Postpsychotic depression in schizophrenia.
Several authors have described a severe depression in patients emerging from psychotic states. The clinical picture usually resembles that of a retarded depression with strong neurasthenic and schizoid components. It frequently emerges after a patient has been discharged from the hospital and may often go unnoticed. When manifest, the syndrome is usually stable phenomenologically, is often lengthy, and may be resistant to all modalities of treatment. Postpsychotic depression is a relatively neglected clinical area despite the risk of suicide and prolonged suffering. Therapeutic perseverence purportedly can improve the patient's long-term prognosis, and the phenomenon itself may be favorable prognostic sign. We present here a review and reformulation of this syndrome.


Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling.
Gap junction proteins form the substrate for electrical coupling between neurons. These electrical synapses are widespread in the CNS and serve a variety of important functions. In the retina, connexin 36 (Cx36) gap junctions couple AII amacrine cells and are a requisite component of the high-sensitivity rod photoreceptor pathway. AII amacrine cell coupling strength is dynamically regulated by background light intensity, and uncoupling is thought to be mediated by dopamine signaling via D(1)-like receptors. One proposed mechanism for this uncoupling involves dopamine-stimulated phosphorylation of Cx36 at regulatory sites, mediated by protein kinase A. Here we provide evidence against this hypothesis and demonstrate a direct relationship between Cx36 phosphorylation and AII amacrine cell coupling strength. Dopamine receptor-driven uncoupling of the AII network results from protein kinase A activation of protein phosphatase 2A and subsequent dephosphorylation of Cx36. Protein phosphatase 1 activity negatively regulates this pathway. We also find that Cx36 gap junctions can exist in widely different phosphorylation states within a single neuron, implying that coupling is controlled at the level of individual gap junctions by locally assembled signaling complexes. This kind of synapse-by-synapse plasticity allows for precise control of neuronal coupling, as well as cell-type-specific responses dependent on the identity of the signaling complexes assembled.


Interlaboratory Comparison of Extractable Organofluorine Measurements in Groundwater and Eel (Anguilla rostrata): Recommendations for Methods Standardization.
Research on per- and polyfluoroalkyl substances (PFAS) frequently incorporates organofluorine measurements, particularly because they could support a class-based approach to regulation. However, standardized methods for organofluorine analysis in a broad suite of matrices are currently unavailable, including a method for extractable organofluorine (EOF) measured using combustion ion chromatography (CIC). Here, we report the results of an international interlaboratory comparison. Seven laboratories representing academia, government, and the private sector measured paired EOF and PFAS concentrations in groundwater and eel (Anguilla rostrata) from a site contaminated by aqueous film-forming foam. Among all laboratories, targeted PFAS could not explain all EOF in groundwater but accounted for most EOF in eel. EOF results from all laboratories for at least one replicate extract fell within one standard deviation of the interlaboratory mean for groundwater and five out of seven laboratories for eel. PFAS spike mixture recoveries for EOF measurements in groundwater and eel were close to the criterion (±30%) for standardized targeted PFAS methods. Instrumental operation of the CIC such as replicate sample injections was a major source of measurement uncertainty. Blank contamination and incomplete inorganic fluorine removal may introduce additional uncertainties. To elucidate the presence of unknown organofluorine using paired EOF and PFAS measurements, we recommend that analysts carefully consider confounding methodological uncertainties such as differences in precision between measurements, data processing steps such as blank subtraction and replicate analyses, and the relative recoveries of PFAS and other fluorine compounds.


The C-terminal domain of light-harvesting chlorophyll-a/b-binding protein is involved in the stabilisation of trimeric light-harvesting complex.
Light-harvesting chlorophyll a/b-binding protein (LHCP) can be reconstituted with pigments in detergent solution to yield stable monomeric light-harvesting chlorophyll a/b complex (LHCII). This reconstitution is not significantly affected when up to ten amino acids are deleted on the C-terminus of LHCP or when a tryptophan, which is 11 positions from the C terminus (W222), is exchanged with other amino acids [Paulsen, H. & Kuttkat, A. (1993) Photochem. Photobiol. 57, 139-142]. Here we show that the exchange of W222 with histidine or glycine completely abolishes the ability of the protein to assemble into trimeric LHCII, either upon reconstitution of monomeric complexes in detergent solution or upon insertion into isolated thylakoids. It is concluded that part of the hydrophilic domain on the C-terminus of LHCP, although not essential for the formation of stable monomeric LHCII, is involved in trimer formation. The different degree to which various amino acids in place of W222 affect trainer formation suggests that a hydrophobic amino acid is needed in this position.


[Electron microscopic diagnosis of oncocytoma and renal cell carcinoma].
Electron microscopic examination of two tumors of the kidneys with similar histological structure (large eosinophilic cells with granular cytoplasm) showed that such tumors may be of different histogenesis (cytogenesis), their morphological picture in the light microscope being similar.


Electrocardiogram Beat-Classification Based on a ResNet Network.
When dealing with electrocardiography (ECG) the main focus relies on the classification of the heart's electric activity and deep learning has been proving its value over the years classifying the heartbeats, exhibiting great performance when doing so. Following these assumptions, we propose a deep learning model based on a ResNet architecture with convolutional 1D layers to classify the beats into one of the 4 classes: normal, atrial premature contraction, premature ventricular contraction and others. Experimental results with MIT-BIH Arrhythmia Database confirmed that the model is able to perform well, obtaining an accuracy of 96% when using stochastic gradient descent (SGD) and 83% when using adaptive moment estimation (Adam), SGD also obtained F1-scores over 90% for the four classes proposed. A larger dataset was created and tested as unforeseen data for the trained model, proving that new tests should be done to improve the accuracy of it.


Adaptive Lipid Immiscibility and Membrane Remodeling Are Active Functional Determinants of Primary Ciliogenesis.
Lipid liquid-liquid immiscibility and its consequent lateral heterogeneity have been observed under thermodynamic equilibrium in model and native membranes. However, cholesterol-rich membrane domains, sometimes referred to as lipid rafts, are difficult to observe spatiotemporally in live cells. Despite their importance in many biological processes, robust evidence for their existence remains elusive. This is mainly due to the difficulty in simultaneously determining their chemical composition and physicochemical nature, whilst spatiotemporally resolving their nanodomain lifetime and molecular dynamics. In this study, a bespoke method based on super-resolution stimulated emission depletion (STED) microscopy and raster imaging correlation spectroscopy (RICS) is used to overcome this issue. This methodology, laser interleaved confocal RICS and STED-RICS (LICSR), enables simultaneous tracking of lipid lateral packing and dynamics at the nanoscale. Previous work indicated that, in polarized epithelial cells, the midbody remnant licenses primary cilium formation through an unidentified mechanism. LICSR shows that lipid immiscibility and its adaptive collective nanoscale self-assembly are crucial for the midbody remnant to supply condensed membranes to the centrosome for the biogenesis of the ciliary membrane. Hence, this work poses a breakthrough in the field of lipid biology by providing compelling evidence of a functional role for liquid ordered-like membranes in primary ciliogenesis.


Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing Bcl-xL.
Combining microtubule-targeting antimitotic drugs with targeted apoptosis potentiators is a promising new chemotherapeutic strategy to treat cancer. In this study, we investigate the cellular mechanism by which navitoclax (previously called ABT-263), a Bcl-2 family inhibitor, potentiates apoptosis triggered by paclitaxel and an inhibitor of kinesin-5 (K5I, also called a KSP inhibitor), across a panel of epithelial cancer lines. By using time-lapse microscopy, we showed that navitoclax has little effect on cell death during interphase, but strongly accelerates apoptosis during mitotic arrest, and greatly increases the fraction of apoptosis-resistant cells that die. By systematically knocking down individual Bcl-2 proteins, we determined that Mcl-1 and Bcl-xL are the primary negative regulators of apoptosis during prolonged mitotic arrest. Mcl-1 levels decrease during mitotic arrest because of an imbalance between synthesis and turnover, and turnover depends in part on the MULE/HUWE1 E3 ligase. The combination of Mcl-1 loss with inhibition of Bcl-xL by navitoclax causes rapid apoptosis in all lines tested. Variation in expression levels of Mcl-1 and Bcl-xL largely determines variation in response to antimitotics alone, and antimitotics combined with navitoclax, across our panel. We concluded that Bcl-xL is a critical target of Bcl-2 family inhibitors for enhancing the lethality of antimitotic drugs in epithelial cancers, and combination treatment with navitoclax and a spindle specific antimitotic, such as a K5I, might be more effective than paclitaxel alone.


A dual effect of cobalt ions on the spontaneous release of transmitter at insect motor nerve terminals.
1. The effect of extracellular cobalt on the frequency of miniature excitatory post-synaptic potentials (MEPSPs) was studied in cockroach leg muscle fibres that had been depolarized with 20.8 mM-K saline. 2. Cobalt ions had a dual effect on the spontaneous release of transmitter, an inhibitory action being followed by an acceleratory. A reciprocal relationship between Ca2+ and Co2+ was found for both the inhibitory and acceleratory effects. 3. The equilibrium dissociation constant for Co2+ as a competitive antagonist of spontaneous release ranged from 0.4 to 0.65 mM. It is concluded that Co2+ is much more potent than Mg2+ in suppressing spontaneous transmitter release at the insect neuromuscular junction. The antagonism by extracellular Co2+ appears to occur only at the external surface site on the terminal membrane.


Neural Mechanisms of Choice Diversification.
When asked to select several options at once, people tend to choose a greater diversity of items than when they are asked to make these selections one at a time. Using functional magnetic resonance imaging (fMRI), we provide novel insight into the neural mechanisms underlying diversification in portfolio choices. We found that, as participants made multiple selections from a menu of different options, the current state of their choice portfolio (i.e., the previously selected options) dynamically modulates activity in the neural valuation system in response to the options under evaluation. More specifically, we found that activity in the ventral striatum (VS) decreases when the option has already been selected ("satiation"), while activity in the ventromedial prefrontal cortex increases when other options have previously been selected ("novelty-seeking"). Our findings reveal two processes that drive diversification in portfolio choices, and suggest that the context of previous selections strongly impacts how the brain evaluates current choice options.


