A Collaborative Multidisciplinary and Without-Walls Research Curriculum in Global Health.
Longitudinal and collaborative global health research curricula to train a well-versed global health corps through skills building in assessment and evaluation are lacking. A without-walls research curriculum was offered to medical and public health students between 2007 and 2015. Mentored cross-disciplinary research projects were developed and implemented in partnership with communities. A multilevel mixed methods design, including semi-structured interviews, post-curriculum surveys, presentations, publications, postgraduation metrics, and feedback from project sites, evaluated educational outcomes. Students (N = 25; aged 27 ± 1.9 years; 90.5% female) participated in the studies in 12 countries, resulting in 26 national-level presentations and 24 peer-reviewed publications, including per student average and range of Institutional Review Board submission (0.95; 0-3), poster presentation (0.85; 0-3), oral presentation (0.65; 0-2), and peer-reviewed submission (1.05; 0-4). On average, the studies (40% mixed methods) lasted 2 years. Analyses and manuscript writing were the most challenging; data collection and presentations were the most rewarding. Majority of the participants strongly agreed with achieving skills in community engagement, interviewing techniques, research design and implementation, research dissemination, and career development. Interview themes included expectations and learning goals, effective mentorship, impact on career goals, and ethical learning. Mentorship qualities were accessibility, real-time problem solving, research expertise, advocate, and balancing guidance with independence. Project sites' feedback was overwhelmingly positive regarding the projects' impact. Postgraduation participants hold positions in humanitarian organizations, research programs serving the underserved, and primary care residencies, fellowships, and faculty. This experience illustrates the feasibility and effectiveness of mentored global health research and underlines the crucial link between community collaboration and scholarship for effective global health practice.


Bidirectional Effects of Positive Affect, Warmth, and Interactions Between Mothers With and Without Symptoms of Depression and Their Toddlers.
Maternal depression has negative implications for parenting and child outcomes, but it is also important to understand the daily transactional interactions that occur between mothers varying in symptoms of depression and their children. The current study aimed to examine immediate bidirectional effects between maternal warmth and positive affect and toddler affect in a sample of mothers varying in symptoms of depression. Ninety-one mothers and their 24-month-old toddlers completed a laboratory free-play/clean-up task. Mothers rated their symptoms of depression using the CES-D, and maternal warmth and positive affect and toddler positive and negative affect were observationally coded from a free-play and clean-up laboratory task. Sequential analyses indicated that mothers with no or mild symptoms of depression exhibited mutual positive affect with their children, but mothers with more severe symptoms of depression did not. Mothers with higher symptoms of depression displayed a decrease in warmth concurrent with toddlers' positive affect. Further, unlike dyads in which mothers had higher symptoms of depression, dyads of mothers with lower symptoms appeared to exhibit some covariation in positive affect across the episode. These results provide evidence that even in non-clinical samples, affective manifestations of mothers' subthreshold levels of depression may have negative immediate effects on toddlers' emotions, and that mothers without symptoms of depression may have more reciprocal affective exchanges with their toddlers.


Field evaluation of Cucurbit yellow stunting disorder virus transmission by Bemisia tabaci.
Cucurbit yellow stunting disorder virus (CYSDV) is a whitefly-transmitted Crinivirus (Closteroviridae) that impacts melon production in many parts of the world including the USA. It has been responsible for melon crop loss in the southwestern U.S. since 2006 when it was first identified. Control strategies have revolved mainly around chemical control, but research to identify suitable products and approaches to implementing them have lagged. The current study investigated the performance of four systemic insecticides in the field while concurrently tracking CYSDV disease progression after controlled and natural whitefly inoculation of young melon plants. Assessments of virus incidence were made using two different visual observation methods in concert with ELISA analyses of leaf disks samples collected biweekly. Infection rates were consistently lowest in plots treated with the butenolide insecticide flupyradifurone while dinotefuran was second in efficacy measures. Flupyradifurone also held whitefly densities to their lowest numbers relative to the other treatments. Two other insecticides, imidacloprid and cyantraniliprole, exacerbated virus incidence in multiple trials. Further investigation into the anomalous finding of increased virus incidence due to insecticide application is ongoing.


Flow rate variance of commonly used IV infusion techniques.
Fluid resuscitation of the acutely hypovolemic shock state may involve the infusion of crystalloid, colloid, or blood components at various flow rates, depending on the clinical status of the patient. A study was designed in which these fluids were infused via gravity, blood pump, pressure infusion cuff, or being pushed in manually by way of a 50-cc syringe. Flow rate for each fluid and corresponding method of administration were established and compared. The flow rates for each fluid were most rapid with the pressure infusion cuff, followed by the blood pump and the 50-cc syringe. Gravity was the slowest method of infusion. These data may help in the choice of an appropriate method of fluid administration in resuscitation of the hypovolemic shock state.


Glycyrrhizin arginine salt protects against cisplation-induced acute liver injury by repressing BECN1-mediated ferroptosis.
The study aimed to investigate the protective effects and biological mechanisms of glycyrrhizin arginine salt (Gly-Arg) against cisplatin (Cis)-induced liver injury. Our data showed that Gly-Arg improved Cis-induced liver injury. Further study showed that BECN1 (beclin1) and LC3-II/LC3-I protein expression was significantly increased in primary hepatocytes and mouse liver tissues after Cis treatment, but Gly-Arg reduced the protein levels of BECN1 and LC3-II/LC3-I in primary hepatocytes and mouse liver tissues. Also, Gly-Arg improved indicators related to Cis-induced ferroptosis. Furthermore, Cis increased colocalization of lysosomal membrane-associated protein 1A (LAMP1) with ferritin heavy chain 1 (FTH1) in primary mouse hepatocytes, while Gly-Arg intervention attenuated this colocalization in primary hepatocytes. More improtantly, Cis enhanced the formation of the BECN1-xCT complex, thus inhibiting solute carrier family 7 member 11 (SLC7A11, xCT) and glutathione peroxidase-4 (GPX4) activity. In contrast, Gly-Arg intervention disrupted the formation of this complex. However, Gly-Arg alleviated Cis-induced liver injury in mice by preventing autophagic death and ferroptosis through the inhibition of BECN1-xCT complex formation.


Assessing Impact: Implementing an Opioid Prescription Protocol in Otolaryngology.
A lack of guidance for pain control after otolaryngology surgery can lead to overprescription of opioids. We implemented a postoperative site-specific opioid prescription protocol and analyzed the impact on opioid prescriptions. This is a retrospective cohort study. A postoperative opioid prescription protocol was implemented within our otolaryngology department at a tertiary academic medical center on January 1, 2020. Retrospective chart review was completed for all patients undergoing otolaryngology surgery from November 1, 2019, to February 29, 2020 (2 months before and after initiation of intervention; n = 1070). The primary outcome was change in the amount of opioid prescribed for the preintervention and postintervention cohorts. Unplanned contact related to pain and opioid refills were tracked to assess pain control. A total of 940 cases were included; adult and pediatric data were analyzed separately. There were 489 pediatric cases, 250 preintervention and 239 postintervention. There was a significant decrease in the amount of opioid prescribed per pediatric patient in the postintervention cohort (2.7 versus 0.32 morphine milligram equivalents, P = 0.02), and 99% of patients were not prescribed opioids at all. There was no significant change in unplanned contact, and no refills were required. There were 451 adult cases, 200 preintervention and 251 postintervention. There was no statistically significant decrease in the amount of opioid prescribed per adult patient (56.8 versus 51.7 morphine milligram equivalents, P = 0.23). There was no significant increase in unplanned contact or refills. A postoperative opioid prescribing protocol can reduce the amount of opioid prescribed without increasing unplanned contact or opioid refills.


Changes in Buprenorphine-Naloxone and Opioid Pain Reliever Prescriptions After the Affordable Care Act Medicaid Expansion.
Expanding Medicaid eligibility could affect prescriptions of buprenorphine with naloxone, an established treatment for opioid use disorder, and opioid pain relievers (OPRs). To examine changes in prescriptions of buprenorphine with naloxone and OPRs after the US Affordable Care Act Medicaid expansion. In this cohort study, longitudinal, patient-level, retail pharmacy claims were extracted from IQVIA real-world data from an anonymized, longitudinal, prescription database. The sample included 11.9 million individuals who filled 2 or more prescriptions for a prescription opioid during at least 1 year between January 1, 2010, and December 31, 2015, from California, Maryland, and Washington (expansion states) and Florida and Georgia (nonexpansion states). Data analysis was conducted from August 1, 2017, to May 31, 2018. Data were aggregated to county-year observations (N = 2082) and linked to county-level covariates. For each outcome, a difference-in-differences regression model was estimated comparing changes before and after expansion in expansion vs nonexpansion counties. Models were adjusted for county demographics, uninsured rate, and overdose mortality in the baseline year (2010). Presence of Medicaid expansion in the year. For buprenorphine with naloxone and OPRs, rates per 100 000 county residents were calculated separately for any prescriptions overall and by different payment sources. Mean days of medication per county among people filling prescriptions for these agents were also determined. The study sample included 11.9 million individuals (expansion states: 40.9% men; mean [SD] age, 44.1 [13.8] years; nonexpansion states: 41.0% men; mean [SD] age, 43.7 [13.7] years). In expansion counties, 68.8 individuals per 100 000 county residents filled buprenorphine with naloxone and 5298.3 filled OPR prescriptions in 2010. After expansion, buprenorphine with naloxone fills per 100 000 county residents increased significantly in expansion relative to nonexpansion counties (8.7; 95% CI, 1.7 to 15.7). Opioid pain reliever fills per 100 000 county residents did not significantly change in expansion counties relative to nonexpansion counties (327.4; 95% CI -202.5 to 857.4). The rate of OPRs per 100 000 county residents paid for by Medicaid significantly increased (374.0; 95% CI, 258.3 to 489.7). There were no significant changes in days per 100 000 county residents of either medication after expansion. Medicaid expansion significantly increased buprenorphine with naloxone prescriptions per 100 000 county residents in expansion counties, suggesting that expansion improved access to opioid use disorder treatment. Expansion did not significantly increase the overall rate per 100 000 county residents of OPR prescriptions, but increased the population with OPRs paid for by Medicaid. This finding therefore suggests the growing importance of Medicaid in pain management and addiction prevention.


