects of a 3-week weight-management program entailing moderate energy restriction, nutritional education, psychological counseling and three different exercise training (a: low intensity, LI: 40 % V'O2max; b: high intensity, HI: 70 % V'O2max; c: high-intensity interval training, HIIT), on body composition, energy expenditure and fat oxidation rate in obese adolescents. Thirty obese adolescents (age: 15-17 years, BMI: 37.5 kg m-2) participated in this study. Before starting (week 0, W0) and at the end of the weight-management program (week 3, W3), body composition was assessed by an impedancemeter; basal metabolic rate (BMR), energy expenditure and substrate oxidation rate were measured during exercise and post-exercise recovery by indirect calorimetry. At W3, body mass (BM) and fat mass (FM) decreased significantly in all groups, the decreases being significantly greater in the LI than in the HI and HIIT subgroups (BM: -8.4 ± 1.5 vs -6.3 ± 1.9 vs -4.9 ± 1.3 kg and FM: -4.2 ± 1.9 vs -2.8 ± 1.2 vs -2.3 ± 1.4 kg, p < 0.05, respectively). V'O2peak, expressed in relative values, changed significantly only in the HI and HIIT groups by 0.009 ± 0.005 and 0.007 ± 0.004 L kg FFM-1 min-1 (p < 0.05). Furthermore, the HI and HIIT subgroups exhibited a greater absolute rate of fat oxidation between 50 and 70 % V'O2peak at W3. No significant changes were observed at W3 in BMR, energy expenditure during exercise and post-exercise recovery. A 3-week weight-management program induced a greater decrease in BM and FM in the LI than in the HI and HIIT subgroups, and greater increase in V'O2peak and fat oxidation rate in the HI and HIIT than in the LI subgroup.


Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem.
Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo® sublingual tablets (zolpidem tartrate). The model was evaluated by the goodness-of-fit between simulated and observed concentrations and the deviation of key PK parameters (e.g., C max, T max, and AUC). In addition, a sensitivity analysis was conducted to demonstrate the interplay and impact of key modeling parameters on the fraction absorbed via oral mucosa (F a_IO). The OCCAT™ model captured the observed pharmacokinetics for Intermezzo® sublingual tablets (R (2) > 0.9). The predicted deviations (%) for C max, AUC0-inf, AUC0-20 min, and T max were 5.7, 28.0, 11.8, and 28.6%, respectively, indicating good prediction accuracy. The model also estimated ~18% of total drug was absorbed via the IO route. Furthermore, the sensitivity analysis indicated that the F a_IO was not only associated with drug diffusivity and unbound fraction in epithelium tissue (f ut) but also depended on the physicochemical properties of compounds for IO delivery (e.g., solubility and logD pH = 7.4). The novel physiologically based IO absorption OCCAT™ model showed satisfactory performance and will be helpful to guide development of future intraoral formulations.


Accuracy of genome-wide imputation of untyped markers and impacts on statistical power for association studies.
Although high-throughput genotyping arrays have made whole-genome association studies (WGAS) feasible, only a small proportion of SNPs in the human genome are actually surveyed in such studies. In addition, various SNP arrays assay different sets of SNPs, which leads to challenges in comparing results and merging data for meta-analyses. Genome-wide imputation of untyped markers allows us to address these issues in a direct fashion. 384 Caucasian American liver donors were genotyped using Illumina 650Y (Ilmn650Y) arrays, from which we also derived genotypes from the Ilmn317K array. On these data, we compared two imputation methods: MACH and BEAGLE. We imputed 2.5 million HapMap Release22 SNPs, and conducted GWAS on approximately 40,000 liver mRNA expression traits (eQTL analysis). In addition, 200 Caucasian American and 200 African American subjects were genotyped using the Affymetrix 500 K array plus a custom 164 K fill-in chip. We then imputed the HapMap SNPs and quantified the accuracy by randomly masking observed SNPs. MACH and BEAGLE perform similarly with respect to imputation accuracy. The Ilmn650Y results in excellent imputation performance, and it outperforms Affx500K or Ilmn317K sets. For Caucasian Americans, 90% of the HapMap SNPs were imputed at 98% accuracy. As expected, imputation of poorly tagged SNPs (untyped SNPs in weak LD with typed markers) was not as successful. It was more challenging to impute genotypes in the African American population, given (1) shorter LD blocks and (2) admixture with Caucasian populations in this population. To address issue (2), we pooled HapMap CEU and YRI data as an imputation reference set, which greatly improved overall performance. The approximate 40,000 phenotypes scored in these populations provide a path to determine empirically how the power to detect associations is affected by the imputation procedures. That is, at a fixed false discovery rate, the number of cis-eQTL discoveries detected by various methods can be interpreted as their relative statistical power in the GWAS. In this study, we find that imputation offer modest additional power (by 4%) on top of either Ilmn317K or Ilmn650Y, much less than the power gain from Ilmn317K to Ilmn650Y (13%). Current algorithms can accurately impute genotypes for untyped markers, which enables researchers to pool data between studies conducted using different SNP sets. While genotyping itself results in a small error rate (e.g. 0.5%), imputing genotypes is surprisingly accurate. We found that dense marker sets (e.g. Ilmn650Y) outperform sparser ones (e.g. Ilmn317K) in terms of imputation yield and accuracy. We also noticed it was harder to impute genotypes for African American samples, partially due to population admixture, although using a pooled reference boosts performance. Interestingly, GWAS carried out using imputed genotypes only slightly increased power on top of assayed SNPs. The reason is likely due to adding more markers via imputation only results in modest gain in genetic coverage, but worsens the multiple testing penalties. Furthermore, cis-eQTL mapping using dense SNP set derived from imputation achieves great resolution, and locate associate peak closer to causal variants than conventional approach.


[Aspergillus infection of severe burns].
Aspergillus, which has a saprophytic life, is an opportunistic fungus and manifests his pathogenicity when a weakened state of the host facilitates its development. The conditions are particularly favorable in severely burned patients like the 54-year-old woman presented here. The criteria of pathogenicity of this opportunistic fungus, the incidence of epidemiology and prognosis of this type of infection and the clinical signs that allow an early diagnosis are discussed here.


Automation of the Timed-Up-and-Go Test Using a Conventional Video Camera.
The Timed-Up-and-Go (TUG) test is a simple clinical tool commonly used to quickly assess the mobility of patients. Researchers have endeavored to automate the test using sensors or motion tracking systems to improve its accuracy and to extract more resolved information about its sub-phases. While some approaches have shown promise, they often require the donning of sensors or the use of specialized hardware, such as the now discontinued Microsoft Kinect, which combines video information with depth sensors (RGBD). In this work, we leverage recent advances in computer vision to automate the TUG test using a regular RGB video camera without the need for custom hardware or additional depth sensors. Thirty healthy participants were recorded using a Kinect V2 and a standard video feed while performing multiple trials of 3 and 1.5 meter versions of the TUG test. A Mask Regional Convolutional Neural Net (R-CNN) algorithm and a Deep Multitask Architecture for Human Sensing (DMHS) were then used together to extract global 3D poses of the participants. The timing of transitions between the six key movement phases of the TUG test were then extracted using heuristic features extracted from the time series of these 3D poses. The proposed video-based vTUG system yielded the same error as the standard Kinect-based system for all six key transitions points, and average errors of less than 0.15 seconds from a multi-observer hand labeled ground truth. This work describes a novel method of video-based automation of the TUG test using a single standard camera, removing the need for specialized equipment and facilitating the extraction of additional meaningful information for clinical use.


Autoimmune encephalitis related to LGI1 antibodies with negative MRI study: Description of two cases.
Leucine-rich glioma inactivated 1 (LGI1) antibody-related autoimmune encephalitis is easily misdiagnosed clinically because of its complex and diverse clinical manifestations. We present two cases of LGI1 antibody-related encephalitis with negative imaging findings and perform a literature review on this disease entity. The first case was that of a 60-year-old man who presented with involuntary movement of the paroxysmal right limb. The second case was that of a 66-year-old man who presented with hearing hallucinations, involuntary shaking of the right limb, and progressive cognitive impairment. Both patients in this study showed negative magnetic resonance imaging (MRI) results. Routine cerebrospinal fluid (CSF) and biochemical examinations showed no significant abnormalities, and positive LGI1 antibodies were detected in both the CSF and serum. Based on our experience and the literature review, we recommend that LGI1 antibody-related encephalitis should be considered when faciobrachial dystonic seizures, acute and subacute-onset seizures, low serum sodium (possibly with low CSF chloride), and cognitive-psychiatric disorders are encountered, even in the absence of specific radiographic and altered CSF findings.


Issues of materiel management in the neonatal intensive care unit.
Managing NICUs can be a challenge not only to the unit manager, but also to those allied areas that provide supplies and services to the unit. If patient census and acuity fluctuate, then the challenge is doubled by the need to maintain a high degree of flexibility in personnel, supplies, and facilities to meet patients' needs. It is necessary that communication among managers occurs so that the equipment and supplies needed to meet physiologic and developmental demands of these vulnerable clients can be achieved efficiently and effectively.


Solitary, Endobronchial Metastasis from Renal Cell Carcinoma 20 Years after Nephrectomy.
Late recurrence over 10 years after surgery and endobronchial metastasis are some of the specific biological behaviors of renal cell carcinoma (RCC). The current report describes a case of solitary endobronchial metastasis at a subsegmental bronchus that developed 20 years after curative nephrectomy for RCC. A 71-year-old male was admitted to our hospital for pneumonia. Chest radiography showed multifocal ill-defined nodular opacities in the right lower lung zone, suggesting pneumonia. Subsequent chest CT confirmed pneumonic infiltration in the right lung. However, a 4.3-cm, well-defined, elongated mass with a branching pattern was also identified in the right lower lobe, and a right nephrectomy scar was detected on the covered upper abdomen. The patient had undergone right nephrectomy 20 years ago due to clear cell RCC. After right lower lobectomy, the postoperative pathological diagnosis was endobronchial metastatic clear cell RCC. Endobronchial metastasis should be considered in a patient with a history of RCC who presents with a suspected endobronchial tumor, even decades after curative surgery.