[Structural and functional characteristics of urinary tract in offspring of Balkan endemic nephropathy patients].
Balkan endemic nephropathy (BEN) is a familial chronic progressive tubulointerstitial disease of unknown aetiology that occurs with high prevalence in endemic rural environments of Serbia, Bosnia and Herzegovina, Croatia, Bulgaria and Romania. It has been documented only in adults. The aim of this study was to examine clinical markers of BEN in children and adolescent offspring of BEN patients. Prospective clinical trial involved two groups of children and adolescents: I consisted of 30 offspring of BEN patients and II of 29 offspring of non-BEN dialysis patients, both of them living in the same South Morava region of Serbia. All of them were healthy at the time of the investigation, not receiving any drugs. The study included personal and family history, physical examination, comprehensive laboratory analyses and renal ultrasound. Blood pressure (BP) was determined by using casual BP and 24 h ABPM in subjects older than 5 years. Urinary proteins were investigated by analysing microalbumin, alfa 1 microglobulin, beta 2 microglobulin and SDS-PAGE electrophoresis. GFR was measured by estimated creatinine clearance and by serum Cystatin C concentrations. There were no statistically significant differences in age, gender, history of urinary tract infections or functional voiding disorders between these two groups. All of the studied subjects had normal BP and GFR. Renal ultrasound was abnormal only in BEN offspring (6.66%) as well as increased urine concentrations of microalbumin (3.3%), alpha 1 microglobulin (10%) and beta 2 microglobulin (13.3%) while low molecular protein (<66,000 D) was prevalent in BEN compared with non-BEN offspring (21.43% vs. 3.7%). Renal abnormalities in offspring of BEN patients may be an early marker of BEN.This has to be confirmed in long term follow-up of a greater number of BEN paediatric offspring.


Coordinated upregulation of two CDP-diacylglycerol synthases, YnbB and CdsA, is essential for cell growth and membrane protein export in the cold.
YnbB is a paralogue of CdsA, a CDP-diacylglycerol synthase. While the cdsA gene is essential, the ynbB gene is dispensable. So far, no phenotype of ynbB knockout has been observed. We found that a ynbB knockout strain acquired cold-sensitivity on growth under CdsA-limited conditions. We found that MPIase, a glycolipid involved in protein export, is cold-upregulated to facilitate protein export in the cold, by increasing the mRNA levels of not only CdsA but also that of YnbB. Under non-permissive conditions, phospholipid biosynthesis proceeded normally, however, MPIase upregulation was inhibited with accumulation of precursors of membrane and secretory proteins such as M13 procoat and proOmpA, indicating that YnbB is dedicated to MPIase biosynthesis, complementing the CdsA function.


The development of a unique physical activity self-report for young children: challenges and lessons learned.
The number of overweight and obese children in the Western world is alarming. Efforts to impact this problem at an individual level have had little effect. Interventions that focus on the whole population may prove more successful. This study reports the development of a unique self-report picture questionnaire designed to assess playground physical activity preferences in young children (4-9 years, N = 1,881) at 14 regional Australian primary schools. Children's picture preferences were compared with observational data using the Children's Activity Scanning tool (CAST2). Results indicate that 62% to 89% of children preferred activities that were moderate or highly active; however, CAST2 data indicated that children spent only 50% to 70% of play time being active. The findings confirm that young children are able to indicate their preferences for physical activity. Important considerations in future attempts to develop a measure of physical activity in young children are discussed.


Use of fetal skeletal mineralization for prediction of parturition date in cats.
To determine the relationship between parturition date and fetal skeletal mineralization detected radiographically in cats. Prospective clinical trial. 31 queens and their 49 pregnancies. Seventeen pregnant queens were radiographed with a computed radiography system every 2 to 3 days from 1 week after pregnancy was identified by abdominal palpation until parturition. Radiographs were evaluated to determine the first identifiable mineralization of 16 bony structures and teeth during each pregnancy. This information was used to establish a table of expected parturition dates on the basis of fetal mineralization. Single radiographs from an additional 32 pregnant cats were evaluated, and predictions of parturition dates were made on the basis of the mineralization table. Mineralization was first detected 25 to 29 days prior to parturition (dpp). Mineralization was determined for the spinal column (22 to 27 dpp), skull (21 to 27 dpp), ribs (20 to 25 dpp), scapula (17 to 24 dpp), humerus (20 to 24 dpp), femur (19 to 23 dpp), radius (15 to 22 dpp), tibia (15 to 21 dpp), ulna (5 to 21 dpp), pelvis (8 to 20 dpp), fibula (0 to 17 dpp), tail (8 to 16 dpp), metacarpals and metatarsals (3 to 14 dpp), phalanges (0 to 11 dpp), calcaneus (0 to 10 dpp), and teeth (1 to 6 dpp). Date of parturition was predictable within 3 days in 75% of cats. Identification of bony structures in the fetus is useful in estimating the time to parturition in queens.


Trends in HIV seroprevalence and needle sharing among Puerto Rican drug injectors in Puerto Rico and New York: 1992-1999.
This study assessed trends in HIV seroprevalence and needle-sharing behaviors among Puerto Rican injection drug users (IDUs) in Puerto Rico and New York. Data from two studies of IDUs conducted from 1992 through 1995 and 1998 through 1999 in Bayamón, Puerto Rico, and East Harlem, New York, were examined to assess trends over this period. Separate analyses were conducted for IDUs who were current crack smokers. Significant decreasing trends in seroprevalence were found among IDUs in the New York and Puerto Rico samples (p <.001). Significant decreasing trends in receptive and distributive needle sharing were found in the New York sample, and a significant decline in receptive sharing was found in the Puerto Rico sample. Overall, higher levels of needle-sharing behaviors were reported in Puerto Rico compared with New York. Decreasing trends in needle sharing and seroprevalence in both communities are an encouraging finding. Ongoing epidemiologic studies to monitor the epidemic and continued prevention efforts to help maintain or further these declines are needed, particularly to address the higher rates of needle sharing in Puerto Rico.


Realization of an Ultrasensitive and Highly Selective OFET NO2 Sensor: The Synergistic Combination of PDVT-10 Polymer and Porphyrin-MOF.
Organic field-effect transistors (OFETs) are emerging as competitive candidates for gas sensing applications due to the ease of their fabrication process combined with the ability to readily fine-tune the properties of organic semiconductors. Nevertheless, some key challenges remain to be addressed, such as material degradation, low sensitivity, and poor selectivity toward toxic gases. Appropriately, a heterojunction combination of different sensing layers with multifunctional capabilities offers great potential to overcome these problems. Here, a novel and highly sensitive receptor layer is proposed encompassing a porous 3D metal-organic framework (MOF) based on isostructural-fluorinated MOFs acting as an NO2 specific preconcentrator, on the surface of a stable and ultrathin PDVT-10 organic semiconductor on an OFET platform. Here, with this proposed combination we have unveiled an unprecedented 700% increase in sensitivity toward NO2 analyte in contrast to the pristine PDVT-10. The resultant combination for this OFET device exhibits a remarkable lowest detection limit of 8.25 ppb, a sensitivity of 680 nA/ppb, and good stability over a period of 6 months under normal laboratory conditions. Further, a negligible response (4.232 nA/%RH) toward humidity in the range of 5%-90% relative humidity was demonstrated using this combination. Markedly, the obtained results support the use of the proposed novel strategy to achieve an excellent sensing performance with an OFET platform.


Theoretical Estimation of Tissue Thermal Response and Associated Thermal Damage During Gold Nanorod-enhanced Photothermal Therapy of Tumors.
In the present work, we implemented a computational framework of in vivo gold nanorod (GNR)-enhanced photothermal therapy (PTT) for tumor treatment. The temperature-dependent thermophysical properties of biological tissue and the optical properties of both GNRs and the biological media were included. The latter were modulated during the treatment simulation to account for their variation, from the native to the coagulated state. The contribution of tissue injury-dependent blood perfusion was also considered. The developed model allowed for the estimation of temperature distribution during the photothermal procedure at different procedural settings and amounts of GNRs embedded in the tumor region (i.e., 12.5 μg, 25 μg, and 50 μg). Furthermore, the influence of GNRs on thermal injury, estimated with different damage models, was assessed. The inclusion of GNRs in the tumor entailed an increment of maximum tissue temperature, and faster heating kinetics, as witnessed by the lower time needed to reach complete thermal damage at the tumor center. The percentage of tumor thermal damage evaluated at the end of the simulated treatment was 48%, 69%, and 90%, for PTT in the presence of 12.5 μg, 25 μg, and 50 μg of GNRs, respectively.Clinical Relevance-This establishes that simulation-based tools, modeling the tissue properties variation during the photothermal treatment, can serve as promising preplanning platforms for nanoparticle-assisted light therapies.


