Regional species pools control community saturation in lake phytoplankton.
Recent research has highlighted that positive biodiversity-ecosystem functioning relationships hold for all groups of organisms, including microbes. Yet, we still lack understanding regarding the drivers of microbial diversity, in particular, whether diversity of microbial communities is a matter of local factors, or whether metacommunities are of similar importance to what is known from higher organisms. Here, we explore the driving forces behind spatial variability in lake phytoplankton diversity in Fennoscandia. While phytoplankton biovolume is best predicted by local phosphorus concentrations, phytoplankton diversity (measured as genus richness, G) only showed weak correlations with local concentrations of total phosphorus. By estimating spatial averages of total phosphorus concentrations on various scales from an independent, spatially representative lake survey, we found that close to 70 per cent of the variability in local phytoplankton diversity can be explained by regionally averaged phosphorus concentrations on a scale between 100 and 400 km. Thus, the data strongly indicate the existence of metacommunities on this scale. Furthermore, we show a strong dependency between lake productivity and spatial community turnover. Thus, regional productivity affects beta-diversity by controlling spatial community turnover, resulting in scale-dependent productivity-diversity relationships. As an illustration of the interaction between local and regional processes in shaping microbial diversity, our results offer both empirical support and a plausible mechanism for the existence of common scaling rules in both the macrobial and the microbial worlds. We argue that awareness of regional species pools in phytoplankton and other unicellular organisms may critically improve our understanding of ecosystems and their susceptibility to anthropogenic stressors.


Chronic mesenteric ischemia: endovascular versus open revascularization.
To review 20 years of literature on chronic mesenteric ischemia (CMI), examining its complex clinical presentation and comparing open and endovascular treatment options. The PubMed and EBSCOHost electronic databases were queried to identify English-language articles published over the last 20 years. Scrutiny of the retrieved articles identified 1939 patients (mean age 65 years). Of these, 1163 patients underwent open surgery: 714 between 2000 and 2009 and 449 between 1990 and 1999. Of the 776 patients undergoing endovascular repairs, the majority (684) were performed between 2000 and 2009; 92 patients were treated between 1990 and 1999. Data were entered in an electronic database and were pooled for categorical analysis. No major differences were seen among open surgeries or among endovascular surgeries performed when comparing the 2 time periods. On comparing open and endovascular surgeries performed between 2000 and 2009, symptom improvement was 2.4 times more likely after open compared to endovascular surgery (95% CI 1.5 to 3.6, p<0.001). Five-year primary patency and 5-year assisted primary patency were 3.8 (95% CI 2.4 to 5.8, p<0.001) and 6.4 (95% CI 1.3 to 30.1, p = 0.02) times greater in the open group. Freedom from symptoms at 5 years was 4.4 times greater for open versus endovascular (95% CI 2.8 to 7.0, p<0.001). The complication rate for open versus endovascular surgery was 3.2 times greater (95% CI 2.5 to 4.2, p<0.001). The difference in mortality was not statistically significant (p = 0.75). Our data demonstrate that open revascularization surpasses endovascular procedures in long-term vessel patency and control of symptoms. Patients undergoing open procedures do, however, develop increased complications perioperatively. The preferred revascularization approach used in treating this condition should be tailored to the anatomy and physiology of each patient.


[PTEN expression and its significance in human primary hepatocellular carcinoma].
To explore the significance of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the development of human primary hepatocellular carcinoma (HCC). PTEN protein expression in cancerous liver tissues and paired para-carcinoma liver tissues from 60 HCC patients was detected by immunohistochemistry and PTEN mRNA expression was analyzed by northern blot. The significance of PTEN in the development of HCC was analyzed by investigating the relationship between the expression levels of PTEN protein and mRNA, and the clinicopathological parameters of HCC patients. PTEN protein was immunohistochemically stained in the cytoplasmic region of para-carcinoma liver tissues in all the 60 patients, while only 48.3% (29/60) of the patients were positive for PTEN protein in cancerous liver tissues. The positive rate of PTEN protein in HCC tissues were relative to the histological gading and the presence of tumor thrombus. In grade I - II, III, and IV, the positive rates were 84.0%, 23.8%, and 21.4% respectively, and in the group with tumor thrombus was 26.7%, while in the group without tumor thrombus was 55.6%. Northern blot showed that there existed four PTEN mRNA transcripts with the length of 5.5kb, 4.4kb, 2.4kb, and 1.8kb respectively. The level of PTEN mRNA expression in HCC tissues was much lower than that in the paired para-carcinoma liver tissues. The low expression level of the 5.5kb and 4.4kb transcripts was significantly associated with serum AFP value, presence of tumor thrombus, state of satellite lesion and histological grading. The low expression level of the 2.4kb transcript in HCC was significantly associated with the presence of tumor thrombus and satellite lesions in HCC patients. However, no evident relationship between the lowered expression level of the 1.8kb transcript and the clinicopathological parameters of HCC was observed in these 60 patients. Down-regulation of PTEN expression may play an important role in the development of HCC and the expression level of PTEN may be a potential adjuvant parameter in forecasting the progress and prognosis of HCC.


Platelet substitutes.
Many experimental approaches have been explored to produce hemostatically active novel human platelet products and substitutes capable of long-term storage. These include: platelet storage in the frozen state; storage in the cold (4 degrees C) in the liquid state; photochemical methods for the inactivation of viruses, bacteria and protozoa; infusible platelet membranes; and rehydrated lyophilized platelets. In addition to products using human platelets as their primary manufacturing source, other approaches have been used to make non-platelet-derived substitutes that might be capable of in vivo hemostasis. These include production of red blood cells, or liposomes, bearing hemostatically active agents on their surfaces; and fibrinogen-coated albumin microcapsules or microspheres. The development of platelet substitutes is an increasing scientific and technological endeavor and there are many reasons to believe that platelet substitutes will become more efficacious and safer to use over time. Ultimately, such work will result in safe and effective platelet substitutes being available for clinical use in thrombocytopenic or other patients with increased risk for bleeding.


Engineering Crystallinity Gradients for Tailored CaO2 Nanostructures: Enabling Alkalinity-Reinforced Anticancer Activity with Minimized Ca2+/H2O2 Production.
CaO2 nanoparticles (CNPs) can produce toxic Ca2+ and H2O2 under acidic pH, which accounts for their intrinsic anticancer activity but at the same time raises safety concerns upon systemic exposure. Simultaneously realizing minimized Ca2+/H2O2 production and enhanced anticancer activity poses a dilemma. Herein, we introduce a "crystallinity gradient-based selective etching" (CGSE) strategy, which is realized by creating a crystallinity gradient in a CNP formed by self-assembled nanocrystals. The nanocrystals distributed in the outer layer have a higher crystallinity and thus are chemically more robust than those distributed in the inner layer, which can be selectively etched. CGSE not only leads to CNPs with tailored single- and double-shell hollow structures and metal-doped compositions but more surprisingly enables significantly enhanced anticancer activity as well as tumor growth inhibition under limited Ca2+/H2O2 production, which is attributed to an alkalinity-reinforced lysosome-dependent cell death pathway.


Advances in the Chromosome-Centric Human Proteome Project: looking to the future.
The mission of the Chromosome-Centric Human Proteome Project (C-HPP), is to map and annotate the entire predicted human protein set (~20,000 proteins) encoded by each chromosome. The initial steps of the project are focused on 'missing proteins (MPs)', which lacked documented evidence for existence at protein level. In addition to remaining 2,579 MPs, we also target those annotated proteins having unknown functions, uPE1 proteins, alternative splice isoforms and post-translational modifications. We also consider how to investigate various protein functions involved in cis-regulatory phenomena, amplicons lncRNAs and smORFs. Areas covered: We will cover the scope, historic background, progress, challenges and future prospects of C-HPP. This review also addresses the question of how we can best improve the methodological approaches, select the optimal biological samples, and recommend stringent protocols for the identification and characterization of MPs. A new strategy for functional analysis of some of those annotated proteins having unknown function will also be discussed. Expert commentary: If the project moves well by reshaping the original goals, the current working modules and team work in the proposed extended planning period, it is anticipated that a progressively more detailed draft of an accurate chromosome-based proteome map will become available with functional information.


Early invasive and in situ warty carcinoma of the vulva: clinical, histologic, and electron microscopic study with particular reference to viral association.
Cases of carcinoma of the vulva with a warty appearance were reviewed. Altogether, 27 cases of warty carcinoma of the vulva were treated at the University of Minnesota Hospitals between 1976 and 1980, which accounted for 22.4% of all vulvar epithelial malignancies. As compared to the previous experience between 1951 and 1970, this relative frequency increased fourfold. Clinical history indicated that warty carcinoma of the vulva was not necessarily preceded by long lead periods of in situ lesions. The lesions seemed to occur in all ages after adolescence, were multifocal in one third of the cases, were frequently locally recurring, and were relatively benign despite their often large size. Many of them were originally diagnosed as condyloma acuminatum. Virus-like particles were seen in eight of the 12 cases (67%) examined with transmission electron microscopy, which included six cases of invasive lesions. These observations suggest that human papillomavirus (HPV) may be the important etiologic agent of this group of tumors. Warty carcinoma of the vulva must be clearly separated from conventional invasive squamous cell carcinoma of the vulva, as its clinical behavior and a possible etiology appear unique.


Relatives' participation in everyday care in special care units for persons with dementia.
Research concerning relatives' participation in the everyday care related to persons living in special care units for persons with dementia is limited. To examine relatives' participation in their near one's everyday care, the level of burden experienced and important factors for participation, in this special context. The study had a cross-sectional design, and data collection was carried out by means of a study-specific questionnaire. A total of 233 relatives from 23 different special care units participated. The study was approved by the Norwegian Social Science Data Services. A great majority of relatives reported that they visited weekly and were the resident's spokesperson, but seldom really participated in decisions concerning their everyday care. Participation was seldom reported as a burden. This study indicated that relatives were able to make a difference to their near one's everyday life and ensure quality of care based on their biographical expertise, intimate knowledge about and emotional bond with the resident. Since knowing the resident is a prerequisite for providing individualised care that is in line with the resident's preferences, information concerning these issues is of utmost importance. This study prompts reflection about what it is to be a spokesperson and whether everyday care is neglected in this role. Even though relatives were satisfied with the care provided, half of them perceived their participation as crucial for the resident's well-being. This indicated that relatives were able to offer important extras due to their biographical expertise, intimate knowledge about and emotional bond with the resident. Good routines securing that written information about the residents' life history and preferences is available and used should be implemented in practice.


