Occurrence of bacteria and biochemical markers on public surfaces.
From 1999-2003, the hygiene of 1061 environmental surfaces from shopping, daycare, and office environments, personal items, and miscellaneous activities (i.e., gymnasiums, airports, movie theaters, restaurants, etc.), in four US cities, was monitored. Samples were analyzed for fecal and total coliform bacteria, protein, and biochemical markers. Biochemical markers, i.e., hemoglobin (blood marker), amylase (mucus, saliva, sweat, and urine marker), and urea (urine and sweat marker) were detected on 3% (26/801); 15% (120/801), and 6% (48/801) of the surfaces, respectively. Protein (general hygiene marker) levels > or = 200 microg/10 cm2 were present on 26% (200/801) of the surfaces tested. Surfaces from children's playground equipment and daycare centers were the most frequently contaminated (biochemical markers on 36%; 15/42 and 46%; 25/54, respectively). Surfaces from the shopping, miscellaneous activities, and office environments were positive for biochemical markers with a frequency of 21% (69/333), 21% (66/308), and 11% (12/105), respectively). Sixty samples were analyzed for biochemical markers and bacteria. Total and fecal coliforms were detected on 20% (12/60) and 7% (4/ 60) of the surfaces, respectively. Half and one-third of the sites positive for biochemical markers were also positive for total and fecal coliforms, respectively. Artificial contamination of public surfaces with an invisible fluorescent tracer showed that contamination from outside surfaces was transferred to 86% (30/ 35) of exposed individual's hands and 82% (29/35) tracked the tracer to their home or personal belongings hours later. Results provide information on the relative hygiene of commonly encountered public surfaces and aid in the identification of priority environments where contaminant occurrence and risk of exposure may be greatest. Children's playground equipment is identified as a priority surface for additional research on the occurrence of and potential exposure to infectious disease causing agents.


HIV-1 latency and virus production from unintegrated genomes following direct infection of resting CD4 T cells.
HIV-1 integration is prone to a high rate of failure, resulting in the accumulation of unintegrated viral genomes (uDNA) in vivo and in vitro. uDNA can be transcriptionally active, and circularized uDNA genomes are biochemically stable in non-proliferating cells. Resting, non-proliferating CD4 T cells are prime targets of HIV-1 infection and latently infected resting CD4 T cells are the major barrier to HIV cure. Our prior studies demonstrated that uDNA generates infectious virions when T cell activation follows rather than precedes infection. Here, we characterize in primary resting CD4 T cells the dynamics of integrated and unintegrated virus expression, genome persistence and sensitivity to latency reversing agents. Unintegrated HIV-1 was abundant in directly infected resting CD4 T cells. Maximal gene expression from uDNA was delayed compared with integrated HIV-1 and was less toxic, resulting in uDNA enrichment over time relative to integrated proviruses. Inhibiting integration with raltegravir shunted the generation of durable latency from integrated to unintegrated genomes. Latent uDNA was activated to de novo virus production by latency reversing agents that also activated latent integrated proviruses, including PKC activators, histone deacetylase inhibitors and P-TEFb agonists. However, uDNA responses displayed a wider dynamic range, indicating differential regulation of expression relative to integrated proviruses. Similar to what has recently been demonstrated for latent integrated proviruses, one or two applications of latency reversing agents failed to activate all latent unintegrated genomes. Unlike integrated proviruses, uDNA gene expression did not down modulate expression of HLA Class I on resting CD4 T cells. uDNA did, however, efficiently prime infected cells for killing by HIV-1-specific cytotoxic T cells. These studies demonstrate that contributions by unintegrated genomes to HIV-1 gene expression, virus production, latency and immune responses are inherent properties of the direct infection of resting CD4 T cells. Experimental models of HIV-1 latency employing directly infected resting CD4 T cells should calibrate the contribution of unintegrated HIV-1.


Borrelia burgdorferi and Anaplasma phagocytophilum Genospecies in Northern California.
The sensu lato (s.l.) complexes of Borrelia burgdorferi and Anaplasma phagocytophilum include pathogenic genospecies each with distinct ecologies in northern California, yet, most work conflates the genospecies of each pathogen into one sensu lato species. Detailed understanding of the differences in geographic distributions and ecology among genospecies is lacking. We aimed to evaluate whether two B. burgdorferi and two A. phagocytophilum genospecies in high-risk locations in coastal northern California were spatially clustered and if presence of a particular genospecies was associated with geographical site, host species, or other demographic or ecological variables. DNA sequencing was performed to differentiate genospecies of Borreliae and Anaplasma from PCR-positive dusky-footed woodrats (Neotoma fuscipes) and sciurids (chipmunks, Tamias spp., and Douglas squirrels, Tamiasciurus douglasii) at four sites in northwestern California. Logistic regression was performed to assess associations of genospecies with the predictor variables host species, host sex, site, season, and year. Spatial clustering was assessed using a Poisson spatial scan statistic in SaTScan. Host species was a significant predictor for Borrelia bissettiae, B. burgdorferi sensu stricto (s.s.), A. phagocytophilum s.s., and the DU1 Anaplasma genospecies. Woodrats were significantly more likely to be PCR-positive for B. bissettiae and A. phagocytophilum DU1 genospecies, while A. phagocytophilum s.s. and B. burgdorferi s.s. were significantly associated with sciurids. We report a single Borrelia lanei in an Allen's chipmunk (Tamias senex) from the Hoopa Valley Tribal Reservation. A significant spatial cluster of A. phagocytophilum s.s. was detected at Hendy Woods State Park in Mendocino County. These results highlight the need to better understand genospecies partitioning according to host species to further assess human risks, aid in future surveillance, and inform targeted research.


Acute Care Surgery: Defining the Economic Burden of Emergency General Surgery.
Trauma centers (TCs) have been shown to provide lifesaving, but more expensive, care when compared with non-TCs (NTC). Limited data exist about the economic impact of emergency general surgery (EGS) patients on health care systems. We hypothesized that the economic burden would be higher for EGS patients managed at TCs vs NTCs. The Maryland Health Services Cost Review Commission database was queried from 2009 to 2013. The American Association for the Surgery of Trauma EGS ICD-9 codes were used to define the top 10 EGS diagnoses. Demographic characteristics, TC designation, severity of illness, and hospital charge data were collected. Differences in total charges between TCs and NTCs were analyzed by Wilcoxon test using SAS 9.3 software (SAS Institute). A total of 435,623 patients were included. Median age was 61 years (interquartile range 47 to 76 years) and 55.9% were female. Median length of stay was 4 days; 90.3% were admitted via emergency department; and overall mortality was 5.1%. Overall median charges were $11,081 for TC vs $8,264 for NTC (p < 0.0001). Minor, moderate, major, and extreme severities of illness all had higher charges at TC vs NTC with no ICU admissions, respectfully ($5,908 vs $5,243; $7,051 vs $6,003; $10,501 vs $8,777; and $23, 997 vs $18,381; p < 0.001). Care at TCs was nearly twice as expensive if patients were admitted to the ICU, even when stratifying by severity of illness. Emergency general surgery patients treated at TCs incurred increased costs compared with NTCs, independent of patient severity. These costs nearly doubled for those admitted to the ICU. As acute care surgery grows as a specialty, additional investigation is required to better understand the reasons for this cost differential.


Selective detection of histologically aggressive prostate cancer: an Early Detection Research Network Prediction model to reduce unnecessary prostate biopsies with validation in the Prostate Cancer Prevention Trial.
Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy. Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model. The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P < .001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P < .01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (<10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD >0.1 ng/mL/cc or abnormal DRE. When PSAD is <0.1 ng/mL/cc, family history or obesity can identify biopsy candidates. A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer.


[Contribution to the study of laterality in professional musicians].
Left-handed professional musicians percentage is not significantly different from normal population, excepted for piano, organ and harpsichord players. For these instruments the melody is always written for the right hand, probably because of the location of the frequencies which are the most easily perceived by the human ear on the right part of the keyboard. Thus for a lefthanded musician to play piano is comparable to write with his right hand, and as a consequence leads him to play an other instrument for his professional activity.


NRF2-regulation in brain health and disease: implication of cerebral inflammation.
The nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulator of endogenous inducible defense systems in the body. Under physiological conditions NRF2 is mainly located in the cytoplasm. However, in response to oxidative stress, NRF2 translocates to the nucleus and binds to specific DNA sites termed "anti-oxidant response elements" or "electrophile response elements" to initiate transcription of cytoprotective genes. Acute oxidative stress to the brain, such as stroke and traumatic brain injury is increased in animals that are deficient in NRF2. Insufficient NRF2 activation in humans has been linked to chronic diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. New findings have also linked activation of the NRF2 system to anti-inflammatory effects via interactions with NF-κB. Here we review literature on cellular mechanisms of NRF2 regulation, how to maintain and restore NRF2 function and the relationship between NRF2 regulation and brain damage. We bring forward the hypothesis that inflammation via prolonged activation of key kinases (p38 and GSK-3β) and activation of histone deacetylases gives rise to dysregulation of the NRF2 system in the brain, which contributes to oxidative stress and injury.


