Obesity management in primary care: assessment of readiness to change among 284 family practice patients.
Most adults in primary care are overweight or obese; two thirds of patients with weight problems have other obesity-related conditions. The study objective was to explore the feasibility of a primary care obesity intervention based on the transtheoretical model (TM) of behavior change and principles of chronic disease (CD) care. A prospective study of the initial version of the TM-CD intervention with obese family practice patients (n = 284) yielded cross-sectional data on baseline stage of change for six target behaviors: dietary fat, portion control, vegetable intake, fruit intake, usual physical activity, and planned exercise. The sample consisted of obese patients scheduled for an office visit during times when recruitment and informed consent did not conflict with acute care. Obese patients volunteering for a TM-CD program are in different stages of change for six target behaviors. Preparation was the most frequently reported stage for increased exercise (49%) or activity (34%), decreased dietary fat consumption (44%), and increased portion control (51%). Patients in a particular stage for one behavior were distributed across all five stages for another behavior. Stage of change for five target behaviors was associated with body mass index or waist girth (P < .05) in a manner consistent with stage-of-change theory. Using the transtheoretical model of behavior change will allow physicians to recognize when obese patients are receptive to specific behavioral interventions.


Disease-causing mutations in the cellular retinaldehyde binding protein tighten and abolish ligand interactions.
Mutations in the human cellular retinaldehyde binding protein (CRALBP) gene cause retinal pathology. To understand the molecular basis of impaired CRALBP function, we have characterized human recombinant CRALBP containing the disease causing mutations R233W or M225K. Protein structures were verified by amino acid analysis and mass spectrometry, retinoid binding properties were evaluated by UV-visible and fluorescence spectroscopy and substrate carrier functions were assayed for recombinant 11-cis-retinol dehydrogenase (rRDH5). The M225K mutant was less soluble than the R233W mutant and lacked retinoid binding capability and substrate carrier function. In contrast, the R233W mutant exhibited solubility comparable to wild type rCRALBP and bound stoichiometric amounts of 11-cis- and 9-cis-retinal with at least 2-fold higher affinity than wild type rCRALBP. Holo-R233W significantly decreased the apparent affinity of rRDH5 for 11-cis-retinoid relative to wild type rCRALBP. Analyses by heteronuclear single quantum correlation NMR demonstrated that the R233W protein exhibits a different conformation than wild type rCRALBP, including a different retinoid-binding pocket conformation. The R233W mutant also undergoes less extensive structural changes upon photoisomerization of bound ligand, suggesting a more constrained structure than that of the wild type protein. Overall, the results show that the M225K mutation abolishes and the R233W mutation tightens retinoid binding and both impair CRALBP function in the visual cycle as an 11-cis-retinol acceptor and as a substrate carrier.


Zika virus has oncolytic activity against glioblastoma stem cells.
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.


Morphology Engineering: A Route to Highly Reproducible and High Efficiency Perovskite Solar Cells.
Despite the rapid increase in the performance of perovskite solar cells (PSC), they still suffer from low lab-to-lab or people-to-people reproducibility. Aiming for a universal condition to high-performance devices, we investigated the morphology evolution of a composite perovskite by tuning annealing temperature and precursor concentration of the perovskite film. Here, we introduce thermal annealing as a powerful tool to generate a well-controlled excess of PbI2 in the perovskite formulation and show that this benefits the photovoltaic performance. We demonstrated the correlation between the film microstructure and electronic property and device performance. An optimized average grain size/thickness aspect ratio of the perovskite crystallite is identified, which brings about a highly reproducible power conversion efficiency (PCE) of 19.5 %, with a certified value of 19.08 %. Negligible hysteresis and outstanding morphology stability are observed with these devices. These findings lay the foundation for further boosting the PCE of PSC and can be very instructive for fabrication of high-quality perovskite films for a variety of applications, such as light-emitting diodes, field-effect transistors, and photodetectors.


The multiple subfunctions of attention: differential developmental gateways to literacy and numeracy.
Attention is construed as multicomponential, but the roles of its distinct subfunctions in shaping the broader developing cognitive landscape are poorly understood. The current study assessed 3- to 6-year-olds (N=83) to: (a) trace developmental trajectories of attentional processes and their structure in early childhood and (b) measure the impact of distinct attention subfunctions on concurrent and longitudinal abilities related to literacy and numeracy. Distinct trajectories across attention measures revealed the emergence of 2 attentional factors, encompassing "executive" and "sustained-selective" processes. Executive attention predicted concurrent abilities across domains at Time 1, whereas sustained-selective attention predicted basic numeracy 1 year later. These concurrent and longitudinal constraints cast a broader light on the unfolding relations between domain-general and domain-specific processes over early childhood.


As(V) and P Competitive Sorption on Soils, By-Products and Waste Materials.
Batch-type experiments were used to study competitive As(V) and P sorption on various soils and sorbent materials. The materials assayed were a forest soil, a vineyard soil, pyritic material, granitic material, coarsely and finely ground mussel shell, calcinated mussel shell ash, pine sawdust and slate processing fines. Competition between As(V) and P was pronounced in the case of both soils, granitic material, slate fines, both shells and pine sawdust, showing more affinity for P. Contrary, the pyritic material and mussel shell ash showed high and similar affinity for As(V) and P. These results could be useful to make a correct use of the soils and materials assayed when focusing on As and P removal in solid or liquid media, in circumstances where both pollutants may compete for sorption sites.


Transcriptional regulation of importin-α1 by JunD modulates subcellular localization of RNA-binding protein HuR in intestinal epithelial cells.
The RNA-binding protein HuR is crucial for normal intestinal mucosal regeneration by modulating the stability and translation of target mRNAs, but the exact mechanism underlying HuR trafficking between the cytoplasm and nucleus remains largely unknown. Here we report a novel function of transcription factor JunD in the regulation of HuR subcellular localization through the control of importin-α1 expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically inhibited importin-α1 at the transcription level, and this repression is mediated via interaction with CREB-binding site that was located at the proximal region of importin-α1 promoter. Reduction in the levels of importin-α1 by JunD increased cytoplasmic levels of HuR, although it failed to alter whole cell HuR levels. Increased levels of endogenous JunD by depleting cellular polyamines also inhibited importin-α1 expression and increased cytoplasmic HuR levels, whereas JunD silencing rescued importin-α1 expression and enhanced HuR nuclear translocation in polyamine-deficient cells. Moreover, importin-α1 silencing protected IECs against apoptosis, which was prevented by HuR silencing. These results indicate that JunD regulates HuR subcellular distribution by downregulating importin-α1, thus contributing to the maintenance of gut epithelium homeostasis.


The hedonic effects of amphetamine and pentobarbital in goldfish.
Goldfish were confined in a distinctive chamber while drugged with amphetamine in Experiment A or pentobarbital in Experiment P. During a later test, the goldfish in Experiment A showed a preference for the chamber associated with amphetamine, whereas those in Experiment P showed an aversion to the chamber associated with pentobarbital. Thus, amphetamine produced a rewarding effect while pentobarbital was aversive. The mechanism of pentobarbital's aversive effect is unknown. However, there is convincing evidence that amphetamine produces a rewarding effect in rats, monkeys and humans by increasing the synaptic concentration of dopamine in the central reward system. Since the goldfish brain has cells containing dopamine, the same mechanism is likely to be responsible for amphetamine's rewarding effect in goldfish. This similarity suggests that the central reward systems of such diverse species as goldfish, rats, monkeys, and humans have a common evolutionary origin.


Efficacy and safety of febuxostat in elderly female patients.
Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent.


Study on the Relation between Colorectal Cancer and Gall Bladder Disease.
Colorectal cancer is cancer of the large intestine, the lower part of digestive system which includes the sigmoid colon and rectum. To study the relation of incidence of colorectal cancer with previous gall bladder disease or post-cholecystectomy status, a relation between gall bladder disease and smoking in particular and the most common region of colon involved in colorectal cancer in gall bladder disease and non-gall bladder disease patients. A total of 256 patients with symptoms of rectal bleeding, change in bowel habit, unexplained tiredness, weight loss, pelvic pain, jaundice and abdominal distension were screened by using colonoscopy among whom 30 patients were diagnosed with colorectal cancer. Detailed history was taken with the help of a modified questionnaire and the patients were assessed, examined and the list of investigations such as faecal occult blood test, ultrasound of abdomen and pelvis, colonoscopy, sigmoidoscopy, barium enema, Computed Tomography (CT), Magnetic Resonance Imaging (MRI) of the abdomen and pelvis, tumour markers like Carcinoembryonic Antigen (CEA) and biopsy were collected. Patient pool was categorized into Gall Bladder Disease (GBD) and Non Gall Bladder Disease (NGBD). Proportions test and Fisher's-Exact test were used to calculate the p-values. Ten patients had previous gall bladder disease (33%) which was significant with a p-value of 0.016 by proportions test. Two patients underwent cholecystectomy, two patients underwent Endoscopic Retrograde Cholangio Pancreatography (ERCP) and the remaining six patients did not take any treatment for their gall bladder disease. Five patients with previous gall bladder disease were found to be smokers with a p-value of 0.091. The average age was 47.2 years in males and 42.2 years in females. Males constituted 66.6% (20 males) of the diseased population whereas, females constituted 33.4% (10 females). Rectal bleeding and altered bowel habits were the commonest symptoms. Confirmation of the disease was proven using CT abdomen and biopsy. Right sided colorectal cancer was common in GBD patients. Left sided colon cancer was common in NGBD patients. This study established a statistically significant risk of colorectal cancer following cholelithiasis though no risk was apparent following cholecystectomy.


