Pollen dispersal in fragmented populations of the dioecious wind-pollinated tree, Allocasuarina verticillata (drooping sheoak, drooping she-oak; Allocasuarinaceae).
Vegetation clearing, land modification and agricultural intensification have impacted on many ecological communities around the world. Understanding how species respond to fragmentation and the scales over which functionality is retained, can be critical for managing biodiversity in agricultural landscapes. Allocasuarina verticillata (drooping sheoak, drooping she-oak) is a dioecious, wind-pollinated and -dispersed species with key conservation values across southeastern Australia. But vegetation clearing associated with agricultural expansion has reduced the abundance and spatial distribution of this species in many regions. Spatial genetic structure, relatedness among trees, pollen dispersal and mating patterns were examined in fragmented A. verticillata populations selected to represent the types of remnants that now characterise this species. Short scale spatial genetic structure (5-25 m) and relatedness among trees were observed in most populations. Unexpectedly, the two male trees closest to each female did not have a reproductive advantage accounting for only 4-15% of the seed produced in larger populations. Biparental inbreeding was also generally low (<4%) with limited evidence of seed crop domination by some male trees. More male trees contributed to seed crops in linear remnants (mean 17) compared to those from patch remnants (mean 11.3) which may reflect differences in pollen dispersal within the two remnant types. On average, pollen travels ~100 m irrespective of remnant type but was also detected to have dispersed as far as 1 km in open landscapes. Low biparental inbreeding, limited reproductive assurance for near-neighbour and probably related males and variability in the distances over which females sample pollen pools suggest that some mechanism to prevent matings between relatives exists in this species.


Clinical correlates of insomnia in patients with acute coronary syndrome.
This study sought to examine the prevalence of insomnia and its association with depression, anxiety, and medical comorbidities in patients after an acute coronary syndrome (ACS). Insomnia increases risk of recurrent cardiac events in ACS patients, but little is known about the prevalence and clinical correlates of insomnia in this setting. Patients (n = 102, 58.3 ± 10.6 years-old) admitted for ACS to a cardiology service at an urban academic medical center completed the Insomnia Severity Index, Epworth Sleepiness Scale, and measures of depression and anxiety. A subset (n = 20) completed ambulatory polysomnography (PSG) in their homes several weeks after discharge. Moderate or severe insomnia was reported by 37% of patients during hospitalization and was associated with 76 minutes more wake after sleep onset measured by home PSG. Although depression and insomnia were strongly associated, about 1 in 4 patients with insomnia did not report significant depressive symptoms. Sleep apnea was documented in 80% of patients on PSG, but insomnia was not associated with sleep apnea, periodic limb movements, demographic factors, or medical conditions other than liver disease. Insomnia is present in over one-third of ACS patients during hospitalization, but at-risk patients could not be readily identified by demographic or medical factors or by depression symptoms.


Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations.
Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (> or = 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 < or = standardized HR < or = 1.67; 0.046 < or = P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P > or = .22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.


Cognitive test results are associated with mortality and rehospitalization in heart failure: Swedish prospective cohort study.
We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort. Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making Test A, and Symbol Digit Modalities Test. The mean follow-up time censored at rehospitalization or death was 13 months (interquartile range, 14) and 28 months (interquartile range, 29), respectively. Relations between cognitive test results, mortality, and rehospitalization risk were analysed using multivariable Cox regression model adjusted for age, sex, body mass index, systolic blood pressure, atrial fibrillation, diabetes, smoking, educational level, New York Heart Association class, and prior cardiovascular disease. A total of 80 patients (29%) had signs of cognitive impairment (MoCA score < 23 points). In the fully adjusted Cox regression model using standardized values per 1 SD change of each cognitive test, lower score on MoCA [hazard ratio (HR), 0.75; confidence interval (CI), 0.60-0.95; P = 0.016] and Symbol Digit Modalities Test (HR, 0.66; CI, 0.48-0.90; P = 0.008) yielded significant associations with increased mortality. Rehospitalization risk (n = 173; 62%) was significantly associated with lower MoCA score (HR, 0.84; CI, 0.71-0.99; P = 0.033). Two included cognitive tests were associated with mortality in hospitalized HF patients, independently of traditional risk factors. In addition, worse cognitive test scores on MoCA heralded increased risk of rehospitalization.


Different immunohistochemical levels of Hsp60 and Hsp70 in a subset of brain tumors and putative role of Hsp60 in neuroepithelial tumorigenesis.
In this work we analysed, by immunohistochemistry, a series of brain tumors to detect the levels and cellular distribution of Hsp60 and Hsp70. We found that Hsp60 levels were significantly higher than those of Hsp70 in neuroepithelial tumors, while levels of both molecules were not significantly different from each other in meningeal neoplasms. In particular, Hsp60 immunopositivity was present mainly at the cytoplasmic level, while Hsp70 immunopositivity was found both in the cytoplasm and in the nucleus of tumor cells. The levels of these molecules in healthy control cells were always very low. Finally, Hsp60 and Hsp70 levels did not correlate with the different types (WHO grade) of neoplasm. Our results are partially in agreement with previous studies and suggest that Hsp60 is not increased by a passive phenomenon (e.g., due to the stress caused by the peritumor environment on cancer cells) but may be actively implicated in tumor progression, e.g. inhibiting tumor cell death or antitumor immune system response, as already postulated in vitro. We also briefly discuss the most recent publications on the extramitochondrial localization of Hsp60 in tumor cells and its role in tumor progression.


Treating PTSD in Pregnant and Postpartum Rural Women with Substance Use Disorders.
The co-occurrence of posttraumatic stress disorder and substance use disorder (PTSD-SUD) can pose significant problems for rural pregnant and postpartum women (PPW) and the well-being of their children. Although effective treatments exist, PPW experience limitations in their ability to access and engage in treatment that may be compounded by various aspects of rural settings, so providers must be attentive to these barriers in order to address this pressing public health need. In addition, as part of increasing rural access to care, it is important to consider the costs and benefits to PPW of selecting exposure-based techniques (e.g., prolonged exposure) to disseminate. The current article discusses the treatment of PTSD-SUD in rural PPW in the context of the authors' experiences providing an exposure-based cognitive behavioral treatment for PTSD in this population. Barriers to treatment access and engagement are discussed and recommendations are provided.


[Teaching of the scientific method in the basic training of the health professional].
In this article the authors explore an innovative methodological proposal for the teaching of research. They begin with an analysis of the overall critical situation, the lack of education and training in that field for health manpower, and the need to develop research as a scientific approach to the solution of problems. They also address the existing need for integrating scientific work with learning experiences in the health services setting, as a contribution to improved care and practices. On this basis, it is proposed that research should be included throughout the learning-teaching process as a dynamic methodological instrument for training people in applying the scientific method, to develop a critical and thoughtful attitude, and to conduct or participate in research projects that may help to improve the quality of life and health of the population. Under this view of professional training in the health area, they discuss some of the principles and characteristics that should be inherent in the teaching of research, which should be used as a unifying axis and be conducted from the outset of the professional training program as an ongoing, progressive, increasingly complex activity intimately bound up with the health services. This comprehensive view requires an interdisciplinary and multidisciplinary approach in the development of studies which will make an important contribution in the quest for solutions to complex problems. For the application of the proposed methodology, a few essential minimum conditions must be present, including: training of the teaching staff to be responsible for conducting the instruction and practice of integrated research at different levels and in both vertical and horizontal directions; and the assimilation of teachers into the research process through practical projects, since the teacher must not be limited to a theoretical knowledge of the subject. However, if this proves impossible when the time comes to start applying the methodology, and teachers are available who could develop this axis, they may assume responsibility, while at the same time training other teachers.


Assessing Anxiety-Related Impairment in Children and Adolescents.
Anxiety disorders (ADs) frequently lead to significant impairment across important domains of youth functioning. Yet until recently, clinical research and assessment have largely neglected the measurement of anxiety-related impairment. In this article, we review the evidence for five extant rating scales of youth anxiety-related impairment, guided by widely used evaluative criteria. Emerging psychometric data show the potential utility of these rating scales for achieving different assessment functions. Of the five scales, the Child Anxiety Impact Scale, particularly the parent-report version, has been the most researched one. Promising psychometric data support its use for assessing anxiety-related impairment in school, social, and family/home domains of functioning. We conclude with recommendations for growing this research base and for incorporating these rating scales into the youth AD clinical and research assessment process.


Vasopressin-elicited water and urea permeabilities are altered in IMCD in hypercalcemic rats.
To investigate how hypercalcemia blunts renal concentrating ability, alterations in basal and arginine vasopressin (AVP)-elicited osmotic water (Pf) and urea (Purea) permeabilities were measured in isolated perfused terminal inner medullary collecting ducts (IMCD) from control and chronically hypercalcemic rats after dihydrotachysterol (DHT) (M. Levi, L. Peterson, and T. Berl. Kidney Int. 23: 489-497, 1983) treatment. The IMCD Pf of DHT-treated rats did not increase significantly after AVP and was accompanied by a significant 87 +/- 4% reduction in aquaporin-2 (AQP-2) protein but not mRNA. In contrast, both basal and AVP-elicited IMCD Purea from DHT rats were significantly increased and accompanied by a significant 41 +/- 11% increase in AVP-regulated urea transporter protein content. Immunoblotting with anti-calcium/polyvalent cation-sensing receptor protein (CaR) antiserum revealed specific alterations in CaR bands in endosomes purified from the apical membranes of inner medulla of DHT rats. These data are the first detailed analyses of hypercalcemia-induced alterations in AVP-regulated permeabilities and membrane transporters in IMCD. We conclude that selective alterations in IMCD transport occur in hypercalcemia, permitting the body to dispose of excess calcium without forming calcium-containing renal stones.


