Adult non-biting midges: possible windborne carriers of Vibrio cholerae non-O1 non-O139.
Vibrio cholerae is a waterborne bacterium native to the aquatic environment. There are over 200 known serogroups yet only two cause cholera pandemics in humans. Direct contact of human sewage with drinking water, sea-born currents and marine transportation, represent modes of dissemination of the bacteria and thus the disease. The simultaneous cholera outbreaks that occur sometimes in distant localities within continental landmasses are puzzling. Here we present evidence that flying, non-biting midges (Diptera; Chironomidae), collected in the air, carry viable non-O1 non-O139 serogroups of V. cholerae. The association of V. cholerae with chironomid egg masses, which serve as a V. cholerae reservoir, was further confirmed. In simulated field experiments, we recorded the transfer of environmental V. cholerae by adult midges from the aquatic environment into bacteria-free water-pools. In laboratory experiments, flying adult midges that emerged from V. cholerae (O1 or O139) contaminated water transferred the green fluorescent protein (GFP)-tagged pathogenic bacteria from one laboratory flasks to another. Our findings show that aerial transfer by flying chironomids may play a role in the dissemination of V. cholerae in nature.


Proliferation of hydroelectric dams in the Andean Amazon and implications for Andes-Amazon connectivity.
Due to rising energy demands and abundant untapped potential, hydropower projects are rapidly increasing in the Neotropics. This is especially true in the wet and rugged Andean Amazon, where regional governments are prioritizing new hydroelectric dams as the centerpiece of long-term energy plans. However, the current planning for hydropower lacks adequate regional and basin-scale assessment of potential ecological impacts. This lack of strategic planning is particularly problematic given the intimate link between the Andes and Amazonian flood plain, together one of the most species rich zones on Earth. We examined the potential ecological impacts, in terms of river connectivity and forest loss, of the planned proliferation of hydroelectric dams across all Andean tributaries of the Amazon River. Considering data on the full portfolios of existing and planned dams, along with data on roads and transmission line systems, we developed a new conceptual framework to estimate the relative impacts of all planned dams. There are plans for 151 new dams greater than 2 MW over the next 20 years, more than a 300% increase. These dams would include five of the six major Andean tributaries of the Amazon. Our ecological impact analysis classified 47% of the potential new dams as high impact and just 19% as low impact. Sixty percent of the dams would cause the first major break in connectivity between protected Andean headwaters and the lowland Amazon. More than 80% would drive deforestation due to new roads, transmission lines, or inundation. We conclude with a discussion of three major policy implications of these findings. 1) There is a critical need for further strategic regional and basin scale evaluation of dams. 2) There is an urgent need for a strategic plan to maintain Andes-Amazon connectivity. 3) Reconsideration of hydropower as a low-impact energy source in the Neotropics.


Colloids vs. crystalloids--a continuing controversy.
The crystalloid vs. colloid controversy is based on a disagreement as to the most effective, safest, and most economical method of maintaining an effective plasma volume in shock patients. This review discusses Starling's law of fluid movement, with a definition of each term in the normal physiological state, and presents examples of how each component of Starling's law differs in the two major types of pulmonary edema: (1) cardiogenic and (2) noncardiogenic. The colloid-crystalloid literature is reviewed briefly with an emphasis on the major studies that support each side, and the deficiencies in each study. The arguments supporting each side of the crystalloid-colloid debate are then listed, with a summary that demonstrates the areas of agreement between the two schools of thought on fluid resuscitation. Each major colloid (albumin, dextran, hetastarch) and a representative crystalloid (lactated Ringer's) are discussed in terms of their chemistry; pharmacology and indications; and precautions, adverse reactions, and side effects. A table is included that summarizes the available products' data regarding composition, volume expansion, duration of expansion, half-life, metabolism, elimination, precautions, adverse reactions, and dose.


Partnership research: a practical trial design for evaluation of a natural experiment to improve depression care.
Translational research is increasingly important as academic health centers transform themselves to meet new requirements of National Institutes of Health funding. Most attention has focused on T1 translation studies (bench to bedside) with considerable uncertainty about how to enhance T2 (effectiveness trials) and especially T3 (implementation studies). To describe an innovative example of a T3 study, conducted as partnership research with the leaders of a major natural experiment in Minnesota to improve the primary care of depression. All health plans in the state have agreed on a new payment model to support clinics that implement the well-evidenced collaborative care model for depression in the Depression Improvement Across Minnesota: Offering a New Direction initiative. The Depression Improvement Across Minnesota: Offering a New Direction study was developed in an ongoing partnership with the Initiative leaders from 7 health plans, 85 clinics, and a regional quality improvement collaborative to evaluate the implementation and its impacts on patients and other stakeholders. We agreed on a staggered implementation, multiple baseline research design, using the concepts of practical clinical trials and engaged scholarship and have collaborated on all aspects of conducting the study, including joint identification of patient and clinic survey recipients. Complex study methods have worked well through 20 months because of the commitment of all stakeholders to both the Initiative and the Study. Over 1500 subjects have been recruited from health plan information delivered weekly, and 99.7% of 316 physicians and administrators from all participating clinical organizations have completed the Study surveys. Partnership research can greatly facilitate translational research studies.


Design and Synthesis of TASIN Analogues Specifically Targeting Colorectal Cancer Cell Lines with Mutant Adenomatous Polyposis Coli (APC).
Despite advances in targeted anticancer therapies, there are still no small-molecule-based therapies available that specifically target colorectal cancer (CRC) development and progression, the second leading cause of cancer deaths. We previously disclosed the discovery of truncating adenomatous polyposis coli (APC)-selective inhibitor 1 (TASIN-1), a small molecule that specifically targets colorectal cancer cells lines with truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor gene through inhibition of cholesterol biosynthesis. Here, we report a medicinal chemistry evaluation of a collection of TASIN analogues and activity against colon cancer cell lines and an isogenic cell line pair reporting on the status of APC-dependent selectivity. A number of potent and selective analogues were identified, including compounds with good metabolic stability and pharmacokinetic properties. The compounds reported herein represent a first-in-class genotype-selective series that specifically target apc mutations present in the majority of CRC patients and serve as a translational platform toward a targeted therapy for colon cancer.


Food and weight-related patterns and behaviors of Hmong adolescents.
Little is known about the food and weight-related behaviors of Hmong adolescents. This study assessed these behaviors in Hmong adolescents and determined if they differed between Hmong and white teens or by country of birth. School-based cross-sectional study. Hmong (n=649) and white (n=2,260) adolescents from 31 public middle and high schools in the Minneapolis/St Paul, MN, metropolitan area who participated in Project EAT (Eating Among Teens). Family meals, grocery shopping, and meal preparation; consumption of breakfast, snacks, and fast foods, physical activity and inactivity; body satisfaction, weight concern, body mass index, and weight-control behaviors. Variables were compared across race/ethnicity and by country of birth using chi(2) tests and general linear model regression. Hmong students reported greater participation in family meals and more involvement with food purchasing and preparation. Fast-food consumption was similar among groups. Hmong teens reported less frequent breakfast consumption. The prevalence of overweight was higher in Hmong male adolescents than white male adolescents, but similar among female adolescents. Hmong students reported higher levels of weight concern, body dissatisfaction, dieting, unhealthful weight-control behaviors, less physical activity, and more inactivity than white students. Hmong male adolescents participated in extreme unhealthful weight-control behaviors four times more often than white male adolescents. Hmong adolescents appear to be at increased risk for obesity, body dissatisfaction, and unhealthful weight-control behaviors compared to white adolescents. There is a need for culturally tailored interventions to address these nutrition and weight issues among Hmong adolescents.


Tertiary intratumor lymphoid tissue in colo-rectal cancer.
Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.


Increased hepatotoxicity and cardiac fibrosis in cocaine-treated butyrylcholinesterase knockout mice.
In mice, cocaine is detoxified to inactive products by butyrylcholinesterase (BChE) and carboxylesterase. In human beings, cocaine detoxification is primarily by BChE. The focus of this investigation was to elucidate the importance of BChE in reducing pathophysiological effects following cocaine exposure. Previous studies examining the effects of cocaine on BChE deficient animals relied on chemical inhibition of BChE with tetraisopropyl pyrophosphoramide (iso-OMPA). The creation of the BChE knockout mouse has provided a model for studying pathological effects of cocaine in mice free of chemical confounders. We hypothesized that mice with low or no BChE activity would have reduced cocaine metabolism, leading to hepatotoxicity and cardiomyopathy. A high-resolution in vivo imaging system recorded cardiac and respiratory function following treatment with a carboxylesterase inhibitor and a high dose of cocaine (100 mg/kg, intraperitoneally). The BChE-/- mice demonstrated depressed respiration through 12 hr after dosing and abnormal respiratory patterns consisting of a pause at full inspiration (apneusis), whereas BChE+/+ mice had recovered normal respiration rates by 30 min. after dosing and exhibited no apneusis. Liver and cardiac histology sections were analysed following a 20 mg/kg intraperitoneally dose of cocaine administered daily for 7 days. BChE-/- mice treated for 7 days with the chronic low dose showed significant hepatotoxicity and cardiac perivascular fibrosis compared to BChE+/+ mice. The observed functional changes following acute high-dose and chronic low-dose cocaine in BChE-/- and +/- mice warrants further investigation into the possibility of increased cocaine toxicity in human beings with BChE deficiency.