Interleukin-8 concentration and neutrophil chemotactic activity in bronchoalveolar lavage fluid of horses with chronic obstructive pulmonary disease following exposure to hay.
To analyze effects of hay dust exposure on interleukin-8 (IL-8) concentration, percentage of neutrophils, and neutrophil chemotactic activity in bronchoalveolar lavage fluid (BALF) of horses with chronic obstructive pulmonary disease (COPD). 16 healthy horses and 29 horses with COPD. IL-8 concentration, percentage of neutrophils, and neutrophil chemotactic activity in BALF were measured. Values were analyzed with respect to hay dust exposure. These variables were also measured in 5 asymptomatic horses with COPD after the induction of clinical signs by changing feed from silage to hay. L-8 concentrations and chemotactic activity in BALF were greater in horses with COPD, compared with healthy horses, and greater in horses with COPD exposed to hay dust, compared with nonexposed affected horses. An increase in IL-8 concentration accompanied by an increase in percentage of neutrophils in BALF and development of clinical signs of COPD were induced in asymptomatic horses with COPD by changing feed from silage to hay. Exposure of horses with COPD to hay dust components resulted in an increase in IL-8 secretion at the bronchoalveolar surface. This chemokine may play a role in the pathogenesis of COPD, because it causes neutrophil accumulation in the bronchoalveolar space. Our results underscore the importance of eliminating dust sources for the treatment and prevention of COPD in horses.


Impact of the COVID-19 pandemic on people with epilepsy: findings from the US arm of the COV-E study.
As part of the COVID-19 and Epilepsy (COV-E) global study, we aimed to understand the impact of COVID-19 on the medical care and well-being of people with epilepsy (PWE) in the United States, based on their perspectives and those of their caregivers. Separate surveys designed for PWE and their caregivers were circulated from April 2020 to July 2021; modifications in March 2021 included a question about COVID-19 vaccination status. We received 788 responses, 71% from PWE (n = 559) and 29% (n=229) from caregivers of persons with epilepsy. A third (n = 308) of respondents reported a change in their health or in the health of the person they care for. Twenty-seven percent (n = 210) reported issues related to worsening mental health. Of respondents taking ASMs (n = 769), 10% (n= 78) reported difficulty taking medications on time, mostly due to stress causing forgetfulness. Less than half of respondents received counseling on mental health and stress. Less than half of the PWE reported having discussions with their healthcare providers about sleep, ASMs and potential side effects, while a larger proportion of caregivers (81%) reported having had discussions with their healthcare providers on the same topics. More PWE and caregivers reported that COVID-19 related measures caused adverse impact on their health in the post-vaccine period than during the pre-vaccine period, citing mental health issues as the primary reason. Our findings indicate that the impact of the COVID-19 pandemic in the US on PWE is multifaceted. Apart from the increased risk of poor COVID-19 outcomes, the pandemic has also had negative effects on mental health and self-management. Healthcare providers must be vigilant for increased emotional distress in PWE during the pandemic and consider the importance of effective counseling to diminish risks related to exacerbated treatment gaps.


Harnessing the potential of epigenetic therapy to target solid tumors.
Epigenetic therapies may play a prominent role in the future management of solid tumors. This possibility is based on the clinical efficacy of existing drugs in treating defined hematopoietic neoplasms, paired with promising new data from preclinical and clinical studies that examined these agents in solid tumors. We suggest that current drugs may represent a targeted therapeutic approach for reprogramming solid tumor cells, a strategy that must be pursued in concert with the explosion in knowledge about the molecular underpinnings of normal and cancer epigenomes. We hypothesize that understanding targeted proteins in the context of their enzymatic and scaffolding functions and in terms of their interactions in complexes with proteins that are targets of new drugs under development defines the future of epigenetic therapies for cancer.


Psoriasis severity and the prevalence of major medical comorbidity: a population-based study.
Despite the growing literature on comorbidity risks in psoriasis, there remains a critical knowledge gap on the degree to which objectively measured psoriasis severity may affect the prevalence of major medical comorbidity. To examine the prevalence of major medical comorbidity in patients with mild, moderate, or severe psoriasis, classified objectively based on body surface area involvement, compared with that in patients without psoriasis. Population-based cross-sectional study of patient data from United Kingdom-based electronic medical records; analysis included 9035 patients aged 25 to 64 years with psoriasis and 90,350 age- and practice-matched patients without psoriasis. Prevalence of major medical comorbidity included in the Charlson comorbidity index. Among patients with psoriasis, 51.8%, 35.8%, and 12.4%, respectively, had mild, moderate, or severe disease based on body surface area criteria. The mean Charlson comorbidity index was increasingly higher in patients with mild (0.375 vs 0.347), moderate (0.398 vs 0.342), or severe psoriasis (0.450 vs 0.348) (each P < .05). Psoriasis overall was associated with higher prevalence of chronic pulmonary disease (adjusted odds ratio, 1.08; 95% CI, 1.02-1.15), diabetes mellitus (1.22; 1.11-1.35), diabetes with systemic complications (1.34; 1.11-1.62), mild liver disease (1.41; 1.12-1.76), myocardial infarction (1.34; 1.07-1.69), peptic ulcer disease (1.27; 1.03-1.58), peripheral vascular disease (1.38; 1.07-1.77), renal disease (1.28; 1.11-1.48), and rheumatologic disease (2.04; 1.71-2.42). Trend analysis revealed significant associations between psoriasis severity and each of the above comorbid diseases (each P < .05). The burdens of overall medical comorbidity and of specific comorbid diseases increase with increasing disease severity among patients with psoriasis. Physicians should be aware of these associations in providing comprehensive care to patients with psoriasis, especially those presenting with more severe disease.


Maternal rheumatoid arthritis and risk of autism in the offspring.
Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD. We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity. Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11-1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12-2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24-1.60). In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.


Probing differential optical and coverage behavior in nanotube-nanocrystal heterostructures synthesized by covalent versus non-covalent approaches.
Double-walled carbon nanotube (DWNT)-CdSe heterostructures with the individual nanoscale building blocks linked together by 4-aminothiophenol (4-ATP) have been successfully synthesized using two different and complementary routes, i.e. covalent attachment and non-covalent π-π stacking. Specifically, using a number of characterization methods, we have probed the effects of these differential synthetic coupling approaches on the resulting CdSe quantum dot (QD) coverage on the underlying nanotube template as well as the degree of charge transfer between the CdSe QDs and the DWNTs. In general, based on microscopy and spectroscopy data collectively, we noted that heterostructures generated by non-covalent π-π stacking interactions evinced not only higher QD coverage density but also possibly more efficient charge transfer behavior as compared with their counterparts produced using covalent linker-mediated protocols.


Extent of resection of epidermoid tumors and risk of recurrence: case report and meta-analysis.
Intracranial epidermoid tumors are slow-growing, histologically benign tumors of epithelial cellular origin that can be symptomatic because of their size and mass effect. Neurosurgical resection, while the treatment of choice, can be quite challenging due to locations where these lesions commonly occur and their association with critical neurovascular structures. As such, subtotal resection (STR) rather than gross-total resection (GTR) can often be performed, rendering residual and recurrent tumor potentially problematic. The authors present a case of a 28-year-old man who underwent STR followed by aggressive repeat resection for regrowth, and they report the results of the largest meta-analysis to date of epidermoid tumors to compare recurrence rates for STR and GTR. The authors conducted a systemic review of PubMed, Web of Science, and the Cochrane Collaboration following the PRISMA guidelines. They then conducted a proportional meta-analysis to compare the pooled recurrence rates between STR and GTR in the included studies. The authors developed fixed- and mixed-effect models to estimate the pooled proportions of recurrence among patients undergoing STR or GTR. They also investigated the relationship between recurrence rate and follow-up time in the previous studies using linear regression and natural cubic spline models. Overall, 27 studies with 691 patients met the inclusion criteria; of these, 293 (42%) underwent STR and 398 (58%) received GTR. The average recurrence rate for all procedures was 11%. The proportional meta-analysis showed that the pooled recurrence rate after STR (21%) was 7 times greater than the rate after GTR (3%). The average recurrence rate for studies with longer follow-up durations (≥ 4.4 years) (17.4%) was significantly higher than the average recurrence rate for studies with shorter follow-up durations (< 4.4 years) (5.7%). The cutoff point of 4.4 years was selected based on the significant relationship between the recurrence rate of both STR and GTR and follow-up durations in the included studies (p = 0.008). STR is associated with a significantly higher rate of epidermoid tumor recurrence compared to GTR. Attempts at GTR should be made during the initial surgery with efforts to optimize success. Surgical expertise, as well as the use of adjuncts, such as intraoperative MRI and neuromonitoring, may increase the likelihood of completing a safe GTR and decreasing the long-term risk of recurrence. The most common surgical complications were transient cranial nerve palsies, occurring equally in STR and GTR cases when reported. In all postoperative epidermoid tumor cases, but particularly following STR, close follow-up with serial MRI, even years after surgery, is recommended.