Health-related quality of life and participation in osteoporosis clinical trials.
Although osteoporosis affects millions of elderly women, the quality of their lives is extremely complex and is only recently being appreciated. We recently used a disease-specific Osteoporosis Quality of Life questionnaire (OQLQ) to measure quality of life for 105 elderly osteoporotic women, and reported that by path analysis, spinal fractures, health perception, and several sociodemographic factors accounted for 63% of the variance in quality of life. On the other hand, bone density, Colles fracture, hip fractures, pharmacologic agents, exercise, and several sociodemographic variables were not significant factors. Of particular note was the positive, indirect effect (via health perception and spinal fractures) that participation in a clinical trial (17.5% of the patients) had on life quality. In order to determine how involvement in a research study might affect health perception in this same cohort we examined OQLQ scores in the five domains of the OQLQ for the 18 post-menopausal osteoporotic women enrolled in two different phase III clinical trials with oral bisphosphonates and 87 osteoporotic women treated conventionally (estrogen, bisphosphonate, calcitonin, calcium/vitamin D) in our metabolic bone clinic. Research and clinical patients did not differ in age, femoral BMD, or number of spinal fractures. However, women in research trials had significantly greater aggregate OQLQ scores (5.67 versus 4.23, P < 0.0001) and perceived health (7.28 versus 5.85, P = 0.001) than clinical patients. These differences were highly significant (P < 0.001) for domains of quality of life including physical function, activities of daily living, symptoms, and leisure/ social activity and marginally significant for the emotional function domain (P = 0.05). Hence, by regression-based path analysis and subgroup analysis of cross-sectional data, participation in a clinical trial had a significant and positive impact on health-related quality of life. If these findings are confirmed by other studies, identifying those factors inherent in clinical studies that positively impact the lives of osteoporotic patients should become as important a priority as development of new therapies for this chronic disease.


Multi-Drug Resistant Coliform: Water Sanitary Standards and Health Hazards.
Water constitutes and sustains life; however, its pollution afflicts its necessity, further worsening its scarcity. Coliform is one of the largest groups of bacteria evident in fecally polluted water, a major public health concern. Coliform thrive as commensals in the gut of warm-blooded animals, and are indefinitely passed through their feces into the environment. They are also called as model organisms as their presence is indicative of the prevalence of other potential pathogens, thus coliform are and unanimously employed as adept indicators of fecal pollution. As only a limited accessible source of fresh water is available on the planet, its contamination severely affects its usability. Coliform densities vary geographically and seasonally which leads to the lack of universally uniform regulatory guidelines regarding water potability often leads to ineffective detection of these model organisms and the misinterpretation of water quality status. Remedial measures such as disinfection, reducing the nutrient concentration or re-population doesn't hold context in huge lotic ecosystems such as freshwater rivers. There is also an escalating concern regarding the prevalence of multi-drug resistance in coliforms which renders antibiotic therapy incompetent. Antimicrobials are increasingly used in household, clinical, veterinary, animal husbandry and agricultural settings. Sub-optimal concentrations of these antimicrobials are unintentionally but regularly dispensed into the environment through seepages, sewages or runoffs from clinical or agricultural settings substantially adding to the ever-increasing pool of antibiotic resistance genes. When present below their minimum inhibitory concentration (MIC), these antimicrobials trigger the transfer of antibiotic-resistant genes that the coliform readily assimilate and further propagate to pathogens, the severity of which is evidenced by the high Multiple Antibiotic Resistance (MAR) index shown by the bacterial isolates procured from the environmental. This review attempts to assiduously anthologize the use of coliforms as water quality standards, their existent methods of detection and the issue of arising multi-drug resistance in them.


Oxyurid nematodes of pet rodents in Slovakia - a neglected zoonotic threat.
The role of rodents as reservoirs of helminths of public health importance is not well known. The zoonotic potential of Syphacia spp. has been confirmed; therefore, the study aimed to estimate the occurrence of oxyurid nematodes in small rodents from pet shops and breeding clubs in Slovakia. Fecal samples of 586 pet rodents kept in 133 cages were collected between 2016 and 2018 and examined by Faust´s flotation method. Four species of oxyurid nematodes, Syphacia muris, S. obvelata, Aspiculuris tetraptera and Paraspidodera uncinata were detected. A. tetraptera was found in the faecal samples of all rodent species included in this survey. The number of positive boxes varied from 5.4% in hamsters to 70.0% with mice. The prevalence of Syphacia muris was highest in Mongolian gerbils where up to 75.0% boxes were positive; S. obvelata was found in 26.7% of boxes with mice, 25.0% of boxes with Mongolian gerbils and 3.2% of boxes with rats. The high prevalence of Syphacia spp. in all animal species points out the infection risk for humans. Animals offered for sale are often in close contact with human beings; therefore they should be regularly tested for parasites and then effectively dewormed.


Changes in splenic microcirculatory pathways in chronic idiopathic thrombocytopenic purpura.
The spleen plays a central role in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP); it produces massive quantities of antiplatelet antibodies, leading to accelerated phagocytosis of platelets. Lymphoid hyperplasia typically occurs in the spleen, characterized by large numbers of lymphatic nodules with active germinal centers. Whether changes in splenic microcirculatory pathways also occur is not known. We have studied this question by scanning electron microscopy of corrosion casts, comparing spleens removed from patients with ITP with normal spleens obtained from organ transplant donors. The casts demonstrate two major changes in microcirculatory pathways in ITP. Firstly, a striking proliferation of arterioles and capillaries is found in the white pulp and marginal zone (MZ), seen as extensive vascularization in 92.3% of lymphatic nodules (n = 191) versus 0.6% (n = 224) in normal spleens. Secondly, the marginal sinus, a series of flattened, anastomosing vascular spaces between the white pulp and MZ, is absent in 89.4% of lymphatic nodules versus 4.9% in normal spleens. The cause of these microcirculatory changes, which may not be exclusive to ITP, is presently unknown. Absence of the marginal sinus may affect distribution of blood flow through the MZ such that platelets spend increased amounts of time in the proximity of macrophages. In the presence of antiplatelet antibodies found in ITP spleens, this delayed transit would lead to greatly increased platelet destruction.


[Painless myocardial ischemia in patients with iron deficiency anemia].
Resting and bicycle ergometric ECGs were examined in 159 patients with iron deficiency anemia, including 100 treated with iron-containing drugs. ST segment depression in the patients undergoing exercise was regarded as a sign of silent myocardial ischemia which is common in anemic patients, its detection rate increases as the disease progresses. In patients with iron deficiency anemia, silent myocardial ischemia results in a substantial decrease of threshold intensity, has a negative effect on cardiac output both at rest and during exercise, and significantly slows down the recovery of cardiac performance during therapy. This should be borne in mind while solving problems in medial labour examinations and making rehabilitative measures in patients with the above abnormality.


Designing and building new local public health agencies in Nebraska.
Prior to 2001, the local public health system in Nebraska was weak, fragmented, and severely under funded. Local public health departments covered only 22 of the state's 93 counties. The Turning Point project provided the impetus for change by allowing a diverse group of public health stakeholders to develop a strategic plan for strengthening and transforming the public health system. The plan acted as a catalyst to use some of the Nebraska Tobacco Settlement Funds to provide dedicated state funding to build the local public health system. By June 2002, 16 new local public health departments had been organized, ultimately covering all of the 93 counties in the state. Some of the keys to long-term sustainability are creating a network of community health partners that support collaborative decision making, continually seeking input from the community, developing and implementing an education and training plan for public health professionals and local board of health members, and demonstrating accountability by documenting results and communicating them to policy makers and the general public.


Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety.
The central nervous system (CNS) has the highest concentration of lipids in the organism after adipose tissue. Among these lipids, the brain is particularly enriched with polyunsaturated fatty acids (PUFAs) represented by the omega-6 (ω6) and omega-3 (ω3) series. These PUFAs include arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively. PUFAs have received substantial attention as being relevant to many brain diseases, including anxiety and depression. This review addresses an important question in the area of nutritional neuroscience regarding the importance of ω3 PUFAs in the prevention and/or treatment of neuropsychiatric diseases, mainly depression and anxiety. In particular, it focuses on clinical and experimental data linking dietary intake of ω3 PUFAs and depression or anxiety. In particular, we will discuss recent experimental data highlighting how ω3 PUFAs can modulate neurobiological processes involved in the pathophysiology of anxiety and depression. Potential mechanisms involved in the neuroprotective and corrective activity of ω3 PUFAs in the brain are discussed, in particular the sensing activity of free fatty acid receptors and the activity of the PUFAs-derived endocannabinoid system and the hypothalamic-pituitary-adrenal axis.


The effects of collaborative goal-focused occupational therapy on self-care skills: a pilot study.
This pilot study examined collaborative, goal-focused therapy to determine its effects on performance of self-care activities, including eating, grooming, bathing, upper body dressing, lower-body dressing, and toileting. Thirty-one patients at a rehabilitation hospital, divided between control and experimental groups, comprised the sample. Participants' performances on self-care activities were measured using the Functional Independence Measure (FIM) at admission to therapy and again at a 2-week follow-up. Attainment of goals was not emphasized in the control group. In the experimental group, new goals and achievement of previously set goals were regularly discussed and documented. Comparisons were made between 2-week FIM scores of the control and experimental groups, and data were analyzed by the Mann-Whitney U test. The experimental group demonstrated greater gains on FIM scores when compared to the control group on all self-care activities, but only upper-body dressing met levels of statistical significance. Findings support the efficacy of collaborative, goal-focused occupational therapy in the treatment of deficits in upper-body dressing, but did not support this approach with toileting, eating, grooming, bathing, and lower-body dressing. Further study, with a larger sample, is recommended.


