Follicular contact dermatitis revisited: A review emphasizing neomycin-associated follicular contact dermatitis.
Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the PubMed database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals (including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agents-either as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions.


Lactate/H+ transport in skeletal muscle from spinal-cord-injured patients.
In order to evaluate the effect of prolonged muscle inactivity on sarcolemmal lactate/H+ transport in humans, the lactate/H+ transport capacity was determined in the thigh muscle of spinal-cord-injured (SCI) individuals. The lactate transport rate was measured in sarcolemmal giant vesicles produced by collagenase treatment of muscle biopsies obtained from the vastus lateralis muscle. Six SCI subjects with total loss of motor and sensory functions of their lower limbs participated in the study. The duration of the injury ranged from 2 to 15 years. The total lactate transport rate in the muscle of SCI patients was 46.5 +/- 2.6 pmol.cm-2.s-1 (mean +/- SEM), which corresponds to a 17% lower (P < 0.05) transport rate than that found in healthy, untrained subjects. The estimated carrier-mediated lactate/H+ transport capacity was approximately 26% lower in the SCI patients than in healthy, untrained subjects. The observed muscle lactate/H+ transport capacity of SCI individuals is in accordance with a positive correlation between the capacity of the lactate/H+ transporters and the percentage occurrence of slow-twitch fibres in a muscle, although there seems to be a wide range of transport capacities within each fibre type. The present results show that the sarcolemmal lactate/H+ transport capacity is lower in SCI individuals than in normally physically active subjects, which indicates that prolonged muscle inactivity reduces the lactate/H+ transport capacity of human muscle.


Construction of a fur null mutant and RNA-sequencing provide deeper global understanding of the Aliivibrio salmonicida Fur regulon.
The ferric uptake regulator (Fur) is a transcription factor and the main regulator of iron acquisition in prokaryotes. When bound to ferric iron, Fur recognizes its DNA binding site and generally executes its function by repressing transcription of its target genes. Due to its importance in virulence, the Fur regulon is well studied for several model bacteria. In our previous work, we used computational predictions and microarray to gain insights into Fur-regulation in Aliivibrio salmonicida, and have identified a number of genes and operons that appear to be under direct control of Fur. To provide a more accurate and deeper global understanding of the biological role of Fur we have now generated an A. salmonicida fur knock-out strain and used RNA-sequencing to compare gene expression between the wild-type and fur null mutant strains. An A. salmonicida fur null mutant strain was constructed. Biological assays demonstrate that deletion of fur results in loss of fitness, with reduced growth rates, and reduced abilities to withstand low-iron conditions, and oxidative stress. When comparing expression levels in the wild-type and the fur null mutant we retrieved 296 differentially expressed genes distributed among 18 of 21 functional classes of genes. A gene cluster encoding biosynthesis of the siderophore bisucaberin represented the highest up-regulated genes in the fur null mutant. Other highly up-regulated genes all encode proteins important for iron acquisition. Potential targets for the RyhB sRNA was predicted from the list of down-regulated genes, and significant complementarities were found between RyhB and mRNAs of the fur, sodB, cysN and VSAL_I0422 genes. Other sRNAs with potential functions in iron homeostasis were identified. The present work provides by far the most comprehensive and deepest understanding of the Fur regulon in A. salmonicida to date. Our data also contribute to a better understanding of how Fur plays a key role in iron homeostasis in bacteria in general, and help to show how Fur orchestrates iron uptake when iron levels are extremely low.


Clinical factor affecting the recovery of kidney function in clinically localized renal cell carcinoma patients who underwent nephron-sparing surgery.
Nephron-sparing surgery (NSS) has become the standard treatment for small renal cell carcinoma because of its comparable oncological outcome and superior patient survival compared to total nephrectomy. However, the precise chronological course of recovery from initial kidney damage and the factors responsible for it remain unknown. Seventy-one patients who underwent NSS were enrolled. To elucidate the chronological changes in kidney function that occur after NSS, the estimated glomerular filtration rate (eGFR) was calculated at different two points, the early (7 days after surgery) and late time points (more than 12 months after surgery), and compared with the preoperative eGFR. Perioperative factors were applied to a multivariate regression model to investigate the factors that most affect patient recovery from nephron damage. eGFR was decreased at the early time point but had partially recovered at the late time point. Male gender, ischemic time, and tumor size were found to be significant predictors of the initial drop in eGFR. The only significant factor that prevented later functional recovery was the presence of DM. Several perioperative factors significantly influence early kidney damage; however, the presence of DM is the only factor affecting the risk of long-term chronic kidney damage.


Effects of Dimensional and Categorical Classification on the Clinical Manifestation of Major Depressive Disorder.
The aim of this study was to combine the dimensional concept with the categorical system in major depressive disorder (MDD) to reduce the complexity of the diagnosis. Furthermore, it was aimed to match categorical and dimensional approaches in a clear and simple manner. The study included a patient group of 131 consecutive outpatients diagnosed with MDD according to the DSM-IV diagnosis criteria, and a control group of 99 people that is matched with the patient group by gender, age and education level. All subjects completed the Beck Depression Inventory, the Beck Anxiety Inventory and the Toronto Alexithymia Scale (TAS). Cronbach's alpha values for the analysis of the internal consistency of the scale for the patients group, control group and the total participants were determined as .94-.97, .87-.92 and .93-.96, respectively. Nine factors were obtained from the results of exploratory factor analysis. According to the Scree-plot, it was decided that the two-factor structure represents best. Although depression and anxiety are two distinct dimensions, the relationship between them was found to be significantly significant. This was valid for both patient and control groups. When the relationship between the DSM-IV diagnosis criteria and all variables (depression and its sub-dimensions, anxiety and its sub-dimensions and the number of symptoms) was evaluated, the number of symptoms was found to be significantly related with all of the criteria. The number of symptoms and the severity of illness are found to be important in the clinical manifestation of MDD. The relationship of the severity of the illness with sleep and appetite seems weaker. While loss of interest was mainly predicting the disorder, weight changes, psychomotor changes, difficulty in concentration, fatigue, and worthlessness were determined not to be predictors of the manifestations. According to dimensional approach, somatic anxiety and deterioration in performance predict the presence of the disorder. According to categorical and dimensional approaches, some of the DSM-IV criteria (#2, #1, #9, #4, number of symptoms, severity of symptoms, somatic anxiety, performance deterioration) are seen to contribute to the matchability between the approaches.


Evaluation of flunarizine in patients with Menière's disease. Subjective and vestibular findings.
In an open multicentre pilot study, 32 patients affected with Menière's disease were treated with the cerebrally effective calcium antagonist flunarizine for 12 weeks. By means of the so-called vestibular index, the therapeutic results could be documented in a rapid and clear manner; the vestibular index takes into account both the subjective statements of the patients and objective pathological vestibular findings in terms of figures. The mean value of this vestibular index of 32 patients with Menière's disease was 9.5 before treatment and only 4.0 at the end of the therapy, which is indicative of a positive therapeutic effect. In the final evaluation, the action of flunarizine was generally considered very beneficial both by the attending physicians and the patients.


Catalytic Protein Film Electrochemistry Provides a Direct Measure of the Tetrathionate/Thiosulfate Reduction Potential.
The tetrathionate/thiosulfate interconversion is a two-electron process: S4O6(2-) + 2 e(-) ↔ 2 S2O3(2-). Both transformations can support bacterial growth since S2O3(2-) provides an energy source, while S4O6(2-) serves as respiratory electron acceptor. Interest in the corresponding S2O3(2-) oxidation also arises from its widespread use in volumetric analysis of oxidizing agents and bleach neutralization during water treatment. Here we report protein film electrochemistry that defines the reduction potential of the S4O6(2-)/S2O3(2-) couple. The relevant interconversion is not reversible at inert electrodes. However, facile reduction of S4O6(2-) to S2O3(2-) and the reverse reaction are catalyzed by enzymes of the thiosulfate dehydrogenase, TsdA, family adsorbed on graphite electrodes. Zero-current potentials measured with different enzymes, at three pH values, and multiple S4O6(2-) and S2O3(2-) concentrations together with the relevant Nernst equation resolved the tetrathionate/thiosulfate reduction potential as +198 ± 4 mV versus SHE. This potential lies in the ∼250 mV window encompassing previously reported values calculated from parameters including the free energy of formation. However, the value is considerably more positive than widely used in discussions of bacterial bioenergetics. As a consequence anaerobic respiration by tetrathionate reduction is likely to be more prevalent than presently thought in tetrathionate-containing environments such as marine sediments and the human gut.


Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys.
The objectives of this study were to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atheroscleroses and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) on a monkey model. Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomized to receive no treatment or women's equivalent doses of BZA (20 mg/d), CEE (0.45 mg/d), or BZA + CEE. The experimental period lasted for 20 months (equivalent to approximately 5 y in humans) during which interim measures of cardiovascular risk factors were made. At the end of the experimental period, the extent and severity of coronary and iliac artery atheroscleroses were quantified. Body weight, adiposity, fasting glucose concentrations, and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on the extent or severity of coronary or common iliac artery atherosclerosis when compared with no treatment. CEE, administered soon after inducing menopause, had robust atheroprotective effects on both the extent and the severity of iliac and coronary artery atheroscleroses. The addition of BZA to CEE treatment antagonized the atheroprotective effects of CEE. In this nonhuman primate trial, treatment with BZA alone, CEE alone, and combined BZA and CEE does not have significant effects on plasma lipid profiles. CEE markedly inhibits the progression and complications of both coronary and iliac artery atheroscleroses. BZA has no adverse effects on atherosclerosis but attenuates the atheroprotective effects of CEE.