N-acetylcysteine protects ovarian follicles from ischemia-reperfusion injury in xenotransplanted human ovarian tissue.
Can antioxidant treatment with N-acetylcysteine (NAC) protect ovarian follicles from ischemia-reperfusion injury in xenotransplanted human ovarian tissue? Daily administration of NAC for 7-12 days post-transplantation reduced ischemia-reperfusion injury and increased follicle survival in human ovarian xenografts by upregulating the antioxidant defense system and exerting anti-inflammatory and antiapoptotic effects. Freezing of human ovarian tissue is performed with high follicular survival rates but up to 70% of follicles appear to be lost due to hypoxia and ischemia-reperfusion injury during ovarian tissue transplantation (OTT). NAC has been demonstrated to possess antioxidant and antiapoptotic properties, and studies in rodents have shown that intraperitoneal administration of NAC reduces ischemia-reperfusion injury and increases follicle survival in autotransplanted murine ovaries. Pieces of frozen-thawed human ovarian tissue from 28 women aged 23-36 years were transplanted to immunodeficient mice in short- and long-term xenograft studies or cultured in vitro. Three short-term xenograft studies (1-week duration) were performed, in which saline or 150 mg/kg NAC was administered for 7 days post-transplantation (n = 12 patients per group). Two long-term xenograft studies (4 weeks of duration) were performed. In one of these studies, saline or 150 mg/kg NAC was administered for 12 days (n = 12 patients per group), while in the other study 50, 150 or 300 mg/kg NAC was administered for 7 days (n = 8 patients per group). In addition, human ovarian tissue (n = 12 pieces from three patients per group) was cultured with increasing concentrations of NAC (0, 5, 25 and 75 mM) for 4 days in vitro. Donated ovarian tissue was obtained from women who had undergone ovarian tissue cryopreservation for fertility preservation at the University Hospital of Copenhagen. Cortical tissue pieces (5 × 5 × 1 mm) were transplanted subcutaneously to immunodeficient mice and NAC or saline was injected intraperitoneally. Grafts were retrieved after 1 or 4 weeks and follicle density was assessed. Gene expression analysis of antioxidant defense markers (superoxide dismutase; Sod1/SOD1, heme oxygenase-1; Hmox1/HMOX1, catalase; Cat/CAT), proinflammatory cytokines (tumor necrosis factor-alpha; Tnf-α, interleukin-1-beta; Il1-β, interleukin 6; Il6), apoptotic factors (B-cell lymphoma 2; Bcl2/BCL2, Bcl-2-associated X protein; Bax/BAX) and angiogenic factors (vascular endothelial growth factor A; Vegfa/VEGFA, angiopoietin-like 4; Angptl4/ANGPTL4) was performed in 1-week-old human ovarian xenografts and in cultured human ovarian tissue. Grafts retrieved after 4 weeks were histologically processed and analyzed for vascularization by CD31 immunohistochemical staining, fibrosis by Masson's Trichrome staining and apoptosis by immunofluorescence using cleaved caspase-3. After 1-week grafting, the relative expression of Sod1, Hmox1 and Cat was significantly higher in the group receiving 150 mg/kg NAC (NAC150-treated group) compared to controls (P = 0.04, P = 0.03, and P = 0.01, respectively), whereas the expression levels of Tnf-α, Il1-β and Il6 were reduced. The Bax/Bcl2 ratio was also significantly reduced in the NAC150-treated group (P < 0.005). In vitro, the relative gene expression of SOD1, HMOX1 and CAT increased significantly in the human ovarian tissue with increasing concentrations of NAC (P < 0.001 for all genes). However, the expression of VEGFA and ANGPTL4 as well as the BAX/BCL2 ratio decreased significantly with increasing concentrations of NAC (P < 0.02, P < 0.001 and P < 0.001, respectively). After 4-week grafting, fibrosis measured by collagen content was similar in the NAC150-treated group compared to controls (control: 56.6% ± 2.2; NAC150: 57.6% ± 1.8), whereas a statistically significant reduction in the CD31-positive vessel area was found (control: 0.69% ± 0.08; NAC150: 0.51% ± 0.07; P < 0.02). Furthermore, a reduced immunoreactivity of cleaved caspase-3 was observed in follicles of the NAC150-treated xenografts compared to controls. Follicle density (follicles/mm3, mean ± SD) was higher in the NAC150-treated group compared to the control group in the 1-week xenografts (control: 19.5 ± 26.3; NAC150: 34.2 ± 53.5) and 4-week xenografts (control: 9.3 ± 11.0; NAC150: 14.4 ± 15.0). Overall, a 2-fold increase in follicle density was observed in the NAC150-group after 1-week grafting where fold changes in follicle density were calculated in relation to grafts from the same patient. Around a 5-fold increase in follicle density was observed in the NAC150 and NAC300 groups after 4-week grafting. N/A. Follicle density in the human ovarian cortex is highly heterogeneous and can vary 100-fold between cortex pieces from the same woman. A high variability in follicle density within and between treatment groups and patients was found in the current study. Thus, solid conclusions cannot be made. While intraperitoneal injections of NAC appeared to reduce ischemia-reperfusion injury in human ovarian xenografts, different administration routes should be investigated in order to optimize NAC for potential clinical use. This is the first study to demonstrate the antioxidant, anti-inflammatory and antiapoptotic properties of NAC in xenotransplanted human ovarian tissue. Therefore, NAC appears to be a promising candidate for protecting ovarian follicles from ischemia-reperfusion injury. This provides the initial steps toward clinical application of NAC, which could potentially reduce the loss of ovarian follicles following OTT. We are grateful to the Danish Childhood Cancer Foundation, Hørslev Foundation, Aase and Einar Danielsen's Foundation (grant number: 10-001999), Dagmar Marshalls Foundation, Else and Mogens Wedell-Wedellsborgs Foundation, Knud and Edith Eriksens Mindefond, and Fabrikant Einar Willumsens Mindelegat for funding this study. None of the authors have any competing interests to declare.


Multiple Spontaneous Intracranial-Extracranial Arterial Dissections in a Patient with Osteogenesis Imperfecta.
A 40-year-old male with osteogenesis imperfecta (OI) was admitted to the hospital with an acute right monoparesis. Diffusion-weighted MRI showed infarction in the territory of the left anterior cerebral artery (ACA) and in the left posterior cerebral artery (PCA). In his vascular imaging, occlusion of the left vertebral artery (VA) starting from V2 segment was consistent with dissection and pseudoaneurysm in the right ACA. We presented this case because of the presence of spontaneous and simultaneous occurrence of both intracranial and extracranial arterial dissections in OI.


Differential white blood cell count and incident heart failure in men and women in the EPIC-Norfolk study.
Markers of inflammation are associated with increased risk of heart failure, but data on differential white blood cell (WBC) count are lacking. We examined the prospective association between differential WBC count and incident heart failure events. Hazard ratios (HRs) (per increase of 1000 cells/μL, 95% confidence interval) of total WBC count and individual components on heart failure were calculated in apparently healthy 7195 men and 8816 women aged 39-79 participating in the 'European Prospective Investigation into Cancer and Nutrition' (EPIC) study in Norfolk. During a mean follow-up of 12.4 years, 935 incident cases of heart failure occurred. In women, neither total WBC count (1.02, 0.96-1.09) nor individual components were associated with HR of heart failure after accounting for known risk factors. In men, HR of heart failure increased with increasing levels of total WBC count (1.09, 1.04-1.15) after accounting for established risk factors; analysis of WBC components showed increased hazard with increasing levels of granulocyte count (1.16, 1.09-1.24) and, independently of this, decreased hazard with increasing levels of monocyte count (0.71, 0.53-0.93); lymphocyte count was not significantly associated with heart failure (0.97, 0.83-1.13). Results did not change materially after excluding smokers, adjusting for intermediate myocardial infarction and coronary heart disease and C-reactive protein. Inflammation as measured by WBC count was independently associated with incident heart failure in apparently healthy men but not women. The association observed in men was driven by granulocyte count, but there was an independent inverse association between monocyte count and incident heart failure.


[Endoscopic (endoluminal) treatment of gastroesophageal reflux disease].
New endoscopic (endoluminal) methods have been developed recently for the treatment of gastroesophageal reflux disease. The options are endoluminal gastroplasty, delivery of radiofrequency to the lower oesophagus reducing transient relaxation of the lower sphincter, or implantation of polymer in the lower oesophagus. The respective results of these procedures are detailed and discussed. The lack of long term follow-up and the number of procedures do not allow to validate the endoluminal procedures which remain in the field of clinical research. When the medical treatment fails or in case of complication, the glod standard is still the laparoscopic fundoplication. But it is possible in the future that one or more endoluminal techniques could change the management of reflux disease.


Intervention mechanisms of an experience sampling intervention for spousal carers of people with dementia: a secondary analysis using momentary data.
Objectives: A psychosocial intervention for spousal carers of people with dementia promoted emotional well-being through self-monitoring and personalized feedback, as demonstrated in a previous randomized controlled trial. The mechanism behind the intervention effects is thought to lie in increased awareness of, and thus, engagement in behaviours that elicit positive emotions (PA). This secondary analysis tests the assumption by investigating momentary data on activities, affect, and stress and explores the relevance of personalized feedback compared to self-monitoring only.Methods: The intervention was based on the experience sampling method (ESM), meaning that carers self-monitored own affect and behaviours 10 times/day over 6 weeks. The experimental group received personalized feedback on behaviours that elicit PA, while the pseudo-experimental group performed self-monitoring only. A control group was also included. ESM-data of 72 carers was analysed using multilevel mixed-effects models.Results: The experimental group reported significant increases in passive relaxation activities over the 6 weeks (B = 0.28, SE = 0.12, Z = 2.43, p < .05). Passive relaxation in this group was negatively associated with negative affect (r = -0.50, p = .01) and positively associated with activity-related stress (r = 0.52, p = .007) from baseline to post-intervention. Other activities in this or the other groups did not change significantly.Conclusion: Carer's daily behaviours were only affected when self-monitoring was combined with personalized feedback. Changing one's daily behaviour while caring for a person with dementia is challenging and aligned with mixed emotions. Acknowledging simultaneously positive and negative emotions, and feelings of stress is suggested to embrace the complexity of carer's life and provide sustainable support.


How accurate is the smoking history in newly diagnosed diabetic patients?
A smoking history was obtained from 94 consecutive newly diagnosed diabetic patients referred to an adult diabetic clinic. The smoking load was measured using urinary cotinine/creatinine ratios (COT/Cr). Fifty-six patients (60%) claimed to be non-smokers, but COT/Cr suggested active smoking in five of these. The patients who admitted to smoking were given standardised anti-smoking advice. At 3 months, 32 smoking patients were reviewed and 21 (66%) claimed to have reduced or stopped smoking. However, the median COT/Cr in the 32 patients showed no significant reduction (11.15 vs. 9.30 micrograms/mg). Urinary COT/Cr indicated that 6 patients had stopped smoking (median COT/Cr 6.98 fell to 0.97 micrograms/mg), but several patients had a marked rise in COT/Cr, demonstrating that their smoking habit had increased considerably. Therefore the smoking history obtained from new diabetic patients can be very misleading. An objective measure of smoking habits in the initial assessment and follow-up of diabetes may be worthwhile. Anti-smoking counselling at diagnosis of diabetes may persuade some smokers to stop.