Integration of oral health in primary health care through motivational interviewing for mothers of young children: A pilot study.
Early childhood caries (ECC) continues to affect children worldwide. In India, primary health centers (PHCs) comprises the primary tier where Accredited Social Health Activist (ASHA) provide integrated curative and preventive health care. The aim of the study was to pilot test the integration of oral health in primary health care through motivational interviewing (MI) for mothers of young children provided by ASHAs. The pilot study was conducted in Kashipur, Uttarakhand. From the six PHCs in Kashipur, three were randomly selected, one each was assigned to MI group, traditional health education group, and control group. From 60 mothers with 8-12 months child, ASHAs of all three groups gathered mother's knowledge regarding child's oral health using close-ended questionnaire and diagnosed clinical risk markers of ECC in children and ASHAs of Group A and B imparted the oral health education as per their training. The comparison of ASHA's performances on the MI training competency pre- and post-test showed an overall average of 74% improvement in post-test scores. Interexaminer reliability of the parallel clinical measurements by 6 ASHAs and the investigator for the maxillary central incisors showed 93% of agreement for both dental plaque and dental caries assessment with 0.86 and 0.89 kappa values, respectively. The health education through MI is feasible and can be cost-effective by utilization of ASHAs at PHCs to provide the oral health education to mothers which will in turn improve the oral health status of children.


Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells.
Glucosylceramide synthase (GCS), the key enzyme in the biosynthesis of glycosphingolipids, has been implicated in many biological phenomena, including multidrug resistance. GCS inhibition, by both antisense and the specific inhibitor (D-threo)-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), results in a drastic decrease of apoptosis induced by the p53-independent chemotherapeutic agent N-(4-hydroxyphenyl)retinamide in neuroepithelioma cells. By using the yeast two-hybrid system, we have identified a member of the reticulon (RTN) family (RTN-1C) as the major GCS-protein partner. Interestingly, RTN-1C not only interacts with GCS at Golgi/ER interface but also modulates its catalytic activity in situ. In fact, overexpression of RTN-1C sensitizes CHP-100 cells to fenretinide-induced apoptosis. These findings demonstrate a novel p53-independent pathway of apoptosis regulated by Golgi/endoplasmic reticulum protein interactions, which is relevant for cancer combined therapy.


How automatic notification of infectious disease specialists impacted the management of Staphylococcus aureus bacteremia in a community hospital setting.
Objective: The objective of this study was to review the impact of an automatic email notification to infectious disease consultants. Design: Cases were identified from a community hospital system microbiology database by at least one positive blood culture. Records were reviewed both before (2013 and 2014) and after (2015 and 2016) the implementation of the automated email system (intervention). Prior to this policy, consultation with the infectious disease (ID) specialist was at the discretion of the primary team. Results: There were no significant differences in 30-day mortality between the two groups (18 vs 20%, p = 0.10). However, a trend of shorter hospital stays (12.2 vs 9.5 days, p = 0.03) and reduced 30 day readmissions (40% vs 19%, p = 0.03) was observed and antibiotics prescribed for complicated cases was more appropriate (57% vs 85%, p = 0.004). Conclusions: In this study population, the implementation of an automatic email generator to ID specialists was associated with a shorter hospital length of stay, less 30-day readmissions and more appropriate length of antibiotics prescribed in complicated cases of SAB. The authors recommend future studies replicating the methodology employed here with larger sample sizes before consideration of employing a similar automatic email ID consult generation at other health systems.


Proposed treatment guidelines for donor care.
The complex care of the organ donor during preparation for organ removal and provision of the best organs for transplantation is often the responsibility of the organ procurement coordinator. To assist in that process the following clinical problem-based guidelines have been developed. A standard order set is recommended to initiate treatment and to provide a continuing laboratory database. As clinical concerns arise from that database, past medical history, or ongoing donor care, section of these guidelines may serve as references for specific interventions. Physician consultation and collaboration with other bedside care providers are encouraged throughout.


Genome variations in herpes simplex virus type 2 strains isolated in Japan and Sweden.
One-hundred and twenty-three epidemiologically unrelated strains of herpes simplex virus type 2 (HSV-2) isolated in Japan and Sweden (68 Japanese and 55 Swedish isolates) were compared by analysis of their genomes using five restriction endonucleases: BamHI, KpnI, EcoRI, HindIII and Bg/II. Seven of the 93 restriction sites examined showed statistically significant variation between isolates from the two countries. However, HSV-2 isolates were less variable than the HSV-1 isolates previously analysed from the same countries. Using 12 restriction sites as markers, the HSV-2 isolates were classified into 41 cleavage patterns; 17 were specific for Japanese isolates and 15 were specific for Swedish isolates. Correlation coefficients between some sets of 12 markers were significant, but significant correlations between Japanese and Swedish isolates were distinct for each country. Both Japanese and Swedish isolates were assigned to three major patterns with no significant difference in incidence. In contrast, in two other major patterns, differences in incidence between the isolates were statistically significant. These results suggest that HSV-2 populations in geographically separated countries have distinct cleavage site distributions.


Magnetic targeting of human mesenchymal stem cells with internalized superparamagnetic iron oxide nanoparticles.
Cell therapies offer exciting new opportunities for effectively treating many human diseases. However, delivery of therapeutic cells by intravenous injection, while convenient, relies on the relatively inefficient process of homing of cells to sites of injury. To address this limitation, a novel strategy has been developed to load cells with superparamagnetic iron oxide nanoparticles (SPIOs), and to attract them to specific sites within the body by applying an external magnetic field. The feasibility of this approach is demonstrated using human mesenchymal stem cells (hMSCs), which may have a significant potential for regenerative cell therapies due to their ease of isolation from autologous tissues, and their ability to differentiate into various lineages and modulate their paracrine activity in response to the microenvironment. The efficient loading of hMSCs with polyethylene glycol-coated SPIOs is achieved, and it is found that SPIOs are localized primarily in secondary lysosomes of hMSCs and are not toxic to the cells. Further, the key stem cell characteristics, including the immunophenotype of hMSCs and their ability to differentiate, are not altered by SPIO loading. Through both experimentation and mathematical modeling, it is shown that, under applied magnetic field gradients, SPIO-containing cells can be localized both in vitro and in vivo. The results suggest that, by loading SPIOs into hMSCs and applying appropriate magnetic field gradients, it is possible to target hMSCs to particular vascular networks.


Selective feeding of tobacco budworm and bollworm (Lepidoptera: Noctuidae) on meridic diet with different concentrations of Bacillus thuringiensis proteins.
Laboratory experiments were conducted to evaluate the behavior of bollworm, Helicoverpa zea (Boddie), and tobacco budworm, Heliothis virescens (F.), larvae on meridic diet with different concentrations of the Cry1Ac and Cry2Ab proteins from Bacillus thuringiensis subsp. kurstaki Berliner. The proteins used in these experiments are the ones in commercially available Bollgard and Bollgard II cotton. Both bollworms and tobacco budworms selectively fed on nontreated diet compared with diet treated with Cry1Ac. In addition, bollworms exhibited a concentration response with Cry1Ac. In general, bollworms selected diet with low concentrations of Cry1Ac compared with diet with higher concentrations of Cry1Ac. For Cry2Ab, the avoidance was not as prominent as that observed for Cry1Ac. Based on results from no-choice assays, the Cry1Ac and Cry2Ab concentrations used in choice assays represented a wide range of biological activity on both species. The lower concentrations provided low levels of mortality, whereas the higher concentrations provided high levels of mortality. Also, the developmental times of larvae were longer at higher concentrations of both proteins. These data provide important information about the behavioral response of key cotton pests to the B. thuringiensis proteins found in commercially available transgenic cotton. This information will be important to develop accurate scouting and management procedures for Bollgard and Bollgard II cotton.


Drosophila PAT1 is required for Kinesin-1 to transport cargo and to maximize its motility.
Kinesin heavy chain (KHC), the force-generating component of Kinesin-1, is required for the localization of oskar mRNA and the anchoring of the nucleus in the Drosophila oocyte. These events are crucial for the establishment of the anterior-posterior and dorsal-ventral axes. KHC is also essential for the localization of Dynein and for all ooplasmic flows. Interestingly, oocytes without Kinesin light chain show no major defects in these KHC-dependent processes, suggesting that KHC binds its cargoes and is activated by a novel mechanism. Here, we shed new light on the molecular mechanism of Kinesin function in the germline. Using a combination of genetic, biochemical and motor-tracking studies, we show that PAT1, an APP-binding protein, interacts with Kinesin-1, functions in the transport of oskar mRNA and Dynein and is required for the efficient motility of KHC along microtubules. This work suggests that the role of PAT1 in cargo transport in the cell is linked to PAT1 function as a positive regulator of Kinesin motility.


Malignant peritoneal mesothelioma: prognostic factors and oncologic outcome analysis.
Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC.


Mn monolayer modified Rh for syngas-to-ethanol conversion: a first-principles study.
Rh is unique in its ability to convert syngas to ethanol with the help of promoters. We performed systematic first-principles computations to examine the catalytic performance of pure and Mn modified Rh(100) surfaces for ethanol formation from syngas. CO dissociation on the surface as well as CO insertion between the chemisorbed CH(3) and the surface are the two key steps. The CO dissociation barrier on the Mn monolayer modified Rh(100) surface is remarkably lowered by ~1.5 eV compared to that on Rh(100). Moreover, the reaction barrier of CO insertion into the chemisorbed CH(3) group on the Mn monolayer modified Rh(100) surface is 0.34 eV lower than that of methane formation. Thus the present work provides new mechanistic insight into the role of Mn promoters in improving Rh's selectivity to convert syngas to ethanol.


