Engineering of human lysozyme as a polyelectrolyte by the alteration of molecular surface charge.
The surface positive charges of human lysozyme were either increased or decreased to alter the electrostatic interaction between enzyme and substrate in the lytic action of human lysozyme using site-directed mutagenesis. The amino acid substitutions accompanying either the addition or the removal of two units of positive charge have shifted the optimal ionic strength (NaCl concentration in 10 mM Mes buffer, pH 6.2) for the lysis of Micrococcus lysodeikticus cell from 0.04 M to 0.1 M and from 0.04 M to 0.02 M respectively. In addition to the change in ionic strength-activity profile, the pH-activity profile and the effect of a polycationic electrolyte, poly-L-Lys-HCl, on the lytic activity were significantly changed. Owing to the shifts in both ionic strength profiles and pH profiles the Arg74/Arg126 mutant has become a better catalyst than wild-type enzyme under the conditions of high ionic strength and high pH, and the Gln41/Ser101 mutant has become a better catalyst under the conditions of low ionic strength and low pH.


Thyroid Cancer in Saudi Arabia: A Histopathological and Outcome Study.
Most data on differentiated thyroid cancer (DTC) came from the Western world. We describe its salient characteristics and outcome from a Middle Eastern country. Patients and Methods. We studied all cases of TC seen during a 2-year period (2004-2005) seen at our institution. Results. A total of 600 consecutive cases of DTC with a median age at diagnosis of 39 years (5-85) and the female : male ratio of 459 : 141 (76.5% : 23.5%). The cases included classical papillary thyroid cancer (PTC) in 77%, follicular variant PTC in 13.3%, follicular thyroid cancer in 3.2%, and other rare subtypes 6.5%. Total or near-total thyroidectomy was performed in 93%, central and/or lateral neck dissection in 64.5% of cases, and radioactive iodine ablation in 82% of cases. Additional therapies were administered to 154 patients (25.7%). At a median follow-up period of 7.63 years (0.22-13.1), 318 patients (53.3%) were in excellent response, 147 (24.5%) having an indeterminate response, 55 (9.2%) biochemically incomplete, 33 (5.5%) structurally incomplete, and 27 (4.5%) unclassifiable. Twenty cases died secondary to DTC (disease-specific mortality 3.3%). Conclusions. In Saudi Arabia, DTC is common and occurs at young age and predominantly in females. Although remission is common, persistent disease is also common but disease-specific mortality is low.


[Stimulation of interferon formation by natural and synthetic inducers in cultures of human tonsil cells].
Conditions of interferon production stimulation were studied in human tonsillar cell cultures exposed to natural and synthetic inducers : poly(I) . poly(C), phage f2 RNA replicase, phytohemagglutinin and the low-molecular inducer gossypol (beta-aminoethyl sulfoxide Na). It has been shown that being inferior in the productivity per one cell to the continuous lymphoblastoid Raji and Namalva cell liness the tonsillar cell cultures, due to their high density, produce rather high interferon titers reaching hundreds of IU50/ml. The viability of the tonsillar cell cultures and their incubation at 37 degrees C during 24 hours are rather important for adequate interferon production.


Body temperature changes in dogs exposed to varying effective temperatures.
Adult male and female Beagle dogs (eight total) were exposed individually, in series, to each of 23 effective temperatures for a period of 2 hours or until rectal temperature increased 1.1 degrees C. Rectal temperature was measured to the nearest 0.1 degree C by thermistor probes in the pre-test condition (basal temperature) and at each 5-minute interval during the test conditions (effective temperatures between 21.1 degrees C and 34.7 degrees C). The frequency at which dogs displayed a 1.1 degree C rise in rectal temperature was related to the magnitude of the effective temperature. At an effective temperature of 32.6 degrees C or greater, 100% of the dogs displayed a 1.1 degree C rise in rectal temperature. Between an effective temperature of 29.3 degrees C and 31.4 degrees C, some animals displayed a 1.1 degree C rise while others did not. At an effective temperature of 28.4 degrees C or below no animals displayed a 1.1 degree C rise. The mean time necessary for a 1.1 degree C rise was negatively correlated (P less than 0.01) to the magnitude of the effective temperature. The minimum effective temperature necessary to increase rectal temperature by 1.1 degree C in male Beagles (29.6 +/- 1.0 degree C) was not significantly different from females (30.8 +/- 0.4 degrees C).


Non-linear signal processing in digital hearing aids.
Three different non-linear digital signal processing algorithms were developed; LinEar, DynEar and RangeEar. All three provided individual frequency shaping via a seven-band low-power filterbank and compression in two channels. RangeEar and DynEar used wide dynamic range syllabic compression in the low-frequency (LF) channel, while LinEar used compression limiting. In the high-frequency (HF) channel, RangeEar used a slow-acting automatic volume control, while DynEar and LinEar used compression limiting. Wearable digital signal processing-based experimental instruments were used to evaluate the fitting algorithms under real world conditions with experienced hearing aid users. Evaluation included laboratory testing of speech recognition in noise and questionnaires on sound quality ratings. Results did not indicate one general good-for-all algorithm, but different algorithms resulting in preference and performance depending on the hearing loss configuration. Preference for any of the new algorithms could be predicted based on auditory dynamic range measurements. It was hypothesized that the different preferences were affected by different susceptibility to masking of HF sounds by amplified LF sounds.


FK506 and pertussis toxin distinguish growth-induced locomotor activation from attractant-stimulated locomotion in human blood lymphocytes.
The locomotor capacity of human lymphocytes is cell cycle-related. Many small blood lymphocytes are non-motile but acquire locomotor capacity in G1 on appropriate activation with e.g. anti-CD3 antibody (aCD3) for T cells, or interleukin-4 (IL-4) for B cells. Once this capacity is acquired, the cells can then respond by polarization and locomotor to chemoattractants such as IL-8 or foetal calf serum (FCS). These two stages in the locomotor process were distinguished by the use of two inhibitors, FK506 and pertussis toxin. FK506 caused a dose-dependent inhibition of cell cycle-related induction of locomotor capacity both of anti-CD3-cultured T cells and IL-4-cultured B cells, with an ID50 of less than 1 ng per ml. This was measured in assays both of morphological polarization and of locomotion into collagen gels. FK506 has no effect on chemoattractant-induced polarization. Conversely, pertussis toxin has little inhibitory effect on growth-induced locomotor capacity, but is an effective inhibitor of the immediate polarization response following addition of FCS or IL-8 to lymphocytes either direct from blood or after overnight culture. These results suggest that different signalling pathways are involved in the two stages. Growth-related locomotor activation does not involve a pertussis toxin-sensitive G protein and may be signalled in the same way as other mitogen-induced events which are sensitive to FK506 and cyclosporin. On the other hand, the locomotor response to attractants, on this and earlier evidence, is transduced via a pertussis toxin-sensitive G protein. However, after prolonged (24-48 hr) culture in the presence of pertussis toxin, lymphocyte locomotor responses to attractants become insensitive to pertussis toxin.


An Improved Interacting Multiple Model Filtering Algorithm Based on the Cubature Kalman Filter for Maneuvering Target Tracking.
In order to improve the tracking accuracy, model estimation accuracy and quick response of multiple model maneuvering target tracking, the interacting multiple models five degree cubature Kalman filter (IMM5CKF) is proposed in this paper. In the proposed algorithm, the interacting multiple models (IMM) algorithm processes all the models through a Markov Chain to simultaneously enhance the model tracking accuracy of target tracking. Then a five degree cubature Kalman filter (5CKF) evaluates the surface integral by a higher but deterministic odd ordered spherical cubature rule to improve the tracking accuracy and the model switch sensitivity of the IMM algorithm. Finally, the simulation results demonstrate that the proposed algorithm exhibits quick and smooth switching when disposing different maneuver models, and it also performs better than the interacting multiple models cubature Kalman filter (IMMCKF), interacting multiple models unscented Kalman filter (IMMUKF), 5CKF and the optimal mode transition matrix IMM (OMTM-IMM).


Sprouty 4 suppresses glioblastoma invasion by inhibiting ERK phosphorylation and ETS-1-induced matrix metalloproteinase-9.
Glioblastoma multiforme (GBM) is the most malignant glioma with highly aggressive behavior and the worst prognosis. Many efforts have been made to develop new drugs and improve the patient's survival, but the effects are not satisfactory. Here we aimed to evaluate the clinical significance and tumor-repressive function of Sprouty4 (SPRY4) in GBM. In our study, we detected the expression of SPRY4 in 109 GBM patients and 12 pairs of GBM tissues and the corresponding adjacent tissues. χ2 test was applied to analyze the association between SPRY4 expression and the clinicopathological factors. The prognostic significances were evaluated with univariate and multivariate analyses, which were carried out by the Kaplan-Meier method and the Cox-regression proportional hazards model, respectively. With in-vitro experiments, we investigated the tumor-suppressing function of SPRY4 in GBM invasion and investigated the underlying mechanism. SPRY4 mRNAs in GBMs were significantly lower than those in adjacent brain tissues. We demonstrated that SPRY4 expression could predict the favorable prognosis of GBM, and SPRY4 was an independent favorable prognostic factor of GBM. SPRY4 repressed GBM invasion via inhibiting ERK phosphorylation; therefore, suppressing ETS-1-induced MMP9 expression. SPRY4 was an independent favorable prognostic factor of GBM, and it could suppress GBM invasion by ERK-ETS-MMP9 axis. Our results indicated that SPRY4 may be a promising drug target of GBM and SPRY4 detection could stratify patients with low SPRY4 expression who may benefit from anti-FGFR therapy.


Macrophages as potential targets in gene therapy for cancer treatment.
Macrophages, as ubiquitous and functionally diverse immune cells, play a central role in innate immunity and initiate adaptive immunity. Especially, tumor-associated macrophages (TAMs) are crucial contributors to the tumorigenesis and development of cancer. Thus, macrophages are emerging potential targets for cancer treatment. Among the numerous targeted therapeutic options, gene therapy is one of the most potential therapeutic strategies via directly and specifically regulating biological functions of macrophages at the gene level for cancer treatment. This short review briefly introduces the characteristics of macrophage populations, the functions of TAM in the occurrence, and the progress of cancer. It also summarized some representative examples to highlight the current progress in TAM-targeted gene therapy. The review hopes to provide new insights into macrophage-targeted gene therapy for precision cancer therapy.