Involvement of Protein Kinase D1 in Signal Transduction from the Protein Kinase C Pathway to the Tyrosine Kinase Pathway in Response to Gonadotropin-releasing Hormone.
The receptor for gonadotropin-releasing hormone (GnRH) belongs to the G protein-coupled receptors (GPCRs), and its stimulation activates extracellular signal-regulated protein kinase (ERK). We found that the transactivation of ErbB4 was involved in GnRH-induced ERK activation in immortalized GnRH neurons (GT1-7 cells). We found also that GnRH induced the cleavage of ErbB4. In the present study, we examined signal transduction for the activation of ERK and the cleavage of ErbB4 after GnRH treatment. Both ERK activation and ErbB4 cleavage were completely inhibited by YM-254890, an inhibitor of Gq/11 proteins. Down-regulation of protein kinase C (PKC) markedly decreased both ERK activation and ErbB4 cleavage. Experiments with two types of PKC inhibitors, Gö 6976 and bisindolylmaleimide I, indicated that novel PKC isoforms but not conventional PKC isoforms were involved in ERK activation and ErbB4 cleavage. Our experiments indicated that the novel PKC isoforms activated protein kinase D (PKD) after GnRH treatment. Knockdown and inhibitor experiments suggested that PKD1 stimulated the phosphorylation of Pyk2 by constitutively activated Src and Fyn for ERK activation. Taken together, it is highly possible that PKD1 plays a critical role in signal transduction from the PKC pathway to the tyrosine kinase pathway. Activation of the tyrosine kinase pathway may be involved in the progression of cancer.


Impaired T cell receptor signaling in Foxp3+ CD4 T cells.
Dominant tolerance to autoantigens is primarily achieved through the action of the CD4(+)CD25(+)Foxp3(+) subset of T cells, which have the capability of suppressing autoreactive T cells that have escaped deletion during thymic selection. The essential role of the forkhead/winged-helix transcription factor Foxp3 in the development and function of these cells has been well documented. What is less clear is the role of Foxp3 in the altered TCR signaling that is seen in Tregs. We have used a Foxp3 transgenic mouse line to demonstrate that Foxp3 expression correlates with attenuated TCR signaling, and that the deficit in Foxp3-transgenic CD4 T cells, as well as in CD4(+)CD25(+) Tregs, affects multiple biochemical pathways.


Silencing ferritin alleviates atherosclerosis in mice via regulating the expression levels of matrix metalloproteinases and interleukins.
This study was conducted to investigate the roles of ferritin in atherosclerosis. The mouse model of atherosclerosis was established by feeding ApoE knockout mice with a high-fat diet. The mice were then treated with ferritin-overexpressing and -silencing constructs, and assessed for interleukins (ILs) and matrix metalloproteinases (MMPs) levels using ELISA and Western blot analysis. After being fed with a high-fat diet, the ApoE knockout mice developed pro-atherogenic lipid profiles with elevated total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). They also showed increased atherosclerotic lesions including narrowed lumen diameter, reduced lumen area, and increased plaque size. Following injection of the overexpression and silencing constructs, mRNA levels of ferritin were increased and decreased, respectively, and at the same time the atherosclerotic lesions were aggravated and alleviated, respectively. Further analysis indicated that silencing of ferritin gene reduced IL-1β and IL-10 levels while overexpressing ferritin increased them. On other hand, the TNF-α levels showed an opposite trend. MMP8, MMP12 and MMP13 levels were increased or decreased significantly after the mice were injected with ferritin over-expression or silencing vectors, respectively. Western blot analysis showed that compared to the control, overexpressing ferritin resulted in increased expression of p-JNK while silencing ferritin decreased the expression. Meanwhile, the levels of pc-Jun remained unchanged. Our work demonstrates that ferritin can regulate the progress of atherosclerosis via regulating the expression levels of MMPs and interleukins. Silencing ferritin inhibits the development of atherosclerosis and is, therefore, worth being further investigated as a potential therapeutic approach for this disease.


Feedback on oral presentations during pediatric clerkships: a randomized controlled trial.
To measure the effects of participating in structured oral presentation evaluation sessions early in pediatric clerkships on students' subsequent presentations. We conducted a single-blind, 3-arm, cluster randomized controlled trial during pediatric clerkships at Boston University School of Medicine, University of Maryland School of Medicine, Oregon Health & Science University, and Case Western Reserve University School of Medicine. Blocks of students at each school were randomly assigned to experience either (1) no formal presentation feedback (control) or a small-group presentation feedback session early in pediatric clerkships in which students gave live presentations and received feedback from faculty who rated their presentations by using a (2) single-item (simple) or (3) 18-item (detailed) evaluation form. At the clerkship end, overall quality of subjects' presentations was rated by faculty blinded to randomization status, and subjects reported whether their presentations had improved. Analyses included multivariable linear and logistic regressions clustered on clerkship block that controlled for medical school. A total of 476 participants were evenly divided into the 3 arms, which had similar characteristics. Compared with controls, presentation quality was significantly associated with participating in detailed (coefficient: 0.38; 95% confidence interval [CI]: 0.07-0.69) but not simple (coefficient: 0.16; 95% CI: -0.12-0.43) feedback sessions. Similarly, student self-report of presentation improvement was significantly associated with participating in detailed (odds ratio: 2.16; 95% CI: 1.11-4.18] but not simple (odds ratio: 1.89; 95% CI: 0.91-3.93) feedback sessions. Small-group presentation feedback sessions led by faculty using a detailed evaluation form resulted in clerkship students delivering oral presentations of higher quality compared with controls.


Modular Three-component Delivery System Facilitates HLA Class I Antigen Presentation and CD8(+) T-cell Activation Against Tumors.
Cell-mediated immunotherapies have potential as stand-alone and adjuvant therapies for cancer. However, most current protocols suffer from one or more of three major issues: cost, safety, or efficacy. Here we present a nanoparticle delivery system that facilitates presentation of an immunogenic measles antigen specifically in cancer cells. The delivery system does not contain viral particles, toxins, or biologically derived material. Treatment with this system facilitates activation of a secondary immune response against cancer cells, bypassing the need to identify tumor-associated antigens or educate the immune system through a primary immune response. The delivery system consists of a stealth liposome displaying a cancer-specific targeting peptide, named H1299.3, on its exterior surface and encapsulating H250, an immunogenic human leukocyte antigen class 1 restricted peptide. This targeted-nanoparticle facilitates presentation of the H250 peptide in major histocompatibility complex class I molecules. Activation is dependent on the targeting peptide, previous antigen exposure, and utilizes a novel autophagy-mediated mechanism to facilitate presentation. Treatment with this liposome results in a significant reduction of tumor growth using an aggressive LLC1 model in vaccinated C57BL/6 mice. These data provide proof-of-principle for a novel cell-mediated immunotherapy that is scalable, contains no biologically derived material, and is an efficacious cancer therapy.


Prospective randomized comparison of repairing vesicovaginal fistula with or without the interposition flap: Result from a tertiary care Institute in Northern India.
Assessment of results of repairing vesicovaginal fistula (VVF) with or without the use of interposition flaps. This prospective randomized study was conducted between January 2012 to December 2017 in the Department of Urology, King George's Medical University, Lucknow, India. Obstetric and gynecological simple fistula of ≤4 cm were included for evaluation. Those with complex or complicated fistula or fistula due to malignancy were excluded. Patients were divided into two groups (group 1 and group 2) depending upon route of repair i.e., transvaginal or transabdominal, respectively, as per the characteristics and location of the fistula. These two groups of patients were randomized into two subgroups (1A, 1B and 2A, 2B) based on the inclusion or omission of the interposition flap during fistula repair. Perioperative and postoperative parameters (blood loss, mean operating time, hospital stay, and requirement of analgesics) and success rates of fistula repair were compared. All complications that occurred in the postoperative period till the last follow-up appointment were recorded. The Clavien-Dindo Classification was used to stratify the complications. Fifty-seven patients underwent transvaginal repair in group 1 (29 with Martius flap: group 1A; 28 without Martius flap: group 1B), while 69 patients underwent transabdominal repair in group 2 (35 with interposition flap: group 2A; 34 without flap: group 2B). Blood loss, mean operating time, hospital stay, and the requirement of analgesics were comparable between each subgroup-1A versus 1B and 2A versus 2B, respectively. The overall success rate of repair across all groups was 96.04% (121/126). The success rate was 93.1% in transvaginal repair with Martius flap versus 96.43% in transvaginal repair with no flap (p=1.0). Success rate was 97.1% in transabdominal repair with an omental flap versus 97.06% in without an omental flap (p=1.0). Mean follow-up period was 39.6 months (range: 6-68 months). Out of 29 patients with Martius flap interposition, 9 (31.03%) of them reported a significantly reduced sensation on the labia majora. Of these 9 patients, 5 reported numbness while the remaining 4 experienced pain as compared to the patients in subgroup IB, who did not report any altered sensation in the labia. (p=0.0019). The success rates are similar in simple VVF repair (fistula size less than 4 cm) irrespective of the use of interposition flaps. However, overall morbidities following repair with the interposition flap are higher when compared with repair without interposition flap, either by the transvaginal or by the transabdominal route.


A field comparison of marine mammal detections via visual, acoustic, and infrared (IR) imaging methods offshore Atlantic Canada.
Impulsive sounds generated during seismic surveys have elicited behavioral responses in marine mammals and could cause hearing impairment or injury. Mitigating exposure to seismic sound often relies on real-time marine mammal detection. Detection performance is influenced by detection method, environmental conditions, and observer experience. We conducted a field comparison of real-time detections made by marine mammal observers (MMOs), a rotating infrared (IR) camera, and via passive acoustic monitoring (PAM). Data were collected from a 38 m research vessel offshore Atlantic Canada. Our results indicate that overall detection rates increase when complementary methods are used. MMOs and PAM are likely the most effective combination during high seas and precipitation. PAM and IR can be used in darkness. In good visibility, MMOs with IR or PAM should increase detections. Our results illustrate the importance of addressing false positive IR detections, matching system capabilities to sea conditions/species of interest, and employing experienced observers.