[Biliary and arterial obstructive processes in regional chemotherapy with FUDR].
By far the majority of 54 patients suffering from hepatic metastases due to colorectal primaries developed obliterations of the arterial vascular bed when being submitted to regional chemotherapy with FUDR. In addition, about 25% exhibited obstructive jaundice in the course of severe sclerosing cholangitis. Either effect, which can be detected by radiological procedures, has to be referred to irritating activities of the chemotherapeutic drug used.


Tumour suppression by targeted intravenous non-viral CRISPRa using dendritic polymers.
Aberrant gene expression is a hallmark of cancer. Although transcription is traditionally considered 'undruggable', the development of CRISPR-associated protein 9 (Cas9) systems offers enormous potential to rectify cancer-associated transcriptional abnormalities in malignant cells. However delivery of this technology presents a critical challenge to overcome in order to realize clinical translation for cancer therapy. In this article we demonstrate for the first time, a fully synthetic strategy to enable CRISPR-mediated activation (CRISPRa) of tumour suppressor genes in vivo using a targeted intravenous approach. We show this via highly efficient transcriptional activation of two model tumour suppressor genes, Mammary Serine Protease Inhibitor (MASPIN, SERPINB5) and cysteine-rich 61/connective tissue growth factor/nephroblastoma-overexpressed 6 (CCN6, WISP3), in a mouse model of breast cancer. In particular, we demonstrate that targeted intravenous delivery of can be achieved using a novel nanoscale dendritic macromolecular delivery agent, with negligible toxicity and long lasting therapeutic effects, outlining a targeted effective formulation with potential to treat aggressive malignancies.


Milk composition of rats feeding restricted litters.
Milk samples were taken from rats feeding ten pups and from both the suckled and non-suckled glands of rats feeding two pups. The lipid, protein and lactose concentrations were similar in the milks from the secreting glands, but the fluid from the non-suckled glands contained less lactose and lipid but significantly higher total protein and transferrin concentrations. The fatty acid compositions of the milk from the three sources were very similar. The mammary tissue from the rats feeding ten pups had a higher DNA content/g wet wt. than either the suckled or non-suckled mammary tissue of the rats feeding two pups. The specific activities of several lipogenic enzymes were significantly lower in the non-suckled mammary tissue.


Impact of a culturally tailored parenting programme on the mental health of Somali parents and children living in Sweden: a longitudinal cohort study.
This study aimed to evaluate the long-term impact (3-year follow-up) of a culturally tailored parenting support programme (Ladnaan) on the mental health of Somali-born parents and their children living in Sweden. In this longitudinal cohort study, Somali-born parents with children aged 11-16 were followed up 3 years after they had participated in the Ladnaan intervention. The Ladnaan intervention comprises two main components: societal information and the Connect parenting programme delivered using a culturally sensitive approach. It consists of 12 weekly group-based sessions each lasting 1-2 hours. The primary outcome was improved mental health in children, as measured by the Child Behaviour Checklist (CBCL). The secondary outcome was improved mental health in parents, as measured by the General Health Questionnaire-12. Data were collected from the parent's perspective. Of the 60 parents who were originally offered the intervention, 51 were included in this long-term follow-up. The one-way repeated measures (baseline to the 3-year follow-up) analysis of variance for the CBCL confirmed maintenance of all the treatment gains for children: total problem scores (95% CI 11.49 to 18.00, d=1.57), and externalising problems (95% CI 2.48 to 5.83, d=0.86). Similar results were observed for the parents' mental health (95% CI 0.40 to 3.11, d=0.46). Positive changes in the mental health of Somali-born parents and their children were maintained 3 years after they had participated in a parenting support programme that was culturally tailored and specifically designed to address their needs. Our findings highlight the long-term potential benefits of these programmes in tackling mental health issues in immigrant families. NCT02114593.


Intake_epis_food(): An R Function for Fitting a Bivariate Nonlinear Measurement Error Model to Estimate Usual and Energy Intake for Episodically Consumed Foods.
We consider a Bayesian analysis using WinBUGS to estimate the distribution of usual intake for episodically consumed foods and energy (calories). The model uses measures of nutrition and energy intakes via a food frequency questionnaire (FFQ) along with repeated 24 hour recalls and adjusting covariates. In order to estimate the usual intake of the food, we phrase usual intake in terms of person-specific random effects, along with day-to-day variability in food and energy consumption. Three levels are incorporated in the model. The first level incorporates information about whether an individual in fact reported consumption of a particular food item. The second level incorporates the amount of intake from those individuals who reported consumption of the food, and the third level incorporates the energy intake. Estimates of posterior means of parameters and distributions of usual intakes are obtained by using Markov chain Monte Carlo calculations. This R function reports to users point estimates and credible intervals for parameters in the model, samples from their posterior distribution, samples from the distribution of usual intake and usual energy intake, trace plots of parameters and summary statistics of usual intake, usual energy intake and energy adjusted usual intake.


Hepatic lipidosis: Liver characteristics and acute phase proteins in affected turkeys.
The hepatic lipidosis (HL) in fattening turkeys is a disease has been known for a long time, but the cause and pathogenesis is still not clarified. A recent study reported unexplained high levels of iron in liver tissue of fattening turkeys suffering from HL. In this study, the iron status, possible infectious or inflammatory influences in form of an acute phase reaction and the analysis of fatty acid pattern in liver tissue of turkeys affected by HL were examined. Three cases of HL on three different fattening turkey farms were investigated during the outbreak of the disease. Clinically affected and non-affected animals were subjected to a pathological examination, where the diagnosis HL or non-affected was made. In total, 70 birds were examined (40 with HL, 30 without HL) and blood and liver samples were taken. Additionally, samples from 15 slaughtered birds were taken as a further control group. In liver tissue, the iron content and the content of long-chain fatty acids were determined; in blood samples, ferritin and transferrin were measured. The iron content in liver tissue was more than three times higher for animals with HL than among non-affected animals and the control group. The transferrin levels were lowest for animals with HL, highest in the control group and in between for non-affected animals. The fatty acid pattern in liver tissue of affected animals indicated a shift from polyunsaturated fatty acids to saturated fatty acids and monounsaturated fatty acids compared to the control group and the non-affected animals. Overall, the non-affected animals of a flock affected by HL were similar to the healthy animals of the abattoir. The low acute phase protein levels for animals with HL together with high iron contents could indicate a previous malnutrition/starvation period and/or severe liver damage for those animals suffering from HL.


Vitamin D levels and other biochemical parameters of mineral bone disorders and their association with diastolic dysfunction and left ventricular mass in young nondiabetic adult patients with chronic kidney disease.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with end-stage renal disease. Chronic kidney disease (CKD)-associated cardiovascular mortality is more prevalent in those with diastolic heart failure and is an early predictor, while increased left ventricular mass (LVM) is a strong independent risk factor. Hypovitaminosis D is extensively being studied as a nontraditional risk factor for CVD. The aim of the present study is to look at the association of Vitamin D and other parameters of mineral bone disorder (MBD) with diastolic dysfunction and LVM in nondiabetic young adult patients with CKD. This was a hospital-based, cross-sectional observational study. Groups I and II comprised nondiabetic predialysis CKD patients (stage 4 and 5) and healthy controls, respectively. Groups IA and IB comprised cases with and without diastolic dysfunction, respectively. Vitamin D level was measured by enhanced chemiluminescence method and intact parathyroid hormone (iPTH) by electrochemiluminescence method. Parameters for diastolic function and LVM were assessed by Doppler echocardiography, tissue Doppler imaging, and M-mode echocardiography. Vitamin D level was significantly lower in Group I as compared to Group II. Diastolic dysfunction was present in 48.8% of the cases and was significantly associated with serum phosphorus and calcium-phosphorous product, but not with Vitamin D level. A statistically significant positive correlation between LVM and iPTH was found in our study. Hyperphosphatemia and high calcium-phosphorous product can be a better early predictor of diastolic dysfunction than Vitamin D while secondary hyperpara-thyroidism with increased LVM may be a bad prognostic marker.


Description and relationships of Chaetopterus pugaporcinus, an unusual pelagic polychaete (Annelida, Chaetopteridae).
An extraordinary new species, Chaetopterus pugaporcinus, is described from eight specimens collected from deep mesopelagic waters off Monterey Bay, California, by remotely operated vehicles. All specimens exhibit a consistent combination of both adult and larval characteristics, leaving in question the maturity of the specimens. All specimens lack ciliated larval bands and the stout, modified chaetae (cutting spines) typically found in segment A4 of chaetopterids. If the specimens described here are larvae, they are remarkable for their size, which ranged from 10 to 21 mm total length, nearly twice the length of the largest polychaete larvae previously reported and 5 to 10 times larger than known chaetopterid larvae. Then too, their lack of segment addition prior to settlement would be atypical. If adult, they are particularly unusual in their habitat choice and body form. Morphology of the uncini and comparison to larval morphology indicated a close relationship to either Chaetopterus or Mesochaetopterus. However, the lack of cutting spines and typical adult morphology made it impossible to determine to what genus this species should be allied. Thus, we carried out the first molecular phylogenetic analysis of the Chaetopteridae in order to appropriately place and name the new species. Three partial genes were sequenced for 21 annelid species. The sequencing also provides the first molecular evidence that Chaetopterus variopedatus sensu Hartman (1959) is not a single cosmopolitan species. The question of C. pugaporcinus being a delayed larva or a genuine holopelagic chaetopterid is discussed.