Loss of intraoperative neurological monitoring signals during flexed prone positioning on a hinged open frame during surgery for kyphoscoliosis correction: case report.
Various complications of prone positioning in spine surgery have been described in the literature. Patients in the prone position for extended periods are subject to neurological deficits and/or loss of intraoperative signals due to compression neuropathies, but positioning-related spinal deficits are rare in the thoracolumbar deformity population. The authors present a case of severe kyphoscoliotic deformity with critical thoracolumbar stenosis in which, during the use of a hinged open frame in the prone position, complete loss of intraoperative neural monitoring signals occurred while the frame was flexed into kyphosis to facilitate exposure and instrumentation placement. When the frame was reset to a neutral position, evoked potentials returned to baseline and the operation proceeded without complications. This case represents, to the authors' knowledge, the first report of loss of evoked potentials due to an alteration of prone positioning on a hinged open frame. When positioning patients in such a manner, careful attention should be directed to intraoperative signals in patients with critical stenosis and kyphotic deformity.


Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA.
DNA vaccination is an effective means of eliciting both humoral and cellular immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al., Science 259:1745-1749, 1993). In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. These responses were mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken together, these results indicate that immunization with NP DNA primes both cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA.


Short overview on the current standard of treatment in newly diagnosed multiple myeloma.
The treatment of newly diagnosed multiple myeloma has changed dramatically over the past 20 years, from near uniform application of chemotherapy to a patient performance status- and risk-based approach. Furthermore, initiation of treatment criteria have evolved from a pure end-organ damage-based definition to include risk factors of transformation to frank myeloma. Besides, the mainly cytogenetically defined Multiple Myeloma (MM) risk status, transplant eligibility of patients still serves primarily to allocate patients within a rational treatment algorithm. While all transplant-eligible MM patients should receive a triplet induction therapy followed by autologous transplantation and, in most cases, lenalidomide maintenance, other therapeutic elements (e. g., other maintenance strategies, consolidation, tandem transplantation,..) have to be decided on an individualized appraisal of risk and toxicities. Standard-risk patients should never be undertreated, as they derive the highest relative benefit from using the best available registered therapies. However, high-risk patients should be preferentially treated inside clinical trials testing additive innovative treatments, as the improvement in the prognosis of this group of patients by standard therapies has been underwhelming. Furthermore, the evaluation process of non-transplant-eligible patients should always comprise an evaluation of performance status, frailty, and comorbidities (e. g., a comprehensive geriatric assessment) to facilitate the allocation of individualized therapies.


Morphofunctional traits and pollination mechanisms of Coronilla emerus L. flowers (Fabaceae).
It is accepted that the papilionaceous corolla of the Fabaceae evolved under the selective pressure of bee pollinators. Morphology and function of different parts of Coronilla emerus L. flowers were related to their role in the pollination mechanism. The corolla has a vexillum with red nectar lines, a keel hiding stamens and pistil, and two wing petals fasten to the keel with two notched folds. Pollinators land on the complex of keel and wings, trigger the protrusion of pollen and finally of the stigma from the keel tip. Data on pollen viability and stigma receptivity prove that flowers are proterandrous. The results of hand-pollination experiments confirmed that insects are fundamental to set seed. Interaction with pollinators allows not only the transport of pollen but also the rupture of the stigmatic cuticle, necessary to achieve both allogamy and autogamy. Field observations showed that Hymenoptera, Lepidoptera, and Diptera visited the flowers. Only some of the Hymenoptera landed on the flowers from the front and elicited pollination mechanisms. Most of the insects sucked the nectar from the back without any pollen transfer. Finally, morphological and functional characteristics of C. emerus flowers are discussed in terms of floral larceny and reduction in pollination efficiency.


Tomato and lycopene consumption is inversely associated with total and cause-specific mortality: a population-based cohort study, on behalf of the International Lipid Expert Panel (ILEP).
No data exist on the associations of dietary tomato and lycopene consumption with total and cause-specific mortality. Using the National Health and Nutrition Examination Surveys 1999-2010, we evaluted the long-term impact of tomato and lycopene intake on total and cause-specific (CHD and cerebrovascular disease) mortality. We also assessed the changes in cardio-metabolic risk factors according to tomato and lycopene intake. Vital status to 31 December 2011 was ascertained. Cox proportional hazard regression models (followed by propensity score matching) were used to investigate the link between tomato and lycopene consumption total, CHD and cerebrovascular mortality. Among the 23 935 participants included (mean age = 47·6 years, 48·8 % men), 3403 deaths occurred during 76·4 months of follow-up. Tomato intake was inversely associated with total (risk ratio (RR) 0·86, 95 % CI 0·81, 0·92), CHD (RR 0·76, 95 % CI 0·70, 0·85) and cerebrovascular (RR 0·70, 95 % CI 0·62, 0·81) mortality. Similar inverse associations were found between lycopene consumption, total (RR 0·76, 95 % CI 0·72, 0·81), CHD (RR 0·73, 95 % CI 0·65, 0·83) and cerebrovascular (RR 0·71, 95 % CI 0·65, 0·78) mortality; these associations were independent of anthropometric, clinical and nutritional parameters. Age and obesity did not affect the association of tomato and lycopene consumption with total, CHD and cerebrovascular mortality. C-reactive protein significantly moderated the link between lycopene and tomato intake with total, CHD and cerebrovascular mortality. ANCOVA showed that participants with a higher tomato and lycopene consumption had a more cardio-protective profile compared with those with a lower intake. Our results highlighted the favourable effect of tomato and lycopene intake on total and cause-specific mortality as well as on cardio-metabolic risk factors. These findings should be taken into consideration for public health strategies.


Mealworms as Food Ingredient-Sensory Investigation of a Model System.
The use of insects as food is a sustainable alternative to meat and as a protein source is fully comparable to meat, fish and soybeans. The next step is to make insects available for use in the more widespread production of food and meals. Sensory attributes are of great importance in being able to increase the understanding of insects as an ingredient in cooking and production. In this pilot study, mealworms were used as the main ingredient in a model system, where the aim was to evaluate the impact on sensory properties of changing particle size, oil/water ratio and salt content of the insects using a factorial design. Twelve different samples were produced according to the factorial design. Further, the effect of adding an antioxidant agent was evaluated. Sensory analysis and instrumental analyses were performed on the samples. Particle size significantly influenced the sensory attributes appearance, odor, taste and texture, but not flavor, whereas salt content affected taste and flavor. The viscosity was affected by the particle size and instrumentally measured color was affected by particle size and oil content. The addition of the antioxidant agent decreased the changes in color, rancidity and separation.


Key aspects defining the development and implementation of a regional genomic surveillance strategy for the Eastern Mediterranean Region.
The COVID-19 pandemic highlighted the critical role of pathogen sequencing in making informed public health decisions. Initially, the Eastern Mediterranean Region faced limitations in sequencing capacity. However, with robust WHO and stakeholder support, the situation significantly improved. By 2022, COVID-19 sequencing was underway in 22 out of 23 regional countries, with varying throughput and capacity. Notably, three genomic hubs were established in Oman, UAE, and Morocco, playing a key role in providing expanded genomics training and support across the region. While primarily for COVID-19 surveillance, this sequencing capacity offers an opportunity to integrate genomic surveillance into existing networks. This integration can enable early detection and response to high-threat pathogens with pandemic potential. To advance this, WHO/EMRO collaborated with stakeholders to formulate the Eastern Mediterranean Regional Genomic Surveillance Strategy for Emerging Pathogens of Pandemic Concern. Consultative meetings with regional and international genomic surveillance experts identified strategy focal points, key partners, priority pathogens, and implementation steps. As the strategy awaits member states' ratification in Q4 2023, this manuscript outlines pivotal facets defined by member states and the strategic document's key deliverables and opportunities. These efforts aim to yield a substantial positive impact within the region.


The effect of dietary fiber on glucose and hormone responses to a mixed meal in normal subjects and in diabetic subjects with and without autonomic neuropathy.
We investigated the effects of fiber on responses of blood glucose, serum insulin, gastric inhibitory polypeptide (GIP), and immunoreactive pancreatic glucagon (IRG) to ingestion of mixed meal with and without added fiber (5 g guar and 5 g pectin) in 12 normal, healthy subjects and in 12 age-, sex-, and weight-matched non-insulin-dependent, maturity-onset diabetic subjects (NIDDM). Fiber markedly enhanced glucose tolerance in the normal subjects without a change in insulin or GIP but with a significant reduction in glucagon responses. Fiber also markedly improved glucose tolerance in the NIDDMs without changing insulin or GIP but with a significant reduction in the glucagon responses. The NIDDMs were divided into two groups of six subjects, with and without autonomic neuropathy (AN). In NIDDMs without AN, glucose tolerance was improved by fiber without a change in insulin, IRG, or GIP. In diabetic subjects with AN, glucose tolerance was not improved, although glucagon levels were lowered and insulin and GIP responses were unchanged. It appears, therefore, that fiber improves glucose tolerance by altering factors other than insulin. It seems also that autonomic nervous supply to the gastrointestinal tract is important in mediating the effect.