A noncanonical postsynaptic transport route for a GPCR belonging to the serotonin receptor family.
Postsynaptic receptor trafficking plays an essential role in tuning neurotransmission and signal plasticity and has emerged as a potential therapeutic target in neuropsychiatric disease. Using a novel application of fluorescence recovery after photobleaching in rat hippocampal neurons, we examined transport from the soma to dendrites of seven G-protein-coupled receptors (GPCRs) implicated in mood disorders. Most GPCRs were delivered to dendrites via lateral diffusion, but one GPCR, the serotonin 1B receptor (5-HT(1B)), was delivered to the dendrites in secretory vesicles. Within the dendrites, 5-HT(1B) were stored in a reservoir of accessible vesicles that were recruited to preferential sites in plasma membrane, as observed with superecliptic pHluorin labeling. After membrane recruitment, 5-HT(1B) transport via lateral diffusion and temporal confinement to inhibitory and excitatory synapses was monitored by single particle tracking. These results suggest an alternative mechanism for control of neuronal activity via a GPCR that has been implicated in mood regulation.


Undocumented migrants' life situations: An exploratory analysis of quality of life and living conditions in a sample of undocumented migrants living in Norway.
To gather insight in conditions important to an understanding of undocumented migrants' life situations and more specifically to explore undocumented migrants' quality of life and how we can understand the various domains of quality of life related to demographics, living conditions, migration history and inflicted burden. Undocumented migrants suffer from economic hardship and acculturative stress, limited psychological and social support and at the same time restricted access to health care and social welfare. An exploratory mixed methods design using primarily quantitative data with a qualitative component was implemented. Sociodemographic data on 90 undocumented migrants were collected, and self-report questionnaires on quality of life and psychological distress were completed, supplemented by qualitative data obtained through interviews and additional qualitative questions. The STROBE checklist for cross-sectional studies was used for reporting this study. Quality of life in our group of undocumented migrants was poor. Leaving their home country because of war or persecution, hunger, having experienced abuse, homelessness and higher age were statistically significantly associated with poorer quality of life. Having membership in a local association and having a partner were statistically significantly associated with better quality of life. Qualitative data indicate that marginal living conditions, fear of death and suffering and conditions associated with dependency were the main components comprising the burden to our respondents, reflecting their precarious juridical status as undocumented migrants. Our respondents' poor quality of life was related to the complex interplay between possible exposures to traumatic experiences before and during flight and post-migration traumatisation in relation to our respondents' experiences of economic, social and acculturative hardship in Norway. Responses called for to improve undocumented migrants' quality of life and eliminate barriers to their health care appeal more to nurses as a professional group and to those in positions of authority than each individual nurse on duty.


Disrupted-in-schizophrenia-1 is required for normal pyramidal cell-interneuron communication and assembly dynamics in the prefrontal cortex.
We interrogated prefrontal circuit function in mice lacking Disrupted-in-schizophrenia-1 (Disc1-mutant mice), a risk factor for psychiatric disorders. Single-unit recordings in awake mice revealed reduced average firing rates of fast-spiking interneurons (INTs), including optogenetically identified parvalbumin-positive cells, and a lower proportion of INTs phase-coupled to ongoing gamma oscillations. Moreover, we observed decreased spike transmission efficacy at local pyramidal cell (PYR)-INT connections in vivo, suggesting a reduced excitatory effect of local glutamatergic inputs as a potential mechanism of lower INT rates. On the network level, impaired INT function resulted in altered activation of PYR assemblies: While assembly activations defined as coactivations within 25 ms were observed equally often, the expression strength of individual assembly patterns was significantly higher in Disc1-mutant mice. Our data, thus, reveal a role of Disc1 in shaping the properties of prefrontal assembly patterns by setting INT responsiveness to glutamatergic drive.


Bariatric surgery for severely overweight adolescents: concerns and recommendations.
As the prevalence of obesity and obesity-related disease among adolescents in the United States continues to increase, physicians are increasingly faced with the dilemma of determining the best treatment strategies for affected patients. This report offers an approach for the evaluation of adolescent patients' candidacy for bariatric surgery. In addition to anthropometric measurements and comorbidity assessments, a number of unique factors must be critically assessed among overweight youths. In an effort to reduce the risk of adverse medical and psychosocial outcomes and increase compliance and follow-up monitoring after bariatric surgery, principles of adolescent growth and development, the decisional capacity of the patient, family structure, and barriers to adherence must be considered. Consideration for bariatric surgery is generally warranted only when adolescents have experienced failure of 6 months of organized weight loss attempts and have met certain anthropometric, medical, and psychologic criteria. Adolescent candidates for bariatric surgery should be very severely obese (defined by the World Health Organization as a body mass index of > or =40), have attained a majority of skeletal maturity (generally > or =13 years of age for girls and > or =15 years of age for boys), and have comorbidities related to obesity that might be remedied with durable weight loss. Potential candidates for bariatric surgery should be referred to centers with multidisciplinary weight management teams that have expertise in meeting the unique needs of overweight adolescents. Surgery should be performed in institutions that are equipped to meet the tertiary care needs of severely obese patients and to collect long-term data on the clinical outcomes of these patients.


Synthesis of Magnetic Wires from Polyol-Derived Fe-Glycolate Wires.
Fe-glycolate wires with micrometer-scale lengths can be synthesized by the polyol process. Although the as-produced wires are in the paramagnetic state at room temperature, they are transformed into ferrimagnetic iron oxides and ferromagnetic metallic iron wires by reductive annealing. The shape of the wires is unchanged by reductive annealing, and it is possible to control the magnetic properties of the resulting wire-shaped ferri/ferromagnets by adjusting the annealing conditions. Consequently, the reductive annealing of polyol-derived Fe-glycolate wires is an effective material-processing route for the production of magnetic wires.


Poliovirus 2C protein determinants of membrane binding and rearrangements in mammalian cells.
Poliovirus protein 2C is a 329-amino acid-protein that is essential for viral RNA synthesis and may perform multiple functions. In infected cells, it is associated with virus-specific membrane vesicles. Recombinant 2C protein expressed in transfected cells has been shown to associate with and induce rearrangement of the intracellular membrane network. This study was designed to map the determinants of membrane binding and rearrangement in the 2C protein. Computer-assisted analysis of the protein sequence led to a prediction that the protein folds into a structure composed of three domains. Expression plasmids that encode each or combinations of these predicted domains were used to examine the abilities of the partial protein sequences to associate with intracellular membranes and to induce rearrangement of these membranes in HeLa cells. Biochemical fractionation procedures suggested that the N-terminal region of the protein was required for membrane association. Electron microscopic and immunoelectron microscopic observation showed that both the N- and C-terminal regions, but not the central portion, of 2C protein interact with intracellular membranes and induce major changes in their morphology. The central portion, when fused to the N-terminal region, altered the specific membrane architecture induced by the N-terminal region, giving rise to vesicles resembling those observed during poliovirus infection.


[Protective properties of doxycycline, rifampicin and sisomycin in experimental pulmonary tularemia of albino mice].
The protective effects of doxycycline, rifampicin and sisomicin were compared in a multifactor experiment with animal infection induced by finally dispersed aerosol of a virulent strain of the European variant of the tularemia causative agent and the optimal regimens for the antibiotic use were determined. By the values of the protective effect rifampicin and sisomicin were shown to provide a high percentage of the animal survival: more than 80 and up to 50-70 per cent of the animals survived when the aerosol infective doses were 100 and 10,000 LD50, respectively. A characteristic feature of doxycycline was its activity only in the infection induced by low doses of the biological agent. The optimal course of the antibiotic therapy in inhalation tularemia was 6 to 8 days. The interval of 1 to 3 days between the infection and the therapy start had no significant effect on the protective efficacies of the antibiotics.


T-VEC for stage IIIB-IVM1a melanoma achieves high rates of complete and durable responses and is associated with tumor load: a clinical prediction model.
Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus and known as an effective oncolytic immunotherapy for injectable cutaneous, subcutaneous and nodal melanoma lesions in stage IIIB-IVM1a patients. This study set out to identify prognostic factors for achieving a complete response that can be used to optimize patient selection for T-VEC monotherapy. Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016-12 and 2020-01 with a follow-up time > 6 months, were included. Data were collected on baseline characteristics, responses and adverse events (AEs). Uni- and multivariable analyses were conducted, and a prediction model was developed to identify prognostic factors associated with CR. A total of 93 patients were included with a median age of 69 years, median follow-up time was 16.6 months. As best response, 58 patients (62%) had a CR, and the overall response rate was 79%. The durable response rate (objective response lasting > 6 months) was 51%. Grade 1-2 AEs occurred in almost every patient. Tumor size, type of metastases, prior treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving CR. The prediction model includes the predictors tumor size, type of metastases and number of lesions. This study shows that intralesional T-VEC monotherapy is able to achieve high complete and durable responses. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting use earlier in the course of the disease.