Low-complexity intrauterine pressure estimation using the Teager energy operator on electrohysterographic recordings.
Monitoring the progression of maternal uterine activity provides important prognostic information during pregnancy and parturition. Currently used methods for intrauterine pressure (IUP) measurement are unsuitable for long-term observation of uterine activity. The abdominally measured electrohysterogram (EHG) provides a non-invasive alternative to the existing methods for long-term ambulatory uterine contraction monitoring. A new low-complexity method for IUP estimation based on the Teager energy (TE) operator is proposed. The TE operator was used as it mimics the physiologic phenomena underlying the generation of the EHG signals. Several EHG signal analysis methods for IUP estimation from the literature are compared with the new TE method. The comparison is based on correlation and root mean square error of the IUP estimate with the gold standard internally measured IUP as well as their respective computational complexity. The proposed method results in a superior IUP estimation accuracy and complexity compared to state-of-the-art methods from the literature, with a complexity as much as 55 times lower. Therefore, the proposed method offers a valuable new option for long-term ambulatory uterine monitoring.


Generation of 4-dimensional CT images based on 4-dimensional PET-derived motion fields.
Respiratory motion can potentially reduce accuracy in anatomic and functional image fusion from multimodality systems. It can blur the uptake of small lesions and lead to significant activity underestimation. Solutions presented to date include respiration-synchronized anatomic and functional acquisitions. To increase the signal-to-noise ratio of the synchronized PET images, methods using nonrigid transformations during the reconstruction process have been proposed. In most of these methods, 4-dimensional (4D) CT images were used to derive the required deformation matrices. However, variations between acquired 4D PET and corresponding CT image series due to differences in respiratory conditions during PET and CT acquisitions have been reported. In addition, the radiation dose burden resulting from a 4D CT acquisition may not be justifiable for every patient. In this paper, we present a method for the generation of dynamic CT images from the combination of one reference CT image and deformation matrices obtained from the elastic registration of 4D PET images not corrected for attenuation. On the one hand, our approach eliminates the need for the acquisition of dynamic CT. On the other hand, it also ensures a good match between CT and PET images, allowing accurate attenuation correction to be performed for respiration-synchronized PET acquisitions. The proposed method was first validated on Monte Carlo-simulated datasets, and then on patient datasets (n = 4) by comparing generated 4D CT images with the corresponding acquired original CT images. Different levels of PET image statistical quality were considered in order to investigate the impact of image noise in the derivation of the 4D CT series. Our results suggest that clinically relevant PET acquisition times can be used for the implementation of such an approach, making this an even more attractive solution considering the absence of the extra dose given by a standard 4D CT acquisition. Finally, this approach may be applicable to other multimodality devices such as PET/MR.


Leveraging the psychology of the salesperson. A conversation with psychologist and anthropologist G. Clotaire Rapaille.
We have to admire salespeople's resilience in the face of endless rejection, their certainty that things will work out in the end. At the same time, we're repelled by what their job can do to them. (Think Death of a Salesman and Glengarry Glen Ross, dramatic portraits of hollowness and moral capitulation.) Just what type of person goes into sales, and how do salespeople cope with their jobs? For insight into these questions, HBR approached G. Clotaire Rapaille, a psychologist, anthropologist, and marketing guru who researches the impact of culture on business and markets. In particular, he studies archetypes--the underlying patterns in psychology that illuminate the human condition--and shows organizations how to use those patterns to sharpen their sales and marketing efforts. He points out, for instance, that a keen understanding of the Great Mother archetype has helped Procter & Gamble achieve great success with Pantene hair products. By promoting nutrition--and reminding consumers that hair must be nurtured--the Pantene brand appeals to the maternal instinct. Rapaille says that salespeople have their own archetype: They are Happy Losers who relish rejection and actually seek out jobs that provide opportunities to be turned down. That, of course, has implications for how they should be managed. Rapaille's research shows that the leading motivator in sales is not money; it's the thrill of the chase. "Hold huge company meetings where you give a salesperson the gold medal of rejection," he advises. "Jonathan sold 500,000 computers last month, but he was rejected 5 million times! It may sound ludicrous, but this is the way to get fire in the belly of your sales force--particularly in America, where beating the odds is highly prized".


Family history of education predicts eating disorders across multiple generations among 2 million Swedish males and females.
To investigate which facets of parent and grandparent socio-economic position (SEP) are associated with eating disorders (ED), and how this varies by ED subtype and over time. Total-population cohort study of 1,040,165 females and 1,098,188 males born 1973-1998 in Sweden, and followed for inpatient or outpatient ED diagnoses until 2010. Proportional hazards models estimated associations with parental education, income and social class, and with grandparental education and income. 15,747 females and 1051 males in our sample received an ED diagnosis, with rates increasing in both sexes over time. ED incidence in females was independently predicted by greater educational level among the father, mother and maternal grandparents, but parent social class and parental income showed little or no independent effect. The associations with education were equally strong for anorexia nervosa, bulimia nervosa and ED not-otherwise-specified, and had increased over time. Among males, an apparently similar pattern was seen with respect to anorexia nervosa, but non-anorexia ED showed no association with parental education and an inverse association with parental income. Family history of education predicts ED in gender- and disorder-specific ways, and in females the effect is observed across multiple generations. Particularly given that these effects may have grown stronger in more recent cohorts, these findings highlight the need for further research to clarify the underlying mechanisms and identify promising targets for prevention. Speculatively, one such mechanism may involve greater internal and external demands for academic success in highly educated families.


Cultural consonance and psychological well-being. Estimates using longitudinal data from an Amazonian society.
Researchers have hypothesized that the degree to which an individual's actual behavior approximates the culturally valued lifestyle encoded in the dominant cultural model has consequences for physical and mental health. We contribute to this line of research by analyzing data from a longitudinal study composed of five annual surveys (2002-2006 inclusive) of 791 adults in one society of foragers-farmers in the Bolivian Amazon, the Tsimane'. We estimate the association between a standard measure of individual achievement of the cultural model and (a) four indicators of psychological well-being (sadness, anger, fear and happiness) and (b) consumption of four potentially addictive substances (alcohol, cigarette, coca leaves and home-brewed beer) as indicators of stress behavior. After controlling for individual fixed effects, we found a negative association between individual achievement of the cultural model and psychological distress and a positive association between individual achievement of the cultural model and psychological well-being. Only the consumption of commercial alcohol bears the expected negative association with cultural consonance in material lifestyle, probably because the other substances analyzed have cultural values attached. Our work contributes to research on psychological health disparities by showing that a locally defined and culturally specific measure of lifestyle success is associated with psychological health.


Domestic violence screening: prevalence and outcomes in a Canadian HIV population.
There is a strong association between domestic violence victimization and HIV infection. This may lead to poor health outcomes including mental health disorders and reduced access to care. A standardized domestic violence screening interview was incorporated into ongoing care in the large and diverse population living with HIV in Southern Alberta, Canada. Results from May through December 2009 are reported, including the prevalence and outcomes of abuse. Thirty-four percent of 853 patients screened reported abuse. Of these, 16% reported abuse in their current relationship, 58% in a previous relationship, and 57% reported a history of childhood abuse. High-risk groups for abuse included females (43%), gay/bisexual males (35%), and Aboriginals (61%). We found an association between a history of domestic violence and delayed access to care (p < 0.05), missed appointments (p < 0.001), and an increased use of clinic resources such as social work (p < 0.0001) and psychiatry (p < 0.001). Mental health conditions prior to HIV diagnosis, including depression (p < 0.0001), suicidal ideation (p < 0.0001), and anxiety disorder (p < 0.0001) were associated with abuse at any time, while a history of adjustment disorder was associated with childhood abuse (p < 0.05). A simple domestic violence screening tool was helpful for identifying patients experiencing abuse in our diverse HIV-infected population. This high prevalence of domestic violence among our HIV patients was associated with poor outcomes and an increased use of medical resources. HIV caregivers should be aware of domestic violence in order to optimize care and refer patients to appropriate support professionals as needed.


Spinal cord lesions in heat stroke.
A clinical and pathological report of a patient who died 15 days after suffering a classic heat stroke is presented. The clinical picture was of a flaccid quadriplegia with anhidrosis and sphincter disturbance. The most severe pathological lesions were to be seen in the anterior and intermedio-lateral horns of the spinal cord. Hyperthermia was the only physiopathological mechanism demonstrated in the patient. It is suggested that the motor neurons and vegetative neurons of the spinal cord are specially sensitive to hyperthermia.


Outcomes in 139 cases of biliary tract reconstructions from a transplant surgery center.
The purpose of this study is to report our single institution transplant surgery referral center's experience with 139 consecutive biliary tract reconstructions performed in a mixed cohort of liver transplant recipients and patients with biliary tract malignancies, iatrogenic injuries, or other benign biliary pathology. Between July 1999 and February 2003, 139 biliary tract reconstructions were performed in 119 patients, using five various types of biliary reconstructions. The records and operative notes of all patients were reviewed with particular attention to surgical technique, operative mortality, post-operative complications and post-operative liver function tests with respect to biliary function. The mean duration of follow-up was 19.4 months (range 1.0 - 44.7 months). We were pleased to find excellent results from bilio-enteric reconstruction as no patient in our series developed cholangitis, jaundice or liver failure. Our goal is to inform the hepatobiliary and general surgeons of the principles of restoring biliary drainage that have arisen from our experience in a variety of reconstruction.