Capillary electrophoresis for the monitoring of phenolic compounds in bioprocesses.
Hydrolysates of lignocellulosic biomass, used as substrates for the sustainable production of fuels and chemicals often contain high amounts of phenolic compounds inhibiting the production microbiota. Quantification of these inhibitor compounds may help to understand possible difficulties in bioprocessing and further the development of more efficient, robust and tolerable processes. A separation method based on capillary electrophoresis with UV detection was developed for the simultaneous quantification of 10 phenolic compounds that may have inhibitor properties. Intraday relative standard deviations were less than 0.7% for migration times and between 2.6% and 6.4% for peak areas. Interday relative standard deviations were less than 3.0% for migration times and between 5.0% and 7.2% for peak areas. The method was applied to demonstrate that Saccharomyces cerevisiae was able to decrease the concentrations of vanillin, coniferyl aldehyde, syringaldehyde, acetoguaiacone and cinnamic acid during the cultivation, whereas the concentrations of phenols increased.


Critical assessment of hydrogen effects on the slip transmission across grain boundaries in α -Fe.
Grain boundaries (GBs) play a fundamental role in the strengthening mechanism of crystalline structures by acting as an impediment to dislocation motion. However, the presence of an aggressive environment such as hydrogen increases the susceptibility to intergranular fracture. Further, there is a lack of systematic investigations exploring the role of hydrogen on the dislocation-grain-boundary (DGB) interactions. Thus, in this work, the effect of hydrogen on the interactions between a screw dislocation and 〈111〉 tilt GBs in α-Fe were examined. Our simulations reveal that the outcome of the DGB interaction strongly depends on the underlying GB dislocation network. Further, there exists a strong correlation between the GB energy and the energy barrier for slip transmission. In other words, GBs with lower interfacial energy demonstrate a higher barrier for slip transmission. The introduction of hydrogen along the GB causes the energy barrier for slip transmission to increase consistently for all of the GBs examined. The energy balance for a crack initiation in the presence of hydrogen was examined with the help of our observations and previous findings. It was found that the presence of hydrogen increases the strain energy stored within the GB which could lead to a transgranular-to-intergranular fracture mode transition.


Breast cancer during pregnancy: quantifying the risk of treatment delay.
To quantify the risk of axillary nodal metastases due to delayed treatment of breast cancer during pregnancy. A mathematical model using recently published data was developed to correlate primary breast tumor size with the percentage of pathologically positive axillary lymph nodes. Using this relationship obtained from pathologic data and the accepted relationship of tumor growth and time, Y2 = Y1e(In2)n/DT, an equation estimating the increased risk of axillary metastases due to each day of treatment delay was derived: delta X = 3.7 n/DT, where X = percent positive axillary lymph nodes, n = number of days delay in treatment, and DT = tumor doubling time. A 1-month delay in treatment for an early-stage primary breast cancer with a 130-day doubling time increases the risk of axillary lymph node involvement by 0.9%. A 3-month delay increases the risk by 2.6%, and a 6-month delay by 5.1%. For breast cancer with a 65-day doubling time, a 1-month delay increases the risk by 1.8%, a 3-month delay by 5.2%, and a 6-month delay by 10.2%. Axillary lymph nodes are the most important prognostic indicator for survival in breast cancer. Our mathematical model suggests the daily increased risk of axillary metastases due to treatment delay is 0.028% for tumors with moderate doubling times of 130 days and 0.057% for tumors with rapid doubling times of 65 days. This minimal maternal risk may be acceptable to some third-trimester pregnant women with early breast cancer, who prefer organ-sparing treatment with radiation after delivery to a mastectomy during pregnancy. This model further quantitates the increased risk of mortality borne by pregnant women whose breast cancer diagnosis is delayed.


[Symptom based approaches in point of care laboratory testing].
Point of care testing (POCT) allows, among others, for efficient care of patients presenting with acute problems to primary care physicians. A combination of clinical information and laboratory results enables physicians to obtain posttest probabilities for the presence or absence of a specific disease. In order to rule in or rule out a disease, the physician has to know both the pretest probability for a disease in a patient as well as the analytical and diagnostic characteristics of the employed test. Pretest probability can be assessed by scores or by personal judgment of the experienced clinician. This article presents the basics of the Bayes theorem together with its clinical applications in acute scenarios in primary health care. These scenarios comprise the use of D-Dimer testing in ruling out venous thromboembolism, rapid testing of group A streptococci in the setting of acute pharyngitis, troponin testing in patients with thoracic pain, c-reactive protein (CRP) testing in patients presenting with acute cough and fever, as well as urine dipstick testing in suspected urinary tract infection. These examples illustrate, that risk stratification before conducting laboratory analysis is of utmost importance in order to obtain valid results for ruling in or ruling out diseases in POCT-settings.


Serotonin 5-HT1A Receptor Biased Agonists Induce Different Cerebral Metabolic Responses: A [18F]-Fluorodesoxyglucose Positron Emission Tomography Study in Conscious and Anesthetized Rats.
Serotonin 5-HT1A receptors constitute an attractive therapeutic target for various psychiatric or neurodegenerative disorders. These receptors are expressed in multiple brain regions on different neuronal populations and can be coupled with distinct G-protein subtypes; such functional diversity complicates the use of 5-HT1A ligands in several pathologies where it would be desirable to stimulate the receptors in a precise region. Therefore, using "biased agonists" able to target specifically certain subpopulations of 5-HT1A receptors would enable achievement of better therapeutic benefit. Several 5-HT1A receptor biased agonists are currently in development, including NLX-101 (aka F15599) and NLX-112 (aka F13640, befiradol), with preclinical data suggesting that they preferentially target different populations of 5-HT1A receptors. However, most previous studies used invasive and regionally limited approaches. In this context, [18F]-fluorodesoxyglucose (FDG)-positron emission tomography (PET) imaging constitutes an interesting technique as it enables noninvasive mapping of the regional brain activity changes following a pharmacological challenge in conscious animals. We report here the evaluation of cerebral glucose metabolism following intraperitoneal injection of different doses of NLX-112 or NLX-101 in conscious or isoflurane-anesthetized rats. The biased agonists produced different metabolic "fingerprints" with distinct regional preferences, consistent with previous studies. At equal doses, the effect of NLX-101 was less marked than NLX-112 in the piriform cortex, in the striatum (in terms of inhibition), and in the pontine nuclei and the cerebellum (in terms of activation); furthermore, only NLX-112 increased the glucose metabolism in the parietal cortex, whereas only NLX-101 induced a clear activation in the colliculi and the frontal cortex, which may be related to its distinctive procognitive profile. Both agonist effects were almost completely unapparent in anesthetized animals, underlining the importance of studying serotonergic neurotransmission in the conscious state. In this regard, [18F]FDG-PET imaging seems very complementary with other functional imaging techniques such as pharmacological MRI.


ERCP-related perforations in the new millennium: A large tertiary referral center 10-year experience.
Endoscopic retrograde cholangiopancreatography (ERCP) is an important diagnostic and therapeutic modality for pancreatic and biliary disorders. Perforation is one of the most dreaded complications of ERCP. Since it is uncommon, there has been little study of incidence, risk factors, and outcomes of management. We aim to assess the incidence of ERCP-related perforations and outcomes at a large tertiary referral center. We undertook a review of an ERCP database for all perforations from 2002 to December 2012. The cumulative incidence of ERCP-related perforations was 0.14% (12 out of 8264), and sphincterotomy-related perforations constituted the most common cause. The mean age of these 12 patients was 58.6 years and majority were female (83.3%). The most common indications for ERCP were: suspected sphincter of Oddi dysfunction (SOD) 41%, and common bile duct stones (CBD stones) 41%. Nine of the 12 patients (75%) had a leak and were managed medically, and four who had a perforation had surgical repair (25%). In our study, leaks were much more common than perforations and the majority of patients were successfully managed with conservative therapy alone. We report a very low perforation rate and most perforations can be managed conservatively with a good outcome.


The evolution of immunosuppression with FK506 in pediatric living-related liver transplantation.
The effects of three FK506 induction regimens on pediatric living-related liver transplantation (LRLT) were studied retrospectively in terms of patient survival and adverse side effects. The patients consisted of 120 children, ranging from 3 to 210 months of age, who underwent a total of 122 LRLTs with a minimum follow-up of 6 months. Immunosuppression consisted of FK506 and low-dose steroids. FK506 was given in 3 ways: (1) high-dose intravenous (i.v.) induction, with FK506 begun at a dose of 0.15 mg/kg/day for the first 16 patients; (2) low-dose i.v. induction, with FK506 begun at a dose of 0.06 mg/kg/day for the next 45 patients; and (3) per os (p.o.) induction, with FK506 begun orally from the day prior to LRLT and continued postoperatively. Whole-blood trough levels of FK506 were monitored daily. Trough levels in the high induction group were often as high as 100 ng/ml compared with the level of 20 ng/ml in the p.o. induction group. Patient survivals were 75%, 89%, and 80% in the high-i.v. vs. low-i.v. vs. p.o. groups. The incidences of acute rejection were 12.5%, 22.2%, and 26.4%, and the incidences of viral infection were 56%, 38%, and 11% in the respective groups. Major adverse effects occurred with higher frequency in the high-i.v. induction group. Oral FK506 induction therapy at a dose of 0.15 mg/kg/day starting from the day before LRLT was safer and associated with a lower incidence of viral infection than therapy with i.v. FK506.