FFPE++: Improving the quality of formalin-fixed paraffin-embedded tissue imaging via contrastive unpaired image-to-image translation.
Formalin-fixation and paraffin-embedding (FFPE) is a technique for preparing and preserving tissue specimens that has been utilized in histopathology since the late 19th century. This process is further complicated by FFPE preparation steps such as fixation, processing, embedding, microtomy, staining, and coverslipping, which often results in artifacts due to the complex histological and cytological characteristics of a tissue specimen. The term "artifacts" includes, but is not limited to, staining inconsistencies, tissue folds, chattering, pen marks, blurring, air bubbles, and contamination. The presence of artifacts may interfere with pathological diagnosis in disease detection, subtyping, grading, and choice of therapy. In this study, we propose FFPE++, an unpaired image-to-image translation method based on contrastive learning with a mixed channel-spatial attention module and self-regularization loss that drastically corrects the aforementioned artifacts in FFPE tissue sections. Turing tests were performed by 10 board-certified pathologists with more than 10 years of experience. These tests which were performed for ovarian carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, and papillary thyroid carcinoma, demonstrate the clear superiority of the proposed method in many clinical aspects compared with standard FFPE images. Based on the qualitative experiments and feedback from the Turing tests, we believe that FFPE++ can contribute to substantial diagnostic and prognostic accuracy in clinical pathology in the future and can also improve the performance of AI tools in digital pathology. The code and dataset are publicly available at https://github.com/DeepMIALab/FFPEPlus.


Oxidative and pro-inflammatory lung injury induced by desflurane inhalation in rats and the protective effect of rutin.
Desflurane is a mainstay of general inhaled anesthetics with a methyl ethyl ether structure and is widely used in clinical practice. It has been reported to induce inflammation and lipid peroxidation in rat pulmonary parenchyma, to increase alveolar macrophages, and to cause peribronchial infiltration and edema. Rutin, a flavonoid vitamin P1, is known to have biological properties including acting as an antioxidant, an anti-inflammatory, and an inhibitor of bronchoalveolar polymorphonuclear leukocyte (PNL) infiltration. The aim of this study is to examine the effects of rutin on desflurane-induced pulmonary injury using biochemical and histopathological methods. The rats were divided into 3 groups (n = 6 each): healthy control (HC), rutin+desflurane-treated (DRT) and desflurane-only (DSF). Briefly, 50 mg/kg of rutin was given orally to the DRT group and an equal volume of normal saline was given to the DSF and HC groups. After 1 h, anesthesia was induced and maintained in the DRT and DSF groups for 2 h. After the rats had been sacrificed, the lungs were removed. Malondialdehyde (MDA), total glutathione (GSH), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF-κB) levels were measured in the excised lung tissue. The removed tissues were also fixed in 10% formalin, and the obtained sections were stained with hematoxylin and eosin (H&E) and evaluated under light microscopy. The biochemical and histopathological results of the DRT group were compared with those obtained from the DSF and HC groups. Desflurane increased MDA, TNF-α and NF-κB, and decreased GSH in lung tissue. The PNL infiltration, alveolar macrophages, hemorrhage, alveolar damage, and edema were observed in the lung tissue of the DSF group. Rutin was histopathologically shown to protect lung tissue from oxidative stress by preventing an increase in oxidant parameters and a decrease in antioxidants. The results suggest that rutin may be useful in the treatment of desflurane-associated lung injury.


Evolution of glycophorin A in the hominoid primates studied with monoclonal antibodies, and description of a sialoglycoprotein analogous to human glycophorin B in chimpanzee.
Comparison of human and primate erythrocyte membrane sialoglycoproteins showed that common chimpanzee, dwarf chimpanzee, gorilla, orangutan, and gibbon have major periodic acid Schiff-positive proteins resembling human glycophorin A (GPA) monomer and dimer in electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels. Immunoperoxidase staining of Western blots with monoclonal antibodies to human GPA showed that these primate bands express some GPA antigenic determinants. A new sialoglycoprotein analogous to human glycophorin B (GPB) was detected in common chimpanzee. Although human MN blood group phenotype results from an amino acid polymorphism of GPA, Western blots showed that in chimpanzee sialoglycoprotein (GPAch) always expresses the M blood group, whereas chimpanzee sialoglycoprotein (GPBch) expresses either the N blood group or a null phenotype. This result explains the detection of M and MN, but not of N, blood group phenotypes in chimpanzee. GPBch has higher apparent m.w. than human GPB, is present in the erythrocyte membrane in greater quantity than human GPB, and contains trypsin cleavage site(s) and the 10F7 determinant (both found on human GPA but not GPB). Expression of human GPA antigenic determinants was consistent with the phylogeny of the hominoid primates; common and dwarf chimpanzee expressed most of the determinants tested, gorilla and orangutan an intermediate number, and gibbon and siamang the least. Of the GPA antigenic determinants examined, the MN blood group determinants were most consistently expressed during evolution of the hominoid primates. The results suggested that variability in expression of GPA antigenic determinants between species was due to both differences in amino acid sequence and glycosylation.


Is lawful discrimination against illicit drug users acceptable?
A Bill currently being considered by the Australian Parliament (the Disability Discrimination Amendment Bill 2003 [Cwlth]) would, if enacted, make discrimination lawful against people who are currently addicted to prohibited drugs and not currently in drug treatment. The government argues that the Bill is needed to keep the work and social environment safe, respond to community concerns, provide certainty to individuals and organisations, and force drug users into treatment. If enacted, we believe the Bill will infringe several national commitments to human rights, damage the wellbeing of family and other associates, and generate expensive litigation because of the difficulty of proving current addiction and current drug treatment; risk deterring drug users from seeking drug treatment and impair their ability to obtain employment and accommodation; represent a further attempt to reduce drug use by increasing the health, social and other costs of using illegal drugs, rather than assisting drug users to deal with their problem through health and social interventions that are less expensive, more effective and less counterproductive.


Warming and top predator loss drive ecosystem multifunctionality.
Global change affects ecosystem functioning both directly by modifications in physicochemical processes, and indirectly, via changes in biotic metabolism and interactions. Unclear, however, is how multiple anthropogenic drivers affect different components of community structure and the performance of multiple ecosystem functions (ecosystem multifunctionality). We manipulated small natural freshwater ecosystems to investigate how warming and top predator loss affect seven ecosystem functions representing two major dimensions of ecosystem functioning, productivity and metabolism. We investigated their direct and indirect effects on community diversity and standing stock of multitrophic macro and microorganisms. Warming directly increased multifunctional ecosystem productivity and metabolism. In contrast, top predator loss indirectly affected multifunctional ecosystem productivity via changes in the diversity of detritivorous macroinvertebrates, but did not affect ecosystem metabolism. In addition to demonstrating how multiple anthropogenic drivers have different impacts, via different pathways, on ecosystem multifunctionality components, our work should further spur advances in predicting responses of ecosystems to multiple simultaneous environmental changes.


The roles played by IL-10, IL-23 and IL-17A in term delivery.
The immune system significantly participates in the development of the successful delivery process. The roles played by cytokine molecules in the induction of term delivery are yet to be clarified. The aim of this project was to explore the serum levels of interleukin-10 (IL-10), IL-17A, and IL-23 in the mothers with term and prolonged pregnancy and their infants. In this study, 60 samples were collected from either mothers with term and prolonged pregnancy or their infants, collectively 240 samples. Serum levels of IL-10, IL-17A and IL-23 were explored using enzyme linked immunosorbent assay (ELISA) technique. IL-10 serum levels significantly decreased in the neonates with prolonged pregnancy when compared to their mothers. Serum levels of IL-23 were increased either in term or prolonged pregnancy neonates when compared to their corresponded mothers. Serum levels of IL-10 and IL-23 significantly decreased and increased, respectively, in the female in comparison to male in the prolonged pregnancy neonates. IL-10 also significantly decreased in the term mothers who had higher gravidity. Although, IL-17A does not play a key role in the delivery mechanism, IL-10 and IL-23 may be considered as potential factors in the modulation of term delivery.


[Current Status of Translational Research on Irritable Bowel Syndrome].
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. The pathophysiology of IBS is not completely understood. Genetic, immune, environmental, inflammatory, neurological and psychological factors contribute to the risk of this condition. Traditional research explored gastrointestinal motor abnormalities, central neural dysregulation, abnormal psychological features, and visceral hypersensitivity. More recent investigations consider bacterial overgrowth, abnormal serotonin pathways, altered gut flora, immune activation and mucosal inflammation. The purpose of this article is to review recent translational research concerning the pathophysiology, biomarker and genetic factors of IBS and to encourage IBS research in Korea.


Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.
The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model.


When the library is located in prime real estate: a case study on the loss of space from the Duke University Medical Center Library and Archives.
The Duke University Medical Center Library and Archives is located in the heart of the Duke Medicine campus, surrounded by Duke Hospital, ambulatory clinics, and numerous research facilities. Its location is considered prime real estate, given its adjacency to patient care, research, and educational activities. In 2005, the Duke University Library Space Planning Committee had recommended creating a learning center in the library that would support a variety of educational activities. However, the health system needed to convert the library's top floor into office space to make way for expansion of the hospital and cancer center. The library had only five months to plan the storage and consolidation of its journal and book collections, while working with the facilities design office and architect on the replacement of key user spaces on the top floor. Library staff worked together to develop plans for storing, weeding, and consolidating the collections and provided input into renovation plans for users spaces on its mezzanine level. The library lost 15,238 square feet (29%) of its net assignable square footage and a total of 16,897 (30%) gross square feet. This included 50% of the total space allotted to collections and over 15% of user spaces. The top-floor space now houses offices for Duke Medicine oncology faculty and staff. By storing a large portion of its collection off-site, the library was able to remove more stacks on the remaining stack level and convert them to user spaces, a long-term goal for the library. Additional space on the mezzanine level had to be converted to replace lost study and conference room spaces. While this project did not match the recommended space plans for the library, it underscored the need for the library to think creatively about the future of its facility and to work toward a more cohesive master plan.