How palatable food disrupts appetite regulation.
Appetite regulation is part of a feedback system that controls the energy balance, involving a complex interplay of hunger and satiety signals, produced in the hypothalamus as well as in peripheral organs. Hunger signals may be generated in peripheral organs (e.g. ghrelin) but most of them are expressed in the hypothalamus (neuropeptide Y, orexins, agouti-related peptide, melanin concentrating hormone, endogenous opiates and dopamine) and are expressed during situations of energy deficiency. Some satiety signals, such as cholecystokinin, glucagon-like peptide 1, peptide YY and enterostatin are released from the digestive tract in response to food intake. Others, such as leptin and insulin, are mobilized in response to perturbations in the nutritional state. Still others are generated in neurones of the hypothalamus (alpha-melanocyte-stimulating hormone and serotonin). Satiety signals act by inhibiting the expression of hunger signals and/or by blunting their effect. Palatable food, i.e. food rich in fat and sugar, up-regulates the expression of hunger signals and satiety signals, at the same time blunting the response to satiety signals and activating the reward system. Hence, palatable food offsets normal appetite regulation, which may explain the increasing problem of obesity worldwide.


Complications after breast augmentation with hyaluronic acid: a case report.
Breast augmentation is a very requested procedure in aesthetic surgery. Over time, various techniques of breast augmentation have been described, both through the use of alloplastic materials and autologous tissues: implants, fat grafting, flap surgery, and injectable fillers. According to the international current trend to perform minimally invasive procedure, injectable fillers have progressively increased their uses and notoriety in aesthetic medicine. Among the various available products, hyaluronic acid is likely to be the most popular synthetic filler all over the world. Nowadays many brands are on the market and this paper focuses on Macrolane which is a NASHA-based (stabilized hyaluronic acid of non-animal origin) filler. However, although highly biocompatible, as any material, foreign to our body, also hyaluronic acid fillers undergo a process of degradation and disposal. In our work, we report the first case in literature of migration of Macrolane in an axillary lymph node in a 45-year-old woman three years after injection for breast augmentation and its related management. The aim of the paper is to discuss and underline further complications and their treatment besides the ones already described in literature in order to provide a deeper knowledge concerning the use and the side effects of injectable fillers in aesthetic medicine.


Removal of the alpha-galactosides of sucrose from soybean meal using either ethanol extraction or exogenous alpha-galactosidase and broiler performance.
Two studies using broiler chicks and one using adult White Leghorn roosters were conducted to determine the influence of stachyose and raffinose (alpha-galactosides of sucrose) present in soybean meal (SBM) on the nutritional value of the meal. In Experiment 1, the addition of four levels (0, .05, .10, or .20 g/kg) of alpha-galactosidase with and without 1 g/kg of invertase to a corn-SBM diet had no effect on weight gain, feed efficiency, protein digestibility, or the digestible energy value of the feed when fed to broiler chicks. However, both enzymes decreased (P < .001) dietary AMEn. In Experiment 2, ethanol extraction and incubation of SBM with alpha-galactosidase decreased the concentrations of the alpha-galactosides of sucrose in SBM from 6.59 to .81 and 1.43%, respectively. However, when broiler chicks were fed semi-purified diets containing SBM, ethanol-extracted SBM, water-incubated SBM, or water plus alpha-galactosidase-incubated SBM, no improvements in weight gain, feed efficiency, or apparent protein digestibility were observed. There was also no improvement in TMEn when the above meals were precision fed to adult White Leghorn roosters (Experiment 3). These results indicate that the removal of up to approximately 90% of the alpha-galactosides of sucrose has no beneficial effect on the nutritional value of SBM for chickens.


Earth as an intense planetary radio source: similarities to jupiter and saturn.
Observations from spacecraft have revealed naturally occurring radio emission emanating from two regions near Earth. The characteristics of these two sources suggest a correlation with areas of known electron precipitation. The possibility of a similar production mechanism for observed nonthermal radio emissions from other planetary magnetospheres permits the polar magnetic field strengths of Jupiter and Saturn to be predicted.


Predictors of Treatment Adequacy During Evidence-Based Psychotherapy for PTSD.
The U.S. Department of Veterans Affairs (VA) has placed increased emphasis on the availability and use of evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD). However, many individuals do not complete a full course of EBP. The current study aimed to quantify the percentage of veterans receiving adequate EBP in VA hospitals and identify factors related to treatment completion. A national sample of 16,559 VA patients who began cognitive processing therapy (CPT) or prolonged exposure (PE) during fiscal year 2015 was obtained via administrative data. Generalized estimating equations were used to evaluate individual-level predictors of treatment adequacy, defined as eight sessions within 14 weeks. Generalized linear models were used to examine facility-level factors. A total of 5,142 (31.1%) veterans completed eight or more sessions of psychotherapy. Older age was associated with greater odds of completing eight or more sessions (odds ratio OR=1.02, 95% confidence interval [CI]=1.01, 1.02, p<0.001), and comorbid bipolar or psychotic disorders were associated with reduced odds of completion (OR=0.89, 95% CI=0.80, 0.99, p=0.03). The percentage of patients who completed eight or more sessions was higher at facilities with higher percentages of EBP use among all patients with PTSD (β=6.55, SE=1.97, p=0.001) and greater numbers of EBP-certified providers (β=0.004, SE=0.002, p=0.038) and lower at facilities with a higher percentage of patients receiving a PTSD Checklist (β=-1.16, SE=0.46, p=0.011). A minority of VA patients with PTSD complete an adequate dose of EBPs for PTSD. Individual and facility-level factors related to treatment adequacy may point to opportunities for intervention.


Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.
To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials.


Smartphone-based artificial intelligence using a transfer learning algorithm for the detection and diagnosis of middle ear diseases: A retrospective deep learning study.
Middle ear diseases such as otitis media and middle ear effusion, for which diagnoses are often delayed or misdiagnosed, are among the most common issues faced by clinicians providing primary care for children and adolescents. Artificial intelligence (AI) has the potential to assist clinicians in the detection and diagnosis of middle ear diseases through imaging. Otoendoscopic images obtained by otolaryngologists from Taipei Veterans General Hospital in Taiwan between Jany 1, 2011 to Dec 31, 2019 were collected retrospectively and de-identified. The images were entered into convolutional neural network (CNN) training models after data pre-processing, augmentation and splitting. To differentiate sophisticated middle ear diseases, nine CNN-based models were constructed to recognize middle ear diseases. The best-performing models were chosen and ensembled in a small CNN for mobile device use. The pretrained model was converted into the smartphone-based program, and the utility was evaluated in terms of detecting and classifying ten middle ear diseases based on otoendoscopic images. A class activation map (CAM) was also used to identify key features for CNN classification. The performance of each classifier was determined by its accuracy, precision, recall, and F1-score. A total of 2820 clinical eardrum images were collected for model training. The programme achieved a high detection accuracy for binary outcomes (pass/refer) of otoendoscopic images and ten different disease categories, with an accuracy reaching 98.0% after model optimisation. Furthermore, the application presented a smooth recognition process and a user-friendly interface and demonstrated excellent performance, with an accuracy of 97.6%. A fifty-question questionnaire related to middle ear diseases was designed for practitioners with different levels of clinical experience. The AI-empowered mobile algorithm's detection accuracy was generally superior to that of general physicians, resident doctors, and otolaryngology specialists (36.0%, 80.0% and 90.0%, respectively). Our results show that the proposed method provides sufficient treatment recommendations that are comparable to those of specialists. We developed a deep learning model that can detect and classify middle ear diseases. The use of smartphone-based point-of-care diagnostic devices with AI-empowered automated classification can provide real-world smart medical solutions for the diagnosis of middle ear diseases and telemedicine. This study was supported by grants from the Ministry of Science and Technology (MOST110-2622-8-075-001, MOST110-2320-B-075-004-MY3, MOST-110-2634-F-A49 -005, MOST110-2745-B-075A-001A and MOST110-2221-E-075-005), Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST111-G6-11-2, VGHUST111c-140), and Taipei Veterans General Hospital (V111E-002-3).


Developing a Cas9-based tool to engineer native plasmids in Synechocystis sp. PCC 6803.
The oxygenic photosynthetic bacterium Synechocystis sp. PCC 6803 (S6803) is a model cyanobacterium widely used for fundamental research and biotechnology applications. Due to its polyploidy, existing methods for genome engineering of S6803 require multiple rounds of selection to modify all genome copies, which is time-consuming and inefficient. In this study, we engineered the Cas9 tool for one-step, segregation-free genome engineering. We further used our Cas9 tool to delete three of seven S6803 native plasmids. Our results show that all three small-size native plasmids, but not the large-size native plasmids, can be deleted with this tool. To further facilitate heterologous gene expression in S6803, a shuttle vector based on the native plasmid pCC5.2 was created. The shuttle vector can be introduced into Cas9-containing S6803 in one step without requiring segregation and can be stably maintained without antibiotic pressure for at least 30 days. Moreover, genes encoded on the shuttle vector remain functional after 30 days of continuous cultivation without selective pressure. Thus, this study provides a set of new tools for rapid modification of the S6803 genome and for stable expression of heterologous genes, potentially facilitating both fundamental research and biotechnology applications using S6803.