Mitochondrial Cardiomyopathy Caused by Elevated Reactive Oxygen Species and Impaired Cardiomyocyte Proliferation.
Although mitochondrial diseases often cause abnormal myocardial development, the mechanisms by which mitochondria influence heart growth and function are poorly understood. To investigate these disease mechanisms, we studied a genetic model of mitochondrial dysfunction caused by inactivation of Tfam (transcription factor A, mitochondrial), a nuclear-encoded gene that is essential for mitochondrial gene transcription and mitochondrial DNA replication. Tfam inactivation by Nkx2.5Cre caused mitochondrial dysfunction and embryonic lethal myocardial hypoplasia. Tfam inactivation was accompanied by elevated production of reactive oxygen species (ROS) and reduced cardiomyocyte proliferation. Mosaic embryonic Tfam inactivation confirmed that the block to cardiomyocyte proliferation was cell autonomous. Transcriptional profiling by RNA-seq demonstrated the activation of the DNA damage pathway. Pharmacological inhibition of ROS or the DNA damage response pathway restored cardiomyocyte proliferation in cultured fetal cardiomyocytes. Neonatal Tfam inactivation by AAV9-cTnT-Cre caused progressive, lethal dilated cardiomyopathy. Remarkably, postnatal Tfam inactivation and disruption of mitochondrial function did not impair cardiomyocyte maturation. Rather, it elevated ROS production, activated the DNA damage response pathway, and decreased cardiomyocyte proliferation. We identified a transient window during the first postnatal week when inhibition of ROS or the DNA damage response pathway ameliorated the detrimental effect of Tfam inactivation. Mitochondrial dysfunction caused by Tfam inactivation induced ROS production, activated the DNA damage response, and caused cardiomyocyte cell cycle arrest, ultimately resulting in lethal cardiomyopathy. Normal mitochondrial function was not required for cardiomyocyte maturation. Pharmacological inhibition of ROS or DNA damage response pathways is a potential strategy to prevent cardiac dysfunction caused by some forms of mitochondrial dysfunction.


Growth and physiology of olive pioneer and fibrous roots exposed to soil moisture deficits.
In woody plants, pioneer roots are the main roots used to expand the root system horizontally and vertically whereas fibrous 'feeder' roots are chiefly used in the absorption of water and nutrients. Because of their different roles, we expected newly emerged pioneer and fibrous roots to respond differently to restrictions in soil moisture. We hypothesized that fibrous roots would exhibit greater growth plasticity and greater physiological impairment from soil moisture deficits, especially under heterogeneous conditions. We compared the responses of fibrous and pioneer roots of olive seedlings (Olea europaea) to localized and uniform soil moisture deficits in transparent containers in the greenhouse. In comparison with uniformly wet conditions, uniformly dry conditions caused reduced shoot photosynthesis and reduced shoot growth, but no significant effect on root morphology, root respiration (measured in aerated buffer solution using excised roots) or electrolyte leakage as a function of root age. Under heterogeneous soil moisture conditions, root growth tended to preferentially occur in the moist sector, especially in the pioneer roots. In comparison with pioneer roots in the moist sector, pioneer roots in the dry sector had higher tissue density and higher suberin content, but no shift in root respiration, non-structural carbohydrates or electrolyte leakage. In contrast, fibrous roots in the dry sector exhibited evidence of impaired physiology in older (>38 days) roots compared with similar age fibrous roots in the moist sector. While we anticipated that, compared with pioneer roots, fibrous roots would be more sensitive to soil moisture deficits as expressed by higher electrolyte leakage, we did not expect the strong growth plasticity of pioneer roots under heterogeneous soil moisture conditions. Differentiating the responses of these two very different root types can improve our understanding of how different portions of the root system of woody plants cope with soil moisture deficits.


Three major dimensions of human brain cortical ageing in relation to cognitive decline across the eighth decade of life.
Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the eighth decade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1376 MRI scans. Volumetric changes among cortical regions of interest (ROIs) were more strongly correlated (average r = 0.805, SD = 0.252) than were cross-sectional volumes of the same ROIs (average r = 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r = 0.431, p < 0.001) and in the domains of visuospatial ability (r = 0.415, p = 0.002), processing speed (r = 0.383, p < 0.001) and memory (r = 0.372, p < 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.


Heterogeneous shear elasticity of glasses: the origin of the boson peak.
The local elasticity of glasses is known to be inhomogeneous on a microscopic scale compared to that of crystalline materials. Their vibrational spectrum strongly deviates from that expected from Debye's elasticity theory: The density of states deviates from Debye's law, the sound velocity shows a negative dispersion in the boson-peak frequency regime and there is a strong increase of the sound attenuation near the boson-peak frequency. By comparing a mean-field theory of shear-elastic heterogeneity with a large-scale simulation of a soft-sphere glass we demonstrate that the observed anomalies in glasses are caused by elastic heterogeneity. By observing that the macroscopic bulk modulus is frequency independent we show that the boson-peak-related vibrational anomalies are predominantly due to the spatially fluctuating microscopic shear stresses. It is demonstrated that the boson-peak arises from the steep increase of the sound attenuation at a frequency which marks the transition from wave-like excitations to disorder-dominated ones.


[Which light for phototherapy of the low birth weight infant?].
We have compared three different fluorescent light sources (true light, blue light, true light + blue light) for phototherapy in 155 low birth weight newborn babies affected with non haemolytic hyperbilirubinaemia. Our data suggest that blue light is significantly more effective than true light. Surprisingly the association of true light with blue light is significantly more effective than both true light and blue light separately. The greater effectiveness associated with the better tolerance of true light + blue light respect to blue light only, makes it preferable than phototherapy regimen, even if more extensive study on its effectiveness and on short and long term side effects are need.


Ruptured true aneurysm of the splenic artery: an unusual cause of haemoperitoneum.
True aneurysm of the splenic artery is rare. Two cases of ruptured true splenic artery aneurysms are presented. The first patient was a 62-year-old female who presented within 6 hours of the onset of symptoms. The other was a 27-year-old non-alcoholic male patient who was admitted in a state of shock after 2 days of observation in a peripheral hospital. Both patients had haemoperitoneum and were subjected to exploratory laparotomy. Aneurysmectomy was performed in both the patients in addition to left splenopancreatectomy in the first case and splenectomy in the second. However, due to the prolonged preoperative shock, the second patient succumbed on the third postoperative day.


[Definition and morphological features of apoptosis].
The term apoptosis, an ancient Greek word used to describe the "falling off" of petals from flowers or leaves from trees, was proposed by Kerr, Wyllie and Currie in 1972 to refer to the peculiar morphology of physiologically occurring cell death which plays a complementary but opposite role to mitosis in the regulation of animal cell populations. Apoptosis is opposed to necrosis-the appearance of accidental and pathological cell death. Apoptosis involves loss of microvilli, smooth-surfaced protuberances, chromatin condensation, nuclear and cytoplasmic condensation, loss of cell volume, and nuclear fragmentation. At an early stage, condensed chromatin tends to marginate in crescents around the nuclear envelope in most cell types, but in certain cells such as thymocytes, it often occupies much of the nuclear volume. Contrasted to necrosis, in apoptotic cells there are neither swelling and rupture of cytoplasmic organelles and plasma membranes nor inflammatory reaction. Apoptotic cells break up into membrane bound apoptotic bodies and they are phagocytosed by nearly resident tissue cells. These morphological changes are often accompanied by the internucleosomal DNA fragmentation. Apoptosis is a representative morphology of programmed cell death (PCD) which occurs within a developmental context in response to a definable physiological stimulus and requires de novo gene expression. However, apoptosis should not be considered synonymous with PCD. Because, there are examples of non-apoptotic PCD and pathological stimuli such as mild cell injury can induce apoptosis.


Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice.
The effects of dorsal root stimulation and of substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) on the basal release of 9 endogenous amino acids, including glutamate (Glu) and aspartate (Asp), have been investigated using the rat spinal cord slice-dorsal root ganglion preparation and high-performance liquid chromatography with fluorimetric detection. High-intensity repetitive electrical stimulation of a lumbar dorsal root produced a Ca2(+)-dependent increase in the basal release of Asp, Glu, glycine (Gly), serine (Ser), and threonine (Thr). Low concentrations of SP (2 x 10(-7) M) caused a selective increase in the rate of basal release of Glu, whereas higher concentrations (1-5 x 10(-6) M) produced, in addition, an increase in the basal release of Asp. The SP-induced increase of Glu persisted in the absence of external Ca2+, but the effect was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP, an SP analog claimed to be an antagonist of the synthetic SP. NKA (5 x 10(-7) - 10(-6) M), a related tachykinin coexpressed with SP in primary sensory neurons, enhanced the basal release of Gly. CGRP (10(-7) M) caused a significant, largely Ca2(+)-independent increase in the basal release of Glu and Asp and a decrease in asparagine. SP and CGRP potentiated the electrically evoked release of Glu and Asp. Neonatal capsaicin treatment did not significantly alter the basal efflux of 9 endogenous amino acids from the spinal slices, but it prevented the dorsal root stimulation-evoked release of Asp, Glu, Gly, and Thr and the SP-induced increase in the basal release of Glu. However, the effect of CGRP was not significantly modified by the capsaicin treatment. These results indicate that tachykinins (SP and NKA) and CGRP are capable of modulating the basal and electrically evoked release of endogenous Glu and Asp, and these actions may provide an important mechanism by which the peptides contribute to the regulation of the primary afferent synaptic transmission. The enhancement of the basal and the dorsal root stimulation-evoked release of Glu and Asp by tachykinins and CGRP may have important physiological implications for strengthening the synaptic connections in the spinal dorsal horn.