Silymarin from Milk Thistle Fruits Counteracts Selected Pathological Changes in the Lenses of Type 1 Diabetic Rats.
Diabetes is a metabolic disease affecting many tissues and organs. The main etiological factor for diabetic complications is hyperglycemia and subsequent pathologies, such as oxidative stress. One of the organs susceptible to the development of diabetic complications is the eye with all of its elements, including the lens. The aim of this study was to evaluate the effect of silymarin, an extract obtained from milk thistle fruit husks, on the oxidative stress markers in the lenses of type 1 diabetic rats. The study was performed on male rats in which type 1 diabetes was induced with 60 mg/kg streptozotocin injection. Diabetic animals were treated via an intragastric tube with silymarin at 50 and 100 mg/kg doses for four weeks. Multiple oxidative stress and polyol pathway-related parameters were measured in the lenses, and auxiliary biochemical tests in the serum were conducted. Diabetes induced severe pathological changes both in the lenses and the serum, and silymarin counteracted several of them. Nevertheless, the qualitative analyses encompassing all tested parameters indicate that silymarin slightly improved the overall state of diabetic animals. Upon the obtained results, it can be concluded that silymarin reveals a faint positive effect on the lenses in type 1 diabetic rats.


Treating low HDL--from bench to bedside.
The inverse relationship between the plasma high-density lipoprotein cholesterol (HDL-C) and the risk of coronary heart disease (CHD) is well recognized in the general population. However, the development of effective therapeutics targeting HDL continues to be challenging, which is due in part to the heterogeneity of its structure and composition and the complexity of its metabolism. In this paper, we review a number of recent advances in our understanding of HDL metabolism and its role in atherogenesis. We discuss the HDL-C raising effect of a selected number of currently available lipid-modifying drugs and on a selected number of novel HDL-targeted therapeutic strategies under development.


[Impact of merging healthcare organizations: a review of the literature].
Over the last two decades, the healthcare sector of different Countries has been involved in a wave of mergers. This wave first started in the US and in the UK and, later, has involved Italy. Despite these activities are still pursued, little attention is paid to the assessment of their impact. The aim of this study is to summarize, through a review of the literature, evidence on the impact of these mergers. The main results are divided into four areas: the impact of mergers on clinical outcome, processes and use of resources; the association between population size and performance of primary care organizations; the analysis of the main drivers; and eventually, staff perception and satisfaction. Evidence is conflicting and small number of indicators of clinical outcome, processes and use of resources show a significant improvement. The performance of the Primary care Organizations does not seem significantly related to the size of the population served but to numerous factors, among others the function of the organization itself. Drivers that lead the pursuing of merging can be distinguished in stated and unstated drivers the first ones originating from public consultation document, the second ones from staff interview. Concerns about mergers derive from responses of personnel interview, in particular about the cultural differences and the distance perceived from top managers. Evidence shows that these processes do not necessarily lead to the expected benefits. It is important, therefore, to periodically and systematically assess the impact of mergers in a continuous quality improvement cycle that makes professionist, recipients and policy maker accountable. These latter, in particular are responsible for protecting the health of the community.


Extending the applicability of the Tkatchenko-Scheffler dispersion correction via iterative Hirshfeld partitioning.
Recently we have demonstrated that the applicability of the Tkatchenko-Scheffler (TS) method for calculating dispersion corrections to density-functional theory can be extended to ionic systems if the Hirshfeld method for estimating effective volumes and charges of atoms in molecules or solids (AIM's) is replaced by its iterative variant [T. Bučko, S. Lebègue, J. Hafner, and J. Ángyán, J. Chem. Theory Comput. 9, 4293 (2013)]. The standard Hirshfeld method uses neutral atoms as a reference, whereas in the iterative Hirshfeld (HI) scheme the fractionally charged atomic reference states are determined self-consistently. We show that the HI method predicts more realistic AIM charges and that the TS/HI approach leads to polarizabilities and C6 dispersion coefficients in ionic or partially ionic systems which are, as expected, larger for anions than for cations (in contrast to the conventional TS method). For crystalline materials, the new algorithm predicts polarizabilities per unit cell in better agreement with the values derived from the Clausius-Mosotti equation. The applicability of the TS/HI method has been tested for a wide variety of molecular and solid-state systems. It is demonstrated that for systems dominated by covalent interactions and/or dispersion forces the TS/HI method leads to the same results as the conventional TS approach. The difference between the TS/HI and TS approaches increases with increasing ionicity. A detailed comparison is presented for isoelectronic series of octet compounds, layered crystals, complex intermetallic compounds, and hydrides, and for crystals built of molecules or containing molecular anions. It is demonstrated that only the TS/HI method leads to accurate results for systems where both electrostatic and dispersion interactions are important, as illustrated for Li-intercalated graphite and for molecular adsorption on the surfaces in ionic solids and in the cavities of zeolites.


Properties of gamma-frequency oscillations initiated by propagating population bursts in retrohippocampal regions of rat brain slices.
1. In the hippocampal formation in vivo, brief periods of gamma-frequency activity follow population bursts called sharp waves. The approximately 200 Hz activity of the sharp wave itself may serve to enhance synaptic connections and the approximately 40 Hz gamma activity has been offered as a mechanism for solving the 'binding' problem. We describe epochs of gamma-frequency activity which follow population spikes evoked by low frequency repetitive extracellular stimuli in retrohippocampal neurons of horizontal rat brain slices. 2. gamma-Frequency activity recorded intracellularly from deep layer neurons of entorhinal cortex, presubiculum and parasubiculum consisted of one action potential correlated with each of the three to five gamma cycles recorded with a proximate field potential electrode. A minority of cells exhibited only sub-threshold gamma-frequency membrane potential oscillations (ranging from 5 to 10 mV). No cells fired more than one spike per gamma cycle under any conditions. 3. The range of synchrony varied from individual cells which showed gamma-frequency firing without corresponding oscillations in close field recordings to field potential recordings of oscillations which were well correlated across regions. The lead or lag between any two retrohippocampal regions was in the direction of the conduction delay for the primary population spike, but typically was less, and approached zero milliseconds for some cycles in most cells. The level of synchrony was stable for particular stimulating conditions (intensity, stimulation rate, stimulus location). 4. The duration of the period of gamma activity had the duration of a slow depolarizing potential which was mediated by NMDA receptor activation. NMDA receptor antagonists or low concentrations of AMPA receptor antagonists reduced the duration of, or completely abolished the slow potential, thereby eliminating the gamma portion of the evoked response. 5. gamma-Frequency firing was eliminated by the GABAA receptor antagonist picrotoxin but small (< 5 mV) membrane potential oscillations remained after focal picrotoxin applications, and these exhibited the voltage dependence of EPSPs. Bath application of thiopental lowered the frequency of gamma oscillations, confirming the involvement of GABAA receptors. 6. The GABAB receptor antagonist 2-hydroxy-saclofen appeared to enhance the gamma activity by increasing the duration of the gamma epoch and increasing the amplitude of individual gamma cycles in field potential recordings. These saclofen-induced cycles were, however, less well synchronized across regions. 7. We show that synchronous gamma (40-100 Hz) activity follows population bursts by deep layer retrohippocampal neurons in undrugged slices from rat brain. Responses from medial entorhinal, parasubicular or presubicular cells were not distinguishable. These events can be initiated by a propagating population spike. We suggest that an NMDA receptor mediated depolarization enables the network of deep layer retrohippocampal neurons to oscillate by providing a sustained excitation, the duration of which determines the duration of the gamma episode. gamma-Frequency firing is primarily the result of GABAA receptor dependent inhibition during this period of sustained depolarization. Recurrent excitation appears to be inconsequential for principal cell firing, but may contribute to interneuron firing.


Game-playing epilepsy.
A 25-year-old woman with documented generalized seizures evoked by playing checkers was given a battery of psychological tests as well as a series of cognitive and non-game-related tasks during a session of intensive EEG-video monitoring. Generalized epileptiform discharges during each task, as well as during intervals of checkers playing, were quantified to determine possible triggering factors. Previous reports have discussed the roles of attention, concentration, stress, thinking, and spatial processing in similar cases. Our analysis showed significant activation of the EEG only with tasks involving strategic thinking, i.e., considering a sequence of moves based on evaluating the consequences of previous moves.


Independent regulation of anterior/posterior and equatorial/polar polarity in the Drosophila eye; evidence for the involvement of Wnt signaling in the equatorial/polar axis.
The Drosophila retina is made from hundreds of asymmetric subunit ommatidia arranged in a crystalline-like array with each unit shaped and oriented in a precise way. One explanation for the precise cellular arrangements and orientations of the ommatidia is that they respond to two axes of polarized information present in the plane of the retinal epithelium. Earlier work showed that one of these axes lies in the anterior/posterior(A/P) direction and that the polarizing influence is closely associated with the sweep of the Hedgehog-dependent morphogenetic wave. Here we present evidence for a second and orthogonal axis of polarity, and show that it can be functionally separated from the A/P axis. Further, we show that the polarizing information acting in this equatorial/polar axis (Eq/Pl) is established in at least two steps - the activity of one signaling molecule functions to establish the graded activity of a second signal.