Results on neutrinoless double-β decay of 76Ge from phase I of the GERDA experiment.
Neutrinoless double beta decay is a process that violates lepton number conservation. It is predicted to occur in extensions of the standard model of particle physics. This Letter reports the results from phase I of the Germanium Detector Array (GERDA) experiment at the Gran Sasso Laboratory (Italy) searching for neutrinoless double beta decay of the isotope (76)Ge. Data considered in the present analysis have been collected between November 2011 and May 2013 with a total exposure of 21.6 kg yr. A blind analysis is performed. The background index is about 1 × 10(-2) counts/(keV kg yr) after pulse shape discrimination. No signal is observed and a lower limit is derived for the half-life of neutrinoless double beta decay of (76)Ge, T(1/2)(0ν) >2.1 × 10(25) yr (90% C.L.). The combination with the results from the previous experiments with (76)Ge yields T(1/2)(0ν)>3.0 × 10(25) yr (90% C.L.).


Sweat collection for testing in Canadian Cystic Fibrosis Centers, is it optimal?
The goal of this study was to examine the ability of the current Canadian CF center network to conduct sweat testing, with a particular focus on testing in infants less than 3 months old. Surveys were sent to the 37 CF centers in Canada supported by the Canadian CF Foundation, and results were interpreted with respect to their ability to obtain adequate sweat volumes in children less than 3 months and potential factors influencing these results. Ten centers that care for adult patients referred patients to their local pediatric CF center for sweat testing; the remaining 27 centers conducted sweat tests and 26 responded. Insufficient sweat volume results in children <3 months occurred in a median of 18.3% of tests. The corresponding proportion for the remaining population was 4.5% (P < 0.001). 15 of 19 centers had an incidence of >5% of insufficient tests in children <3 months of age, and 9 of 19 had an incidence of <20% in this age group. Six of 19 had an incidence of >5% of insufficient sweat volumes in older children and adults. Standardization of testing procedures is required to reduce the rates of insufficient sweat volumes in both infants less than 3 months old and children >3 months old. This will decrease the need for repeat testing and delay in diagnosis.


Outcomes for root-fractured permanent incisors: a retrospective study.
The objective of this study was to assess the outcomes for treated root-fractured permanent incisors with respect to pulp vitality, root tissue union, and tooth survival and to examine the effects of clinical and radiographic parameters and rigid splinting on the outcome. Eighty-four teeth were identified and data extracted from case notes prior to transfer to an SPSS data base for analysis. The odds ratios for each factor were calculated and the significance of differences was determined. Tooth loss and relevant risk variables were examined using Cox's regression model and Kaplan-Meyer survival curves. Fourteen (17%) had fractures in the apical third, 47 (56%) in the middle third, and 23 (27%) in the coronal (gingival) third. Twenty-four (29%) also had crown fractures involving enamel and dentine. Crown fractures were identified as significant risk factors for pulp vitality. Loss of pulp vitality, horizontal displacement, and extrusive displacement of the coronal fragment were significant risk factors for hard root tissue union. Survival was poorest with gingival third fractures with 14 (61%) of these teeth being lost. Splinting rigidly had no significant effect on pulp vitality and type of root tissue healing. Loss of pulp vitality was significantly associated with enamel-dentine crown fracture. Hard root tissue union was significantly affected by pulp necrosis and luxation of the coronal fragment. Survival was poorest for root fractures within the gingival third of the root. Splinting with rigid fixation had no significant effect on pulp vitality and type of root tissue union.


Association between beta-adrenoceptor antagonist-induced sympathicolysis and severity of coronary artery disease as assessed by coronary computed tomography angiography (CCTA).
Enhanced sympathetic nervous system activity is associated with increased mortality in many cardiac conditions including heart failure and coronary artery disease (CAD). To ensure adequate image quality of coronary CT angiography (CCTA), pre-scan β-adrenergic blockers (BB) are routinely administered. It is currently unknown whether sensitivity to sympathicolytic compounds is associated with severity of CAD. A total of 2633 consecutive patients (1733 [65.8%] men and 900 [34.2%] women, mean age 56.7 ± 11.5 years) undergoing CCTA for exclusion of significant CAD at our department between 06/2013 and 12/2016 were evaluated. Acute heart rate (HR) responses to BB administration were recorded in all patients. Coronary plaque burden as indicated by segment severity score (SSS), segment involvement score (SIS), and significant CAD (i.e. > 50% luminal narrowing) was higher in weak responders to BB as compared to strong responders to BB (p = 0.001 for SSS and SIS, and p = 0.021 for significant CAD). Accordingly, in a multiple linear regression model adjusted for known risk factors of CAD such as smoking, hypertension, diabetes and dyslipidaemia, as well as age, sex, body mass index (BMI), glomerular filtration rate, and HR during CCTA scan, a strong response to BB was selected as a significant independent negative predictor of coronary plaque burden (beta coefficient - 0.08, p = 0.001). We demonstrate that individuals with a weak acute response to BB administration encounter an increased risk of severe CAD. Taking into account sensitivity to sympatho-inhibition may add complementary information in patients undergoing CCTA for evaluation of CAD.


Leiomyosarcoma of the broad ligament arising in a pre-existing pure neurilemmoma-like leiomyoma.
A 35-year-old woman presented with an adnexal mass which came out as a leiomyosarcoma of the broad ligament arising in a pre-existing pure neurilemmoma-like leiomyoma. This is the first reported case of leiomyosarcoma arising in a pure neurilemmoma-like leiomyoma, the third reported case at an unusually young age showing evidence of a pre-existing leiomyoma and the 12th reported case of leimyosarcoma of the broad ligament. Is the likelihood of malignant transformation, especially in large leiomyomas of the broad ligament, a rare event?


An essential role for de novo biosynthesis of L-serine in CNS development.
L-serine plays a versatile role in intermediary metabolism in eukaryotic cells. The physiological significance of its de novo biosynthesis, however, remains largely unexplored. We demonstrated previously that neurons lose the ability to synthesize L-serine after their final differentiation and thus depend on astrocytes to supply this amino acid. This is due to a lack of neuronal expression of 3-phosphoglycerate dehydrogenase (Phgdh), which initiates de novo L-serine synthesis via the phosphorylated pathway from the glycolytic intermediate 3-phosphoglycerate. In rodent brain, Phgdh is expressed exclusively by the neuroepithelium/radial glia/astrocyte lineage. In humans, serine deficiency disorders can result from a deficiency of Phgdh or other enzymes involved in serine biosynthesis in the phosphorylated pathway. Patients with such disorders have lower serine levels in plasma and cerebrospinal fluid; they exhibit severe neurological symptoms including congenital microcephaly, feeding disabilities, and psychomotor retardation. L-serine supplementation can attenuate developmental defects in these patients. To define the physiological importance of de novo L-serine production, we generated Phgdh knockout mice using targeted gene disruption technique. Phgdh deletion drastically reduced serine and glycine levels in the body. Phgdh knockout mice exhibited overall growth retardation with severe brain malformation, culminating in embryonic lethality. These observations highlight the vital role of de novo L-serine synthesis in the formation and function of the mammalian central nervous system. Furthermore, the embryonic lethal phenotype of Phgdh knockouts indicates that L-serine must be synthesized endogenously in mouse (and probably humans) during embryonic development.


Impact of social support in preventing burnout syndrome in nurses: A systematic review.
Burnout is a reality in the nursing profession. It is composed of three dimensions: emotional exhaustion, depersonalization and reduced personal accomplishment, and results from being subjected to chronic stress in the healthcare context. Social support (SS), that is, the assistance and protection given by others, is a predictive and protective factor against burnout syndrome. The aim of this study is to analyze the relationship between SS, in its different forms, and burnout syndrome in nurses, and to identify the risk factors for burnout. A systematic literature review was carried out, following the PRISMA recommendations. The databases CINAHL, PsycINFO, Proquest Platform (Proquest Health & Medical Complete), Pubmed and Scopus were consulted, using the descriptors: "burnout, professional AND social support AND nursing". To minimize potential publication bias, the search had no time or sample size limitation. Burnout was reported, to a greater or lesser extent, in all the articles analyzed, and the SS received by nurses in the workplace from supervisors and coworkers was found to play a fundamental role in preventing the syndrome. However, to date the bibliography on this issue is scant, and there is little consensus as to the degree of SS received. Burnout prevention plans, with particular attention to SS, should be developed to improve nurses' quality of life and to enhance the care they provide.


Mutagenesis by alkylating agents: coding properties for DNA polymerase of poly (dC) template containing 3-methylcytosine.
After treatment of poly(dC) by the simple alkylating agent (3H)dimethylsulfate, 90 per cent of the radioactivity cochromatographied with 3-methylcytosine and 10 per cent with 5-methylcytosine which is the normally occurring methylated base. In order to study the influence of 3-methylcytosine on DNA replication, untreated and DMS-treated poly(dC) were used as templates for E. coli DNA polymerase I. The alkylation of poly(dC) inhibits DNA chain elongation, and does not induce any mispairing under high fidelity conditions. The alteration of DNA polymerase I fidelity by manganese ions allows some replication of 3-methylcytosine which mispairs with either dAMP or dTMP. Our results suggest that 3-methylcytosine could be responsible, at least partially, for the killing and the mutagenesis observed after cell treatment by alkylating agents.


Neurotrophic factors in development and regulation of respiratory control.
Neurotrophic factors (NTFs) are a heterogeneous group of extracellular signaling molecules that play critical roles in the development, maintenance, modulation and plasticity of the central and peripheral nervous systems. A subset of these factors, including members of three multigene families-the neurotrophins, neuropoetic cytokines and the glial cell line-derived neurotrophic factor ligands-are particularly important for development and regulation of neurons involved in respiratory control. Here, we review the functional biology of these NTFs and their receptors, as well as their roles in regulating survival, maturation, synaptic strength and plasticity in respiratory control pathways. In addition, we highlight recent progress in identifying the role of abnormal NTF signaling in the molecular pathogenesis of respiratory dysfunction in Rett syndrome and in the development of potential new NTF-targeted therapeutic strategies.