[Pathological-anatomical findings after serologic and molecular biologic evidence of Hantaan virus infection].
Post-mortem findings in a girl aged 2 years and 4 months who had been infected with Hantaan virus are reported. The child fell ill with acute renal failure in her 8th month of life and had to be subjected to chronic dialysis. There was a progressive cardiac insufficiency. Specific IgG and IgM antibodies to Hantaan virus were demonstrated by serology from the 18th month of life. Autopsy revealed endomyocardial fibrosis and cardiomegaly. Hantaan RNA could be demonstrated in formalin-fixed, paraffin-embedded specimens of lung, liver and spleen tissue by means of RT-PCR followed by DNA sequencing. A possible association between the Hantaan virus infection and the pathological findings in the heart are discussed.


Association Between Anthropometric Indicators of Nutrition Status and Length of Hospital Stay in Hospitalized Patients.
Undernutrition is associated with increased hospital length of stay (LOS). Anthropometrics is required for undernutrition screening and diagnosis. However, the measurements which are more strongly associated with LOS are to be specified. This study aims to measure the independent association of weight, triceps skinfold thickness (TST), mid-upper arm circumference (MUAC), adductor pollicis muscle thickness (APMT), mid-upper arm muscle area (AMA), mid-upper arm muscle circumference (AMC), and body mass index (BMI) with LOS and investigating whether these indicators had similar validity in predicting LOS. Six hundred ninety-five patients participated in a prospective observational study. Participants were dichotomized indicators studied according to the 5th and 25th percentiles described in the literature (for APMT only the 5th percentile was used). Cox regression analysis was used to estimate adjusted hazard ratios (HRs) and corresponding 95% CIs. Patients that presented values <5th percentile for TST (HR, 0.759; 95% CI, 0.579-0.995), MUAC (HR, 0.822; 95% CI, 0.687-0.983), APMT (HR, 0.791; 95% CI, 0.671-0.933), AMA (HR, 0.797, 95% CI, 0.660-0.962), and AMC (HR, 0.746; 95% CI, 0.611-0.911) showed a lower probability of being discharged to usual residence. Patients whose TST values were <25th percentile also presented lower probability of being discharged to usual residence (HR, 0.798; 95% CI, 0.673-0.946). No associations were found between weight and BMI with LOS. Depletion of TST, MUAC, APMT, AMA, and AMC was associated with lower probability of being discharged to usual residence. A thicker TST was independently associated with this outcome and thus TST should be considered for undernutrition screening and diagnosis.


New insights into the mechanisms behind mechanical itch.
Gentle tactile stimuli, such as insects crawling on the skin, can cause itching sensation called mechanical itch. Recent studies have begun to shed light on the neural mechanisms of mechanical itch. Interestingly, the neural pathway for mechanical itch is apparently different from that for chemical itch triggered by the activation of pruriceptors with various mediators. Mechanical itch dysesthesia is frequently seen in patients with chronic itch. Mechanisms of this dysesthesia are plausibly involved in central sensitization. In this review, we summarize the current knowledge of mechanical itch under normal and pathological conditions.


Production of a dendritic cell-based vaccine containing inactivated autologous virus for therapy of patients with chronic human immunodeficiency virus type 1 infection.
In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8(+) and CD4(+) T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4(+) T cells with the virus; (iii) inactivation of the virus in CD4(+) T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4(+) T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4(+) T cells. CD4(+) T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID(50); which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4(+) T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID(50) of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 microg/ml) and UVB irradiation (312 nm) reduced the TCID(50) of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4(+) T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137).


Endovascular therapy of traumatic vascular lesions of the head and neck.
Pseudoaneurysm and fistula formation are well-documented complications of arterial vascular injury and may be associated with significant morbidity and mortality. The purpose of this manuscript is to review the presentation and therapy of patients with traumatic vascular injuries of the head and neck. Eight patients were admitted to a Level 1 Trauma Center and diagnostic angiography of the carotid artery and vertebral circulation was performed. The mechanisms of injury included motor vehicle accident, gunshot wound, stab wound and aggravated assault. Cause of trauma, vascular lesion, endovascular therapy and outcome were analyzed retrospectively. The angiographic findings, clinical presentation and hospital course were reviewed. There were eight patients, seven males and one female, aged 17-65. Four patients (50%) had multiple lesions; four had pseudoaneurysms, two with fistula formation and two with active arterial hemorrhage. A total of 17 lesions were embolized using coils. Polyvinyl Alcohol (PVA), Gelfoam or a combination. Two of the 17 lesions received stents. Six of the eight patients remained clinically improved or stable at varying follow-up intervals. One of the four patients who presented with penetrating trauma and neurological deficits had resolution of right hemiplegia at the 8th month follow-up. One of the four patients who sustained blunt trauma and carotid-cavernous fistula presented with a new pseudoaneurysm at the 2-month post-embolization follow-up. The evolution of diagnostic neuroangiographic techniques provides opportunities for endovascular therapy of traumatic vascular lesions of the head and neck that are minimally invasive, attractive options in selected cases.


Exploring the macro-level, meso-level and micro-level barriers and facilitators to the provision of good quality early inflammatory arthritis (EIA) care in England and Wales.
Evidence from a national clinical audit of early inflammatory arthritis (EIA) shows considerable variability between hospitals in performance, unexplained by controlling for case-mix. To explore the macro-level, meso-level and micro-level barriers and facilitators to the provision of good quality EIA care. A qualitative study within 16 purposively sampled rheumatology units across England and Wales. Quality was assessed in relation to 11 quality indicators based on clinical opinion, evidence and variability observed in the data. Data from semi-structured interviews with staff (1-5 from each unit, 56 in total) and an online questionnaire (n=14/16 units) were integrated and analysed using the framework method for thematic analysis using a combined inductive and deductive approach (underpinned by an evidence-based framework of healthcare team effectiveness), and constant comparison of data within and between units and its relationship with the quality criteria. Quality of care was influenced by an interplay between macro, meso and micro domains. The macro (eg, shared care arrangements and relationships with general practitioners) and meso (eg, managerial support and physical infrastructure) factors were found to act as crucial enablers of and barriers to higher quality service provision at the micro (team) level. These organisational factors directly influenced team structure and function, and thereby EIA care quality. Variability in quality of EIA care is associated with an interplay between macro, meso and micro service features. Tackling macro and meso barriers is likely to have a significant impact on quality of EIA service, and ultimately patient experience and outcomes.


Epidemiology and pathogenicity of human retroviruses.
The human retroviruses can be divided into oncovirus (HTLV-I and HTLV-II) and lentivirus strains (HIV-1 and -2). The HTLVs are endemic in Central Africa, the Caribbean Islands and in southwest Japan, but now tend to spread through the i.v.-drug user population in the USA and in some countries in Western Europe. HTLV infection is associated with a malignant form of adult T-cell leukemia, tropical spastic paraparesis (TSP) and an associated myelopathy (HAM). The pathogenic mechanisms of HTLV are as yet poorly understood. HIV infection is spreading rapidly almost world-wide and has reached epidemic proportions in Central Africa, parts of South America and in certain populations in industrialized countries that have risk behaviour for contracting venereal or blood-borne infections. The mechanisms of HIV-induced immune suppression are still not entirely clear, as direct T-lymphocyte destruction after viral infection cannot account for the almost complete loss of CD4 T-cells in the final stages of disease. Various indirect mechanisms of HIV-induced immune cell destruction are outlined below.


Perceptions of HIV and Mental Illness as "Western" or "Traditional" Illnesses: A Cross-Sectional Study from Limpopo Province, South Africa.
Although Western biomedical treatment has dramatically increased across sub-Saharan African health systems, traditional medicine as a form of healing and beliefs in supernatural powers as explanations for disease remain prevalent. Research in this region has identified HIV in particular as a disease located within both the traditional African and Western medical paradigms, whilst mental illness is ascribed to primarily supernatural causes. Within this context, this study sought to understand and explore the perceptions of HIV and mental illness among a population of rural women in Limpopo, South Africa. 82 in-depth interviews were conducted between January and December, 2022. Interviews were transcribed and translated into English. Data were managed using NVivo 11 software and thematically analyzed. The majority of participants identified HIV as a Western illness requiring biomedical treatment with causation largely attributed to biological mechanisms. A traditional form of HIV only cured using traditional treatments was also denoted. Unlike for HIV, the majority of respondents felt that there was no biological or behavioral cause for mental illness but rather the illness was conceptualized supernaturally thus likely impacting patient care pathways. Further research to study HIV and mental health perceptions among a larger sample in different regions of sub-Saharan Africa is warranted.


Propagating Wigner-Negative States Generated from the Steady-State Emission of a Superconducting Qubit.
We experimentally demonstrate the steady-state generation of propagating Wigner-negative states from a continuously driven superconducting qubit. We reconstruct the Wigner function of the radiation emitted into propagating modes defined by their temporal envelopes, using digital filtering. For an optimized temporal filter, we observe a large Wigner logarithmic negativity, in excess of 0.08, in agreement with theory. The fidelity between the theoretical predictions and the states generated experimentally is up to 99%, reaching state-of-the-art realizations in the microwave frequency domain. Our results provide a new way to generate and control nonclassical states, and may enable promising applications such as quantum networks and quantum computation based on waveguide quantum electrodynamics.