[Treatment of claw toes deformity].
Within pathologic alterations that affect foot and ankle, claw toes deformity is one of the most frequent with an incidence of 20%. There are many surgical options to treat this deformity reported in literature. To show clinical experience of the Orthopedic Department of Hospital "Victorio de la Fuente Narváez" in lesser toes claw deformity treated with resection of the proximal interphalangic joint, as a treatment for alignment and better function. We performed a retrospective clinical trial, in the period between January 2001 and December 2003 with a mean follow up of 14 months. Twenty three patients were included (43 fingers) 17 female and 6 male (mean age 54) bilateral deformity in 7 patients (19 fingers) unilateral in 16 patients (24 fingers); the most commonly affected finger was the second (55.8%). Clinical and radiographic diagnosis were made. Surgical treatment indication was determined in relation to functional impairment, type of shoe used and concomitant pathology. Functional assessment was done with AOFAS scale and a visual analogue scale. Satisfactory results were reported in 18 patients (78.3%), not entirely satisfactory results 3 patients (13%) and not satisfactory results in 2 patients (8.7%). Accordingly with the results obtained we can conclude that the surgical technique is simple and effective in treatment of lesser toes claw deformity, returning function and morphology of the forefoot.


Power production among different sports with similar maximum strength.
The purpose of this study was to compare 1 repetition maximum (1RM) strength, maximum power (MP), linear momentum (Mp), and the loads of 1RM responsible for maximum power (MP%) and for linear momentum (Mp%) generated in explosive concentric bench press (CBP) motion among athletes from different sports. A total of 56 athletes (13 sprinters, 16 basketball players, 16 handball players, 5 volleyball players, and 6 bodybuilders) performed CBP in the loads of 40, 50, 60, 70, and 80% of 1RM with 1-minute rest intervals. MP and Mp were assessed during CBP by customized apparatus with 3 separate displacement transducers. There were no significant differences in MP, Mp, MP%, and Mp% among the athletes. The only significant positive correlation was found between overall 1RM and Mp for athletes (r = 0.37). In conclusion, long-term sport-specific training adaptations do not play a major role on speed-strength parameters in athletes with similar strength from different sports backgrounds.


Reproducible biofilm cultivation of chemostat-grown Escherichia coli and investigation of bacterial adhesion on biomaterials using a non-constant-depth film fermenter.
Biomaterials-associated infections are primarily initiated by the adhesion of microorganisms on the biomaterial surfaces and subsequent biofilm formation. Understanding the fundamental microbial adhesion mechanisms and biofilm development is crucial for developing strategies to prevent such infections. Suitable in vitro systems for biofilm cultivation and bacterial adhesion at controllable, constant and reproducible conditions are indispensable. This study aimed (i) to modify the previously described constant-depth film fermenter for the reproducible cultivation of biofilms at non-depth-restricted, constant and low shear conditions and (ii) to use this system to elucidate bacterial adhesion kinetics on different biomaterials, focusing on biomaterials surface nanoroughness and hydrophobicity. Chemostat-grown Escherichia coli were used for biofilm cultivation on titanium oxide and investigating bacterial adhesion over time on titanium oxide, poly(styrene), poly(tetrafluoroethylene) and glass. Using chemostat-grown microbial cells (single-species continuous culture) minimized variations between the biofilms cultivated during different experimental runs. Bacterial adhesion on biomaterials comprised an initial lag-phase I followed by a fast adhesion phase II and a phase of saturation III. With increasing biomaterials surface nanoroughness and increasing hydrophobicity, adhesion rates increased during phases I and II. The influence of materials surface hydrophobicity seemed to exceed that of nanoroughness during the lag-phase I, whereas it was vice versa during adhesion phase II. This study introduces the non-constant-depth film fermenter in combination with a chemostat culture to allow for a controlled approach to reproducibly cultivate biofilms and to investigate bacterial adhesion kinetics at constant and low shear conditions. The findings will support developing and adequate testing of biomaterials surface modifications eventually preventing biomaterial-associated infections.


Associations of periodontal disease with femoral bone mineral density and estrogen replacement therapy: cross-sectional evaluation of US adults from NHANES III.
The objectives of this study were to evaluate the possible association of periodontal disease with (1) femoral bone mineral density (BMD), and (2) estrogen replacement therapy in a large sample of US adults (N= 11,655). The mean clinical attachment loss (CAL) per person was the main outcome variable. Based on the total BMD of the proximal femur and using the WHO diagnostic criteria, subjects were classified as having osteoporosis, osteopenia, or normal BMD. After adjusting for confounders, females with high calculus scores and low BMD had significantly more CAL than females with normal BMD and similar calculus scores (p<0.0001). No association was observed among women with low and intermediate levels of calculus. The greater CAL present among women with low BMD was associated with gingival recession. Patterns of findings were similar but equivocal among men, of whom only 66 were osteoporotic. After adjustment for possible confounders, postmenopausal women who reported having used estrogen replacement therapy presented significantly less mean CAL than those who never used estrogen. These findings indicate that in the presence of high calculus scores, females with osteoporosis are at increased risk for attachment loss and that this risk may be attenuated by the use of estrogen replacement therapy.


Sensorimotor modulation of human cortical swallowing pathways.
1. Transcranial magnetic stimulation over motor areas of cerebral cortex in man can activate short latency bilateral cortical projections to the pharynx and oesophagus. In the present paper we investigate the interaction between pathways from each hemisphere and explore how activity in these pathways is modulated by afferent feedback from the face, pharynx and oesophagus. 2. Comparison of unilateral and bilateral stimulation (using interstimulus intervals (ISIs) of 1, 5 or 10 ms between shocks) showed spatial summation of responses from each hemisphere at an ISI of 1 ms, indicating that cortical efferents project onto a shared population of target neurones. Such summation was not evident at ISIs of 5 or 10 ms. There was little evidence for transcallosal inhibition of responses from each hemisphere, as described for limb muscles. 3. Single stimuli applied to the vagus nerve in the neck or the supraorbital nerve, which alone produce intermediate (onset 20-30 ms) and long (50-70 ms) latency reflex responses in the pharynx and oesophagus, were used to condition the cortical responses. Compared with rest, responses evoked by cortical stimulation were facilitated when they were timed to coincide with the late part of the reflex. The onset latency was reduced during both parts of the reflex response. No facilitation was observed with subthreshold reflex stimuli. 4. Single electrical stimuli applied to the pharynx or oesophagus had no effect on the response to cortical stimulation. However, trains of stimuli at frequencies varying from 0.2 to 10 Hz decreased the latency of the cortically evoked responses without consistently influencing their amplitudes. The effect was site specific: pharyngeal stimulation shortened both pharyngeal and oesophageal response latencies, whereas oesophageal stimulation shortened only the oesophageal response latencies. 5. Cortical swallowing motor pathways from each hemisphere interact and their excitability is modulated in a site-specific manner by sensory input. The latter may produce a mixture of excitation and inhibition at both brainstem and cortical levels.


Understanding the complex interplay of barriers to physical activity amongst black and minority ethnic groups in the United Kingdom: a qualitative synthesis using meta-ethnography.
To conduct a meta-ethnographic analysis of qualitative studies to identify barriers to Black and Minority Ethnic (BME) individuals engaging in physical activity in the UK context. A qualitative synthesis using meta-ethnographic methods to synthesis studies of barriers to engaging in physical activity among BME groups in the UK. A comprehensive search strategy of multiple databases was employed to identify qualitative research studies published up to October 2012. The eleven searched databases included ASSIA, MEDLINE, EMBASE, CINAHL, Health Technology Assessment (HTA), NHS Scotland Library, Physical Activity Health Alliance (PAHA), PsyINFO, Social Services Abstract, Sport discuss and Web of Science. The Noblit and Hare's meta-ethnographic approach was undertaken to develop an inductive and interpretive form of knowledge synthesis. Fourteen papers met the inclusion criteria. The synthesis indicated that barriers to physical activity among BME individuals were influenced by four main concepts: perceptions; cultural expectations; personal barriers; and factors limiting access to facilities. BME individuals had different understandings of physical activity were influenced by migration history, experiences, cultural and health beliefs. This in turn may have a disempowering effect on BME individuals in terms of adopting or maintaining physical activity. These barriers to physical activity were explained at a higher conceptual level by a socio-ecological model. The social construct 'individual perception and understanding of physical activity' was particularly relevant to theoretical models and interventions. Interventions to promote engagement with physical activity need to address perceptions of this behaviour. The elicited concepts and contexts could be used to enhance the development of tailored effective health promotion interventions for BME individuals.


Water intake of weaned piglets from three to seven weeks old.
One hundred and two large white cross landrace piglets weaned at 21 (+/- 1) days old were randomly allocated to one of two commercial early weaning diets for a four week growth trial. The piglets were housed in groups of between six and 10. After initial moderate restriction the piglets were fed ad libitum. Food intakes and weight gains were recorded weekly. Water consumption of individual pens of piglets was recorded daily. Dietary treatment had no significant effect on mean daily feed intake, daily liveweight gain or food conversion ratio. The relationship between water and food intake, piglet weight and daily gain was examined using regression and multiple regression analyses. Water intake was related to all these parameters, with daily feed intake being the best single predictor of water intake. The relationship was described by the equation: water intake (litres/day) = 0.149 + 3.053 feed intake (kg/day).


Effects of age and inactivity due to prolonged bed rest on atrophy of trunk muscles.
This study investigated the effects of age and inactivity due to being chronically bedridden on atrophy of trunk muscles. The subjects comprised 33 young women (young group) and 41 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into two groups: independent elderly group who were able to perform activities of daily living involving walking independently (n = 28) and dependent elderly group who were chronically bedridden (n = 13). The thickness of the following six trunk muscles was measured by B-mode ultrasound: the rectus abdominis, external oblique, internal oblique, transversus abdominis, thoracic erector spinae (longissimus) and lumbar multifidus muscles. All muscles except for the transversus abdominis and lumbar multifidus muscles were significantly thinner in the independent elderly group compared with those in the young group. The thicknesses of all muscles in the dependent elderly group was significantly smaller than that in the young group, whereas there were no differences between the dependent elderly and independent elderly groups in the muscle thicknesses of the rectus abdominis and internal oblique muscles. In conclusion, our results suggest that: (1) age-related atrophy compared with young women was less in the deep antigravity trunk muscles than the superficial muscles in the independent elderly women; (2) atrophy associated with chronic bed rest was more marked in the antigravity muscles, such as the back and transversus abdominis.