Cold-acclimation in Peromyscus: temporal effects and individual variation in maximum metabolism and ventilatory traits.
Thermal acclimation in small endotherms provides an excellent model for the study of physiological plasticity, as energy requirements can be easily manipulated and the results are relevant for natural conditions. Nevertheless, how physiology changes throughout acclimation, and how individuals vary in their response to acclimation, remain poorly understood. Here we describe a high temporal-resolution study of cold acclimation in the deer mouse Peromyscus maniculatus. The experimental design was based on repeated measures at short intervals throughout cold acclimation, with controls (maintained at constant temperature) for measurement artifacts. We monitored body mass, maximum metabolic rate in cold exposure and ventilatory traits (respiratory frequency, tidal and minute volume and oxygen extraction) for 3 weeks at 23 degrees C. Then, half of the individuals were held for 7 weeks at 5 degrees C. Body mass was differently affected by cold acclimation depending on sex. Maximal metabolism ((O(2)max)) increased significantly during the first week of cold acclimation, "overshot" after 5 weeks and dropped to a plateau about 34% above control values at week 7. Similarly, ventilatory traits increased during cold acclimation, though responses were different in their kinetics and magnitude. Body mass, maximum metabolism, and most ventilatory traits were repeatable after 7 weeks in control and cold-acclimated animals. However, repeatability tended to be lower in the cold-acclimated group, especially while animals were still acclimating. Our results show that acclimation effects may be under- and/or overestimated, depending on when trials are performed, and that different traits respond differently, and at different rates, to acclimation. Hence, future studies should be designed to ensure that animals have attained steady-state values in acclimation experiments.


Role of the primary health care team in preventing accidents to children.
Accidents are the most common cause of mortality in children and account for considerable childhood morbidity. The identification of risk factors for childhood accidents suggests that many are predictable and therefore preventable. Numerous interventions have been found to be effective in reducing the morbidity and mortality from childhood accidents. The scope for accident prevention within the primary care setting and the roles of the members of the primary health care team are discussed. Finally, the problems associated with the team undertaking accident prevention work are explored and solutions suggested.


[Displaced women's opinion of the impact of forced displacement on their health].
To analyze the adaptation process of women internally displaced to the city and the relationship between displacement and their self-perceived main health problems. A qualitative, exploratory, descriptive study was carried out by means of semi-structured individual interviews with a maximum variation sample of 25 internally displaced women. A narrative content analysis was conducted with mixed generation of categories and data segmentation by age and themes. The area under study consisted of five localities in the city of Bogotá (Colombia). According to the interviewed women's discourses, their adaptation to city life depended on the new socioeconomic and environmental conditions and the psychosocial impact of displacement on the family. Precarious economic conditions forced them to live in an unhealthy environment and, occasionally, to adopt the role of head of household. In this role, many of these women, particularly young women, faced great difficulties in ensuring that the family's needs were met. Young women and teenagers reported behavioral changes due to displacement, including reproduction of violence in the home. The main self-perceived health problems among displaced women were mental health, access to food, infections and gynecological alterations. Displaced women identified the main factors hindering their access to health services as their economic situation and home responsibilities. Displaced women face new environmental and family challenges that negatively affect their health and access to healthcare. Specific interventions aimed at displaced women are required to foster better health through access to work and long -term socioeconomic stability.


Foxl2a and Foxl2b are involved in midbrain-hindbrain boundary development in zebrafish.
Foxl2 plays conserved central function in ovarian differentiation and maintenance in several fish species. However, its expression pattern and function in fish embryogenesis are still largely unknown. In this study, we first presented a sequential expression pattern of zebrafish foxl2a and foxl2b during embryo development. They were predominantly expressed in the cranial paraxial mesoderm (CPM) and cranial venous vasculature (CVV) during somitogenesis and subsequently expressed in the pharyngeal arches after 48 h post-fertilization (hpf). Then, we compared the brain structures among zebrafish wildtype (WT) and three homozygous foxl2 mutants (foxl2a-/-, foxl2b-/- and foxl2a-/-;foxl2b-/-) and found the reduction of the fourth ventricle in the three foxl2 mutants, especially in foxl2a-/-;foxl2b-/- mutant. Finally, we detected several key transcription factors involved in the gene regulatory network of midbrain-hindbrain boundary (MHB) patterning, such as wnt1, en1b and pax2a. Their expression levels were obviously downregulated in MHB of foxl2a-/- and foxl2a-/-;foxl2b-/- mutants. Thus, we suggest that Foxl2a and Foxl2b are involved in MHB and the fourth ventricle development in zebrafish. The current study provides insights into the molecular mechanism underlying development of brain ventricular system.


Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1.
We have identified the physical interaction between the Breast Cancer susceptibility gene product BRCA1 and the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and DNA mismatch repair (MMR) gene product hMSH2, both in vitro and in vivo. The BRCA1-hMSH2 association involved several well-defined regions of both proteins which include the adenosine nucleotide binding domain of hMSH2. Moreover, the interaction of BRCA1 with purified hMSH2-hMSH6 appears to be modulated by adenosine nucleotide much like G protein downstream interaction/signaling is modulated by guanosine nucleotide. BARD1, another BRCA1-interacting protein, was also found to interact with hMSH2. In addition, BRCA1 was found to associate with both hMSH3 and hMSH6, the heterodimeric partners of hMSH2. These observations implicate BRCA1/BARD1 as downstream effectors of the adenosine nucleotide-activated hMSH2-hMSH6 signaling complex, and suggest a global role for BRCA1 in DNA damage processing. The functional interaction between BRCA1 and hMSH2 may provide a partial explanation for the background of gynecological and colorectal cancer in both HNPCC and BRCA1 kindreds, respectively.


Expression of the liver X receptor alpha and beta in embryonic and adult mice.
We characterized the expression pattern of the nuclear receptors liver X receptor (LXR) alpha and beta during mouse embryonic development and in adulthood by in situ hybridization experiments. LXRalpha and LXRbeta are detected in the liver starting at 11.5 days postcoitum. Later, LXRalpha expression remains high in organs involved in lipid homeostasis, such as liver, intestine, and brown adipose tissue, whereas LXRbeta is more ubiquitously expressed and enriched in tissues of neuronal and endocrine origin.


Why a d-β-hydroxybutyrate monoester?
Much of the world's prominent and burdensome chronic diseases, such as diabetes, Alzheimer's, and heart disease, are caused by impaired metabolism. By acting as both an efficient fuel and a powerful signalling molecule, the natural ketone body, d-β-hydroxybutyrate (βHB), may help circumvent the metabolic malfunctions that aggravate some diseases. Historically, dietary interventions that elevate βHB production by the liver, such as high-fat diets and partial starvation, have been used to treat chronic disease with varying degrees of success, owing to the potential downsides of such diets. The recent development of an ingestible βHB monoester provides a new tool to quickly and accurately raise blood ketone concentration, opening a myriad of potential health applications. The βHB monoester is a salt-free βHB precursor that yields only the biologically active d-isoform of the metabolite, the pharmacokinetics of which have been studied, as has safety for human consumption in athletes and healthy volunteers. This review describes fundamental concepts of endogenous and exogenous ketone body metabolism, the differences between the βHB monoester and other exogenous ketones and summarises the disease-specific biochemical and physiological rationales behind its clinical use in diabetes, neurodegenerative diseases, heart failure, sepsis related muscle atrophy, migraine, and epilepsy. We also address the limitations of using the βHB monoester as an adjunctive nutritional therapy and areas of uncertainty that could guide future research.


The IgG subclasses of platelet-associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura.
The majority of patients with idiopathic thrombocytopenic purpura (ITP) have antiplatelet autoantibodies that are most frequently directed against platelet glycoproteins IIb/IIIa or Ib/IX/V. However, there is some debate whether the immune response is oligoclonal or polyclonal in nature. We investigated the subclass distribution of anti-IIb/IIIa IgG autoantibodies in 59 prospectively studied patients with ITP. We also tested patients with a variety of thrombocytopenic disorders (n=31) and healthy controls (n=30). Platelet lysates were tested for IgG anti-IIb/IIIa autoantibodies, and the specific IgG subclass distribution was measured using antigen capture assays. All testing was done blinded to diagnosis and other assay results. After unblinding, we found that 43 of the 59 ITP patients had anti-IIb/IIIa autoantibodies (sensitivity=73%). Anti-IIb/IIIa autoantibodies were also detected in five of the 31 non-ITP patients, but in none of the 30 healthy controls (specificity=91%). The IgG subclass assay was positive in 39 of the 43 ITP patients with anti-IIb/IIIa antibodies (sensitivity=92%) and in 12 samples that had no detectable anti-IIb/IIIa antibodies including two ITP patients (specificity=83%). The most common subclass in the ITP patient samples was IgG1 (77%), either alone (n=14) or with other IgG subclass antibodies (n=19). However, there were also patients with only IgG2 (n=2), IgG3 (n=3) or IgG4 (n=3) antibodies. Our results are consistent with the hypothesis that ITP is a heterogeneous disorder and that some patients have evidence of oligoclonality, whereas other patients have polyclonal autoantibodies.