Cranial nerve preservation in surgery for large acoustic neuromas.
Facial nerve outcomes and surgical complication rates for other cranial nerves were evaluated retrospectively after the resection of large acoustic neuromas. The charts of all patients who underwent surgical removal of an acoustic neuroma between 1992 and 2001 at New York University Medical Center were reviewed. Fifty-four patients with tumors measuring 3 cm or larger were included in the study. Four patients had neurofibromatosis type 2, two of whom underwent bilateral removal of acoustic neuromas. Translabyrinthine microsurgical removal of tumor was performed in 47 of 56 cases (84%). In all cases, EMG monitoring, improved sharp microdissection, and ultrasonic aspiration were employed. Facial nerve function was assessed using the House-Brackmann facial nerve grading system immediately after surgery and at follow-up visits. A House-Brackmann grade III or better was achieved in 90% of patients, and a grade II or better was achieved in 84% of patients. Ultimate facial nerve outcome was excellent after the surgical resection of large acoustic neuromas. Preoperative cranial nerve palsies also improved after surgery. The translabyrinthine approach for tumor removal is our treatment of choice for acoustic neuromas 3 cm or larger.


Neural pathways in processing of sexual arousal: a dynamic causal modeling study.
Three decades of research have investigated brain processing of visual sexual stimuli with neuroimaging methods. These researchers have found that sexual arousal stimuli elicit activity in a broad neural network of cortical and subcortical brain areas that are known to be associated with cognitive, emotional, motivational and physiological components. However, it is not completely understood how these neural systems integrate and modulated incoming information. Therefore, we identify cerebral areas whose activations were correlated with sexual arousal using event-related functional magnetic resonance imaging and used the dynamic causal modeling method for searching the effective connectivity about the sexual arousal processing network. Thirteen heterosexual males were scanned while they passively viewed alternating short trials of erotic and neutral pictures on a monitor. We created a subset of seven models based on our results and previous studies and selected a dominant connectivity model. Consequently, we suggest a dynamic causal model of the brain processes mediating the cognitive, emotional, motivational and physiological factors of human male sexual arousal. These findings are significant implications for the neuropsychology of male sexuality.


Binocular rivalry disrupts stereopsis.
Does the shift from binocular rivalry to fusion or stereopsis take time? We measured stereoacuity after rivalry suppression of one half-image of a stereoacuity line target. After the observer signalled that the single stereo half-image had been suppressed, the other half-image was presented for a variable duration. Stereoacuity thresholds were elevated for 150-200 ms. A control experiment demonstrated that the threshold elevation was due to rivalry suppression per se, rather than masking effects associated with the rivalry-inducing target. Monocular Vernier thresholds, measured as the smallest identifiable abrupt shift in the upper line of an aligned Vernier target that had previously been suppressed by rivalry, were elevated for a much longer duration. This result shows that an appropriately matched stereo pair can break rivalry suppression more easily than can monocular changes in position. With the aid of a similar paradigm, we also measured the duration needed to detect a disparate feature in a random-dot stereogram after rivalry suppression of one half-image of the stereogram. Observers could correctly identify the location of the disparate feature (upper or lower visual field) when the other half-image was presented for a duration ranging from 150-650 ms. In the absence of the matching half-image, the first half-image was suppressed by the rival target for a far longer duration (a few seconds). These findings show that although stereopsis and fusion terminate rivalry, both are initially disrupted for a few hundred milliseconds by rivalry suppression.


Testing the Stability of Plasma Protein and Whole Blood RNA in Archived Blood of Loggerhead Sea Turtles, Caretta caretta.
Sample storage conditions can affect accuracy and reproducibility of biological measurements. Storing samples rapidly at the lowest available temperatures is considered ideal but is not always feasible when sampling in remote and logistically challenging field conditions, as is often the case with sea turtles. The objective of this study was to examine the stability of plasma proteins and quality of whole blood RNA from loggerhead sea turtle samples collected as part of an eighteen-year-long curated specimen collection. These biological variables are often used to assess sea turtle health; therefore, it is necessary to maintain the integrity of these components during storage. Protein electrophoresis was conducted on heparinized plasma from individual turtles collected in 2018 (n = 3), 2008 (n = 3), and 2001 (n = 3). Plasma was also pooled from four turtles sampled in 2018 and subjected to various storage temperatures. Whole blood was collected in blood collection tubes containing sodium heparin or PAXgene tubes with an RNA preservative. These were subjected to different storage treatments that can possibly occur during logistically difficult field sampling. Following various treatments, plasma proteins showed minor differences across collection years and no differences among storage treatments were observed, even when exposed to 38°C for three hours. RNA quality was assessed from whole blood using an RNA integrity number (RIN). RINs were poor from sodium heparin tubes that were frozen and from PAXgene tubes after an extended thaw. High-quality RNA was obtained from sodium heparin tubes that were never frozen and from PAXgene tubes with freezing delayed by up to 11 days. Overall, these results indicate that plasma proteins remain stable over time and when exposed to undesirable storage conditions, and RNA degrades rapidly in sea turtle blood after freezing and when not properly preserved. These aspects are important to consider when planning sampling protocols and logistics for optimal long-term sample preservation.


A study on trunk muscle activation patterns according to tilt angle during whole body tilts.
Lower back pain has a lifetime prevalence of 80% for people in a modern society, and in recent years, spinal stabilization movement has been highlighted as a method to treat lower back pain and an unbalanced position. The objectives of this study were to assess the trunk muscle activities in accordance with the tilt angles (10∘, 20∘, 30∘, 40∘) during trunk tilt exercises with a 3D dynamic exercise device. Active tilt mode (a self-generated active movement in the angle and direction steered by the user) was used in this study. The rotation capability enabled the investigation of the anterior (A), anterior right (AR), right (R), posterior right (PR), posterior (P), posterior left (PL), left (L), and anterior left (AL) tilt directions. EMG signals of the trunk (3 global muscles: rectus abdominis, RA, external obliques, EO, latissimus dorsi, LD, and 1 local muscle: multifidus, MF) muscles were obtained. The MF muscle activity was higher while the anterior tilt was maintained, and the abdominal muscle activity was higher while the posterior tilt was maintained. Also, as the tilt angle increased, the activity of the muscles opposite the tilt direction increased. The results indicate that to maintain equilibrium through posture stabilization during whole body tilting, the human body maintains a proper interaction among the body segments as well as between the body and the execution environment. Moreover, stability is maintained through the co-contraction of antagonistic and agonistic muscles. In future studies, it will be important to conduct research on improving imbalance in the trunk muscles.


Structural and dynamic inhomogeneities induced by curvature gradients in elliptic colloidal halos of paramagnetic particles.
Paramagnetic colloidal particles distributed along an ellipse are used as a model system to study the effects of curvature gradients on the structure and dynamics of colloids in curved manifolds. Unlike what happens for circular and spherical systems, in the present case, the equilibrium one-particle distribution function displays inhomogeneities due to the changing curvature along the ellipse. The ensuing effects on the two-body correlations are also analyzed, leading to the observation of anisotropic and long-ranged effects. Another noticeable consequence is the slowing down of the self-diffusion of these particles, which for large eccentricities may induce metastable states; this is evaluated by means of the time-dependent self-distribution.


Ascending colon cecal junction carcinoma with prostate metastasis: A case report and literature review.
Colon carcinoma is the most common type of cancer, and a leading cause of cancer-related death. Clinically, the most common sites of metastases from colon carcinoma are the liver, lungs, peritoneum, and lymph nodes, while the incidence of metastases to the prostate is low. There are few relevant studies on colon carcinoma, most of them being case reports. A 76-year-old man treated with radical resection of right colon carcinoma due to primary poorly differentiated adenocarcinoma of the cecum. Postoperative pathological examination suggested that he had cancer at the junction of the ascending colon and the cecum. He had received adjuvant chemotherapy after surgery. One year later, he received transurethral plasma resection of the prostate due to urinary system discomfort. Postoperative pathological immunohistochemistry suggested prostate metastasis of colorectal carcinoma, and he received individualized treatment, but this produced no clear survival benefit. Ascending colon cecal junction carcinoma with prostate metastasis. Radical resection, chemotherapy, anti-androgen therapy, surgery to relieve primary lesion obstruction symptoms, and local radiotherapy of the prostate. At present, clinical cases of colon carcinoma with prostate metastasis are rare. By sharing a rare case of ascending colon cecal junction carcinoma with prostate metastasis and reviewing the relevant literature, this paper explores and optimizes the clinical treatment of colon carcinoma with prostate metastasis.


Electromyographic studies in calves with spastic paresis.
As part of the investigation into the cause of spastic paresis in cattle, electromyographic studies were done in a number of calves with spastic paresis of one limb and in a number of normal calves. The calves with spastic paresis were also studied at various intervals after total neurectomy of the tibial nerve or tenotomy of the Achilles tendon structure. A marked increase in activity was perceptible in a number of muscles but characteristic changes in the EMG were not observed.


Externalizing and internalizing problems at school as signs of health-damaging behaviour and incipient marginalization.
This study aimed to investigate whether behavioural or emotional problems in adolescents detected by their teachers are signs of a common psychosocial maladjustment and of the beginning of social marginalization. Altogether, 171 pupils (15 years of age) from the eastern part of Finland participated in the survey. Behavioural and emotional problems and academic achievements were assessed separately by two teachers. Pupils filled in a questionnaire about alcohol use, smoking, physical exercise and fitness, self-rated health, psychosomatic symptoms, social relationships and future educational plans. Results showed that poor success at school and the absence of or limited educational plans were associated with both externalizing and internalizing problems. Externalizing problems were associated with health-damaging behaviour and with bullying others. Internalizing problems were associated with poor perceived health and a low level of exercise, with mental symptoms, and with problems in social relationships. Thus, the pupils in both problem groups had a clustering of different risk factors. We conclude that the accumulation in adolescents of self-reported health-damaging behaviour, problems related to school, to future educational plans and to social relationships are already obvious in pupils with externalizing and/ or internalizing problems detected by their teachers at the age of 15 years. The capacity of teachers to identify pupils at risk as early as possible should therefore be utilized. The development of a vicious circle might be prevented through early intervention at school, by offering pupils guidance, counselling and treatment.