Functional analysis of a light-responsive plant bZIP transcriptional regulator.
Common plant regulatory factor 1 (CPRF1) is a parsley basic region/leucine zipper (bZIP) transcription factor that recognizes specific nucleotide sequences containing ACGT cores. Such a sequence is contained within LRU1, the composite light regulatory unit that is necessary and sufficient for light-dependent activity of the parsley chalcone synthase (CHS) promoter. After light treatment of both etiolated and green seedlings, CPRF1 mRNA levels increased prior to CHS mRNA accumulation. The change in CPRF1 mRNA leads to a light-responsive increase in CPRF1 protein. Transient expression analysis in parsley protoplasts using the CPRF1 promoter fused to the beta-glucuronidase (GUS) open reading frame indicated that light-dependent CPRF1 mRNA accumulation was under transcriptional control. The 5' untranslated region of the CPRF1 gene includes a cis-acting nucleotide sequence that contains two ACGT elements at a distance of 12 bp between their palindromic centers. This feature is reminiscent of as-1 and octopine synthase (ocs) elements identified in promoters from plant pathogens. This double ACGT Element element, designated dACECPRF1, stimulated transcription when placed 5' to a heterologous core promoter. CPRF1 bound to dACECPRF1 DNA as well as to the ACGT element from the CHS promoter in vitro. Cotransfection experiments demonstrated that CPRF1 interacts with these elements in vivo and that overexpression of CPRF1 actually reduced light-dependent transcription from the CHS promoter. CPRF1 thus appears to contribute to the regulation of the CPRF1 gene and to interfere with the activities of light-regulated promoters.


A bibliometric analysis of scientific production in cancer molecular epidemiology.
The main purpose of this research was to compare the scientific production in the field of cancer molecular epidemiology among countries and to evaluate the publication trend between 1995 and 2004. A bibliometric study was carried out searching the PubMed database with a combined search strategy based on the keywords listed in the medical subject headings and a free text search. Only articles from a representative subset of 92 journals--accounting for 80% of papers identified--were selected for the analysis, and the resulting 13,240 abstracts were manually checked according to a list of basic inclusion criteria. The study evaluated the number of publications and the impact factor (mean and sum), absolute and normalized by country population and gross domestic product. A total of 3,842 citations were finally selected for the analysis. Thirty-seven percent came from the European Union (UK, Germany, Italy, France and Sweden ranking at the top), 31.6% from USA and 9.7% from Japan. The highest mean impact factor was reported for Canada (6.3), USA (5.9), Finland (5.8) and UK (5.2). Finland, Sweden and Israel had the best ratio between scientific production and available resources. 'Genetic polymorphism, glutathione transferase, breast neoplasm, risk factors, case-control studies and polymerase chain reaction' were the most used keywords in each of the subgroups evaluated, although inclusion criteria may have privileged studies dealing with exogenous carcinogens. Cancer molecular epidemiology is an expanding area attracting an increasing interest. The identification of an operative definition is a necessary condition to give to this discipline a unique scientific identity.


The Longterm Effect of Early Intensive Treatment of Seniors with Rheumatoid Arthritis: A Comparison of 2 Population-based Cohort Studies on Time to Joint Replacement Surgery.
Disease-modifying antirheumatic drugs (DMARD) have the greatest effect when initiated early. We evaluated the influence of early exposure to DMARD on time to joint replacement surgery among patients with incident rheumatoid arthritis (RA). Using a common protocol, we undertook 2 independent population-based cohort studies of patients with incident RA aged 66 years or older in Ontario (ON) and Quebec (QC) covering the period 2000-2013. We used Cox proportional hazards regression with time-dependent variables measuring duration of drug use in the first year, separately for methotrexate (MTX) and other DMARD, adjusting for baseline demographics, clinical factors, and other potentially confounding drug exposures. Our outcome measure was any joint replacement derived from standardized procedure codes. Adjusted HR and 95% CI were estimated. Among 20,918 ON and 6754 QC patients with RA followed for a median of 4.5 years, 2201 and 494 patients underwent joint replacement surgery for crude event rates of 2.0 and 1.4 per 100 person-years, respectively. Greater cumulative exposure to MTX (HR 0.97, 95% CI 0.95-0.98) and other DMARD (HR 0.98, 95% CI 0.97-0.99) in the first year after diagnosis was associated with longer times to joint replacement in ON, corresponding to a 2-3% decrease in the hazard of surgery with each additional month of early use. Similar results were observed in QC. Greater duration of exposure to DMARD soon after RA diagnosis was associated with delays to joint replacement surgery in both provinces. Early intensive treatment of RA may ultimately reduce demand for joint replacement surgery.


Changing therapy from timolol to betaxolol. Effect on intraocular pressure in selected patients with glaucoma. Timolol-Betaxolol Study Group.
Three hundred fifty-three patients whose intraocular pressure was controlled with a timolol maleate ophthalmic solution were studied. Following a baseline period, half were switched (masked and randomized) to treatment with a betaxolol hydrochloride ophthalmic solution and were followed up for 12 weeks. Intraocular pressure, signs, and symptoms were recorded at weeks 1, 4, 8, and 12. Those patients switched to the betaxolol ophthalmic solution had a significant increase in both ocular side effects (burning/stinging and tearing) and intraocular pressure at weeks 4, 8, and 12 when compared with those patients who continued to receive timolol.


When to advise surgery for severe obesity.
A typical severely obese patient will have about 50 kg excess weight to lose, which is equivalent to a store of 350,000 kcal. The optimum rate of weight loss in such a patient is about 1 kg/week, which involves an energy deficit of 1000 kcal/day for about a year. It is difficult to maintain this degree of dietary restriction over such a long period, and procedures such as jaw wiring or stomach stapling may help in some cases. Maintenance of weight loss is difficult to achieve and may be helped by fitting a nylon waist cord after weight loss. On theoretical grounds, patients who do not lose weight despite keeping to a properly-designed reducing diet would not benefit from surgery, but in practice this problem does not arise. It is dangerous to resort to surgery for the treatment of severely obese patients who cannot diet by reason of psychiatric disorder.


Suprachiasmatic nucleus: phase-dependent activation during the hibernation cycle.
The suprachiasmatic nucleus (SCN) of the golden-mantled ground squirrel undergoes a phase-dependent change in its accumulation of 2-[14C]deoxy-D-glucose (2-DG) relative to other brain structures during the hibernation cycle. The greatest relative 2-DG uptake (R2DGU) is observed in the SCN during entrance into and during deep hibernation. A circadian fluctuation in R2DGU of the SCN is not evident in the euthermic ground squirrel but can be increased during the subjective day by photic stimulation. An increase in R2DGU by the paraventricular nucleus (PVN) correlates with the increase in R2DGU by the SCN during entrance to hibernation but not with the increase in SCN R2DGU evoked by photic stimulation during euthermia. The periventricular nuclei of the hypothalamus (PEV) also have high levels of R2DGU during the latter phase of the entrance. These observations support the hypothesis that the SCN, PEV, and PVN may play important roles in hibernation and suggest progressive activation of synaptic input to and within the SCN during entrance into this state.


Genetic evidence from mitochondrial, nuclear, and endosymbiont markers for the evolution of host plant associated species in the aphid genus Hyalopterus (Hemiptera: Aphididae).
Over the past several decades biologists' fascination with plant-herbivore interactions has generated intensive research into the implications of these interactions for insect diversification. The study of closely related phytophagous insect species or populations from an evolutionary perspective can help illuminate ecological and selective forces that drive these interactions. Here we present such an analysis for aphids in the genus Hyalopterus (Hemiptera: Aphididae), a cosmopolitan group that feeds on plants in the genus Prunus (Rosaceae). Hyalopterus currently contains two recognized species associated with different Prunus species, although the taxonomy and evolutionary history of the group is poorly understood. Using mitochondrial COI sequences, 16S rDNA sequences from the aphid endosymbiont Buchnera aphidicola, and nine microsatellite loci we investigated population structure in Hyalopterus from the most commonly used Prunus host species throughout the Mediterranean as well as in California, where the species H. pruni is an invasive pest. We found three deeply divergent lineages structured in large part by specific associations with plum, almond, and peach trees. There was no evidence that geographic or temporal barriers could explain the overall diversity in the genus. Levels of genetic differentiation are consistent with that typically attributed to aphid species and indicate divergence times older than the domestication of Prunus for agriculture. Interestingly, in addition to their typical hosts, aphids from each of the three lineages were frequently found on apricot trees. Apricot also appears to act as a resource mediated hybrid zone for plum and almond associated lineages. Together, results suggest that host plants have played a role in maintaining host-associated differentiation in Hyalopterus for as long as several million years, despite worldwide movement of host plants and the potential for ongoing hybridization.


MicroRNA Expression and Association with Clinicopathologic Features in Papillary Thyroid Cancer: A Systematic Review.
Studies have suggested that microRNAs (miR) may be useful prognostic markers and are associated with aggressive clinicopathologic features in papillary thyroid cancer (PTC). This systematic review examined associations between miRs and aggressive clinicopathologic features in PTC. A literature search was performed within the PubMed, Embase, Cochrane, Web of Science, and Scopus databases for papers published prior to November 24, 2014. The search was performed by combining the concepts "thyroid tumor" with "microRNA" and by using "and" as the Boolean operator. Upon retrieval of candidate studies, full-text publications were reviewed in their entirety and selected if they examined the prognostic significance between miR expression and established aggressive clinicopathologic features of PTC. Fifteen studies from 13 unique groups that included 807 patients were reviewed. Most of the studies were retrospective, and none included patients who had undergone routine central lymph node dissection. Expression levels of miRs-21, -34b, -130b, -135b, -146b, -151, -181b, -199b-5p, -221, -222, -451, -623, -1271, -2861, and let-7e showed significant association with at least one aggressive feature, such as large tumor size, extrathyroidal extension, multifocality, lymphovascular invasion, lymph node metastases, distant metastasis, advanced American Joint Cancer Committee stage, and presence of the BRAF(V600E) mutation. Herein we summarize the literature with regard to these associations. Further studies are needed to investigate whether miRs are independent predictors of aggressive clinicopathologic features before it can be recommended that miR expression levels should be incorporated into the management algorithm for patients with PTC. A well-designed prospective study is needed to assess these potential associations.