Low-level toluene disrupts auditory function in guinea pigs.
Toluene appears to have adverse effects on the human auditory system, but it is difficult to estimate its potency since it is commonly present in the workplace in combination with noise exposure; workplace noise exposures are often highly variable. Studies designed to assess toluene ototoxicity specifically have been limited to high-dose studies in a single laboratory animal model, the rat. Here permanent hearing loss has been observed at concentrations of 1000 ppm toluene and greater after inhalation exposure for 5 days, 6 h/day. The OSHA threshold limit value for toluene is only 100 ppm. The current study focuses on the onset of toluene ototoxicity acutely in the guinea pig and in adducing a mechanism of effect. In this study, evidence is presented for the impairment of auditory function by toluene in the guinea pig, at a concentration substantially lower than that used for studying permanent impairment in the rat. The impaired function was correlated with reduced energy metabolism in outer hair cells. Assessment of auditory function was made using distortion product otoacoustic emissions (DPOAE) with subsequent measurement of succinate dehydrogenase (SDH) staining density in hair cells using surface preparations. Temporary disruption of auditory function in guinea pigs is seen in subjects exposed to 250, 500, and 1000 ppm toluene for 8 h/day, 5 day/week for 1 and 4 weeks. Concentrations as low as 250 ppm toluene were able to disrupt auditory function acutely in the guinea pig, and 500 and 1000 ppm toluene produced greater acute dysfunction. SDH staining suggests that reduced enzyme activity in the midfrequency region of the cochlea occurs acutely following toluene exposure. Although the auditory dysfunction progressed between 1 and 4 weeks of exposure, a permanent loss did not develop for these subjects and hair cell death was not seen. The current study identifies early evidence of auditory system impairment in the guinea pig at low toluene concentration and evidence for impairment of energy production in hair cells. While even a transient auditory impairment has implications for workplace safety, additional study on the transition from such acute effects to permanent impairment is essential.


Benefits of Teledermatology for Geriatric Patients: Population-Based Cross-Sectional Study.
Teledermatology is a health care tool that has been increasingly used around the world, mostly because dermatology has an emphasis on visual diagnosis. Many studies have shown that access to specialized care improves using teledermatology, which provides accurate diagnosis and reduces the time taken for treatment, with high patient satisfaction. As the population around the world grows old, there will be even more demand for dermatologists in years to come. It is essential to know which are the most prevalent skin conditions in the primary care population and if they can be addressed through teledermatology. Our main goal was to evaluate the proportion of lesions in individuals aged 60 years and older that could be managed using teledermatology in conjunction with primary care physicians. Second, we aimed to assess the most frequent skin lesions, the most common treatments provided to patients, and the distribution and causes of referrals made by the teledermatologists. This was a retrospective cohort study from July 2017 to July 2018 in São Paulo, Brazil. We included 6633 individuals aged 60 years and older who presented with 12,770 skin lesions. Teledermatologists had three options to refer patients: (1) to undergo biopsy directly, (2) to an in-person dermatologist visit, and (3) back to the primary care physician with the most probable diagnosis and treatment. Teledermatology managed 66.66% (8408/12614) of dermatoses with the primary care physician without the need for an in-presence visit; 27.10% (3419/12614) were referred to dermatologists, and 6.24% (787/12614) directly to biopsy. The most frequent diseases were seborrheic keratosis, solar lentigo, onychomycosis, melanocytic nevus, benign neoplasms, actinic keratosis, epidermoid cyst, xerosis, leucoderma, and wart, with significant differences between sexes. Malignant tumors increased with age and were the leading cause for biopsies, while infectious skin conditions and pigmentary disorders decreased. Emollient was the most frequent treatment prescribed, in 31.88% (909/2856) of the cases. Teledermatology helped to treat 67% of the dermatoses of older individuals, addressing cases of minor complexity quickly and conveniently together with the primary care physician, thus optimizing dermatological appointments for the most severe, surgical, or complex diseases. Teledermatology does not aim to replace a face-to-face visit with the dermatologist; however, it might help to democratize dermatological treatment access for patients and decrease health care expenses.


Completely thoracoscopic right upper lobectomy and mediastinal lymph node dissection.
Video-assisted thoracoscopic surgery (VATS) has been constantly used in the diagnosis and treatment of intrathoracic disease. The focus of VATS is primarily concerned with the completeness of mediastinal lymph node dissection for lung cancer and the safety of surgery. Here we discuss the feasibility of VATS right upper lobectomy and systematic lymph node dissection, for a 60-year-old woman who was admitted for tumor of the right upper lobe, and describe this treatment method and the major indications. The technique of single-direction lobectomy and mediastinal lymph node dissection is a safe and feasible completely thoracoscopic lobectomy in minimally invasive approach. Single-direction lobectomy can shorten the operation time and reduce the difficulty and complexity of the procedure. The video demonstrates the manipulation of arterial and venous bleeding in thoracoscopic surgery and the skill of single-direction operation.


Positron emission tomography and bone metastases.
The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant. The most important question, however, is irrespective of whether a lesion is seen on x-ray, CT, or bone scan and irrespective of lytic of blastic morphology: if the FDG-PET study is negative, what is the clinical relevance of that lesion?


Residential environment index system and evaluation model established by subjective and objective methods.
In this research, the residential environment index system and evaluation model were established by means of subjective and objective methods. The methodology for establishing the evaluation system for residential environment was first analyzed; then the subjective evaluation data-base was established by questionnaire survey; and at the same time, the objective evaluation data-base was constructed by Geographic Information System (GIS); and then the related equation system between subjective and objective system was developed by multiple regression analysis. This research could benefit evaluation of the residential environment quality for various purposes, and also provide important rudimentary data-base for the development and improvement of residential environment for officials. Furthermore, the index system and evaluation model established in this research could construct a strong relation between subjective evaluation and objective data; and thus could provide a comprehensive, efficient and effective methodology for the evaluation of residential environment.


Processing and analysis of potentiometric data.
Potentiometric titration curves have traditionally been collected as the difference in absorbance at two wavelengths, and analyzed by plotting voltage vs. log (oxidized/reduced). The collection method, designed to monitor changes in local peak height, is effective for that purpose only when spectral backgrounds do not change slope as voltage changes, and the analysis method is valid only for a single isolated component (one whose midpoint potential is far from that of anything else in the mixture). Yet these methods are commonly used where such restrictions do not pertain, e.g. the study of cytochromes in mitonchondria. In this paper, we present more appropriate methods of collection and analysis, and suggest that, even with the best available methods, any conclusion should be confirmed in several ways. Experimental results are presented in accompanying papers.


Sleep in restrictive lung disorders.
Abnormalities in sleep occur in patients with both extrapulmonary restriction and intrapulmonary restriction. Patients with extrapulmonary restriction such as kyphoscoliosis may develop severe apneas during sleep, particularly during the REM stage. Patients with interstitial lung disease continue to have a rapid shallow breathing pattern during sleep, but may also develop abnormalities in the breathing pattern. During periods of snoring patients with interstitial lung disease may develop further hypoxemia.


The virtues of the virtual world. Enhancing the technology/knowledge professional interface for life-long learning.
Nurses are quintessential learners. Nested between the fields of science and technology, the professional mandate for life-long learning has never been greater. The expanding demands for performance and quality coupled with the reality of diminishing time and resources increasingly frustrate and challenge providers in the field. By blending the best of current training and education with the emerging potential of virtual learning, new models for enhancing clinical reasoning and performance will simplify the challenges of complexity, moving it to higher order. In this transition lies the key to restoring the joy and commitment of professional practice while enhancing the capacity to care with competence.


A GDP/GTP exchange factor involved in linking a spatial landmark to cell polarity.
In both animal and yeast cells, signaling pathways involving small guanosine triphosphatases (GTPases) regulate polarized organization of the actin cytoskeleton. In the budding yeast Saccharomyces cerevisiae, the Ras-like GTPase Bud1/Rsr1 and its guanosine 5'-diphosphate (GDP)/guanosine 5'-triphosphate (GTP) exchange factor Bud5 are involved in the selection of a specific site for growth, thus determining cell polarity. We found that Bud5 is localized at the cell division site and the presumptive bud site. Its localization is dependent on potential cellular landmarks, such as Bud3 and Axl2/Bud10 in haploid cells and Bud8 and Bud9 in diploid cells. Bud5 also physically interacts with Axl2/Bud10, a transmembrane glycoprotein, suggesting that a receptor-like transmembrane protein recruits a GDP/GTP exchange factor to connect an intrinsic spatial signal to oriented cell growth.


The potential role of contraception in reducing abortion.
This study examines the potential role of further increases in contraceptive prevalence and effectiveness in reducing abortion rates. The model used in this analysis links the abortion rate to its direct determinants, including couples' reproductive preferences, the prevalence and effectiveness of contraceptive practice to implement these preferences, and the probability of undergoing an abortion to avoid an unintended birth when a contraceptive fails or is not used. An assessment of the tradeoff between contraception and abortion yields estimates of the decline in the total abortion rate that would result from an illustrative increase of 10 percentage points in prevalence. This effect varies among societies, primarily because the tendency to obtain an abortion after an unintended pregnancy varies. For example, in a population with an abortion probability of 0.5, a 10 percentage-point increase in prevalence would avert approximately 0.45 abortions per woman, assuming contraception is 95 percent effective. If all unintended pregnancies were aborted, this effect would be three times larger. Eliminating all unintended pregnancies and subsequent abortions would require a rise in contraceptive prevalence to the level at which all fecund women who do not wish to become pregnant practice contraception that is 100 percent effective. A procedure is provided for estimating this "perfect" level of contraceptive prevalence.