Low muscle mass is associated with a higher risk of all-cause and cardiovascular disease-specific mortality in cancer survivors.
Individuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)-specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history. We used cohort data from the 1999-2006 and 2011-2014 National Health and Nutrition Examination Survey. Participants included 946 adults surviving for ≥1 since cancer diagnosis and a matched cohort (by age, sex, and race) without cancer history (N = 1857). LMM was defined by appendicular lean mass and body height (men <7.26 kg/m2, women <5.45 kg/m2). Death was ascertained via the National Death Index and cause of death was assessed via International Classification of Diseases, Tenth Revision. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI) of LMM. The mean age of cancer survivors and matched cohort was 60.6 y (SD 15) and 60.2 y (SD 14.9), respectively. The median follow-up was 10.5 y for survivors and 10.9 y for matched cohort. Overall, 22.2% of cancer survivors and 19.7% of the matched cohort had LMM, respectively. In all, 321 survivors (33.9%) and 495 participants (26.7%) in the matched cohort died during follow-up. CVD-specific deaths were identified in 58 survivors (6.1%) and 122 participants in the matched cohort (6.6%). The multivariable Cox model suggested that LMM was positively associated with all-cause (aHR, 1.73; 95% CI, 1.31-2.29) and CVD-specific (aHR, 2.13; 95% CI, 1.14-4.00) mortality in cancer survivors. The associations between LMM and risk for all-cause (aHR, 1.24; 95% CI, 0.98-1.56) and CVD-specific (aHR, 1.21; 95% CI, 0.75-1.93) mortality were not statistically significant in the matched cohort. Cancer survivors with LMM have an increased risk for all-cause and CVD-specific mortality. This increase appears to be larger than that in counterparts without cancer history.


A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease.
This study evaluated the anti-graft versus host disease (GVHD) potential of a combination of immunotoxins (IT), consisting of a murine CD3 (SPV-T3a) and CD7 (WT1) monoclonal antibody both conjugated to deglycosylated ricin A. In vitro efficacy data demonstrated that these IT act synergistically, resulting in an approximately 99% elimination of activated T cells at 10(-8 )mol/L (about 1.8 microg/mL). Because most natural killer (NK) cells are CD7(+), NK activity was inhibited as well. Apart from the killing mediated by ricin A, binding of SPV-T3a by itself impaired in vitro cytotoxic T-cell cytotoxicity. Flow cytometric analysis revealed that this was due to both modulation of the CD3/T-cell receptor complex and activation-induced cell death. These results warranted evaluation of the IT combination in patients with refractory acute GVHD in an ongoing pilot study. So far, 4 patients have been treated with 3 to 4 infusions of 2 or 4 mg/m(2) IT combination, administered intravenously at 48-hour intervals. The T(1/2) was 6.7 hours, and peak serum levels ranged from 258 to 3210 ng/mL. Drug-associated side effects were restricted to limited edema, fever, and a modest rise of creatine kinase levels. One patient developed low-titer antibodies against ricin A. Infusions were associated with an immediate drop of circulating T cells, followed by a more gradual but continuing elimination of T/NK cells. One patient mounted an extensive CD8 T-cell response directly after treatment, not accompanied with aggravating GVHD. Two patients showed nearly complete remission of GVHD, despite unresponsiveness to the extensive pretreatment. These findings justify further investigation of the IT combination for treatment of diseases mediated by T cells. (Blood. 2000;95:3693-3701)


Estimation of the number of virus particles transmitted by an insect vector.
Plant viruses are submitted to narrow population bottlenecks both during infection of their hosts and during horizontal transmission between host individuals. The size of bottlenecks exerted on virus populations during plant invasion has been estimated in a few pathosystems but is not addressed yet for horizontal transmission. Using competition for aphid transmission between two Potato virus Y variants, one of them being noninfectious but equally transmissible, we obtained estimates of the size of bottlenecks exerted on an insect-borne virus during its horizontal transmission. We found that an aphid transmitted on average 0.5-3.2 virus particles, which is extremely low compared with the census viral population into a plant. Such narrow bottlenecks emphasize the strength of stochastic events acting on virus populations, and we illustrate, in modeling virus emergence, why estimating this parameter is important.


Seagrass sedimentary deposits as security vaults and time capsules of the human past.
Seagrass meadows form valuable ecosystems, but are considered to have low cultural value due to limited research efforts in this field. We provide evidence that seagrass deposits play a hitherto unrealized central role in preserving valuable submerged archaeological and historical heritage across the world, while also providing an historical archive of human cultural development over time. We highlight three case studies showing the significance of seagrass in protecting underwater cultural heritage in Denmark, the Mediterranean and Australia. Moreover, we present an overview of additional evidence compiled from the literature. We emphasize that this important role of seagrasses is linked to their capacity to form thick sedimentary deposits, accumulating over time, thereby covering and sealing submerged archaeological heritage. Seagrass conservation and restoration are key to protecting this buried heritage while also supporting the role of seagrass deposits as carbon sinks as well as the many other important ecosystem functions of seagrasses.


Clinical characteristics and outcomes of elderly patients treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy in a real-world setting: data from the Israeli ICD Registry.
Elderly patients are underrepresented in clinical trials of device therapy. To provide real-world data regarding outcomes associated with device-based therapy in a large cohort of elderly patients enrolled in the Israeli ICD Registry. Between July 2010 and June 2012, a total of 2807 consecutive patients undergoing implanted cardioverter-defibrillator/cardiac resynchronization therapy-defibrillator (ICD/CRT-D) implantation were prospectively enrolled in the Israeli ICD Registry. For the present analysis, patients were categorized into 3 age groups: ≤60 years (n = 1378 [49%]), 61-75 years (n = 863 [31%]), and >75 years (n = 566 [20%]). Elderly patients (>75 years of age) had more comorbid conditions and were more likely to undergo CRT-D implantation (all P < .01). However, the rate of device-related complications associated with surgical reinterventions at 1 year was <3% regardless of age (P = .70 for the comparison among the 3 age groups). Multivariate analysis showed that the risk of heart failure or death and of appropriate ICD therapy for ventricular arrhythmias was significantly increased with increasing age among patients who received an ICD. In contrast, the age-related increase in the risk of all end points was attenuated among patients who received CRT-D devices (all P values for age-by-device-type interactions are <.05). In a real-world scenario, elderly patients (>75 years of age) comprise approximately 20% of the ICD/CRT-D recipients and experience a device reintervention rate similar to that of their younger counterparts. Our data suggest that the association between advanced age and adverse clinical outcomes is attenuated in elderly patients implanted with CRT-D devices.


Cellular DNA surrounding integration sites of an avian retrovirus.
The size of the direct repeats of cellular DNA next to a spleen necrosis virus (SNV) provirus from infected rat cells and the nature of the cellular DNA surrounding SNV integration sites in chicken DNA were studied. A five-base pair repeat, ATTTT, was observed at the SNV-rat cell junctions. Five of ten SNV proviruses from chicken cells were flanked by unique DNA and five others were flanked by repetitive DNA. No large rearrangements of cellular DNA at SNV integration sites were observed. A clone of uninfected chicken DNA containing the presumptive unoccupied integration site for one SNV provirus was obtained and part of it was sequenced. A small substitution, approximately 60 nucleotides, was observed at the site of virus DNA insertion. Its significance is not known.


Role of pH as a transduction device in triggering electrical and secretory responses in islet B cells.
Changes in pH alter the oscillatory pattern of glucose-induced electrical activity of mouse islet B cells, thereby supporting the hypothesis that changes in intracellular pH (pHi) resulting from glucose metabolism serve as a coupling factor between metabolic and cationic events. A decrease in pHi in the present of 11.1 mM glucose induces an increase in the duration of the active phase similar to that evoked by higher concentrations of glucose. Regulation of pHi appears to occur by Na:H and HCO3:Cl exchange in the plasma membrane, because inhibition by 0.1 mM amiloride and 0.5 mM 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS), respectively, induces constant spike activity in the presence of 11.1 mM glucose. If the pH coupling hypothesis is correct, then inhibition of the putative pH regulatory mechanisms and the subsequent decrease in pHi should elicit electrical activity in the presence of subthreshold glucose (less than 7.0 mM). Amiloride induced electrical activity (threshold) at 4.4 +/- 0.3 mM (mean +/- SEM) glucose. The threshold for DIDS was 5.4 +/- 0.2 glucose, whereas with glucose alone the threshold was achieved at 7.0 +/- 0.4 mM. Thus the generation of H+ by glucose may trigger changes in ionic conductances that induce the typical electrical response. Amiloride was found to elicit a secretory response at subthreshold glucose (4.2-7.0 mM) in perifused rat islets. This indicates that pH-induced changes in the ionic events in the B cells also play an important role in information transfer to the secretory complex.


The side-effects to CPAP treatment inventory: the development and initial validation of a new tool for the measurement of side-effects to CPAP treatment.
Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), but side-effects are common. No validated self-rating scale measuring side-effects to CPAP treatment exists today. The aim was to develop the side-effects to CPAP treatment inventory (SECI), and investigate the validity and reliability of the instrument among patients with OSAS. SECI was developed on the basis of: (1) in-depth interviews with 23 patients; (2) examination of the scientific literature and (3) consensus agreement of a multi-professional expert panel. This yielded 15 different types of side-effects related to CPAP treatment. Each side-effect has three sub-questions (scales): perceived frequency (a) and magnitude (b) of the side-effect, as well as its perceived impact on CPAP use (c). A cross-sectional descriptive design was used. A total of 329 patients with OSAS with an average use of CPAP treatment for 39 months (2 weeks to 182 months) were recruited. Data were collected with SECI, and obtained from medical records (clinical variables and data related to CPAP treatment). Construct validity was confirmed with factor analysis (principal component analysis with orthogonal rotation). A logical two-factor solution, the device subscale and symptom subscale, emerged across all three scales. The symptom subscale describing physical and psychological side-effects and the device subscale described mask and device-related side-effects. Internal consistency reliability of the three scales was good (Cronbach's α = 0.74-0.86) and acceptable for the subscales (Cronbach's α = 0.62-0.86). The satisfactory measurement properties of this new instrument are promising and indicate that SECI can be used to measure side-effects to CPAP treatment.