Pregnancy in systemic lupus erythematosus.
Issues concerning contraception, fertility, and pregnancy usually arise during a typical lupus patient's disease course. Pregnancy superimposed on established lupus may alter the course of the disease, and, conversely, lupus may affect the natural history of pregnancy. Two recently described autoantibody markers, anti-SSA (Ro) and anticardiolipin, have provided new insights concerning fetal risks in these patients. Furthermore, they should lead to improved understanding of mechanisms of tissue injury and to new ideas about therapeutic interventions and/or prevention of pregnancy complications.


B1 siRNA Increases de novo DNA Methylation of B1 Elements and Promotes Wound Healing in Diabetic Rats.
Alu (B1 in rodents) hypomethylation, commonly found in diabetes mellitus patients, increases DNA damage and, consequently, delays the healing process. Alu siRNA increases Alu methylation, reduces DNA damage, and promotes cell proliferation. Aim: To explore whether B1 siRNA treatment restores B1 hypomethylation, resulting in a reduction in DNA damage and acceleration of the healing process in diabetic rat wounds. Methods: We generated splinted-excisional wounds in a streptozotocin (STZ)-induced type I diabetic rat model and treated the wounds with B1 siRNA/Ca-P nanoparticles to generate de novo DNA methylation in B1 intersperse elements. After treatment, we investigated B1 methylation levels, wound closure rate, wound histopathological structure, and DNA damage markers in diabetic wounds compared to nondiabetic wounds. Results: We reported that STZ-induced diabetic rat wounds exhibited B1 hypomethylation, wound repair defects, anatomical feature defects, and greater DNA damage compared to normal rats. We also determined that B1 siRNA treatment by Ca-P nanoparticle delivery restored a decrease in B1 methylation levels, remedied delayed wound healing, and improved the histological appearance of the wounds by reducing DNA damage. Conclusion: B1 hypomethylation is inducible in an STZ-induced type I diabetes rat model. Restoration of B1 hypomethylation using B1 siRNA leads to increased genome stability and improved wound repair in diabetes. Thus, B1 siRNA intervention may be a promising strategy for reprogramming DNA methylation to treat or prevent DNA damage-related diseases.


Hematocrit-Independent Quantitation of Stimulants in Dried Blood Spots: Pipet versus Microfluidic-Based Volumetric Sampling Coupled with Automated Flow-Through Desorption and Online Solid Phase Extraction-LC-MS/MS Bioanalysis.
A workflow overcoming microsample collection issues and hematocrit (HCT)-related bias would facilitate more widespread use of dried blood spots (DBS). This report describes comparative results between the use of a pipet and a microfluidic-based sampling device for the creation of volumetric DBS. Both approaches were successfully coupled to HCT-independent, fully automated sample preparation and online liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis allowing detection of five stimulants in finger prick blood. Reproducible, selective, accurate, and precise responses meeting generally accepted regulated bioanalysis guidelines were observed over the range of 5-1000 ng/mL whole blood. The applied heated flow-through solvent desorption of the entire spot and online solid phase extraction (SPE) procedure were unaffected by the blood's HCT value within the tested range of 28.0-61.5% HCT. Enhanced stability for mephedrone on DBS compared to liquid whole blood was observed. Finger prick blood samples were collected using both volumetric sampling approaches over a time course of 25 h after intake of a single oral dose of phentermine. A pharmacokinetic curve for the incurred phentermine was successfully produced using the described validated method. These results suggest that either volumetric sample collection method may be amenable to field-use followed by fully automated, HCT-independent DBS-SPE-LC-MS/MS bioanalysis for the quantitation of these representative controlled substances. Analytical data from DBS prepared with a pipet and microfluidic-based sampling devices were comparable, but the latter is easier to operate, making this approach more suitable for sample collection by unskilled persons.


Salvinorin A ameliorates cerebral vasospasm through activation of endothelial nitric oxide synthase in a rat model of subarachnoid hemorrhage.
This study aimed to demonstrate the potential of salvinorin A (SA) for cerebral vasospasm after subarachnoid hemorrhage (SAH) and investigate mechanisms of therapeutic effect using rat SAH model. Salvinorin A was injected intraperitoneally, and the neurobehavioral changes were observed at 12 hours, 24 hours, 48 hours, and 72 hours after SAH. Basilar artery was observed by magnetic resonance imaging (MRI). The inner diameter and thickness of basilar artery were measured. The morphological changes and the apoptosis in CA1 area of hippocampus were detected. Endothelin-1 (ET-1) and nitric oxide (NO) levels were detected by ELISA kit. The protein expression of endothelial NO synthase (eNOS) and aquaporin-4 (AQP-4) was determined by Western blot for potential mechanism exploration. Salvinorin A administration could relieve neurological deficits, decrease the neuronal apoptosis, and alleviate the morphological changes in CA1 area of hippocampus. SA alleviated CVS by increasing diameter and decreasing thickness of basilar artery, and such changes were accompanied by the decreased concentration of ET-1 and increased level of NO. Meanwhile, SA increased the expression of eNOS and decreased the expression of AQP-4 protein in the basilar artery and hippocampus. Salvinorin A attenuated CVS and alleviated brain injury after SAH via increasing expression of eNOS and NO content, and decreasing ET-1 concentration and AQP-4 protein expression.


Participant-guided development of bilingual genomic educational infographics for Electronic Medical Records and Genomics Phase IV study.
Developing targeted, culturally competent educational materials is critical for participant understanding of engagement in a large genomic study that uses computational pipelines to produce genome-informed risk assessments. Guided by the Smerecnik framework that theorizes understanding of multifactorial genetic disease through 3 knowledge types, we developed English and Spanish infographics for individuals enrolled in the Electronic Medical Records and Genomics Network. Infographics were developed to explain concepts in lay language and visualizations. We conducted iterative sessions using a modified "think-aloud" process with 10 participants (6 English, 4 Spanish-speaking) to explore comprehension of and attitudes towards the infographics. We found that all but one participant had "awareness knowledge" of genetic disease risk factors upon viewing the infographics. Many participants had difficulty with "how-to" knowledge of applying genetic risk factors to specific monogenic and polygenic risks. Participant attitudes towards the iteratively-refined infographics indicated that design saturation was reached. There were several elements that contributed to the participants' comprehension (or misunderstanding) of the infographics. Visualization and iconography techniques best resonated with those who could draw on prior experiences or knowledge and were absent in those without. Limited graphicacy interfered with the understanding of absolute and relative risks when presented in graph format. Notably, narrative and storytelling theory that informed the creation of a vignette infographic was most accessible to all participants. Engagement with the intended audience who can identify strengths and points for improvement of the intervention is necessary to the development of effective infographics.


Evaluating the Impact of Adaptive Personalized Goal Setting on Engagement Levels of Government Staff With a Gamified mHealth Tool: Results From a 2-Month Randomized Controlled Trial.
Although the health benefits of physical activity are well established, it remains challenging for people to adopt a more active lifestyle. Mobile health (mHealth) interventions can be effective tools to promote physical activity and reduce sedentary behavior. Promising results have been obtained by using gamification techniques as behavior change strategies, especially when they were tailored toward an individual's preferences and goals; yet, it remains unclear how goals could be personalized to effectively promote health behaviors. In this study, we aim to evaluate the impact of personalized goal setting in the context of gamified mHealth interventions. We hypothesize that interventions suggesting health goals that are tailored based on end users' (self-reported) current and desired capabilities will be more engaging than interventions with generic goals. The study was designed as a 2-arm randomized intervention trial. Participants were recruited among staff members of 7 governmental organizations. They participated in an 8-week digital health promotion campaign that was especially designed to promote walks, bike rides, and sports sessions. Using an mHealth app, participants could track their performance on two social leaderboards: a leaderboard displaying the individual scores of participants and a leaderboard displaying the average scores per organizational department. The mHealth app also provided a news feed that showed when other participants had scored points. Points could be collected by performing any of the 6 assigned tasks (eg, walk for at least 2000 m). The level of complexity of 3 of these 6 tasks was updated every 2 weeks by changing either the suggested task intensity or the suggested frequency of the task. The 2 intervention arms-with participants randomly assigned-consisted of a personalized treatment that tailored the complexity parameters based on participants' self-reported capabilities and goals and a control treatment where the complexity parameters were set generically based on national guidelines. Measures were collected from the mHealth app as well as from intake and posttest surveys and analyzed using hierarchical linear models. The results indicated that engagement with the program inevitably dropped over time. However, engagement was higher for participants who had set themselves a goal in the intake survey. The impact of personalization was especially observed for frequency parameters because the personalization of sports session frequency did foster higher engagement levels, especially when participants set a goal to improve their capabilities. In addition, the personalization of suggested ride duration had a positive effect on self-perceived biking performance. Personalization seems particularly promising for promoting the frequency of physical activity (eg, promoting the number of suggested sports sessions per week), as opposed to the intensity of the physical activity (eg, distance or duration). Replications and variations of our study setup are critical for consolidating and explaining (or refuting) these effects. ClinicalTrials.gov NCT05264155; https://clinicaltrials.gov/ct2/show/NCT05264155.