Efficacy of the cushing response in maintaining cerebral blood flow in premature and near-term fetal sheep.
Fetal head compression during labor may increase intracranial pressure (ICP) and decrease cerebral perfusion pressure (CPP). An increase in mean arterial pressure (MAP) associated with the Cushing response normally acts to mitigate an ischemic insult when the increase in ICP approaches MAP. However, the premature fetus may be limited in its ability to increase MAP. We compared the efficacy of the pressor response in sustaining CPP, cerebral blood flow (CBF), and cerebral O2 consumption (CMRO2) in chronically catheterized fetal sheep at 0.6 gestation (92 d; n = 7) and 0.9 gestation (133 d; n = 7). When fetal ICP was increased to baseline MAP (41 +/- 3 mm Hg; +/-SEM) in 92-d fetuses, MAP increased by 7 +/- 2 mm Hg and remained stable during 30 min of constant ICP elevation; CBF decreased by 72% and CMRO2 decreased by 46%. In 133-d fetuses, MAP increased from 53 +/- 2 to 65 +/- 4 mm Hg at 3 min of elevated ICP; CBF decreased by 62% and CMRO2 decreased 30%. However, MAP continued to increase after 3 min and reached a stable level of 75 +/- 3 mmHg at 30 min in 133-d fetuses. The additional increase in MAP restored CBF and CMRO2 to baseline values. Plasma epinephrine and vasopressin concentrations increased between 6 and 33 min of elevated ICP to levels, exceeding those in 92-d fetuses. We conclude that the arterial pressure response to intracranial hypertension is present at 0.6 gestation but is less well developed than at 0.9 gestation in fetal sheep, possibly due to immaturity of the sympathoadrenal and vasopressin systems. Consequently, CBF and CMRO2 are not as well defended at mid-gestation against elevated ICP as might occur during difficult labor.


Iodinated fibroblast beta-glucuronidase as a ligand for receptor-mediated endocytosis.
Antibodies raised to human placental beta-glucuronidase were shown to cross-react with the beta-glucuronidase secreted by mouse 3T3 fibroblasts, but did not react with other lysosomal enzymes. The beta-glucuronidase secreted by 3T3 cells was purified 15000-fold by chromatography on an affinity column made from this antibody and resolved into a single component, of Mr 68000, by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Iodinated samples of purified enzyme were taken up into mouse peritoneal macrophages by receptor-mediated endocytosis at a rate similar to that calculated previously for unlabelled enzyme, and uptake was competitively inhibited by yeast mannan. Binding of beta-glucuronidase to macrophages was saturable, with a Kd of 7 X 10(-9)l/mol, an affinity comparable with that calculated for the binding of mannosylated bovine serum albumin (Kd 1.3 X 10(-9)l/mol), a ligand specific for mannose receptors. Four times as many molecules of mannosylated albumin (12000) as of beta-glucuronidase (3000), however, bound to each cell. This purification and iodination procedure did not therefore have any adverse effect on the uptake properties of secreted beta-glucuronidase, and provides a ligand with which to investigate binding and specific endocytosis into a range of different types of cell.


The use of composites as core material in root-filled teeth. I. In vitro study.
To study how repeated temperature variations, "thermal stress", will influence the cement retention between composite materials--formed as cores--and gold crowns, extracted permanent teeth were prepared to core form. Stylized gold crowns were waxed up on the dentine preparations and cast, four for each of three chosen preparations, which in their turn were used to form cores in gold and three different composite materials. The attempt was to achieve four as similar test-pieces as possible for each core shape. Two new cements and four zinc phosphate cements were used as retaining medium for 48 test series. Four similar test-pieces have each time been subject to thermo-cycling during 12 hours in a specially designed apparatus. The temperature intervals were 0 degree C, 25 degrees C and 50 degrees C. Each series has then been loaded into a tensiometer and stressed until the cement retention was overcome. The test results showed that microfill composite cores were associated with least retention values. For the other materials: gold and macrofill composites (two paste system and single paste system), no differences were to be seen. The retentive ability for one (a zinc phosphate cement, normal- and fast-setting) of five different cements differed remarkably: about double the load was required to loosen the core from its crown than when any of the other cements was used.


Discrepancies between immunological and caseinolytic plasma plasminogen assays in health and hyperfibrinolytic states.
A sensitive immunological assay for plasminogen and/or plasmin was developed by using a haemagglutination inhibition technique. Plasma and the corresponding euglobulin fraction of healthy subjects and of patients with hyperfibrinolysis (liver cirrhosis, thrombolytic treatment) were assayed for plasminogen using immunological and caseinolytic techniques. In hyperfibrinolytic states discrepancies were found between immunoreactive and caseinolytic plasma plasminogen whereas a good correlation was observed between immunoreactive and caseinolytic euglobulin plasminogen. Experiments in vitro suggested that these discrepancies might depend on the presence in hyperfibrinolytic plasma of variable amounts of plasmin(ogen)-related antigen which has no caseinolytic activity and is not precipitated with euglobulin.


Transient global forebrain ischemia induces a prolonged expression of the caspase-3 mRNA in rat hippocampal CA1 pyramidal neurons.
The authors recently cloned a cDNA for an ICE/CED3-related cysteine protease from rat brain, which is closely related to human CPP32 (now designated caspase-3). In situ hybridization histochemistry revealed a profound developmental regulation of the caspase-3 transcript in rat brain, with relatively high levels of caspase-3 mRNA observed in neurons of the fetal and neonatal brain and low levels of mRNA in neurons of the adult brain. The authors report that transient forebrain ischemia, which results in a delayed apoptotic death of CA1 pyramidal neurons, results in prolonged expression of caspase-3 mRNA in these same pyramidal neurons. Up-regulation of caspase-3 mRNA in CA1 pyramidal neurons is prominent 24 hours after transient global ischemia, and expression is maintained at higher levels for at least 72 hours after ischemia. However, by 96 hours after ischemia, a marked decrease in caspase-3 mRNA expression is observed in CA1 pyramidal neurons, showing severe degenerative changes (e.g., nuclear condensation). By contrast, there is no change in the expression of a closely related member of caspase family, caspase-2, in CA1 pyramidal neurons after global ischemia. Instead, caspase-2 mRNA is induced in lamina layers of cerebral cortex 24 hours after the ischemia. A selective and prolonged induction of the caspase-3 gene in committed CA1 pyramidal neurons suggests that transcriptional activation of this caspase-3 gene may be involved in the apoptotic cell death cascade of CA1 neurons after transient global ischemia.


Critical Issues in Food Allergy: A National Academies Consensus Report.
The National Academies of Sciences, Engineering, and Medicine convened an expert, ad hoc committee to examine critical issues related to food allergy. The authors of the resulting report, "Finding a Path to Safety in Food Allergy: Assessment of the Global Burden, Causes, Prevention, Management, and Public Policy," evaluated the scientific evidence on the prevalence, diagnosis, prevention, and management of food allergy and made recommendations to bring about a safe environment for those affected. The committee recommended approaches to monitor prevalence, explore risk factors, improve diagnosis, and provide evidence-based health care. Regarding diagnostics, emphasis was placed on utilizing allergy tests judiciously in the context of the medical history because positive test results are not, in isolation, diagnostic. Evidence-based prevention strategies were advised (for example, a strategy to prevent peanut allergy through early dietary introduction). The report encourages improved education of stakeholders for recognizing and managing as well as preventing allergic reactions, including an emphasis on using intramuscular epinephrine promptly to treat anaphylaxis. The report recommends improved food allergen labeling and evaluation of the need for epinephrine autoinjectors with a dosage appropriate for infants. The committee recommended policies and guidelines to prevent and treat food allergic reactions in a various settings and suggested research priorities to address key questions about diagnostics, mechanisms, risk determinants, and management. Identifying safe and effective therapies is the ultimate goal. This article summarizes the key findings from the report and emphasizes recommendations for actions that are applicable to pediatricians and to the American Academy of Pediatrics.


Earliest filter-feeding pterosaur from the Jurassic of China and ecological evolution of Pterodactyloidea.
Pterosaurs were a unique clade of flying reptiles that were contemporaries of dinosaurs in Mesozoic ecosystems. The Pterodactyloidea as the most species-diverse group of pterosaurs dominated the sky during Cretaceous time, but earlier phases of their evolution remain poorly known. Here, we describe a 160 Ma filter-feeding pterosaur from western Liaoning, China, representing the geologically oldest record of the Ctenochasmatidae, a group of exclusive filter feeders characterized by an elongated snout and numerous fine teeth. The new pterosaur took the lead of a major ecological transition in pterosaur evolution from fish-catching to filter-feeding adaptation, prior to the Tithonian (145-152 Ma) diversification of the Ctenochasmatidae. Our research shows that the rise of ctenochasmatid pterosaurs was followed by the burst of eco-morphological divergence of other pterodactyloid clades, which involved a wide range of feeding adaptations that considerably altered the terrestrial ecosystems of the Cretaceous world.