Emperipolesis: An Unreported Novel Phenomenon in Oral Squamous Cell Carcinoma.
Emperipolesis is a phenomenon characterized by engulfment of hematopoietic cells by megakaryocytes, monocytes, fibroblasts, and malignant cells within their cytoplasm. This phenomenon has been reported in various physiological and pathological conditions including malignancies. However, emperipolesis has never been reported in oral squamous cell carcinoma (OSCC) till date. We have analyzed histopathological slides of 56 cases of OSCC to see lymphocyte engulfment by tumor cells. Five cases showing features of this phenomenon were observed. Lymphocytes were typically identified as small round cells with oval nuclei and scanty cytoplasm. Both partial and complete engulfment of lymphocytes by tumor cells was appreciated. Nuclei of the host tumor cells were crescent shaped and illustrated small concave indentation, so as to accommodate the internalized lymphocyte. The intercellular bridges were not seen between the internalized cell and the host cell. There were no signs of degeneration appreciable in either cell, thus ruling out the possibility of cannibalism phenomenon. Although emperipolesis is a well-known phenomenon in pathology, this is the first report showing its evidence in OSCC.


ParticleCall: a particle filter for base calling in next-generation sequencing systems.
Next-generation sequencing systems are capable of rapid and cost-effective DNA sequencing, thus enabling routine sequencing tasks and taking us one step closer to personalized medicine. Accuracy and lengths of their reads, however, are yet to surpass those provided by the conventional Sanger sequencing method. This motivates the search for computationally efficient algorithms capable of reliable and accurate detection of the order of nucleotides in short DNA fragments from the acquired data. In this paper, we consider Illumina's sequencing-by-synthesis platform which relies on reversible terminator chemistry and describe the acquired signal by reformulating its mathematical model as a Hidden Markov Model. Relying on this model and sequential Monte Carlo methods, we develop a parameter estimation and base calling scheme called ParticleCall. ParticleCall is tested on a data set obtained by sequencing phiX174 bacteriophage using Illumina's Genome Analyzer II. The results show that the developed base calling scheme is significantly more computationally efficient than the best performing unsupervised method currently available, while achieving the same accuracy. The proposed ParticleCall provides more accurate calls than the Illumina's base calling algorithm, Bustard. At the same time, ParticleCall is significantly more computationally efficient than other recent schemes with similar performance, rendering it more feasible for high-throughput sequencing data analysis. Improvement of base calling accuracy will have immediate beneficial effects on the performance of downstream applications such as SNP and genotype calling.


Clinical indicators for diabetic eyecare delivered by optometrists in Australia: a Delphi study.
Valid and updated clinical indicators can serve as important tools in assessing and improving eyecare delivery. Indicators for diabetic eyecare in Australia were previously developed from guidelines published before 2013 and then used to assess the appropriateness of care delivery through a nationwide patient record card audit (the iCareTrack study). To reflect emerging evidence and contemporary practice, this study aimed to update clinical indicators for optometric care for people with type 2 diabetes in Australia. Forty-five candidate indicators, including existing iCareTrack and new indicators derived from nine high-quality evidence-based guidelines, were generated. A two-round modified Delphi process where expert panel members rated the impact, acceptability, and feasibility of the indicators on a 9-point scale and voted for inclusion or exclusion of the candidate indicators was used. Consensus on inclusion was reached when the median scores for impact, acceptability, and feasibility were ≥7 and >75% of experts voted for inclusion. Thirty-two clinical indicators with high acceptability, impact and feasibility ratings (all median scores: 9) were developed. The final indicators were related to history taking (n = 12), physical examination (n = 8), recall period (n = 5), referral (n = 5), and patient education/communication (n = 2). Most (14 of 15) iCareTrack indicators were retained either in the original format or with modifications. New indicators included documenting the type of diabetes, serum lipid level, pregnancy, systemic medications, nephropathy, Indigenous status, general practitioner details, pupil examination, intraocular pressure, optical coherence tomography, diabetic retinopathy grading, recall period for high-risk diabetic patients without retinopathy, referral of high-risk proliferative retinopathy, communication with the general practitioner, and patient education. A set of 32 updated diabetic eyecare clinical indicators was developed based on contemporary evidence and expert consensus. These updated indicators inform the development of programs to assess and enhance the eyecare delivery for people with diabetes in Australia.


Workplace Disruption following Psychological Trauma: Influence of Incident Severity Level on Organizations' Post-Incident Response Planning and Execution.
Psychologically traumatic workplace events (known as critical incidents), which occur globally, are increasing in prevalence within the USA. Assisting employers in their response is a growing practice area for occupational medicine, occupational social work, industrial psychology and other occupational health professions. Traumatic workplace events vary greatly in their level of organizational disruption. To explore whether extent of workplace disruption influences organizations' decisions for post-incident response planning and plan execution. Administrative data mining was employed to examine practice data from a workplace trauma response unit in the USA. Bivariate analyses were conducted to test whether scores from an instrument measuring extent of workplace disruption associated with organizational decisions regarding post-incident response. The more severe and disruptive the incident, the more likely organizations planned for and followed through to deliver on-site interventions. Following more severe incidents, organizations were also more likely to deliver group sessions and to complete follow-up consultations to ensure ongoing worker recovery. Increasing occupational health practitioners' knowledge of varying levels of organizational disruption and familiarity with a range of organizational response strategies improves incident assessment, consultation and planning, and ensures interventions delivered are consistent with the level of assistance needed on both worker and organizational levels.


Left ventricular regional work from wall tension-area loop in canine heart.
To quantitatively evaluate left ventricular (LV) regional work, LV pressure-volume relation and wall tension-regional area (TA) relation were analyzed in the excised cross-circulated left ventricle connected to a volume servo pump system. Wall tension was calculated using Laplace's law for a spherical model, and regional area was determined from orthogonal segment lengths measured with pairs of ultrasonic crystals. Data were obtained by changing LV end-diastolic volume or stroke volume before and after dobutamine infusion and before and after global ischemia. Regional work, assessed from the area within a TA loop during one cardiac cycle, correlated well with simultaneously obtained LV stroke work under all of the above experimental conditions (r = 0.90 +/- 0.09 to 0.97 +/- 0.02), and the linear regression line was not altered by changes in stroke volume, end-diastolic volume, or contractile state. Furthermore, measured regional work (RWm) proved to agree closely with the predicted value (RWp) calculated from LV stroke work and regional area [RWm = 0.91 RWp - 0.69 (mmHg . ml), r = 0.93]. Thus we conclude that TA relation may be useful for quantitative evaluation of regional work of the LV wall.


Enhanced N170 elicited by words in Chinese developmental dyslexia.
Impaired print tuning in dyslexia has been shown in alphabetic languages; whether we can observe the same in a nonalphabetic language such as Chinese is still questionable. The present study investigated the N170 component in response to Chinese words versus nonword pseudo-words in 10-year-old children with developmental dyslexia (DD) when they were asked to performed a lexical decision task. The N170 was enhanced for DD group than control group, regardless of Chinese words or pseudo-words. The group effect of N170 amplitudes was more robust for Chinese words over pseudo-words. Although the N170 did not show the word advantage in the control group, larger N170 for Chinese words versus pseudo-words was found in the DD group. These findings suggest that there was a dysfunction/inefficient processing in the early stage of processing Chinese words in patients with DD.


Effect of dietary fiber intake on breast cancer risk according to estrogen and progesterone receptor status.
There is few data on the association between dietary fiber intake and estrogen receptor (ER)/progesterone receptor (PR)-defined breast cancer risk. The present study aimed to investigate the associations between total dietary fiber and dietary fiber fractions intake and breast cancer risk by ER and PR status in a hospital-based case-control study among Chinese women. Four hundred and thirty-eight cases with primary breast cancer were consecutively recruited from June 2007 to August 2008 and frequency matched to 438 controls by age (5-year interval) and residence (rural/urban). A validated food frequency questionnaire was used to assess the dietary intake through a face-to-face interview. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for various potential confounders. A statistically significant inverse association was found between total dietary fiber and fiber fractions intake and breast cancer risk. The adjusted ORs (95% CIs) for the highest versus the lowest quartile of intake were 0.31 (0.20-0.47) for total dietary fiber, 0.73 (0.48-1.11) for soy fiber, 0.48 (0.22-0.97) for vegetable fiber and 0.54 (0.31-0.92) for fruit fiber. No association was observed for cereal fiber intake and risk. An inverse association between dietary fiber intake and breast cancer risk was observed in ER+, ER-, PR+, ER+PR+ and ER-PR+ tumors. Our results suggest that consumption of total dietary fiber and fiber from vegetable and fruit was inversely associated with breast cancer risk. These inverse associations were more prominent in some subtypes of ER and PR breast cancers.


Cloning and expression of Legionella pneumophila antigens in Escherichia coli.
To isolate and characterize Legionella pneumophila antigens, we constructed a genomic library of L. pneumophila serogroup 1 (strain 130b). L, pneumophila DNA fragments (2.5 to 7.5 megadaltons) obtained by partial digestion with Sau 3A endonuclease and size fractionation on a sucrose density gradient were inserted into the dephosphorylated BamHI site of vector pBR322; CaCl2-treated Escherichia coli cells of strain HB101 were transformed with hybrid plasmids. To detect expression of antigens, 2,559 ampicillin-resistant transformants were transferred to nitrocellulose paper, lysed in situ, and screened by enzyme immunoassay (EIA) with E. coli-absorbed rabbit anti-L. pneumophila sera. A total of 77 (3%) of the colonies were reactive by EIA; 31 (1.2%) were strongly reactive, and 6 were strongly reactive by EIA without colony lysis. Analysis of 29 stable, strongly reactive clones by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting showed antigenic bands in 18 clones by EIA with E. coli-absorbed antisera. Absorption of antisera with heat- and Formalin-killed L. pneumophila antigen eliminated or diminished the reactivity of the antigenic bands in representative clones. These studies confirm that several L. pneumophila antigens can be cloned and expressed in E. coli.