[Comparative efficacies of selenite and tetrathionate broth and Leifson- and Wilson-Blair agar for the isolation of salmonellae (author's transl)].
The statistical interpretation of the isolation of 3,581 Salmonella strains belonging to 30 species or serovars (S) shows that the efficacy of selenite and tetrathionate broth as enrichment media was of similar magnitude for 631 strains for 13 S. The tetrathionate broth was better in the case of 2,520 strains from 11 S and the selenite broth in 430 strains from 6 S including the two pathogenetic most important species S. typhi and S. schottmuelleri. Therefore, this point needs the unconditional use of selenite broth (Table 2). Wilson-Blair agar was more efficient than Leifson agar in the isolation of the most salmonella (Table 2). Also the percentage of suspicious and false-positive colonies on Leifson agar is higher and is due to more expensive work than on Wilson-Blair agar (Table 3).


Key dilemmas in prescribing and the provision of health.
Decision-making in health provision is rarely straightforward. Choices are probably easiest when trial data are clear and the consequences essentially trivial. As information becomes more speculative, outcomes more critical and the environment more hostile, dilemmas arise. These and related issues were addressed in the fifth annual Drug and Therapeutics Bulletin symposium 'Key Dilemmas in Prescribing and the Provision of Health,' which was held in March. Here we summarise the key views raised in the talks and subsequent discussion.


The complexity of patient adherence in orthopaedics: A qualitative study to identify barriers and develop strategies for adherence partnerships.
While the importance of patient adherence to treatment protocols is firmly accepted, a definition for adherence and mechanisms to address non-adherence are not well established. The goals of this study were to define adherence and identify barriers and enablers for adherence partnerships through the lens of the orthopaedic healthcare team. The qualitative study was designed using concepts from grounded theory. Eight focus groups, comprised of orthopaedic healthcare team members, were conducted to identify factors influencing orthopaedic patient adherence to treatment plans. Healthcare team members identified a range of factors affecting patient adherence. Participants conveyed that patient non-adherence can be a deliberate decision but can also result from barriers faced by the patient. Synthesis of themes identified distinct phases of adherence and culminated in the creation of a preliminary model that encapsulates healthcare team and patient factors impacting adherence, which was entitled, The Barriers and Enablers to Treatment Adherence (BETA) Model. The study findings alleviate the patient from the sole burden of adherence, recognising the influences that the healthcare team and system have on patients' ability to adhere. The BETA model of patient adherence represents the first step to mitigating non-adherence by providing a foundation for programmatic research aimed at developing and evaluating interventions and management strategies that empower healthcare teams to effectively equip patients for adherence, leading to optimised patient outcomes following orthopaedic interventions.


[Health and dietetics in medieval preventive medicine: the health regimen of Peter of Spain (thirteenth century)].
This text is an analysis of a preventive medical work, Liber de conservanda sanitate, composed in the thirteenth century by the Portuguese physician and doctor, Peter of Spain (?1210-1277). His work enables us to look at the conceptions of health and hygiene and understand the social role of university physicians in medieval preventive medicine. The work constantly displays the notion of the balance in corporal health between internal elements, or natural things (complexion, for example), and external ones, or non-natural things (air, sleep, exercise, food, baths, passions of the soul).


Reduced peanut sensitization with maternal peanut consumption and early peanut introduction while breastfeeding.
New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother-child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14-0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01-0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this "triple exposure" hypothesis.


Potent suppression of HIV-1 cell attachment by Kudzu root extract.
There is a constant need to improve antiretrovirals against HIV since therapy is limited by cost, side effects and the emergence of drug resistance. Kudzu is a climbing vine from which the root extract (Pueraria lobata), rich in isoflavones and saponins, has long been used in traditional Chinese medicine for a variety of purposes, from weight loss to alcoholism prevention. Here we show that Kudzu root extract significantly inhibits HIV-1 entry into cell lines, primary human CD4+T lymphocytes and macrophages, without cell-associated toxicity. Specifically, Kudzu inhibits the initial attachment of the viral particle to the cell surface, a mechanism that depends on the envelope glycoprotein gp120 but is independent from the HIV-1 cell receptor CD4 and co-receptors CXCR4/CCR5. This activity seems selective to lentiviruses since Kudzu inhibits HIV-2 and simian immunodeficiency virus, but does not interfere with Hepatitis C, Influenza, Zika Brazil and adenovirus infection. Importantly, depending on the dose, Kudzu can act synergistically or additively with the current antiretroviral cocktails against HIV-1 and can block viruses resistant to the fusion inhibitor Enfuvirtide. Together our results highlight Kudzu's root extract value as a supplement to current antiretroviral therapy against HIV.


Lateral rhinotomy. Indications, technique, and review of 226 patients.
Lateral rhinotomy provides excellent exposure of the interior of the nose, the paranasal sinuses, and the nasopharynx with minimal postoperative deformity. A review of 226 lateral rhinotomies performed at the Mayo Clinic, Rochester, Minn, from 1970 through 1979, was made to determine the versatility of this incision and some of its limitations and risks. The suitability of this technique to approach the wide variety of pathologic conditions that occur in the midfacial structures was reaffirmed.


Effects of nautical traffic and noise on foraging patterns of Mediterranean damselfish (Chromis chromis).
Chromis chromis is a key species in the Mediterranean marine coastal ecosystems where, in summer, recreational boating and its associated noise overlap. Anthropogenic noise could induce behavioural modifications in marine organisms, thereby affecting population dynamics. In the case of an important species for the ecosystem like C. chromis, this could rebound on the community structure. Here, we measured nautical traffic during the summer of 2007 in a Southern Mediterranean Marine Protected Area (MPA) and simultaneously the feeding behaviour of C. chromis was video-recorded, within both the no-take A-zone and the B-zone where recreational use is allowed. Feeding frequencies, escape reaction and school density were analysed. C. chromis specimens were also collected from 2007 to 2008 to evaluate their physiological state using the Body Condition Index as a proxy of feeding efficiency. The MPA was more exploited by nautical tourism during holidays than on weekdays, particularly in the middle of the day. Greater traffic volume corresponded with lower feeding frequencies. The escape reaction was longer in duration (>1 min) when boat passed nearby, while moored boats did not induce an escape response. We found no differences in density between schools in the A- and B-zones and worse body conditions among those individuals inhabiting the B-zone in one area only. Overall, our findings revealed a significant modification of the daily foraging habits of C. chromis due to boat noise, which was slightly buffered by no-take zones established within the MPA.


Neurokinin-1 receptor localisation in guinea pig autonomic ganglia.
We have used multiple-labelling immunohistochemistry and confocal microscopy to determine the distribution of immunoreactivity to the tachykinin neurokinin-1 (NK(1)) receptors in guinea pig sympathetic ganglia. Although nerve fibres containing immunoreactivity to substance P were common in all ganglia except the superior cervical ganglia, most neurons expressing NK(1) receptor immunoreactivity were not closely surrounded by pericellular baskets of substance P-immunoreactive boutons. Conversely, many neurons surrounded by baskets of substance P-immunoreactive boutons lacked NK(1) immunoreactivity. In the coeliac and inferior mesenteric ganglia, NK(1) receptor expression was restricted almost entirely to noradrenergic neurons that contained somatostatin immunoreactivity and projected to the enteric plexuses. In the lumbar chain and paracervical ganglia, NK(1) immunoreactivity was expressed by nonnoradrenergic vasodilator neurons containing immunoreactivity to vasoactive intestinal peptide. Taken together, our results show that sympathetic neurons in different functional pathways express NK(1) receptor immunoreactivity. However, the neurons that could respond to endogenously released substance P through NK(1) receptors may be distant from presynaptic release sites. These observations suggest that, in sympathetic ganglia, substance P may modulate ganglionic transmission through heterosynaptic actions on NK(1) receptors.


Estimates of smoking-related property costs in California multiunit housing.
We systematically evaluated smoking-related costs in multiunit housing. From 2008 to 2009, we surveyed California multiunit housing owners or managers on their past-year smoking-related costs and smoke-free policies. A total of 27.1% of respondents had incurred smoking-related costs (mean $4935), and 33.5% reported complete smoke-free policies, which lowered the likelihood of incurring smoking-related costs. Implementing statewide complete smoke-free policies may save multiunit housing property owners $ 18,094,254 annually.


Sex differences in mitochondrial respiratory function in human skeletal muscle.
Mitochondrial bioenergetic contributions to sex differences in human skeletal muscle metabolism remain poorly defined. The primary aim of this study was to determine whether mitochondrial respiratory kinetics differed between healthy young men and women in permeabilized skeletal muscle fibers. While men and women displayed similar ( P > 0.05) maximal respiration rates and abundance of mitochondrial/adenosine diphosphate (ADP) transport proteins, women had lower ( P < 0.05) mitochondrial ADP sensitivity (+30% apparent Km) and absolute respiration rates at a physiologically relevant ADP concentration (100 μM). Moreover, although men and women exhibited similar carnitine palmitoyl transferase-I protein content- and palmitoyl-CoA-supported respiration, women displayed greater sensitivity to malonyl-CoA-mediated respiratory inhibition. These data establish baseline sex differences in mitochondrial bioenergetics and provide the foundation for studying mitochondrial function within the context of metabolic perturbations and diseases that affect men and women differently.