Effect of Plasma Unit Weight and Donor Sex on Post-Donation Citrate Level: An Experimental Study on Plasmapheresis Donors.
Plasmapheresis donation is considered safe and well tolerated, although long-term effects need to be clarified. The volumes of anticoagulant (ACD-A) used are variable and depend primarily on hematocrit (HCT), total blood processed, amount of plasma collected, and donor characteristics. To elucidate the effect of the plasma unit weight setting on plasmapheresis efficiency and ACD-A distribution, we enrolled male donors undergoing a controlled apheresis process donating 700 g and 720 g in two different sessions. In parallel, we investigated a possible effect of sex, recruiting women donating 700 g of plasma. The study was conducted on men donating 720 g and (12 months later) 700 g of plasma, and on women donating 700 g of plasma. The main outcomes were pre-/post-donation delta (Δ) citrate concentration in donor plasma and ACD-A reinfused to the donor. Information concerning the annual check-up and the procedure was also collected. Intergroup comparisons (men donating 720 g vs. men donating 700 g and men vs. women both donating 700 g) and intragroup associations with donor and procedural characteristics were reported. With the procedure set at 720 g, the machine processed around 44 mL more whole blood to collect 20 g more plasma, and 720 g donors received around 12 mL more anticoagulant than 700 g donors. Accordingly, Δ citrate concentration was 1.5 times higher (12 μm), with a greater variability observed for 720 g donations. Citrate concentration in the plasma unit was lower in the 720 g group, although not significantly. Comparing outcomes between women and men donating 700 g, we observed higher (and highly variable) Δ citrate and reinfused ACD-A in women, accompanied by lower anticoagulant levels in the unit. Increased Δ citrate is inversely associated with HCT and age in men and with HCT and triglycerides in women. Reinfused ACD-A correlates with HCT in women but not in men. Unit weight setting and sex influence an ACD-A shift from the estimated values toward an increased reinfusion to donor. In parallel, we observed an impact of age and sex on post-donation citrate metabolism. Altogether, these elements should be taken into account for the development of tailored approaches aimed at maintaining similar safety profiles for all donors using different plasmapheresis settings.


Attention deficit disorder with hyperactivity: differential effects of methylphenidate on impulsivity.
The impulsivity component of attention deficit disorder with hyperactivity requires regulation because its effects interfere with children's school performance and persist into adulthood. The present investigation examined the effects of low to intermediate doses of methylphenidate on impulsivity (measured by the Matching Familiar Figures test, a primary index of cognitive tempo) in 14 children with attention deficit disorder with hyperactivity. The mean percentile error score in the highest dose (15 mg) group was significantly lower than those in placebo (P less than .01), 5-mg (P less than .01), and 10-mg (P less than .01) groups. Trend analysis revealed a linear relationship between dose and error score with total errors decreasing as dose increased. Changes in children's error scores were examined using both fixed-dose and milligram per kilogram data-plotting methods. This work demonstrates the need to consider specific task and child characteristics while assessing the child's responsivity to psychostimulants across a range of safe doses and a variety of behavioral domains.


[Study on cellular and serum concentration of calcium and magnesium in peripheral blood cells of cirrhosis].
To study on the changes of intracellular calcium and magnesium in cirrhosis and its clinical significance. The calcium and magnesium were determined in serum (SCa, SMg), platelets (PCa, PMg), mononuclear cells (MNCCa, MNCMg), polymorphonuclear cells (PMNCa, PMNMg) and erythrocytes (RCa, RMg) of 50 patients with uncompensative cirrhosis (group A) and of 35 patients with compensative cirrhosis (group B). 35 health persons were the control group. The SCa and SMg of group A were lower significantly than those of both group B and control group. The MNCCa, PMNCa, RCa, PMg, MNCMg, PMNMg, RMg of group A [(4.76+/-1.91) micromol/10(9), (7.56+/-2.88) micromol/10(9), (0.66+/-0.13) mmol/L, (5.53+/-2.25) micromol/10(11), (6.64+/-3.53) micromol/10(9), (10.12+/-4.32) micromol/10(9), (2.02+/-0.76) mmol/L] and those of group B [(5.34+/-2.41) micromol/10(9), (8.32+/-2.34) micromol/10(9), (0.67+/-0.11) mmol/L, (5.55+/-2.67) micromol/10(11), (6.56+/-3.44) micromol/10(9), (10.95+/-4.45) micromol/10(9), (2.21+/-0.74) mmol/L] were lower significantly than those of control group [(6.86+/-2.02) micromol/10(9), (9.89+/-3.23) micromol/10(9), (0.72+/-0.10) mmol/L, (7.43+/-2.78) micromol/10(11), (8.68+/-4.1) micromol/10(9), (13.96+/-5.76) micromol/10(9), (2.74+/-0.92) mmol/L]; t (group A vs. control group)=4.88, 3.48, 2.31, 3.45, 2.46, 3.52, 4.00, 0.01, 0.01, 0.05, 0.01, 0.02, 0.01, 0.01; t (group B vs. control group)=2.87, 2.34, 2.00, 2.89, 2.33, 2.45, 2.65, 0.01, 0.05, 0.05, 0.01, 0.05, 0.02, 0.02. The PCa of the patients with hepatic encephalopathy was higher, the SMg, PMg, MNCMg, PMNMg and RMg were lower than those of the patients without hepatic encephalopathy significantly. The SCa, SMg, PMg, MNCMg, PMNMg and RMg of the patients in Child stage C were lower significantly than those of the patients in Child stage B. There were no significant differences of PCa, MNCCa, PMNCa and RCa between Child stage C and Child stage B. There were no significant differences of SCa, MNCCa, PMNCa and RCa between the patients with and without hepatic encephalopathy. The ratios of PCa/SCa, MNCCa/SCa and PMNCa/SCa of the patients with decreased SMg were lower than those of control group. The SMg, MNCMg, PMNMg and RMg were correlated directly with the level of serum albumin. There are calcium and magnesium deficiencies in the patients with uncompensative cirrhosis and compensative cirrhosis, this deficiency aggravates with the severity of the disease. There is relative increase of intracellular calcium. The magnesium deficiency may be one of the reasons for both hepatic encephalopathy and relative increase of intracellular calcium.


MGC: a metagenomic gene caller.
Computational gene finding algorithms have proven their robustness in identifying genes in complete genomes. However, metagenomic sequencing has presented new challenges due to the incomplete and fragmented nature of the data. During the last few years, attempts have been made to extract complete and incomplete open reading frames (ORFs) directly from short reads and identify the coding ORFs, bypassing other challenging tasks such as the assembly of the metagenome. In this paper we introduce a metagenomics gene caller (MGC) which is an improvement over the state-of-the-art prediction algorithm Orphelia. Orphelia uses a two-stage machine learning approach and computes a model that classifies extracted ORFs from fragmented sequences. We hypothesise and demonstrate evidence that sequences need separate models based on their local GC-content in order to avoid the noise introduced to a single model computed with sequences from the entire GC spectrum. We have also added two amino-acid features based on the benefit of amino-acid usage shown in our previous research. Our algorithm is able to predict genes and translation initiation sites (TIS) more accurately than Orphelia which uses a single model. Learning separate models for several pre-defined GC-content regions as opposed to a single model approach improves the performance of the neural network as demonstrated by the experimental results presented in this paper. The inclusion of amino-acid usage features also helps improve the overall accuracy of our algorithm. MGC's improvement sets the ground for further investigation into the use of GC-content to separate data for training models in machine learning based gene finders.


Evaluation of the Bio-Rad Dx CT/NG/MG® assay for simultaneous detection of Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium in urine.
We evaluated the performance of the Bio-Rad real-time Dx CT/NG/MG® assay for detection of C. trachomatis, N. gonorrhoeae and M. genitalium on a collection of 441 urine samples from sexually transmitted infections, or travellers consultations and from anonymous sperm donors that were previously analysed with the Abbott RealTime CT/NG assay. Samples positive for C. trachomatis or N. gonorrhoeae with the Abbott assay had all previously been confirmed with an in-house real-time PCR assay. Samples positive for M. genitalium with the Bio-Rad assay were subsequently analysed by an in-house real-time PCR. On a total of 441 urines, 104 samples were positive for C. trachomatis, 12 were positive for N. gonorrhoeae and seven were positive for M. genitalium. After retesting of discrepant results, the test results were completely concordant, resulting in a calculated sensitivity and specificity of the Bio-Rad assay of 98.1 % and 100 % for C. trachomatis and of 91.7 % and 100 % for N. gonorrhoeae. Results for M. genitalium with the Bio-Rad assay were also concordant with the results of an in house PCR. We also evaluated the performance of automated nucleic acid extractions of urine samples with the NucliSENS easyMAG (bioMérieux) compared to the manual DNA extraction prescribed by the insert of the kit. The easyMAG extraction gave lower Ct values, relieved inhibition and had a lower hands-on time.


Caregiver Behaviors and Child Distress in Trauma Narration and Processing Sessions of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT).
Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is an effective treatment for children impacted by trauma, and non-offending caregivers play an important role in this treatment. This study aims to identify correlates of four caregiver variables that have been identified as predictors of child outcomes in TF-CBT: support, cognitive-emotional processing, avoidance, and blame/criticism. Audio recorded sessions were coded from a community effectiveness trial of TF-CBT that included 71 child-caregiver dyads participating in the trauma narration and processing phase of treatment. Regression analyses were conducted to examine caregiver trauma history and child baseline symptoms (internalizing, externalizing, and posttraumatic stress disorder [PTSD] symptoms) as predictors of caregiver behavior during the trauma processing sessions. Caregivers who reported exposure to more trauma types exhibited more in-session avoidance and also processing during the trauma processing phase of treatment. Child symptoms at baseline did not predict caregiver in-session behaviors. Bivariate correlations were used to investigate concurrent associations between mean levels of in-session caregiver behaviors and in-session child distress (negative emotion, hopelessness, negative behaviors). More caregiver blame/criticism was associated with more in-session child distress on all three measures. Caregiver avoidance was associated with more child negative emotion and hopelessness. Findings may help identify therapeutic targets when working with caregivers to promote change and enhance TF-CBT outcomes.