Live imaging of companion cells and sieve elements in Arabidopsis leaves.
The phloem is a complex tissue composed of highly specialized cells with unique subcellular structures and a compact organization that is challenging to study in vivo at cellular resolution. We used confocal scanning laser microscopy and subcellular fluorescent markers in companion cells and sieve elements, for live imaging of the phloem in Arabidopsis leaves. This approach provided a simple framework for identifying phloem cell types unambiguously. It highlighted the compactness of the meshed network of organelles within companion cells. By contrast, within the sieve elements, unknown bodies were observed in association with the PP2-A1:GFP, GFP:RTM1 and RTM2:GFP markers at the cell periphery. The phloem lectin PP2-A1:GFP marker was found in the parietal ground matrix. Its location differed from that of the P-protein filaments, which were visualized with SEOR1:GFP and SEOR2:GFP. PP2-A1:GFP surrounded two types of bodies, one of which was identified as mitochondria. This location suggested that it was embedded within the sieve element clamps, specific structures that may fix the organelles to each another or to the plasma membrane in the sieve tubes. GFP:RTM1 was associated with a class of larger bodies, potentially corresponding to plastids. PP2-A1:GFP was soluble in the cytosol of immature sieve elements. The changes in its subcellular localization during differentiation provide an in vivo blueprint for monitoring this process. The subcellular features obtained with these companion cell and sieve element markers can be used as landmarks for exploring the organization and dynamics of phloem cells in vivo.


Treatment of class II malocclussion: A comparative study of the effects of twin-block and fatigue resistant device.
This is a retrospective cephalometric study aimed to compare the treatment effects of Twin-Block (TB) appliance with The Forsus Fatigue Resistant Device (FRD) appliance in class II division I patients in a composite of peak and post peak growth of period time. The experimental sample consisted of the lateral cephalograms of 40 patients who were treated with either TB appliance (n = 15), FRD (n = 15) or the untreated control ones. In treatment groups lateral cephalograms taken before therapy as initial records (T1) and at the completion of functional therapy (T2) were used. The control group comprised 10 children with untreated skeletal Class II malocclusions. The normality of distribution of continuous variables was tested by Shaphiro wilk test. Oneway ANOVA and LSD test in parametric; Kruskall Wallis and all pairwaise multible comparison tests in non-parametric samples were used for comparing differences among 3 groups. Cephalometric analysis revealed that both TB and FRD appliances stimulated mandibular growth (P < 0.05) and no restriction was seen in maxilla in both groups (P > 0.05). The unwanted mandibular proclination was seen more in FRD group (P ≤ 0.001). Soft tissue didn't imitate the hard tissue (P > 0.05). FRD group produced skeletal effects as much as TB group in peak and post peak period of growth with still more mandibular incisor proclination.


Testing performance of large-scale surveys in determining trends for the critically endangered Great Indian Bustard Ardeotis nigriceps.
Great Indian Bustard (GIB) is listed as Critically Endangered, with less than 250 individuals surviving in three fragmented populations. The species is under tremendous threat due to various anthropogenic pressures. Effective management and conservation of GIB requires a proper monitoring protocol, which we propose using an occupancy framework approach to detect changes in the species' population. We used occupancy estimates from various landscape level surveys and simulated scenarios to evaluate the effectiveness of the proposed protocol. Our result showed there is >70% chance of detecting 100% change in the occupancy with 100 sampling sites and 10 temporal replicates. While with double sampling sites, the same change can be detected with 4-6 temporal replicates. In absence of a robust population estimation method, we argue for the use of occupancy as a surrogate to detect change in population as it provides better insights for rare elusive species such as GIB. Our proposed methodological framework is more precise than previous methods, which will help in evaluating efficacy of management interventions proposed and the implementation of species recovery plans.


Immunological consequences of transplanting rat insulinomas.
We investigated the genetics of transplanting a NEDH rat insulinoma in various donor-recipient combinations. The insulinoma survived indefinitely when it was transplanted in the NEDH strain. Mean survival times of 8.6 +/- 1.2 and 3.3 +/- 1.0 days were recorded in allogeneic and xenogeneic combinations, respectively. No prolongation of mean survival time was found when the rat insulinoma was first passed through the athymic nude mouse and then transplanted as either an allograft or xenograft. The findings of the major histocompatibility antigen (Ag-B7) on the original insulinoma and the tumor that had been passed through the nude mouse demonstrates no demonstrable loss of transplantation antigens during passage.


PsaD is required for the stable binding of PsaC to the photosystem I core protein of Synechococcus sp. PCC 6301.
The psaC gene product from Synechococcus sp. PCC 7002 and the psaD gene product from Nostoc sp. PCC 8009 were synthesized in Escherichia coli and purified to homogeneity. Incubation of the PsaC apoprotein with the Synechoccus sp. PCC 6301 photosystem I core protein in the presence of FeCl3, Na2S, and beta-mercaptoethanol resulted in a time-dependent transition in the flash-induced absorption change from a 1.2-ms, P700+ FX- back-reaction to a long-lived, P700+ [FA/FB]- back-reaction. ESR studies showed that FB and FA were photoreduced about equally at 19 K, and while the resonances were shifted upfield, they remained as broad as in the free PsaC holoprotein. When the reconstituted complex was purified in a sucrose gradient containing 0.1% Triton X-100, most of the optical absorption transient reverted to that characteristic of the P700+ FX- back-reaction. Addition of purified PsaD to the incubation mixture led to a greater extent of recovery of electron flow to FA/FB for any given concentration of PsaC. ESR studies showed that FA, rather than FB, became the preferred electron acceptor at 19 K; moreover, the resonances moved upfield and sharpened to become nearly identical with those of a control photosystem I complex. When the sample was purified in a sucrose gradient containing 0.1% Triton X-100, the long-lived P700+ [FA/FB]- optical transient remained stable. Analysis by denaturing polyacrylamide gel electrophoresis showed that the PsaC and PsaD proteins had rebound to the photosystem I core. The data indicate that although PsaC can bind loosely, the presence of PsaD leads to a stable, isolatable photosystem I complex which is spectroscopically indistinguishable from the native complex. Since a PsaC1 fusion protein which contains an amino-terminal extension of five amino acids (MEHSM...) does not bind in the absence of PsaD [Zhao, J., et al. (1990) FEBS Lett. 276, 175-180], the N-terminus of the PsaC protein could provide a site of interaction with the photosystem I core. We propose that the binding of PsaC to the PsaA/PsaB heterodimer is potentiated by insertion of the FA/FB clusters into PsaC, and stabilized by the presence of PsaD.


Role of Contact Force Sensing in Catheter Ablation of Cardiac Arrhythmias: Evolution or History Repeating Itself?
Adequate catheter-tissue contact facilitates efficient heat energy transfer to target tissue. Tissue contact is thus critical to achieving lesion transmurality and success of radiofrequency (RF) ablation procedures, a fact recognized more than 2 decades ago. The availability of real-time contact force (CF)-sensing catheters has reinvigorated the field of ablation biophysics and optimized lesion formation. The ability to measure and display CF came with the promise of dramatic improvement in safety and efficacy; however, CF quality was noted to have just as important an influence on lesion formation as absolute CF quantity. Multiple other factors have emerged as key elements influencing effective lesion formation, including catheter stability, lesion contiguity and continuity, lesion density, contact homogeneity across a line of ablation, spatiotemporal dynamics of contact governed by cardiac and respiratory motion, contact directionality, and anatomic wall thickness, in addition to traditional ablation indices of power and RF duration. There is greater appreciation of surrogate markers as a guide to lesion formation, such as impedance fall, loss of pace capture, and change in unipolar electrogram morphology. In contrast, other surrogates such as tactile feedback, catheter motion, and electrogram amplitude are notably poor predictors of actual contact and lesion formation. This review aims to contextualize the role of CF sensing in lesion formation with respect of the fundamental principles of biophysics of RF ablation and summarize the state-of-the-art evidence behind the role of CF in optimizing lesion formation.


Nuclear envelope formation around metaphase chromosomes: chromosome decondensation and nuclear envelope reconstitution during mitosis.
The hypothesis of a possible correlation between reconstitution of the nuclear envelope and decondensation of the chromosomes has been experimentally examined. In the presence of colcemid, which delays C-metaphase chromosome decondensation for several hours, compared to normal mitosis, nuclear envelope formation is also significantly delayed. On the contrary, the treatment of the cells with a hypotonic solution, resulting in some swelling of metaphase chromosomes, induces the establishment of contacts between these chromosomes and membranes and the formation of an envelope around them. A new method, by which micronuclei are formed under hypotonic treatment, is discussed.