Bridge to surgery using partially covered self-expandable metal stents (PCMS) in malignant biliary stricture: an acceptable paradigm?
Partially covered self-expanding metal stents (PCMS) have been extensively used for palliation of malignant distal biliary stricture. Many centers have been using them as a bridge to surgery (BTS) regardless of resectability with or without eventual neoadjuvant therapy. We analyzed the outcome of all patients receiving PCMS and subsequently referred for surgery in our institution. Our prospectively established pancreaticobiliary database was retrospectively analyzed to retrieve all patients with malignant biliary stricture who underwent PCMS placement and subsequently went for curative surgical attempt at our institution. Cancer type and staging, adverse events related to stent placement or surgery, type of surgery performed, time between stenting and surgery, length of postoperative hospitalization, and postoperative follow-up were recorded. 27 patients (21 men; median age 66 years, range 39-82 years) received PCMS. Indications for placement included biliary stricture related to pancreatic cancer (n=23) or other malignancies (n=4). Median time between stenting and surgery was 32 days (range 6-569 days). Median time of hospitalization post surgery was 7 days (1-40 days). All patients underwent exploratory laparoscopy, followed in 9 (33.3%) by Whipple procedure with uneventful removal of the PCMS. Eighteen patients (66.6%) had their attempted curative resection terminated early due to intraoperative evidence of metastatic spread, with 8 (30%) patients undergoing peritoneal or liver metastasis biopsy. PCMS were left in place in those 18 patients. Complications related to PCMS in the bridge-to-surgery period included migration (n=2, 7.4%) and tissue overgrowth (n=1, 3.4%), all of them managed by endoscopic removal and replacement with PCMS. Median follow-up post surgery was 210 days (range 9-1,642 days). PCMS are an appropriate BTS option. For resectable patients, PCMS results in biliary drainage and allows for neoadjuvant treatment without portending subsequent curative resection (Whipple). For unresectable patients, long-term biliary drainage is provided by PCMS.


Rheology and microstructure of non-Brownian suspensions in the liquid and crystal coexistence region: strain stiffening in large amplitude oscillatory shear.
Concentrated hard-sphere suspensions in the liquid and crystal coexistence region show a unique nonlinear behavior under a large amplitude oscillatory shear flow, the so-called strain stiffening, in which the viscosity or modulus suddenly starts to increase near a critical strain amplitude. Even though this phenomenon has been widely reported in experiments, its key mechanism has never been investigated in a systematic way. To have a good understanding of this behavior, a numerical simulation was performed using the lattice Boltzmann method (LBM). Strain stiffening was clearly observed at large strain amplitudes, and the critical strain amplitude showed an angular frequency dependency. The distortion of the shear stress appeared near the critical strain amplitude, and the nonlinear behavior was quantified by the Fourier transformation (FT) and the stress decomposition methods. Above the critical strain amplitude, an increase in the global bond order parameter Ψ(6) was observed at the flow reversal. The maximum of Ψ(6) and the maximum shear stress occurred at the same strain. These results show how strongly the ordered structure of the particles is related to the stress distortion. The ordered particles maintained a bond number of "two" with alignment with the compressive axis, and they were distributed over a narrow range of angular distribution (110°-130°). In addition, the ordered structure was formed near the lowest shear rate region (the flow reversal). The characteristics of the ordered structure were remarkably different from those of the hydroclusters which are regarded as the origin of shear thickening. It is clear that strain stiffening and shear thickening originate from different mechanisms. Our results clearly demonstrate how the ordering of the particles induces strain stiffening in the liquid and crystal coexistence region.


Clusters of competence: Relationship between self-reported professional competence and achievement on a national examination among graduating nursing students.
To identify clusters based on graduating nursing students' self-reported professional competence and their achievement on a national examination. Furthermore, to describe and compare the identified clusters regarding sample characteristics, students' perceptions of overall quality of the nursing programme, and students' general self-efficacy (GSE). A cross-sectional study combining survey data and results from a national examination. Data were collected at two universities and one university college in Sweden in January 2017, including 179 students in the final term of the nursing programme. The study was based on the Nurse Professional Competence Scale, the GSE scale, and results from the National Clinical Final Examination. A two-step cluster analysis was used to identify competence profiles, followed by comparative analyses between clusters. Three clusters were identified illustrating students' different competence profiles. Students in Clusters 1 and 2 passed the examination, but differed in their self-assessments of competence, rating themselves under and above the overall median value, respectively. Students in Cluster 3 failed the examination but rated themselves at the overall median level or higher. The study illustrates how nursing students' self-assessed competence might differ from competency assessed by examination, which is challenging for nursing education. Self-evaluation is a key learning outcome and is, in the long run, essential to patient safety. The study has identified clusters of students where some overestimate and others underestimate their competence. Students who assessed their competence low but passed the exam assessed their GSE lower than other students. The findings illuminate the need for student-centred strategies in nursing education, including elements of self-assessment in relation to examination to make the students more aware of their clinical competence.


ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes.
Amyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease that causes motor neuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause for the familial form of this disease. Transgenic mice expressing mutant SOD1 develop age-dependent motor neuron degeneration, skeletal muscle weakness, paralysis and death similar to humans. The mechanism whereby mutant SOD1 induces motor neuron degeneration is not understood but widespread mitochondrial vacuolation has been observed during early phases of motor neuron degeneration. How this vacuolation develops is not clear, but could involve autophagic vacuolation, mitochondrial permeability transition (MPT) or uncharacterized mechanisms. To determine which of these possibilities are true, we examined the vacuolar patterns in detail in transgenic mice expressing mutant SOD1G93A. Vacuolar patterns revealed by electron microscopy (EM) suggest that vacuoles originate from the expansion of the mitochondrial intermembrane space and extension of the outer mitochondrial membrane. Immunofluorescence microscopy and immuno-gold electron microscopy reveal that vacuoles are bounded by SOD1 and mitochondrial outer membrane markers, but the inner mitochondrial membrane marker is located in focal areas inside the vacuoles. Small vacuoles contain cytochrome c while large vacuoles are porous and lack cytochrome c. Vacuoles lack lysosomal signal but contain abundant peroxisomes and SOD1 aggregates. These findings demonstrate that mutant SOD1, possibly by toxicity associated with its aggregation, causes mitochondrial degeneration by inducing extension and leakage of the outer mitochondrial membrane, and expansion of the intermembrane space. This could release the pro-cell death molecules normally residing in the intermembrane space and initiate motor neuron degeneration. This Mitochondrial Vacuolation by Intermembrane Space Expansion (MVISE) fits neither MPT nor autophagic vacuolation mechanisms, and thus, is a previously uncharacterized mechanism of mitochondrial degeneration in mammalian CNS.


Ultrathin endoscope equipped with ultrasonic miniprobe for upper GI US in a porcine model.
Ultrathin EGD (UT-EGD) is an ideal tool for unsedated upper GI examination and pediatric gastroenterology but is rarely competent for EUS miniprobe (EUS-MP). We developed a UT-EGD US method (UT-EUS) and verified its clinical application value through animal experiments. Five Bama miniature pigs were selected. Using an acoustic medium, we performed US on the duodenum, stomach, and esophagus, respectively, with conventional 20-MHz EUS miniprobe (EUS-MP-20), 20-MHz UT-EUS (UT-EUS-20), and 30-MHz UT-EUS (UT-EUS-30). The times to acquire 5 consecutive stable US images, number of identifiable wall layers, and quality and penetration depth of the images were recorded. No significant differences were found in the time required to obtain images between EUS-MP-20 and UT-EUS-20 at each site (P > .05). UT-EUS-30 showed more wall levels than UT-EUS-20 (P < .05). No significant differences were noted between EUS-MP-20 and UT-EUS-20 in imaging quality and penetration depth (P > .05). The UT-EUS is easy to use with a satisfactory image quality and has potential clinical application value.


Galectin-9 as a Potential Modulator of Lymphocyte Adhesion to Endothelium via Binding to Blood Group H Glycan.
The recruitment of leukocytes from blood is one of the most important cellular processes in response to tissue damage and inflammation. This multi-step process includes rolling leukocytes and their adhesion to endothelial cells (EC), culminating in crossing the EC barrier to reach the inflamed tissue. Galectin-8 and galectin-9 expressed on the immune system cells are part of this process and can induce cell adhesion via binding to oligolactosamine glycans. Similarly, these galectins have an order of magnitude higher affinity towards glycans of the ABH blood group system, widely represented on ECs. However, the roles of gal-8 and gal-9 as mediators of adhesion to endothelial ABH antigens are practically unknown. In this work, we investigated whether H antigen-gal-9-mediated adhesion occurred between Jurkat cells (of lymphocytic origin and known to have gal-9) and EA.hy 926 cells (immortalized endothelial cells and known to have blood group H antigen). Baseline experiments showed that Jurkat cells adhered to EA.hy 926 cells; however when these EA.hy 926 cells were defucosylated (despite the unmasking of lactosamine chains), adherence was abolished. Restoration of fucosylation by insertion of synthetic glycolipids in the form of H (type 2) trisaccharide Fucα1-2Galβ1-4GlcNAc restored adhesion. The degree of lymphocyte adhesion to native and the "H-restored" (glycolipid-loaded) EA.hy 926 cells was comparable. If this gal-9/H (type 2) interaction is similar to processes that occur in vivo, this suggests that only the short (trisaccharide) H glycan on ECs is required.


Epigenetic Silencing of THY1 Tracks the Acquisition of the Notch1-EGFR Signaling in a Xenograft Model of CD44+/CD24low/CD90+ Myoepithelial Cells.
The surface glycoprotein THY is a marker of myoepithelial precursor cells, which are basal cells with epithelial-mesenchymal intermediate phenotype originating from the ectoderm. Myoepithelial precursor cells are lost during progression from in situ to invasive carcinoma. To define the functional role of Thy1-positive cells within the myoepithelial population, we tracked Thy1 expression in human breast cancer samples, isolated THY1-positive myoepithelial progenitor cells (CD44+/CD24low/CD90+), and established long-term cultures (parental cells). Parental cells were used to generate a xenograft model to examine Thy1 expression during tumor formation. Post-transplantation cell cultures lost THY1 expression through methylation at the THY1 locus and this is associated with an increase in EGFR and NOTCH1 transcript levels. Thy1-low cells are sensitive to the EGFR/HER2 dual inhibitor lapatinib. High THY1 expression is associated with poorer relapse-free survival in patients with breast cancer. THY1 methylation may track the shift of bipotent progenitors into differentiated cells. Thy1 is a good candidate biomarker in basal-like breast cancer. IMPLICATIONS: Our findings provide evidence that THY1 expression is lost in xenografts due to promoter methylation. Thy1-low cells with increased EGFR and Notch1 expression are responsive to target therapy. Because DNA methylation is often altered in early cancer development, candidate methylation markers may be exploited as biomarkers for basal-like breast cancer.