Boron-Doped Diamond Electrode Outperforms the State-of-the-Art Electrochemiluminescence from Microbeads Immunoassay.
Electrochemiluminescence (ECL) is a powerful transduction technique where light emission from a molecular species is triggered by an electrochemical reaction. Application to biosensors has led to a wide range of electroanalytical methods with particular impact on clinical analysis for diagnostic and therapeutic monitoring. Therefore, the quest for increasing the sensitivity while maintaining reproducible and easy procedures has brought investigations and innovations in (i) electrode materials, (ii) luminophores, and (iii) reagents. Particularly, the ECL signal is strongly affected by the electrode material and its surface modification during the ECL experiments. Here, we exploit boron-doped diamond (BDD) as an electrode material in microbead-based ECL immunoassay to be compared with the approach used in commercial instrumentation. We conducted a careful characterization of ECL signals from a tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+)/tri-n-propylamine (TPrA) system, both homogeneous (i.e., free diffusing Ru(bpy)32+) and heterogeneous (i.e., Ru(bpy)32+ bound on microbeads). We investigated the methods to promote TPrA oxidation, which led to the enhancement of ECL intensity, and the results revealed that the BDD surface properties greatly affect the ECL emission, so it does the addition of neutral, cationic, or anionic surfactants. Our results from homogeneous and heterogeneous microbead-based ECL show opposite outcomes, which have practical consequences in ECL optimization. In conclusion, by using Ru(bpy)32+-labeled immunoglobulins bound on microbeads, the ECL resulted in an increase of 70% and a double signal-to-noise ratio compared to platinum electrodes, which are actually used in commercial instrumentation for clinical analysis. This research infers that microbead-based ECL immunoassays with a higher sensitivity can be realized by BDD.


Expanding role of a blood center.
The study was performed on prospective donors who reported to the Department of Transfusion Medicine. Individuals deferred due to hypertension contributed the study population. They were compared with age and sex matched donor controls. Demographic details were recorded in a proforma. On identification of a hypertensive individual, consequent two comparable donors were taken as controls with a total of 50 hypertensive subjects. Hypertensive status of the subjects were assessed based on the criteria formulated by the WHO-ISH and US Seventh Joint National Committee report on prevention, detection, evaluation and treatment of high blood pressure. About 0.95% of healthy blood donors had undetected hypertension. Mean age at detection of hypertension in the study group was 35.44 ± 7.69 years. Higher BMI was observed in the hypertensive group compared to normotensive control group with P value significant at 0.0001. About 1% of healthy individuals were found to have undetected hypertension. Though the study was not designed to determine the prevalence of hypertension in the region, it is a rough estimate of the proportion of undetected hypertension in the local population as donors are considered as representative of healthy population.


Search via recursive rejection (SERR): visual search for single and dual form-conjunction targets.
Models of visual search that assume spatially serial processing of conjunction stimuli break down when displays contain 2 identical conjunction targets: (a) They fail to account for the slopes of the target-absent reaction time (RT)/display size functions, both when the target-present response requires the detection of only 1 of the 2 targets and when it requires the detection of both targets and (b) under redundant target conditions, the probability of "fast" present RTs is greater than that expected from the independent (serial) processing of the target stimuli. This article shows that G. W. Humphreys and H.J. Müller's (1993) parallel search via recursive rejection (SERR) model can account for human search performance under dual-target conditions. In SERR, simple form conjunctions are coded and grouped (on the basis of their similarity) in a spatially parallel manner, and targets are detected through the activation of a temporary "template" or through the recursive rejection of grouped distractors.


Influence of dog appeasing pheromone (DAP) on dogs housed in a long-term kennelling facility.
Kennel facilities are commonly acknowledged as a stressful environment for many domestic dogs (Canis familiaris). One therapeutic measure used to reduce anxiety in dogs is dog appeasing pheromone (DAP), which has been found effective in reducing stress-related behaviours in a number of contexts. A pilot study was conducted to assess whether DAP would reduce frequency of stress-related behaviours in a group of eight dogs housed for teaching purposes in a long-term kennelling facility. Using video analysis, proportion of time spent in stress-related behaviours for six dogs fitted with DAP collars, versus two control dogs (without collars), was compared for the time before and during DAP exposure. No significant differences were found either in the proportion of time spent in stress-related behaviours in the baseline versus treatment periods or between the collared and control dogs in the change in proportion of time they spent in any of the focal behaviours in the baseline versus treatment periods. Possible reasons for these findings include an actual lack of effect of DAP on dogs housed in this long-term kennelling facility, an apparent lack of effect due to small sample size in this pilot study and high behavioural variation among individual dogs. Despite lack of a demonstrated effect of the DAP collars on these dogs, attention brought by this study to the behavioural issues seen in some of the dogs did have a positive impact, as it contributed to the development of an active, coordinated behavioural wellness and enrichment programme for the colony.


An outbreak of Cotyledon orbiculata L. poisoning in a flock of Angora goat rams.
An acute outbreak of C. orbiculata L. poisoning in a flock of 16 Angora Goat rams is described. Typical signs of acute bufadienolide cardiac glycoside toxicity were manifested and 6 animals died. In the 2 animals examined histopathologically multiple foci of myocardial degeneration and necrosis were present. Treatment consisted, inter alia, of drenching with a mixture of activated charcoal, potassium chloride and a commercial preparation, Universal Antidote (Centaur) and parenteral administration of atropine sulphate.


Sensitivity of coccolithophores to carbonate chemistry and ocean acidification.
About one-third of the carbon dioxide (CO(2)) released into the atmosphere as a result of human activity has been absorbed by the oceans, where it partitions into the constituent ions of carbonic acid. This leads to ocean acidification, one of the major threats to marine ecosystems and particularly to calcifying organisms such as corals, foraminifera and coccolithophores. Coccolithophores are abundant phytoplankton that are responsible for a large part of modern oceanic carbonate production. Culture experiments investigating the physiological response of coccolithophore calcification to increased CO(2) have yielded contradictory results between and even within species. Here we quantified the calcite mass of dominant coccolithophores in the present ocean and over the past forty thousand years, and found a marked pattern of decreasing calcification with increasing partial pressure of CO(2) and concomitant decreasing concentrations of CO(3)(2-). Our analyses revealed that differentially calcified species and morphotypes are distributed in the ocean according to carbonate chemistry. A substantial impact on the marine carbon cycle might be expected upon extrapolation of this correlation to predicted ocean acidification in the future. However, our discovery of a heavily calcified Emiliania huxleyi morphotype in modern waters with low pH highlights the complexity of assemblage-level responses to environmental forcing factors.


Effects of a new fish oil concentrate on plasma lipids and lipoproteins in patients with hypertriglyceridaemia.
The effect of a fish oil preparation, K-85, in which the omega-3 fatty acid content was concentrated to 92% of total fat, on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia. The study was a randomized, double-blind, placebo-controlled study. Seven centres participated in the study, five secondary referral centres and two general practices. Men and women aged 18-70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied. Patients with diabetes mellitus, hypothyroidism, serious illness in the previous 3 months or severe concurrent illness were excluded from the study, as were drug or alcohol abusers and pregnant and lactating women. Ninety-five subjects entered the study, 79 completed the study. Patients were randomized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks. The serum concentrations of triglycerides and cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein (a). Fasting blood glucose and blood pressure. Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6, 10 and 14 weeks (all P < 0.01) and there was a decrease in the serum triglyceride concentration from 3.99 (2.94-9.47) to 2.87 (1.2-9.93) mmol/l (P < 0.001) and in VLDL-cholesterol from 1.47 (0.77-3.63) to 1.12 (0.21-3.67) mmol/l (P < 0.01) in patients receiving K-85. Serum HDL-cholesterol increased from 0.98 (0.95-1.01) to 1.11 (1.07-1.15) mmol/l (P < 0.01) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb. Serum LDL-cholesterol, lipoprotein (a) and fasting blood glucose were unaffected by K-85. Diastolic blood pressure decreased from 86 +/- 11 to 80 +/- 12 mmHg (P < 0.02) and was also lower than in the placebo group (P < 0.05). The corn oil placebo did not affect any of the parameters. K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent.


Immunoglobulin treatment in human and experimental epilepsy.
The relationship between human immunoglobulin administration, and human and experimental epilepsy was investigated by reviewing the literature as well as the authors' clinical and experimental studies. The focus was: 1) the possible efficacy of IVIg; 2) the possibility that IVIg significantly increases CSF IgG and could reach the brain, and 3) the interaction between the IVIg preparation and epilepsy. There is still no formal proof of efficacy of IVIg treatment in epilepsy. However, the clinical data presented suggests that IVIg is likely to be effective in a subgroup of patients with intractable and epilepsy, and may be considered as a safe add-on medication in various types of idiopathic and symptomatic intractable epilepsy. From the authors' study on cerebrospinal fluid IgG concentrations before and after IVIg treatment in patients with epilepsy, it is concluded that the main component of the IVIg preparation (the IgG molecule) crosses the blood-CSF barrier, significantly increases CSF IgG concentration, and may reach the brain and act centrally. From a review of previous reports and two immunological studies carried out by the authors it is concluded that immunogenetic mechanisms may play a role in triggering or maintaining some types of epilepsy. In view of this, IVIg could act on epilepsy by its broad immunomodulatory mechanism of action. In addition, preliminary data are reported that contribute to the hypothesis that IVIg may have a direct neuromodulating effect.