Regulation of cell-mediated immunity in cryptococcosis. I. Induction of specific afferent T suppressor cells by cryptococcal antigen.
By injecting cryptococcal antigen i.v. into CBA/J mice, we have simulated a level of antigenemia that is known to occur naturally in murine and human cryptococcosis. The cryptococcal antigen induced a population of lymph node (LN) cells that, upon adoptive transfer, could specifically suppress the delayed-type hypersensitivity (DTH) response to cryptococcal antigen and the splenic T lymphocytes responsible for in vitro inhibition of growth of Cryptococcus neoformans. The cryptococcal-antigen-induced suppressor cell could be detected in the LN as early as 5 days and was still in significant numbers 7 days after antigen injection. Suppressor cells were not found in the spleens of tolerized mice, nor could serum from these animals adoptively transfer suppression. The suppressor cells in this model were shown to be T lymphocytes, which exerted their effect on the afferent limb of the DTH response; therefore, they were similar to the Ts1 cell in the ABA-DTH, NP-DTH, and NP cutaneous sensitivity models and to the afferent suppressor cells in the DNFB contact sensitivity system. The percent suppression of the cryptococcal DTH response was dependent on the amount of antigen injected. Approximately, 35 micrograms of cryptococcal antigen per ml of serum was sufficient to induce significant suppression of the cell-mediated immune response.


Non-suppressible insulin-like activity and sulphaton activity in serum extracts of normal subjects, acromegalics and pituitary dwarfs.
Non-suppressible insulin-like activity (NSILA) is a term used for a variety of substances in serum, excluding insulin, which promote glucose uptake of adipose tissue and diaphragm in vitro. NSILA-S is a peptide with a molecular weight of 7000 which is soluble in acid ethanol and which has been purified on a large scale from human serum. This study describes a simple chromatographic one step procedure by which NSILA-S can be extracted and quantitatively measured in individual sera. Using Sephadex G-75 equilibrated with 1 M acetic acid, NSILA-S was detected only in one peak containing small molecular peptides. NSILA-S obtained with this one step chromatographic procedure exerted all the effects of purified NSILA-S including sulphation activity on the rat cartilage. All chromatographic fractions with NSILA-S also had sulphation activity. Both, NSILA-S and sulphation activity were increased in acromegalics and decreased in pituitary dwarfs. It is suggested that one molecule in serum is responsible for both activities which are, at least in part, under the control of growth hormone.


Prediabetes Awareness and Practice Among Indian Doctors- A Cross-sectional Study.
Prediabetes is an intermediate state between diabetes and normoglycaemia, where the glucose levels are higher than normal but not significant to be diagnosed as diabetes mellitus. Guidelines from various associations suggest different types of management in this situation. To assess knowledge and attitude of the doctors regarding prediabetes using questionnaire. A cross-sectional questionnaire based study was conducted to assess the knowledge, attitude and practice among doctors regarding prediabetes treatment. One hundred twenty two (of 150) filled questionnaires were received from general practitioners, post graduates (PGs), physicians and super specialists in and around Kolar and Bangalore. Data was analysed using descriptive statistics and expressed as percentage. A total of 81.3% responded to the questionnaire, of which 14 were general practitioners (MBBS), 48 PGs in General Medicine, 46 physicians (MD General Medicine), and 14 super specialists (DM). Knowledge response was 85.7% (definition - 100%, prevalence - 50.8%, approved drug- 45.2%, progression- 86.2%). Screening for prediabetes was done by 71% of the general practitioners and physicians, but specialists would screen all. 100% general practitioners, 97.9% post graduates, 91.3% of physicians and 64.2 % specialist preferred diet and exercise and rest of them opted for oral antidiabetic drug (OAD) along with diet and exercise, but none of the doctors considered OAD alone for prediabetes. Among OADs metformin (77.45%) was the most preferred followed by voglibose (20.6%) and sitagliptin (1.9%). All doctors had awareness of prediabetes and most of them would regularly screen and treat prediabetes. Majority considered diet and exercise as first modality of treatment. The OAD opted commonly was metformin.


Prevalence and incidence density of unavoidable pressure ulcers in elderly patients admitted to medical units.
To describe the prevalence and incidence density of hospital-acquired unavoidable pressure sores among patients aged ≥65 years admitted to acute medical units. A secondary analysis of longitudinal study data collected in 2012 and 2013 from 12 acute medical units located in 12 Italian hospitals was performed. Unavoidable pressure ulcers were defined as those that occurred in haemodynamically unstable patients, suffering from cachexia and/or terminally ill and were acquired after hospital admission. Data at patient and at pressure ulcer levels were collected on a daily basis at the bedside by trained researchers. A total of 1464 patients out of 2080 eligible (70.4%) were included. Among these, 96 patients (6.5%) hospital-acquired a pressure ulcer and, among 19 (19.7%) were judged as unavoidable. The incidence of unavoidable pressure ulcer was 8.5/100 in hospital-patient days. No statistically significant differences at patient and pressure ulcers levels have emerged between those patients that acquired unavoidable and avoidable pressure sores. Although limited, evidence on unavoidable pressure ulcer is increasing. More research in the field is recommended to support clinicians, managers and policymakers in the several implications of unavoidable pressure ulcers both at the patient and at the system levels.


Why exercise has a crucial role in cancer prevention, risk reduction and improved outcomes.
Exercise is one of several factors known to lower the risk of developing cancer, as well as improve outcomes in patients already diagnosed. People who exercise after cancer have lower rates of cancer complications, treatment toxicities, relapse and improved survival. This review highlights the supportive data and biochemical processes, which explain these potential benefits. PubMed, Embase, Medline and Cochrane libraries were searched for papers which addressed the effects of exercise and physical activity on cancer for this review. The search terms used were physical activity, exercise and cancer up to February 2021. We also referred to the background research required for international exercise intervention study involving men with prostate cancer (INTERVAL-GAP4) and scrutinized references within the robust papers published on this subject to ensure we did not miss any clinically studies. One hundred and eighty eight papers were included. Exercise programmes mitigate many of the complications and risks associated with cancer, particularly thromboembolism, fatigue, weight gain, arthralgia, cognitive impairment and depression. Molecular and biomarker changes, resulting from exercise, suggest that exercise elicits beneficial changes in insulin-related pathways, down-regulates inflammation and serum oestrogen levels, and enhances oxidative, immune and cellular repair pathways. Nonetheless, the evidence remains preliminary. The timing, intensity and challenges of prehabilitation, adjunct and rehabilitation exercise programmes are being increasingly understood but their implementation remains sporadic. More robust clinical trial data are needed to substantiate a causal effect of exercise on overall and cancer-specific survival. These studies are ongoing. Research evaluating the most cost-efficient ways of incorporating prehabilitation, adjunct and rehabilitation programmes into routine practice would be helpful to funding bodies and health care strategists.


A comparative study of various dosages of danazol in the treatment of endometriosis.
The results of a randomized trial to investigate the efficacy of different dosage regimens of danazol in the treatment of endometriosis indicate that for mild endometriosis 200 mg/day of danazol is adequate therapy with less severe side effects than higher dosages. However, more extensive disease requires a higher dose.


Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity.
Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation. The UPR influences cytokine production on multiple levels, from stimulation of pattern recognition receptors, to modulation of inflammatory signaling pathways, and the regulation of cytokine transcription factors. This review will focus on the mechanisms underlying cytokine regulation by the UPR, and the repercussions of this relationship for infection and autoimmune/autoinflammatory diseases. Interrogation of viral and bacterial infections has revealed increasing numbers of examples where pathogens induce or modulate the UPR and implicated UPR-modulated cytokines in host response. The flip side of this coin, the UPR/ER stress responses have been increasingly recognized in a variety of autoimmune and inflammatory diseases. Examples include monogenic disorders of ER function, diseases linked to misfolding protein (HLA-B27 and spondyloarthritis), diseases directly implicating UPR and autophagy genes (inflammatory bowel disease), and autoimmune diseases targeting highly secretory cells (e.g., diabetes). Given the burgeoning interest in pharmacologically targeting the UPR, greater discernment is needed regarding how the UPR regulates cytokine production during specific infections and autoimmune processes, and the relative place of this interaction in pathogenesis.


[Effects of perindopril and its combination with indapamide on risk stratification in patients with hypertension].
To study effects of perindopril, indapamid and their combination on stratification of essential hypertension (EH) risk factors. The 10-year risk to develop cardiovascular complications was assessed in 85 EH patients before and after 12 months of treatment with perindopril, indapamid and their combination. The high risk of cardiovascular complications in the above patients reduced by 21.5, 14.8 and 26.6% 12 months after treatment with perindopril, indapamid and their combination, respectively. Low risk of cardiovascular complications was related not only with a fall in systolic and diastolic blood pressure but also with positive effect on left ventricular hypertrophy, absence of negative influence on total cholesterol, glucose in blood plasma.


A health and social survey of a group of children from rural New South Wales.
Between the middle of May and middle of July, 1972, 177 children aged up to 15 years were admitted to a nursing home in Sydney on referral from their doctors in country areas of New South Wales for specialized investigation and treatment mainly of respiratory infections, congenital malformations and orthopaedic and ophthalmic conditions. Specimens of faeces from these children were examined for bacterial pathogens and parasites. These tests revealed the presence of intestinal parasites (mostly Giardia lamblia) in 91 of the children and of bacterial pathogens in 14 (a salmonella in one and shigellas in 13). The general health and development of the children and the socioeconomic status of their families were below the average for New South Wales.


Green Neutrophilic Inclusions and Acute Hepatic Failure: Clinical Significance and Brief Review of the Literature.
Medical literature has documented an association between acute hepatic failure and coarse, bright-green neutrophilic inclusions. Upon identification of these unique inclusions patients have been reported to have poor outcomes and usually die within 24-72 hours. The exact nature of these inclusions has yet to be determined; it is postulated that they arise from lipofusion-like substance. Here, we describe five cases of acute hepatic failure, with associated bright-green neutrophilic inclusions, where four patients survived beyond the ominous 72-hour window period.