Seroprevalence rates of antibodies against Leishmania infantum and other protozoan and rickettsial parasites in dogs.
Canine visceral leishmaniasis (CVL) is caused by the protozoan Leishmania infantum, which infects dogs and humans in many regions of Brazil. The present study involved an indirect fluorescent antibody test (IFAT) to analyze L. infantum, Ehrlichia spp., Babesia canis, Toxoplasma gondii and Neospora caninum infection rates in serum samples from 93 dogs in a rural settlement in Ilha Solteira, SP, Brazil. The seroprevalence rates of anti-L. infantum, anti-Ehrlichia, anti-B. canis, anti-T. gondii and anti-N. caninum antibodies were 37.6%, 75.3%, 72%, 47.3% and 6.4%, respectively. In addition to IFAT, direct microscopic examination of popliteal lymph node aspirates revealed 26.9% of CVL positive dogs. Serological tests revealed that 17.2% of the dogs were seropositive for a single parasite, 29% for two parasites, 33% for three, 16.1% for four, and 1.1% for five parasites, while 3.2% were seronegative for five parasites. The presence of antibodies against these parasites in serum samples from dogs confirmed their exposure to these parasites in this rural area. Because of the potential zoonotic risk of these diseases, mainly leishmaniasis, ehrlichiosis and toxoplasmosis, special attention should focus on programs for the improvement of diagnostic assays and control measures against these parasites.


Automated interpretation of MS/MS spectra of oligosaccharides.
The emerging glycomics and glycoproteomics projects aim to characterize all forms of glycoproteins in different tissues and organisms. Tandem mass spectrometry (MS/MS) is the key experimental methodology for high-throughput glycan identification and characterization. Fragmentation of glycans from high energy collision-induced dissociation generates ions from glycosidic as well as internal cleavages. The cross-ring ions resulting from internal cleavages provide additional information that is important to reveal the type of linkage between monosaccharides. This information, however, is not incorporated into the current programs for analyzing glycan mass spectra. As a result, they can rarely distinguish from the mass spectra isomeric oligosaccharides, which have the same saccharide composition but different types of sequences, branches or linkages. In this paper, we describe a novel algorithm for glycan characterization using MS/MS. This algorithm consists of three steps. First, we develop a scoring scheme to identify potential bond linkages between monosaccharides, based on the appearance pattern of cross-ring ions. Next, we use a dynamic programming algorithm to determine the most probable oligosaccharide structures from the mass spectrum. Finally, we re-evaluate these oligosaccharide structures, taking into account the double fragmentation ions. We also show the preliminary results of testing our algorithm on several MS/MS spectra of oligosaccharides. The program GLYCH is available upon request from the authors.


Opportunities for community awareness platforms in personal genomics and bioinformatics education.
Precision and personalized medicine will be increasingly based on the integration of various type of information, particularly electronic health records and genome sequences. The availability of cheap genome sequencing services and the information interoperability will increase the role of online bioinformatics analysis. Being on the Internet poses constant threats to security and privacy. While we are connected and we share information, websites and internet services collect various types of personal data with or without the user consent. It is likely that genomics will merge with the internet culture of connectivity. This process will increase incidental findings, exposure and vulnerability. Here we discuss the social vulnerability owing to the genome and Internet combined security and privacy weaknesses. This urges more efforts in education and social awareness on how biomedical data are analysed and transferred through the internet and how inferential methods could integrate information from different sources. We propose that digital social platforms, used for raising collective awareness in different fields, could be developed for collaborative and bottom-up efforts in education. In this context, bioinformaticians could play a meaningful role in mitigating the future risk of digital-genomic divide.


Cardiovascular responses to chemical stimulation of the inferior olive in the cat.
Previous studies have suggested that electrical stimulation of the inferior olivary nucleus of anesthetized cats does not alter arterial pressure but does inhibit the depressor response to baroreceptor stimulation. However, it was not determined if the observed alteration of the baroreceptor reflex was due to an effect on cell bodies or on fibers of passage. The purpose of the present study was to determine the responses to selective activation of cell bodies in the inferior olive in anesthetized cats. Unilateral microinjections of kainic acid, D,L-homocysteic acid and glutamate were made into the inferior olive at the level of or just rostral to the obex. In addition, the baroreceptor reflex was examined before and after microinjection of kainic acid. The microinjections produced an increase in arterial pressure accompanied by variable effects on heart rate. However, the cardiovascular responses to activation of arterial baroreceptors were not altered by kainic acid microinjections. These results indicate that neurons in the inferior olivary nucleus can exert effects which increase arterial pressure but the inferior olive at this level does not modulate the baroreceptor reflex in anesthetized cats.


Coronary flow reserve estimated by positron emission tomography to diagnose significant coronary artery disease and predict cardiac events.
Coronary artery disease (CAD) is a major cause of death in Japan. Coronary angiography is useful to assess the atherosclerotic burden in CAD patients, but its ability to predict whether patients will respond favorably to optimal medical therapy and revascularization is limited. The measurement of the fractional flow reserve with angiography is a well-validated method for identifying ischemic vessels. However, neither an anatomical assessment nor a functional assessment can delineate microvasculature or estimate its function. The quantitative coronary flow reserve (CFR) estimated from sequential myocardial perfusion images obtained by positron emission tomography (PET) during stress provides an accurate index of hyperemic reactivity to vasodilatory agents in the myocardium. In fact, there is growing evidence that the CFR reflects disease activity in the entire coronary circulation, including epicardial coronary artery stenosis, diffuse atherosclerosis, and microvascular dilatory function. Importantly, reduced CFR is observed even in patients without flow-limiting coronary stenosis, and its evaluation can improve the risk stratification of patients at any stage of CAD. This review focuses on the application of CFR estimated by cardiac PET for the diagnosis and risk stratification of patients with CAD.


Evaluation of Threshold Values for Root Canal Filling Voids in Micro-CT and Nano-CT Images.
While several materials and techniques have been used to assess the quality of root canal fillings in micro-CT images, the lack of standardization in scanning protocols has produced conflicting results. Hence, the aim of this study was to determine a cutoff voxel size value for the assessment of root canal filling voids in micro-CT and nano-CT images. Twenty freshly extracted mandibular central incisors were used. Root canals were prepared with nickel titanium files to an ISO size 40/0.06 taper and then filled with a single cone (40/0.06 taper) and AH Plus sealer. The teeth were scanned with different voxel sizes with either micro-CT (5.2, 8.1, 11.2, and 16.73 μm) or nano-CT (1.5 and 5.0 μm) equipment. Images were reconstructed and analyzed with the NRecon and CTAn software. Void proportion and void volume were calculated for each tooth in the apical, middle, and coronal thirds of the root canal. Kruskal-Wallis and post hoc Mann-Whitney U tests were performed with a significance level of 5%. In micro-CT images, significantly different results were detected among the tested voxel sizes for void proportion and void volume, whereas no such differences were found in nano-CT images (p > 0.05). Micro-CT images showed higher void numbers over the entire root length, with statistically significant differences between the voxel size of 16.73 μm and the other sizes (p < 0.05). The values of the different nano-CT voxel sizes did not significantly differ from those of the micro-CT (5.2, 8.1, and 11.2 μm), except for the voxel size of 16.73 μm (p < 0.05). All tested voxel sizes enabled the detection of root canal filling voids except for the voxel size of 16.73 μm. Bearing in mind the limitations of this study, it seems that a voxel size of 11.2 μm can be used as a reliable cutoff value for the assessment of root canal filling voids in micro-CT imaging.


[Clinical finding and treatment of festered hepatic echinococcosis].
Results of treatment of 72 patients with festered hepatic echinococcosis were analyzed. Ultrasonic examination was the main method of examination. Method of residual cavity liquidation was determined by localization of cyst. Original method of liquidation of residual cavity using omentum and oxygen insufflations has been successfully applied in 21 patients. Open methods of residual cavity liquidation are often accompanied by complications (bile-purulent fistulas, residual purulent cavities, long period of treatment).


The way in which a physiotherapy service is structured can improve patient outcome from a surgical intensive care: a controlled clinical trial.
The physiological basis of physiotherapeutic interventions used in intensive care has been established. We must determine the optimal service approach that will result in improved patient outcome. The aim of this article is to report on the estimated effect of providing a physiotherapy service consisting of an exclusively allocated physiotherapist providing evidence-based/protocol care, compared with usual care on patient outcomes. An exploratory, controlled, pragmatic, sequential-time-block clinical trial was conducted in the surgical unit of a tertiary hospital in South Africa. Protocol care (3 weeks) and usual care (3 weeks) was provided consecutively for two 6-week intervention periods. Each intervention period was followed by a washout period. The physiotherapy care provided was based on the unit admission date. Data were analyzed with Statistica in consultation with a statistician. Where indicated, relative risks with 95% confidence intervals (CIs) are reported. Significant differences between groups or across time are reported at the alpha level of 0.05. All reported P values are two-sided. Data of 193 admissions were analyzed. No difference was noted between the two patient groups at baseline. Patients admitted to the unit during protocol care were less likely to be intubated after unit admission (RR, 0.16; 95% CI, 0.07 to 0.71; RRR, 0.84; NNT, 5.02; P = 0.005) or to fail an extubation (RR, 0.23; 95% CI, 0.05 to 0.98; RRR, 0.77; NNT, 6.95; P = 0.04). The mean difference in the cumulative daily unit TISS-28 score during the two intervention periods was 1.99 (95% CI, 0.65 to 3.35) TISS-28 units (P = 0.04). Protocol-care patients were discharged from the hospital 4 days earlier than usual-care patients (P = 0.05). A tendency noted for more patients to reach independence in the transfers (P = 0.07) and mobility (P = 0.09) categories of the Barthel Index. A physiotherapy service approach that includes an exclusively allocated physiotherapist providing evidence-based/protocol care that addresses pulmonary dysfunction and promotes early mobility improves patient outcome. This could be a more cost-effective service approach to care than is usual care. This information can now be considered by administrators in the management of scarce physiotherapy resources and by researchers in the planning of a multicenter randomized controlled trial. PACTR201206000389290.