[Clinical management of patients with new diagnosis of liver cirrhosis].
Liver cirrhosis is a major healthcare problem and is associated with an increased mortality due to the development of complications. Therefore, after diagnosis of liver cirrhosis, it is highly clinically relevant to evaluate the reason for liver cirrhosis and to assess the presence of complications in order to prevent progression of liver cirrhosis.


Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model.
Surgical resection of the primary tumor provides the best chance of cure for patients with colorectal carcinoma (CRC). However, bacterial translocation during intestinal surgery has been correlated with poor long-term oncological outcome. Therefore, we investigated the influence of bacterial contamination during colon surgery on CRC liver metastases development. Blood and liver samples of patients undergoing resection of primary CRC or liver metastases were collected. Cell numbers, activation markers and inflammatory mediators were determined. Tumor cell adhesion and outgrowth after sham- or colectomy operations were determined in a rat model, in which tumor cells had been injected into the portal vein. White blood cells and granulocytes were increased in per- and post-operative patient blood samples. IL-6 was also increased post-operatively compared to the preoperative level. Expression of NOX-2, NOX-4 and polymorphonuclear cells (PMNs) numbers were elevated in post-operative human liver samples. In vitro stimulation of macrophages with plasma of rats after colectomy resulted in production of reactive oxygen species (ROS). Colectomy in rats increased D-lactate levels in plasma, supporting bacterial translocation. Decreased expression of tight junction molecules and increased tumor cell adhesion and outgrowth was observed. Treatment with a selective decontamination of the digestive tract (SDD) cocktail decreased tumor cell adherence after colectomy. In conclusion, postoperative bacterial translocation may activate liver macrophages and PMNs, resulting in ROS production. As we previously showed that ROS release led to liver vasculature damage, circulating tumor cells may adhere to exposed extracellular matrix and grow out into liver metastases. This knowledge is pivotal for development of therapeutic strategies to prevent surgery-induced liver metastases development.


MR-guided catheter navigation of the intracranial subarachnoid space.
Percutaneous intraspinal navigation (PIN) is a new minimally invasive approach to the CNS. The authors studied the utility of MR-guided intracranial navigation following access to the subarachnoid compartment via PIN. The passive tracking technique was employed to visualize devices during intracranial navigation. Under steady-state free precession (SSFP) MR-guidance a microcatheter-microguidewire was successfully navigated to multiple brain foci in two cadavers. SSFP MR fluoroscopy possesses adequate contrast and temporal resolution to allow MR-guided intracranial navigation.


Left out in the cold: Homicide amongst persons experiencing homelessness.
There is no American population-level study comparing the characteristics of homicides involving victims who were vs were not experiencing homelessness at time of death. We aim to identify variables surrounding homeless homicide that are unique, and intervenable. In this retrospective cohort study, we reviewed the National Violent Death Reporting System (NVDRS) from 2003 to 2018 and compared the characteristics surrounding homicides of victims who were not-homeless (cohort 1) vs experiencing homelessness (cohort 2) at death. We utilized the available perpetrator data to characterize the average perpetrator for each cohort. We considered housing status to be our primary predictor and recorded NVDRS variables, such as age of victims and likelihood to know perpetrators, to be our primary outcomes. 81,212 Homicide Victims and 60,982 Homicide Perpetrators were included in analysis. Homeless cohort victims were more likely younger, White, male, and to have a known mental health or substance abuse disorder. PEH were also more likely to have co-morbid mental health and substance abuse disorders but were roughly half as likely to be getting treatment for said disorders. Circumstances surrounding incidents, including geographic location, mechanism of injury, and premeditation, varied; homeless cohort victims were more likely to die in random acts of violence, but were less likely to die via firearm. There is room for targeted interventions against homeless homicides. Epidemiological, Level IV.


[Maintenance dose requirement for phenytoin is lowered in genetically impaired drug metabolism independent of concommitant use of other antiepileptics].
To investigate the effect of genetically determined impaired drug metabolism and of the use of comedication on phenytoin maintenance dose requirement. Descriptive. In 60 patients on long-term phenytoin therapy the concentration of phenytoin in serum was measured and CYP2C9 genotyping was performed (mutant alleles of CYP2C9 are associated with impaired phenytoin metabolism). In addition, the use of other antiepileptics concurrently with phenytoin was reviewed: phenobarbital, carbamazepine and valproic acid. CYP2C9 genotype and comedication were connected to phenytoin daily dose requirement. The 60 patients were 38 men and 22 women, between 16 and 74 years of age, and all mentally disabled. Genotyping revealed that of the 60 patients 38% (n = 23) carried at least one mutant CYP2C9 allele. Their mean dose of phenytoin was 199 mg dd, while the mean required maintenance dose in non-carriers (n = 37) was 287 mg dd (p < 0.01). When the use of comedication was taken into account, it appeared that the mean phenytoin daily doses in the different comedication groups did not differ significantly. Patients with a genetically determined impaired phenytoin metabolism required on average a 30% lower dose than those with a normal metabolism, while the concomitant use of other antiepileptics appeared to have no effect on phenytoin dose requirement.


Femtosecond gain and index dynamics in an InAs/InGaAsP quantum dot amplifier operating at 1.55 microm.
We report on the characterization of the ultrafast gain and refractive index dynamics of an InAs/InGaAsP self-assembled quantum dot semiconductor optical amplifier (SOA) operating at 1.55 mum through heterodyne pump-probe measurements with 150 fs resolution. The measurements show a 15 ps gain recovery time at a wavelength of 1560 nm, promising for ultrafast switching at >40 GHz in the important telecommunications wavelength bands. Ultrafast dynamics with 0.2-1.5 ps lifetimes were also found consistent with carrier heating and spectral hole burning. Comparing with previous reports on quantum dot SOAs at 1.1-1.3 mum wavelengths, we conclude that the carrier heating is caused by a combination of free-carrier absorption and stimulated transition processes.


Lung function profiles and aerobic capacity of adult cigarette and hookah smokers after 12 weeks intermittent training.
Pulmonary function is compromised in most smokers. Yet it is unknown whether exercise training improves pulmonary function and aerobic capacity in cigarette and hookah smokers and whether these smokers respond in a similar way as do non-smokers. To evaluate the effects of an interval exercise training program on pulmonary function and aerobic capacity in cigarette and hookah smokers. Twelve cigarette smokers, 10 hookah smokers, and 11 non-smokers participated in our exercise program. All subjects performed 30 min of interval exercise (2 min of work followed by 1 min of rest) three times a week for 12 weeks at an intensity estimated at 70% of the subject's maximum aerobic capacity (VO2max). Pulmonary function was measured using spirometry, and maximum aerobic capacity was assessed by maximal exercise testing on a treadmill before the beginning and at the end of the exercise training program. As expected, prior to the exercise intervention, the cigarette and hookah smokers had significantly lower pulmonary function than the non-smokers. The 12-week exercise training program did not significantly affect lung function as assessed by spirometry in the non-smoker group. However, it significantly increased both forced expiratory volume in 1 second and peak expiratory flow (PEF) in the cigarette smoker group, and PEF in the hookah smoker group. Our training program had its most notable impact on the cardiopulmonary system of smokers. In the non-smoker and cigarette smoker groups, the training program significantly improved VO2max (4.4 and 4.7%, respectively), v VO2max (6.7 and 5.6%, respectively), and the recovery index (7.9 and 10.5%, respectively). After 12 weeks of interval training program, the increase of VO2max and the decrease of recovery index and resting heart rate in the smoking subjects indicated better exercise tolerance. Although the intermittent training program altered pulmonary function only partially, both aerobic capacity and life quality were improved. Intermittent training should be advised in the clinical setting for subjects with adverse health behaviors.


Sublethal acute and chronic exposure of Colorado potato beetle (Coleoptera: Chrysomelidae) to the delta-endotoxin of Bacillus thuringiensis.
Sublethal exposure of Colorado potato beetle, Leptinotarsa decemlineata (Say), larvae to the delta-endotoxin of Bacillus thuringiensis variety tenebrionis (Berliner) caused a dose-dependent reduction in feeding and weight gain when tested in a leaf disk bioassay. The highest doses of chronic (continuous-lower concentration) exposure resulted in peak foliage consumption on day 1 as compared with peak consumption on days 3 and 4 when exposure was acute (24-h higher concentration). Dose and exposure regimen interacted significantly in their effects on the extension of development. When development time was analyzed separately for each exposure regimen, only acute exposure caused significant delays in development that extended through to adult eclosion. The efficiency of conversion of ingested material to biomass (ECI) declined significantly with both exposure regimens. The lethal and most sublethal effects of exposure to delta-endotoxin were not cumulative, in that similar total doses, whether delivered acutely or chronically, produced different effects. Female adults that survived acute and chronic exposure to delta-endotoxin as larvae had significantly reduced weight and longevity, and tended to produce fewer eggs (45 and 44% reductions in acute and chronic exposures, respectively) when compared with control adults. The intrinsic rate of increase (r) and net reproductive rate (R0) also appeared to be reduced.