Some properties of human erythrocyte pyrimidine 5'-nucleotidase.
In haemolysates human erythrocyte pyrimidine 5'-nucleotidase had a single optimum at pH 7.2 with CMP and 6.75 with UMP as substrate. The purified enzyme showed two pH optima at pH 6.25 and 7.2 with UMP as substrate. The enzyme was inhibited by both its products - inorganic phosphate and pyrimidine nucleoside. The inhibition by inorganic phosphate appeared to be non-competitive with Ki = 1.5 mM. Contrary to previous reports adenosine and inosine did not inhibit the enzyme.


Large litter rearing improves leptin sensitivity and hypothalamic appetite markers in offspring of rat dams fed high-fat diet during pregnancy and lactation.
Maternal high-fat (HF) diet has long-term consequences on the offspring's metabolic phenotype. Here, we determined the effects of large litter (LL) rearing in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on standard chow (CHOW) or HF diet throughout gestation and lactation. Pups were raised in normal litters (NLs) (10 pups/dam) or LLs (16 pups/dam) during lactation, resulting in 4 groups: CHOW-NL, CHOW-LL, HF-NL, and HF-LL. The offspring were weaned onto to either CHOW or HF diet on postnatal day 21. Male and female pups with maternal HF diet (HF-NL) had greater body weight and adiposity, higher plasma leptin levels, impaired glucose tolerance, abnormal hypothalamic leptin signaling pathways (lower leptin receptor-b [OB-Rb] and signal transducer and activator of transcription 3, higher suppressor of cytokine signaling 3 mRNA expression) and appetite markers (lower neuropeptide Y and Agouti-related peptide mRNA expression), and reduced phospho-signal transducer and activator of transcription 3 level in response to leptin in the arcuate nucleus at weaning, whereas LL rearing normalized these differences. When weaned onto CHOW diet, adult male offspring from HF diet-fed dams continued to have greater adiposity, higher leptin levels, and lower hypothalamic OB-Rb, and LL rearing improved them. When weaned onto HF diet, both adult male and female offspring with maternal HF diet had greater body weight and adiposity, higher leptin levels, impaired glucose tolerance, lower OB-Rb, and higher suppressor of cytokine signaling 3 in hypothalamus compared with those of CHOW dams, whereas LL rearing improved most of them except male OB-Rb expression. Our data suggest that LL rearing improves hypothalamic leptin signaling pathways and appetite markers in an age- and sex-specific manner in this model.


Science of cryopreservation in reproductive medicine - Embryos and oocytes as exemplars.
The modern successes of reproductive medicine are based on the achievements in the fields of artificial fertilization and cryobiology over the last 50years. Cryopreservation of oocytes makes it possible to preserve their reproductive potential after surgical interventions, treatment of cancer, for delayed pregnancy and to use cells for donation. Cryopreservation of embryos allows not only to reduce the multiple pregnancies rate and to increase the cumulative pregnancy rate as a result of embryo transfer in the following favorable cycles of the patient, but is also a necessary procedure in case of genetic diagnosis or in the case of contraindications for embryo transfer in the stimulated cycle due to possible complications. However, the viability of cryopreserved oocytes and embryos depends on the degree of their cryo damage during the process of freeze-warming. In this regard, it is very important to develop such freezing protocols that minimize the damages caused by the intra- and extracellular ice crystal formation, toxic effect of high concentrations of cryoprotectants and osmotic stresses. The effectiveness of cryopreservation of gametes and embryos is assessed on the basis of morphological, functional and genetic changes in the cells after warming. Special attention should be paid to the ethical issues of assisted reproductive technology, including cryobiotech technologies, which in many countries remain open and in need of settlement.


Exceptionally high titres in atypical presentation of occult epididymo-orchitis due to brucellosis.
A male patient of 32 years was referred for surgical drainage and orchidectomy of the right testis following a cycling injury. A Venereal Disease Research Laboratory (VDRL) test was requested by the surgery department to rule out secondary syphilis. Although serum samples gave a negative result in the VDRL test, qualitative screening was performed for Brucella antibodies, as per hospital policy, since brucellosis is endemic in this region. Following a positive reaction, a quantitative standard tube agglutination test was carried out yielding titres that were exceptionally high (STAT = 40 960 IU ml(-1); 2-ME = 1 : 5120). This finding correlated with the patient's history which included a number of predisposing factors for contracting brucellosis including exposure to cattle, consumption of raw milk and assisting in the parturition of cattle. Consequently, surgery was postponed and treatment was changed from injections of ceftriaxone to the WHO regimen for the treatment of brucellosis: 1 g streptomycin once daily, administered intra-muscularly, plus 100 mg doxycycline twice daily, taken orally. Following 3 days of this treatment, the testicular swelling reduced considerably and orchidectomy was not required. Indeed, after a week, swelling was completely resolved and the patient was discharged. To our knowledge, this is the first case of such high titres in a patient as a result of epididymo-orchitis without the typical clinical presentation of fever and joint pain that is normally associated with brucellosis.


Sex-linked transcriptional divergence in the hermaphrodite fungus Neurospora tetrasperma.
In the filamentous ascomycete Neurospora tetrasperma, a large (approx. 7 Mbp) region of suppressed recombination surrounds the mating-type (mat) locus. While the remainder of the genome is largely homoallelic, this region of recombinational suppression, extending over 1500 genes, is associated with sequence divergence. Here, we used microarrays to examine how the molecular phenotype of gene expression level is linked to this divergent region, and thus to the mating type. Culturing N. tetrasperma on agar media that induce sexual/female or vegetative/male tissue, we found 196 genes significantly differentially expressed between mat A and mat a mating types. Our data show that the genes exhibiting mat-linked expression are enriched in the region genetically linked to mating type, and sequence and expression divergence are positively correlated. Our results indicate that the phenotype of mat A strains is optimized for traits promoting sexual/female development and the phenotype of mat a strains for vegetative/male development. This discovery of differentially expressed genes associated with mating type provides a link between genotypic and phenotypic divergence in this taxon and illustrates a fungal analogue to sexual dimorphism found among animals and plants.


[Phase angle as an indicator of nutritional status and prognosis in critically ill patients].
The phase angle (PA) has been considered a sensitive tool to assess nutritional status and effectiveness of interventions dietetics. To evaluate the PA as an indicator of nutritional status and prognosis in critically ill patients. Prospective observational study of patients admitted to the Coronary Intensive Care Unit between May and October 2013. The PA was determined by bioelectrical impedance analysis, PA was considered low below 5º values for men and 4.6º for women. The values obtained were related to other evaluation parameters of nutritional status: anthropometric (arm circumference - AC , triceps skinfold thickness - TST , corrected arm muscle area - AMAc and calf circumference - CC) and biochemical (total lymphocyte count, hemoglobin, hematocrit), in addition to clinical prognostic APACHE II (Acute Physiology and Chronic Health Disease Classification System II) and serum albumin. The tabulation and analysis were performed using SPSS version 13.0. The sample consisted of 110 patients, in which an association was found between low AF and renal failure on dialysis (p < 0.001), % adequacy AC (p = 0.028), % adequacy of TST (p = 0.043), albumin level (p = 0.042), anemia (p = 0.040) and APACHE II (p = 0.012) scores. The AF was positively correlated with CC (p= 0.043) and inversely with the length of hospitalization (p = 0.006). PA in the ICU may be useful to identify early and malnourished patients as a prognostic indicator.


On measuring miRNAs after transient transfection of mimics or antisense inhibitors.
The ability to alter microRNA (miRNA) abundance is crucial for studying miRNA function. To achieve this there is widespread use of both exogenous double-stranded miRNA mimics for transient over-expression, and single stranded antisense RNAs (antimiRs) for miRNA inhibition. The success of these manipulations is often assessed using qPCR, but this does not accurately report the level of functional miRNA. Here, we draw attention to this discrepancy, which is overlooked in many published reports. We measured the functionality of exogenous miRNA by comparing the total level of transfected miRNA in whole cell extracts to the level of miRNA bound to Argonaute following transfection and show that the supraphysiological levels of transfected miRNA frequently seen using qPCR do not represent the functional levels, because the majority of transfected RNA that is detected is vesicular and not accessible for loading into Argonaute as functionally active miRNAs. In the case of microRNA inhibition by transient transfection with antisense inhibitors, there is also the potential for discrepancy, because following cell lysis the abundant inhibitor levels from cellular vesicles can directly interfere with the PCR reaction used to measure miRNA level.


Surgical Versus Non-Surgical Treatment for Thoracolumbar Burst Fractures Without Neurological Deficit: A Systematic Review and Meta-Analysis.
A systematic review and meta-analysis. To update the systematic review comparing the outcomes between surgical and non-surgical treatment for thoracolumbar burst fractures without neurological deficit. We registered a protocol in PROSPERO (ID: CRD42021291769) and searched Medline, Embase, Web of Science, and Google Scholar databases. Surgical and non-surgical treatments were compared in patients with thoracolumbar burst fractures without neurological deficits. Predefined outcomes at ≥6 months included pain (defined as a visual analog scale [VAS] of 0-100), functional outcomes (Oswestry Disability Index [ODI] of 0-50 and Roland-Morris Disability Questionnaire [RMDQ] of 0-24), and kyphotic angulation. Nineteen studies involving 1056 patients were included in the analyses. For outcomes at ≥6 months, little to no difference was found in pain VAS score (mean difference, .95 [95% confidence interval {CI}, -6.02 to 7.92]; 827 participants; 15 studies; I2 = 92%), ODI (mean difference, -1.40 [95% CI, -5.11 to 2.31]; 446 participants; 7 studies; I2 = 79%), and RMDQ (mean difference, -.73 [95% CI, -5.13 to 3.66]; 216 participants; 5 studies; I2 = 77%). The kyphotic angulation in the surgery group was 6.35° lower than that in the non-surgery group (mean difference, -6.56° [95% CI, -10.26° to -2.87°]; 527 participants; ten studies; I2 = 86%). The trial sequential analysis indicated all outcomes reached adequate statistical power. The certainty of the evidence for all 4 outcomes was very low. For the analysis of minimally invasive procedures compared to traditional open surgeries, a statistically significant subgroup difference was found for VAS and ODI (P < .01 and P < .04, respectively). Surgical and non-surgical treatments showed little or no difference in outcomes at ≥6 months. This review provides a conclusion with adequate statistical power by including non-randomized studies. However, non-randomized studies also lowered the certainty of the evidence to a very low level.