Precise Ensemble Face Representation Given Incomplete Visual Input.
Humans can recognize faces in the presence of environmental noise. Here, we explore whether ensemble perception of faces is similarly robust. Is summary statistical information available from crowds of faces that are visually incomplete? Observers viewed sets of faces varying in identity or expression and adjusted a test face to match the perceived average. In one condition, faces amodally completed behind horizontal bars. In another condition, identical facial information was presented, but in the foreground (i.e., face parts appeared on fragmented strips in front of a background). Baseline performance was determined by performance on sets of fully visible faces. The results revealed that the ensemble representation of amodally completing sets was significantly better than the fragmented sets and marginally worse than in the fully visible condition. These results suggest that some ensemble information is available given limited visual input and supports a growing body of work suggesting that ensembles may be represented in the absence of complete visual information.


Competing effects of particle and medium inertia on particle diffusion in viscoelastic materials, and their ramifications for passive microrheology.
We analyze the appropriate form for the generalized Stokes-Einstein relation (GSER) for viscoelastic solids and fluids when bead inertia and medium inertia are taken into account, which we call the inertial GSER. It was previously shown for Maxwell fluids that the Basset (or Boussinesq) force arising from medium inertia can act purely dissipatively at high frequencies, where elasticity of the medium is dominant. In order to elucidate the cause of this counterintuitive result, we consider Brownian motion in a purely elastic solid where ordinary Stokes-type dissipation is not possible. The fluctuation-dissipation theorem requires the presence of a dissipative mechanism for the particle to experience fluctuating Brownian forces in a purely elastic solid. We show that the mechanism for such dissipation arises from the radiation of elastic waves toward the system boundaries. The frictional force associated with this mechanism is the Basset force, and it exists only when medium inertia is taken into consideration in the analysis of such a system. We consider first a one-dimensional harmonic lattice where all terms in the generalized Langevin equation--i.e., the elastic term, the memory kernel, and Brownian forces-can be found analytically from projection-operator methods. We show that the dissipation is purely from radiation of elastic waves. A similar analysis is made on a particle in a continuum, three-dimensional purely elastic solid, where the memory kernel is determined from continuum mechanics. Again, dissipation arises only from radiation of elastic shear waves toward infinite boundaries when medium inertia is taken into account. If the medium is a viscoelastic solid, Stokes-type dissipation is possible in addition to radiational dissipation so that the wave decays at the penetration depth. Inertial motion of the bead couples with the elasticity of the viscoelastic material, resulting in a possible resonant oscillation of the mean-square displacement (MSD) of the bead. On the other hand, medium inertia (the Basset force) tends to attenuate the oscillations by the dissipation mechanism described above. Thus competition between bead inertia and medium inertia determines whether or not the MSD oscillates. We find that, if the medium density is larger than 4/7 of the bead density, the Basset damping will suppress oscillations in the MSD; this criterion is sufficient but not necessary to present oscillations.


Two-year carcinogenicity studies with the oral direct thrombin inhibitor ximelagatran in the rat and the mouse.
The results of 18 months mouse and 24 months rat carcinogenicity studies with the oral direct thrombin inhibitor ximelagatran are presented. In the mouse, gavage doses of ximelagatran up to 180 μmol/kg per d produced no neoplastic changes in any of the tissues examined. In the rat, gavage doses up to 240 μmol/kg per d produced multiple macroscopically detectable nodules in the pancreas, which are seen to be focal/multifocal acinar cell hyperplasia and focal/multifocal acinar cell adenoma upon histological evaluation. There were no other treatment-related effects on tumor incidence or distribution in the rat. The studies show a clear species difference in pancreatic effects between the rat and the mouse to long-term treatment with ximelagatran.


Ethnicity and difference in dengue virus-specific memory T cell responses in Cuban individuals.
The different risk factors associated with dengue hemorrhagic fever pathogenesis needs yet additional clarification. The exceptional epidemiological circumstances in Cuba allow their evaluation in a well-defined situation. In the present study the memory T cell response of 80 Cuban donors previously infected with dengue-1 and dengue-2 during the 1977 and 1981 epidemics, and belonging to different ethnic groups, was examined. White people showed, in contrast to black people, stronger and remarkably cross-reactive dengue virus-specific memory CD4(+) T lymphocyte proliferation and interferon-gamma release. The observed variation in T cell response according to ethnicity could be related to the immunopathogenesis of dengue hemorrhagic fever, and may partially explain the epidemiological evidence that black individuals are at lower risk for the most severe dengue clinical course compared with white individuals.


How children process over-regularizations: evidence from event-related brain potentials.
This study examines the mental processes involved in children's on-line recognition of inflected word forms using event-related potentials (ERPs). Sixty children in three age groups (20 six- to seven-year-olds, 20 eight- to nine-year-olds, 20 eleven- to twelve-year-olds) and 23 adults (tested in a previous study) listened to sentences containing correct or incorrect German noun plural forms. In the two older child groups, as well as in the adult group, over-regularized plural forms elicited brain responses that are characteristic of combinatorial (grammatical) violations. We also found that ERP components associated with language processing change from child to adult with respect to their onsets and their topography. The ERP violation effects obtained for over-regularizations suggest that children (aged eight years and above) and adults employ morphological computation for processing purposes, consistent with dual-mechanism models of inflection. The observed differences between children's and adults' ERP responses are argued to result from children's smaller lexicons and from slower and less efficient processing.


Controlled infrared heating of an artic meadow: challenge in the vegetation establishment stage.
Global warming is going to affect both agricultural production and carbon storage in soil worldwide. Given the complexity of the soil-plant-atmosphere continuum, in situ experiments of climate warming are necessary to predict responses of plants and emissions of greenhouse gases (GHG) from soils. Arrays of infrared (IR) heaters have been successfully applied in temperate and tropical agro-ecosystems to produce uniform and large increases in canopy surface temperature across research plots. Because this method had not yet been tested in the Arctic where consequences of global warming on GHG emission are expected to be largest, the objective of this work was to test hexagonal arrays of IR heaters to simulate a homogenous 3 °C warming of the surface, i.e. canopy and visible bare soil, of five 10.5-m2 plots in an Arctic meadow of northern Norway. Our results show that the IR warming setup was able to simulate quite accurately the target + 3 °C, thereby enabling us to simulate the extension of the growing season. Meadow yield increased under warming but only through the lengthening of the growing season. Our research also suggests that, when investigating agricultural systems on the Arctic, it is important to start the warming after the vegetation is established,. Indeed, differential emergence of meadow plants impaired the homogeneity of the warming with patches of bare soil being up to 9.5 °C warmer than patches of vegetation. This created a pattern of soil crusting, which further induced spatial heterogeneity of the vegetation. However, in the Arctic these conditions are rather rare as the soil exposed by snow melt is often covered by a layer of senescent vegetation which shelters the soil from direct radiation. Consistent continuous warming can be obtained on average with IR systems in an Arctic meadow, but homogenous spatial distribution requires that the warming must start after canopy closure.


A new surgical approach to the innominate and subclavian vein.
A new technique extending the incision used for thoracic outlet decompression with a subclavicular approach to the first rib is presented. After the first rib and scalenotomy are removed, the subclavicular incision is continued into the sternum medially and superiorly to the sternal notch. This gives easy access to the innominate-subclavian-axillary vein segment. Eight patients with extensive chronic fibrotic obstruction of the subclavian-innominate vein segment underwent operation with this technique. It allows placement of either long patches of saphenous vein to reestablish normal caliber or replacement, as is our choice, with a small-sized cryopreserved descending thoracic aortic homograft. The operation is carried out in an extrapleural plane preserving the sternoclavicular joint, avoiding the deformity caused by transclavicular techniques. Repair of the sternotomy creates a stable incision. Follow-up to 14 months shows patency of the venous channel with no complications. This surgical approach is recommended to solve the problem of satisfactory exposure of the subclavian-innominate venous channel after decompression of the thoracic outlet.


Intentional deep overfit learning for patient-specific dose predictions in adaptive radiotherapy.
The framework of adaptive radiation therapy (ART) was crafted to address the underlying sources of intra-patient variation that were observed throughout numerous patients' radiation sessions. ART seeks to minimize the consequential dosimetric uncertainty resulting from this daily variation, commonly through treatment planning re-optimization. Re-optimization typically consists of manual evaluation and modification of previously utilized optimization criteria. Ideally, frequent treatment plan adaptation through re-optimization on each day's computed tomography (CT) scan may improve dosimetric accuracy and minimize dose delivered to organs at risk (OARs) as the planning target volume (PTV) changes throughout the course of treatment. Re-optimization in its current form is time-consuming and inefficient. In response to this ART bottleneck, we propose a deep learning based adaptive dose prediction model that utilizes a head and neck (H&N) patient's initial planning data to fine-tune a previously trained population model towards a patient-specific model. Our fine-tuned, patient-specific (FT-PS) model, which is trained using the intentional deep overfit learning (IDOL) method, may enable clinicians and treatment planners to rapidly evaluate relevant dosimetric changes daily and re-optimize accordingly. An adaptive population (AP) model was trained using adaptive data from 33 patients. Separately, 10 patients were selected for training FT-PS models. The previously trained AP model was utilized as the base model weights prior to re-initializing model training for each FT-PS model. Ten FT-PS models were separately trained by fine-tuning the previous model weights based on each respective patient's initial treatment plan. From these 10 patients, 26 ART treatment plans were withheld from training as the test dataset for retrospective evaluation of dose prediction performance between the AP and FT-PS models. Each AP and FT-PS dose prediction was compared against the ground truth dose distribution as originally generated during the patient's course of treatment. Mean absolute percent error (MAPE) evaluated the dose differences between a model's prediction and the ground truth. MAPE was calculated within the 10% isodose volume region of interest for each of the AP and FT-PS models dose predictions and averaged across all test adaptive sessions, yielding 5.759% and 3.747% respectively. MAPE differences were compared between AP and FT-PS models across each test session in a test of statistical significance. The differences were statistically significant in a paired t-test with two-tailed p-value equal to 3.851 × 10 - 9 $3.851 \times {10}^{ - 9}$ and 95% confidence interval (CI) equal to [-2.483, -1.542]. Furthermore, MAPE was calculated using each individually segmented structure as an ROI. Nineteen of 24 structures demonstrated statistically significant differences between the AP and FT-PS models. We utilized the IDOL method to fine-tune a population-based dose prediction model into an adaptive, patient-specific model. The averaged MAPE across the test dataset was 5.759% for the population-based model versus 3.747% for the fine-tuned, patient-specific model, and the difference in MAPE between models was found to be statistically significant. Our work demonstrates the feasibility of patient-specific models in adaptive radiotherapy, and offers unique clinical benefit by utilizing initial planning data that contains the physician's treatment intent.