Parasitism in Pterois volitans (Scorpaenidae) from coastal waters of Puerto Rico, the Cayman Islands, and the Bahamas.
Recently, Pterois volitans, a Pacific species of lionfish, invaded the Atlantic Ocean, likely via the aquarium trade. We examined for internal and external parasites 188 individuals from 8 municipalities of Puerto Rico collected during 2009-2012, 91 individuals from Little Cayman, Cayman Islands, collected during the summers of 2010 and 2011, and 47 individuals from Lee Stocking Island, Bahamas, collected during the summer of 2009. In total, 27 parasite taxa were found, including 3 previously reported species from lionfish, the digenean Lecithochirium floridense, the leech Trachelobdella lubrica, and an Excorallana sp. isopod. We also report another 24 previously unreported parasite taxa from lionfish, including digeneans, monogeneans, cestodes, nematodes, isopods, a copepod, and an acanthocephalan. Among these parasites, several were previously unreported at their respective geographic origins: We report 5 new locality records from Puerto Rico, 9 from Cayman Islands, 5 from the Bahamas, 5 from the Caribbean, and 3 from the subtropical western Atlantic region. Three parasites are reported to associate with a fish host for the first time. The parasite faunas of P. volitans among our 3 study sites were quite different; most of the species infecting lionfish were generalists and/or species that infect carnivorous fishes. Although our study did not assess the impact of parasites on the fitness of invasive lionfish, it provides an important early step. Our results provide valuable comparative data for future studies at these and other sites throughout the lionfish's invaded range.


Human factors and online learning.
A human factors approach to patient safety offers a means of minimising the incidence and effect of adverse events in the healthcare setting. This article explains how human factors informed the development of an online patient safety course by the Royal College of Nursing. It also describes a novel educational technique called action mapping, which was used to design the online learning course.


[Improvement of health-related quality of life in breast cancer patients by inpatient rehabilitation].
Improvement of health-related quality of life in women with breast cancer after primary therapy by standardized inpatient rehabilitation. 129 women with breast cancer, 25-75 years old, and 42 healthy women were interviewed about their health-related quality of life by using the EORTC-QLQ-C30. This questionnaire assesses different aspects of quality of life as well as overall quality of life. Quality of life of breast cancer patients was assessed before and after inpatient rehabilitation, considering especially their age and the interval between diagnosis and rehabilitation. Compared with healthy women, the breast cancer patients had distinctly reduced values in the beginning of rehabilitation. By specific therapy, the overall quality of life as well as physical, emotional and role function could be improved significantly (p < 0.0001). Concerning cognitive and social function, there were also significant changes after rehabilitation (p < 0.0001), but only in 50% of the women an improvement could be shown. There was no evidence of correlation between quality of life after the end of primary therapy and the patients' age or the interval between diagnosis and rehabilitation. Up to 3 years after the end of primary therapy, the health-related quality of life is noticeably reduced in breast cancer patients, without showing a tendency toward spontaneous improvement. By an intensive therapy with psychooncologic measures and activating physiotherapy, the quality of life can be improved in these patients. Whether this improvement leads to a long-term effect must be shown by a presently conducted randomized, prospective study.


Intracranial Hematoma Detection by Near Infrared Spectroscopy in a Helicopter Emergency Medical Service: Practical Experience.
In (helicopter) emergency medical services, (H)EMS, the prehospital detection of intracranial hematomas should improve patient care and the triage to specialized neurosurgical hospitals. Recently, noninvasive detection of intracranial hematomas became possible by applying transcranial near infrared spectroscopy (NIRS). Herein, second-generation devices are currently available, for example, the Infrascanner 2000 (Infrascan), that appear suited also for prehospital (H)EMS applications. Since (H)EMS operations are time-critical, we studied the Infrascanner 2000 as a "first-time-right" monitor in healthy volunteers (n = 17, hospital employees, no neurologic history). Further, we studied the implementation of the Infrascanner 2000 in a European HEMS organization (Lifeliner 1, Amsterdam, The Netherlands). The principal results of our study were as follows: The screening for intracranial hematomas in healthy volunteers with first-time-right intention resulted in a marked rate of virtual hematomas (false positive results, i.e., 12/17), rendering more time consuming repeat measurements advisable. The results of the implementation of the Infrascanner in HEMS suggest that NIRS-based intracranial hematoma detection is feasible in the HEMS setting. However, some drawbacks exist and their possible solutions are discussed. Future studies will have to demonstrate how NIRS-based intracranial hematoma detection will improve prehospital decision making in (H)EMS and ultimately patient outcome.


Cell-wall determinants of the bactericidal action of group IIA phospholipase A2 against Gram-positive bacteria.
We have shown previously that a group IIA phospholipase A2 (PLA2) is responsible for the potent bactericidal activity of inflammatory fluids against many Gram-positive bacteria. To exert its antibacterial activity, this PLA2 must first bind and traverse the bacterial cell wall to produce the extensive degradation of membrane phospholipids (PL) required for bacterial killing. In this study, we have examined the properties of the cell-wall that may determine the potency of group IIA PLA2 action. Inhibition of bacterial growth by nutrient deprivation or a bacteriostatic antibiotic reversibly increased bacterial resistance to PLA2-triggered PL degradation and killing. Conversely, pretreatment of Staphylococcus aureus or Enterococcus faecium with subinhibitory doses of beta-lactam antibiotics increased the rate and extent of PL degradation and/or bacterial killing after addition of PLA2. Isogenic wild-type (lyt+) and autolysis-deficient (lyt-) strains of S. aureus were equally sensitive to the phospholipolytic action of PLA2, but killing and lysis was much greater in the lyt+ strain. Thus, changes in cell-wall cross-linking and/or autolytic activity can modulate PLA2 action either by affecting enzyme access to membrane PL or by the coupling of massive PL degradation to autolysin-dependent killing and bacterial lysis or both. Taken together, these findings suggest that the bacterial envelope sites engaged in cell growth may represent preferential sites for the action and cytotoxic consequences of group IIA PLA2 attack against Gram-positive bacteria.


The long noncoding RNA H19 regulates tumor plasticity in neuroendocrine prostate cancer.
Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.


RBC Transfusion Strategies in the ICU: A Concise Review.
To critically assess available high-level clinical studies regarding RBC transfusion strategies, with a focus on hemoglobin transfusion thresholds in the ICU. Source data were obtained from a PubMed literature review. English language studies addressing RBC transfusions in the ICU with a focus on the most recent relevant studies. Relevant studies were reviewed and the following aspects of each study were identified, abstracted, and analyzed: study design, methods, results, and implications for critical care practice. Approximately 30-50% of ICU patients receive a transfusion during their hospitalization with anemia being the indication for 75% of transfusions. A significant body of clinical research evidence supports using a restrictive transfusion strategy (e.g., hemoglobin threshold < 7 g/dL) compared with a more liberal approach (e.g., hemoglobin threshold < 10 g/dL). A restrictive strategy (hemoglobin < 7 g/dL) is recommended in patients with sepsis and gastrointestinal bleeds. A slightly higher restrictive threshold is recommended in cardiac surgery (hemoglobin < 7.5 g/dL) and stable cardiovascular disease (hemoglobin < 8 g/dL). Although restrictive strategies are generally supported in hematologic malignancies, acute neurologic injury, and burns, more definitive studies are needed, including acute coronary syndrome. Massive transfusion protocols are the mainstay of treatment for hemorrhagic shock; however, the exact RBC to fresh frozen plasma ratio is still unclear. There are also emerging complimentary practices including nontransfusion strategies to avoid and treat anemia and the reemergence of whole blood transfusion. The current literature supports the use of restrictive transfusion strategies in the majority of critically ill populations. Continued studies of optimal transfusion strategies in various patient populations, coupled with the integration of novel complementary ICU practices, will continue to enhance our ability to treat critically ill patients.


Successful treatment of ulcerative colitis complicated by Sweet's syndrome by corticosteroid therapy and leukocytapheresis.
Ulcerative colitis is occasionally complicated by dermatological disorders presenting as extra-intestinal manifestations, including erythema nodosum and pyoderma gangrenosum. Sweet's syndrome is considered to be a rare cutaneous disease in patients with ulcerative colitis. To date, only 17 cases of Sweet's syndrome complicating ulcerative colitis have been reported in the English literature. Here, we report a case of a 41-year-old male who had been suffering from ulcerative colitis for 20 years. He was admitted to hospital with hematochezia, diarrhea and fever, and painful erythematous nodules on the face and arms. Histological examination of skin biopsies showed inflammatory cell infiltration composed mainly of neutrophils without evidence of necrotizing vasculitis, and the condition was diagnosed as Sweet's syndrome. The patient was treated with prednisolone and leukocytapheresis and the erythematous nodules on the skin, as well as the abdominal symptoms and endoscopic findings of ulcerative colitis, immediately improved. In this paper we report on this case and review the literature concerning ulcerative colitis and Sweet's syndrome.


Androgen receptor isoforms in human and rat prostate.
To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatic tissues. Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained from patients undergoing prostatectomy, and rat ventral prostate was incised 3 days after castration. Forty-one AR-positive BPH specimens, 3 prostatic cancer specimens, and 6 rat prostates were used. After processing at 4 degrees C, the tissues were examined by means of high resolution isoelectric focusing (IEF) technique to determine their AR isoforms. From the prostatic specimens, 3 types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. In human BPH tissues, 15/41 (36.6%) specimens showed all the three types of isoforms, while 19/41 (46.3%) showed 2 isoforms at various combinations and 7/41 (17.1%), 1 isoform. For the 3 prostatic cancer specimens, one showed 3 isoforms, one, 2 isoforms, and the other failed to show any isoform. All rat prostatic tissues showed 2 isoforms at different combinations. Binding of 3H-dihydrotestosterone (DHT) to the isoforms was inhibited by the addition of 100-fold excess of DHT or testosterone, but not progesterone, oestradiol or diethylstilboestrol. AR isoforms are different in different patients. Although their genesis is not clear, the therapeutic implication of the present observation appears to be interesting, that may help clarifying the individual differences in the response to hormonal therapy.