Modified osteo-odonto keratoprosthesis--the Indian experience--results of the first 50 cases.
To study the results of the modified osteo-odonto keratoprosthesis (MOOKP) surgery in bilateral end-stage ocular surface disorders. The MOOKP surgery is performed as a routine in 3 stages. Stage 1A involves removal of the iris and anterior vitrectomy with a corneal transplant if indicated. Stage 1B + 1C usually performed simultaneously involves harvesting the buccal mucosa and transplanting it onto the ocular surface along with fashioning of the osteo-odonto alveolar lamina. Stage 2 involves transplanting the osteo-odonto alveolar lamina to the eye 3 months later. The MOOKP surgery was completed in 50 eyes of 47 patients with a mean follow-up of 15.38 months (range: 1-54 months). Anatomic success was achieved in 96% of the eyes. Functional success of visual acuity > or = 20/60 was noted in 66% of eyes. Complications included oroantral fistula (6%), trophic mucosal alterations (8%), lamina exposure (central 6% and peripheral 8%), mucous membrane overgrowth (2%), hypotony (2%), expulsion of optic cylinder (4%), endophthalmitis (2%), glaucoma (20%), sterile vitritis (6%), and retinal detachment (2%). MOOKP is the keratoprosthesis of choice in bilateral end-stage ocular surface disorders in the Indian subcontinent. Complications do occur and have to be recognized and treated early.


Reading characters in voices: Ratings of personality characteristics from voices predict proneness to auditory verbal hallucinations.
People rapidly make first impressions of others, often based on very little information-minimal exposure to faces or voices is sufficient for humans to make up their mind about personality of others. While there has been considerable research on voice personality perception, much less is known about its relevance to hallucination-proneness, despite auditory hallucinations being frequently perceived as personified social agents. The present paper reports two studies investigating the relation between voice personality perception and hallucination-proneness in non-clinical samples. A voice personality perception task was created, in which participants rated short voice recordings on four personality characteristics, relating to dimensions of the voice's perceived Valence and Dominance. Hierarchical regression was used to assess contributions of Valence and Dominance voice personality ratings to hallucination-proneness scores, controlling for paranoia-proneness and vividness of mental imagery. Results from Study 1 suggested that high ratings of voices as dominant might be related to high hallucination-proneness; however, this relation seemed to be dependent on reported levels of paranoid thinking. In Study 2, we show that hallucination-proneness was associated with high ratings of voice dominance, and this was independent of paranoia and imagery abilities scores, both of which were found to be significant predictors of hallucination-proneness. Results from Study 2 suggest an interaction between gender of participants and the gender of the voice actor, where only ratings of own gender voices on Dominance characteristics are related to hallucination-proneness scores. These results are important for understanding the perception of characterful features of voices and its significance for psychopathology.


Causal interaction in high frequency turbulence at the biosphere-atmosphere interface: Structural behavior.
High-frequency (e.g., 10 Hz) eddy covariance measurements are typically used to estimate fluxes at the land-atmosphere interface at timescales of 15-60 min. These multivariate data contain information about the interdependency at high frequency between the interacting variables such as wind, humidity, temperature, and CO2. We use data at 10 Hz from an eddy covariance instrument located at 25 m above agricultural land in the Midwestern US, which offers an opportunity to move beyond the traditional spectral analyses to explore causal dependency among variables. In this study, we quantify the structure of inter-dependencies of interacting variables at high frequency represented by a directed acyclic graph (DAG). We compare DAGs to investigate changes in structural differences in causal interactions. We then apply a distance-based classification and k-means clustering approach to identify the evolution of the causal structure represented by a DAG. Our method selects an unbiased number of clusters of similar structures and characterizes the similarities and differences between them. We explore a range of dynamic behavior using data from a clear sky day and during a solar eclipse in 2017. Our results show well-defined clusters of similar causal dependencies as the system evolves. Our approach provides a methodological framework to understand how causal dependence in turbulence manifests in high-frequency data when represented through a DAG.


S- and C-start escape responses of the muskellunge (Esox masquinongy) require alternative neuromotor mechanisms.
The startle response is a model system for examining the neural basis of behavior because of its relatively simple neural circuit organization and kinematic pattern. In fishes, the two primary types of startle behavior differ in their initial movements. In the C-start type of startle, the fish bends into a C shape, while the S-start involves an S-shaped body bend. Although considerable research has focused on determining how the C-start is generated neurally, S-start neurobiology has not been examined. I quantify the kinematics and electromyographic patterns of the initial movements of the C-start and S-start behaviors of the muskellunge (Esox masquinongy) to test three hypotheses for how the S-start is generated. (i) The S-start is generated by the same motor neural circuit as the C-start, but passive bending of the tail causes the body to take on an S shape. (ii) The S-start is generated by the same motor neural circuit as undulatory swimming. (iii) The S-start is generated by an independent neural mechanism from that used either in the C-start or in undulatory swimming. Results from kinematics and muscle activity patterns support the third hypothesis. In the muskellunge, the S-start is a high-performance startle behavior with peak angular velocity and peak angular acceleration of its initial bending comparable with those of the C-start and higher than would be expected for undulatory swimming. The S-start motor pattern, however, is distinct from the C-start motor pattern in having simultaneous muscle activity anteriorly on one side of the body and posteriorly on the opposite side. In contrast, the C-start is characterized by simultaneous unilateral muscle activity along the full length of the body. Alternative models are proposed for S-start neural circuit organization involving reticulospinal and local control of muscle activity.


Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans.
The aim of this study was to assess the effects of recombinant human brain-derived neurotrophic factor (r-metHuBDNF) and recombinant human neurotrophic factor 3 (r-metHuNT-3) on gastrointestinal motor functions in healthy people and in patients with constipation. Gastrointestinal and colonic transit was measured by scintigraphy before and after 2 weeks of treatment. Daily diaries documented symptoms over 6 weeks before, during, and after treatment. In a randomized study of healthy subjects, 40 received 100 microg/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study, 8 healthy subjects and 8 patients with constipation received 300 microg/kg r-metHuNT-3 SC thrice weekly. r-met-HuBDNF accelerated overall and proximal colonic emptying (P<0.05) in health. r-metHuNT-3 accelerated overall colonic transit in health and constipation (all P<0.05) and gastric and small bowel transit (both P<0.05) in health. r-metHuBDNF tended to increase stool frequency compared with placebo in health (P = 0.09). r-metHuNT-3 increased stool frequency (P = 0.05) and facilitated passage of stool (P < 0.01) in constipated patients. The effects on stool frequency started within 3 days of the beginning of neurotrophin administrations and lasted up to 5 days after treatment ended. r-metHu neurotrophic factors were well tolerated, although half of the participants in the 2 studies developed injection site reactions or paresthesiae. Exogenous neurotrophic factors stimulate human gut motility in health and constipation.


Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study.
In patients with brain tumors, the choice of antiepileptic medication is guided by tolerability and pharmacokinetic interactions. This study investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non-enzyme-inducing agents, in this setting. In this pragmatic, randomized, unblinded phase II trial (NCT00629889), patients with primary brain tumors and epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability were assessed using structured questionnaires. The primary composite endpoint was the need to discontinue the study drug, add-on of a further antiepileptic treatment, or occurrence of at least 2 seizures with impaired consciousness during 1 year follow-up. Over 40 months, 25 patients were randomized to LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue: side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor progression. This study shows that LEV and PGB represent valuable monotherapy options in this setting, with very good antiepileptic efficacy and an acceptable tolerability profile, and provides important data for the design of a phase III trial.


Recombinant protein composed of Pseudomonas exotoxin A, outer membrane proteins I and F as vaccine against P. aeruginosa infection.
We have constructed a chimeric protein composed of the receptor binding and membrane translocation domains of Pseudomonas exotoxin A (PE) with the outer membrane proteins I and F, together designated as PEIF. The potential of PEIF as a vaccine against Pseudomonas infection was evaluated in BALB/c mice and New Zealand white rabbits. We examined titers of anti-PE and anti-OprF antibodies, and the ability both to neutralize PE cytotoxicity and to increase opsonophagocytic uptake of Pseudomonas aeruginosa strain PAO1, serogroups 2 and 6. The results showed that PEIF can induce antibodies not only to neutralize the PE cytotoxicity but also to promote the uptake of various strains of P. aeruginosa by murine peritoneal macrophages. In a burned mouse model, PEIF afforded significant protection against infection by the homologous P. aeruginosa strain PAO1, heterologous serogroup 2, and the PE hyperproducing strain PA103. These observations thus indicate that PEIF may be used as a novel vaccine against P. aeruginosa infection.