Evaluation of dynamic thiol-disulfide homeostasis in very low-birth-weighted preterms.
Thiols are organic compounds containing sulfhydryl groups which exert antioxidant effects via dynamic thiol-disulfide homeostasis. The shift towards disulfides indicates the presence of oxidative environment. Thiol-disulfide homeostasis has not been evaluated in neonates. We aimed to evaluate dynamic thiol-disulfide homeostasis in preterm infants. Preterm infants with birth weight less than 1500 g (25-32 weeks of gestation) were included. Infants with major congenital anomaly, perinatal asphyxia, twin to twin transfusion and infants who were mechanically ventilated and nil by mouth for more than 3 days or fed with formula, had intraventricular hemorrhage ≥ grade 2 or sepsis, received blood/blood product transfusion or inotrope treatment and developed bronchopulmonary dysplasia or retinopathy of prematurity (≥ stage 3), and died were excluded thereafter. Serum thiol-disulfide homeostasis was evaluated for three times: (Baseline, first week, third week). Serum native thiol, total thiol and disulfide were measured (µmol/Lt), disulfide:native thiol, disulfide:total thiol, and native thiol:total thiol ratios were calculated. Wilcoxon's test was used to analyze the significance of change in measurements. Baseline results were analyzed for gender and mode of delivery. Eighty preterm infants [1255 (1080-1415) grams] were included. Baseline values were native thiol: 209.54 ± 41.83 µmol/L; total thiol: 251.70 ± 45.82 µmol/L; disulfide: 21.08 ± 7.43 µmol/Lt; disulfide:native thiol: 10.49 ± 4.62; disulfide:total thiol: 8.45 ± 2.93; native thiol:total thiol: 83.10 ± 5.87. Thiol levels increased in each measurement, disulfide and disulfide/thiol ratios increased in the first week, decreased in the third week, ratio of native/total thiol decreased in the first week, increased in the third week. No effect of gender or mode of delivery on baseline thiol-disulfide homeostasis was detected. The shift in the thiol-disulfide equilibrium towards disulfides in the first week can be attributed to subjection of infants to many oxidative insults. Furthermore, the thiol predominance in the third week could be explained by the decrease in oxidative events and increase in feeding as a supply of antioxidants. This study, displaying the levels of the dynamic thiol-disulfide homeostasis in preterm infants without obvious risks for increased oxidative stress, may provide acceptable range for thiol-disulfide homeostasis in recovering preterm infants.


Clinical assessment in Takayasu's arteritis: major challenges and controversies.
Takayasu's arteritis (TAK) is a rare, chronic, large-vessel vasculitis (LVV) that predominantly affects aorta, its major branches and the pulmonary arteries. Recent controversial issues in the diagnosis, disease assessment and prognosis in TAK are discussed in this review. In recent years, conventional angiography, the standard method for the initial diagnosis, seems to have been replaced by the new imaging modalities, such as MRI and 18F-FDG-PET. Less invasive techniques (CT/MRI) are now suggested first, compared to conventional angiography, and MRI is preferable to CT with less contrast load/radiation. Ultrasound is useful for carotid assessment, but being a user-dependent technique, imaging of deeper vessels (subclavian and aorta) are not reliable. 18F-FDG-PET is useful especially in patients with no vascular symptoms/signs, fever of unknown origin or unexplained acute-phase response. MRI and 18F-FDG-PET are also promising for the assessment of disease activity. New tools for disease assessment such as Indian Takayasu Arteritis Score (ITAS2010) aim to better characterise and quantify disease activity. Prognosis is recently possibly getting better with lower mortality, but a substantial damage is present even in early cases. There is a clear need to develop a validated set of outcome measures to be used in clinical trials of TAK. The OMERACT Vasculitis Working Group has taken on this task, finished a Delphi exercise with experts and aims to develop a core set of outcomes for LVV.


Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.
A large number of aggressive cancer cell lines display elevated levels of activated Rac1, a small GTPase widely implicated in cytoskeleton reorganization, cell motility, and metastatic dissemination. A commonly accepted methodological approach for detecting Rac1 activation in cancer cells involves the use of a conformation-sensitive antibody that detects the active (GTP-bound) Rac1 without interacting with the GDP-bound inactive form. This antibody has been extensively used in fixed cell immunofluorescence and immunohistochemistry. Taking advantage of prostate and pancreatic cancer cell models known to have high basal Rac1-GTP levels, here we have established that this antibody does not recognize Rac1 but rather detects the intermediate filament protein vimentin. Indeed, Rac1-null PC3 prostate cancer cells or cancer models with low levels of Rac1 activation still show a high signal with the anti-Rac1-GTP antibody, which is lost upon silencing of vimentin expression. Moreover, this antibody was unable to detect activated Rac1 in membrane ruffles induced by epidermal growth factor stimulation. These results have profound implications for the study of this key GTPase in cancer, particularly because a large number of cancer cell lines with characteristic mesenchymal features show simultaneous up-regulation of vimentin and high basal Rac1-GTP levels when measured biochemically. This misleading correlation can lead to assumptions about the validity of this antibody and inaccurate conclusions that may affect the development of appropriate therapeutic approaches for targeting the Rac1 pathway.


The flexible approach hypothesis: unification of effort and cue-responding hypotheses for the role of nucleus accumbens dopamine in the activation of reward-seeking behavior.
Dopamine released in the nucleus accumbens is thought to contribute to the decision to exert effort to seek reward. This hypothesis is supported by findings that performance of tasks requiring higher levels of effort is more susceptible to disruption by manipulations that reduce accumbens dopamine function than tasks that require less effort. However, performance of some low-effort cue-responding tasks is highly dependent on accumbens dopamine. To reconcile these disparate results, we made detailed behavioral observations of rats performing various operant tasks and determined how injection of dopamine receptor antagonists into the accumbens influenced specific aspects of the animals' behavior. Strikingly, once animals began a chain of operant responses, the antagonists did not affect the ability to continue the chain until reward delivery. Instead, when rats left the operandum, the antagonists severely impaired the ability to return. We show that this impairment is specific to situations in which the animal must determine a new set of approach actions on each approach occasion; this behavior is called "flexible approach." Both high-effort operant tasks and some low-effort cue-responding tasks require dopamine receptor activation in the accumbens because animals pause their responding and explore the chamber, and accumbens dopamine is required to terminate these pauses with flexible approach to the operandum. The flexible approach hypothesis provides a unified framework for understanding the contribution of the accumbens and its dopamine projection to reward-seeking behavior.


Pulmonary alveolar hemorrhage in a pregnancy complicated by systemic lupus erythematosus.
We present a case of a pregnant patient with fulminant systemic lupus erythematosus complicated by alveolar hemorrhage, a rare and potentially fatal manifestation of lupus. It typically presents in the context of a pulmonary-renal syndrome. Active lupus nephritis with hypoalbuminemia is a major risk factor for alveolar hemorrhage. Treatment with high-dose corticosteroids is the mainstay of therapy.


Endoscopic gastrostomy button with double-lasso U-stitch in children.
Placement of surgical gastric access is a common operative procedure, with multiple techniques. We describe a cost-effective, safe, and easy-to-perform primary endoscopic gastrostomy button placement in the pediatric population, using a novel double-transcutaneous lasso U-stitch push technique. This is a retrospective review of a single center's experience of 24 consecutively performed primary gastrostomy button placements in infants and children aged 3 weeks to 20 years, from October 2012 through October 2014. The procedure was generally well tolerated, with no intraoperative complications. No conversions to laparoscopic or open procedures were necessary. There were no early tube dislodgements and no postoperative complications within the first 4 weeks. The endoscopic primary gastrostomy button placement with a transcutaneous lasso U-stitch is a safe, fast, elegant, and cost-effective alternative to a standard percutaneous endoscopic gastrostomy placement.


Heterobasidion-growth inhibiting Bacillus subtilis A18 exhibits medium- and age-dependent production of lipopeptides.
Heterobasidion annosum s.s. and H. parviporum are severe pathogens of conifers causing butt rot and root rot thus reducing the economic value of timber. Here, the antifungal activity of Bacillus subtilis isolate A18 against these two Heterobasidion species was investigated. Five different culture media with different culture age were investigated to study the effect of substrate composition and culture age for metabolite production. Bacterial cultures and cell-free culture filtrates were tested for antifungal activity. Inhibition of fungal growth was analysed using the agar disc-diffusion method. MALDI-TOF and LC-HRMS analyses were used to identify the antifungal metabolites. Substrate composition and age of culture were found to be active variables with direct effect on the antifungal activity of bacterial culture extracts. High anti-fungal activity was observed when B. subtilis was cultured in PDB, SGB and LB media for four days. Mass-spectrometry analysis showed the presence of lipopeptides in culture filtrates identified as members of the surfactins, polymixins, kurstakins and fengycins. A culture filtrate containing fengycin-type lipopeptides showed the highest bioactivity against Heterobasidion species. Bacterial cultures had higher bioactivity compared to their respective cell free culture filtrates. The results of the present study suggest that B. subtilis A18 is a powerful biocontrol agent against Heterobasidion infections of tree wounds and stumps.


[Retros Flt-1 decelerates the growth of a murine experimental osteosarcoma].
To examine the influence of vascular endothelial growth factors (VEGF) in controlling the growth of an experimental osteosarcoma in mice by performing retrovirus-mediated sFlt-1 gene modification. From March to October 2010 human osteosarcoma G-292 cells were in vitro infected with retroviral vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal tibiae of immune deficient SCID mice to establish experimental orthotopic osteosarcoma. Daily observation and biweekly microCT were performed to monitor tumor development and progression till sacrifice at 8 weeks after tumor cell inoculation for histological and molecular analyses. Successful transgene expression was confirmed in the culture media of sFlt-1 transduced G-292 cells using ELISA, and with positive X-gal staining of the LacZ transduced cells. Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell inoculation, with clear detection on microCT images starting 2 weeks after inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292 cells were distinctively smaller in size compared to the ones from wide-type G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics including severe cellular pleomorphism, bone erosions, and neo-vascularization. Real-time polymerase chain reaction indicated significantly higher sFlt-1 expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ treated groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along with the expression of VEGF in the primary tumor tissue. Retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.


Lycopene II--effect on osteoblasts: the carotenoid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells.
We explored the possibility that lycopene, a carotenoid that is abundant in tomatoes, has effects on proliferation and differentiation of osteoblasts, the cells responsible for bone formation. Human osteoblast-like osteosarcoma SaOS-2 cells were cultured for 24 hours, after which varying doses of a water-dispersible microemulsion preparation of lycopene or vehicle of the same dilution were added. The cells were further cultured for 24 to 144 hours, and then the cell numbers were counted. Lycopene at 10(-6) and 10(-5) M had significant stimulatory effects on cell numbers, compared with the corresponding vehicle treatment, at all time points from 24 to 144 hours. The effects of lycopene on activity of the differentiation marker alkaline phosphatase activity in the absence or presence of dexamethasone were shown to be dependent on the stage of cell differentiation. This is the first report on the effects of lycopene on osteoblasts of human origin; the results may have important applications in the prevention of osteoporosis.