Assessing Elementary Lesions in Gout by Ultrasound: Results of an OMERACT Patient-based Agreement and Reliability Exercise.
To test the reliability of the consensus-based ultrasound (US) definitions of elementary gout lesions in patients. Eight patients with microscopically proven gout were evaluated by 16 sonographers for signs of double contour (DC), aggregates, erosions, and tophi in the first metatarsophalangeal joint and the knee bilaterally. The patients were examined twice using B-mode US to test agreement and inter- and intraobserver reliability of the elementary components. The prevalence of the lesions were DC 52.8%, tophus 61.1%, aggregates 29.8%, and erosions 32.4%. The intraobserver reliability was good for all lesions except DC, where it was moderate. The best reliability per lesion was seen for tophus (κ 0.73, 95% CI 0.61-0.85) and lowest for DC (κ 0.53, 95% CI 0.38-0.67). The interobserver reliability was good for tophus and erosions, but fair to moderate for aggregates and DC, respectively. The best reliability was seen for erosions (κ 0.74, 95% CI 0.65-0.81) and lowest for aggregates (κ 0.21, 95% CI 0.04-0.37). This is the first step to test consensus-based US definitions on elementary lesions in patients with gout. High intraobserver reliability was found when applying the definition in patients on all elementary lesions while interobserver reliability was moderate to low. Further studies are needed to improve the interobserver reliability, particularly for DC and aggregates.


Isolation and culture of hair cell progenitors from postnatal rat cochleae.
Cochlear hair cells are a terminally differentiated cell population that is crucial for hearing. Although recent work suggests that there are hair cell progenitors in postnatal mammalian cochleae, isolation and culture of pure hair cell progenitors from a well-defined cochlear area have not been reported. Here we present an experimental method that allows isolation and culture of hair cell progenitors from postnatal rat cochleae. These progenitor cells are isolated from the lesser epithelial ridge (LER, or outer spiral sulcus cell) area of pre-plated neonatal rat cochlear segments. They express the same markers as LER cells in vivo, including ZO1, Islet1, Hes1, and Hes5. When these cells are induced to express Hath1, they show the potential to differentiate into hair cell-like cells. Interestingly, these cells can be lifted from monolayer cultures and maintained in aggregate cultures in which spheres can be formed. Hair cell progenitors in the spheres display their proliferating capability and express only epithelial markers. Furthermore, when these spheres are mixed with dissociated mesenchymal cells prepared from postnatal rat utricular whole mounts, and replated onto a collagen substratum, the epithelial progenitor cells are able to differentiate into cells expressing markers of hair cells and supporting cells in epithelial islands, which mirrors the inner ear sensory epithelium in vivo. Successful isolation and culture of hair cell progenitors from the mammalian cochlea will facilitate studies on gene expression profiling and mechanism of differentiation/regeneration of hair cells, which are crucial for repairing hearing loss.


Bayesian Model Assessment for Jointly Modeling Multidimensional Response Data with Application to Computerized Testing.
Computerized assessment provides rich multidimensional data including trial-by-trial accuracy and response time (RT) measures. A key question in modeling this type of data is how to incorporate RT data, for example, in aid of ability estimation in item response theory (IRT) models. To address this, we propose a joint model consisting of a two-parameter IRT model for the dichotomous item response data, a log-normal model for the continuous RT data, and a normal model for corresponding paper-and-pencil scores. Then, we reformulate and reparameterize the model to capture the relationship between the model parameters, to facilitate the prior specification, and to make the Bayesian computation more efficient. Further, we propose several new model assessment criteria based on the decomposition of deviance information criterion (DIC) the logarithm of the pseudo-marginal likelihood (LPML). The proposed criteria can quantify the improvement in the fit of one part of the multidimensional data given the other parts. Finally, we have conducted several simulation studies to examine the empirical performance of the proposed model assessment criteria and have illustrated the application of these criteria using a real dataset from a computerized educational assessment program.


Pheochromocytoma--analysis of 15 consecutive cases from one centre.
Pheochromocytoma is a rare tumour, but one of great clinical importance as a risk factor of malignancy, cardiovascular diseases and sudden death. 15 consecutive patients (eight women and seven men) were hospitalised and submitted for adrenalectomy with pheochromocytoma confirmed by histopathologic examination. Adrenalectomies were performed laparoscopically in 14 cases (93.3%): in nine by the retroperitoneal posterior mode and in five by the transperitoneal lateral approach. Molecular-genetic examination of VHL, RET, SDHB, SDHC and SDHD genes revealed inherited predisposition for PHEO in three of 15 patients (20%): RET mutations typical for MEN 2a in two patients and VHL mutation in one patient. Disturbances of the carbohydrate metabolism occurred in nine patients (60%). Ten patients (66%) reported paroxysmal symptoms. In all cases, with the exception of a von Hippel-Lindau patient, density of tumours exceeded 20 HU. In all studied patients, urine concentration of normetanephrines exceeded their normal range and greatly prevailed over metanephrines values, which were increased in six of them (40%). Urine metoxycatecholamines and increased tissue density are sufficient in pheochromocytoma detection. However, taking into account clinical and supplemental biochemical data may be helpful in the diagnostic process. Laparoscopic adrenalectomy is a fully sufficient and safe method of pheochromocytoma excision.


Orthodontic treatment-induced temporal alteration of jaw-opening reflex excitability.
The impairment of orofacial motor function during orthodontic treatment needs to be addressed, because most orthodontic patients experience pain and motor excitability would be affected by pain. In the present study, the temporal alteration of the jaw-opening reflex excitability was investigated to determine if orthodontic treatment affects orofacial motor function. The excitability of jaw-opening reflex evoked by electrical stimulation on the gingiva and recorded bilaterally in the anterior digastric muscles was evaluated at 1 (D1), 3 (D3), and 7 days (D7) after orthodontic force application to the teeth of right side; morphological features (e.g., osteoclast genesis and tooth movement) were also evaluated. To clarify the underlying mechanism of orthodontic treatment-induced alteration of orofacial motor excitability, analgesics were administrated for 1 day. At D1 and D3, orthodontic treatment significantly decreased the threshold for inducing the jaw-opening reflex but significantly increased the threshold at D7. Other parameters of the jaw-opening reflex were also evaluated (e.g., latency, duration and area under the curve of anterior digastric muscles activity), and only the latency of the D1 group was significantly different from that of the other groups. Temporal alteration of the jaw-opening reflex excitability was significantly correlated with changes in morphological features. Aspirin (300 mg·kg-1·day-1) significantly increased the threshold for inducing the jaw-opening reflex, whereas a lower dose (75-150 mg·kg-1·day-1) of aspirin or acetaminophen (300 mg·kg-1·day-1) failed to alter the jaw-opening reflex excitability. These results suggest that an increase of the jaw-opening reflex excitability can be induced acutely by orthodontic treatment, possibly through the cyclooxygenase activation.NEW & NOTEWORTHY It is well known that motor function is affected by pain, but the effect of orthodontic treatment-related pain on the trigeminal motor excitability has not been fully understood. We found that, during orthodontic treatment, trigeminal motor excitability is acutely increased and then decreased in a week. Because alteration of trigeminal motor function can be evaluated quantitatively by jaw-opening reflex excitability, the present animal model may be useful to search for alternative approaches to attenuate orthodontic pain.


Involvement of informal caregivers in supporting patients with COPD: a review of intervention studies.
Caregivers of individuals with COPD have a key role in maintaining patient adherence and optimizing patient function. However, no systematic review has examined how the caregiver role has been operationalized in interventions to improve outcomes of individuals with COPD or the quality or effectiveness of these interventions. The aims of this review were to 1) determine whether caregivers have been involved as part of interventions to improve outcomes of individuals with COPD; 2) determine the risk of bias within included intervention studies; and 3) examine the effectiveness of interventions that have involved caregivers in improving outcomes of individuals with COPD. The electronic databases of Medline, Embase, PsycINFO, and Cochrane Library were searched from January 2000 to November 2015. Experimental studies testing interventions that involved a caregiver to improve COPD patient outcomes were eligible. Nine studies involving caregivers met inclusion criteria. No studies reported any intervention components targeted solely at caregivers, with most instead including caregivers in dyadic or group education sessions about COPD delivered by health care professionals. The risk of bias identified in included studies was mixed. Seven of the nine studies were effective in improving a broad range of outcomes. These findings highlight that there is an urgent need for methodologically rigorous interventions to examine the effectiveness of strategies to assist caregivers to provide direct care, encourage adherence to health care provider recommendations, act as a health care advocate, and provide emotional and psychosocial support to individuals with COPD.


Advances in Glomeromycota taxonomy and classification.
Concomitant morphological and molecular analyses have led to major breakthroughs in the taxonomic organization of the phylum Glomeromycota. Fungi in this phylum are known to form arbuscular mycorrhiza, and so far three classes, five orders, 14 families and 29 genera have been described. Sensulato, spore formation in 10 of the arbuscular mycorrhiza-forming genera is exclusively glomoid, one is gigasporoid, seven are scutellosporoid, four are entrophosporoid, two are acaulosporoid, and one is pacisporoid. Spore bimorphism is found in three genera, and one genus is associated with cyanobacteria. Here we present the current classification developed in several recent publications and provide a summary to facilitate the identification of taxa from genus to class level.