The role of stress in interpreting the dexamethasone suppression test.
Stress has been implicated as a major confounding factor in the interpretation of Dexamethasone Suppression Test (DST) results. This study was designed to examine the effects of stress on DST results. Fifty patients with high levels of acute, chronic, and environmental stress participated in the study. Each patient was given a comprehensive psychiatric and psychological assessment, a routine administration of dexamethasone, and blood tests of cortisol values. The results indicate that the three measures of stress do not appear to affect levels of cortisol suppression, however, all three measures of stress predicted depression. As expected, DST cortisol levels were related to depression. Results are discussed in terms of their implications for understanding the associations among stress, depression and DST results.


Shifting Vital Rate Correlations Alter Predicted Population Responses to Increasingly Variable Environments.
Time series of vital rates are often used to construct "environment-blind" stochastic population projections and calculate the elasticity of population growth to increased temporal variance in vital rates. Here, we show that the utility of this widely used demographic tool is greatly limited by shifts in vital rate correlations that occur as environmental drivers become increasingly variable. The direction and magnitude of these shifts are unpredictable without environmentally explicit models. Shifting vital rate correlations had the largest fitness effects on life histories with short to medium generation times, potentially hampering comparative analyses based on elasticities to vital rate variance for a wide range of species. Shifts in vital rate correlations are likely ubiquitous in increasingly variable environments, and further research should empirically evaluate the life histories for which detailed mechanistic relationships between vital rates and environmental drivers are required for making reliable predictions versus those for which summarized demographic data are sufficient.


From white to blue light: evolution of endoscope-assisted intracranial tumor neurosurgery and expansion to intraaxial tumors.
Intraoperative use of the endoscope to assist in visualization of intracranial tumor pathology has expanded with increasing surgeon experience and improved instrumentation. The authors aimed to study how advancements in endoscopic technology have affected the evolution of endoscope use, with particular focus on blue light-filter modification allowing for discrimination of fluorescent tumor tissue following 5-ALA administration. A retrospective analysis of patients undergoing craniotomy for tumor resection at a single institution between February 2012 and July 2021 was performed. Patients were included if the endoscope was used for diagnostic tumor cavity inspection or therapeutic assistance with tumor resection following standard craniotomy and microsurgical tumor resection, with emphasis on those cases in which blue light endoscopy was used. Medical records were queried for patient demographics, operative reports describing the use of the endoscope and extent of resection, associations with tumor pathology, and postoperative outcomes. Preoperative and postoperative MR images were reviewed for radiographic extent of resection. A total of 52 patients who underwent endoscope-assisted craniotomy for tumor were included. Thirty patients (57.7%) were men and the average age was 52.6 ± 16.1 years. Standard white light endoscopes were used for assistance with tumor resection in 28 cases (53.8%) for tumors primarily located in the ventricular system, parasellar region, and cerebellopontine angle. A blue light endoscope for detection of 5-ALA fluorescence was introduced into our practice in 2014 and subsequently used for assistance with tumor resection in 24 cases (46.2%) (intraaxial: n = 22, extraaxial: n = 2). Beyond the use of the surgical microscope as the primary visualization source, the blue light endoscope was used to directly perform additional tumor resection in 19/21 cases as a result of improved fluorescence detection as compared to the surgical microscope. No complications were associated with the use of the endoscope or with additional resection performed under white or blue light visualization. Endoscopic assistance to visualize intracranial tumors had previously been limited to white light, assisting mostly in the visualization of extraaxial tumors confined to intraventricular and cisternal compartments. Blue light-equipped endoscopes provide improved versatility and visualization of 5-ALA fluorescing tissue beyond the capability of the surgical microscope, thereby expanding its use into the realm of intraaxial tumor resections.


LncRNA NONMMUT055714 acts as the sponge of microRNA-7684-5p to protect against postoperative cognitive dysfunction.
Postoperative cognitive dysfunction (POCD) is a neurological complication of surgery especially common in elderly patients. In this study, we investigated the role of NONMMUT055714 in POCD via regulation of miR-7684-5p. In a POCD mouse model, we induced overexpression of NONMUTT055714 via transfection of lentivrus into the hippocampus, and used the Morris water maze for assessment of cognitive function. Silencing of NONMUTT055714 and miR-7684-5p was induced in primary hippocampal neurons to observe the effects of these regulatory RNAs on cellular processes. Bioinformatics analysis and a double luciferase reporter experiment were performed to further explore the relationship between NONMMUT055714, miR-7684-5p, and SORLA. Cell and animal rescue experiments were performed to verify the ability of miR-7684-5p to reverse the protective effects of NONMMUT055714 overexpression in POCD. We observed that NONMMUT055714 has decreased expression in the POCD mouse model. Overexpression of NONMMUT055714 protected against cognitive impairment of the POCD mouse model in vivo. We identified miR-7684-5p as a NONMMUT055714-related miRNA and in turn as an upstream regulator of SORLA. We found that NONMMUT055714 downregulation is associated with decreased SORLA, increased Aβ and p-tau expression, increased inflammatory biomarkers, increased markers of oxidative stress, and increased neuronal apoptosis in vitro. The effects of NONMMUT055714 downregulation were reversed by silencing miR-7684-5p in vitro and in vivo. Taken together, our findings suggest that NONMMUT055714 is protective against the development of POCD via its function as a ceRNA (or miRNA sponge) in the regulation of miR-7684-5p and SORLA. We therefore propose NONMMUT055714 as a novel target for the investigation and prevention of POCD.


Prospective study of the yield of physical examination compared with chest radiography in penetrating thoracic trauma.
A prospective study was conducted on 102 patients (84 male), with a median age of 27 years, who had sustained a penetrating chest wound to evaluate the ability of physical examination in comparison with chest radiography to determine management of these injuries. Knife wounds accounted for 92% of the injuries. Fifty three patients had a small collection of air or fluid in their pleural cavity that was not drained. Fifty six hemithoraces had a large collection of fluid or air and were treated by tube thoracostomy. Physical examination at presentation detected large collections of air and fluid correctly and predicted appropriate management (sensitivity 96%, specificity 94%). Residual collections of air or fluid or both were also predicted correctly by clinical examination. Seven small collections increased in size and required intubation. Routine pre-extubation radiographs were found to be of little value in management and their routine use is not recommended. Four patients required late thoracotomy for decortication. By using a policy of selective intubation, frequent clinical reassessment, and chest radiography when relevant, experienced trauma surgeons can manage most penetrating pleural injuries with an acceptably low complication rate.


Prostaglandin F2α regulates the expression of uterine activation proteins via multiple signalling pathways.
Prostaglandin F2α (PGF2A) has multiple roles in the birth process in addition to its vital contractile role. Our previous study has demonstrated that PGF2A can modulate uterine activation proteins (UAPs) in cultured pregnant human myometrial smooth muscle cells (HMSMCs). The objective of this study was to define the signalling pathways responsible for PGF2A modulation of UAPs in myometrium. It was found that PGF2A stimulated the expression of (GJA1) connexin 43 (CX43), prostaglandin endoperoxide synthase 2 (PTGS2) and oxytocin receptor (OTR) in cultured HMSMCs. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked PGF2A-stimulated expression of CX43. The inhibitors of ERK, P38 and NFκB also blocked the effect of PGF2A on CX43 expression, whereas PI3K and calcineurin/nuclear factor of activated T-cells (NFAT) pathway inhibitors did not reverse the effect of PGF2A on CX43. For PTGS2 and OTR, PLC, PI3K, P38 and calcineurin/NFAT signalling pathways were involved in PGF2A action, whereas PKC and NFκB signalling were not involved. In addition, PGF2A activated NFAT, PI3K, NFκB, ERK and P38 signalling pathways. Our data suggest that PGF2A stimulates CX43, PTGS2 and OTR through divergent signalling pathways.


Low functional diversity promotes niche changes in natural island pollinator communities.
Functional diversity loss among pollinators has rapidly progressed across the globe and is expected to influence plant-pollinator interactions in natural communities. Although recent findings suggest that the disappearance of a certain pollinator functional group may cause niche expansions and/or shifts in other groups, no study has examined this prediction in natural communities with high plant and pollinator diversities. By comparing coastal pollination networks on continental and oceanic islands, we examined how community-level flower visit patterns are influenced by the relative biomass of long-tongued pollinators (RBLP). We found that RBLP significantly correlated with pollinator functional diversity and was lower in oceanic than in continental islands. Pollinator niches shifted with decreasing RBLP, such that diverse species with various proboscis lengths, especially short-tongued species, increasingly visited long-tubed flowers. However, we found no conspicuous negative impacts of low RBLP and the consequent niche shifts on pollinator visit frequencies to flowers in oceanic island communities. Notably, fruit set significantly decreased as RBLP decreased in a study plant species. These results suggest that niche shifts by other functional groups can generally compensate for a decline in long-tongued pollinators in natural communities, but there may be negative impacts on plant reproduction.