Utilization of upper endoscopy for surveillance of gastric ulcers in the United States.
Current guidelines recommend that all gastric ulcers (GUs) be biopsied extensively to exclude underlying malignancy. However, many gastroenterologists opt to also perform surveillance endoscopy (EGD) to document ulcer healing. The purpose of this study was to examine frequency of utilization of surveillance EGD in patients found to have GUs using a national endoscopic database. The Clinical Outcomes Research Initiative (CORI) database was used to identify ambulatory patients diagnosed with a GU between 2001 and 2005. A surveillance EGD was defined as any EGD performed < or =3 months after index EGD. Results were stratified by patient demographic factors, index ulcer size and location, practice setting, and geographic region. Multivariate logistic regression was performed to identify independent predictors of surveillance EGD utilization. In the database, 6,113 patients met our inclusion/exclusion criteria, of which 1,510 (24.7%) underwent surveillance EGD. Older patients were more likely to undergo surveillance than younger patients (P < 0.0001), though a substantial minority (15.2%) of patients <40 years of age underwent a surveillance examination. Index ulcer size > or =1 cm and care in a Veterans Affairs (VA) setting were also independent predictors of surveillance EGD utilization. Significant geographic variation was noted, with surveillance rates varying from 16.0% to 35.9% across the United States (P < 0.0001). In contrast to guideline recommendations, approximately 25% of ambulatory patients diagnosed with GUs underwent surveillance EGD within 3 months. Notably, patients at low-risk for gastric cancer, including young patients, those with small index ulcers, and those with antral ulcers, underwent surveillance at higher than expected rates, which suggests overuse of surveillance EGD.


Transposon mutagenesis of Campylobacter jejuni identifies a bipartite energy taxis system required for motility.
Campylobacter jejuni constitutes the leading cause of bacterial gastroenteritis in the United States and a major cause of diarrhoea worldwide. Little is known about virulence mechanisms in this organism because of the scarcity of suitable genetic tools. We have developed an efficient system of in vitro transposon mutagenesis using a mariner-based transposon and purified mariner transposase. Through in vitro transposition of C. jejuni chromosomal DNA followed by natural transformation of the transposed DNA, large random transposon mutant libraries consisting of approximately 16 000 individual mutants were generated. The first genetic screen of C. jejuni using a transposon-generated mutant library identified 28 mutants defective for flagellar motility, one of the few known virulence determinants of this pathogen. We developed a second genetic system, which allows for the construction of defined chromosomal deletions in C. jejuni, and demonstrated the requirement of sigma28 and sigma54 for motility. In addition, we show that sigma28 is involved in the transcription of flaA and that sigma54 is required for transcription of three other flagellar genes, flaB and flgDE. We also identified two previously uncharacterized genes required for motility encoding proteins that we call CetA and CetB, which mediate energy taxis responses. Through our analysis of the Cet proteins, we propose a unique mechanism for sensing energy levels and mediating energy taxis in C. jejuni.


Analytic first-order derivatives of partially contracted n-electron valence state second-order perturbation theory (PC-NEVPT2).
A balanced treatment of dynamic and static electron correlation is important in computational chemistry, and multireference perturbation theory (MRPT) is able to do this at a reasonable computational cost. In this paper, analytic first-order derivatives, specifically gradients and dipole moments, are developed for a particular MRPT method, state-specific partially contracted n-electron valence state second-order perturbation theory (PC-NEVPT2). Only one linear equation needs to be solved for the derivative calculation if the Z-vector method is employed, which facilitates the practical application of this approach. A comparison of the calculated results with experimental geometrical parameters of O3 indicates excellent agreement although the calculated results for O3 - are slightly outside the experimental error bars. The 0-0 transition energies of various methylpyrimidines and trans-polyacetylene are calculated by performing geometry optimizations and seminumerical second-order geometrical derivative calculations. In particular, the deviations of 0-0 transition energies of trans-polyacetylene from experimental values are consistently less than 0.1 eV with PC-NEVPT2, indicating the reliability of the method. These results demonstrate the importance of adding dynamic electron correlation on top of methods dominated by static electron correlation and of developing analytic derivatives for highly accurate methods.


Observation of Bacteriophage Ultrastructure by Cryo-Electron Microscopy.
Transmission electron microscopy (TEM) is an ideal method to observe and determine the structure of bacteriophages. From early studies by negative staining to the present atomic structure models derived from cryo-TEM, bacteriophage detection, classification, and structure determination have been mostly done by electron microscopy. Although embedding in metal salts has been a routine method for virus observation for many years, the preservation of bacteriophages in a thin layer of fast frozen buffer has proven to be the most convenient preparation method for obtaining images using cryo-electron microscopy (cryo-EM). In this technique, frozen samples are observed at liquid nitrogen temperature, and the images are acquired using different recording media. The incorporation of direct electron detectors has been a fundamental step in achieving atomic resolution images of a number of viruses. These projection images can be numerically combined using different approaches to render a three-dimensional model of the virus. For those viral components exhibiting any symmetry, averaging can nowadays achieve atomic structures in most cases. Image processing methods have also evolved to improve the resolution in asymmetric viral components or regions showing different types of symmetries (symmetry mismatch).


Quantification of femoral neck exposure through a minimally invasive Smith-Petersen approach.
To quantify the area of osseous exposure and identify six anatomic landmarks using a direct anterior approach to the hip. Ten fresh-frozen hemipelves were dissected using a minimally invasive Smith-Petersen approach. Upon completion of the exposure, a calibrated digital image was taken from the surgeon's perspective. Identification of six osseous landmarks (anterior-superior acetabulum, anterior-inferior acetabulum, greater trochanter, lesser trochanter, anterior inferior iliac spine, and vastus ridge) was attempted either by direct visualization or palpation with a tonsil clamp. These landmarks exceed the border for any intracapsular hip fracture. The digital images were then analyzed using a computer software program, ImageJ (National Institutes of Health, Bethesda, MD), to calculate the square area of proximal femur exposed. The average square area of proximal femur exposed was 20.31 cm(2) (standard deviation: 3.09, range: 15.16-24.18). The area exposed correlated with the original height of the cadaver (r = 0.69, P < 0.05). With the numbers available, there was no correlation between exposure and weight (P = 0.71) or body mass index (P = 0.87). In all 10 cadaver specimens, the 6 osseous landmarks were easily identified, 5 by direct visualization and 1 by palpation (lesser trochanter, deep portion) because of incomplete visualization. The minimally invasive Smith-Petersen approach to the hip allows for a wide exposure of the femoral neck averaging 20.31 cm(2) and identification of six bony critical landmarks of the hip. It may be used for open reduction of subcapital, mid-cervical, and basicervical femoral neck fractures.


Translationally controlled tumor protein is a target of tumor reversion.
By analyzing the gene expression profile between tumor cells and revertant counterparts that have a suppressed malignant phenotype, we previously reported a significant down-regulation of translationally controlled tumor protein (TCTP) in the revertants. In the present study, we derived, by using the H1 parvovirus as a selective agent, revertants from three major solid cancers: colon, lung, and melanoma cell lines. These cells have a strongly suppressed malignant phenotype both in vitro and in vivo. The level of TCTP is decreased in most of the revertants. To verify whether inhibition of TCTP expression induces changes in the malignant phenotype, in the classical, well established model of "flat reversion," v-src-transformed NIH3T3 cells were transfected with antisense TCTP. By inhibiting the expression of TCTP, the number of revertant cells was raised to 30%, instead of the reported rate for spontaneous flat revertants of 10(-6). Because TCTP encodes for a histamine-releasing factor, we tested the hypothesis that inhibitors of the histaminic pathway could be effective against tumor cells. We show that some antihistaminic compounds (hydroxyzine and promethazine) and other pharmacological compounds with a related structure (including thioridazine and sertraline) kill tumor cells and significantly decrease the level of TCTP. All together, these data suggest that, with tumor reversion used as a working model, TCTP was identified as a target and drugs were selected that decrease its expression and kill tumor cells.


Relationship between regional cerebral blood flow and electrocorticographic activities under sevoflurane and isoflurane anesthesia.
The aims of this study are (1) to assess the effects of volatile anesthetics on regional cerebral blood flow (rCBF) and electrocorticography (ECoG), and (2) to investigate the relationship between rCBF and ECoG influenced by volatile anesthetics. The authors measured rCBF using laser Doppler flowmetry and ECoG simultaneously and continuously from the same cortex during craniotomy, using the specially arranged probe. Patients received intravenous anesthetics with nitrous oxide until craniotomy, and after opening of dura, volatile anesthetic, either isoflurane or sevoflurane, was started and was gradually increased for the measurement. Four of the nine cases (44.4%) of the sevoflurane group showed no change both in rCBF and ECoG. In three cases (33.3%), rCBF increased as the frequency of the paroxysmal activities increased. In two cases (22.2%), decreased rCBF was accompanied by slow waves. In 12 cases of the isoflurane group, no apparent rCBF and ECoG changes were seen, except a case with decreased rCBF and slow waves. This is the first report of simultaneous recordings of regional CBF and neuronal activity under general anesthesia. During sevoflurane and isoflurane anesthesia <2.5 minimum alveolar anesthetic concentration, rCBF is affected by ECoG activities rather than pharmacologic action of inhalational anesthetics.


The Online Misinformation Engagement Framework.
Research on online misinformation has evolved rapidly, but organizing its results and identifying open research questions is difficult without a systematic approach. We present the Online Misinformation Engagement Framework, which classifies people's engagement with online misinformation into four stages: selecting information sources, choosing what information to consume or ignore, evaluating the accuracy of the information and/or the credibility of the source, and judging whether and how to react to the information (e.g., liking or sharing). We outline entry points for interventions at each stage and pinpoint the two early stages-source and information selection-as relatively neglected processes that should be addressed to further improve people's ability to contend with misinformation.