Relationship Between Serum Fetuin-A Levels and Carotid Intima-media Thickness in Turkish Patients with Mild to Moderate Psoriasis. A Case-control Study.
Previous studies have associated severe psoriasis and psoriatic arthritis with an increased risk of atherosclerosis. However, the association between patients with mild-to-moderate plaque-type psoriasis and atherosclerosis has yet to be studied in depth. This study investigates a) possible correlations between carotid intima-media thickness (CIMT) and serum fetuin-A levels in patients with mild-to-moderate psoriasis and b) correlations between psoriasis severity index (PASI) and fetuin-A levels. The latter correlation was recently reported to be important for wound healing and vascular calcification. In this prospective study, a total of 70 patients with mild-to-moderate psoriasis and 66 control participants were included. PASI, CIMT, and serum fetuin-A levels were examined in all patients. Although the difference in fetuin-A values was not statistically significant between patients with mild-to-moderate plaque-type psoriasis and control groups (P=0.401), the CIMT levels in the psoriasis group were significantly higher than the control group (P=0.002). There were no correlations among fetuin-A levels, CIMT, and PASI. This study establishes an association between mild to moderate psoriasis and atherosclerosis. This study also concludes that, similarly to patients with severe psoriasis, CIMT levels are a better indicator of cardiovascular risk than serum fetuin-A levels in patients diagnosed with mild-to-moderate plaque-type psoriasis.


Absence of the musculocutaneous nerve together with unusual innervation of the median nerve.
During routine anatomical dissections, absence of the musculocutaneous nerve was determined in a 58-year-old male cadaver. Moreover, the biceps brachii and brachialis muscles were innervated by two separate branches which divided from the median nerve instead of the musculocutaneous nerve. From a branch that divides from the main trunk of the median nerve at nearly the middle of the arm a motor branch again divided that innervated the brachialis muscle and a sensory branch that conveyed the sense of the lateral part of the forearm. Furthermore, it was found that the brachial artery divided into its terminal branches, the radial and ulnar arteries. We believe that this rare variation of the median nerve will shed light upon surgical procedures involving the median nerve.


ATP diphosphohydrolase from Schistosoma mansoni egg: characterization and immunocytochemical localization of a new antigen.
The fact that the Schistosoma mansoni egg has two ATP diphosphohydrolase (EC 18.104.22.168) isoforms with different net charges and an identical molecular weight of 63,000, identified by non-denaturing polyacrylamide gel electrophoresis and immunological cross-reactivity with potato apyrase antibodies, is shown. In soluble egg antigen (SEA), only the isoform with the lower net negative charge was detected and seemed to be the predominant species in this preparation. By confocal fluorescence microscopy, using anti-potato apyrase antibodies, the S. mansoni egg ATP diphosphohydrolase was detected on the external surface of miracidium and in von Lichtenberg's envelope. Intense fluorescence was also seen in the outer side of the egg-shell, entrapped by the surface microspines, suggesting that a soluble isoform is secreted. ATP diphosphohydrolase antigenicity was tested using the vegetable protein as antigen. The purified potato apyrase was recognized in Western blots by antibodies present in sera from experimentally S. mansoni-infected mice. In addition, high levels of IgG anti-ATP diphosphohydrolase antibodies were detected by ELISA in the same sera. This work represents the first demonstration of antigenic properties of S. mansoni ATP diphosphohydrolase and immunological cross-reactivity between potato apyrase and sera from infected individuals.


Selected epidemiological and clinical aspects of malaria in the material of the Institute of Maritime and Tropical Medicine in Gdynia.
Despite numerous endeavours to eradicate malaria remains a problem to be solved. This is reflected in high morbidity and mortality rates in endemic zones of this disease, and in the continually growing parasites resistance to the drugs applied within chemoprophylaxis and the treatment employed. In the compass of 1976-1987 a group of 20 thousand people, back from the tropics, was examined. In that number 415 having suffered from malaria while stay in the endemic zone of the disease, in 64 patients malaria was diagnosed in the course of the examinations. They were all subjected to the therapy in the IMTM. In several cases serious complications occurred. In the conclusions the authors point at the insufficient and inaccurate use of chemoprophylaxis the necessity of adopting individual procedure towards each patient and of considering the possibility of Plasmodium sp. infection in the people with the fever of the aetiology unknown, referring their stay in malarial regions.


A qualitative study on the socialization of beginning physical education teacher educators.
Few studies have focused on how university faculty learn and understand expectations of their professional role. The purpose of this study was to describe the experiences of five female physical education teacher educators in their first positions as assistant professors in research oriented universities. Data were collected using primarily qualitative methods--weekly journals and in-depth interviews. Quantitative data were gathered to compare organizational factors such as salary, load allocation, equipment, and travel funds. Data yielded five main categories concerning how and what participants learned about their faculty roles. These categories included participants' perceptions of (a) organizational structure and job facilitation, (b) work tasks, (c) support systems, (d) evaluation and feedback, and (e) participants' psychological states. All participants reported experiencing role ambiguity and stress. Clear criteria for job performance, collegial support and mentoring, and regular evaluation and feedback were cited by all participants as important factors for reducing stress and facilitating their roles as faculty.


Experiences of COVID-19-related anti-Asian discrimination and affective reactions in a multiple race sample of U.S. young adults.
Little remains known about both Asian and Asian American (A/AA) and non-Asian young adults' experiences and affective reactions regarding COVID-19 anti-Asian discrimination. To our knowledge, this is the first study that explores the nature and impact of COVID-19 anti-Asian discrimination within a multi-racial sample. This study uses qualitative open-ended responses from a sub-sample of Wave I of the COVID-19 Adult Resilience Experiences Study (CARES) data collected between March to September 2020. Thematic analysis was used to explore two open-ended questions: "Are there experiences we missed in the survey so far that you wish to describe?" and "What are your thoughts about the current social climate?" The data analysis for this study focused on 113 discrimination or racism-related comments. A total of 1331 young adults completed an online survey of which 611 provided comments; a multi-racial sample of 95 individuals (65.3% non-Asians, 24.7% A/AA) contributed 113 COVID-19 anti-Asian discrimination or racism-related comments. Two overarching themes were: types of discrimination (societal, interpersonal, intrapersonal) and affective reactions to discrimination (fear, anxiety/distress, hopelessness/depression, and avoidance). Not only did both A/AA and non-Asian participants report witnessing or hearing reports of anti-Asian discrimination, but both groups described having negative affective reactions to anti-Asian discrimination. Anti-Asian discrimination in the face of COVID may be more widespread than initial reports indicate. Our finding suggests that anti-Asian discrimination is a societal illness that impacts all populations in the U.S. This calls for cross-racial coalitions and solidarity in the fight against discrimination and racism.


Impact of Tailored-Enhanced Recovery After Surgery Versus Conventional Care in Patients of Gastro-Duodenal Perforation: A Pilot Randomized Control Trial.
The enhanced recovery after surgery (ERAS) program established improved clinical outcomes in elective surgery; however, its role in emergencies is uncertain. This study was designed to assess the feasibility, safety, and efficacy of a tailored-ERAS (t-ERAS) protocol in patients undergoing modified Graham's patch closure for gastro-duodenal perforation. A single-centre, prospective, parallel-arm, open-label, randomized controlled trial was conducted from February 2021 to December 2021. Patients with gastroduodenal perforation undergoing modified Graham's patch were randomly assigned to either conventional care or the t-ERAS pathway. Patients with refractory septic shock, psychiatric or neurological disorders, pregnancy, multiple perforations, sealed-off perforations, and perforation sizes greater than 1.5 cm were excluded. The primary outcome was to compare the length of hospitalization (LOH). Functional recovery parameters and morbidity were compared in secondary outcomes. Twenty-five patients each were included in conventional care and the t-ERAS group. In the t-ERAS group, LOH was significantly shorter (6.3 SD2.15 days versus 9.56 SD4.33 days, p = 0.001). Patients in the t-ERAS group had significantly early functional recovery (days) with time to first bowel sound (1.8 SD0.41; p 0.002), first flatus (2.52 SD0.65; p = 0.026), first stool (3.04 SD0.68; p < 0.001), first liquid diet (2.24 SD0.60; p = 0.002), and duration of ileus (2.64 SD0.86; p = 0.038). There was no significant difference in morbidity such as post-operative nausea and vomiting, SSI, or pulmonary complications between the two groups. Tailored ERAS pathways are safe and effective in reducing the LOH and promoting early functional recovery in patients undergoing emergency closure of gastro-duodenal perforation.


Prevalence of mcr-1 in Colonized Inpatients, China, 2011-2019.
In response to the spread of colistin resistance gene mcr-1, China banned the use of colistin in livestock fodders. We used a time-series analysis of inpatient colonization data from 2011-2019 to accurately reveal the associated fluctuations of mcr-1 that occurred in inpatients in response to the ban.


Molecular mechanism of Fast Endophilin-Mediated Endocytosis.
Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Clathrin-mediated endocytosis (CME) is the housekeeping pathway in resting cells but additional Clathrin-independent endocytic (CIE) routes, including Fast Endophilin-Mediated Endocytosis (FEME), internalize specific cargoes and support diverse cellular functions. FEME is part of the Dynamin-dependent subgroup of CIE pathways. Here, we review our current understanding of the molecular mechanism of FEME. Key steps are: (i) priming, (ii) cargo selection, (iii) membrane curvature and carrier formation, (iv) membrane scission and (v) cytosolic transport. All steps are controlled by regulatory mechanisms mediated by phosphoinositides and by kinases such as Src, LRRK2, Cdk5 and GSK3β. A key feature of FEME is that it is not constitutively active but triggered upon the stimulation of selected cell surface receptors by their ligands. In resting cells, there is a priming cycle that concentrates Endophilin into clusters on discrete locations of the plasma membrane. In the absence of receptor activation, the patches quickly abort and new cycles are initiated nearby, constantly priming the plasma membrane for FEME. Upon activation, receptors are swiftly sorted into pre-existing Endophilin clusters, which then bud to form FEME carriers within 10 s. We summarize the hallmarks of FEME and the techniques and assays required to identify it. Next, we review similarities and differences with other CIE pathways and proposed cargoes that may use FEME to enter cells. Finally, we submit pending questions and future milestones and discuss the exciting perspectives that targeting FEME may boost treatments against cancer and neurodegenerative diseases.