Inorganic Phosphate and Sulfate Transport in S. cerevisiae.
Inorganic ions such as phosphate and sulfate are essential macronutrients required for a broad spectrum of cellular functions and their regulation. In a constantly fluctuating environment microorganisms have for their survival developed specific nutrient sensing and transport systems ensuring that the cellular nutrient needs are met. This chapter focuses on the S. cerevisiae plasma membrane localized transporters, of which some are strongly induced under conditions of nutrient scarcity and facilitate the active uptake of inorganic phosphate and sulfate. Recent advances in studying the properties of the high-affinity phosphate and sulfate transporters by means of site-directed mutagenesis have provided further insight into the molecular mechanisms contributing to substrate selectivity and transporter functionality of this important class of membrane transporters.


Enhancement of the conductivity detection signal in capillary electrophoresis systems using neutral cyclodextrins as sweeping agents.
Conductivity detection is a universal detection technique often encountered in electrophoretic separation systems, especially in modern chip-electrophoresis based devices. On the other hand, it is sparsely combined with another contemporary trend of enhancing limits of detection by means of various preconcentration strategies. This can be attributed to the fact that a preconcentration experimental setup usually brings about disturbances in a conductivity baseline. Sweeping with a neutral sweeping agent seems a good candidate for overcoming this problem. A neutral sweeping agent does not hinder the conductivity detection while a charged analyte may preconcentrate on its boundary due to a decrease in its effective mobility. This study investigates such sweeping systems theoretically, by means of computer simulations, and experimentally. A formula is provided for the reliable estimation of the preconcentration factor. Additionally, it is demonstrated that the conductivity signal can significantly benefit from slowing down the analyte and thus the overall signal enhancement can easily overweight amplification caused solely by the sweeping process. The overall enhancement factor can be deduced a priori from the linearized theory of electrophoresis implemented in the PeakMaster freeware. Sweeping by neutral cyclodextrin is demonstrated on an amplification of a conductivity signal of flurbiprofen in a real drug sample. Finally, a possible formation of unexpected system peaks in systems with a neutral sweeping agent is revealed by the computer simulation and confirmed experimentally.


Free jejunal mucosal patch graft reconstruction of the oropharynx.
We used microvascular anastomoses to transpose free pedicle jejunal mucosal patch grafts in seven patients. The procedure has been particularly helpful in rebuilding large intra-oral mucosal defects created by extensive resections for advanced carcinomas. Some of the benefits of this technique have included a one-stage procedure, which requires two to three weeks for healing; abundant donor tissue with characteristics similar to oral mucosa; near-normal facial appearance; and preservation of maximum tongue function. An unexpected benefit has been relief of annoying xerostomia by the jejunal mucous secretion. The most severe complication, which resulted in one death, was the excessive oral jejunal mucous secretion in the early postoperative period. It led to significant aspiration pneumonitis. To prevent this problem, we recommend a routine tracheostomy combined with rigorous pulmonary care whenever a jejunal patch graft is used.


The differentiation of hepatocyte-like cells from monkey embryonic stem cells.
Embryonic stem cells (ESC) hold great potential for the treatment of liver diseases. Here, we report the differentiation of rhesus macaque ESC along a hepatocyte lineage. The undifferentiated monkey ESC line, ORMES-6, was cultured in an optimal culture condition in an effort to differentiate them into hepatocyte-like cells in vitro. The functional efficacy of the differentiated hepatic cells was evaluated using RT-PCR for the expression of hepatocyte specific genes, and Western blot analysis and immunocytochemistry for hepatic proteins such as alpha-fetoprotein (AFP), albumin and alpha1-antitrypsin (alpha1-AT). Functional assays were performed using the periodic acid schiff (PAS) reaction and ELISA. The final yield of ESC-derived hepatocyte-like cells was measured by flow cytometry for cells that were transduced with a liver-specific lentivirus vector containing the alpha1-AT promoter driving the expression of green fluorescence protein (GFP). The treatment of monkey ESC with an optimal culture condition yielded hepatocyte-like cells that expressed albumin, alpha1-AT, AFP, hepatocyte nuclear factor 3beta, glucose-6-phophatase, and cytochrome P450 genes and proteins as determined by RT-PCR and Western blot analysis. Immunofluorescent staining showed the cells positive for albumin, AFP, and alpha1-AT. PAS staining demonstrated that the differentiated cells showed hepatocyte functional activity. Albumin could be detected in the medium after 20 days of differentiation. Flow cytometry data showed that 6.5 +/- 1.0% of the total differentiated cells were positive for GFP. These results suggest that by using a specific, empirically determined, culture condition, we were able to direct monkey ESC toward a hepatocyte lineage.


The role of endotoxin and the innate immune response in the pathophysiology of acute graft versus host disease.
Allogeneic stem cell transplantation (SCT) is an important therapy for a number of malignant diseases, and acute graft versus host disease (GVHD) and leukemic relapse remain the two major obstacles to successful outcomes of this treatment strategy. The therapeutic potential of allogeneic SCT relies on the graft versus leukemia (GVL) effect, during which donor T lymphocytes eradicate residual malignant cells via immunological mechanisms. Unfortunately, beneficial GVL effects are closely associated with the toxicity of GVHD. The pathophysiology of GVHD is complex and fundamentally depends upon aspects of adaptive immunity and interactions between donor T cells and foreign host tissue antigens. Recent work has revealed that components of the innate immune response and the secretion of inflammatory cytokine effectors are also important. In this context, experimental studies have demonstrated that loss of gastrointestinal (GI) tract integrity plays a major role in the amplification of systemic GVHD. Specifically, translocation of endotoxin across a damaged GI tract and into the circulation promotes local and systemic cytokine release. This effect perpetuates further gut mucosal injury and endotoxin leak, thus establishing a positive feedback loop for progressive target organ injury and systemic inflammation. Data obtained using murine SCT models have shown that disruption of the cellular activating effects of lipopolysaccharide (LPS) significantly reduces cytokine secretion and GVHD severity without altering T-cell responses to host antigens. These findings support a critical role for LPS in the early inflammatory events responsible for GVHD and suggest that strategies which target the innate immune response and LPS receptor-ligand interactions may help prevent GVHD while preserving donor T-cell responses and GVL activity.


International consensus (ICON) on: clinical consequences of mite hypersensitivity, a global problem.
Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the current knowledge on mite allergens, routes of sensitization, the genetics of IgE responses to mites, the epidemiologic aspects of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis, specific immunotherapeutic approaches, and prevention.


Development and function of CD94-deficient natural killer cells.
The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions.


[Combined injuries of the eye by shots from gas barrel guns for self defense].
Combined (mechanical and chemical) injury to the eye was induced by shooting from gas guns of 8 and 9 mm caliber to the eyes of biomannequins from a distance of 50 cm. Mechanical particles released during shot (intact and partially burnt gunpowder and other components of the shell) may be carrying a chemical on their surface, which, when getting into the wound channel of ocular membranes, diffuses to the adjacent tissues and injures them. These data necessitate comprehensive studies of injuries to the eyes caused by shots from gas barrel guns, which are to be carried out by clinical ophthalmologists, toxicologists, and forensic medics in order to identify all the possible consequences of injuries caused by irritants, accurately assess the duration of the posttraumatic process in the victims, and evaluate bodily injuries.


[Intellectual activities of twins. II. Heredity and environment].
A study was carried out of the relative role of the genotype and the environment on the variability of intellectual abilities in children of 7--16 years old. 118 twin pairs were studied by WISC method: 57 MZ and 61 DZ. It is established that every parameter of the intellectual activity is characterized by the definite component of phenotypic variance, i. e. by genetic and environmental components. With that the genetic variance of intellectual parameters is determined mainly by the additive interaction of genetic factors, and the environmental variance -- by intrafamily (random) factors. It is noted the essential role of genotype of the population variability of verbal intellectual parameters. Components of phenotypic variance intellectual parameters -- genetic (additive and dominant) and environmental (interfamily and intrafamily) are changing during the ontogenesis. The role of environmental factors is increased in variability of most intellectual characteristics in the age of 14--16 years, i. e. the intellectual behavior is becoming more supple in regard to the factors of environment.


Narcissistic disorders in clinical practice.
In this paper, the concept of narcissism in the psychoanalytic literature is reviewed and three uses of the term are defined, firstly, clinical narcissism, secondly, an innate force or tendency opposed to relationships and thirdly, narcissistic personality disorders. The latter can be further differentiated on the basis of the transference/countertransference into borderline (thin-skinned), aloof (thick-skinned) and as-if (false-self) narcissistic disorders. The characteristics of each of these patterns are described. The author suggests that narcissistic disorders arise when there is a failure of containment in infancy and childhood that gives rise to an ego-destructive super-ego leading to the evolving of a narcissistic organization. The libidinal defensive organization arises when parental failure of containment is the primary factor and destructive organization when the infant has an excess of object-hostility. Two case descriptions are given to illustrate the distinction between a predominantly destructive and a predominantly libidinal narcissistic disorder and the author suggests that both arise from the production, by projective identification, of a narcissistic relationship with an ego ideal in order to evade a relationship with a destructive parental super-ego.