Single-molecule observation of protein adsorption onto an inorganic surface.
Understanding the interactions between silicon-based materials and proteins from the bloodstream is of key importance in a myriad of realms, such as the design of nanofluidic devices and functional biomaterials, biosensors, and biomedical molecular diagnosis. By using nanopores fabricated in 20 nm-thin silicon nitride membranes and highly sensitive electrical recordings, we show single-molecule observation of nonspecific protein adsorption onto an inorganic surface. A transmembrane potential was applied across a single nanopore-containing membrane immersed into an electrolyte-filled chamber. Through the current fluctuations measured across the nanopore, we detected long-lived captures of bovine serum albumin (BSA), a major multifunctional protein present in the circulatory system. Based upon single-molecule electrical signatures observed in this work, we judge that the bindings of BSA to the nitride surface occurred in two distinct orientations. With some adaptation and further experimentation, this approach, applied on a parallel array of synthetic nanopores, holds potential for use in methodical quantitative studies of protein adsorption onto inorganic surfaces.


Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations.
Human serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow's drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.


Demographics, management, and welfare of nonracing horses in Prince Edward Island.
There are no detailed, representative, horse-level data about equine management practices in different parts of Canada. To help address this, the demographics, management, and welfare of 312 nonracing horses in Prince Edward Island were examined in a randomized, horse-level survey during summer 2002. Owners completed a pretested questionnaire, and a veterinarian examined each horse. Owners were experienced caregivers and the horses were generally in good condition. Areas for improvement included parasite control, dental and hoof care, and tail docking. The mean fecal egg count was 428 eggs per gram; 76% of owners never removed manure from the pasture. Sixty-two percent of horses had never had a veterinary dental examination. Many horses had hoof defects (excessively long hooves, 26.8%; hoof wall breaks, 32.0%; and white line disease, 8.5%). Many (54.9%) draft horses had docked tails. These results suggest owners might benefit their horses by receiving education in aspects of equine care.


Photoinitiated growth of sub-7 nm silver nanowires within a chemically active organic nanotubular template.
Self-assembled supramolecular nanotubes of J-aggregated amphiphilic cyanine dye in aqueous solution are employed as chemically active templates for the photoinitiated formation of silver nanowires with a very small and homogeneous diameter of (6.4 +/- 0.5) nm. Key features of the template are (1) its small and well-defined diameter; (2) its photochemical activity, which allows photoinitiation of the structure formation; and (3) the processability in aqueous solution. The latter includes the potential to remove the template after the reaction, or to functionalize it further, e.g. with optoelectronically active polycations, providing access to quasi one-dimensional hybrid structures with well-defined metallic nanowires as a core.


Increased hospital admissions associated with extreme-heat exposure in King County, Washington, 1990-2010.
Increased morbidity and mortality have been associated with extreme heat events, particularly in temperate climates. Few epidemiologic studies have considered the impact of extreme heat events on hospitalization rates in the Pacific Northwest region. This study quantifies the historic (May to September 1990-2010) heat-morbidity relationship in the most populous Pacific Northwest County, King County, Washington. A relative risk (RR) analysis was used to explore the association between heat and all non-traumatic hospitalizations on 99th percentile heat days, whereas a time series analysis using a piecewise linear model approximation was used to estimate the effect of heat intensity on hospitalizations, adjusted for temporal trends and day of the week. A non-statistically significant 2% [95% CI: 1.02 (0.98, 1.05)] increase in hospitalization risk, on a heat day vs. a non-heat day, was noted for all-ages and all non-traumatic causes. When considering the effect of heat intensity on admissions, we found a statistically significant 1.59% (95% CI: 0.9%, 2.29%) increase in admissions per degree increase in humidex above 37.4°C. Admissions stratified by cause and age produced statistically significant results with both relative risk and time series analyses for nephritis and nephrotic syndromes, acute renal failure, and natural heat exposure hospitalizations. This study demonstrates that heat, expressed as humidex, is associated with increased hospital admissions. When stratified by age and cause of admission, the non-elderly age groups (<85 years) experience significant risk for nephritis and nephrotic syndromes, acute renal failure, natural heat exposure, chronic obstructive pulmonary disease, and asthma hospitalizations.


A human functional protein interaction network and its application to cancer data analysis.
One challenge facing biologists is to tease out useful information from massive data sets for further analysis. A pathway-based analysis may shed light by projecting candidate genes onto protein functional relationship networks. We are building such a pathway-based analysis system. We have constructed a protein functional interaction network by extending curated pathways with non-curated sources of information, including protein-protein interactions, gene coexpression, protein domain interaction, Gene Ontology (GO) annotations and text-mined protein interactions, which cover close to 50% of the human proteome. By applying this network to two glioblastoma multiforme (GBM) data sets and projecting cancer candidate genes onto the network, we found that the majority of GBM candidate genes form a cluster and are closer than expected by chance, and the majority of GBM samples have sequence-altered genes in two network modules, one mainly comprising genes whose products are localized in the cytoplasm and plasma membrane, and another comprising gene products in the nucleus. Both modules are highly enriched in known oncogenes, tumor suppressors and genes involved in signal transduction. Similar network patterns were also found in breast, colorectal and pancreatic cancers. We have built a highly reliable functional interaction network upon expert-curated pathways and applied this network to the analysis of two genome-wide GBM and several other cancer data sets. The network patterns revealed from our results suggest common mechanisms in the cancer biology. Our system should provide a foundation for a network or pathway-based analysis platform for cancer and other diseases.


Development of microsatellite markers for the rapid and reliable genotyping of Brettanomyces bruxellensis at strain level.
Although many yeasts are useful for food production and beverage, some species may cause spoilage with important economic loss. This is the case of Dekkera/Brettanomyces bruxellensis, a contaminant species that is mainly associated with fermented beverages (wine, beer, cider and traditional drinks). To better control Brettanomyces spoilage, rapid and reliable genotyping methods are necessary to determine the origins of the spoilage, to assess the effectiveness of preventive treatments and to develop new control strategies. Despite several previously published typing methods, ranging from classical molecular methods (RAPD, AFLP, REA-PFGE, mtDNA restriction analysis) to more engineered technologies (infrared spectroscopy), there is still a lack of a rapid, reliable and universal genotyping approach. In this work, we developed eight polymorphic microsatellites markers for the Brettanomyces/Dekkera bruxellensis species. Microsatellite typing was applied to the genetic analysis of wine and beer isolates from Europe, Australia and South Africa. Our results suggest that B. bruxellensis is a highly disseminated species, with some strains isolated from different continents being closely related at the genetic level. We also focused on strains isolated from two Bordeaux wineries on different substrates (grapes, red wines) and for different vintages (over half a century). We showed that all B. bruxellensis strains within a cellar are strongly related at the genetic level, suggesting that one clonal population may cause spoilage over decades. The microsatellite tool now paves the way for future population genetics research of the B. bruxellensis species.


Tuberculosis and patient gender: An analysis and its implications in tuberculosis control.
To analyze the profile of pulmonary tuberculosis patients with respect to gender and its implications in tuberculosis control. DOTS center at a tertiary, teaching hospital in South India. A retrospective study was undertaken by screening medical records of 446 patients with pulmonary tuberculosis. Data studied included age, gender, and sputum smear status. Patients with comorbid conditions were excluded. No other data were considered. The male to female ratio in patients of pulmonary tuberculosis was 2:1, which was also maintained when smear positive and smear negative were studied separately. The ratio of smear positive to smear negative patients was statistically significant at 4.4:1. A large proportion of patients (65-68%) were in the young and reproductive age group. Approximately, one-fifth patients were in the geriatric age group. The observation that two-thirds of all female smear-positive patients were found in the young and reproductive age group has strong implications in tuberculosis control strategies because of higher chances of mother to child transmission and higher probability of complications because of attendant antenatal and postnatal morbidity. Geriatric patients comprise another significant group because of higher chances of default, complications, inconvenience, and existence of other comorbid conditions.