Introduced birds and the fate of hawaiian rainforests.
The Hawaiian Islands have lost nearly all their native seed dispersers, but have gained many frugivorous birds and fleshy-fruited plants through introductions. Introduced birds may not only aid invasions of exotic plants but also may be the sole dispersers of native plants. We assessed seed dispersal at the ecotone between native- and exotic-dominated forests and quantified bird diets, seed rain from defecated seeds, and plant distributions. Introduced birds were the primary dispersers of native seeds into exotic-dominated forests, which may have enabled six native understory plant species to become reestablished. Some native plant species are now as common in exotic forest understory as they are in native forest. Introduced birds also dispersed seeds of two exotic plants into native forest, but dispersal was localized or establishment minimal. Seed rain of bird-dispersed seeds was extensive in both forests, totaling 724 seeds of 9 native species and 2 exotics with over 85% of the seeds coming from native plants. Without suitable native dispersers, most common understory plants in Hawaiian rainforests now depend on introduced birds for dispersal, and these introduced species may actually facilitate perpetuation, and perhaps in some cases restoration, of native forests. We emphasize, however, that restoration of native forests by seed dispersal from introduced birds, as seen in this study, depends on the existence of native forests to provide a source of seeds and protection from the effects of ungulates. Our results further suggest that aggressive control of patches of non-native plants within otherwise native-dominated forests may be an important and effective conservation strategy.


Development of a semi-automatic segmentation method for retinal OCT images tested in patients with diabetic macular edema.
To develop EdgeSelect, a semi-automatic method for the segmentation of retinal layers in spectral domain optical coherence tomography images, and to compare the segmentation results with a manual method. SD-OCT (Heidelberg Spectralis) scans of 28 eyes (24 patients with diabetic macular edema and 4 normal subjects) were imported into a customized MATLAB application, and were manually segmented by three graders at the layers corresponding to the inner limiting membrane (ILM), the inner segment/ellipsoid interface (ISe), the retinal/retinal pigment epithelium interface (RPE), and the Bruch's membrane (BM). The scans were then segmented independently by the same graders using EdgeSelect, a semi-automated method allowing the graders to guide/correct the layer segmentation interactively. The inter-grader reproducibility and agreement in locating the layer positions between the manual and EdgeSelect methods were assessed and compared using the Wilcoxon signed rank test. The inter-grader reproducibility using the EdgeSelect method for retinal layers varied from 0.15 to 1.21 µm, smaller than those using the manual method (3.36-6.43 µm). The Wilcoxon test indicated the EdgeSelect method had significantly better reproducibility than the manual method. The agreement between the manual and EdgeSelect methods in locating retinal layers ranged from 0.08 to 1.32 µm. There were small differences between the two methods in locating the ILM (p = 0.012) and BM layers (p<0.001), but these were statistically indistinguishable in locating the ISe (p = 0.896) and RPE layers (p = 0.771). The EdgeSelect method resulted in better reproducibility and good agreement with a manual method in a set of eyes of normal subjects and with retinal disease, suggesting that this approach is feasible for OCT image analysis in clinical trials.


Regulated production of the chemokine CCL28 in human colon epithelium.
The chemokine CCL28 is constitutively expressed by epithelial cells at several mucosal sites and is thought to function as a homeostatic chemoattractant of subpopulations of T cells and IgA B cells and to mediate antimicrobial activity. We report herein on the regulation of CCL28 in human colon epithelium by the proinflammatory cytokine IL-1, bacterial flagellin, and n-butyrate, a product of microbial metabolism. In vivo, CCL28 was markedly increased in the epithelium of pathologically inflamed compared with normal human colon. Human colon and small intestinal xenografts were used to model human intestinal epithelium in vivo. Xenografts constitutively expressed little, if any, CCL28 mRNA or protein. After stimulation with the proinflammatory cytokine IL-1, CCL28 mRNA and protein were significantly increased in the epithelium of colon but not small intestinal xenografts, although both upregulated the expression of another prototypic chemokine, CXCL8, in response to the identical stimulus. In studies of CCL28 regulation using human colon epithelial cell lines, proinflammatory stimuli, including IL-1, bacterial flagellin, and bacterial infection, significantly upregulated CCL28 mRNA expression and protein production. In addition, CCL28 mRNA expression and protein secretion by those cells were significantly increased by the short-chain fatty acid n-butyrate, and IL-1- or flagellin-stimulated upregulation of CCL28 by colon epithelial cells was synergistically increased by pretreatment of cells with n-butyrate. Consistent with its upregulated expression by proinflammatory stimuli, CCL28 mRNA expression was attenuated by pharmacological inhibitors of NF-kappaB activation. These findings indicate that CCL28 functions as an "inflammatory" chemokine in human colon epithelium and suggest the notion that CCL28 may act to counterregulate colonic inflammation.


[Nephron sparing surgery as a treatment modality for renal angiomyolipoma].
There is no consensus concerning the indications for active treatment (selective angioembolization (SAE) or surgery) versus observation alone, and the treatment modality for patients with renal angiomyolipoma (AML). Our study aimed to analyze the results of long-term follow-up of patients with renal AML treated by nephron-sparing surgery (NSS). The medical records of thirteen patients with renal AML were retrospectively reviewed for clinical and histopathologic features. There were twelve women and one man (mean age 55 years) who were treated by NSS in our medical center between the years 1993-2001. One patient with tuberous sclerosis had bilateral multifocal tumors, another patient that presented with shock and retroperitoneal bleeding underwent an urgent NSS. Overall, eight patients were symptomatic at diagnosis. The mean tumor diameter was 5.5 cm (range 2.5-13 cm). There was no need to perform nephrectomy in any of the patients. Two patients had enucleation of more than one tumor in the same session. In one case the adrenal gland was surrounded by the AML and was removed with the specimen. No other serious complications were recorded. Four patients required blood transfusions. The mean follow-up period was 26 months (range: 6-62 months) and during that time there was no evidence of recurrence or decreased renal function. Only one patient developed AML in the contralateral kidney, there was one case of incisional hernia and another patient continued to suffer from flank pain. The results of the present study suggest that NSS is a safe and effective treatment modality for renal AML.


Identification of A Novel Variant of Filamin A Destroying the Attraction Between Benzene Rings and Sulfhydryl in Developmental Dysplasia of the Hip.
Developmental dysplasia of the hip (DDH), characterized by acetabular deformity that manifests from loose ligaments to complete dislocation of the hip, can cause notable pain and dysfunction and lead to hip dislocation, secondary fractures, scoliosis, and osteoarthritis of hip. Variants in FLNA may produce a spectrum of malformations in multiple organs, especially the skeleton. This study aimed to identify the genetic etiologies of DDH patients and provide genetic testing information for further diagnosis and treatment of DDH. We recruited a Chinese woman with DDH and her family members. Whole-exome sequencing was used to identify the patient's genetic etiologies. Protein models were used to analyze the pathogenic mechanism of the identified variants. A novel variant (c.3493T>G, p.C1165G) of FLNA was detected. The structural models of the mutant FLNA protein indicated that the variant would lose its sulfhydryl side chain and destroy the attraction between benzene rings and sulfhydryl. We reported a novel variant (c.3493T>G, p.C1165G) of FLNA in a Chinese woman with DDH. Our research outcome enriches the gene pool for hip dysplasia and emphasizes the pathogenicity of sulfhydryl side chain disruption in FLNA.


Specific Features of the Ukrainian Urban Adolescents' Physical Activity: A Cross-Sectional Study.
An increase in the proportion of physically active peoples is one of the public health priorities. Particular attention should be addressed to the adolescent group with regard to their sensitivity. The purpose of our study is to determine the overall level of physical activity (PA) of urban adolescents and to evaluate its components. The study included the results of a survey of 415 children aged 11-15 years from public schools in Ukraine. We have adapted the standardized questionnaire QAPACE, which allows characterizing the level of adolescent's PA by indicators: type, duration, and intensity. A sedentary lifestyle is typical for most Ukrainian urban adolescents. Only 30.8% of Ukrainian urban adolescents (45.4% of boys and 21.4% of girls; p < 0.001) meet the recommended level of moderate-to-vigorous PA (at least 60 minutes per day). The chances to follow the recommended moderate-to-vigorous PA are almost 5 times higher in the group of adolescents exercising at their own wish and not by parents' direction (OR = 4.96; 95% CI: 2.77-8.90; p < 0.001). Girls have a 3.0 higher chance of not adhering to recommendations for duration of PA (OR = 3.01; 95% CI: 1.95-4.63). They are 2.5 times more likely to lead a sedentary lifestyle (OR = 2.48; 95% CI: 1.54-3.98) than boys. The obtained results are indicative of a lack of implementation of measures to increase physical activity, which requires public attention to this problem. A search for ways to improve public policy towards optimizing adolescents' PA is still an urgent goal for scholars and practitioners. PA-promoting measures should be developed taking into account the impact of family traditions, accessibility of sports facilities, leisure, advertising, and other factors. The obtained results are the initial stage for developing the program of physical inactivity prevention.


Ki-67 as a prognostic marker in colorectal cancer but not in gastric cancer.
The growth of tumors is highly variable and this probably reflects even its clinical course. The monoclonal antibody Ki-67 recognises an antigen present in the nuclei of cells in all phases of the cell cycle except G0. In the current study, we examined by immunohistochemistry the proliferative activity, based on Ki-67 labeling index (Ki67LI), in formalin-fixed and paraffin-embedded sections of 152 tumors, being 70 gastric and 89 colorectal cancers. The results obtained were correlated with the clinicopathologic factors. The carcinomas showed a wide range of Ki-67LI, reflecting a variation in proliferative activity. The tumor labeling index ranged from 10 to 85 per cent positivity, being the mean level in gastric cancer tissue 0.52 and in colorectal cancer 0.44. There was also heterogeneity of labeling within many of the tumors. No significant correlation was found between Ki-67LI and sex, age, clinical stage in these cancers. In colorectal cancer, but not in gastric cancer, high levels of Ki67LI have been correlated with poor survival. Ki-67 staining is a simple and useful method for estimating proliferative activity. The importance of Ki-67 as an indicator of tumor behaviour is not clear. In colorectal cancer this index may be used as a marker of prognosis.