ST-elevation myocardial infarction diagnosed after hospital admission.
Treatment times for ST-elevation myocardial infarction (STEMI) patients presenting to percutaneous coronary intervention hospitals have improved dramatically over the past 10 years, particularly for patients using emergency medical services. Limited data exist regarding treatment times and outcomes for patients who develop STEMI after hospital admission. With the use of a comprehensive prospective regional STEMI program database, we evaluated the characteristics and outcomes for patients who develop STEMI after hospital admission. Of the 3795 consecutive STEMI patients treated by the use of the Minneapolis Heart Institute regional STEMI program from March 2003 to January 2013, 990 (26.1%) presented initially to the percutaneous coronary intervention facility, including 640 arriving via emergency medical services, 267 self/family driven, and 83 already admitted to the hospital. Patients with in-hospital presentation were older with higher body mass indexes, were more likely to have hypertension, and to present with pre-percutaneous coronary intervention cardiac arrest and cardiogenic shock. Door-to-balloon times (diagnostic ECG-to-balloon for in-hospital patients) were longer than for patients using emergency medical services (76 versus 51 minutes; P<0.001), but similar to self/family-driven patients (76 versus 66 minutes; P=0.13). In-hospital patients had longer lengths of stay (5 versus 3 versus 3 days; P<0.001) and higher 1-year mortality (16.9% versus 10.3% versus 7.1%; P=0.032). These patients frequently had high-risk and complex reasons for admission, including 30.1% with acute coronary syndrome, 22.9% postsurgery, 13.3% respiratory failure, and 8.4% ventricular fibrillation. Patients who develop STEMI while in-hospital represent a unique, high-risk subset of patients. They have increased treatment time and lengths of stay and higher mortality rates than the patients presenting via emergency medical services or who are self/family driven.


Cryopreservation of pathogenic free-living amebae.
A variety of conditions of cryopreservation were evaluated in order to define a single procedure for freezing the amebae of pathogenic Naegleria and Acanthamoeba. The average best conditions for freezing the three species studied were: 1 x 10(6) exponentially growing amebae/ml of freezing medium consisting of 12% dimethylsulfoxide, 20% heat-inactivated bovine calf serum, 4% glucose, in Mix ameba medium; 30 min equilibration at 23 degrees C (room temperature), followed by 60 min at -20 degrees C, with storage at -70 degrees C. Under these conditions viability after 1 month of freezing was 53% for Acanthamoeba castellanii, 64% for Naegleria fowleri, and 66% for Naegleria australiensis. After 12 months of freezing, viability was 39% for A. castellanii, 47% for N. fowleri, and 53% for N. australiensis.


[Ultrastructural observations of the dorsal lateral geniculate nucleus following non-surgical retinal lesion of the rats].
By intravitreal injection of arsenous pentoxide (As2O5), which had been used in the pulpectomy in the dentistry, the retina, including the ganglion cell layer, fell selectively into necrosis and the lesions were uniform throughout all part of the retina. Following these non-surgically induced retinal lesions, the dorsal lateral geniculate nucleus of the rats was examined by electron microscope over varying periods of time. From 2 days after the injection, dark atrophic axon terminals appeared in the dorsal lateral geniculate nucleus and these terminals were in most instances surrounded by swollen astrocytic processes with glycogen particles. The quantity of the degenerating terminals maximized at 6 to 7 days after injection and then decreased by 60 days. It was also shown that various features of the degenerating terminals were related to the postsynaptic dendrites. In early stages these degenerating axon terminals had dense, swollen mitochondria and many synaptic vesicles in the electron dense matrix. Then these terminals were deeply indented to the apposed dendrites and by this indentation the astrocytic process seemed to insinuate into the synaptic junction. In these situations, the cytoplasm of astrocytes increased in electron density around the terminals. The postsynaptic density and the subsynaptic organellas were clearly shown to be identical through the course of the degeneration. There were also dendro-astroglial junctions, and these junctions seemed to be one of the features of degeneration of the terminals. It was suggested that there was an obvious course of the degenerating terminals separated from their post-synaptic sites without disruption of integrity of the post-synaptic membrane specialization by astrocytic cell process in Wallerian degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)


Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair.
Mesenchymal stem cells (MSCs) have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-gamma with TNF-alpha, IL-1alpha or IL-1beta. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression: immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide (NO), whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase (IDO). Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.


Routine preoperative biliary drainage: effect on management of obstructive jaundice.
The routine application of preoperative percutaneous transhepatic biliary drainage (PTBD) to patients who have obstructive jaundice has a significant effect on overall morbidity, mortality, and patient survival by allowing selective application of the most appropriate therapeutic modality. Surgical patients who undergo PTBD were compared with those for whom PTBD was not available. The surgical complication rate was 44% for those who did not undergo PTBD and 15% for those who did. The surgical procedure-related mortality rate was 30% for those who did not undergo PTBD and 12% for those who did. These differentials may have been due either to a beneficial effect of presurgical decompression or to the fact that only more favorable candidates were selected for operative internal bypass. There was an overall increase in length of survival following the application of PTBD, especially in those patients who were surgical candidates.


Musical scales and evaluations of happiness and awkwardness: effects of pitch, direction, and scale mode.
Participants rated the perceived happiness, brightness, awkwardness, pitch velocity, and tempo change of ascending and descending musical scales in four modes (natural, melodic, and harmonic minor modes and the major mode). Only minor differences between ratings of natural, harmonic, or melodic minor scales or between ratings of parallel and relative major scales were found. Ascending scales were rated as happier, brighter, and more accelerating than were descending scales; ascending minor scales were rated as faster and more awkward than were descending minor scales. Musical keys in each mode were compared, and significant differences were found. Musical keys that started on a higher pitch were rated as happier, brighter, and faster and as speeding up more than were keys that started on a lower pitch. The data were consistent with previous findings and suggest that pitch and direction (contour), rather than mode or key, influence listeners' judgments of musical stimuli.


Pseudo color night vision correlated imaging without an infrared focal plane array.
Night vision is the ability to see in low-light conditions. However, conventional night vision imaging technology is limited by the requisite high-performance infrared focal plane array. In this article, we propose a novel scheme of color night vision imaging without the use of an infrared focal plane array. In the experimental device, the two-wavelength infrared laser beam reflected by the target is modulated by a spatial light modulator, and the output light is detected by a photomultiplier tube. Two infrared night vision images are reconstructed by measuring the second-order intensity correlation function between two light fields. Thus, the processing mode of optical electric detection in conventional night vision imaging is transformed into the processing mode of light field control. Furthermore, two gray images with different spectra are processed to form a color night vision image. We show that a high-quality color night vision image can be obtained by this method.


Adverse events, placebo and nocebo effects in placebo-treated paediatric patients with refractory focal epilepsies. Analysis of double-blind studies.
Assessment of placebo and nocebo effects and evaluation of background incidence of some predefined adverse effects (AEs) of antiepileptic drugs (AEDs) in placebo-treated paediatric patients recruited in randomized controlled studies (RCTs) of refractory focal epilepsies. We searched all add-on, double-blind, placebo-controlled trials investigating any AED in paediatric patients with focal epilepsies and extracted both for patients treated with placebo and for those treated with the active drug, number of patients, number of responders (≥50% reduction of seizure frequency) number of patients withdrawing because of AEs, number of patients with AEs, and number of patients with 11 predefined AEs. The association between placebo and active treatment AEs was also explored. Seven RCTs were included in our study with a total of 668 children treated with the experimental drug and 634 with placebo. In placebo-treated patients, overall responder rate was 19.7% [(95% CI), (16.0, 23.4)], proportion of placebo-treated patients withdrawing because of AEs was 3.6% (2.1, 5.1%), and proportions of patients with any AE was 81.3% (68.5, 94.1%). The three most frequently reported AEs were headache (PR=11.4%, 6.4,16.3%) somnolence (PR=9.6%, 4.9, 14.3%), and ataxia (PR=4.6, -1.1, 10.2). A significant correlation between placebo-treated patients and those treated with the active drug was found for the outcome measure any AE and the AEs somnolence, headache and fatigue. Both placebo and nocebo effects assessed in this paediatric population did not differ from findings reported in adults. This is in partial contrast to what has been previously reported and with observations in other diseases. Also specific AEs, which are at least in part, caused by the background treatment, failed to show significant differences from what previously observed in adult RCTs.