B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor.
A helper factor(s) distinct from interleukin 2 (IL-2) was shown to be present in the concanavalin A-stimulated supernatant of normal mouse spleen cells (normal Con A Sn). Spleen cells thoroughly depleted of T cells required both IL-2 and this factor to produce antibody-secreting cells in response to sheep erythrocytes, although in the presence of IL-2 and a few T cells the requirement for the factor was less apparent. The factor had an apparent approximately 40,000 mol wt. The factor was found in normal Con A Sn that had been depleted of IL-2 by absorption with IL-2-dependent T cells and was absent from Con A-stimulated supernatants of the IL-2-producing T cell hybridoma, FS6-14.13. These results indicate that multiple helper factors control the B cell response to antigen and that IL-2, in addition to its T cell growth promoting activity, plays a direct role in B cell responses.


Imaging the time-integrated cerebral metabolic activity with subcellular resolution through nanometer-scale detection of biosynthetic products deriving from (13)C-glucose.
Glucose is the primary source of energy for the brain but also an important source of building blocks for proteins, lipids, and nucleic acids. Little is known about the use of glucose for biosynthesis in tissues at the cellular level. We demonstrate that local cerebral metabolic activity can be mapped in mouse brain tissue by quantitatively imaging the biosynthetic products deriving from [U-(13)C]glucose metabolism using a combination of in situ electron microscopy and secondary ion mass-spectroscopy (NanoSIMS). Images of the (13)C-label incorporated into cerebral ultrastructure with ca. 100 nm resolution allowed us to determine the timescale on which the metabolic products of glucose are incorporated into different cells, their sub-compartments and organelles. These were mapped in astrocytes and neurons in the different layers of the motor cortex. We see evidence for high metabolic activity in neurons via the nucleus (13)C enrichment. We observe that in all the major cell compartments, such as e.g. nucleus and Golgi apparatus, neurons incorporate substantially higher concentrations of (13)C-label than astrocytes.


Cold adaptive traits revealed by comparative genomic analysis of the eurypsychrophile Rhodococcus sp. JG3 isolated from high elevation McMurdo Dry Valley permafrost, Antarctica.
The permafrost soils of the high elevation McMurdo Dry Valleys are the most cold, desiccating and oligotrophic on Earth. Rhodococcus sp. JG3 is one of very few bacterial isolates from Antarctic Dry Valley permafrost, and displays subzero growth down to -5°C. To understand how Rhodococcus sp. JG3 is able to survive extreme permafrost conditions and be metabolically active at subzero temperatures, we sequenced its genome and compared it to the genomes of 14 mesophilic rhodococci. Rhodococcus sp. JG3 possessed a higher copy number of genes for general stress response, UV protection and protection from cold shock, osmotic stress and oxidative stress. We characterized genome wide molecular adaptations to cold, and identified genes that had amino acid compositions favourable for increased flexibility and functionality at low temperatures. Rhodococcus sp. JG3 possesses multiple complimentary strategies which may enable its survival in some of the harshest permafrost on Earth.


Ethics of artificial intelligence in radiology: summary of the joint European and North American multisociety statement.
This is a condensed summary of an international multisociety statement on ethics of artificial intelligence (AI) in radiology produced by the ACR, European Society of Radiology, RSNA, Society for Imaging Informatics in Medicine, European Society of Medical Imaging Informatics, Canadian Association of Radiologists, and American Association of Physicists in Medicine.AI has great potential to increase efficiency and accuracy throughout radiology, but also carries inherent pitfalls and biases. Widespread use of AI-based intelligent and autonomous systems in radiology can increase the risk of systemic errors with high consequence, and highlights complex ethical and societal issues. Currently, there is little experience using AI for patient care in diverse clinical settings. Extensive research is needed to understand how to best deploy AI in clinical practice.This statement highlights our consensus that ethical use of AI in radiology should promote well-being, minimize harm, and ensure that the benefits and harms are distributed among stakeholders in a just manner. We believe AI should respect human rights and freedoms, including dignity and privacy. It should be designed for maximum transparency and dependability. Ultimate responsibility and accountability for AI remains with its human designers and operators for the foreseeable future.The radiology community should start now to develop codes of ethics and practice for AI which promote any use that helps patients and the common good and should block use of radiology data and algorithms for financial gain without those two attributes.


Cumulative life course and adult socioeconomic status and markers of inflammation in adulthood.
To examine the association between cumulative life course and adult socioeconomic status (SES) and adult levels of inflammatory risk markers (fibrinogen, white blood cell count (WBC), C-reactive protein (CRP), von Willebrand factor (vWF) and an overall inflammatory score). Retrospective cohort study. 12,681 white and African-American participants in the Atherosclerosis Risk in Communities (ARIC) study and two ancillary studies. Participants provided information on SES and place of residence in childhood and young (30-40 years) and mature (45+) adulthood. Residences were linked to census data for neighbourhood SES information. Multiple imputation (MI) was used for missing data. Linear regression and adjusted geometric means were used to estimate the effects of SES on inflammatory risk marker levels. Graded, statistically significant associations were observed between greater cumulative life-course exposure to low education and social class and elevated levels of fibrinogen and WBC among white participants. Stronger graded, statistically significant associations were observed between low adult education, social class and neighbourhood SES and elevated inflammatory levels. Associations were weaker and less consistent in African-Americans. Covariate adjustment attenuated results but many associations remained strong. Our results suggest that cumulative exposure to adverse SES conditions across the life course and low adult SES are associated with an elevated systemic inflammatory burden in adulthood. Chronic systemic inflammation may be one pathway linking low life-course SES and elevated cardiovascular disease risk.


Chemical stability of CdSe quantum dots in seawater and their effects on a marine microalga.
With the increasing use of nanotechnologies, it is expected that nanomaterials end up in natural aquatic systems, from freshwater to the sea. In this work we studied the chemical behaviour of water-soluble CdSe QDs in seawater and their effects on the marine diatom Phaeodactylum tricornutum, as a model of a biological receptor in the marine environment. We evaluated QD toxicity in terms of growth rate inhibition, oxidative stress and ROS accumulation. In addition, we used the synthesis of phytochelatins (PCs) as a biomarker of the presence of free Cd(2+) ions released from QDs. The optical and chemical characterization demonstrated the propensity of QDs to aggregate after dispersion in raw seawater. In addition, bare CdSe QDs, lacking the ZnS shell, underwent a salinity-dependent degradation process. Short-term exposure experiments showed that the ease of degradation of QDs in seawater correlated with the synthesis of PCs in P. tricornutum cells. Long-term exposure experiments, carried out with the most stable CdSe/ZnS QDs, showed that algae accumulated Cd, but synthesized negligible amounts of PCs. Since the production of PCs is a specific signal of the presence of bioavailable metal ions, our findings suggest that QDs, associated to P. tricornutum cells, did not release PC-inducing metal species. Our data also showed a gradual decrease in algal growth rate at concentrations of QDs higher than 0.5nM. Measurements of the activity of the antioxidant enzymes showed that superoxide dismutase (SOD) and catalase (CAT) activities were increased by exposure to [QDs]≥0.5 nM, whereas ascorbate peroxidase (APX) and glutathione reductase (GR) activities were not significantly affected. The increase in SOD and CAT activity can be considered a symptom of oxidative stress induced by an enhanced production of ROS. This hypothesis was confirmed by the concomitant increase in the intracellular ROS concentration.


Parallel two-step phase-shifting digital holograph microscopy based on a grating pair.
An optical configuration for parallel two-step phase-shifting digital holographic microscopy (DHM) based on a grating pair is proposed for the purpose of real-time phase microscopy. Orthogonally circularly polarized object and reference waves are diffracted twice by a pair of gratings, and two parallel copies for each beams come into being. Combined with polarization elements, parallel two-step phase-shifting holograms are obtained. Based on the proposed configuration, two schemes of DHM, i.e., slightly off-axis and on-axis DHM, have been implemented. The slightly off-axis DHM suppresses the dc term by subtracting the two phase-shifting holograms from each other, thus the requirement on the off-axis angle and sampling power of the CCD camera is reduced greatly. The on-axis DHM has the least requirement on the resolving power of the CCD camera, while it requires that the reference wave is premeasured and its intensity is no less than 2 times the maximal intensity of the object wave.


Evaluation of a multiple ecological level child obesity prevention program: Switch what you Do, View, and Chew.
Schools are the most frequent target for intervention programs aimed at preventing child obesity; however, the overall effectiveness of these programs has been limited. It has therefore been recommended that interventions target multiple ecological levels (community, family, school and individual) to have greater success in changing risk behaviors for obesity. This study examined the immediate and short-term, sustained effects of the Switch program, which targeted three behaviors (decreasing children's screen time, increasing fruit and vegetable consumption, and increasing physical activity) at three ecological levels (the family, school, and community). Participants were 1,323 children and their parents from 10 schools in two states. Schools were matched and randomly assigned to treatment and control. Measures of the key behaviors and body mass index were collected at baseline, immediately post-intervention, and 6 months post-intervention. The effect sizes of the differences between treatment and control groups ranged between small (Cohen's d = 0.15 for body mass index at 6 months post-intervention) to large (1.38; parent report of screen time at 6 months post-intervention), controlling for baseline levels. There was a significant difference in parent-reported screen time at post-intervention in the experimental group, and this effect was maintained at 6 months post-intervention (a difference of about 2 hours/week). The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant. At the 6-month follow-up, parent-reported screen time was significantly lower, and parent and child-reported fruit and vegetable consumption was significantly increased. There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group. The intervention effects were moderated by child sex (for fruit and vegetable consumption, physical activity, and weight status), family involvement (for fruit and vegetable consumption), and child body mass index (for screen time). The perception of change among the experimental group was generally positive with 23% to 62% indicating positive changes in behaviors. The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children's fruit and vegetable consumption and minimizing screen time. The Switch program offers promise for use in youth obesity prevention.