Life events and depression in a community sample of siblings.
The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices. We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations. Life events showed sibling correlations of 0-37 for network events and between 0-10 and 0.19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects. Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.


Cardiovascular reactivity and oxidative stress in young and older adults: the African-PREDICT and SABPA studies.
Background: Oxidative stress and increased cardiovascular reactivity are associated with endothelial dysfunction and cardiovascular disease development. These factors along with early vascular compromise are more pronounced in black populations. We aimed to compare cardiovascular reactivity and investigate associations thereof with oxidative stress in two bi-ethnic cohorts (younger: 25.0 ± 3.19yrs; older: 44.7 ± 9.61yrs). Methods: Cardiovascular reactivity using the color-word conflict test was measured with the Finometer device. Oxidative stress markers included superoxide dismutase (SOD), γ-glutamyl transferase (γ-GT) and reactive oxygen species (ROS). Results: Black groups displayed greater cardiovascular responses to stress than white groups. In younger white participants, diastolic blood pressure (DBP) (β = 0.31; p = 0.001) and mean arterial blood pressure (MAP) (β = 0.28; p = 0.002) associated with ROS. In older black participants, DBP (β = 0.23; p = 0.009), MAP (β = 0.18; p = 0.033), stroke volume (β = -0.20; p = 0.023) and arterial compliance (β = -0.25; p = 0.005) associated with γ-GT. In older white participants, systolic blood pressure (β = -0.20; p = 0.006) and MAP (β = -0.19; p = 0.009) associated with SOD. Conclusions: In the older black group, cardiovascular reactivity associated with markers of glutathione metabolism, suggesting a possible compensatory up-regulation thereof in order to correct their heightened responses to stress. Independent of age, findings in the white groups support a regulatory role of ROS to maintain vascular tone during stress.


SLA2 is a prognostic marker in HNSCC and correlates with immune cell infiltration in the tumor microenvironment.
To investigate Src-like adaptor 2 gene (SLA2) expression in head and neck squamous cell carcinoma (HNSCC), its potential prognostic value, and its effect on immune cell infiltration. Through a variety of bioinformatics analyses, we extracted and analyzed data sets from the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), and Gene Expression Profile Interaction Analysis (GEPIA) to analyze the correlation between SLA2 and the prognosis, immune checkpoint, tumor microenvironment (TME) and immune cell infiltration of HNSCC, and to explore its potential oncogenic mechanism. To further explore the potential role of SLA2 in HNSCC by Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. SLA2 messenger ribonucleic acid (mRNA) levels were increased in HNSCC tumor tissues compared with normal tissues. In addition, we found that SLA2 may be an independent prognostic factor for HNSCC, and high SLA2 expression is associated with favorable prognosis in HNSCC. SLA2 expression was positively correlated with B cells, cluster of differentiation 8-positive T cells (CD8 + T cells), cluster of differentiation 4-positive T cells (CD4 + T cells), macrophages, neutrophil and dendritic cells infiltration. SLA2 has also been shown to co-express immune-related genes and immune checkpoints. Significant GO term analysis by Gene Set Enrichment Analysis (GSEA) indicated that genes correlated with SLA2 were located mainly in the side of membrane, receptor complex, secretory granule membrane, endocytic vesicle, membrane region, and endosome membrane, where they were involved in leukocyte cell-cell adhesion, response to interferon-gamma, and regulation of immune effector process. These related genes also served as antigen binding, cytokine receptor activity, phosphatidylinositol 3-kinase activity, peptide receptor activity, Src homology domain 3 (SH3) domain binding, and cytokine receptor binding. KEGG pathway analysis demonstrated that these genes related to SLA2 were mainly enriched in signal pathways, such as hematopoietic cell lineage, cell adhesion molecules (CAMs), natural killer cell mediated cytotoxicity, measles, and chemokine signaling pathway. SLA2 is increased in HNSCC, and high SLA2 expression is associated with favorable prognosis. SLA2 may affect tumor development by regulating tumor infiltrating cells in TME. SLA2 may be a potential target for immunotherapy.


Risk of postoperative hemorrhage after intracranial surgery after early nadroparin administration: results of a prospective study.
Early postoperative pharmacological prophylaxis of deep vein thrombosis after intracranial surgery is still a matter of debate because of concerns regarding the formation of postoperative hematoma. The objective of this study was to prospectively analyze the rate of postoperative hemorrhage during a 3-year period of early postoperative administration of the low molecular weight heparin nadroparin (Fraxiparin) plus compression stockings in a large cohort of patients undergoing intracranial surgery. A total of 2823 intracranial neurosurgical procedures, performed between June 1999 and 2002, were studied. Of these operations, 1319 (46.7%) were major intracranial surgical procedures (Group 1). Group 2 comprised 1504 operations (53.3%) considered to be minor surgical procedures (e.g., shunt procedures, biopsies). All patients except those with transnasal transsphenoidal removal of pituitary tumors underwent early postoperative imaging (computed tomography or magnetic resonance imaging) to determine postoperative hemorrhage. All significant postoperative hematomas (defined as those requiring surgical evacuation because of relevant space occupation and/or neurological deterioration) were treated surgically. Prophylaxis of venous thromboembolic events included early (<24 h) postoperative administration of 0.3 ml nadroparin subcutaneously plus intra- and postoperative compression stockings until discharge. Forty-three major postoperative hemorrhages (1.5%) were observed after 2823 intracranial procedures (95% confidence interval, 1.1-2.05). Forty-two (3.2%) of 1319 postoperative hematomas occurred in patients undergoing major intracranial procedures (Group 1). There was only 1 (0.07%) significant hemorrhage after 1504 minor intracranial procedures (Group 2). A subgroup analysis of patients who needed preoperative anticoagulation because of medical comorbidity did not reveal an increased frequency of postoperative hematoma when anticoagulation was stopped 24 hours before surgery P = 0.1, chi(2) test; 95% confidence interval, 0.89-3.0). This report describes the largest prospective study conducted to date to determine the hemorrhage rate after early postoperative anticoagulation. The results support the concept of postoperative pharmacological thromboembolic prophylaxis in patients undergoing intracranial surgery.


The correlation method for rapid monitoring of Escherichia coli in foods.
A new rapid method was developed to rapidly monitor Escherichia coli counts in foods. One ml of modified selective broth with 4-methylumbelliferyl beta-D-glucuronide and 1 ml of food sample were mixed in a sterile test tube and incubated at 37 degrees C. The positive reaction (fluorescence under u.v. light) was monitored at regular 30 min intervals. The positive reaction times in test tubes were compared with actual E. coli numbers from tested samples. The growth of E. coli in test tubes (broth) was much faster than growth on agar. The first experiment was performed to evaluate the rapid correlation method using pure E. coli cultures. The correlation between E. coli counts by the conventional plating method and positive reaction (fluorescence production) times in test tubes was highly agreeable (r(2) = 0 x 95). In the case of low E. coli numbers, such as 2 x 0 log10 cfu ml(-1), the rapid correlation method detected their presence after 10 h incubation. When highly contaminated samples were assayed (8 log10 cfu ml(-1)), the rapid correlation method detected the presence of E. coli after 4 h incubation. In the ground beef experiment, the correlation between fluorescence production time and actual E. coli numbers was also strongly agreeable (r(2) = 0 x 92). From these results, it is obvious that the new rapid method can rapidly monitor E. coli counts in foods. The results indicated that the new method saved about 10-14 h incubation time compared to conventional plating methods. The rapid correlation method required much shorter incubation times compared to conventional plating methods for monitoring E. coli.


DCE-MRI of Brain Fluid Barriers: In Vivo Water Cycling at the Human Choroid Plexus.
Metabolic deficits at brain-fluid barriers are an increasingly recognized feature of cognitive decline in older adults. At the blood-cerebrospinal fluid barrier, water is transported across the choroid plexus (CP) epithelium against large osmotic gradients via processes tightly coupled to activity of the sodium/potassium pump. Here, we quantify CP homeostatic water exchange using dynamic contrast-enhanced MRI and investigate the association of the water efflux rate constant (kco) with cognitive dysfunction in older individuals. Temporal changes in the longitudinal relaxation rate constant (R1) after contrast agent bolus injection were measured in a CP region of interest in 11 participants with mild cognitive dysfunction [CI; 73 ± 6 years] and 28 healthy controls [CN; 72 ± 7 years]. kco was determined from a modified two-site pharmacokinetic exchange analysis of the R1 time-course. Ktrans, a measure of contrast agent extravasation to the interstitial space was also determined. Cognitive function was assessed by neuropsychological test performance. kco averages 5.8 ± 2.7 s-1 in CN individuals and is reduced by 2.4 s-1 [ca. 40%] in CI subjects. Significant associations of kco with global cognition and multiple cognitive domains are observed. Ktrans averages 0.13 ± 0.07 min-1 and declines with age [-0.006 ± 0.002 min-1 yr-1], but shows no difference between CI and CN individuals or association with cognitive performance. Our findings suggest that the CP water efflux rate constant is associated with cognitive dysfunction and shows an age-related decline in later life, consistent with the metabolic disturbances that characterize brain aging.