Educating Emergency Department Nurses About Miscarriage.
Miscarriage is the unwanted ending of a pregnancy before 20 weeks gestation. Women experiencing miscarriage require specialized care from nurses and other healthcare professionals. Many women are dissatisfied with emergency care related to miscarriage and desire honest communication, validation of urgency, and more robust information at discharge. Perinatal bereavement education offers an opportunity for emergency department nurses to acquire specific knowledge and communication skills that assist with understanding the individualized experience of early pregnancy loss. For many women, a miscarriage is devastating, whereas for some, a part of life. Therefore, assessing the meaning of miscarriage is an essential step to providing sensitive, supportive care. Education was offered to emergency department nurses based on a 4-hour Resolve Through Sharing curriculum. Education focused on knowledge of policy and practice, medical aspects of pregnancy loss, information on how to assess the meaning of the miscarriage, respectful handling and disposition of the remains, and communication strategies to initiate and sustain a meaningful relationship with the woman and her family, within the barriers to care that are exclusive to the emergency department. Participants embraced the information and actively participated in dialogue of an evaluation process to identify needed revisions in current policies and practices for caring for this patient population. Recommendations and guidance for emergency room nurses who care for women experiencing miscarriage are offered.


Synthesis of nitrogen mustard-based fluorophores for cell imaging and cytotoxicity studies.
Nitrogen mustards are important alkylating anticancer drugs used for neoplasms treatment. However, little research about the integration of luminophore into nitrogen mustard-based compounds for both imaging and therapeutic application was reported. In this study, we report a series of novel nitrogen mustard-containing 1-furyl-2-en-1-one and 1-thienyl-2-en-1-one derivatives as intramolecular charge transfer-based luminophore for research in both imaging subcellular localization and antiproliferation toward lung cancer cells. The target products were prepared by Knoevenagel condensation and characterized by nuclear magnetic resonance and high-resolution mass spectrometer. The absorption and fluorescence studies were carried out by ultraviolet-visible and fluorescence spectrophotometers, respectively. Cell morphology was observed under an inverted microscope. Cytotoxicity test was detected by MTT assay. Cellular localization was observed by a confocal laser scanning microscope. Colony formation ability was carried out by colony formation assay. Cell migration ability was detected by transwell migration assay. Differences between the two groups were analyzed by two-tailed Student's t-test. The difference with P < 0.05 (*) was considered statistically significant. The compounds were synthesized in high yield. The λmax and Stokes shift of these compounds reach up to 567 and 150 nm, respectively. These compounds exhibited good antiproliferative activity against lung cancer cells, with compound 3h exhibiting the best IC50 of 13.1 ± 2.7 μM. Furthermore, the selected compound 3h is located preferentially in lysosomes and a small amount in nuclei, effectively inhibiting cell colony formation and migration abilities toward A549 cells. These findings suggested that nitrogen mustard-based fluorophores might be a potential effective chemotherapeutic agent in lung cancer therapy.


[Psychiatric consultations in a general hospital].
A statistical analysis of psychiatric referrals for inpatients in a urban general hospital are presented: Data are compared to reports from the last twenty years. Significant differences for age, sex and diagnosis are noted. These are attributed to the specific vocation of the hospital as a chest and cardio center for eastern Quebec. The discussion deals with various aspects of the clinical material. References from out-patient clinics are not included.


Identification of Beet necrotic yellow vein virus in Lakes District: A Major Beet Growing Area in Turkey.
This study was conducted to determine the prevalence of Beet necrotic yellow vein virus (BNYVV) causal agent of rhizomania, in sugar beet cultivation areas in the Lakes District of Turkey, in 2006-2007. During surveys BNYVV suspected leaf, root, and soil samples were collected. Total of 203 soil samples were collected from different locations in the region. Sugar beet cultivar Kasandra plants were grown in these soil samples using bait plant techniques. In order to detect the structures of the vector protozoa Polymyxa betae Keskin in the root tissue of the bait plants, roots were stained with lactofuchsin and examined for the fungal cystosori under a light microscope. Presence of BNYVV was investigated using Double antibody sandwich enzyme linked immunosorbent assay (DAS-ELISA). ELISA test results showed that 85 samples were infected with BNYVV (41.87%). ELISA-positive samples for BNYVV were used in the mechanical inoculation studies. Test plants produced typical BNYVV symptoms. Fifty ELISA negative samples when tested by reverse transcription polymerase chain reaction (RT-PCR), BNYVV could be detected in 50% of these samples. The present study provides evidence for occurrence of BNYVV in a major beet growing area in Turkey based on biological, serological and molecular detection of the virus. RT-PCR method was found more suitable and sensitive than DAS-ELISA for the detection of BNYVV.


Eastern geothermal resources: should we pursue them?
A geothermal resource that consists of hot water at moderate temperatures (below 125 degrees C) underlies many areas in the central and eastern United States. Programs funded by the Department of Energy have revealed that this resource is definable and economically competitive with conventional fuels for use in direct heat applications. The resource, therefore, has the potential for reducing our dependence on the imported oil used for space heating. However, front-end costs and risks to explore, drill, test, and evaluate the magnitude of the resource have inhibited development. The question is, therefore, how much federal stimulation will be needed to convince private capital to exploit this widespread low-quality energy source.


Impact of early glycemic variability on mortality and neurologic outcome of very low birth weight infants: Data from a continuous glucose monitoring system.
Background: Glycemic variability (GV) has been a matter of interest in recent years. However, glycemic variability in preterm infants has not been adequately investigated. Objectives: To evaluate the impact of glycemic variability obtained from continuous glucose monitoring on mortality and neurologic outcomes: grade 3 or 4 intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP) requiring treatment among very low birth weight infants. Material and methods:A prospective, single-center, open cohort study enrolled 74 very low birth weight infants with a mean birthweight of 1066 g (+/-267). A continuous glucose monitoring system (CGM) was used to measure glucose during the first week of life. The impact of glycemic variability (standard deviation SD; coefficient of variation CV; and mean amplitude of glucose excursion MAGE) on mortality and neurologic outcomes of infants was evaluated. Results: Univariate analysis revealed that glycemic variability occurring during the first week of life was not be associated with mortality before term-equivalent age and PVL. Higher GV was associated with grade 3 or 4 IVH (CV p=0.025; MAGE p=0.032) and ROP requiring treatment (SD p=0.019; CV p=0.026; MAGE=0.029). However, logistic regression models did not show a significant association between GV occurring during the first week of life and grade 3 or 4 IVH (MAGE OR 2.64; 95% CI 0.71-9.92) or ROP requiring treatment (MAGE OR 1.74; 95% CI 0.57-5.32). Conclusions: Further prospective studies are needed to fully investigate the impact of GV on mortality and morbidity in premature infants. The potential benefits of reducing glucose blood fluctuations in VLBW infants need to be addressed.


[Topographic-surgical anatomy of the pediatric pars plana].
The width of the pars plana and the distances between the corneo-limbal junction and the posterior aspect of the pars plicata as well as of the ora serrata were determined by measurement in 17 autopsy eyes and additional 12 dissected autopsy eyes of premature and mature babies and infants. The data were correlated to age and length of the globe. The site of sclerotomy in transscleral lensectomy of congenital cataracts is discussed.


Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of chemical diabetes.
The contractile RhoA/Rho-kinase (ROCK) signaling pathway is upregulated in penile tissue in animal models of experimental diabetes and has been proposed to contribute to diabetes-related erectile dysfunction (ED). To investigate the effect of testosterone (T) on the RhoA/ROCK signaling in diabetes. We used two distinct animal models of chemical diabetes (alloxan-induced in the rabbit and streptozotocin-induced in the rat) with or not T supplementation. The effect of diabetes and T supplementation on RhoA/ROCK signaling was evaluated as responsiveness to the selective ROCK inhibitor Y-27632 either by "in vitro" contractility study (diabetic rabbit) or "in vivo" as erectile response elicited by intracavernous injections (diabetic rats). RhoA/ROCK gene and protein expression were also analyzed. In both models, hypogonadism was observed, characterized by reduced T plasma level and androgen-dependent accessory glands atrophy. Diabetic animals showed a significant increase in responsiveness to increasing concentrations of Y-27632. T substitution (30 mg/kg, weekly) completely prevented hypogonadism and diabetes-induced penile hypersensitivity to Y-27632. To test whether this effect was due to a T-dependent regulation of RhoA/ROCK gene expression, we measured RhoA/ROCK mRNA. Both isoforms of ROCK (ROCK1/ROCK2) were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in rat penile samples. We found that ROCK1 mRNA was significantly increased (P < 0.05) in penile tissues from diabetic animals and maintained at the control values by T, as also confirmed by semiquantitative RT-PCR in rabbit. Conversely, RhoA and ROCK2 mRNA expression was not influenced either by diabetic condition or by T administration. Accordingly, ROCK1 protein expression, as evaluated by Western blot and immunohistochemistry analysis, was increased in penile samples from diabetic animals and normalized by T. Our data further support the hypothesis that the overexpression of RhoA/ROCK signaling contributes to diabetes-related ED. Moreover, treating hypogonadism in course of diabetes may maintain erectile function also by normalizing RhoA/ROCK pathway upregulation.


Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.
The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR(-/-) and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR(-/-) mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1(+) ) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C-C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that are consistent with a possible role of AhR in wet AMD. The data discussed in this paper have been deposited in NCBI's Gene Expression Omnibus; GEO Submission No. GSE56983, NCBI Tracking System No. 17021116.


Urinary tract infection induced by intermittent urethral catheterization in dogs.
Sterilized and unsterilized catheters were passed into the urinary bladders of 9 clinically normal adult male dogs once daily for 5 consecutive days, and the dogs were examined for up to 30 days to determine whether urinary tract infections developed. Two dogs that were catheterized with clean unsterilized catheters (1 clinically normal dog and 1 dog given immunosuppressant drugs) developed persistent cystitis and pyelonephritis due to infection with Proteus sp. One dog given immunosuppressant drugs developed a mixed bacterial infection (Proteus sp and Escherichia coli) that resolved without treatment between 22 and 30 days later.