[Drugs use among adolescents: results from the National Survey on Addictions, 1998].
The aim of this paper is to describe drug and associated factors use among adolescents (12 to 17 years of age). Data come from the recent Encuesta Nacional de Adicciones, 1998 (National Survey on Addictions) undertaken in urban areas of Mexico. A probabilistic, multi-stage, stratified cluster sampling design was used to select the study population. The sampling unit was the individual in each household. Statistical analysis consisted of the estimation of prevalences of drug use, with 95% confidence intervals. Associations were analyzed using logistic regressions models. Excluding tobacco and alcohol, 3.57% of males and 0.6% of females have used one or more drugs; 2.14% and 0.45% used them in the 12 months previous to the survey, and 1.4% and 0.3% in the previous 30 days, respectively. Marihuana was the drug more often used by males (2.4%) and females (0.45%), followed by inhaled solvents (1.08% and 0.20%), and cocaine (0.99% and 0.22%), respectively. The risk of using illicit drugs was associated to being male, having dropped out from school, perceiving availability, drug use by family and friends, social tolerance among friends, and symptoms of depression. Adolescents between 12 to 17 years of age are exposed to increasing drug use. The rates of drug use have risen, especially in the northern region of Mexico and in the big urban areas (Tijuana, Mexico City and Guadalajara). These findings emphasize the need to develop campaigns to detect emotional problems. Preventive measures should provide appropriate care to prevent drug use as a mechanism to cope with such emotional conflicts. Also, more intense preventive interventions should be targeted to adolescents with a high probability of developing drug abuse.


Physical Fitness and Dyslipidemia Among Japanese: A Cohort Study From the Niigata Wellness Study.
Grip strength reflects systemic muscle strength and mass and is reportedly associated with various metabolic variables. However, its prognostic association with dyslipidemia is unknown. We examined the association of grip strength and other physical fitness markers with the incidence of dyslipidemia among Japanese adults. A total of 16,149 Japanese (6,208 women) individuals aged 20-92 years who underwent a physical fitness test between April 2001 and March 2002 were included in this cohort study. Grip strength, vertical jump, single-leg balance with eyes closed, forward bending, and whole-body reaction time were evaluated at baseline. Dyslipidemia was annually determined based on fasting serum lipid profiles and self-reported dyslipidemia from April 2001 to March 2008. During the follow-up period, 4,458 (44.9%) men and 2,461 (39.6%) women developed dyslipidemia. A higher relative grip strength (grip strength/body mass index) was associated with a lower incidence of dyslipidemia among both men and women (P for trend <0.001). Compared with those for the first septile, the hazards ratios and 95% confidence intervals (CIs) for the seventh septile were 0.56 (95% CI, 0.50-0.63) for men and 0.69 (95% CI, 0.58-0.81) for women. Moreover, relative vertical jump (vertical jump strength/body mass index) was also inversely associated with the incidence of dyslipidemia among both men and women (P for trend <0.001). There was no association between other physical fitness and dyslipidemia among both men and women. Relative grip strength and vertical jump may be useful risk markers of the incidence of dyslipidemia.


Associations between respiratory health and ozone and fine particulate matter during a wildfire event.
Wildfires have been increasing in frequency in the western United States (US) with the 2017 and 2018 fire seasons experiencing some of the worst wildfires in terms of suppression costs and air pollution that the western US has seen. Although growing evidence suggests respiratory exacerbations from elevated fine particulate matter (PM2.5) during wildfires, significantly less is known about the impacts on human health of ozone (O3) that may also be increased due to wildfires. Using machine learning, we created daily surface concentration maps for PM2.5 and O3 during an intense wildfire in California in 2008. We then linked these daily exposures to counts of respiratory hospitalizations and emergency department visits at the ZIP code level. We calculated relative risks of respiratory health outcomes using Poisson generalized estimating equations models for each exposure in separate and mutually-adjusted models, additionally adjusted for pertinent covariates. During the active fire periods, PM2.5 was significantly associated with exacerbations of asthma and chronic obstructive pulmonary disease (COPD) and these effects remained after controlling for O3. Effect estimates of O3 during the fire period were non-significant for respiratory hospitalizations but were significant for ED visits for asthma (RR = 1.05 and 95% CI = (1.022, 1.078) for a 10 ppb increase in O3). In mutually-adjusted models, the significant findings for PM2.5 remained whereas the associations with O3 were confounded. Adjusted for O3, the RR for asthma ED visits associated with a 10 μg/m3 increase in PM2.5 was 1.112 and 95% CI = (1.087, 1.138). The significant findings for PM2.5 but not for O3 in mutually-adjusted models is likely due to the fact that PM2.5 levels during these fires exceeded the 24-hour National Ambient Air Quality Standard (NAAQS) of 35 μg/m3 for 4976 ZIP-code days and reached levels up to 6.073 times the NAAQS, whereas our estimated O3 levels during the fire period only occasionally exceeded the NAAQS of 70 ppb with low exceedance levels. Future studies should continue to investigate the combined role of O3 and PM2.5 during wildfires to get a more comprehensive assessment of the cumulative burden on health from wildfire smoke.


Changes in cardiac glycoside receptor sites, 86rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phases of treatment of cardiac failure in regular rhythm and of atrial fibrillation.
1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocytic 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of patients receiving digoxin in the short-term for atrial fibrillation or cardiac failure in regular rhythm. 2 During the first few days of treatment [3H]-digoxin binding and 86rubidium uptake fall and intraerythrocytic sodium concentrations rise. 3 Subsequently parallel fluctuations occur in [3H]-digoxin binding and 86rubidium uptake but not in intraerythrocytic sodium concentrations and the significance of the fluctuations is discussed. 4 The values of all three measurements correlate significantly with the response of the heart in sinus rhythm as measured by QS2I. 5 Plasma digoxin concentrations do not correlate with QS2I.


Are deficits in cognition associated with psychotic-like experiences after cannabis?
Not all individuals who smoke cannabis report psychotic-like experiences. Given that risk factors for psychotic disorders are multifaceted, precipitating factors to psychotic-like experiences after cannabis are likely to be equally complex. Reduced neurocognitive performance is associated with both psychosis risk and cannabis use. Therefore, it is possible cognitive performance may differentiate those who report psychotic-like experiences after cannabis from those who do not. We determined whether those reporting psychotic/dysphoric experiences after cannabis had reduced neurocognitive performance compared to those reporting primarily euphoric experiences. Participants were recruited on the basis of responses to the cannabis high captured by the Psychosis-Dysphoric and Euphoric experiences subscales from the Cannabis Experiences Questionnaire (CEQ). Compared to participants reporting primarily euphoric cannabis experiences (n = 36; 44% male; mean age (SD) = 28 (9) years), those who reported psychotic/dysphoric experiences (n = 40; 45% male; mean age (SD) = 26 (5) years) demonstrated significantly faster responses to a trial and error learning task. In the presence of distracters, those with psychotic/dysphoric experiences after cannabis made more errors on a Continuous Performance Task. Those who report psychotic/dysphoric experiences after cannabis have subtle inefficiencies in their cognitive processes. The multiple factors which predict vulnerability to psychotic-like experiences after cannabis require further investigation.


Impact of the topology of global macroeconomic network on the spreading of economic crises.
Throughout economic history, the global economy has experienced recurring crises. The persistent recurrence of such economic crises calls for an understanding of their generic features rather than treating them as singular events. The global economic system is a highly complex system and can best be viewed in terms of a network of interacting macroeconomic agents. In this regard, from the perspective of collective network dynamics, here we explore how the topology of the global macroeconomic network affects the patterns of spreading of economic crises. Using a simple toy model of crisis spreading, we demonstrate that an individual country's role in crisis spreading is not only dependent on its gross macroeconomic capacities, but also on its local and global connectivity profile in the context of the world economic network. We find that on one hand clustering of weak links at the regional scale can significantly aggravate the spread of crises, but on the other hand the current network structure at the global scale harbors higher tolerance of extreme crises compared to more "globalized" random networks. These results suggest that there can be a potential hidden cost in the ongoing globalization movement towards establishing less-constrained, trans-regional economic links between countries, by increasing vulnerability of the global economic system to extreme crises.