The functional expression and characterisation of a cysteine peptidase from the invasive stage of the neuropathogenic schistosome Trichobilharzia regenti.
A transcriptional product of a gene encoding cathepsin B-like peptidase in the bird schistosome Trichobilharzia regenti was identified and cloned. The enzyme was named TrCB2 due to its 77% sequence similarity to cathepsin B2 from the important human parasite Schistosoma mansoni. The zymogen was expressed in the methylotropic yeast Pichia pastoris; procathepsin B2 underwent self-processing in yeast media. The peptidolytic activity of the recombinant enzyme was characterised using synthetic fluorogenic peptide substrates at optimal pH 6.0. Functional studies using different specific inhibitors proved the typical cathepsin B-like nature of the enzyme. The S(2) subsite specificity profile of recombinant TrCB2 was obtained. Using monospecific antibodies against the recombinant enzyme, the presence of cathepsin B2 was confirmed in extracts from cercariae (infective stage) and schistosomula (early post-cercarial stage) of T. regenti on Western blots. Also, cross-reactivity was observed between T. regenti and S. mansoni cathepsins B2 in extracts of cercariae, schistosomula or adults. In T. regenti, the antisera localised the enzyme to post-acetabular penetration glands of cercariae implying an important role in the penetration of host skin. The ability of recombinant TrCB2 to degrade skin, serum and nervous tissue proteins was evident. Elastinolytic activity suggests that the enzyme might functionally substitute the histolytic role of the serine class elastase known from S. mansoni and Schistosoma haematobium but not found in Schistosoma japonicum or in bird schistosomes.


Stereotypical spatiotemporal activity patterns during slow-wave activity in the neocortex.
Alternating epochs of activity and silence are a characteristic feature of neocortical networks during certain sleep cycles and deep states of anesthesia. The mechanism and functional role of these slow oscillations (<1 Hz) have not yet been fully characterized. Experimental and theoretical studies show that slow-wave oscillations can be generated autonomously by neocortical tissue but become more regular through a thalamo-cortical feedback loop. Evidence for a functional role of slow-wave activity comes from EEG recordings in humans during sleep, which show that activity travels as stereotypical waves over the entire brain, thought to play a role in memory consolidation. We used an animal model to investigate activity wave propagation on a smaller scale, namely within the rat somatosensory cortex. Signals from multiple extracellular microelectrodes in combination with one intracellular recording in the anesthetized animal in vivo were utilized to monitor the spreading of activity. We found that activity propagation in most animals showed a clear preferred direction, suggesting that it often originated from a similar location in the cortex. In addition, the breakdown of active states followed a similar pattern with slightly weaker direction preference but a clear correlation to the direction of activity spreading, supporting the notion of a wave-like phenomenon similar to that observed after strong sensory stimulation in sensory areas. Taken together, our findings support the idea that activity waves during slow-wave sleep do not occur spontaneously at random locations within the network, as was suggested previously, but follow preferred synaptic pathways on a small spatial scale.


Adaptive visual re-weighting in children's postural control.
This study investigated how children's postural control adapts to changes in the visual environment and whether they use previous experience to adjust postural responses to following expositions. Four-, eight-, and twelve-year-old children (10 in each group) and 10 young adults stood upright inside of a moving room during eight trials each lasting one-minute. In the first trial, the room was stationary. In the following seven trials, the room oscillated at 0.2 Hz, amplitude of 0.5 cm, with the exception of the fifth trial, in which the room oscillated with amplitude of 3.2 cm. Body sway responses of young adults and older children down-weighted more to the increased visual stimulus amplitude when compared to younger children. In addition, four- and eight-year-old children quickly up-weighted body responses to visual stimulus in the subsequent two trials after the high amplitude trial. Sway variability decreased with age and was greatest during the high-amplitude trial. These results indicate that four year olds have already developed the adaptive capability to quickly down-weight visual influences. However, the increased gain values and residual variability observed for the younger children suggest that they have not fully calibrated their adaptive response to that of the young adults tested. Moreover, younger children do not carry over their previous experience from the sensorial environment to adapt to future changes.


Reductive Electrochemical Activation of Hydrogen Peroxide as an Advanced Oxidation Process for Treatment of Reverse Osmosis Permeate during Potable Reuse.
The UV/hydrogen peroxide (H2O2) advanced oxidation process (AOP) frequently employed to generate hydroxyl radical (•OH) to treat reverse osmosis permeate (ROP) in potable reuse treatment trains is inefficient, using only 10% of the H2O2. This study evaluated ·OH generation by electron transfer from a low-cost stainless steel cathode. In deionized water, the electrochemical system achieved 0.5 log removal of 1,4-dioxane, a benchmark for AOP validation for potable reuse, within 4 min using only 1.25 mg/L H2O2. Hydrogen peroxide and 1,4-dioxane degradations were maximized near -0.18 and + 0.02 V versus standard hydrogen electrode, respectively. Degradations of positively and negatively charged compounds were comparable to neutral 1,4-dioxane, indicating that degradation occurs by ·OH generation from neutral H2O2 and that electrostatic repulsion of contaminants from the electrode is not problematic. For ROP without chloramines, 0.5 log 1,4-dioxane removal was achieved in 6.7 min with 7 mM salts for ionic strength and 2.5 mg/L H2O2. For ROP with 1.4 mg/L as Cl2 chloramines, 0.5 log 1,4-dioxane removal was achieved in 13.2 min with 7 mM salts and 4.5 mg/L total H2O2 dosed in three separate injections in 5 min intervals. Initial estimates based on lab-scale electrochemical AOP treatment indicated that, except for the cost of salts, the electrochemical AOP featured lower reagent costs than the UV/H2O2 AOP but higher electricity costs that could be reduced by optimization of the electrochemical design.


Micropatterned "adherent/repellent" glass surfaces for studying the spreading kinetics of individual red blood cells onto protein-decorated substrates.
We report in this paper two simple and effective methods to decorate glass surfaces that enable protein micropatterning and subsequent spatially controlled adhesion of cells. The first method combines simultaneously the potentialities of two existing techniques, namely microcontact printing (muCP) and microfluidic networks (muFN) to achieve dual protein patterning in a single step. The second method is mainly based on the well-known property of poly(ethylene glycol) (PEG) to resist against protein adsorption. Both approaches were used to produce heterogeneous surfaces on which micron-size or submicronic streptavidin-coated lines alternate with cell-repellent areas. We first describe the implementation of the two methods and discuss the main pitfalls to avoid. Then, using these templates, we have monitored the kinetics of attachment of individual biotinylated (i.e. "attractant" towards streptavidin) red blood cells by directly measuring the propagation velocity of the adhesion front. Depending on the surface density of biotin, we found two distinct regimes, in agreement with existing theoretical models.


Predicting the effects of copy-number variation in double and triple mutant combinations.
The study of genetic interactions is a powerful tool in inferring structure and function of biological networks. To date, genetic interaction studies have been dominated by pair-wise gene deletion screens. However, classical genetic analysis and natural genetic variation involve diverse gene forms ranging from null alleles to copy number variants. Moreover, genetic variation is typically multifactorial. Addressing multiple combinatorial genetic variations ranging in gene activity is therefore of critical value. We approach this problem using genetic network modeling that quantitatively encodes how genes influence the activity of one another and phenotype outcomes. A network model was initially inferred from linear decomposition of gene expression data. We used this network to predict the effects of combining multi-copy and deletion mutations of specific gene pairs and a gene triplet. Predicted expression patterns across hundreds of genes were experimentally validated. Prediction success was critically dependent on how a multi-copy gene interacted with other genes in the network model. This strategy provides a template for the inference, prediction, and testing of genetically complex hypotheses involving diverse genetic variation.


Suicide plasmid vehicles for insertion mutagenesis in Rhizobium meliloti and related bacteria.
We describe the construction and use of a set of plasmid vectors of the transposons Tn1, Tn5, and Tn9 that are suicidal in Rhizobium species and therefore suitable for mutagenesis with these three transposons. The vectors are composed of the p15A replicon which functions in Escherichia coli but not in Rhizobium species and a region encoding the N type of bacterial conjugation system which is very efficient in matings between E. coli and Rhizobium species. The usefulness of the vectors has been most extensively assessed in Rhizobium meliloti. It is likely that they will be useful for mutagenesis and genome manipulation in other bacteria as well.


Autonomic control of ventricular tachycardia: sympathetic neural influence on spontaneous tachycardia 24 hours after coronary occlusion.
This study was performed to determine whether sympathetic nerves influence the rate of ventricular tachycardia occurring spontaneously in dogs 24 hr after occlusion of the anterior descending coronary artery. Seventeen chloralose-anesthetized dogs underwent activation mapping during spontaneous ventricular tachycardia with QRS morphologies similar to those recorded in the conscious state. Bilateral stellate ganglionectomy (n = 8) decreased mean arterial pressure from 71 +/- 4 (mean +/- SE) to 52 +/- 5 mm Hg (p less than .001) and heart rate from 121 +/- 9 to 79 +/- 15 beats/min (p less than .025) by decreasing the number of complexes of ventricular tachycardia from 120 +/- 9 to 49 +/- 15 per minute (p less than .001). Subsequent unilateral sympathetic nerve stimulation (n = 4) was shown to accelerate ventricular tachycardia foci originating from the ipsilateral aspect of the infarction. Regional sympathetic denervation (n = 7) was performed by application of phenol to the epicardium surrounding an electrode at the site of origin of at least one morphology of ventricular tachycardia. Mean arterial pressure did not change, but total heart rate decreased from 122 +/- 9 to 106 +/- 9 beats/min (p less than .01) and the number of complexes of ventricular tachycardia with a morphology arising from the phenol-treated area fell from 68 +/- 12 to 28 +/- 9 (p less than .001). Evidence for regional denervation was documented by prolongation of duration of electrograms and local repolarization times limited to the phenol-treated area. We conclude that sympathetic nerves directly control rate of spontaneous ventricular tachycardia 24 hr after myocardial infarction in the dog.