Relation between consumption of alcohol and fatty acids esterifying serum cholesterol in healthy men.
The relation between consumption of alcohol (established by interview), two of its typical markers (gamma-glutamyltransferase activity and mean corpuscular volume), and the composition of fatty acids in plasma cholesterol esters was investigated in an epidemiological study of 1467 actively employed men aged 35-45. In this group of subjects mean consumption of alcohol was 34.6 (SD 25.2) g/day. Palmitoleic acid and oleic acid were positively correlated with consumption of alcohol, gamma-glutamyltransferase activity, and mean corpuscular volume, while linoleic acid was negatively correlated with these variables. When these three fatty acids, gamma-glutamyltransferase activity, mean corpuscular volume, and the fat content of the diet were introduced into a multivariate regression analysis, with consumption of alcohol as the dependent variable, only palmitoleic acid, gamma-glutamyltransferase activity, mean corpuscular volume, and the monounsaturated fat content of the diet remained significant. Palmitoleic acid seems to be an independent correlate of consumption of alcohol and could be useful in epidemiological and clinical studies as a variable of consumption.


Replication of rhesus cytomegalovirus in life-expanded rhesus fibroblasts expressing human telomerase.
The kinetics of rhesus cytomegalovirus (RhCMV) infection were compared in primary and telomerase-immortalized (Telo-) rhesus fibroblasts (RF). Equivalent viral titers were achieved with both cell types. However, the production of infectious virions was slightly faster and plaque size was larger in Telo-RF, compared with primary cells. Comparable RhCMV growth curves and viral susceptibility were observed using Telo-RF passaged for different time periods in culture, whereas the ability of primary cells to support robust RhCMV replication declined as the cells approached senescence. Analysis of cell growth kinetics suggested that the rate of RhCMV replication was directly related to the rate of cell proliferation. RT-PCR analysis of representative RhCMV genes demonstrated that the presence of telomerase did not alter the temporal profile of RhCMV gene expression. In addition, Telo-RF cells were observed to have a significantly increased efficiency of transfection with cationic lipids, compared with primary RF. These results demonstrated that Telo-RF represents a stable, permissive cell line for RhCMV infection, facilitating standardization of in vitro assays for this important non-human primate CMV. The ease of transfection will enable molecular analyses and the generation of complementing cell lines for the propagation of defective RhCMV variants.


Demographics and outcomes of patients diagnosed with pulmonary hypertension with pulmonary capillary wedge pressures 16 to 18 mm Hg: insights from the REVEAL Registry.
The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) is a multicenter, US-based, observational study of patients diagnosed with group 1 pulmonary hypertension enrolled consecutively from March 2006 to December 2009. Of 3,128 patients in this analysis, inclusion criteria permitted enrollment of 268 patients with mean pulmonary capillary wedge pressure (PCWP) 16 to 18 mm Hg at diagnostic right-sided heart catheterization (RHC) (above currently accepted pulmonary arterial hypertension [PAH] diagnostic criteria). This study compared the demographics and outcomes of those 268 patients with an elevated mean PCWP to patients with a mean PCWP ≤ 15 mm Hg. Demographic characteristics and outcomes were compared for patients with mean PCWP ≤ 12, 13 to 15, and 16 to 18 mm Hg at diagnostic and follow-up RHC. At diagnostic RHC, patients with PCWP 16 to 18 mm Hg were older, had more severe hemodynamic impairments, and were more likely to be obese and have other comorbidities than patients with PCWP ≤ 15 mm Hg. There were no clinically relevant differences in 5-year survival rates from diagnostic RHC regardless of PCWP at diagnosis (≤ 15 mm Hg vs 16-18 mm Hg, P = .07). Two-year survival rates of 108 patients with PAH whose PCWP increased to 19 mm Hg (regardless of PCWP at diagnosis) were significantly lower than that of patients with PAH with PCWP ≤ 18 mm Hg at subsequent RHC. Patients with PCWP 16 to 18 mm Hg who were diagnosed and treated for PAH were older, heavier, and more likely to have comorbidities associated with left ventricular diastolic dysfunction at diagnosis than those with PCWP ≤ 15 mm Hg. Five-year survival rates were similarly low for all PCWP subgroups. ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov


The Banff 2022 Kidney Meeting Work Plan: Data-driven refinement of the Banff Classification for renal allografts.
The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell-mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized. This paper summarizes the key Banff Meeting 2022 sessions not covered in the Banff Kidney Meeting 2022 Report paper and also provides an update on other Banff Working Group activities relevant to kidney allografts.


Crystallographic raw data, education and refereeing.
This article provides an overview of the preservation of raw diffraction data, then addresses the impact on future plans in the education and training of our community with respect to raw diffraction data and its potential reuse, and, thirdly presents the issue of referee access to the underpinning diffraction data and coordinates, as well as the Protein Data Bank Validation Report, in the review process of structural biology articles submitted for publication. Overall I pay tribute to the scientific achievements of Alex Wlodawer, who is also an ardent advocate of the importance of experimental data.


Determination of caspase-3 activation fails to predict chemosensitivity in primary acute myeloid leukemia blasts.
Ex-vivo chemosensitivity tests that measure cell death induction may predict treatment outcome and, therefore, represent a powerful instrument for clinical decision making in cancer therapy. Such tests are, however, work intensive and, in the case of the DiSC-assay, require at least four days. Induction of apoptosis is the mode of action of anticancer drugs and should, therefore, result in the induction of caspase activation in cells targeted by anticancer therapy. To determine, whether caspase activation can predict the chemosensitivity, we investigated enzyme activation of caspase-3, a key executioner caspase and correlated these data with chemosensitivity profiles of acute myeloid leukemia (AML) blasts. There was, however, no correlation between the ex-vivo chemosensitivity assessed by measuring the overall rates of cell death by use of the DiSC-assay and caspase-3 activation. Thus, despite a significant reduction of duration of the assay from four to one day, induction of apoptosis evaluated by caspase-3 activity does not seem to be a valid surrogate marker for chemosensitivity.


Hepatitis C Virus Treatment: Is It Possible To Cure All Hepatitis C Virus Patients?
The recent advances in hepatitis C virus (HCV) therapeutics have brought combinations of direct acting antiviral medications that offer interferon-free, well-tolerated regimens with sustained virologic response rates greater than 90% in clinical trials for many patient groups. The successes have prompted discussions regarding cure for all patients. These regimens have already demonstrated the ability to cure previously challenging patient groups, including human immunodeficiency virus-HCV coinfection, decompensated cirrhosis, and post-liver transplantation. Limitations exist in the current portfolio of agents, with suboptimal outcomes for genotype 3 and limited data in genotypes 5 and 6. More data are urgently needed in patients with chronic kidney disease and in children. With ongoing developments, highly effective regimens for all these patient groups are within reach. To deliver HCV treatment throughout the world and particularly in low- and middle-income countries, regimens need to be affordable but also pan-genotypic, well-tolerated, and delivered once daily for 4-8 weeks. With such a regimen, cure for all patients would then hinge on the ability to identify patients with HCV infection and deliver treatment within their communities. This review will discuss the strategies that will be necessary to realize this opportunity to cure all persons with HCV infection.


Laparoscopic Major Vascular Injury Simulation Using a Synthetic Compared With Porcine Model.
Major vascular injury training may improve clinical skills and reduce patient morbidity during gynecologic laparoscopy; thus, reliable models for simulation should be identified. Two laparoscopic major vascular injury simulations using synthetic or live porcine models were constructed. The primary surgeon was given the opportunity to complete both simulations. After obtaining peritoneal access, the surgeon quickly encountered a major vascular injury. Degrading vital signs and estimated blood loss coupled with the replay of a human heartbeat that increased in volume and intensity were provided to heighten tension during the synthetic simulation. Twenty-two gynecologic surgery educators evaluated the simulations. Educators considered the porcine model superior to the synthetic model with regard to tissue handling. The synthetic model simulation was found to be equivalent to the porcine model on how likely the simulation would be able to improve performance in a clinical setting. Educators were more likely to implement the synthetic simulation over the porcine simulation. The synthetic model was found to be more feasible and as effective as the porcine model to simulate and teach the initial management steps of major vascular injury at laparoscopy by gynecologic educators.


Chronic ulcerative dermatopathy in cultured marine fishes. Comparative study in sharpsnout sea bream, Diplodus puntazzo (Walbaum).
Chronic ulcerative dermatopathy (CUD) also known as chronic erosive dermatopathy, hole-in-the-head, head and lateral line erosion syndrome (HLLE) and lateral line depigmentation (LLD) is a chronic disease of unknown aetiology that affects the lateral line canals of the head and the trunk of various fish species. It has been described only in freshwater species although there are reports that it also affects marine fish. Here, we describe the disease in cultured sharpsnout sea bream using histology and scanning electron microscopy and identify several marine species as CUD sensitive. The results of this study correlate the development of the disease with the use of borehole water, indicating that the aetiology is probably associated with water quality rather than nutritional imbalance or infectious agents.


Ligand Recognition by the Macrophage Galactose-Type C-Type Lectin: Self or Non-Self?-A Way to Trick the Host's Immune System.
The cells and numerous macromolecules of living organisms carry an array of simple and complex carbohydrates on their surface, which may be recognized by many types of proteins, including lectins. Human macrophage galactose-type lectin (MGL, also known as hMGL/CLEC10A/CD301) is a C-type lectin receptor expressed on professional antigen-presenting cells (APCs) specific to glycans containing terminal GalNAc residue, such as Tn antigen or LacdiNAc but also sialylated Tn antigens. Macrophage galactose-type lectin (MGL) exhibits immunosuppressive properties, thus facilitating the maintenance of immune homeostasis. Hence, MGL is exploited by tumors and some pathogens to trick the host immune system and induce an immunosuppressive environment to escape immune control. The aims of this article are to discuss the immunological outcomes of human MGL ligand recognition, provide insights into the molecular aspects of these interactions, and review the MGL ligands discovered so far. Lastly, based on the human fetoembryonic defense system (Hu-FEDS) hypothesis, this paper raises the question as to whether MGL-mediated interactions may be relevant in the development of maternal tolerance toward male gametes and the fetus.