A case of late onset leukoencephalopathy with cerebral calcifications and cysts in a 59-year-old woman.
Leukoencephalopathy with cerebral calcifications and cysts (LCC) is a recently described, very rare entity, clinically characterized by progressive neurological deficits such as cognitive decline, epileptic seizures, pyramidal, extrapyramidal and cerebellar symptoms/signs. With the exception of two patients with adult onset, in all previously described cases symptoms onset occurred between early infancy and adolescence. We report a case of late onset LCC in a 59-year-old woman presenting with urinary and fecal incontinence and behavioural changes, then rapid progression with hemianopia, hemiparesis, ataxia and cognitive decline. Extensive work-up was performed, including brain magnetic resonance imaging, magnetic resonance spectroscopy, cyst fluid analysis and brain biopsy, confirming the final diagnosis of LCC. Our case supports the existence of a late onset adult form of LCC.


Macromolecular networks and intelligence in microorganisms.
Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of information and communication technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity - particularly activity of the human brain - with a phenomenon we call "intelligence." Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as "human" and "brain" out of the defining features of "intelligence," all forms of life - from microbes to humans - exhibit some or all characteristics consistent with "intelligence." We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo.


Open by default: a proposed copyright license and waiver agreement for open access research and data in peer-reviewed journals.
Copyright and licensing of scientific data, internationally, are complex and present legal barriers to data sharing, integration and reuse, and therefore restrict the most efficient transfer and discovery of scientific knowledge. Much data are included within scientific journal articles, their published tables, additional files (supplementary material) and reference lists. However, these data are usually published under licenses which are not appropriate for data. Creative Commons CC0 is an appropriate and increasingly accepted method for dedicating data to the public domain, to enable data reuse with the minimum of restrictions. BioMed Central is committed to working towards implementation of open data-compliant licensing in its publications. Here we detail a protocol for implementing a combined Creative Commons Attribution license (for copyrightable material) and Creative Commons CC0 waiver (for data) agreement for content published in peer-reviewed open access journals. We explain the differences between legal requirements for attribution in copyright, and cultural requirements in scholarship for giving individuals credit for their work through citation. We argue that publishing data in scientific journals under CC0 will have numerous benefits for individuals and society, and yet will have minimal implications for authors and minimal impact on current publishing and research workflows. We provide practical examples and definitions of data types, such as XML and tabular data, and specific secondary use cases for published data, including text mining, reproducible research, and open bibliography. We believe this proposed change to the current copyright and licensing structure in science publishing will help clarify what users - people and machines - of the published literature can do, legally, with journal articles and make research using the published literature more efficient. We further believe this model could be adopted across multiple publishers, and invite comment on this article from all stakeholders in scientific research.


An extensively glycosylated archaeal pilus survives extreme conditions.
Pili on the surface of Sulfolobus islandicus are used for many functions, and serve as receptors for certain archaeal viruses. The cells grow optimally at pH 3 and ~80 °C, exposing these extracellular appendages to a very harsh environment. The pili, when removed from cells, resist digestion by trypsin or pepsin, and survive boiling in sodium dodecyl sulfate or 5 M guanidine hydrochloride. We used electron cryo-microscopy to determine the structure of these filaments at 4.1 Å resolution. An atomic model was built by combining the electron density map with bioinformatics without previous knowledge of the pilin sequence-an approach that should prove useful for assemblies where all of the components are not known. The atomic structure of the pilus was unusual, with almost one-third of the residues being either threonine or serine, and with many hydrophobic surface residues. While the map showed extra density consistent with glycosylation for only three residues, mass measurements suggested extensive glycosylation. We propose that this extensive glycosylation renders these filaments soluble and provides the remarkable structural stability. We also show that the overall fold of the archaeal pilin is remarkably similar to that of archaeal flagellin, establishing common evolutionary origins.


Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT).
Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/μL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections. Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected. IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/μL (IL-2 arm) and 463cells/μL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/μL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively. Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration.


Migration and activation of antigen-specific CD8+ T cells upon in vivo stimulation with allogeneic tumor.
The response of CD8+ T cells to allogeneic tumor was studied by adoptive transfer of cells from TCR transgenic 2C mice specific for Ld alloantigen. Transferred cells were monitored during the course of a response to i.p. challenge with live P815 (H-2d) using the 1B2 mAb specific for the 2C TCR. Tumor was present in the draining LN and spleen within 3 to 4 days of challenge. The first changes in 1B2+ cells occurred in the spleen on day 4; VLA-4 expression increased in an Ag-specific manner and L-selectin expression decreased in an Ag-nonspecific manner. The number of 1B2+ cells in the spleen declined over days 4 to 6. The first detectable increase in CD25 expression and blast transformation was in the peritoneal cavity beginning days 5 and 6. Clonal expansion was largely limited to this site and was maximal on day 8. As expansion occurred in the peritoneal cavity; the number of 1B2+ cells in the draining LN and spleen also increased. These cells had an activated phenotype (CD44(high), VLA-4(high)) but most did not express CD25 and were not blasts. These results suggest that initial Ag recognition in the spleen results in altered expression of adhesion receptors so that cells gain access to the peritoneal cavity where they undergo clonal expansion and differentiation. Following the response, 1B2+ cells decline in number but a memory population (CD44(high), L-selectin(high and low)) persists for long times in the spleen and LN.


Human resource leadership: the key to improved results in health.
This article is the lead article in the Human Resources for Health journal's first quarterly feature. The series of seven articles has been contributed by Management Sciences for Health (MSH) under the theme of leadership and management in public health and will be published article by article over the next few weeks. The journal has invited Dr Manuel M. Dayrit, Director of the WHO Department of Human Resources for Health and former Minister of Health for the Philippines to launch the feature with an opening editorial to be found in the journal's blog. This opening article describes the human resource challenges that managers around the world report and analyses why solutions often fail to be implemented. Despite rising attention to the acute shortage of health care workers, solutions to the human resource (HR) crisis are difficult to achieve, especially in the poorest countries. Although we are aware of the issues and have developed HR strategies, the problem is that some old systems of leading and managing human resources for health do not work in today's context. The Leadership Development Program (LDP) is grounded on the belief that good leadership and management can be learned and practiced at all levels. The case studies in this issue were chosen to illustrate results from using the LDP at different levels of the health sector. The LDP makes a profound difference in health managers' attitudes towards their work. Rather than feeling defeated by a workplace climate that lacks motivation, hope, and commitment to change, people report that they are mobilized to take action to change the status quo. The lesson is that without this capacity at all levels, global policy and national HR strategies will fail to make a difference.


Slowing down the Ras lane: miRNAs as tumor suppressors?
MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression by promoting the degradation of transcribed messages or by inhibiting translation. Although bioinformatic approaches suggest that miRNAs may regulate the expression of a large fraction of the genome, the determination of miRNA gene targets and biological functions has been comparatively limited. Emerging studies suggest that many miRNAs may participate in human disease, including oncogenesis; but for the most part, the observations have been correlative. A recent study by Johnson and colleagues indicates that the let-7 miRNA negatively regulates the oncogenic family of Ras guanosine triphosphatases in both Caenorhabditis elegans and human tumor cell lines, suggesting that let-7 may act as a tumor suppressor. This work raises several important questions: Can other miRNAs act as tumor suppressors or oncogenes? Is miRNA deregulation a critical aspect of tumor development and maintenance? A number of recent studies have begun to address some of these functional questions, providing the field with a greater understanding of the role of miRNAs in cancer.


Too little but not too late: results of a literature review to improve routine immunization programs in developing countries.
Globally, immunization services have been the center of renewed interest with increased funding to improve services, acceleration of the introduction of new vaccines, and the development of a health systems approach to improve vaccine delivery. Much of the credit for the increased attention is due to the work of the GAVI Alliance and to new funding streams. If routine immunization programs are to take full advantage of the newly available resources, managers need to understand the range of proven strategies and approaches to deliver vaccines to reduce the incidence of diseases. In this paper, we present strategies that may be used at the sub-national level to improve routine immunization programs. We conducted a systematic review of studies and projects reported in the published and gray literature. Each paper that met our inclusion criteria was rated based on methodological rigor and data were systematically abstracted. Routine-immunization - specific papers with a methodological rigor rating of greater than 60% and with conclusive results were reported. Greater than 11,000 papers were identified, of which 60 met our inclusion criteria and 25 papers were reported. Papers were grouped into four strategy approaches: bringing immunizations closer to communities (n = 11), using information dissemination to increase demand for vaccination (n = 3), changing practices in fixed sites (n = 4), and using innovative management practices (n = 7). Immunization programs are at a historical crossroads in terms of developing new funding streams, introducing new vaccines, and responding to the global interest in the health systems approach to improving immunization delivery. However, to complement this, actual service delivery needs to be strengthened and program managers must be aware of proven strategies. Much was learned from the 25 papers, such as the use of non-health workers to provide numerous services at the community level. However it was startling to see how few papers were identified and in particular how few were of strong scientific quality. Further well-designed and well-conducted scientific research is warranted. Proposed areas of additional research include integration of additional services with immunization delivery, collaboration of immunization programs with new partners, best approaches to new vaccine introduction, and how to improve service delivery.