Comparing counseling outcome for college students: Metaverse and in-person approaches.
ABSTRACTObjective This study compared metaverse counseling with in-person counseling, using in-person counseling as a comparison group. To achieve this, we assessed whether metaverse counseling, a novel treatment approach, is comparable to traditional in-person counseling. Method: A total of 60 participants voluntarily participated in the study. Among the participants, 28 preferred in-person counseling, whereas 32 selected metaverse counseling as their preferred treatment option. Results and Conclusion: The findings indicated no statistically significant differences in the psychological symptom change patterns between the two counseling modalities. Both metaverse and in-person counseling demonstrated a common pattern of reduced symptom levels from pre-to post-session (Metaverse counseling Cohen's d = 1.04, In-person counseling Cohen's d = .62), which remained stable from post-session to follow-up regardless of the chosen counseling modality. Furthermore, the study revealed that the metaverse counseling group exhibited a higher level of working alliances than the in-person counseling group. Additionally, there was a slight tendency toward higher levels of counseling satisfaction in the metaverse counseling group than in the in-person counseling group. The results of this study support the use of synchronous metaverse programs to treat college students. The implications and limitations of this study are discussed. (195 words).


Comparison of macrophage scavenger receptor-A knockout mice with wild type ones in the immune response against repeated infestation with Haemaphysalis longicornis.
Using macrophage scavenger receptor-A knockout (SRKO) mice, we examined the role of macrophage class A scavenger receptors (MRS-A) on the immune response and acquisition of host resistance against repeated infestation with Haemaphysalis longicornis. Except for one batch of nymphs that infested one of the SRKO (SR-/-) mice and showed no appreciable reduction in body weight, all the other groups of nymphs manifested significant decrease in body weight. Both SR-/- and wild type (SR+/+) mice showed a sustained increase in anti-tick antibody titers, but SR+/+ mice showed significantly higher titers. The IFN-gamma assayed in SR-/- mouse immune sera was substantially less compared with that in SR+/+ mice. Immune sera from SR-/- and SR+/+ mice recognized the 51 and 44 kDa, and 44 kDa proteins, respectively, of the salivary gland antigen. The difference in the level of anti-tick resistance manifested by both groups of mice may be influenced by less efficient trapping and processing of tick antigens by macrophages in mice lacking for the macrophage scavenger receptors, and consequently affected the cascade of Th1 and Th2 responses. We have thus obtained valuable data that strongly infer the role of MSR-A in enhancing host defense against repeated infestation with H. longicornis.


The impact of exacerbation frequency on mortality following acute exacerbations of COPD: a registry-based cohort study.
To examine the association between exacerbation frequency and mortality following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Cohort study using medical databases. Northern Denmark. On 1 January 2005, we identified all patients with prevalent hospital-diagnosed chronic obstructive pulmonary disease (COPD) who had at least one AECOPD during 1 January 2005 to 31 December 2009. We followed patients from the first AECOPD during this period until death, emigration or 31 December 2009, whichever came first. We flagged all AECOPD events during follow-up and characterised each by the exacerbation frequency (0, 1, 2 or 3+) in the prior 12-month period. Using Cox regression, we computed 0-30-day and 31-365-day age-adjusted, sex-adjusted, and comorbidity-adjusted mortality rate ratios (MRRs) with 95% CIs entering exacerbation frequency as a time-varying exposure. We identified 16,647 eligible patients with prevalent COPD, of whom 6664 (40%) developed an AECOPD and were thus included in the study cohort. The 0-30-day MRRs were 0.97 (95% CI 0.80 to 1.18), 0.90 (95% CI 0.70 to 1.15) and 1.03 (95% CI 0.81 to 1.32) among patients with AECOPD with 1, 2 and 3+ AECOPDs versus no AECOPD within the past 12 months, respectively. The corresponding MRRs were 1.47 (95% CI 1.30 to 1.66), 1.89 (95% CI 1.59 to 2.25) and 1.59 (95% CI 1.23 to 2.05) for days 31-365. Among patients with AECOPD, one or more exacerbations in the previous year were not associated with 30-day mortality but were associated with an increased 31-365-day mortality.


ATG8 is conserved between Saccharomyces cerevisiae and psychrophilic, polar-collected fungi.
Autophagy is a conserved catabolic process by which eukaryotic cells respond to stress by targeting damaged or unneeded molecules or organelles for sequestration into specialized vesicles known as autophagosomes. Autophagosomes ultimately facilitate the digestion and recycling of their contents by fusing with the degradative organelle of the cell. Studies of the budding yeast Saccharomyces cerevisiae have revealed various types of stress that can regulate autophagy, including starvation and extreme temperatures. While autophagy has not yet been directly shown to confer the ability to survive extreme cold or freeze-thaw stress in yeast, upregulation of autophagy has been directly implicated in the ability of arctic insects to survive cold temperatures. We are interested in investigating the potential role of autophagy in polar habitat survival by cold-loving (psychrophilic) yeast like Mrakia blollopsis. To begin to examine the conservation of Atg machinery in polar-collected yeast, we focused on Atg8, a small, ubiquitin-like protein that plays an important role in autophagy. We report that Atg8 is conserved between S. cerevisiae and polar-collected yeast, using Atg8 from Mrakia blollopsis (strain TGK1-2) as an example. This study represents the first direct examination of autophagy machinery conservation across mesophilic and psychrophilic species of yeast.


Influence of the pretreatment of occlusal pits and fissures on the retention of a fissure sealant.
To evaluate different regimens of enamel conditioning on the retention of a pit and fissure sealant. 100 extracted human molars were randomized into 10 experimental groups (n = 10). Conditioning of occlusal pits and fissures was performed with either 37% H3PO4, diamond bur and 37% H3PO4, Er:YAG laser, Er:YAG laser and 37% H3PO4, air abrasion (3 different settings), air abrasion (3 different settings) and subsequent acid etching with 37% H3PO4. 24 hours after placing a compomer-based sealant, the specimens were artificially aged by thermocycling (5/55 degrees C; x1000) and immersed in basic fuchsin dye for another 24 hours. After sectioning, dye penetration along the enamel-resin-interface was determined (% of the fissure depth). Data were statistically analyzed with Kruskal-Wallis H test and Mann-Whitney U test. For qualitative investigations, two further specimens of each group were analyzed in the SEM. Conventional acid etching resulted in significantly superior sealant retention than conditioning with either the Er:YAG laser or air abrasion (irrespective of particle size or air pressure). If mechanical conditioning of the laser or air abrasion was followed by acid-etching, results were statistically equal to the acid-etch only group.


Urinary and renal tissue insulin-like growth factor 1 in compensatory renal hypertrophy.
Twenty Wistar rats were nephrectomized unilaterally or sham-operated for the study of compensatory response of renal growth, including kidney weight, creatinine clearance (Ccr), and the role of insulin-like growth factor 1 (IGF-1). The remaining kidney weight had increased 26% above the control level on day 6, and 58% on day 28 after nephrectomy. The overall Ccr in rats with one functioning kidney was 75%, 88%, and 87% of the control values in two-kidney rats on days 1, 6, and 28, respectively after surgery. Serum IGF-1 concentrations were not different between the nephrectomy and sham groups. There was a nearly 2-fold increase in renal tissue IGF-1 concentration on day 6 in nephrectomized rats versus sham-operated controls (107.1 +/- 19.1 and 61.0 +/- 6.1 ng/g tissue, respectively), but no difference between the 2 groups on day 28 after surgery. Urinary IGF-1 excretion was found to be significantly elevated on day 6 after nephrectomy in association with high renal IGF-1 levels. This data suggests that renal IGF-1 production may be involved during the later phases of rapid compensatory renal growth.


Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER-mitochondria contacts.
Coenzyme Q (CoQ) lipids are ancient electron carriers that, in eukaryotes, function in the mitochondrial respiratory chain. In mitochondria, CoQ lipids are built by an inner membrane-associated, multicomponent, biosynthetic pathway via successive steps of isoprenyl tail polymerization, 4-hydroxybenzoate head-to-tail attachment, and head modification, resulting in the production of CoQ. In yeast, we discovered that head-modifying CoQ pathway components selectively colocalize to multiple resolvable domains in vivo, representing supramolecular assemblies. In cells engineered with conditional ON or OFF CoQ pathways, domains were strictly correlated with CoQ production and substrate flux, respectively, indicating that CoQ lipid intermediates are required for domain formation. Mitochondrial CoQ domains were also observed in human cells, underscoring their conserved functional importance. CoQ domains within cells were highly enriched adjacent to ER-mitochondria contact sites. Together, our data suggest that CoQ domains function to facilitate substrate accessibility for processive and efficient CoQ production and distribution in cells.


Establishment of hospital-based surgical residency programs as a health policy for surgical needs provision: an Indonesian perspective.
One of the health interventions that can be implemented cost-effectively in developing countries is the provision of basic surgical procedures. One way to increase access to surgical services is to increase the production of surgeons, in this case through increasing the surgical residency program. There are similarities between university-based surgical residency programs and hospital-based surgical residency programs. However, in Indonesia, the differences between them are stark; the establishment of hospital-based surgical residency programs is challenging and requires collaboration between the government, university, college of surgery, and private sector. The author reviewed the literature on post-graduate medical education for surgical programs and the contrast between university-based and hospital-based surgical residency programs. Information collected from the Indonesian Health Education Independent Accreditation Institution and varied literature was included. Not applicable. In Indonesia, the implementation of an academic surgery environment in the hospital-based surgical residency program is challenging, and the implementation of the academic health system can increase student intake and provide more both from the university and the hospital-based surgical residency program.


The operation of a superconducting wiggler at TERAS.
A superconducting wiggler has been successfully installed at the ETL 800 MeV electron storage ring facility (TERAS). The operation of the wiggler at magnetic field strengths of 5 T with electron beam energy of 750 MeV has been accomplished. The wiggler has been designed and constructed to produce synchrotron radiation with critical photon energy around 3 keV for scientific, industrial and medical applications. We report here experiments that demonstrate the possibility of stable operation of a superconducting wiggler in a small storage ring.