New totally intracorporeal reconstructive approach after robotic total gastrectomy: Technical details and short-term outcomes.
To show outcomes of our series of patients that underwent a total gastrectomy with a robotic approach and highlight the technical details of a proposed solution for the reconstruction phase. Data of gastrectomies performed from May 2014 to October 2016, were extracted and analyzed. Basic characteristics of patients, surgical and clinical outcomes were reported. The technique for reconstruction (Parisi Technique) consists on a loop of bowel shifted up antecolic to directly perform the esophago-enteric anastomosis followed by a second loop, measured up to 40 cm starting from the esojejunostomy, fixed to the biliary limb to create an enteroenteric anastomosis. The continuity between the two anastomoses is interrupted just firing a linear stapler, so obtaining the Roux-en-Y by avoiding to interrupt the mesentery. Fifty-five patients were considered in the present analysis. Estimated blood loss was 126.55 ± 73 mL, no conversions to open surgery occurred, R0 resections were obtained in all cases. Hospital stay was 5 (3-17) d, no anastomotic leakage occurred. Overall, a fast functional recovery was shown with a median of 3 (3-6) d in starting a solid diet. Robotic surgery and the adoption of a tailored reconstruction technique have increased the feasibility and safety of a minimally invasive approach for total gastrectomy. The present series of patients shows its implementation in a western center with satisfying short-term outcomes.


Development of olmesartan medoxomil optimized nanosuspension using the Box-Behnken design to improve oral bioavailability.
The aim of the present investigation was to enhance the oral bioavailability of olmesartan medoxomil by improving its solubility and dissolution rate by preparing nanosuspension (OM-NS), using the Box-Behnken design. In this, four factors were evaluated at three levels. Independent variables include: concentration of drug (X1), concentration of surfactant (X2), concentration of polymer (X3) and number of homogenization cycles (X4). Based on preliminary studies, the size (Y1), zeta potential (ZP) (Y2) and % drug release at 5 min (Y3) were chosen as dependent responses. OM-NS was prepared by high pressure homogenization method. The size, PDI, ZP, assay, in vitro release and morphology of OM-NS were characterized. Further, the pharmacokinetic (PK) behavior of OM-NS was evaluated in male wistar rats. Statistically optimized OM-NS formulation exhibited mean particle size of 492 nm, ZP of -27.9 mV and 99.29% release in 5 min. OM-NS showed more than four times increase in its solubility than pure OM. DSC and XRD analyses indicated that the drug incorporated into OM-NS was in amorphous form. The morphology of OM-NS was found to be nearly spherical with high dispersity by scanning electron microscopic studies. The PK results showed that OM lyophilized nanosuspension (NS) exhibited improved PK properties compared to coarse powder suspension and marketed tablet powder suspension (TS). Oral bioavailability of lyophilized NS was increased by 2.45 and 2.25 folds when compared to marketed TS and coarse powder suspension, respectively. Results of this study lead to conclusion that NS approach was effective in preparing OM formulations with enhanced dissolution and improved oral bioavailability.


Modelling nutrient transfer based on 3D imaging of the human placental microstructure.
Impaired transfer of nutrients from mother to fetus can affect pregnancy outcomes. The placenta has a complex microstructure, including the maternal intervillous space and fetal capillaries. Previous computational models of placental transfer either assumed a simplified idealized local geometry or were based on 2D imaging. In this study, we present a novel 3D computational model to assess the placental transfer of nutrients at the microscale in interaction with the maternal flow environment. A stack of confocal microscopy images of the placental terminal villi was collected and reconstructed. The 3D simulation framework was tested for the transport of oxygen. Preliminary results identified local stagnant zones, as well as areas of high nutrient transfer into the fetal capillaries in the most exposed branches of the villi as a result of better perfusion, combined with a smaller thickness of the tissue barrier. Overall, the current model may serve as a tool for assessing pregnancy conditions affected by inefficient nutrient transfer due to altered microscale placental morphology.


Sexual Dysfunction in Unmedicated Patients with Schizophrenia and in Healthy Controls.
Sexual dysfunction figures prominently in patients with schizophrenia; however, medication effects may play a role. The objective of this case control study was to assess differences in the presence of sexual dysfunction in unmedicated patients with schizophrenia versus healthy controls. Sexual dysfunction was assessed using the Derogatis Inventory for Sexual Function self-rating in a cross-sectional design controlling for age and gender effects. A brief sexual anamnesis was applied to describe the psychosocial background of the mostly male sample further. Results show a significant difference with patients reporting more problems in most domains and with a significant correlation between severity of psychosis (Positive and Negative Syndrome Scale total scores) and the impairment of orgasm experience. The study revealed reduced sexual activities and less pleasure during sexual activities of patients. This study implies that schizophrenia has an impact on the presence of sexual dysfunction and that sexual dysfunction is partly independent of antipsychotic treatment. Since the sample consisted mostly of first-episode males, conclusions might only be valid for this subgroup.


Increasing PCP and Hospital Medicine Physician Verbal Communication During Hospital Admissions.
During hospital admission, communication between primary care physicians (PCPs) and hospital medicine (HM) physicians provides an opportunity for collaboration. Two-way communication facilitates collaboration by allowing the receiver to ask and respond to questions. At our institution, most HM-to-PCP communication occurred by telephone call after discharge. Our specific aim was to increase the percentage of patients for whom a telephone conversation occurred between HM and PCPs during hospital admission from 40% to >80%. An improvement team that included PCPs and HM physicians redesigned the process for communication with PCPs to emphasize collaboration during hospitalization. Interventions were used to target key drivers of information transparency, PCP and HM provider buy-in, the value of early call initiation, process standardization, accommodating provider availability, and preoccupation with failure. We used improvement-science methods and run charts to measure our progress and attain our goal. The median weekly percentage of patients with a phone call completed during hospitalization increased from 40% to 85% at the satellite campus and 40% to 80% at the main campus. In addition to the standardized use of a telephone operator system to route calls and follow-up on unplaced calls, critical interventions included feedback on PCP call preferences to providers and the provider script for calls. PCPs and HM physicians applied quality-improvement methodology to ensure reliable HM-PCP communication during hospital admission. Interventions to facilitate communication between providers and learners (who may otherwise have limited interaction), such as the scripting of phone calls and feedback from PCPs to HM physicians, were important for success.


Mucoadhesive formulation containing Curcuma longa L. reduces oral mucositis induced by 5-fluorouracil in hamsters.
We explored the effects of a mucoadhesive formulation containing curcuminoid (MFC) from Curcuma longa L. extract on oral mucositis (OM) induced by 5-fluorouracil (5-FU) in hamsters. Seventy-two golden Syrian hamsters were randomly allocated into four groups: control, placebo, chamomilla, and MFC. Animals received an intraperitoneal injection of 5-FU at Days 0 and 2. On Days 3 and 4, the buccal mucosa was scratched. Therapy was initiated on Day 5. Animals received two applications of the substances per day according to the experimental group. Six animals were euthanized on Days 8, 10, and 14. Clinical analysis were performed using photography and histopathological sections of 3 μm were stained by hematoxylin-eosin for semiquantitative analysis of re-epithelization and inflammation. Immunohistochemistry was used for angiogenesis (CD31) and transforming growth factor beta 1 (TGF-β1) analysis. On Day 5, all groups exhibited OM. Clinical and histopathological findings revealed that on Day 8, both MFC and chamomilla groups exhibited better wound healing. In addition, the MFC group demonstrated lower angiogenesis and TGF-β1 levels on Day 8 compared with placebo and control groups. Collectively, these findings suggest that MFC has a therapeutic effect on OM, accelerating wound healing through re-epithelization and anti-inflammatory action as modulation of angiogenesis and TGF-β1 expression.


Long-term outcome of extensive skull reconstruction using demineralized perforated bone in Siamese twins joined at the skull vertex.
The successful use of cortical demineralized perforated bone in the treatment of extensive skeletal defects in children is exemplified by this case involving Siamese twins joined at the skull vertex. Four years following extensive skull reconstruction using demineralized perforated bone, an examination revealed successful calvarial reconstruction in one twin. The other twin required additional implants of demineralized perforated bone to fill in defects. However, a histologic examination taken following this additional procedure revealed that these implants neither caused tissue reaction over a 4-year period, nor showed signs of resorption. Bony remodeling and new bone formation were in progress. Compared with other bone substitutes, demineralized perforated bone has proven to be effective in the treatment of large skull defects in children.


Is soft tissue radiology useful in acromegaly?
Twenty-six acromegalics had measurements of serum growth hormone (GH) levels during a glucose tolerance test, X rays of the heel for heel pad thickness, and of the hand for bone/soft tissue ratio. These measurements were performed before and between 2 and 7 years after treatment, which was by transethmoidal hypophysectomy, external irradiation or a combination of the two. Neither the heel pad thickness nor bone/soft tissue ratio correlated with the mean serum GH nor with each other before and after treatment. The nine patients who were assessed as showing a good clinical response to treatment showed a significantly greater fall in mean serum GH than the 17 patients who were assessed as unchanged or partial responders (40.1 +/- 20 mmu/l compared with 9.9 +/- 14.0 mmu/l, p = 0.02). However, there were no significant differences in changes of heel pad thickness nor bone/soft tissue ratio between these groups. It is concluded that these radiological measurements of soft tissues are unhelpful in the follow-up of acromegalic patients.