Perspectives on molecular targeted therapies and clinical trials for neurodegenerative diseases.
Recent advancements in neurobiology have provided increasing insights into the pathophysiology of neurodegenerative diseases, and opened doors to the development of molecular targeted therapies. Although many compounds showed positive results in animal studies, there is almost no drug for which the efficacy has been confirmed in clinical trials. This failure reflects a number of unsolved problems: limited knowledge of the exact pathways of neuron loss; safety and delivery issues of compounds; lack of established animal models that faithfully recapitulate human pathology; lack of validated, sensitive outcome measures; and limited tools to diagnose pre-symptomatic patients. To investigate the efficacy of potential disease modifying agents with limited financial and patient resources, the efficiency of both basic and clinical studies should be improved by integrated approaches. The reproduction of positive results from animal experiments that analyse the efficacy of compounds at symptomatic stages is needed to improve the credibility of preclinical studies. To effectuate proof of concept processes, novel designs of phase 2 clinical trials, such as the futility study, are being developed. Given the modest effects of molecular targeted therapies in human, it is necessary to explore clinical outcome measures that are resistant to variability, subjectivity and placebo. Furthermore, there is an increasing need for testing interventions before the onset of symptoms. Analyses of natural histories of biological and neurophysiological markers may provide indispensable information for designing such preventive trials. As it is now clear that conventional approaches are not necessarily appropriate for the development of molecular targeted therapies, both basic and clinical studies require conceptual innovation.


SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
We have identified the yeast and human homologs of the SKP1 gene as a suppressor of cdc4 mutants and as a cyclin F-binding protein. Skp1p indirectly binds cyclin A/Cdk2 through Skp2p, and directly binds Skp2p, cyclin F, and Cdc4p through a novel structural motif called the F-box. SKP1 is required for ubiquitin-mediated proteolysis of Cin2p, Clb5p, and the Cdk inhibitor Sic1p, and provides a link between these molecules and the proteolysis machinery. A large number of proteins contain the F-box motif and are thereby implicated in the ubiquitin pathway. Different skp1 mutants arrest cells in either G1 or G2, suggesting a connection between regulation of proteolysis in different stages of the cycle.


Mass Spectrometry Techniques: Principles and Practices for Quantitative Proteomics.
In the current omics-age of research, major developments have been made in technologies that attempt to survey the entire repertoire of genes, transcripts, proteins, and metabolites present within a cell. While genomics has led to a dramatic increase in our understanding of such things as disease morphology and how organisms respond to medications, it is critical to obtain information at the proteome level since proteins carry out most of the functions within the cell. The primary tool for obtaining proteome-wide information on proteins within the cell is mass spectrometry (MS). While it has historically been associated with the protein identification, developments over the past couple of decades have made MS a robust technology for protein quantitation as well. Identifying quantitative changes in proteomes is complicated by its dynamic nature and the inability of any technique to guarantee complete coverage of every protein within a proteome sample. Fortunately, the combined development of sample preparation and MS methods have made it capable of quantitatively comparing many thousands of proteins obtained from cells and organisms.


Knowing your nose better than your thumb: measures of over-grasp reveal that face-parts are special for grasping.
Typically, when a grasping response is made, the hand opens wider than the target object. We show that this "over-grasp" response is reduced when we reach to parts of our own face, relative to when we reach to other body parts or to neutral objects. This is not due to reaching to different parts of body space, as over-grasp responses are indifferent to whether or not other body parts or neutral objects are placed close to the face. It is also not due to differences in perceptual knowledge of the size of the target object. We conclude instead that the familiarity of face parts influences the grasping response directly. Subsequent experiments demonstrate that the movement representation determining any effect is not based on a torso-centred frame, and not abstracted from the specific hand used for grasping. We discuss the implications of the results for understanding and measuring motor representations for familiar actions.


Cerebral ventricular size and neuropsychological impairment in young chronic schizophrenics. Measurement by the standardized Luria-Nebraska Neuropsychological Battery.
The relationship between size of cerebral ventricles in chronic schizophrenics and performance on a comprehensive neuropsychological battery, the Standardized Luria-Nebraska Neuropsychological Battery, was investigated. Ventricular size was determined by using a planimeter to measure the size of the lateral ventricles and the ventricular body, if present, on the computerized tomographic (CT) scan image that showed the largest lateral ventricles. This number was divided by the size of the brain as a whole on the same image of the CT scan to yield a ventricular brain ratio. This ratio was then correlated with the scores on the Luria-Nebraska Neuropsychological Battery. Eight of the 14 scales of the Luria-Nebraska Neuropsychological Battery correlated significantly at the .05 level with the ventricular brain ratio in a sample of 42 chronic schizophrenics with an average age of 32.3 years. Overall, there was a multiple correlation of .72 between the ventricular brain ratio and Luria scores. The overall ventricular brain ratio for the schizophrenics was significantly above that found in normal populations. Changes in the size of the ventricles in schizophrenics appear to have significant correlates with measures of neuropsychological performance.


An Escherichia coli O157-specific engineered pyocin prevents and ameliorates infection by E. coli O157:H7 in an animal model of diarrheal disease.
AvR2-V10.3 is an engineered R-type pyocin that specifically kills Escherichia coli O157, an enteric pathogen that is a major cause of food-borne diarrheal disease. New therapeutics to counteract E. coli O157 are needed, as currently available antibiotics can exacerbate the consequences of infection. We show here that orogastric administration of AvR2-V10.3 can prevent or ameliorate E. coli O157:H7-induced diarrhea and intestinal inflammation in an infant rabbit model of infection when the compound is administered either in a postexposure prophylactic regimen or after the onset of symptoms. Notably, administration of AvR2-V10.3 also reduces bacterial carriage and fecal shedding of this pathogen. Our findings support the further development of pathogen-specific R-type pyocins as a way to treat enteric infections.


First Report of Erwinia persicinus Causing Wilting of Medicago sativa Sprouts in China.
Medicago sativa L. is one of the most important perennial forage crops and has been cultivated for more than 2,000 years in China. A previously unreported sprout wilt disease of M. sativa, affecting as much as 25% of the seedlings, was observed in northwest China (Gansu Province) in March 2011. First symptoms on the sprouts were dehydration and yellowing. Within 24 to 48 h, the sprouts stopped growing, wilted, turned brown, and bacteria began oozing from the material. Three symptomatic sprout samples collected from a grower with the wilt problem were processed for microbiological analysis. Bacteria isolated from symptomatic samples produced a pink, diffusible pigment in King's medium B and nutrient agar supplemented with glucose, sucrose, and maltose. The three isolates were negative for gram stain reaction, oxidase, production of hydrogen sulfide and indole, growth in KCN broth, arginine dihydrolase activity, hydrolysis of casein, hydrolysis of gelatin, and acid production from L-arabinose, dulcitol, glycerol, lyxose, and starch. In contrast, they were positive for catalase, nitrate reduction, Voges-Proskauer, hydrolysis of aesculin, acid production from D-ribose, maltose and sucrose, assimilation of adonitol, L-lactate, mannitol, Myo-inositol, erythritol, sorbitol, and sucrose, and growth in 5% NaCl at 36°C. The 16S rDNA of three isolates (Cp1, Cp2, and Cp3) was amplified using the 7F (5'-CAGAGTTTGATCCTGGCT-3') and 1540R (5'-AGGAGGTGATCCAGCCGCA-3') primers. The sequences for the 1,428-bp amplicon from the isolates were identical (GenBank Accession No. JN900058) and had 99% sequence identity with 16S rDNA of Erwinia persicinus strains (including the type strain LMG 11254 [GenBank Accession No. Z96086.1], GS 04 [GenBank Accession No. DQ365580.1], LPPA 373 [GenBank Accession No. AJ937837.1], LPPA 408 [GenBank Accession No. AM294946.1], LMG 2691 [GenBank Accession No. AJ001190.1], and HK 204 [GenBank Accession No. NR_026049.1]). The three isolates were also evaluated in pathogenicity tests. Bacterial suspensions (108 CFU/ml) were spray inoculated on 7-day-old M. sativa sprouts of cv. Algonquin. The inoculated sprouts were placed onto 2% water agar in petri dishes (five sprouts per 9-cm dish) with four dishes for each bacterial isolate and control. The dishes were sealed with Parafilm for 2 days and held in an incubator at 25°C with a 12-h photoperiod. Assays were repeated twice. Symptoms that developed within 7 days were similar to those originally observed, whereas symptoms did not occur on control sprouts sprayed with sterile distilled water. Bacteria sharing the characteristics of the inoculated isolates were recovered from symptomatic sprouts, hence fulfilling Koch's postulates. E. persicinus has been isolated previously from Phaseolus vulgaris (1), Pisum sativum (2), tomato, banana, and cucumber (3). To our knowledge, this is the first report of E. persicinus from M. sativa. References: (1) A. J. González et al. Plant Dis. 89:109, 2005. (2) A. J. González et al. Plant Dis. 91:460, 2007. (3) M. V. Hao et al. Int. J. Syst. Bacteriol. 40:379, 1990.