Variables that affect the school-age child's reaction to hospitalization and surgery: a review of the literature.
The purpose of this paper has been to identify the variables documented in the literature that affect the school-age child's reaction to hospitalization and surgery. The variables were categorized as pertaining to the child, the parents, or the hospital. Variables in the category pertaining to the child that affect the child's reaction to hospitalization and surgery are developmental level and mechanisms used to cope with hospitalization and surgery. In the parent category, presence of the mother, preparation of the mother, support of the child by the mother, parental values, and socioeconomic status were considered variables that affect the child's reaction to hospitalization and surgery. The hospital environment is generally considered to be threatening to school-age children. The major variables identified in the hospital category that affect the child's reaction to hospitalization and surgery were specific events, length of hospitalization, nature and degree of illness, type of procedure, and method of preparation for the hospital experience.


The Effects of Job Characteristics on Retirement.
Along with data about actual, desired and anticipated job characteristics, this paper uses a novel data element, the subjective conditional probability of working at age 70, to estimate the causal effects of job characteristics on retirement in the U.S. Having flexible work hours is the most consistent predictor of retirement preferences and expectations: if all current workers had flexible hours, the fraction working at age 70 would be 0.322, but it would be just 0.172 if none had this option. Job stress, physical and cognitive job demands, the option to telecommute, and commuting times were additional predictors of retirement expectations.


Earth's Variable Rotation.
Recent improvements in geodetic data and practical meteorology have advanced research on fluctuations in the Earth's rotation. The interpretation of these fluctuations is inextricably linked with studies of the dynamics of the Earth-moon system and dynamical processes in the liquid metallic core of the Earth (where the geomagnetic field originates), other parts of the Earth's interior, and the hydrosphere and atmosphere. Fluctuations in the length of the day occurring on decadal time scales have implications for the topography of the core-mantle boundary and the electrical, magnetic, and other properties of the core and lower mantle. Investigations of more rapid fluctuations bear on meteorological studies of interannual, seasonal, and intraseasonal variations in the general circulation of the atmosphere and the response of the oceans to such variations.


Breast cancer treatment and chemoprevention.
To outline modern principles of surgery, radiation therapy, and systemic treatment of breast cancer, and to review preliminary data on breast cancer prevention. A MEDLINE search was conducted from 1966 to the beginning of 1999; most of the studies reviewed are randomized clinical trials. Breast conservation surgery should be offered to all women with early breast cancer because studies demonstrate survival rates equivalent to those with mastectomy. If mastectomy is chosen, breast reconstruction should be offered. Most women with breast cancer are treated systemically with either chemotherapy or tamoxifen, or both, and mortality is substantially reduced. Data indicating that tamoxifen prevents breast cancer are promising; more studies with both tamoxifen and raloxifene are under way. All women should be strongly encouraged to enter clinical trials. Because many issues face women recently diagnosed with breast cancer, they often seek out family physicians as advisors to help negotiate a complex treatment path. The possibility of preventing breast cancer will undoubtedly raise questions among family members of women with breast cancer that should appropriately be answered and referred, if necessary, by family physicians.


Detection of babesia species from infected dog blood by polymerase chain reaction.
Polymerase chain reaction (PCR) was first applied to diagnosis of canine babesiosis in Japan. Blood samples from 13 dogs suffering from canine babesiosis were used for examination of specificity and sensitivity of the PCR diagnosis. Of the 13 dogs, three were experimentally infected, and ten were naturally infected with Babesia species in west part of Japan. We designed a nested PCR to amplify the babesial small subunit ribosomal RNA gene and found that only the nested PCR produced a visual band, which were not apparent by the first-round PCR to the positive samples. Specificity of the nested PCR was confirmed by amplification after the second-round PCR. Sensitivity of the nested PCR was examined by diluting the blood samples from infected and uninfected dogs. The nested PCR was found to show positive results on the most diluted blood at 0.0001% parasitemia. These results indicate that the nested PCR is highly sensitive and useful for diagnosis of canine babesiosis.


Overexpression of human stem cell factor impairs melanocyte, mast cell, and thymocyte development: a role for receptor tyrosine kinase-mediated mitogen activated protein kinase activation in cell differentiation.
Stem cell factor (SCF) is synthesized as both soluble (S) and membrane-associated (MA) proteins. Indirect insight into the function of MA and S isoforms of SCF has come from studies performed in Steel (Sl) mutant mice. However, the physiologic role(s) of these two isoforms remain unknown. In an attempt to better understand the in vivo role of c-kit/SCF interactions on various cell lineages, transgenic mice were generated that overexpress MA isoform of human SCF (hSCF). In murine cells, hSCF behaves as an antagonist to normal SCF function, due to interference with the interaction between endogenous murine SCF and its receptor, c-kit, encoded by the dominant white spotting (W) gene. Mice expressing the hSCF transgene display a variety of phenotypic abnormalities, which are accentuated when combined with W alleles. Here we show that mice homozygous for the hSCF transgene demonstrate a coat color deficiency seen in some mice homozygous for mild W alleles. Specifically, homozygous hSCF transgenic mice (hSCF220) display a pronounced forehead blaze, with additional white spots over the cervical region, as well as a very large belly spot. Doubly heterozygous animals that carry both a mutated W allele and the hSCF transgene also display an unusual pigment defect and a dramatic reduction in the number of dermal mast cells. Furthermore, overexpression of MA hSCF in the thymus results in abnormal thymocyte differentiation and proliferation, which is associated with reduced mitogen activated protein (MAP) kinase activation. Thus, MAP kinase activation by a receptor tyrosine kinase, such as c-kit, may be critical for the differentiation of thymocytes in vivo.


Structure, Activity and Function of a Singing CPG Interneuron Controlling Cricket Species-Specific Acoustic Signaling.
The evolution of species-specific song patterns is a driving force in the speciation of acoustic communicating insects. It must be closely linked to adaptations of the neuronal network controlling the underlying singing motor activity. What are the cellular and network properties that allow generating different songs? In five cricket species, we analyzed the structure and activity of the identified abdominal ascending opener interneuron, a homologous key component of the singing central pattern generator. The structure of the interneuron, based on the position of the cell body, ascending axon, dendritic arborization pattern, and dye coupling, is highly similar across species. The neuron's spike activity shows a tight coupling to the singing motor activity. In all species, current injection into the interneuron drives artificial song patterns, highlighting the key functional role of this neuron. However, the pattern of the membrane depolarization during singing, the fine dendritic and axonal ramifications, and the number of dye-coupled neurons indicate species-specific adaptations of the neuronal network that might be closely linked to the evolution of species-specific singing.SIGNIFICANCE STATEMENT A fundamental question in evolutionary neuroscience is how species-specific behaviors arise in closely related species. We demonstrate behavioral, neurophysiological, and morphological evidence for homology of one key identified interneuron of the singing central pattern generator in five cricket species. Across-species differences of this interneuron are also observed, which might be important to the generation of the species-specific song patterns. This work offers a comprehensive and detailed comparative analysis addressing the neuronal basis of species-specific behavior.


Tolerance and contact sensitivity to DNFB in mice. VI. Inhibition of afferent sensitivity by suppressor T cells in adoptive tolerance.
Tolerance in contact sensitivity to DNFB can be adoptively transferred to normal mice with lymph node cells from tolerant donors. This tolerance is antigen specific and is mediated by T cells, i.e., "suppressor" T cells. Experiments were carried out to investigate the mechanism(s) by which the suppressor T cells induce tolerance to DNFB contact sensitivity. The suppressor cells were effective only if they were present during the early stages of the afferent limb of sensitization. As measured by DNA synthesis, cell proliferation in the draining lymph nodes of recipients of suppressor cells was found to be significantly less than in control animals indicating that the suppressor cells acted, at least in part, by limiting or inhibiting DNFB-induced cell proliferation. This inhibition was shown to be antigen specific since the DNFB suppressor cells did not inhibit cell proliferation induced by oxazolone, an unrelated contact sensitizer. The ability to DNFB tolerant cells to block afferent sensitization pathways differs from the mechanism of tolerance to picryl chloride, reported by others, where efferent pathways are blocked.


Xbp1-mediated histone H4 deacetylation contributes to DNA double-strand break repair in yeast.
Xbp1 has been shown to regulate the cell cycle as a transcriptional repressor in budding yeast Saccharomyces cerevisiae. In this study, we demonstrated that Xbp1 regulates DNA double-strand break (DSB) repair in S. cerevisiae. Xbp1 physically and genetically interacts with the histone deacetylase Rpd3 complex. Chromatin immunoprecipitation revealed that Xbp1 is required for efficient deacetylation of histone H4 flanking DSBs by the Rpd3 complex. Deletion of XBP1 leads to the delayed deacetylation of histone H4, which is coupled with increased nucleosome displacement, increased DNA end resection and decreased non-homologous end-joining (NHEJ). In response to DNA damage, Xbp1 is upregulated in a Mec1-Rad9-Rad53 checkpoint pathway-dependent manner and undergoes dephosphorylation. Cdk1, a central regulator of S. cerevisiae cell cycle, is responsible for Xbp1 phosphorylation at residues Ser146, Ser271 and Ser551. Substitution of these serine residues with alanine not only increases the association of Xbp1 with the Rpd3 complex and its recruitment to a DSB, but also promotes DSB repair. Together, our findings reveal a role for Xbp1 in DSB repair via NHEJ through regulation of histone H4 acetylation and nucleosome displacement in a positive feedback manner.