Generators of middle- and long-latency auditory evoked potentials: implications from studies of patients with bitemporal lesions.
We recorded middle- and long-latency auditory evoked potentials (AEPs) in 5 patients (ages 39-72 years) with bilateral lesions of the superior temporal plane. Reconstructions of CT sections revealed that primary auditory cortex had been damaged bilaterally in four of the patients, while in the fifth an extensive left hemisphere lesion included primary auditory cortex while a right hemisphere lesion had damaged anterior auditory association areas but spared primary auditory cortex. Normal middle-latency AEPs (MAEPs) were recorded at the vertex electrode in all of the patients. In 3 of the 5 patients, MAEPs also showed normal coronal scalp distributions and were comparable in amplitude following stimulation of either ear. Two patients showed abnormalities. In one case, Na (latency 17 msec)-Pa (latency 30 msec) amplitudes were reduced over both hemispheres following stimulation of the ear contralateral to the more extensive lesion. In another, with both subcortical and cortical involvement, the Pa was abolished over the hemisphere with the more extensive lesion. Long-latency AEPs were normal in 2 patients whose lesions were largely confined to the superior temporal plane. In 2 patients with lesions extending into the inferior parietal lobe, N1s were abolished bilaterally. In the fifth patient, the N1 showed a slight reduction over the hemisphere with the more extensive lesion. Middle- and long-latency AEPs were differentially affected by some lesions. For example, patients with absent N1s could produce normal Pas. A review of these results and those of previous studies of bitemporal patients suggests that abnormalities in middle- and long-latency AEPs do not necessarily reflect damage to primary auditory cortex per se, but rather the degree of damage to adjacent areas. Abnormalities in MAEPs are associated with subcortical lesions, or cortical lesions extensive enough to denervate thalamic projection nuclei. Abnormalities in the long-latency N1 reflect lesion extension into the multi-modal areas of the inferior parietal lobule. This area appears to exert a critical modulatory influence over N1 generators outside of the superior temporal plane.


Studying C-reactive protein and D-dimer levels in blood may prevent severe complications: A study in Bangladeshi COVID-19 patients.
The ongoing COVID-19 pandemic has been a scientific, medical and social challenge. Since clinical course of this disease is largely unpredictable and can develop rapidly causing severe complications, it is important to identify laboratory biomarkers, which may help to classify patient's severity during initial stage. Previous studies have suggested C-reactive protein (inflammatory) and D-dimer (biochemical) as an effective biomarker. The differential severity in patients across the world and our limited understanding in the progression of the disease calls for a multi-country analysis for biomarkers. Therefore, we have analyzed these biomarkers among 228 Bangladeshi COVID-19 patients. We observed significant association of COVID-19 severity with these two biomarkers. Thus, we suggest to use these biomarkers for Bangladeshi COVID-19 patients for better disease monitoring. Such validated preventive measures may decrease the case fatality ratio substantially.


ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors.
Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases.


Liposome-encapsulated chemotherapy: Current evidence for its use in companion animals.
Cytotoxic drugs encapsulated into liposomes were originally designed to increase the anticancer response, while minimizing off-target adverse effects. The first liposomal chemotherapeutic drug was approved for use in humans more than 20 years ago, and the first publication regarding its use in a canine cancer patient was published shortly thereafter. Regardless, no general application for liposomal cytotoxic drugs has been established in veterinary oncology till now. Due to the popularity of canines as experimental models for pharmacokinetic analyses and toxicity studies, multiple publications exist describing various liposomal drugs in healthy dogs. Also, some evidence for its use in veterinary cancer patients exists, especially in canine lymphoma, canine splenic hemangiosarcoma and feline soft tissue sarcoma, however, the results have not been overwhelming. Reasons for this may be related to inherent issues with the enhanced permeability and retention effect, the tumour phenomenon which liposomal drugs exploit. This effect seems very heterogeneously distributed in the tumour. Also, it is potentially not as ubiquitously occurring as once thought, and it may prove important to select patients for liposomal therapy on an individual, non-histology-oriented, basis. Concurrently, new developments with active-release modified liposomes in experimental models and humans will likely be relevant for veterinary patients as well, and holds the potential to improve the therapeutic response. It, however, does not resolve the other challenges that liposomal chemotherapy faces, and more work still needs to be done to determine which veterinary patients may benefit the most from liposomal chemotherapy.


Response of plants to ectomycorrhizae in N-limited conditions: which factors determine its variation?
In the present work, the following hypotheses were tested: (1) the negative effects of mycorrhization over host plant productivity in N-limited conditions are due to N retention by the fungal partner and not due to excessive C drainage; (2) If mycorrhization results in decreased N uptake, the host plant decreases its C investment in fungal growth. The effects of mycorrhization over a wide range of combinations between N availability, N concentration in plant tissues, and degree of mycorrhizal colonization were studied in Pinus pinaster L. mycorrhizal with Pisolithus tinctorius. Several plant productivity parameters, the seedlings' N status, chl a fluorescence (JIP test), and mycorrhizal colonization were measured. N was always limiting. A gradient of mycorrhizal effects over the host plant's growth and vitality was successfully obtained. The mycorrhizal effects on plant growth and N uptake were very strongly and positively correlated, and no evidence was found of a C limitation to growth, confirming hypothesis 1. Indications were found that the plants continued to provide C to the fungus although the N supplied by it was increasingly lower, denying hypothesis 2. A new index, the mycorrhizal N demand-supply balance, was found to efficiently explain, and to have a curvilinear relation with, the variation in response to mycorrhization. The mycorrhizal effect on host plant growth was not related to a negative effect on its photosynthetic performance and, therefore, reflected changes in resource allocation between host plant and mycorrhizal fungus, not in plant vitality.


T cells specific to multiple Bet v 1 peptides are highly cross-reactive toward the corresponding peptides from the homologous group of tree pollens.
Allergens from Fagales trees frequently cause spring allergy in Europe, North America, and some parts of Asia. The definition of the birch homologous group, which includes birch (Bet v), oak (Que a), alder (Aln g), hazel (Cor a), hornbeam (Car b), beech (Fag s), and chestnut (Cas s), is based on high allergen sequence identity and extensive IgE cross-reactivity. Clinical effect was seen during the alder/hazel, birch, and oak pollen seasons after treatment with tree SLIT-tablets containing only birch allergen extract. Here, we characterize T-cell reactivity with respect to epitope specificities and cross-reactivity toward various Bet v 1 family members, (PR-10/group 1 major allergens). This cross-reactivity may be part of the immunological basis of clinical effect or cross-protection when exposed to birch homologous tree species. T-cell lines were generated from 29 birch-allergic individuals through stimulation of peripheral blood mononuclear cells (PBMCs) with birch/Bet v or oak/Que a allergen extracts. T-cell responses to allergen extracts, purified group 1 allergens, and overlapping 20-mer peptides (Bet v 1, Aln g 1, Cor a 1, and Que a 1) were investigated by T-cell proliferation and cytokine production. Cross-reactivity was evaluated based on Pearson's correlations of response strength and further investigated by flow cytometry using tetramer staining for homologous peptide pairs. T-cell reactivity toward extracts and group 1 allergens from across the birch homologous group was observed for birch/Bet v as well as oak/Que a T-cell lines. T-cell lines responded to multiple Bet v 1 homologous peptides from Aln g 1 and Cor a 1 and a subset of Que a 1 peptides. Significant Pearson's correlations between frequently recognized peptides derived from Bet v 1 and the corresponding peptides derived from alder, hazel, and oak strongly supported the T-cell cross-reactivity toward these allergens. Cross-reactivity between birch and birch homologous peptides was confirmed by pMHCII tetramer staining. T cells from birch tree pollen allergic individuals respond to multiple trees within the birch homologous group in accordance with the level of sequence homology between Bet v 1 family members, (PR-10 allergens) from these allergen sources, confirming the basis for clinical cross-protection.


[Efficiency of microbe filtration of air filter for rearing germfree animals (author's transl)].
Filtration efficiency of 3 types of air filter frame and cylinder (Fig. 1) was examined by culture of the air obtained from the operating isolators at intervals of 3 to 21 days. The air of isolator was bubled in 30 ml of nutrient broth for 30 or 120 minutes (4approximately15 l/min.) and each of 1 ml of the broth was inoculated into thioglycollate medium (TGC), cooked meat medium (CMM), heart infustion broth (HIB) and glucose peptone water (GPW). The media were incubated for 7 to 14 days at 30 or 25 degrees C. As seen in Table 1, microbes could be effectively removed through all types of filter for over 10 months, though there were a very few positive cases suggesting technically acidental contamination at sampling.


Polarimetric surface plasmon resonance imaging biosensor.
We report the realization of a polarimetric surface plasmon resonance imaging system capable of dynamically resolving a change in the optical anisotropy of biochemical films. Anisotropies as small as 10(-3) refractive index unit on nanometer-thick samples can be resolved. As an example, we present here the dynamical anisotropy obtained by the electrical patterning of a film consisting of a self-assembled monolayer deposited on gold, covered with a phospholipid hemimembrane.