Protein dynamics and the diversity of an antibody response.
The immune system is remarkable in its ability to produce antibodies (Abs) with virtually any specificity from a limited repertoire of germ line precursors. Although the contribution of sequence diversity to this molecular recognition has been studied for decades, recent models suggest that protein dynamics may also broaden the range of targets recognized. To characterize the contribution of protein dynamics to immunological molecular recognition, we report the sequence, thermodynamic, and time-resolved spectroscopic characterization of a panel of eight Abs elicited to the chromophoric antigen 8-methoxypyrene-1,3,6-trisulfonate (MPTS). Based on the sequence data, three of the Abs arose from unique germ line Abs, whereas the remaining five comprise two sets of siblings that arose by somatic mutation of a common precursor. The thermodynamic data indicate that the Abs recognize MPTS via a variety of mechanisms. Although the spectroscopic data reveal small differences in protein dynamics, the anti-MPTS Abs generally show similar levels of flexibility and conformational heterogeneity, possibly representing the convergent evolution of the dynamics necessary for function. However, one Ab is significantly more rigid and conformationally homogeneous than the others, including a sibling Ab from which it differs by only five somatic mutations. This example of divergent evolution demonstrates that point mutations are capable of fixing significant differences in protein dynamics. The results provide unique insight into how high affinity Abs may be produced that bind virtually any target and possibly, from a more general perspective, how new protein functions are evolved.


DNA-dependent SUMO modification of PARP-1.
Poly(ADP-ribose) polymerase 1 (PARP-1) plays an important role in DNA repair, but also contributes to other aspects of nucleic acid metabolism, such as transcriptional regulation. Modification of PARP-1 with the small ubiquitin-related modifier (SUMO) affects its function as a transcriptional co-activator of hypoxia-responsive genes and promotes induction of the heat shock-induced HSP70.1 promoter. We now report that PARP-1 sumoylation is strongly influenced by DNA. Consistent with a function in transcription, we show that sumoylation in vitro is enhanced by binding to intact, but not to damaged DNA, in a manner clearly distinct from the mechanism by which DNA damage stimulates PARP-1's catalytic activity. An enhanced affinity of PARP-1 for the SUMO-conjugating enzyme Ubc9 upon binding to DNA is likely responsible for this effect. Sumoylation does not interfere with the catalytic or DNA-binding properties of PARP-1, and structural analysis reveals no significant impact of SUMO on the conformation of PARP-1's DNA-binding domain. In vivo, sumoylated PARP-1 is associated with chromatin, but the modification is not responsive to DNA damage and is not affected by PARP-1 catalytic activity. Our results suggest that PARP-1's alternative modes of DNA recognition serve as a means to differentiate between distinct aspects of the enzyme's function.


Design and efficacy of a single-use bioreactor for heart valve tissue engineering.
Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 249-259, 2017.


Racemic methyl 3,10-dioxa-2-aza-tri-cyclo-[18.104.22.168]undecane-4-carboxyl-ate.
The structure of the racemic title compound, C(10)H(15)NO(4), consists of a tricyclic skeleton comprising a six-membered piperidine ring and five-membered isoxazolidine and tetra-hydro-furan rings. The piperidine ring adopts a distorted chair conformation, while the isoxazolidine and tetra-hydro-furan rings have envelope conformations.


[New methods for the evaluation of bone quality. Bone Quality Marker.]
In recent years, undercarboxylated osteocalcin(ucOC), advanced glycation endproducts(AGEs)and homocysteine are attracting attention as factors defining bone strength. However, there are still many problems in its measurement, and it has not yet been routinely used in clinical practice. If solving the problem in the future, it is expected that the utility on bone quality will also increase.


BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulum stress transducer.
Endoplasmic reticulum (ER) stress transducers IRE1 (inositol requiring 1), PERK (PKR-like endoplasmic reticulum kinase), and ATF6 (activating transcription factor 6) are well known to transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins accumulate in the ER. Recently, we identified OASIS (old astrocyte specifically induced substance) as a novel ER stress transducer expressed in astrocytes. We report here that BBF2H7 (BBF2 human homolog on chromosome 7), an ER-resident transmembrane protein with the bZIP domain in the cytoplasmic portion and structurally homologous to OASIS, is cleaved at the membrane in response to ER stress. The cleaved fragments of BBF2H7 translocate into the nucleus and can bind directly to cyclic AMP-responsive element sites to activate transcription of target genes. Interestingly, although BBF2H7 protein is not expressed under normal conditions, it is markedly induced at the translational level during ER stress, suggesting that BBF2H7 might contribute to only the late phase of unfolded protein response signaling. In a mouse model of focal brain ischemia, BBF2H7 protein is prominently induced in neurons in the peri-infarction region. Furthermore, in a neuroblastoma cell line, BBF2H7 overexpression suppresses ER stress-induced cell death, while small interfering RNA knockdown of BBF2H7 promotes ER stress-induced cell death. Taken together, our results suggest that BBF2H7 is a novel ER stress transducer and could play important roles in preventing accumulation of unfolded proteins in damaged neurons.


Measuring feeding difficulty in patients with dementia: multivariate analysis of feeding problems, nursing intervention and indicators of feeding difficulty.
The feeding difficulty of 196 elderly people with dementia was investigated by means of an 11-item questionnaire administered to nursing staff. The questionnaire was analysed by means of multivariate statistics, namely factor analysis. The factor analysis demonstrated that the original items could be reduced to three factors. These three factors were named: (a) patient obstinacy or passivity; (b) nursing intervention; and (c) indicator of feeding difficulty. This quantitative analysis confirms a previous qualitative distinction between items in the questionnaire and suggests avenues of research into the relationship between the factors.


[Treatment of peripheral nerves in a district hospital].
The authors submit the results of 23 operations performed on peripheral nerves of the upper extremity in a district hospital. They emphasize the good cooperation of the surgeon with the neurologist, the importance of clinical and EMG examinations for diagnosis as well as during evaluation of the accomplished operation. In cooperation with the Physical Institute of the Czech Academy of Sciences it proved possible to reconstruct for surgical purposes a common colposcope so that it can be used for microsurgical operations. A brief description of the apparatus is given in the paper. From a total of 23 performed operations a satisfactory result was recorded in 87% of the operated patients.


Metabolic clearance of norepinephrine in normotensive and borderline hypertensive subjects.
Metabolic clearance of norepinephrine ( CmNE ) has been calculated in 10 normotensive subjects (NT) and 10 borderline hypertensive subjects (HT) at two different infusion rates of 1-NE. Plasma catecholamines have been determined by radio-enzymatic method from arterial blood samples. In these conditions, CmNE is similar in NT and HT.


[Significance of Epstein-Barr virus DNA quantitation in donors of hematopoietic stem cell transplantation].
Epstein-Barr virus (EBV) is a well-known causative agent of various diseases including post-transplant lymphoproliferative disorders. Although the level of EBV viral load in donors is expected to have a direct effect on recipients after hematopoietic stem cell transplantation (HSCT), little has been studied providing a clear evidence for that. We performed EBV DNA quantitation in donors and analyzed the effect of donors' EBV viral load on the recipients after HSCT. EBV DNA quantitation of peripheral blood in 94 healthy HSCT donors was performed by real-time PCR. We analyzed the distribution of EBV viral load in HSCT donors and EBV positivity in the recipients transplanted from donors who had detectable EBV. Fifteen HSCT donors (16%) showed positive results in EBV real-time quantitative PCR. EBV viral load was below 500 copies/mL in 5 donors and above 500 (680-11,300) copies/mL in 10 donors. Five of the recipients (33.3%) transplanted from these 15 donors showed positivity in EBV PCR after HSCT. All of the EBV PCR positive recipients were transplanted from donors with viral load of >1,000 copies/mL, and 5 (71%) of 7 donors with viral load of >1,000 copies/mL was associated with posttransplant EBV PCR positivity in the recipients. Higher levels of EBV viral load in donors appear to be associated with EBV transmission to recipients in HSCT. EBV real-time quantitative PCR may be needed for screening EBV DNA level in HSCT donors.


Comparative effectiveness of adrenal sparing radical nephrectomy and non-adrenal sparing radical nephrectomy in clear cell renal cell carcinoma: Observational study of survival outcomes.
We compare the survival outcomes of patients with clear cell renal cell carcinoma (RCC) treated with adrenal sparing radical nephrectomy (ASRN) and non-adrenal sparing radical nephrectomy (NASRN). We conducted an observational study based on a composite patient population from two university teaching hospitals who underwent RN for RCC between January 2000 and December 2012. Only patients with pathologically confirmed RCC were included. We excluded patients undergoing cytoreductive nephrectomy, with loco-regional lymph node involvement. In total, 579 patients (ASRN = 380 and NASRN = 199) met our study criteria. Patients were categorized by risk groups (all stage, early stage and locally advanced RCC). Overall survival (OS) and cancer-specific survival (CSS) were analyzed for risk groups. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression. The median follow-up was 41 months (range: 12-157). There were significant benefits in OS (ASRN 79.5% vs. NASRN 63.3%; p = 0.001) and CSS (84.3% vs. 74.9%; p = 0.001), with any differences favouring ASRN in all stage. On multivariate analysis, there was a trend towards worse OS (hazard ratio [HR] 1.759, 95% confidence interval [CI] 0.943-2.309, p = 0.089) and CSS (HR 1.797, 95% CI 0.967-3.337, p = 0.064) in patients with NASRN (although not statistically significant). Of these patients, only 11 (1.9%) had adrenal involvement. The inherent limitations in our study include the impracticality of conducting a prospective randomized trial in this scenario. Our observational study with a 13-year follow-up suggests ASRN leads to better survival than NASRN. ASRN should be considered the gold standard in treating patients with RCC, unless it is contraindicated.


The effect of menstruation on psychiatric hospitalization.
This study evaluated the effect of menstruation on psychiatric hospitalization. We conducted a retrospective chart review of the medical records of 177 women who met the eligibility criteria. Data collected included demographic details, primary and secondary diagnoses, date of last menstrual period (LMP), medication adherence, psychiatric hospitalization length of stay, previous psychiatric admissions (including those related to menstruation), discharge referrals, and readmissions. The majority of women were admitted for major depression, were single, Caucasian, and had a mean age of 34. A disproportionate percentage (37%) of women had their LMP within 5 days of psychiatric hospitalization (p = 0.0006). The overall average length of stay was 4.37 days, and 48.3% had a previous psychiatric admission. Medication adherence was routinely not documented (77.4%). Psychiatric hospitalizations for women are significantly greater within 5 days of their LMP. Nursing education and improved documentation are warranted to decrease the potential for readmission.