A comparative evaluation of the effect of Internet-based CME delivery format on satisfaction, knowledge and confidence.
Internet-based instruction in continuing medical education (CME) has been associated with favorable outcomes. However, more direct comparative studies of different Internet-based interventions, instructional methods, presentation formats, and approaches to implementation are needed. The purpose of this study was to conduct a comparative evaluation of two Internet-based CME delivery formats and the effect on satisfaction, knowledge and confidence outcomes. Evaluative outcomes of two differing formats of an Internet-based CME course with identical subject matter were compared. A Scheduled Group Learning format involved case-based asynchronous discussions with peers and a facilitator over a scheduled 3-week delivery period. An eCME On Demand format did not include facilitated discussion and was not based on a schedule; participants could start and finish at any time. A retrospective, pre-post evaluation study design comparing identical satisfaction, knowledge and confidence outcome measures was conducted. Participants in the Scheduled Group Learning format reported significantly higher mean satisfaction ratings in some areas, performed significantly higher on a post-knowledge assessment and reported significantly higher post-confidence scores than participants in the eCME On Demand format that was not scheduled and did not include facilitated discussion activity. The findings support the instructional benefits of a scheduled delivery format and facilitated asynchronous discussion in Internet-based CME.


Are there ethnic differences in lithium pharmacokinetics and side-effects?
Possible ethnic differences in the pharmacokinetics of lithium carbonate were systematically examined in Caucasian and Afro-Caribbean volunteer subjects under standardized conditions. The two groups did not differ with regard to weight, age or renal function. Rates of absorption were similar, but there was a non-statistically significant trend towards more rapid distribution and elimination, smaller area under the serum curve and greater urinary excretion in the Caucasian group. There were no differences in side-effects. The results support the view that ethnic differences in blood levels found with other psychotropic drugs are due to altered drug metabolism and suggest that lithium pharmacokinetic data derived from Caucasian subjects can be safely extrapolated to Afro-Caribbean.


Septic pulmonary emboli and bacteremia associated with deep tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus.
We report four adult patients who presented with septic pulmonary emboli and community-acquired methicillin-resistant Staphylococcus aureus bacteremia associated with deep tissue infections, such as pyomyositis, osteomyelitis, and prostatic abscess. The patients lacked evidence of right-sided endocarditis or thrombophlebitis. This association, previously described in children, may also be important in adults.


An update on snail and trematode communities in the Sanyati Basin of Lake Kariba: New snail and trematode species but no human schistosomes.
The construction of Lake Kariba brought about a rise in the incidence of schistosomiasis in its surrounding towns of Kariba (Zimbabwe) and Siavonga (Zambia). After extensive control programs in Kariba, schistosomiasis prevalence dropped significantly. The objective of this study was to revisit the same localities sampled by Chimbari et al. (2003), and provide an update on the snail community and prevalence of trematodes in the Northern shore of Lake Kariba while focusing on planorbid species. Monthly sampling of snails at 16 sites along the Northern shoreline of Lake Kariba, near Kariba town, was undertaken for one year. Minimum one specimen per morphotype was identified using molecular barcoding (sequencing a fragment of cytochrome c oxidase I subunit (COI)). The infection status of snails was assessed by Rapid Diagnostic PCRs (RD-PCR), and trematode infections were genotyped by sequencing COI and 18S rDNA markers. We collected and identified seven snail species: Bulinus truncatus, Bulinus forskalii, Gyraulus sp., Physella acuta, Bellamya sp., Radix affinis plicatula and Pseudosuccinea columella. Physella acuta was the most abundant snail species (comprising 56.95% of the total snail count) and present at all sites. The B. truncatus population was found to be infected with the stomach fluke Carmyerius cruciformis, a Petasiger sp. and a trematode species belonging to the family Notocotylidae. No Schistosoma sp. infections were detected in our collected snail specimens. We report B. truncatus as an intermediate snail host for Carmyerius cruciformis, and the presence of three non-schistosome trematode species that have not been reported in Lake Kariba before. Furthermore, we detect a possible shift in the snail community when compared to the report by Chimbari et al. (2003): this is the first record of Gyraulus sp. in Lake Kariba, and we did not observe the previously reported B. pfeifferi, B. globosus and Radix natalensis. Although this shift in snail communities might have contributed to the absence of Schistosoma spp. detection in this study, further monitoring of final and intermediate hosts across the Kariba basin is essential to prove a decrease of schistosomiasis in the area.


[Influence of electroacupuncture on p38-mitogen activated protein kinase in substantia nigra cells of rats with Parkinson disease model].
To explore the role of inflammatory reaction mediated by p38-mitogen activated protein kinase (p38-MAPK) signal path on prevention and treatment of Parkinson disease (PD) model rats by electroacupuncture (EA). Thirty-two healthy male SD rats were randomly divided into a normal group, a sham operation group, a model group and an EA group, eight rats in each one. The PD model was established in the model group and EA group by subcutaneous injection of rotenone in skin-back area (2 mg/kg, dissolved in sunflower oil, 2 mg/mL in density), while the injection of sunflower oil emulsion without rotenone at the same point and quantity as the model group was applied in the sham operation group. The normal group was not given any intervention. The EA treatment (continuous wave, 2 Hz in frequency, 1 mA in intensity, 20 min) was applied at "Fengfu" (GV 16) and "Taichong" (LR 3) in the EA group, once a day for continuously 14 days. No treatment was given in the other groups. The expression of tyrosine hydroxylase (TH), phosphorylated p38-MAPK, cyclooxygenase-2 (COX-2) in the substantia nigra were detected with immunohistochemical method. There was typical PD ethology change in the model group. Compared with the normal group and sham operation group, the expression of TH positive neuron in the substantia nigra in the model group was significantly decreased, while the expression of phosphorylated p38-MAPK and COX-2 were significantly increased (all P < 0.01). Compared with the model group, the expression of TH positive neuron in the EA group was apparently increased, while the expression of phosphorylated p38-MAPK and COX-2 were significantly decreased (all P < 0.01). The EA therapy could obviously reduce the expression of inflammation mediator COX-2, inhibit the phosphorylation of p38-MAPK, reduce the damage of dopaminergic neurons in the rats with PD, and this effect may be related with the impact of p38-MAPK signal path


A Reliable Method to Assess Keel Bone Fractures in Laying Hens From Radiographs Using a Tagged Visual Analogue Scale.
Up to 97% of laying hens housed in aviary systems are affected by keel bone fractures. Due to the scope of the problem, multiple efforts investigating causes and consequences of fractures have been conducted. The most frequently used techniques to detect fractures lack accuracy and provide only vague information (palpation) or cannot be conducted longitudinally (dissection). Radiographic imaging overcomes these weaknesses as it allows longitudinal observations and provides detailed information for individual fractures of which a single keel may have several at different locations and of different origins. However, no standardized system exists to assess fracture severity from radiographs if multiple fractures are present. The aim of this study was therefore to test the reliability of a scoring system assessing the aggregate severity of multiple fractures, taking into account the characteristics of all present fractures (e.g., locations, callus formation, width of fracture gaps). We developed a scoring system based on a tagged visual analogue scale, ranging from score 0 (no fracture) to score 5 (extremely severe) with intermediate tags for scores 1, 2, 3, and 4. A catalog of example scores was provided to describe the range of each score visually. An online tutorial with an introduction, training and scoring session was completed by 14 participants with varying experience involving laying hens and keel bone damage. For inter-observer reliability, we found an Intraclass correlation coefficient (ICC) of 0.985 with a 95% confidence interval of 0.974 < ICC < 0.993 (average-rating, absolute-agreement, two-way random-effects model). Intraclass correlation coefficient for intra-observer reliability was 0.923 with a 95% confidence interval of 0.879 < ICC < 0.951 (single-rating, absolute-agreement, two-way mixed-effects model). Intra-observer reliability ranged from 0.704 to 1.0 indicating excellent agreement and similar ratings across and within participants. Further, high ICCs suggest that the introduction and the training sessions provided were adequate tools to prepare observers for the assessment task despite various backgrounds of the participants. Nonetheless, the validity of this scoring system needs to be investigated further in order to link responses of interest and biological relevance with the specific severity values resulting from our scoring system.


Social acceptance, emissions analysis and potential applications of paper-waste briquettes in Andean areas.
The research assessed waste-based briquettes consumption compared to conventional fuels in the Andes. Laboratory tests were conducted together with on-field analysis in Colquencha (Bolivia). The laboratory study shows that the performances of briquettes are better in terms of PM2.5 (933.4 ± 50.8 mg kg-1) and CO emissions (22.89 ± 2.40 g kg-1) compared to animal dung (6265.7 ± 1273.5 mgPM2.5 kg-1 and 48.10 ± 12.50 gCO kg-1), although the boiling time increased due to the lower fuel consumption rate and firepower compared to shrubs. The social survey organized with 150 Bolivian citizens suggested that low-income households are not able to pay for an alternative fuel: about 40% would pay less than 4 USD per month, while methane use for cooking is positively correlated with the income level (r = 0.244, p < 0.05). On field analysis suggested that local cookstoves are not appropriate for briquettes combustion since indoor air pollution overcomes 30 ppm of CO and 10 mgPM2.5 m-3. On balance, local small manufactures can be the main target for selling waste-based briquettes to reduce shrubs and wood consumption. However, briquettes production costs seem not yet competitive to natural easy-to-obtain fuels (i.e., animal dung). The research encourages the use of cellulosic and biomass waste-based briquettes in the Andean area for cooking, heating, or manufacturing and strongly advises policy-makers to introduce economic incentives for the recovery of secondary raw materials.