Earlier age of smoking initiation may not predict heavier cigarette consumption in later adolescence.
Previous studies suggest that earlier cigarette smoking initiation in adolescence predicts greater cigarette consumption later in adolescence or adulthood. Results from these studies have been used to inform interventions for adolescent smoking. However, previous studies suffer from several important methodological limitations. The objective of the present study was to address these limitations by longitudinally and prospectively examining whether and how age of initiation of smoking among adolescents predicts cigarette consumption by age 16 or 17. Participants completed an in-class survey every 6 months for 2-3 school years. Participants included 395 adolescents (Mean age=14 years at baseline; 53.2% female) from two public high schools in Northern California (Schools A and B) who completed self-report measures of smoking initiation, number of friends who smoke, and number of whole cigarettes smoked by the final survey time point. Adolescents who were older when they first smoked one whole cigarette were 5.3 to 14.6 times more likely in School A and 2.9 to 4.3 times more likely in School B to have smoked a greater number of cigarettes by age 16 or 17. Results suggested that earlier smoking initiation may not lead to heavier cigarette consumption later in time, as has been previously shown. There may be a period of heightened vulnerability in mid- or late adolescence where smoking experimentation is more likely to lead to greater cigarette consumption. Targeting prevention efforts to adolescents aged 14 to 17 years may further reduce smoking initiation among youth, thus limiting subsequent smoking-related morbidity and mortality in adulthood.


High electrical conductivity and high porosity in a Guest@MOF material: evidence of TCNQ ordering within Cu3BTC2 micropores.
The host-guest system TCNQ@Cu3BTC2 (TCNQ = 7,7,8,8-tetracyanoquinodimethane, BTC = 1,3,5-benzenetricarboxylate) is a striking example of how semiconductivity can be introduced by guest incorporation in an otherwise insulating parent material. Exhibiting both microporosity and semiconducting behavior such materials offer exciting opportunities as next-generation sensor materials. Here, we apply a solvent-free vapor phase loading under rigorous exclusion of moisture, obtaining a series of the general formula xTCNQ@Cu3BTC2 (0 ≤ x ≤ 1.0). By using powder X-ray diffraction, infrared and X-ray absorption spectroscopy together with scanning electron microscopy and porosimetry, we provide the first structural evidence for a systematic preferential arrangement of TCNQ along the (111) lattice plane and the bridging coordination motif to two neighbouring Cu-paddlewheels, as was predicted by theory. For 1.0TCNQ@Cu3BTC2 we find a specific electrical conductivity of up to 1.5 × 10-4 S cm-1 whilst maintaining a high BET surface area of 573.7 m2 g-1. These values are unmatched by MOFs with equally high electrical conductivity, making the material attractive for applications such as super capacitors and chemiresistors. Our results represent the crucial missing link needed to firmly establish the structure-property relationship revealed in TCNQ@Cu3BTC2, thereby creating a sound basis for using this as a design principle for electrically conducting MOFs.


Group versus individual academic detailing to improve the use of antihypertensive medications in primary care: a cluster-randomized controlled trial.
To compare group versus individual academic detailing to increase diuretic or beta-blocker use in hypertension. We conducted a cluster-randomized controlled trial in a large health maintenance organization. Subjects (N=9820) were patients with newly treated hypertension in the year preceding the intervention (N=3692), the 9 months following the intervention (N=3556), and the second year following intervention (N=2572). We randomly allocated 3 practice sites to group detailing (N=227 prescribers), 3 to individual detailing (N=235 prescribers), and 3 to usual care (N=319 prescribers). Individual detailing entailed a physician-educator meeting individually with clinicians to address barriers to prescribing guideline-recommended medications. The group detailing intervention incorporated the same social marketing principles in small groups of clinicians. In the first year following the intervention, the rates of diuretic or beta-blocker use increased by 13.2% in the group detailing practices, 12.5% in the individual detailing practices, and 6.2% in the usual care practices. As compared with usual care practices, diuretic or beta-blocker use was more likely in group detailing practices (adjusted odds ratio (OR), 1.40; 95% confidence interval (CI), 1.11 - 1.76) and individual detailing practices (adjusted OR, 1.30; 95% CI, 0.95 - 1.79). Neither intervention affected blood pressure control. Two years following this single-visit intervention, there was still a trend suggesting a persistent effect of individual (OR, 1.22; 95% CI, 0.92 - 1.62), but not group, detailing (OR, 1.06; 95% CI, 0.80 - 1.39), as compared with usual care. Both group and individual academic detailing improved antihypertensive prescribing over and above usual care but may require reinforcement to sustain improvements.


DNA-binding properties of Smc6, a core component of the Smc5-6 DNA repair complex.
The Smc5-6 complex is an essential regulator of chromosome integrity and a key component of the DNA damage response. As an essential DNA repair factor, the Smc5-6 complex is expected to interact with DNA and/or chromatin during the execution of its functions. How the Smc6 protein promotes the binding of the Smc5-6 complex to DNA lesions is currently unknown. We show here that Smc6 is a strong DNA-binding protein with a clear preference for single-stranded DNA substrates. Importantly, Smc6 associates with DNA in the absence of other Smc5-6 complex components and its activity is modulated by nucleotides. Our results also show that the minimal size of single-stranded DNA required for tight association with Smc6 is ~60 nucleotides in length. Taken together, our results suggest that Smc6 contributes to DNA repair in vivo by targeting the Smc5-6 complex to single-stranded DNA substrates created during the processes of homologous recombination and/or DNA replication.


During IVF treatment patient preference shifts from singletons towards twins but only a few patients show an actual reversal of preference.
Knowledge of patients' preferences for elective single embryo transfer (eSET) or double embryo transfer (DET) and for singletons or twins is of great importance in counselling for embryo transfer (ET) strategies. In this study, the stability of IVF patients' preferences over time for either a healthy single child or healthy twins was measured and we investigated which factors could explain preference shifts. Infertile women (n = 177) who participated in an RCT comparing one cycle eSET with one cycle DET were included. A satisfaction questionnaire was developed to measure patient preferences and attitudes at two moments in time, i.e. at 2 weeks before ET and at 2 weeks following ET, after the results of the pregnancy test. Regression analysis examined the effect of several variables on preference shifts. Before ET, most patients expressed a preference for a singleton, whereas most patients were indifferent 2 weeks after ET, resulting in an overall preference shift towards twins (P = 0.002; n = 145). Overall, 62% of patients showed a preference shift. Preference shifts were explained by patients' global satisfaction of the information given by the fertility clinic staff received by the fertility clinic staff, and an interaction between the occurrence of pregnancy and transfer policy (eSET or DET). In general, patients' preferences for a singleton or twins are not stable during IVF treatment. Possible explanations of a shift in preference are that pregnant patients attuned their preferences to what they expect their pregnancy to result in, whereas non-pregnant patients shifted towards a preference for twins in order to be able to fulfil their ultimate child wish.


Virus transmission by subcutaneous jet injection.
An animal model was used to establish the risk of transmitting a virus infection by subcutaneous jet injection. Virus transmission was studied with mice chronically infected with LDH virus. The virus infection was transmitted by subcutaneous jet injection in 16 cases out of 49. Other routes of cross-infection were ruled out. Before using the jet injector as a harmless instrument for mass subcutaneous injection, further experiments on the risks of virus transmission should be performed.


Energetic Control of Redox-Active Polymers toward Safe Organic Bioelectronic Materials.
Avoiding faradaic side reactions during the operation of electrochemical devices is important to enhance the device stability, to achieve low power consumption, and to prevent the formation of reactive side-products. This is particularly important for bioelectronic devices, which are designed to operate in biological systems. While redox-active materials based on conducting and semiconducting polymers represent an exciting class of materials for bioelectronic devices, they are susceptible to electrochemical side-reactions with molecular oxygen during device operation. Here, electrochemical side reactions with molecular oxygen are shown to occur during organic electrochemical transistor (OECT) operation using high-performance, state-of-the-art OECT materials. Depending on the choice of the active material, such reactions yield hydrogen peroxide (H2 O2 ), a reactive side-product, which may be harmful to the local biological environment and may also accelerate device degradation. A design strategy is reported for the development of redox-active organic semiconductors based on donor-acceptor copolymers that prevents the formation of H2 O2 during device operation. This study elucidates the previously overlooked side-reactions between redox-active conjugated polymers and molecular oxygen in electrochemical devices for bioelectronics, which is critical for the operation of electrolyte-gated devices in application-relevant environments.


Association of low prostate-specific antigen concentration and panhypopituitarism.
To report the association of undetectable or very low prostate-specific antigen (PSA) concentrations with hypopituitarism. We present a case series of 4 patients with low or undetectable PSA concentrations and associated panhypopituitarism and summarize the clinical presentation and pertinent laboratory and radiologic findings. We review related literature and discuss possible mechanisms explaining the described association. Four men with PSA values below the second percentile of a healthy population had hypopituitarism. In 3 men, low PSA concentrations were noted before large pituitary tumors were diagnosed. No man had headaches, visual problems, or other symptoms that were severe enough to prompt a search for tumor. All 4 patients had undetectable total testosterone levels. Luteinizing hormone and follicle-stimulating hormone levels were low to low-normal in 3 of the 4 patients. Baseline growth hormone level was low in 1 patient and undetectable in the other 3. The insulinlike growth factor 1 concentration was less than 73 ng/mL in each patient. We believe that the association of low PSA concentrations and hypopituitarism is not incidental and that the extremely low PSA values in this case series were a consequence of both gonadal and growth hormone deficiency. We suggest that low PSA is a marker of combined profound testosterone and growth hormone deficiency in men with panhypopituitarism. This marker is important because PSA is frequently measured during routine health care visits; a low concentration may be the first clue to the presence of hypopituitarism in an otherwise asymptomatic patient.