RNA-mediated gene silencing of FUT1 and FUT2 influences expression and activities of bovine and human fucosylated nucleolin and inhibits cell adhesion and proliferation.
In a previous article, we demonstrated the existence of fucosyl-containing O-glycans forms of nucleolin in bovine post-capillary venular endothelial cells (CVEC) and malignant cultured human A431 cells. The tool for this discovery was an antibody found to interact strongly and exclusively with nucleolin in total protein extracts. The antibody was originally raised against a mollusc glycoprotein and was demonstrated to be directed against its O-glycans, recently found to belong prevalently to the blood group H-antigen type with fucose linked in alpha1, 2 to galactose. Here, we show that si-RNA induced down-regulation of the expression of FUT1 and FUT2, the fucosyltransferases required for the biosynthesis of the terminal glycan motif Fucalpha-2-Galbeta-R, reduced expression of the fucosylated nucleolin glycoforms and their exposure at the cell surface in CVEC. Treatment of the cells with FUT1/2 siRNA also reduced their ability to bind and internalize endostatin and their adhesion efficiency and inhibited cell growth. Expression of FUT1, FUT2, and FUT6 was also analyzed in serum-stimulated versus serum-starved cells and in cells treated with FUT1 and FUT2 siRNA. A reduced expression of fucosylated nucleolin and inhibition of cell growth by suppressing FUT1/2 expression was also tested and shown to be exhibited in human A431 cells.


Evidence of a Mild Mutator Phenotype in Cambodian Plasmodium falciparum Malaria Parasites.
Malaria control efforts have been continuously stymied by drug-resistant strains of Plasmodium falciparum, which typically originate in Southeast Asia prior to spreading into high-transmission settings in Africa. One earlier proposed explanation for Southeast Asia being a hotbed of resistance has been the hypermutability or "Accelerated Resistance to Multiple Drugs" (ARMD) phenotype, whereby multidrug-resistant Southeast Asian parasites were reported to exhibit 1,000-fold higher rates of resistance to unrelated antimalarial agents when compared to drug-sensitive parasites. However, three recent studies do not recapitulate this hypermutability phenotype. Intriguingly, genome sequencing of recently derived multidrug-resistant Cambodian isolates has identified a high proportion of DNA repair gene mutations in multidrug-resistant parasites, suggesting their potential role in shaping local parasite evolution. By adapting fluctuation assays for use in P. falciparum, we have examined the in vitro mutation rates of five recent Cambodian isolates and three reference laboratory strains. For these studies we also generated a knockout parasite line lacking the DNA repair factor Exonuclease I. In these assays, parasites were typed for their ability to acquire resistance to KAE609, currently in advanced clinical trials, yielding 13 novel mutations in the Na+/H+-ATPase PfATP4, the primary resistance determinant. We observed no evidence of hypermutability. Instead, we found evidence of a mild mutator (up to a 3.4-fold increase in mutation rate) phenotype in two artemisinin-resistant Cambodian isolates, which carry DNA repair gene mutations. We observed that one such mutation in the Mismatch Repair protein Mlh1 contributes to the mild mutator phenotype when modeled in yeast (scmlh1-P157S). Compared to basal rates of mutation, a mild mutator phenotype may provide a greater overall benefit for parasites in Southeast Asia in terms of generating drug resistance without incurring detrimental fitness costs.


Crystal growth of nanoporous metal organic frameworks.
Nanoporous metal organic frameworks (MOFs) form one of the newest families of crystalline nanoporous material that is receiving worldwide attention. Successful use of MOFs for application requires not only development of new materials but also a need to control their crystal properties such as size, morphology, and defect concentration. An understanding of the crystal growth processes is necessary in order to aid development of routes to control such properties of the crystallites. In this Perspective article we aim to provide a short overview of the current work and understanding concerning the nucleation and growth processes of nanoporous MOFs and how this work may be expanded upon to further our comprehension of this subject. We also focus heavily on in situ studies that provide real time information on the developing materials and generally provide the most conclusive findings on the processes under investigation.


A morphological study of cooling rate response in normal and neoplastic human liver tissue: cryosurgical implications.
The process of freezing in normal human livers and in human liver tumors was studied by freezing samples of these tissues with constant cooling rates and then examining the morphology of the frozen tissue, after freeze substitution, with the light microscope. Cooling rates varied from 2 degrees C/min up to approximately 2000 degrees C/min. It was observed that high cooling rates produce extensive intracellular ice in both normal and neoplastic liver. At slow rates of cooling, normal and neoplastic liver cells dehydrated and large extracellular ice crystals formed. Comparison of the frozen normal liver and the frozen malignant tumors shows that for the same rates of freezing, the tumor cells retain more cellular water and therefore show less susceptibility to dehydration at low rates of cooling. At slow cooling rates, the amount of cellular dehydration and consequent vascular and interstitial space engorgement changed with the type of tissue frozen. The greatest amount of dehydration occurred in normal human liver, followed by metastatic colon carcinoma and finally primary hepatocellular carcinoma. These results are important for cryosurgery since they suggest that malignant tissues have a different response to freezing than normal tissues.


Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism.
Acute myeloid leukemia (AML) is characterized by multiple mutagenic events that affect proliferation, survival, as well as differentiation. Recently, gain-of-function mutations in the α helical structure within the linker sequence of the E3 ubiquitin ligase CBL have been associated with AML. We identified four novel CBL mutations, including a point mutation (Y371H) and a putative splice site mutation in AML specimens. Characterization of these two CBL mutants revealed that coexpression with the receptor tyrosine kinases FLT3 (Fms-like tyrosine kinase 3) or KIT-induced ligand independent growth or ligand hyperresponsiveness, respectively. Growth of cells expressing mutant CBL required expression and kinase activity of FLT3. In addition to the CBL-dependent phosphorylation of FLT3 and CBL itself, transformation was associated with activation of Akt and STAT5 and required functional expression of the small GTPases Rho, Rac, and Cdc42. Furthermore, the mutations led to constitutively elevated intracellular reactive oxygen species levels, which is commonly linked to increased glucose metabolism in cancer cells. Inhibition of hexokinase with 2-deoxyglucose blocked the transforming activity of CBL mutants and reduced activation of signaling mechanisms. Overall, our data demonstrate that mutations of CBL alter cellular biology at multiple levels and require not only the activation of receptor proximal signaling events but also an increase in cellular glucose metabolism. Pathways that are activated by CBL gain-of-function mutations can be efficiently targeted by small molecule drugs.


Dopamine -hydroxylase of bovine adrenal medullae. A rapid purification procedure.
1. A rapid purification procedure for dopamine beta-hydroxylase from bovine adrenal-medulla chromaffin granules is presented. The homogeneity of the purified enzyme was demonstrated by means of three independent criteria. The specific activity of the enzyme compares favourably with that obtained by more involved procedures. 2. The stability of the enzyme was investigated and storage in polypropylene tubes was found preferable to storage in glass. 3. The soluble and particulate forms of dopamine beta-hydroxylase appear to be identical, since membrane-bound and membrane-enclosed forms of the enzyme exhibit similar properties as regards size, charge and amino acid composition. 4. Ca(2+) was found to stimulate the release of dopamine beta-hydroxylase from bovine chromaffin granules in vitro. 5. An endogenous inhibitor of the enzyme was found in the chromaffin granules. This inhibitor was not inactivated either by heating at 100 degrees C or by pretreatment with p-chloromercuribenzoate or Cu(2+) ions.


Clinical outcome following a modified approach for psoas lengthening for coxa saltans in adults.
Internal snapping often resolves with conservative treatment but persistent significant symptoms may require surgical treatment. Different surgical approaches have been suggested in the literature with varying results. We describe a modified surgical approach for internal snapping of hip in adults with good results. Patients who failed conservative treatment for internal snapping over 11/2 years were included. A skin crease incision was made just lateral to the ASIS in supine position. The psoas tendon was reached sub-periosteally along the internal iliac surface and a hole was made in periosteum. Then the tendon was hooked into the wound and divided releasing its musculotendinous junction. The patients were allowed to mobilise as able in the postoperative period. There were 8 snapping hips (7 patients, 6 females) with average age of 30 years (17-51 yrs). The mean follow-up was 11 months. The average duration of symptoms before operation was 4.5 years (range 2-10 years). Painful symptomatic clicking was relieved in all patients. Two patients felt slight weakness of hip flexion. One patient had temporary neuropraxia of lateral cutaneous nerve of thigh. The diagnosis is made by ultrasound or examination for a palpable click. Surgical correction of snapping is considered after failure of conservative treatment. Different extrapelvic (medial and iliofemoral) and intrapelvic extraperitoneal approaches have been described with varying results. With our slightly modified intrapelvic and subperiosteal approach through oblique inguinal incision in adults, psoas muscle release at musculotendinous junction seems a safe and effective method and could be used as an alternative surgical approach for treatment of internal snapping of hip in adults.


Reduced resting state connectivity and gray matter volume correlate with cognitive impairment in minimal hepatic encephalopathy.
Minimal hepatic encephalopathy (MHE) is associated with cognitive alterations and changes in connectivity. We assessed the relationship of the abnormalities of resting-state functional connectivity (rs-FC) and gray matter (GM) volume with different cognitive alterations and biochemical parameters associated to MHE. Thirty-nine cirrhotic patients (26 without and 13 with MHE) and 24 controls were widely cognitive assessed with a battery of psychometric tests. Atrophy was determined using Voxel-Based Morphometry and rs-FC was assessed by independent component analysis. Receiver operating characteristic (ROC) curves was performed to assess the diagnostic utility of rs-FC and GM reduction for the discrimination of patients with and without MHE. Blood ammonia, cGMP, and levels of pro-inflammatory interleukins were measured. MHE patients showed significant decrease of GM volume and lesser degree of rs-FC in different networks related to attention and executive functions as compared to controls and patients without MHE. There is a progressive reduction in rs-FC in the default mode network with the progression of cognitive impairment. MHE patients showed GM reduction in the right frontal lobe, right insula and right cerebellum compared to patients without MHE. Alterations in GM volume and rs-FC correlated with the scores of different cognitive tests. Decreased cognitive performance is associated by reduced rs-FC and GM atrophy in MHE patients. These changes could have predictive value for detecting MHE.