Sacral neuromodulation as treatment for refractory idiopathic urge urinary incontinence: 5-year results of a longitudinal study in 60 women.
We evaluated the results of sacral neuromodulation after 5-year followup in women with refractory idiopathic urge urinary incontinence. A neuromodulation system with an original (nontined) lead was implanted by open surgery after a positive percutaneous nerve evaluation in 60 women from 1990 to 2004. Voiding incontinence diary parameters were used to evaluate efficacy. Success was defined as at least a 50% decrease in the number of incontinence episodes or pads used daily. Safety was also evaluated. The success rate gradually decreased from 52 patients (87%) at 1 month to 37 (62%) at 5 years. Complete continence persisted in 15% of patients. The system was still used by 80% of patients at 5 years. In 32 patients a total of 57 adverse events occurred, which were not severe (Clavien grade I and IIIb in 61% and 39%, respectively). Sacral neuromodulation appears to be a safe technique for refractory idiopathic urge urinary incontinence in women. The success rate gradually decreased to 62% after 5 years with 15% of patients completely continent.


Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in rat and human hepatocytes.
Metabolism of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been compared in human and rat hepatocytes. The identities of seven metabolites were confirmed by UV and mass spectroscopy and by co-elution with reference standards using HPLC. In human hepatocytes, the major biotransformation pathway of PhIP was cytochrome P4501A2 (CYP1A2)-mediated N-oxidation to form the genotoxic metabolite 2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), which underwent glucuronidation at the N(2) and N3 positions of PhIP to form stable conjugates. These products combined accounted for as much as 60% of the added PhIP. Direct glucuronidation of PhIP at the N(2) and N3 positions also occurred, accounting for up to 20% of the amount added. Glucuronide and sulfate conjugates of 2-amino-4'-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine (4'-HO-PhIP) were also detected, comprising 5 and 12% of the products, respectively. The CYP1A2 inhibitor furafylline diminished the formation of both HONH-PhIP glucuronide conjugates in a concentration-dependent manner, however, levels of 4'-HO-PhIP were unchanged, indicating that CYP1A2 does not significantly contribute to 4'-hydroxylation of PhIP. Hepatocytes of male rats, both untreated and pretreated with the CYP1A2 inducer 3-methylcholanthrene (3-MC) transformed PhIP into 4'-HO-PhIP as the prominent product. Unconjugated and conjugated 4'-HO-PhIP metabolites combined accounted for 18 and 46% of the PhIP products in untreated and in 3-MC-pretreated rat hepatocytes, respectively. The isomeric glucuronide conjugates of HONH-PhIP combined accounted for 11 and 26% of the PhIP, respectively, in untreated and 3-MC-pretreated hepatocytes. The regioselectivity of glucuronidation of PhIP was different in human and rat hepatocytes. Human liver UDP-glucuronosyltransferases favored conjugation to the N(2) positions of PhIP and HONH-PhIP, while the N3 atom was the preferred site of conjugation for the rat enzymes. Thus, important differences exist between human and rat enzymes in catalytic activity and regioselectivity of PhIP metabolism. Some human hepatocyte populations are more active at transforming PhIP to a genotoxic species than rat hepatocytes pretreated with the potent CYP1A2 inducer 3-MC.


Patients with sacroiliac joint dysfunction exhibit altered movement strategies when performing a sit-to-stand task.
The ability to rise from a chair is a basic functional task that is frequently compromised in individuals diagnosed with orthopedic disorders in the low back and hip. There is no published literature that describes how this task is altered by sacroiliac joint dysfunction (SIJD). The objective of this study was to compare lower extremity biomechanics and the onset of muscle activity when rising from a chair in subjects with SIJD and in healthy persons. Six women with unilateral SIJD and six age-matched healthy controls performed a sit-to-stand task while we measured kinematics, kinetics, and muscle activity. Subjects stood up at a preferred speed from a seated position on an armless and backless adjustable stool. We measured kinematics with a 10-camera motion capture system, ground reaction forces for each leg with force plates, and muscle activity with surface electromyography. Joint angles and torques were calculated using inverse dynamics. Leg-loading rate was quantified as the average slope of vertical ground reaction (VGRF) force during the 500-millisecond interval preceding maximal knee extension. Between-leg differences in loading rates and peak VGRFs were significantly greater for the SIJD group than for the control group. Maximal hip angles were significantly less for the SIJD group (p=.001). Peak hip moment in the SIJD group was significantly greater in the unaffected leg (0.75±0.22 N⋅m/kg) than in the affected leg (0.47±0.29 N⋅m/kg, p=.005). There were no between-leg or between-group differences for peak knee or ankle moments. The onset of activity in the latissimus dorsi muscle on the affected side was delayed and the erector spinae muscles were activated earlier in the SIJD group than in the control group. Subjects with SIJD have a greater VGRF on the unaffected leg, generate a greater peak hip moment in the unaffected leg, use a smaller range of motion at the hip joint of the affected leg, and delay the onset of a key muscle on the affected side when rising from a seated position.


Amplitude of low frequency fluctuations (ALFF) of spontaneous and induced rumination in major depression: An fNIRS study.
In the current study, we investigated the amplitude of low frequency fluctuations (ALFF) at rest and during a rumination induction. Specifically, we explored the differences of cortical blood oxygenation using fNIRS in subjects with Major Depressive Disorder (MDD) and healthy controls (HC). Rumination was assessed as state and trait measure, as well as with a qualitative semi-structured interview. Qualitative and quantitative measures of rumination indicated that the MDD group showed elevated rumination regarding state and trait measures. Furthermore, rumination differed qualitatively between the groups. The MDD group showed higher levels of general rumination and increased rumination during the rumination induction. However, the MDD group did not show a carry-over effect of elevated rumination after the induction paradigm to the following resting-state measurement. On a neuronal level, we observed a general hypoactivity in the MDD group compared to the HC group. Moreover, both groups showed increased ALFF during the rumination induction compared to the rest phase, especially in temporo-parietal areas. However, no interaction effect of MDD status and rumination induction was found. The current findings are discussed with respect to the literature of paradigms used in the investigation of rumination and suggestions on general improvements in rumination research are given.


[Radiosynoviorthese in the treatment of patients with rheumatoid arthritis].
Radiosynoviorthese, a new method for the treatment of patients with rheumatoid arthritis, was developed. Altogether 260 patients with rheumatoid arthritis were treated. The therapeutic activity of radioactive colloid Au was administered intra-articularly to all the patients. Indications and contraindications for radiation therapy of rheumatoid arthritis were developed. Good short- and long-term results were noted in most of the patients after radiation therapy. Radiosynoviorthese as a method of local active therapy of affected joints with colloid Au in the multiple modality treatment of rheumatoid arthritis is effective; its prolonged stable therapeutic effect in patients is observed.


Television viewing duration during childhood and long- association with adolescent neuropsychological outcomes.
This study is aiming to evaluate the association between television viewing during childhood and long-term adolescent neuropsychological outcomes and the potential explanatory pathways. This is a longitudinal study based on 278 children participating in the INMA birth cohort (1998) in Menorca Island, Spain. The exposure is parent-reported duration of child television viewing (hours per week) at 6 and 9 years of age. Neuropsychological outcomes were assessed at 14 years of age using the N-back test. Behavioral outcomes at 14 years of age were assessed using the Strengths and Difficulties Questionnaire (SDQ) and school performance was assessed by the global school score. Regression models were developed to quantify the associations between duration of television viewing and neuropsychological outcomes adjusted for child and parents' characteristics. The average of weekly TV viewing from 6 to 9 years was 9.2 h (SD: 4.1). Only N-back test outcomes exhibited statistically significant differences in crude models. Children viewing > 14 h per week tended to show larger latencies in working memory reaction time (HRT in ms), beta (CI) = 53 (0-107). After adjusting for potential social confounders, the association weakened and became non-significant but adverse trends were slightly preserved. Early life TV viewing was not associated with adolescent neuropsychological outcomes after adjustment for potential confounders. Further research including larger and exhaustive population-based cohort studies is required in order to verify our conclusions.


The potential impact of animal protein intake on global and abdominal obesity: evidence from the Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study.
To examine the association of total animal protein intake and protein derived from different dietary sources (meat; fish and shellfish; eggs; milk products) with global and abdominal obesity among adults in Luxembourg. Binary logistic regression analysis was used to assess the relationship between animal protein intake (as a percentage of total energy intake) and global obesity (BMI ≥ 30.0 kg/m(2)) and abdominal obesity (waist circumference ≥ 102 cm for men and ≥ 88 cm for women), after controlling for potential confounders. Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study. The study population was derived from a national cross-sectional stratified sample of 1152 individuals aged 18-69 years, recruited between November 2007 and January 2009. There was an independent positive association between total animal protein intake and both global (OR = 1.18; 95% CI 1.12, 1.25) and abdominal obesity (OR = 1.14; 95% CI 1.08, 1.20) after adjustment for age, gender, education, smoking, physical activity and intakes of total fat, carbohydrate, fibre, and fruit and vegetables. Protein intakes from meat, fish and shellfish were positively associated with global and abdominal obesity with further adjustment for vegetal protein and other sources of animal-derived protein (all P < 0.01). Protein derived from eggs or milk products was unrelated to global or abdominal obesity. Our findings suggest that protein derived from animal sources, in particular from meat, fish and shellfish, may be associated with increased risk of both global and abdominal obesity among presumably healthy adults in Luxembourg. These findings suggest that lower animal protein intakes may be important for maintenance of healthy body weight.