General simultaneous motion estimation and image reconstruction (G-SMEIR).
To achieve better performance for 4D multi-frame reconstruction with the parametric motion model (MF-PMM), a general simultaneous motion estimation and image reconstruction (G-SMEIR) method is proposed. In G-SMEIR, projection domain motion estimation and image domain motion estimation are performed alternatively to achieve better 4D reconstruction. This method can mitigate the local optimum trapping problem in either domain. To improve computational efficiency, the image domain motion estimation is accelerated by adapting fast convergent algorithms and graphics processing unit (GPU) computing. The proposed G-SMEIR method is tested using a cone-beam computed tomography (CBCT) simulation study of 4D XCAT phantom at different dose levels and compared with 3D total variation-based reconstruction (3D TV), 4D reconstruction with image domain motion estimation (IM4D), and SMEIR. G-SMEIR shows strong denoising capability and achieves similar performance at regular dose and half dose. The root mean squared error (RMSE) of G-SMEIR is the best among the four methods and improved about 12% over SMEIR for all respiratory phase images at full dose. G-SMEIR also achieved the best structural similarity index (SSIM) values among all methods. More importantly, G-SMEIR leads to more than 40% improvement of the mean deviation from the phantom tumor motion over SMEIR. A preliminary patient CBCT image reconstruction also shows better image quality of G-SMEIR than that of the frame-by-frame reconstruction (3D TV) and MF-PMM either using image domain motion estimation (IM4D) or using projection domain motion estimation (SMEIR) alone. G-SMEIR with a flexible combination of image domain and projection domain motion estimation provides an effective tool for 4D tomographic reconstruction.


Controllable heterogeneity in a supramolecular hydrogel.
A dispersion of a peptide amphiphile into water forms hierarchical fibril structures, leading to a supramolecular hydrogel. We here report that there exists dynamic heterogeneity in the gel, which might be induced by the heterogeneous fibril network. The network, and therefore, the heterogeneity, can be easily regulated by changing the temperatures used to dissolve the gelator in water.


Changes of TCR repertoire diversity in colorectal cancer after Erbitux (cetuximab) in combination with chemotherapy.
We have previous found a positive correlation between post-therapy TCR repertoire normalization and remission of colorectal cancer (CRC) patients following fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or Rh-endostatin therapy. To further define the TCR repertoire diversity changes following treatment in CRC patients, and confirm its potential prognostic value, the present study extended the sample size of follow-up and used an alternative therapy regime to investigate changes of TCR repertoires following Erbitux plus FOLFIRI therapy. Inclusion and exclusion criteria have been established to screen out 26 patients to receive Erbitux plus FOLFIRI therapy. Efficacy and toxicity assessment have been made for them after 3 months' treatment as well as the TCR repertoire diversity has been determined. A CDR3 complex scoring system was used to quantify the diversity of TCR repertoire. The results showing that the diversity of CD4(+) T cells in PR group was significantly higher than that of SD and PD groups, and the difference was enlargement after treatment. The diversity of CD8(+) T cells in PR group has no difference before and after treatment, but significant decrease in SD and PD group after treatment. In conclusion, analysis the diversity of T cell repertoire has an important prognosis value for CRC patients.


Suppression of Proinflammatory Cytokines by Etlingera alba (A.D.) Poulsen Rhizome Extract and Its Antibacterial Properties.
Etlingera alba is one of the Etlingera plants that has not been studied intensively. Plants that belong to the same genus have similar constituents and pharmacological activities. Thus, we aim to investigate the chemical composition and pharmacological activities, namely, anti-inflammatory and antibacterial properties, of E. alba rhizome extract (EA). The chemical constituent was detected using the test tube method. The inflammatory model rats were obtained by inducing them with 1% carrageenan, and their palm edema volume and cytokine levels, namely, IL-6, IL-12, and TNF-α, were measured. Antibacterial activity was performed with broth microdilution. The phytochemical screening of EA was detecting alkaloids, flavonoids, tannins, steroids, and phenols. The EA has anti-inflammatory activity by reducing the palms' edema volume and cytokine levels (IL-6, IL-12, and TNF-α), and the optimal concentration was 400 mg/kg body weight (BW). On the other hand, EA also exhibited antibacterial properties against E. coli and S. enterica. In conclusion, similar to other Etlingera plants, EA also demonstrates pharmacological activities, namely, anti-inflammatory and antibacterial properties.


SQ HDM sublingual immunotherapy tablet for the treatment of HDM allergic rhinitis and asthma improves subjective sleepiness and insomnia: an exploratory analysis of the real-life CARIOCA study.
There are still gaps in the knowledge regarding the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma (AA)-associated sleep disorders. A non-interventional study was conducted to assess the effect of the Standardized quality (SQ) HDM SLIT-tablet on safety and symptoms in adults with HDM respiratory allergies. The aim was to describe the status of insomnia and daytime sleepiness in AR and/or AA patients treated with the SQ HDM SLIT-tablet. This was a 12-month multicenter, longitudinal and prospective study. Participants started the SQ HDM SLIT-tablet for moderate-to-severe HDM AR, persistent despite the use of symptom-relieving medication; or HDM AA not well controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS). A total of 1,526 adult patients were enrolled and 1,483 were included in the analysis. At baseline, 41.5% of patients reported sleep disorders: 77.0% of them had insomnia and 28.9% suffered from excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than those with controlled AR (52.6%) (p<0.0001). Over time, 48.3% and 59.7% of patients reported an improvement greater than the minimal clinically important difference on the ISI and ESS scales respectively. In patients with HDM AR and/or asthma associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after one year of treatment with the SQ HDM SLIT-tablet in a real-life setting.


Relationship between biomarkers of oxidized low-density lipoprotein, statin therapy, quantitative coronary angiography, and atheroma: volume observations from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) study.
This study was designed to test the hypothesis that circulating biomarkers of oxidized low-density lipoprotein (OxLDL) are affected by statin therapy and predict changes in atheroma volume. Oxidative stress is thought to play an important role in atherogenesis but the relationship between OxLDL, statin therapy, and atheroma volume in humans is not known. In a subgroup of 214 patients from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) trial, oxidized phospholipids (OxPL) and malondialdehyde (MDA) epitopes per apolipoprotein B-100 (apoB), immunoglobin (Ig) G and IgM apoB immune complexes, and OxLDL autoantibodies were measured at baseline and after 18 months of treatment with atorvastatin or pravastatin. Relationships between changes of OxLDL biomarkers and quantitative coronary angiography (QCA), total atheroma volume, and percentage atheroma volume were analyzed. There were no differences in QCA parameters or atheroma volume in the 2 groups at baseline. Compared with baseline values, OxPL/apoB and MDA/apoB, and lipoprotein (a) levels increased 21% to 48% (p < 0.001 for all) in response to atorvastatin and 17% to 39% (p < 0.001 for all) in response to pravastatin. In contrast, IgG apoB immune complexes, IgM apoB immune complexes, and IgM OxLDL autoantibodies were significantly reduced by both atorvastatin and pravastatin (p value range 0.003 to <0.001). There were no significant differences between the atorvastatin and pravastatin groups. In the entire cohort, there were no correlations between changes in any OxLDL biomarkers and changes in QCA parameters or atheroma volume. Statin therapy results in significant increases in OxPL/apoB, MDA/apoB, and lipoprotein (a) levels and decreases in apoB immune complexes and OxLDL autoantibodies. However, these measures did not correlate with changes in QCA parameters or atheroma volume.


Heme oxygenase is downregulated in stress-triggered and interleukin-12-mediated murine abortion.
Heme oxygenases (HOs) are responsible for heme degradation. Besides their enzymatic activities, HOs are involved in tissue protection. Failing upregulation of HOs has been linked to increased necrosis in inflammatory tissues. Interestingly, previously published data indicated that mice exposed to sonic stress during early gestation show an augmented production of decidual inflammatory T-helper 1 (Th1) cytokines, thus resulting in increased abortion rate. No data linked the Th1-inducer interleukin (IL)-12 with the event of abortion. As little is known about the role of HO in pregnancy maintenance, we evaluated the expression of decidual and placental HO-1 and HO-2 in the abortion-prone murine mating combination CBA/J x DBA/2 J with (1) CBA/J female control mice, (2) CBA/J mice exposed to stress during early gestation and (3) CBA/J females injected with recombinant IL-12. Decidual and placental HOs protein expression was analysed by immunohistochemistry and mRNA levels by real time polymerase chain reaction (PCR). As expected, an increased abortion rate was present in mice exposed to stress compared with the control. IL-12 injections also boosted the abortion rate compared with control mice, mimicking the effect of stress. HOs' proteins could be detected in placenta and decidua. Real time PCR revealed lower levels of HO-1 and HO-2 mRNA in stress-triggered and IL-12-injected mice. We conclude that increased Th1-cytokine levels during murine pregnancy may result in low expression of HO-1 and HO-2, thus leading to placental necrosis and foetal rejection.


[Air-convection heater for abdominal surgery. Study of the relation between surgical time and the efficacy of body temperature maintenance].
1) To quantify the efficacy of forced air warming for maintaining body temperature during general anesthesia of adults, and 2) to study the relation between the duration of surgery and the level of thermal protection provided by the device used. We studied 30 adult patients of both sexes who were scheduled for abdominal surgery involving laparotomy. After three patients were excluded because surgery was unfeasible, the remaining 27 were allocated randomly to a control group (n = 14) or a group (n = 13) to be warmed by a Bair Hugger (Augustine Medical Inc.) heater. Esophageal temperature was checked every 30 min by one probe of a modular thermometric channel (Mon-a-therm) 6510 Mallincrodt, while ambient temperature was monitored by the second probe. Significant differences in esophageal temperature were observed between the two groups from the second hour after start of surgery, and the differences increased over time. Differences were observed at the end of surgery (Bair group: 36.4 +/- 0.5 degrees C; control group: 34.7 +/- 1.1 degrees C) and upon admission to the intensive care recovery unit (Biar group: 36.3 +/- 0.6 degrees C; control 34.8 +/- 1.0 degrees C) (p < 0.0001). The Bair Hugger heater is effective during abdominal operations lasting two or more hours. The device not only prevented hypothermia from deepening during surgery, but also reversed hypothermia in spite of being used after anesthetic induction and in spite of the loss of heat produced by secondary vasodilation.