Growth and genome-based insights of Fe(III) reduction of the high-temperature and NaCl-tolerant Shewanella xiamenensis from Changqing oilfield of China.
A facultative anaerobe bacterium Shewanella xiamenensis CQ-Y1 was isolated from the wastewater of Changqing oilfield in Shaanxi Province of China. Shewanella is the important dissimilatory metal-reducing bacteria. It exhibited a well potential application in biodegradation and bioremediation. Genome sequencing, assembling and functional annotation were conducted to explore the genome information of CQ-Y1. The effect of temperatures and NaCl concentrations on the CQ-Y1 growth and Fe(III) reduction were investigated by UV visible spectrophotometry, SEM and XRD. Genomic analysis revealed its complete genome was a circular chromosome of 4,710,887 bp with a GC content of 46.50% and 4,110 CDSs genes, 86 tRNAs and 26 rRNAs. It contains genes encoding for Na+/H+ antiporter, K+/Cl- transporter, heat shock protein associated with NaCl and high-temperature resistance. The presence of genes related to flavin, Cytochrome c, siderophore, and other related proteins supported Fe(III) reduction. In addition, CQ-Y1 could survive at 10% NaCl (w/v) and 45°C, and temperature showed more pronounced effects than NaCl concentration on the bacterial growth. The maximum Fe(III) reduction ratio of CQ-Y1 reached 70.1% at 30°C without NaCl, and the reduction reaction remained active at 40°C with 3% NaCl (w/v). NaCl concentration was more effective than temperature on microbial Fe(III) reduction. And the reduction products under high temperature and high NaCl conditions were characterized as Fe3(PO4)2, FeCl2 and Fe(OH)2. Accordingly, a Fe(III) reduction mechanism of CQ-Y1 mediated by Cytochrome c and flavin was hypothesised. These findings could provide information for a better understanding of the origin and evolution of genomic and metabolic diversity of S. xiamenensis.


Psychometric properties of a Spanish-language version of the Short Inventory of Problems.
Hispanic Americans are substantially underrepresented in clinical and research samples for substance use treatment, with language cited as one of the major barriers to their participation, indicating a need for more validated assessments in Spanish. This study evaluated the psychometric properties of a Spanish version of the Short Inventory of Problems (SIP), used in a multisite, randomized trial conducted for Spanish-speaking substance users. The sample included 405 Spanish-speaking treatment seekers, mostly male (88%) and legally mandated to treatment (71%). The Spanish version of the revised SIP (SIP-RS), as well as other commonly used assessment measures translated into Spanish, were administered at baseline and at the end of treatment. Internal consistency was excellent (α = .96), and construct validity was supported through correlations with composite scores from the Addiction Severity Index (ASI) (e.g., r = .57, p < .01 for ASI drug composite), and through differential SIP-RS scores according to diagnostic criteria. The SIP-RS also demonstrated an association with substance use and treatment retention, with higher baseline scores associated with significantly less abstinence during treatment (β = -.22, p < .01) and fewer days retained in treatment (β = -.14, p < .05). However, the latter association was moderated by participants' legal status. Nevertheless, this Spanish-translated version of the SIP (SIP-RS) appears to be a reliable and valid assessment of adverse consequences associated with alcohol and drug use, with psychometric properties comparable with the English version.


Assessing the prevention effectiveness of local Lyme disease control.
The effectiveness of any public health intervention is determined by its theoretical efficacy and by the level of engagement of the target population. A computer simulation model and basic epidemiologic concepts were used to estimate the effectiveness of interventions for preventing Lyme disease in a hypothetical community. The process for estimating numbers of Lyme disease cases prevented by each intervention is described. This assessment compares the effectiveness of alternative community-based prevention strategies, illuminates the limitations and distributive effects of interventions, and helps clarify available prevention options for community residents.


An indicator cell assay for T-cell tropic, macrophage-tropic, and primary isolates of HIV-1 based on green fluorescent protein.
Quantitation of HIV-1 in blood is now widely used by clinicians to manage antiviral therapy. Current methods to detect viral RNA are expensive, have slow turnaround times, and do not directly quantitate infectious particles. Indicator cell assay (ICA) methods for titering HIV-1 rely on the activation of HIV-1 long terminal repeat (LTR)-driven expression of a reporter gene by the viral tat gene product, which is expressed early in the course of infection. The Aequorea victoriana green fluorescent protein (GFP) has proven to be a useful reporter gene for detecting tat-mediated HIV-LTR activation. A general approach to developing a clinically useful ICA required a method of introducing the LTR-GFP expression cassette into various HIV1-infectable cell lines. The LTR-GFP expression cassette was inserted into the LXSN retrovector in a reverse orientation with respect to transcription from the 5' LTR. In cells transduced by the RH5 retrovector, GFP expression was tightly dependent on expression of HIV-1 tat. The PM1 human T-cell line was transduced with RH5 and was further engineered to express the CCR5 HIV-1 CD4 coreceptor constitutively. The resulting cell line, D5-R5, was susceptible to infection by primary HIV-1 strains, macrophage-tropic (M-tropic) and T-cell tropic (T-tropic) laboratory strains, and syncytium-inducing (SI) and and non-SI (NSI) variants. Four days after HIV-1 infection of the indicator cells, GFP expression was detected and quantitated by fluorescence activated cell sorter (FACS), without any false-positive signals. This GFP-based ICA method is of potential use in clinical management of HIV-1, especially in the detection and recovery of drug-resistant virus and the direct determination of antiviral drug sensitivities.


Moyamoya disease presenting with symptomatic ischemic stroke during new-generation tyrosine kinase inhibitor treatment: two illustrative cases.
Tyrosine kinase inhibitors (TKIs) have been widely used to treat chronic myeloid leukemia. Nilotinib and ponatinib, which are second- and third-generation TKIs, have been reported to cause cerebrovascular arterial complications. Here, we present two cases of moyamoya disease presenting with symptomatic ischemic stroke during new-generation TKI treatment. We judged that new-generation TKI treatment was a factor in symptomatic ischemic stroke of unknown moyamoya disease in both cases. Noninvasive examinations using magnetic resonance imaging or carotid ultrasonography should be performed before and during new-generation TKI treatment in order to prevent symptomatic ischemic stroke.


Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.
The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.


GATA1 Activity Governed by Configurations of cis-Acting Elements.
The transcription factor GATA1 regulates the expression of essential erythroid and megakaryocytic differentiation genes through binding to the DNA consensus sequence WGATAR. The GATA1 protein has four functional domains, including two centrally located zinc-finger domains and two transactivation domains at the N- and C-termini. These functional domains play characteristic roles in the elaborate regulation of diversified GATA1 target genes, each of which exhibits a unique expression profile. Three types of GATA1-related hematological malignancies have been reported. One is a structural mutation in the GATA1 gene, resulting in the production of a short form of GATA1 that lacks the N-terminal transactivation domain and is found in Down syndrome-related acute megakaryocytic leukemia. The other two are cis-acting regulatory mutations affecting expression of the Gata1 gene, which have been shown to cause acute erythroblastic leukemia and myelofibrosis in mice. Therefore, imbalanced gene regulation caused by qualitative and quantitative changes in GATA1 is thought to be involved in specific hematological disease pathogenesis. In the present review, we discuss recent advances in understanding the mechanisms of differential transcriptional regulation by GATA1 during erythroid differentiation, with special reference to the binding kinetics of GATA1 at conformation-specific binding sites.


Prognostic Performance of Hematological and Serum Iron and Metabolite Indices for Detection of Early Iron Deficiency Induced Metabolic Brain Dysfunction in Infant Rhesus Monkeys.
The current pediatric practice of monitoring for infantile iron deficiency (ID) via hemoglobin (Hgb) screening at one year of age does not identify preanemic ID, nor protect against later neurocognitive deficits. To identify biomarkers of iron-related metabolic alterations in the serum and brain and determine the sensitivity of conventional iron and heme indices for predicting risk of brain metabolic dysfunction using a nonhuman primate model of infantile ID. Simultaneous serum iron and RBC indices, and serum and cerebrospinal fluid (CSF) metabolomic profiles were determined in 20 rhesus infants, comparing iron sufficient (IS; N = 10) and ID (N = 10) infants at 2 and 4 months of age. Reticulocyte hemoglobin (RET-He) was lower at 2 weeks in the ID group. Significant IS vs. ID differences in serum iron indices were present at 2 months, but Hgb and RBC indices differed only at 4 months (P < 0.05). Serum and CSF metabolomic profiles of the ID and IS groups differed at 2 and 4 months (P < 0.05). Key metabolites, including homostachydrine and stachydrine (4-5-fold lower at 4 months in ID group, P < 0.05), were altered in both serum and CSF. Iron indices and RET-He at 2 months, but not Hgb or other RBC indices, were correlated with altered CSF metabolic profile at 4 months and had comparable predictive accuracy (area under the receiver operating characteristic curve scores, 0.75-0.80). Preanemic ID at 2 months was associated with metabolic alterations in serum and CSF in infant monkeys. Among the RBC indices, only RET-He predicted the future risk of abnormal CSF metabolic profile with a predictive accuracy comparable to serum iron indices. The concordance of homostachydrine and stachydrine changes in serum and CSF indicates their potential use as early biomarkers of brain metabolic dysfunction in infantile ID.