Heparan Sulfate: A Potential Candidate for the Development of Biomimetic Immunomodulatory Membranes.
Clinical trials have demonstrated that heparan sulfate (HS) could be used as a therapeutic agent for the treatment of inflammatory diseases. Its anti-inflammatory effect makes it suitable for the development of biomimetic innovative strategies aiming at modulating stem cells behavior toward a pro-regenerative phenotype in case of injury or inflammation. Here, we propose collagen type I meshes fabricated by solvent casting and further crosslinked with HS (HS-Col) to create a biomimetic environment resembling the extracellular matrix of soft tissue. HS-Col meshes were tested for their capability to provide physical support to stem cells' growth, maintain their phenotypes and immunosuppressive potential following inflammation. HS-Col effect on stem cells was investigated in standard conditions as well as in an inflammatory environment recapitulated in vitro through a mix of pro-inflammatory cytokines (tumor necrosis factor-α and interferon-gamma; 20 ng/ml). A significant increase in the production of molecules associated with immunosuppression was demonstrated in response to the material and when cells were grown in presence of pro-inflammatory stimuli, compared to bare collagen membranes (Col), leading to a greater inhibitory potential when mesenchymal stem cells were exposed to stimulated peripheral blood mononuclear cells. Our data suggest that the presence of HS is able to activate the molecular machinery responsible for the release of anti-inflammatory cytokines, potentially leading to a faster resolution of inflammation.


[Acute mastoiditis in children].
We retrospectively studied seventeen cases of acute mastoiditis admitted to the Paediatric Ward of S. Francisco Xavier Hospital during 8 years and 8 months. Seven patients were admitted in 1995. We found no reason for this increase. Eleven children were male and 5 were under 2 years of age. All cases, except one of post-traumatic mastoiditis, occurred after acute otitis media. Only 5 children referred symptoms for more than seven days before admission. Seven patients had surgery. The surgical group of children had a longer period of illness when compared to those only treated medically (7.6 versus 3.9 days). Tympanocentesis was performed in 6 patients, but it did not affect the outcome of the illness. In three children there were complications: Bezold abscess, labyrinthitis and cholesteatoma. The latter was the only patient in our series with permanent hearing loss.


Prioritising health service innovation investments using public preferences: a discrete choice experiment.
Prioritising scarce resources for investment in innovation by publically funded health systems is unavoidable. Many healthcare systems wish to foster transparency and accountability in the decisions they make by incorporating the public in decision-making processes. This paper presents a unique conceptual approach exploring the public's preferences for health service innovations by viewing healthcare innovations as 'bundles' of characteristics. This decompositional approach allows policy-makers to compare numerous competing health service innovations without repeatedly administering surveys for specific innovation choices. A Discrete Choice Experiment (DCE) was used to elicit preferences. Individuals chose from presented innovation options that they believe the UK National Health Service (NHS) should invest the most in. Innovations differed according to: (i) target population; (ii) target age; (iii) implementation time; (iv) uncertainty associated with their likely effects; (v) potential health benefits; and, (vi) cost to a taxpayer. This approach fosters multidimensional decision-making, rather than imposing a single decision criterion (e.g., cost, target age) in prioritisation. Choice data was then analysed using scale-adjusted Latent Class models to investigate variability in preferences and scale and valuations amongst respondents. Three latent classes with considerable heterogeneity in the preferences were present. Each latent class is composed of two consumer subgroups varying in the level of certainty in their choices. All groups preferred scientifically proven innovations, those with potential health benefits that cost less. There were, however, some important differences in their preferences for innovation investment choices: Class-1 (54%) prefers innovations benefitting adults and young people and does not prefer innovations targeting people with 'drug addiction' and 'obesity'. Class- 2 (34%) prefers innovations targeting 'cancer' patients only and has negative preferences for innovations targeting elderly, and Class-3 (12%) prefers spending on elderly and cancer patients the most. DCE can help policy-makers incorporate public preferences for health service innovation investment choices into decision making. The findings provide useful information on the public's valuation and acceptability of potential health service innovations. Such information can be used to guide innovation prioritisation decisions by comparing competing innovation options. The approach in this paper makes, these often implicit and opaque decisions, more transparent and explicit.


Bees, birds and yellow flowers: pollinator-dependent convergent evolution of UV patterns.
Colour is one of the most obvious advertisements of flowers, and occurs in a huge diversity among the angiosperms. Flower colour is responsible for attraction from a distance, whereas contrasting colour patterns within flowers aid orientation of flower visitors after approaching the flowers. Due to the striking differences in colour vision systems and neural processing across animal taxa, flower colours evoke specific behavioural responses by different flower visitors. We tested whether and how yellow flowers differ in their spectral reflectance depending on the main pollinator. We focused on bees and birds and examined whether the presence or absence of the widespread UV reflectance pattern of yellow flowers predicts the main pollinator. Most bee-pollinated flowers displayed a pattern with UV-absorbing centres and UV-reflecting peripheries, whereas the majority of bird-pollinated flowers are entirely UV- absorbing. In choice experiments we found that bees did not show consistent preferences for any colour or pattern types. However, all tested bee species made their first antennal contact preferably at the UV-absorbing area of the artificial flower, irrespective of its spatial position within the flower. The appearance of UV patterns within flowers is the main difference in spectral reflectance between yellow bee- and bird-pollinated flowers, and affects the foraging behaviour of flower visitors. The results support the hypothesis that flower colours and the visual capabilities of their efficient pollinators are adapted to each other.


[Elderly patients, classical monoamine oxidase inhibitors and intercurrent somatic diseases].
Three patients, a woman aged 70, a man aged 74 and a woman aged 78 years, all using tranylcypromine, a monoamine oxidase inhibitor (MAOI), to prevent the recurrence of severe depressive disorders, developed an intercurrent somatic disease. On admission to a general hospital, the first patient was initially refused her MAOI. The second patient was twice refused anaesthesia and the depression recurred twice when the MAOI was tapered off in connection with his operation. Both recovered after being given tranylcypromine. The third patient received tramadol from her surgeon and read in the directions for use that this drug should not be combined with a MAOI. After discontinuation of the MAOI the depression recurred, her medical condition deteriorated and she died. MAOIs are often a treatment of last resort. Discontinuation of an effective treatment and hence compromising the patient's psychiatric status increases the risk of medical and psychiatric complications and therefore should be avoided. Interdisciplinary consultation is essential in such cases.


A novel training scheme for multilayered perceptrons to realize proper generalization and incremental learning.
The response of a multilayered perceptron (MLP) network on points which are far away from the boundary of its training data is generally never reliable. Ideally a network should not respond to data points which lie far away from the boundary of its training data. We propose a new training scheme for MLPs as classifiers, which ensures this. Our training scheme involves training subnets for each class present in the training data. Each subnet can decide whether a data point belongs to a certain class or not. Training each subnet requires data from the class which the subnet represents along with some points outside the boundary of that class. For this purpose we propose an easy but approximate method to generate points outside the boundary of a pattern class. The trained subnets are then merged to solve the multiclass classification problem. We show through simulations that an MLP trained by our method does not respond to points which lies outside the boundary of its training sample. Also, our network can deal with overlapped classes in a better manner. In addition, this scheme enables incremental training of an MLP, i.e., the MLP can learn new knowledge without forgetting the old knowledge.


Generation and Molecular Characterization of CRISPR/Cas9-Induced Mutations in 63 Immunity-Associated Genes in Tomato Reveals Specificity and a Range of Gene Modifications.
The CRISPR/Cas9 system is a powerful tool for targeted gene editing in many organisms including plants. However, most of the reported uses of CRISPR/Cas9 in plants have focused on modifying one or a few genes, and thus the overall specificity, types of mutations, and heritability of gene alterations remain unclear. Here, we describe the molecular characterization of 361 T0 transgenic tomato plants that were generated using CRISPR/Cas9 to induce mutations in 63 immunity-associated genes. Among the T0 transformed plants, 245 carried mutations (68%), with 20% of those plants being homozygous for the mutation, 30% being heterozygous, 32% having two different mutations (biallelic), and 18% having multiple mutations (chimeric). The mutations were predominantly short insertions or deletions, with 87% of the affected sequences being smaller than 10 bp. The majority of 1 bp insertions were A (50%) or T (29%). The mutations from the T0 generation were stably transmitted to later generations, although new mutations were detected in some T1 plants. No mutations were detected in 18 potential off-target sites among 144 plants. Our study provides a broad and detailed view into the effectiveness of CRISPR/Cas9 for genome editing in an economically important plant species.


Central inflammation and sickness-like behavior induced by the food contaminant deoxynivalenol: a PGE2-independent mechanism.
Deoxynivalenol (DON), one of the most abundant trichothecenes found on cereals, has been implicated in mycotoxicoses in both humans and farm animals. Low-dose toxicity is characterized by reduced weight gain, diminished nutritional efficiency, and immunologic effects. The levels and patterns of human food commodity contamination justify that DON consumption constitutes a public health issue. DON stability during processing and cooking explains its large presence in human food. We characterized here DON intoxication by showing that the toxin concomitantly affects feeding behavior, body temperature, and locomotor activity after both per os and central administration. Using c-Fos expression mapping, we identified the neuronal structures activated in response to DON and observed that the pattern of neuronal populations activated by the toxin resembled those induced by inflammatory signals. By real-time PCR, we report the first evidences for a DON-induced central inflammation, attested by the strong upregulation of interleukin-1β, interleukin-6, tumor necrosis factor-α, cyclooxygenase-2, and microsomal prostaglandin synthase-1 (mPGES-1) messenger RNA. However, silencing prostaglandins E2 signaling pathways using mPGES-1 knockout mice, which are resistant to cytokine-induced sickness behavior, did not modify the responses to the toxin. These results reveal that, despite strong similarities, behavioral changes observed after DON intoxication differ from classical sickness behavior evoked by inflammatory cytokines.


Rigid model-based 3D segmentation of the bones of joints in MR and CT images for motion analysis.
There are several medical application areas that require the segmentation and separation of the component bones of joints in a sequence of images of the joint acquired under various loading conditions, our own target area being joint motion analysis. This is a challenging problem due to the proximity of bones at the joint, partial volume effects, and other imaging modality-specific factors that confound boundary contrast. In this article, a two-step model-based segmentation strategy is proposed that utilizes the unique context of the current application wherein the shape of each individual bone is preserved in all scans of a particular joint while the spatial arrangement of the bones alters significantly among bones and scans. In the first step, a rigid deterministic model of the bone is generated from a segmentation of the bone in the image corresponding to one position of the joint by using the live wire method. Subsequently, in other images of the same joint, this model is used to search for the same bone by minimizing an energy function that utilizes both boundary- and region-based information. An evaluation of the method by utilizing a total of 60 data sets on MR and CT images of the ankle complex and cervical spine indicates that the segmentations agree very closely with the live wire segmentations, yielding true positive and false positive volume fractions in the range 89%-97% and 0.2%-0.7%. The method requires 1-2 minutes of operator time and 6-7 min of computer time per data set, which makes it significantly more efficient than live wire-the method currently available for the task that can be used routinely.