Diagnostic imaging of lung cancer.
Carcinoma of the bronchus is the most common malignancy in the Western world. It is also the leading cause of cancer-related death accounting for 32% of all cancer deaths in males and 25% in females. In the USA it causes more deaths than cancers of the colon, breast and prostate combined. Disappointingly, in a recent UK survey of improvements in cancer survival, carcinoma of the bronchus showed the smallest percentage reduction in the number of deaths avoided between 1981-1990 (0.2%). This compares badly with breast (11% reduction) and melanoma (32%). The overall 5-yr survival for lung cancer diagnosed between 1986-1990 was only 5.3% (against 66% for breast and 76% for melanoma). It is on this background that the radiologist remains actively employed in the detection, diagnosis, staging and review of this common malignancy.


Basal serum-free culture system which supports growth of fetal rat adrenal cells in primary monolayer cell culture.
A serum-free culture system has been developed which allows primary cultures of fetal rat adrenal cells to divide in response to insulin 10 micrograms/l, yet retain their ability to respond to adrenocorticotropic hormone (ACTH) by increased corticosterone production. The essential components of this culture system are: (1) a high initial plating number of 125-130 x 10(3) cells/cm2; (2) a low oxygen concentration of 2.5% O2; (3) an initial plating period of 48 h in greater than or equal to 5% (v/v) fetal bovine serum. In contrast to reported requirements for the serum-free growth of adult adrenal cells, the fetal adrenal cells do not require the provision of any special matrix or a competence factor for serum-free growth or steroidogenic activity. This suggests that they are capable of rapidly generating their own matrix and competence factor in primary culture.


Hot flash management: update of the evidence for patients with cancer
Hot flashes are a distressing symptom frequently experienced by survivors of breast cancer or prostate cancer who are receiving estrogen or androgen-deprivation therapies. The frequency and intensity of hot flashes can lead to diminished quality of life and decreased adherence with prescribed antineoplastic therapies. This evidence-based review synthesizes and updates the findings of the highest quality evidence-based studies of interventions to manage hot flashes resulting from cancer therapies in patients with breast or prostate cancer since the initial Putting Evidence Into Practice review of hot flashes in 2011. Recent studies involving a variety of pharmacologic and nonpharmacologic interventions were evaluated and, as reported in 2011, the drugs gabapentin and venlafaxine were the only therapies rated as likely to be effective. In addition, a strong placebo effect was noted in several studies that included a placebo intervention and should be considered when reviewing interventions for hot flashes.


The area of faith in Winnicott, Lacan and Bion.
The area of faith is distinguishable from operations which primarily emphasize ego mastery and introjection-internalization processes. Faith is implicit in Winnicott's transitional experiencing and carried forward in object usage. In Bion faith is linked with openness to O or the (unknowable) ultimate reality of a session and is the operative principle of the psychoanalytic attitude. This paper emphasizes the play of faith in Winnicott's object usage and Bion's O. A certain faith is also required to tolerate the movement of meaning in Lacan's Symbolic order. Faith as a fundamental dimension is in tension with the defensive use of mastery and introjective-projective representational networks. In its various forms this complex tension is part of the structure of human life and constitutes the arena in which faith may evolve.


The effects of castration on histamine levels and 24-hour rhythm in the male rat hypothalamus.
Holtzman male rats were castrated or sham-operated at 22 days of age and raised in a 12 h light: 12 h dark illumination cycle. At age 63 days they were sacrificed by decapitation at six different times during the light:dark (L:D) cycle, and hypothalamic histamine (H) concentrations were measured using a modified single isotope-enzyme microassay. Hypothalamic H was significantly elevated in the castrated rats at all but two of the six times sampled during the L:D cycle, when compared with the sham-operated controls. Both surgical groups had similar 24-h rhythms of hypothalamic H concentrations, with the peak concentration occurring during the light phase followed by a rapid drop to the minimum 2-3 h later. However, the castrated rats appeared to attain both maximal and minimal concentrations somewhat earlier in the day. These results provide circumstantial evidence that hypothalamic H may have a role in the hypothalamo-hypophyseal-gonadal axis in the male rat.


An unusual case of right upper quadrant pain in a pregnant woman.
Uterine fibroids occur in up to 30% of women of reproductive age and can cause complications during pregnancy that can harm mother and fetus, such as prematurity and increased risk of miscarriage. This article describes a pregnant woman whose abdominal pain was diagnosed as degenerating uterine fibroids.


The effect of desferrioxamine on iron metabolism and lipid peroxidation in hepatocytes of C57BL/10 mice in experimental uroporphyria.
The effects of the iron chelator desferrioxamine (DFx) on liver iron accumulation, malondialdehyde (MDA) production, porphyrin accumulation and uroporphyrinogen decarboxylase (URO-D; EC 126.96.36.199) activity were investigated over a period of 14 weeks in C57BL/10 mice, made porphyric by the administration of hexachlorobenzene (HCB) and iron-dextran (Imferon, IMF) or IMF alone. In addition, we measured the amount of low molecular weight (LMW) iron in liver tissue to determine a possible correlation with MDA production. These experiments showed that combined treatment with HCB + IMF, as well as IMF alone, resulted in porphyrin accumulation, increased MDA production and reduced URO-D activity, whereas HCB alone had no effect. DFx caused a reduction in hepatic porphyrins, this reduction being more distinct in the IMF group than in the HCB + IMF group. The effect of DFx on MDA production and URO-D activity was in agreement with the results on porphyrin accumulation. LMW iron pool measurements at 11 weeks correlated well with data on MDA production in all treated groups in that period (r2 = 0.84), suggesting both variables are interdependent. In conclusion, these results suggest an important role for iron in porphyrin accumulation, probably through its catalytic role in the generation of oxygen-related free radicals, resulting in direct damage to URO-D. The effectiveness of DFx in reducing porphyrin accumulation is probably the result of a reduction in LMW iron, thus diminishing the amount of iron available for a catalytic role in the generation of oxygen-related free radicals.


Haemophilus parasuis cytolethal distending toxin induces cell cycle arrest and p53-dependent apoptosis.
Haemophilus parasuis is the causative agent of Glasser's disease in pigs. Cytolethal distending toxin (CDT) is an important virulence factor of H. parasuis. It is composed of three subunits: CdtA, CdtB and CdtC and all were successfully expressed in soluble form in Escherichia coli when the signal peptides were removed. Purified CdtB had DNase activity, i.e. caused DNA double strand damage, in vitro and in vivo prior to cell arrest and apoptosis. Flow cytometry analysis showed CdtB alone could induce cell cycle arrest and apoptosis in PK-15 porcine kidney and pulmonary alveolar macrophage (PAM) cells, which could be enhanced by CdtA or/and CdtC. CDT holotoxin could lead to significant cell distension, G2 arrest and apoptotic death in PK-15 and PAM cells. The apoptosis induced by CDT holotoxin was significantly inhibited by pifithrin-α, which indicates that it is p53-dependent. The results suggest that H. parasuis CDT holotoxin is a major virulence factor.


Mismatch repair deficient metastatic colon cancer and urothelial cancer: A case report of sequential immune checkpoint therapy.
A major recent advance in cancer therapy involves the use of immune checkpoint therapy for tumors with mismatch repair deficiency, as they have a high tumor mutation load and neoantigen burden. Approximately 4% of advanced colorectal cancer harbors a mismatch repair deficiency. When mismatch repair deficiency exists in the germline, there is increased susceptibility to a variety of cancers including colorectal cancer, uterine cancer, urothelial carcinoma, and skin cancer. Herein we report the case of a 62-year-old man with mismatch repair deficient metastatic colorectal adenocarcinoma, urothelial carcinoma and a history of sebaceous carcinomas. As the patient in 2016 was ineligible for clinical trials he received immune checkpoint anti-PD-1 therapy with pembrolizumab (200 mg every 3 weeks), on compassionate use basis, after the failure of second-line treatment. The patient's CEA initially responded to pembrolizumab for 4 months and then kept rising for 5 months before mildly declining again. His treatment was then switched to anti-PD-L1 therapy with atezolizumab as it was approved for urothelial carcinoma at that time, and his CEA declined again. This case raises interesting questions about caring for patients with mismatch repair deficient colorectal cancer, including the role of PD-L1 therapy, sequencing of immunotherapy, relying on CEA trends and determining future therapies after progression on pembrolizumab.


Effects of non-sinusoidal pitching motion on the propulsion performance of an oscillating foil.
Numerical simulations have been used in this paper to study the propulsion device of a wave glider based on an oscillating hydrofoil, in which the profile of the pitching and heaving motion have been prescribed for the sake of simplicity. A grid model for a two-dimensional NACA0012 hydrofoil was built by using the dynamic and moving mesh technology of the Computational Fluid Dynamics (CFD) software FLUENT and the corresponding mathematical model has also been established. First, for the sinusoidal pitching, the effects of the pitching amplitude and the reduced frequency were investigated. As the reduced frequency increased, both the mean output power coefficient and the optimal pitching amplitude increased. Then non-sinusoidal pitching was studied, with a gradual change from a sinusoid to a square wave as the value of β was increased from 1. It was found that when the pitching amplitude was small, the trapezoidal pitching profile could indeed improve the mean output power coefficient of the flapping foil. However, when the pitching amplitude was larger than the optimal value, the non-sinusoidal pitching motion negatively contributed to the propulsion performance. Finally, the overall results suggested that a trapezoidal-like pitching profile was effective for the oscillating foil of a wave glider when the pitching amplitude was less than the optimal value.


Parallel beta/alpha-barrels of alpha-amylase, cyclodextrin glycosyltransferase and oligo-1,6-glucosidase versus the barrel of beta-amylase: evolutionary distance is a reflection of unrelated sequences.
The structures of functionally related beta/alpha-barrel starch hydrolases, alpha-amylase, beta-amylase, cyclodextrin glycosyltransferase and oligo-1,6-glucosidase, are discussed, their mutual sequence similarities being emphasized. Since these enzymes (except for beta-amylase) along with the predicted set of more than ten beta/alpha-barrels from the alpha-amylase enzyme superfamily fulfil the criteria characteristic of the products of divergent evolution, their unrooted distance tree is presented.