[Effect of luliberin and chorionic gonadotropin on luteinizing hormone and testosterone levels in the blood of monkeys under acute stress].
The effect of immobilization stress on luteinizing hormone (LH) and testosterone (T) secretion following injections of luliberin (LH-RH) and human chorionic gonadotropin (HCG) was investigated in male hamadryas baboons. It was established that in control animals a single injection of HCG (4500 IU) led to a more prolonged and more demonstrable increase of plasma testosterone concentration than injection of a pharmacological dose (100 micrograms) of LH-RH. Preliminary stimulation of the testes with LH-RH did not prevent the stress-induced inhibition of testosterone despite the fact that LH secretion in intact and stress-exposed baboons did not differ significantly over 2.5 h after drug injection. At the same time stress did not inhibit the testicular response in baboons pretreated with HCG (4500 IU), although the level of T concentration in stress-exposed animals was lower than in control. The data obtained suggest that disturbed interaction between hypophyseal tropic hormone and the testes underlie the inhibitory effect of stress.


Flavonoids Targeting HIF-1: Implications on Cancer Metabolism.
Tumor hypoxia is described as an oxygen deprivation in malignant tissue. The hypoxic condition is a consequence of an imbalance between rapidly proliferating cells and a vascularization that leads to lower oxygen levels in tumors. Hypoxia-inducible factor 1 (HIF-1) is an essential transcription factor contributing to the regulation of hypoxia-associated genes. Some of these genes modulate molecular cascades associated with the Warburg effect and its accompanying pathways and, therefore, represent promising targets for cancer treatment. Current progress in the development of therapeutic approaches brings several promising inhibitors of HIF-1. Flavonoids, widely occurring in various plants, exert a broad spectrum of beneficial effects on human health, and are potentially powerful therapeutic tools against cancer. Recent evidences identified numerous natural flavonoids and their derivatives as inhibitors of HIF-1, associated with the regulation of critical glycolytic components in cancer cells, including pyruvate kinase M2(PKM2), lactate dehydrogenase (LDHA), glucose transporters (GLUTs), hexokinase II (HKII), phosphofructokinase-1 (PFK-1), and pyruvate dehydrogenase kinase (PDK). Here, we discuss the results of most recent studies evaluating the impact of flavonoids on HIF-1 accompanied by the regulation of critical enzymes contributing to the Warburg phenotype. Besides, flavonoid effects on glucose metabolism via regulation of HIF-1 activity represent a promising avenue in cancer-related research. At the same time, only more-in depth investigations can further elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism.


Rad52 promotes second-end DNA capture in double-stranded break repair to form complement-stabilized joint molecules.
Saccharomyces cerevisiae Rad52 performs multiple functions during the recombinational repair of double-stranded DNA (dsDNA) breaks (DSBs). It mediates assembly of Rad51 onto single-stranded DNA (ssDNA) that is complexed with replication protein A (RPA); the resulting nucleoprotein filament pairs with homologous dsDNA to form joint molecules. Rad52 also catalyzes the annealing of complementary strands of ssDNA, even when they are complexed with RPA. Both Rad51 and Rad52 can be envisioned to promote "second-end capture," a step that pairs the ssDNA generated by processing of the second end of a DSB to the joint molecule formed by invasion of the target dsDNA by the first processed end. Here, we show that Rad52 promotes annealing of complementary ssDNA that is complexed with RPA to the displaced strand of a joint molecule, to form a complement-stabilized joint molecule. RecO, a prokaryotic homolog of Rad52, cannot form complement-stabilized joint molecules with RPA-ssDNA complexes, nor can Rad52 promote second-end capture when the ssDNA is bound with either human RPA or the prokaryotic ssDNA-binding protein, SSB, indicating a species-specific process. We conclude that Rad52 participates in second-end capture by annealing a resected DNA break, complexed with RPA, to the joint molecule product of single-end invasion event. These studies support a role for Rad52-promoted annealing in the formation of Holliday junctions in DSB repair.


Review of donor and recipient surgical procedures in lung transplantation.
Lung transplant remains the only durable treatment of end stage lung disease. Efficient surgical technique and preservation strategy are of critical importance in avoiding ischemia reperfusion injury and primary graft dysfunction (PGD), both associated with poorer outcomes. We present our surgical and preservation strategy for both donor and recipient procedures, including endobronchial and intracorporeal lung assessment, mediastinal dissection, lung preservation, donor pneumonectomy, back bench preparation, recipient approach, pneumonectomy, along with the bronchial, pulmonary artery, and pulmonary venous anastomoses.


Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000.
The incidence of kidney failure treatment in the United States increased 57% from 1991 to 2000. Chronic kidney disease (CKD) prevalence was 11% among U.S. adults surveyed in 1988 to 1994. The objective of this study was to estimate awareness of CKD in the U.S. population during 1999 to 2000 and to determine whether the prevalence of CKD in the United States increased compared with 1988 to 1994. Analysis was conducted of nationally representative samples of noninstitutionalized adults, aged 20 yr and older, in two National Health and Nutrition Examination Surveys conducted in 1988 to 1994 (n = 15,488) and 1999 to 2000 (n = 4101) for prevalence +/- SE. Awareness of CKD is self-reported. Kidney function (GFR), kidney damage (microalbuminuria or greater), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine, spot urine albumin to creatinine ratio (ACR), age, gender, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation. Self-reported awareness of weak or failing kidneys in 1999 to 2000 was strongly associated with decreased kidney function and albuminuria but was low even in the presence of both conditions. Only 24.3 +/- 6.4% of patients at GFR 15 to 59 ml/min per 1.73 m(2) and albuminuria were aware of CKD compared with 1.1 +/- 0.3% at GFR of 90 ml/min per 1.73 m(2) or greater and no microalbuminuria. At moderately decreased kidney function (GFR 30 to 59 ml/min per 1.73 m(2)), awareness was much lower among women than men (2.9 +/- 1.6 versus 17.9 +/- 5.9%; P = 0.008). The prevalence of moderately or severely decreased kidney function (GFR 15 to 59 ml/min per 1.73 m(2)) remained stable over the past decade (4.4 +/- 0.3% in 1988 to 1994 and 3.8 +/- 0.4% in 1999 to 2000; P = 0.23). At the same time, the prevalence of albuminuria (ACR >/= 30 mg/g) in single spot urine increased from 8.2 +/- 0.4% to 10.1 +/- 0.7% (P = 0.01). Overall CKD prevalence was similar in both surveys (9% using ACR > 30 mg/g for persistent microalbuminuria; 11% in 1988 to 1994 and 12% in 1999 to 2000 using gender-specific ACR cutoffs). Despite a high prevalence, CKD awareness in the U.S. population is low. In contrast to the dramatic increase in treated kidney failure, overall CKD prevalence in the U.S. population has been relatively stable.


Selective-area growth of single-crystal wurtzite GaN nanorods on SiOx/Si(001) substrates by reactive magnetron sputter epitaxy exhibiting single-mode lasing.
Selective-area growth (SAG) of single-crystal wurtzite GaN nanorods (NRs) directly onto Si(001) substrates with un-etched native SiOx amorphous layer, assisted by a patterning TiNx mask fabricated by nanosphere lithography (NSL), has been realized by reactive magnetron sputter epitaxy (MSE). The GaN NRs were grown vertically to the substrate surface with the growth direction along c-axis in the well-defined nano-opening areas. A 5-step structural and morphological evolution of the SAG NRs observed at different sputtering times depicts a comprehensive growth model, listed in sequence as: formation of a polycrystalline wetting layer, predominating c-axis oriented nucleation, coarsening and coalescence of multi-islands, single NR evolution, and finally quasi-equilibrium crystal shape formation. Room-temperature cathodoluminescence spectroscopy shows a strong GaN bandedge emission with a uniform luminescence across the NRs, indicating that the SAG NRs are grown with high quality and purity. In addition, single-longitudinal-mode lasing, attributed to well-faceted NR geometry forming a Fabry-Pérot cavity, was achieved by optical pumping, paving a way for fabricating high-performance laser optoelectronics using MSE.


Neurocognitive Correlates in Driving Under the Influence of Cannabis.
Delta (9)-tetrahydrocannabinol (THC) is the main psychoactive compound in cannabis and is frequently identified in blood samples from apprehended drivers suspected for driving under the influence of drugs. Changing social norms towards cannabis and higher acceptability towards the drug emphasize the need for in-depth understanding of the acute neurocognitive and psychomotor effects caused by cannabis and how these effects are correlated to driving skills and performance. In this review, PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar databases were used to identify and select publications up to January 2017 dealing with acute and chronic neurocognitive effects induced by cannabis and ability to drive. Thirty-six publications were selected for this review. The studies conducted were experimental, using simulators or on-road studies and brain imaging (structural and functional) to better understand the acute and chronic effects on cognitive functions comprised in the short and long-term fitness to drive after cannabis consumption. In a case-crossover self-report study a significant odds ratio increase was found for driving- related injury after combined exposure to cannabis and alcohol compared to cannabis alone (OR of 10.9 and 5.8 respectively). Both, experimental and epidemiological studies have revealed that THC affects negatively both, psychomotor skills and cognitive functions. Studies of the acute effects of cannabis on driving have shown that drivers under the influence of this substance are impaired. Indeed, driving under the influence of cannabis doubles or triples the risk of a crash. Specifically, cannabis use impairs critical-tracking tasks, increases lane weaving, decreases reaction time, and divided attention.


Exercise and cardiac oxidative stress.
Cardiac muscle is frequently affected by many stimuli responsible for loss of cell homeostasis, including physical exercise. While exercise has been presented as a recommended activity for health reasons, it also provides favorable conditions for additional production of reactive oxygen species. These compounds are associated with fundamental mechanisms of cell metabolism but are also related to the etiology and pathophysiology of some cardiac diseases. Cardiac muscle tissue has a high oxidative metabolic rate and relatively low activity of the main antioxidant enzymes, which could enhance its susceptibility to oxidative injury after acute exercise. However, physical training could be considered an important stimulus for the different antioxidant systems like glutathione and those related to the activity of some important antioxidant enzymes in myocardial protection such as superoxide dismutase and glutathione peroxidase. Endurance training seems to induce up-regulation in some antioxidant defenses, protecting cardiac muscle in potentially harmful situations that induce additional oxidative stress. Nevertheless, the mechanisms related to this cross-tolerance effect of training are not yet well understood.