The back-step method--method for obtaining unbiased population parameter estimates for ordered categorical data.
A significant bias in parameters, estimated with the proportional odds model using the software NONMEM, has been reported. Typically, this bias occurs with ordered categorical data, when most of the observations are found at one extreme of the possible outcomes. The aim of this study was to assess, through simulations, the performance of the Back-Step Method (BSM), a novel approach for obtaining unbiased estimates when the standard approach provides biased estimates. BSM is an iterative method involving sequential simulation-estimation steps. BSM was compared with the standard approach in the analysis of a 4-category ordered variable using the Laplacian method in NONMEM. The bias in parameter estimates and the accuracy of model predictions were determined for the 2 methods on 3 conditions: (1) a nonskewed distribution of the response with low interindividual variability (IIV), (2) a skewed distribution with low IIV, and (3) a skewed distribution with high IIV. An increase in bias with increasing skewness and IIV was shown in parameters estimated using the standard approach in NONMEM. BSM performed without appreciable bias in the estimates under the 3 conditions, and the model predictions were in good agreement with the original data. Each BSM estimation represents a random sample of the population; hence, repeating the BSM estimation reduces the imprecision of the parameter estimates. The BSM is an accurate estimation method when the standard modeling approach in NONMEM gives biased estimates.


[Experimental and biochemical aspects of crystalline lens induction during embryogenesis].
The lens induction is a two-step process and involves morphogenetic influences from the archencepalic endoderm and optic vesicle. One can suggest that the lens induction is primed by specific proteins which are synthesized and secreted by the optic vesicle cells. The proteins-inductors appear to penetrate in the cells and, while interacting (directly or via the cytoplasm) with the nuclei, "programme" the ectodermal cells towards the lens differentiation. The contact interactions and extracellular matrix are of substantial, but not crucial value for the lens induction. The synthesis of specific proteins (crystallins) is to be considered as the most objective criterion of lens differentiation. In vertebrates, there is a lag-period between the moment of lens induction and synthesis of crystallins which is the most long-term in amphibians. The chick embryos constitute an exception and the synthesis of crystallin mRNA occurs in them a few hours after the lens induction. The developing retina loses its capacity to induce lens but stimulates the processes of fiber formation and synthesis of crystallins. A factor was found in the definitive lens epithelium which may be considered as a possible regulator of lens differentiation. On the basis of experiments with heterogenous and native lens inductors, a suggestion is put forward to the effect that the activity of inducing substances is determined by a definite determinant group of the molecule, rather than by the whole molecule.


Tinnitus and Self-Perceived Hearing Handicap in Firefighters: A Cross-Sectional Study.
Firefighters are susceptible to auditory dysfunction due to long-term exposure to noise from sirens, air horns, equipment, and tools used in forcible entry, ventilation, and extrication. In addition, they are exposed to ototoxic chemicals, particularly, during overhaul operations. Studies indicate that 40% of firefighters have hearing loss in the noise-sensitive frequencies of 4 and 6 kHz. Noise-induced hearing loss (NIHL) is often accompanied by tinnitus, which is characterized by ringing noise in the ears. The presence of phantom sounds can adversely affect the performance of firefighters. However, there has been limited research conducted on the prevalence of tinnitus in firefighters. We enrolled firefighters from Michigan, with at least 5 years of continuous service. The hearing handicap inventory for adults (HHIA) was used to determine the difficulty in hearing perceived by the firefighters and the tinnitus functional index (TFI) was used to determine the severity of tinnitus. Self-perceived hearing handicap was reported by 36% of the participants, while tinnitus was reported by 48% of the participants. The TFI survey indicated that 31% perceived tinnitus as a problem. More importantly, self-perceived hearing handicap was significantly associated with the incidence of tinnitus in firefighters, suggesting a potential link between occupational exposure to ototraumatic agents and tinnitus in firefighters.


How Did the COVID-19 Pandemic Affect Migrant Populations in Lisbon, Portugal? A Study on Perceived Effects on Health and Economic Condition.
Increasing evidence on the effects of the COVID-19 pandemic suggests that its social and health impacts are being disproportionately shouldered by socioeconomically disadvantaged populations, including migrants. Knowledge of how these populations are experiencing the COVID-19 crisis is scarce. We examined the effects of the pandemic on the perceived individual financial situation and health condition of migrants in Lisbon, Portugal, and described the most affected subgroups. A cross-sectional survey was conducted with a diverse community-based sample of 1126 migrants. A worsening of their financial situation since the pandemic was reported by 55.6% of the participants and a worsening of their health condition by 19.9%. A worsened financial situation was most often reported by those ≥45 years old and with a lower income (<EUR 650). Likewise, a worsened health condition was most often reported by older and lower-income migrants, as well as by women and those with a lower level of education. Migration-related factors such as length of stay and migration status were not associated with worsened health conditions. Socioeconomic characteristics appear to be more important when assessing differences in perceived effects of the pandemic among migrants. The social impact of the pandemic both exacerbates economic and gender inequalities and may lead to worse health conditions within the population in the medium and long terms.


A simple noniterative principal component technique for rapid noise reduction in parallel MR images.
The utilization of parallel imaging permits increased MR acquisition speed and efficiency; however, parallel MRI usually leads to a deterioration in the signal-to-noise ratio when compared with otherwise equivalent unaccelerated acquisitions. At high accelerations, the parallel image reconstruction matrix tends to become dominated by one principal component. This has been utilized to enable substantial reductions in g-factor-related noise. A previously published technique achieved noise reductions via a computationally intensive search for multiples of the dominant singular vector which, when subtracted from the image, minimized joint entropy between the accelerated image and a reference image. We describe a simple algorithm that can accomplish similar results without a time-consuming search. Significant reductions in g-factor-related noise were achieved using this new algorithm with in vivo acquisitions at 1.5 T with an eight-element array.


Update on cluster headache.
Although cluster headache has traditionally been thought of as a vascular headache disorder, its periodicity suggests an involvement of central areas such as the hypothalamus. This review covers the past 3 years, which have seen remarkable progress in understanding the pathophysiology of circadian headache syndromes and have brought exciting news. As more cluster headache patients are seen by headache specialists, new forms of this well-defined primary headache syndrome are being identified. In addition, we discuss recent findings with regard to abnormalities in the secretion of hormones, genetic influences, neuroimaging of cluster headache attacks, and the use of newer substances as preventive therapy in cluster headache. We have entered a new diagnostic and therapeutic era in primary headache disorders. In recent reports, the use of deep brain stimulation of the hypothalamus has enabled intractable chronic cluster headache patients to be successfully operated upon. Further research in this field is urgently needed and the recent possibility of combining deep brain stimulation with positron emission tomography will certainly help to unravel the brain circuitry implicated in stimulation-produced analgesia. The time has come to use the evidence for a disorder of circadian rhythm in cluster headache to further the development of chronobiotics in the treatment of this disorder.


Growth hormone at breeding modifies conceptus development and postnatal growth in sheep.
Experiments were performed to determine the effects of components of the GH-IGF axis on conceptus development and postnatal growth in sheep. In Exp. 1, ewes received one of the following treatments: 1) sustained release GH at breeding, 2) sustained release GH at breeding and estradiol-17beta at d 5 and 6, 3) only estradiol-17beta at d 5 and 6, or 4) no treatment. Uteri were flushed on d 7, and flushings were analyzed for content of IGF-I. A single injection of sustained-release bovine GH at breeding increased IGF-I content in uterine luminal flushings compared with control ewes (P < 0.05). Treatment with estradiol-17beta on d 5 and 6 after breeding did not alter IGF-I content compared with control ewes, and it blocked the effect of GH on uterine luminal IGF-I content. In Exp. 2, sustained release GH or no treatment was administered at breeding, and gravid uteri were collected at d 25, 80, or 140 of gestation. On d 80, GH-treated ewes had smaller chorioallantoic weights (P < 0.05) and tended to have more efficient placentae (fetal weight/total placental weight; P = 0.052), with a higher percentage of placental weight as cotyledons (P = 0.068) compared with control ewes. In Exp. 3, ewes were treated with or without sustained release GH at progesterone withdrawal. Lambs from GH-treated ewes were heavier at birth (P < 0.05). Lambs from GH-treated ewes reared as singles, but not lambs reared as multiples, were heavier at 30, 60 (P < 0.05), and 75 d (P = 0.075) of age than lambs from control ewes. In conclusion, ewes treated with sustained-release GH at breeding developed smaller, more efficient placentas, and had larger lambs at birth.


Effect of dopamine and bromocriptine on rat ileal and colonic transport. Stimulation of absorption and reversal of cholera toxin-induced secretion.
Water and electrolyte transport were determined in rat ileum and colon using the single-pass perfusion technique. Intraperitoneal dopamine caused prompt stimulation of both ileal and colonic water absorption. The dopamine effect was mediated by both specific dopamine and alpha 2-adrenergic receptors. Haloperidol, a specific dopamine antagonist, and yohimbine, an alpha 2-adrenergic antagonist, inhibited the effect of dopamine in ileal absorption; both antagonists alone had no effect on basal water transport. Bromocriptine (intravenous and intraluminal) stimulated ileal and colonic water absorption, which was inhibited by haloperidol and yohimbine, and reversed cholera toxin-induced ileal secretion. Magnitude and time-courses of the increased water absorption in ileal loops, inoculated with saline, were the same as in loops, inoculated with saline, suggesting that bromocriptine acted to reverse cholera toxin-induced secretion by stimulating absorption. Bromocriptine had no effect on the cyclic adenosine monophosphate increase caused by cholera toxin. We conclude (a) dopamine stimulates water absorption in vivo in rat ileum and colon; (b) this dopamine effect is via specific dopamine and alpha 2-receptors; (c) bromocriptine stimulates water absorption in ileum and colon and also acts by dopamine and alpha 2-receptors; and (d) bromocriptine reverses cholera toxin-induced secretion.